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Alamri MA, Prinsa, Kawsar SMA, Saha S. Exploring marine-derived bioactive compounds for dual inhibition of Pseudomonas aeruginosa LpxA and LpxD: integrated bioinformatics and cheminformatics approaches. Mol Divers 2025; 29:1033-1047. [PMID: 38780832 DOI: 10.1007/s11030-024-10888-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Accepted: 04/27/2024] [Indexed: 05/25/2024]
Abstract
Pseudomonas aeruginosa can cause serious nosocomial infections. Targeting the biosynthesis of Lipid A, a major structural domain of lipopolysaccharide (LPS) in P. aeruginosa has emerged as a valuable strategy for developing novel therapeutic agents. The biosynthesis of Lipid A involves the activation of homolog enzymes including LpxA and LpxD. LpxA enzyme facilitates the transfer of R-3-hydroxydecanoic fatty acid to uridine diphosphate N-acetylglucosamine in the first step. While LPxD is accountable in third step, wherein R-3-hydroxydodecanoate is transferred to the 2' amine of UDP-3-O-(3-hydroxydecanoyl) utilizing an ACP donor. The exploration of LpxA and LpxD has been largely neglected, as no specific small-molecule inhibitors have been identified, thus far, except for peptide inhibitors. Here, we report the identification of potential dual inhibitors of the lipid A biosynthesis pathway that target both the LpxA and LpxD enzymes as novel antibiotic agents. Among the virtually screened 32,000 marine bioactive compounds Oscillatoxin A, NCI60_041046, and LTS0192263 exhibited optimal docking interactions with LpxA and LpxD, respectively. MD simulation and MMPBSA data showcased stable interactions between selected marine products and LpxA/LpxD. FMO analysis showed that Oscillatoxin A and NCI60_041046 are the most chemically active molecules. MEP analysis data highlighted the possible electrophilic and nucleophilic distribution zones present in the structure. In addition, these bioactive molecules showed acceptable ADMET profiles. These data confirmed that Oscillatoxin A, NCI60_041046, and LTS0192263 could serve as seeds for the development of potential therapeutics to combat P. aeruginosa infection.
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Affiliation(s)
- Mubarak A Alamri
- Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, P.O. Box 173, 11942, Al-Kharj, Saudi Arabia
| | - Prinsa
- Siddhartha Institute of Pharmacy, Near IT-Park, Sahastradhara Road, Dehradun, 248001, Uttarakhand, India
| | - Sarkar M A Kawsar
- Laboratory of Carbohydrate and Nucleoside Chemistry, Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong, 4331, Bangladesh
| | - Supriyo Saha
- Department of Pharmaceutical Chemistry, Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, 248001, Uttarakhand, India.
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Chaudhari MA, Wankhede PR, Dalal KS, Kale AD, Dalal DS, Chaudhari BL. Lentilactobacillus farraginis FSI (3): a whole cell biocatalyst for the synthesis of kojic acid derivative under aquatic condition. Biotechnol Lett 2024; 46:1107-1120. [PMID: 39162862 DOI: 10.1007/s10529-024-03514-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Revised: 07/05/2024] [Accepted: 07/21/2024] [Indexed: 08/21/2024]
Abstract
Kojic acid derivatives are useful in the cosmetics and pharmaceutical industries. The current investigation focuses on the search for a safe and environmentally friendly newer whole-cell biocatalyst for the synthesis of kojic acid derivative especially 2-amino-6-(hydroxymethyl)-8-oxo-4-phenyl-4,8-dihydropyrano[3,2-b]pyran-3-carbonitrile (APhCN). In this context, a total of six cultures were isolated from fecal samples of infants and subjected to probiotic characterization followed by screening as whole cell biocatalyst (WCB). In this multicomponent reaction, benzaldehyde, malononitrile, and kojic acid were used to synthesize APhCN at room temperature under aqueous conditions. The screening of potent whole cell biocatalyst (WCB) from isolated cultures was done by comparing reaction time and percent yield. The potent WCB gave a good yield of 95% within 15 h of time and hence further characterized biochemically and identified as Lentilactobacillus farraginis by using 16S rRNA gene sequencing. Lactobacilli having GRAS (generally regarded as safe) status and being able to carry out this transformation under moderate reaction conditions with easy recovery of both product and biocatalyst, it has the potential to replace some of the chemical catalytic methods.
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Affiliation(s)
- Mangal A Chaudhari
- School of Life Sciences, Kavayitri Bahinabai Chaudhari North Maharashtra University, Jalgaon, MS, 425 001, India
| | - Pratiksha R Wankhede
- School of Life Sciences, Kavayitri Bahinabai Chaudhari North Maharashtra University, Jalgaon, MS, 425 001, India
| | - Kiran S Dalal
- School of Life Sciences, Kavayitri Bahinabai Chaudhari North Maharashtra University, Jalgaon, MS, 425 001, India
| | - Arun D Kale
- School of Chemical Sciences, Kavayitri Bahinabai Chaudhari North Maharashtra University, Jalgaon, MS, 425 001, India
| | - Dipak S Dalal
- School of Chemical Sciences, Kavayitri Bahinabai Chaudhari North Maharashtra University, Jalgaon, MS, 425 001, India
| | - Bhushan L Chaudhari
- School of Life Sciences, Kavayitri Bahinabai Chaudhari North Maharashtra University, Jalgaon, MS, 425 001, India.
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Hsu HC, Wang M, Kovach A, Darwin AJ, Li H. P. aeruginosa CtpA protease adopts a novel activation mechanism to initiate the proteolytic process. EMBO J 2024; 43:1634-1652. [PMID: 38467832 PMCID: PMC11021448 DOI: 10.1038/s44318-024-00069-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 02/19/2024] [Accepted: 02/26/2024] [Indexed: 03/13/2024] Open
Abstract
During bacterial cell growth, hydrolases cleave peptide cross-links between strands of the peptidoglycan sacculus to allow new strand insertion. The Pseudomonas aeruginosa carboxyl-terminal processing protease (CTP) CtpA regulates some of these hydrolases by degrading them. CtpA assembles as an inactive hexamer composed of a trimer-of-dimers, but its lipoprotein binding partner LbcA activates CtpA by an unknown mechanism. Here, we report the cryo-EM structures of the CtpA-LbcA complex. LbcA has an N-terminal adaptor domain that binds to CtpA, and a C-terminal superhelical tetratricopeptide repeat domain. One LbcA molecule attaches to each of the three vertices of a CtpA hexamer. LbcA triggers relocation of the CtpA PDZ domain, remodeling of the substrate binding pocket, and realignment of the catalytic residues. Surprisingly, only one CtpA molecule in a CtpA dimer is activated upon LbcA binding. Also, a long loop from one CtpA dimer inserts into a neighboring dimer to facilitate the proteolytic activity. This work has revealed an activation mechanism for a bacterial CTP that is strikingly different from other CTPs that have been characterized structurally.
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Affiliation(s)
- Hao-Chi Hsu
- Department of Structural Biology, Van Andel Institute, Grand Rapids, MI, USA
| | - Michelle Wang
- Department of Microbiology, New York University Grossman School of Medicine, New York, NY, USA
| | - Amanda Kovach
- Department of Structural Biology, Van Andel Institute, Grand Rapids, MI, USA
| | - Andrew J Darwin
- Department of Microbiology, New York University Grossman School of Medicine, New York, NY, USA.
| | - Huilin Li
- Department of Structural Biology, Van Andel Institute, Grand Rapids, MI, USA.
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Li Q, Zhou X, Yang R, Shen X, Li G, Zhang C, Li P, Li S, Xie J, Yang Y. Carbapenem-resistant Gram-negative bacteria (CR-GNB) in ICUs: resistance genes, therapeutics, and prevention - a comprehensive review. Front Public Health 2024; 12:1376513. [PMID: 38601497 PMCID: PMC11004409 DOI: 10.3389/fpubh.2024.1376513] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Accepted: 03/20/2024] [Indexed: 04/12/2024] Open
Abstract
Intensive care units (ICUs) are specialized environments dedicated to the management of critically ill patients, who are particularly susceptible to drug-resistant bacteria. Among these, carbapenem-resistant Gram-negative bacteria (CR-GNB) pose a significant threat endangering the lives of ICU patients. Carbapenemase production is a key resistance mechanism in CR-GNB, with the transfer of resistance genes contributing to the extensive emergence of antimicrobial resistance (AMR). CR-GNB infections are widespread in ICUs, highlighting an urgent need for prevention and control measures to reduce mortality rates associated with CR-GNB transmission or infection. This review provides an overview of key aspects surrounding CR-GNB within ICUs. We examine the mechanisms of bacterial drug resistance, the resistance genes that frequently occur with CR-GNB infections in ICU, and the therapeutic options against carbapenemase genotypes. Additionally, we highlight crucial preventive measures to impede the transmission and spread of CR-GNB within ICUs, along with reviewing the advances made in the field of clinical predictive modeling research, which hold excellent potential for practical application.
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Affiliation(s)
- Qi Li
- Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
- Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Xiaoshi Zhou
- Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
- Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Rou Yang
- Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
- Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Xiaoyan Shen
- Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
- Department of Pharmacy, Chengdu Qingbaijiang District People's Hospital, Chengdu, China
| | - Guolin Li
- Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
- School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
| | - Changji Zhang
- Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
- School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
| | - Pengfei Li
- Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Shiran Li
- Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
- Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Jingxian Xie
- Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Yong Yang
- Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
- Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
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Gangar T, Patra S. Antibiotic persistence and its impact on the environment. 3 Biotech 2023; 13:401. [PMID: 37982084 PMCID: PMC10654327 DOI: 10.1007/s13205-023-03806-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Accepted: 10/10/2023] [Indexed: 11/21/2023] Open
Abstract
From boon molecules to molecules contributing to rising concern has been the sojourn of antibiotics. The problem of antibiotic contamination has gotten worse due to antibiotics' pervasive use in every aspect of the environment. One such consequence of pollution is the increase in infections with antibiotic resistance. All known antimicrobials being used for human benefit lead to their repetitive and routine release into the environment. The misuse of antibiotics has aggravated the situation to a level that we are short of antibiotics to treat infections as organisms have developed resistance against them. Overconsumption is not just limited to human health care, but also occurs in other areas such as aquaculture, livestock, and veterinary applications for the purpose of improving feed and meat products. Due to their harmful effects on non-target species, the trace level of antibiotics in the aquatic ecosystem presents a significant problem. Since the introduction of antibiotics into the environment is more than their removal, they have been given the status of persistent pollutants. The buildup of antibiotics in the environment threatens aquatic life and may lead to bacterial strains developing resistance. As newer organisms are becoming resistant, there exists a shortage of antibiotics to treat infections. This has presented a very critical problem for the health-care community. Another rising concern is that the development of newer drug molecules as antibiotics is minimal. This review article critically explains the cause and nature of the pollution and the effects of this emerging trend. Also, in the latter sections, why we need newer antibiotics is questioned and discussed.
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Affiliation(s)
- Tarun Gangar
- Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, North Guwahati, Assam 781039 India
| | - Sanjukta Patra
- Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, North Guwahati, Assam 781039 India
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Baba H, Kuroda M, Sekizuka T, Kanamori H. Highly sensitive detection of antimicrobial resistance genes in hospital wastewater using the multiplex hybrid capture target enrichment. mSphere 2023; 8:e0010023. [PMID: 37222510 PMCID: PMC10449491 DOI: 10.1128/msphere.00100-23] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Accepted: 04/18/2023] [Indexed: 05/25/2023] Open
Abstract
Wastewater can be useful in monitoring the spread of antimicrobial resistance (AMR) within a hospital. The abundance of antibiotic resistance genes (ARGs) in hospital effluent was assessed using metagenomic sequencing (mDNA-seq) and hybrid capture (xHYB). mDNA-seq analysis and subsequent xHYB targeted enrichment were conducted on two effluent samples per month from November 2018 to May 2021. Reads per kilobase per million (RPKM) values were calculated for all 1,272 ARGs in the constructed database. The monthly numbers of patients with presumed extended-spectrum β-lactamase (ESBL)-producing and metallo-β-lactamase (MBL)-producing bacteria, methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE) were compared with the monthly RPKM values of blaCTX-M, blaIMP, mecA, vanA, and vanB by xHYB. The average RPKM value for all ARGs detected by xHYB was significantly higher than that of mDNA-seq (665, 225, and 328, respectively, and P < 0.05). The average number of patients with ESBL producers and RPKM values of blaCTX-M-1 genes in 2020 were significantly higher than that in 2019 (17 and 13 patients per month and 921 vs 232 per month, respectively, both P < 0.05). The average numbers of patients with MBL-producers, MRSA, and VRE were 1, 28, and 0 per month, respectively, while the average RPKM values of blaIMP, mecA, vanA, and vanB were 6,163, 6, 0, and 126 per month, respectively. Monitoring ARGs in hospital effluent using xHYB was found to be more useful than conventional mDNA-seq in detecting ARGs including blaCTX-M, blaIMP, and vanB, which are important for infection control.IMPORTANCEEnvironmental ARGs play a crucial role in the emergence and spread of AMR that constitutes a significant global health threat. One major source of ARGs is effluent from healthcare facilities, where patients are frequently administered antimicrobials. Culture-independent methods, including metagenomics, can detect environmental ARGs carried by non-culturable bacteria and extracellular ARGs. mDNA-seq is one of the most comprehensive methods for environmental ARG surveillance; however, its sensitivity is insufficient for wastewater surveillance. This study demonstrates that xHYB appropriately monitors ARGs in hospital effluent for sensitive identification of nosocomial AMR dissemination. Correlations were observed between the numbers of inpatients with antibiotic-resistant bacteria and the ARG RPKM values in hospital effluent over time. ARG surveillance in hospital effluent using the highly sensitive and specific xHYB method could improve our understanding of the emergence and spread of AMR within a hospital.
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Affiliation(s)
- Hiroaki Baba
- Department of Infectious Diseases, Internal Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Makoto Kuroda
- Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo, Japan
| | - Tsuyoshi Sekizuka
- Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo, Japan
| | - Hajime Kanamori
- Department of Infectious Diseases, Internal Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
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Hussain MA, Mohamed MS, Altayb HN, Mohamed AO, Ashour A, Osman W, Sherif AE, Ghazawi KF, Miski SF, Ibrahim SRM, Mohamed GA, Sindi IA, Alshamrani AA, Elgaml A. Comparative Genomic Analysis of Multi-Drug Resistant Pseudomonas aeruginosa Sequence Type 235 Isolated from Sudan. Microorganisms 2023; 11:1432. [PMID: 37374934 DOI: 10.3390/microorganisms11061432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Revised: 05/20/2023] [Accepted: 05/24/2023] [Indexed: 06/29/2023] Open
Abstract
Pseudomonas aeruginosa (P. aeruginosa) is known to be associated with resistance to practically all known antibiotics. This is a cross-sectional, descriptive, laboratory-based analytical study in which 200 P. aeruginosa clinical isolates were involved. The DNA of the most resistant isolate was extracted and its whole genome was sequenced, assembled, annotated, and announced, strain typing was ascribed, and it was subjected to comparative genomic analysis with two susceptible strains. The rate of resistance was 77.89%, 25.13%, 21.61%, 18.09%, 5.53%, and 4.52% for piperacillin, gentamicin, ciprofloxacin, ceftazidime, meropenem, and polymyxin B, respectively. Eighteen percent (36) of the tested isolates exhibited a MDR phenotype. The most MDR strain belonged to epidemic sequence type 235. Comparative genomic analysis of the MDR strain (GenBank: MVDK00000000) with two susceptible strains revealed that the core genes were shared by the three genomes but there were accessory genes that were strain-specific, and this MDR genome had a low CG% (64.6%) content. A prophage sequence and one plasmid were detected in the MDR genome, but amazingly, it contained no resistant genes for drugs with antipseudomonal activity and there was no resistant island. In addition, 67 resistant genes were detected, 19 of them were found only in the MDR genome and 48 genes were efflux pumps, and a novel deleterious point mutation (D87G) was detected in the gyrA gene. The novel deleterious mutation in the gyrA gene (D87G) is a known position behind quinolone resistance. Our findings emphasize the importance of adoption of infection control strategies to prevent dissemination of MDR isolates.
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Affiliation(s)
- Mohamed A Hussain
- Department of Pharmaceutical Microbiology, Faculty of Pharmacy, International University of Africa, Khartoum P.O. Box 2469, Sudan
| | - Malik Suliman Mohamed
- Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka 72388, Saudi Arabia
- Department of Pharmaceutics, Faculty of Pharmacy, University of Khartoum, Khartoum 11111, Sudan
| | - Hisham N Altayb
- Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah 23589, Saudi Arabia
| | - Ahmed Osman Mohamed
- Department of Pharmaceutical Microbiology, Faculty of Pharmacy, International University of Africa, Khartoum P.O. Box 2469, Sudan
| | - Ahmed Ashour
- Department of Pharmacognosy, Faculty of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj 11942, Saudi Arabia
- Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
| | - Wadah Osman
- Department of Pharmacognosy, Faculty of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj 11942, Saudi Arabia
- Department of Pharmacognosy, Faculty of Pharmacy, University of Khartoum, Khartoum 11115, Sudan
| | - Asmaa E Sherif
- Department of Pharmacognosy, Faculty of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj 11942, Saudi Arabia
- Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
| | - Kholoud F Ghazawi
- Clinical Pharmacy Department, College of Pharmacy, Umm Al-Qura University, Makkah 24382, Saudi Arabia
| | - Samar F Miski
- Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Al-Madinah Al-Munawwarah 30078, Saudi Arabia
| | - Sabrin R M Ibrahim
- Department of Chemistry, Preparatory Year Program, Batterjee Medical College, Jeddah 21442, Saudi Arabia
- Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt
| | - Gamal A Mohamed
- Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Ikhlas A Sindi
- Department of Biology, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Ahmad A Alshamrani
- Pharmaceutical Care Department, Ministry of National Guard-Health Affairs, Jeddah 22384, Saudi Arabia
| | - Abdelaziz Elgaml
- Microbiology and Immunology Department, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
- Microbiology and Immunology Department, Faculty of Pharmacy, Horus University, New Damietta 34511, Egypt
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Kim KJ, Yun SG, Cho Y, Nam MH, Ko YJ, Lee CK. Evaluation of a sterile, filter-based, in-house method for rapid direct bacterial identification and antimicrobial susceptibility testing using positive blood culture. Eur J Clin Microbiol Infect Dis 2023; 42:691-700. [PMID: 37012540 DOI: 10.1007/s10096-023-04592-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Accepted: 03/24/2023] [Indexed: 04/05/2023]
Abstract
This study aimed to assess the performance of our in-house method for rapid direct bacterial identification (ID) and antimicrobial susceptibility testing (AST) using a positive blood culture (BC) broth. For Gram-negative bacteria, 4 mL of BC broth was aspirated and passed through a Sartorius Minisart syringe filter with a pore size of 5 µm. The filtrate was then centrifuged and washed. A small volume of the pellet was used for ID, using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and for AST, using automated broth microdilution. For Gram-positive cocci, 4 mL of BC broth was passed through the Minisart syringe filter. Then, 4 mL of sterile distilled water was injected in the direction opposite to that of the filtration to collect the bacterial residue trapped in the filter. Compared with the conventional method performed with pure colonies on agar plates, 94.0% (234/249) were correctly identified using the in-house method, with rates of 91.4% (127/139) and 97.3% (107/110) for Gram-positive and Gram-negative isolates, respectively. Of 234 correctly identified isolates, 230 were assessed by AST. Categorical agreement and essential agreement were 93.3% and 94.5%, respectively, with a minor error rate of 3.8%, a major error rate of 3.4%, and a very major error rate of 1.6%. Our in-house preparation method showed good performance in rapid direct ID and AST using positive BC broths compared to the conventional method. This simple method can shorten the conventional turnaround time for ID and AST by at least 1 day, potentially contributing to better patient management.
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Affiliation(s)
- Keun Ju Kim
- Department of Laboratory Medicine, College of Medicine, Korea University, Seoul, Korea
| | - Seung Gyu Yun
- Department of Laboratory Medicine, College of Medicine, Korea University, Seoul, Korea
| | - Yunjung Cho
- Department of Laboratory Medicine, College of Medicine, Korea University, Seoul, Korea
| | - Myung-Hyun Nam
- Department of Laboratory Medicine, College of Medicine, Korea University, Seoul, Korea
| | - Young Jin Ko
- Department of Laboratory Medicine, College of Medicine, Chosun University, Gwangju, Korea
| | - Chang Kyu Lee
- Department of Laboratory Medicine, College of Medicine, Korea University, Seoul, Korea.
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Maurici M, D’Alò GL, Fontana C, Santoro V, Gaziano R, Ciotti M, Cicciarella Modica D, De Filippis P, Sarmati L, De Carolis G, Pica F. Microbiology and Clinical Outcome of Hospital-Acquired Respiratory Infections in an Italian Teaching Hospital: A Retrospective Study. Healthcare (Basel) 2022; 10:2271. [PMID: 36421594 PMCID: PMC9691183 DOI: 10.3390/healthcare10112271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Revised: 11/03/2022] [Accepted: 11/09/2022] [Indexed: 11/16/2022] Open
Abstract
The burden, microbial etiology and clinical impact of hospital-acquired respiratory infections (HARIs) were determined at an Italian teaching hospital over a 12-month period. For this purpose, overall ordinary hospitalizations ≥ 2 days of subjects over 18 years old with discharge from 1 January 2018 to 31 December 2018 were examined by cross-referencing demographic and clinical data from hospital discharge forms with microbiological data from the computer system of the Microbiology Unit. We identified 329 individuals with HARIs (96 females and 233 males; median age 70 years, range 18−93), who represented ¼ of the total hospital-acquired infections (HAIs) in the period. The inpatient setting was medical and surgical in similar proportions (169 vs. 160, respectively) and the mean hospital stay was 38.9 ± 33.6 days. One hundred and forty patients (42.6% of the total sample) were suffering from one or more chronic diseases. A total of 581 microorganisms (82 antibiotic-resistant and 499 non-resistant) were detected in HARI patients. The most common isolated species were Staphylococcus aureus (16.7%), Klebsiella pneumoniae (13.3%), Pseudomonas spp. (12.6%) and Acinetobacter baumannii (10.5%), followed by Enterobacter spp. (5.3%), Escherichia coli (5.2%) and Enterococcus spp. (4.8%). One hundred and sixty-seven individuals (49.0% of the total) had polymicrobial infections. One hundred thirty-one patients (39.8% of the total) underwent endotracheal intubation and mechanical ventilation and 62.6% of them died, compared to 17.7% of the non-intubated patients. Multivariable analysis confirmed a positive correlation between death and increased age (p = 0.05), surgical MDC (p = 0.007), number of microorganisms over the sample mean (p = 0.001), the presence of chronic diseases (p = 0.046), and intubation and mechanical ventilation (p < 0.0001). A positive correlation between intubation and antibiotic-resistant organisms (p = 0.003) was also found. HARIs are still a major public health problem and require constant surveillance due to their severe clinical outcome.
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Affiliation(s)
- Massimo Maurici
- Department of Biomedicine and Prevention, University of Rome “Tor Vergata”, 00133 Rome, Italy
| | - Gian Loreto D’Alò
- Department of Biomedicine and Prevention, University of Rome “Tor Vergata”, 00133 Rome, Italy
| | - Carla Fontana
- IRCCS Istituto Nazionale per le Malattie Infettive “Lazzaro Spallanzani” (INMI), Via Portuense 292, 00149 Rome, Italy
| | - Viviana Santoro
- Department of Biomedicine and Prevention, University of Rome “Tor Vergata”, 00133 Rome, Italy
| | - Roberta Gaziano
- Department of Experimental Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy
| | - Marco Ciotti
- Laboratory of Microbiology and Virology, Fondazione Policlinico Tor Vergata, 00133 Rome, Italy
| | | | - Patrizia De Filippis
- Department of Biomedicine and Prevention, University of Rome “Tor Vergata”, 00133 Rome, Italy
| | - Loredana Sarmati
- Department of System Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy
| | - Gerardo De Carolis
- Hospital Health Direction, Fondazione Policlinico Tor Vergata, 00133 Rome, Italy
| | - Francesca Pica
- Department of Experimental Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy
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Bharadwaj A, Rastogi A, Pandey S, Gupta S, Sohal JS. Multidrug-Resistant Bacteria: Their Mechanism of Action and Prophylaxis. BIOMED RESEARCH INTERNATIONAL 2022; 2022:5419874. [PMID: 36105930 PMCID: PMC9467707 DOI: 10.1155/2022/5419874] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 07/11/2022] [Accepted: 08/20/2022] [Indexed: 11/18/2022]
Abstract
In the present scenario, resistance to antibiotics is one of the crucial issues related to public health. Earlier, such resistance to antibiotics was limited to nosocomial infections, but it has now become a common phenomenon. Several factors, like extensive development, overexploitation of antibiotics, excessive application of broad-spectrum drugs, and a shortage of target-oriented antimicrobial drugs, could be attributed to this condition. Nowadays, there is a rise in the occurrence of these drug-resistant pathogens due to the availability of a small number of effective antimicrobial agents. It has been estimated that if new novel drugs are not discovered or formulated, there would be no effective antibiotic available to treat these deadly resistant pathogens by 2050. For this reason, we have to look for the formulation of some new novel drugs or other options or substitutes to treat such multidrug-resistant microorganisms (MDR). The current review focuses on the evolution of the most common multidrug-resistant bacteria and discusses how these bacteria escape the effects of targeted antibiotics and become multidrug resistant. In addition, we also discuss some alternative mechanisms to prevent their infection as well.
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Affiliation(s)
- Alok Bharadwaj
- Department of Biotechnology, GLA University, Mathura (U.P.)-281 406, India
| | - Amisha Rastogi
- Department of Biotechnology, GLA University, Mathura (U.P.)-281 406, India
| | - Swadha Pandey
- Department of Biotechnology, GLA University, Mathura (U.P.)-281 406, India
| | - Saurabh Gupta
- Department of Biotechnology, GLA University, Mathura (U.P.)-281 406, India
| | - Jagdip Singh Sohal
- Department of Biotechnology, GLA University, Mathura (U.P.)-281 406, India
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Li H, Maimaitiming M, Zhou Y, Li H, Wang P, Liu Y, Schäberle TF, Liu Z, Wang CY. Discovery of Marine Natural Products as Promising Antibiotics against Pseudomonas aeruginosa. Mar Drugs 2022; 20:192. [PMID: 35323491 PMCID: PMC8954164 DOI: 10.3390/md20030192] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Revised: 03/02/2022] [Accepted: 03/03/2022] [Indexed: 12/29/2022] Open
Abstract
Pseudomonas aeruginosa, one of the most intractable Gram-negative bacteria, has become a public health threat due to its outer polysaccharide layer, efflux transporter system, and high level of biofilm formation, all of which contribute to multi-drug resistance. Even though it is a pathogen of the highest concern, the status of the antibiotic development pipeline is unsatisfactory. In this review, we summarize marine natural products (MNPs) isolated from marine plants, animals, and microorganisms which possess unique structures and promising antibiotic activities against P. aeruginosa. In the last decade, nearly 80 such MNPs, ranging from polyketides to alkaloids, peptides, and terpenoids, have been discovered. Representative compounds exhibited impressive in vitro anti-P. aeruginosa activities with MIC values in the single-digit nanomolar range and in vivo efficacy in infectious mouse models. For some of the compounds, the preliminary structure-activity-relationship (SAR) and anti-bacterial mechanisms of selected compounds were introduced. Compounds that can disrupt biofilm formation or membrane integrity displayed potent inhibition of multi-resistant clinical P. aeruginosa isolates and could be considered as lead compounds for future development. Challenges on how to translate hits into useful candidates for clinical development are also proposed and discussed.
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Affiliation(s)
- Haoran Li
- Institute of Evolution & Marine Biodiversity, School of Medicine and Pharmacy, College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China
- Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China
| | - Mireguli Maimaitiming
- Institute of Evolution & Marine Biodiversity, School of Medicine and Pharmacy, College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China
- Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China
| | - Yue Zhou
- Institute of Evolution & Marine Biodiversity, School of Medicine and Pharmacy, College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China
- Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China
| | - Huaxuan Li
- Institute of Evolution & Marine Biodiversity, School of Medicine and Pharmacy, College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China
- Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China
| | - Pingyuan Wang
- Institute of Evolution & Marine Biodiversity, School of Medicine and Pharmacy, College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China
- Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China
| | - Yang Liu
- Institute for Insect Biotechnology, Justus-Liebig-University Giessen, Ohlebergsweg 12, 35392 Giessen, Germany
| | - Till F Schäberle
- Institute for Insect Biotechnology, Justus-Liebig-University Giessen, Ohlebergsweg 12, 35392 Giessen, Germany
- Branch for Bioresources, Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), 35392 Giessen, Germany
- Partner Site Giessen-Marburg-Langen, German Center for Infection Research (DZIF), 35392 Giessen, Germany
| | - Zhiqing Liu
- Institute of Evolution & Marine Biodiversity, School of Medicine and Pharmacy, College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China
- Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China
| | - Chang-Yun Wang
- Institute of Evolution & Marine Biodiversity, School of Medicine and Pharmacy, College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China
- Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China
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12
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Pseudomonas aeruginosa C-Terminal Processing Protease CtpA Assembles into a Hexameric Structure That Requires Activation by a Spiral-Shaped Lipoprotein-Binding Partner. mBio 2022; 13:e0368021. [PMID: 35038915 PMCID: PMC8764530 DOI: 10.1128/mbio.03680-21] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
Pseudomonas aeruginosa CtpA is a carboxyl-terminal processing protease that partners with the outer membrane lipoprotein LbcA to degrade at least five cell wall-associated proteins, four of which are cell wall hydrolases. This activity plays an important role in supporting P. aeruginosa virulence in a mouse model of acute pneumonia. However, almost nothing is known about the molecular mechanisms underlying CtpA and LbcA function. Here, we used structural analysis to show that CtpA alone assembles into an inactive hexamer comprising a trimer of dimers, which limits its substrate access and prevents nonspecific degradation. The adaptor protein LbcA is a right-handed open spiral with 11 tetratricopeptide repeats, which might wrap around a substrate to deliver it to CtpA for degradation. By structure-guided mutagenesis and functional assays, we also showed that the interfaces of the CtpA trimer of dimers and an N-terminal helix of LbcA are important for LbcA-mediated substrate degradation by CtpA both in vitro and in vivo. This work improves our understanding of the molecular mechanism of the LbcA-CtpA proteolytic system and reveals some striking differences from the arrangements found in some other bacterial CTPs. IMPORTANCE Carboxyl-terminal processing proteases (CTPs) are found in all three domains of life. In bacteria, some CTPs have been associated with virulence, raising the possibility that they could be therapeutic targets. However, relatively little is known about their molecular mechanisms of action. In Pseudomonas aeruginosa, CtpA supports virulence by working in complex with the outer membrane lipoprotein LbcA to degrade cell wall hydrolases. Here, we report structure-function analyses of CtpA and LbcA, which reveals that CtpA assembles into an inactive hexamer comprising a trimer of dimers. LbcA is monomeric, with the first N-terminal helix important for binding to and activating CtpA, followed by a spiral structure composed of 11 tetratricopeptide repeats, which could wrap around a substrate for delivery to CtpA. This work reveals a unique mutimeric arrangement for a CTP and insight into how the important LbcA-CtpA proteolytic system functions.
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Pascale R, Corcione S, Bussini L, Pancaldi L, Giacobbe DR, Ambretti S, Lupia T, Costa C, Marchese A, De Rosa FG, Bassetti M, Viscoli C, Bartoletti M, Giannella M, Viale P. Non-fermentative gram-negative bloodstream infection in northern Italy: a multicenter cohort study. BMC Infect Dis 2021; 21:806. [PMID: 34384380 PMCID: PMC8359066 DOI: 10.1186/s12879-021-06496-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Accepted: 07/29/2021] [Indexed: 12/12/2022] Open
Abstract
Background The management of non-fermentative gram-negative bloodstream infection (NFGN-BSI) offers numerous challenges. In this study the aim is to analyse a large cohort of patients with NFGN-BSI recruited in the northern Italy to describe epidemiology, etiological and susceptibility pattern, therapeutic management and outcome. Methods Multicentre retrospective cohort study of patients hospitalised at three large teaching hospitals in northern Italy in a fourth year period. Results 355 BSI episodes were analyzed, due to P. aeruginosa (72.7%), A. baumannii (16.6%), and Stenotrophomonas maltophilia (10.7%). Overall, 21.4% of isolates were defined as DTR, highest rate among A. baumannii (64.4%). All-cause 30-day mortality rate was 17.5%. Rates of XDR or DTR A. baumannii isolation were significantly higher in non-surviving patients. Independent risk factors for 30-day mortality were: age (HR 1.03, 95%CI 1.00–1.04, p = 0.003), septic shock (HR 2.84, 95%CI 1.67–4.82, p < 0.001) and BSI due to Acinetobacter baumannii (HR 2.23, 95%CI 1.27–3.94, p = 0.005). Conclusion The overall prevalence of DTR was high in the NFGN BSI cohort analyzied, mainly among Acinetobacter baumannii episodes (64.4%). Acinetobacter baumannii is showed to be an independent predictor of mortality. These evidences marked the urgent need of new therapeutic options against this pathogen. Trial registration number: 79/2017/O/OssN. Approved: March14th, 2017. Supplementary Information The online version contains supplementary material available at 10.1186/s12879-021-06496-8.
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Affiliation(s)
- Renato Pascale
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Massarenti 11, 40137, Bologna, Italy.
| | - Silvia Corcione
- Department of Medical Sciences, Infectious Diseases, University of Turin, Turin, Italy
| | - Linda Bussini
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Massarenti 11, 40137, Bologna, Italy
| | - Livia Pancaldi
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Massarenti 11, 40137, Bologna, Italy
| | - Daniele Roberto Giacobbe
- Infectious Diseases Unit, Ospedale Policlinico San Martino-IRCCS, Genoa, Italy.,Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy
| | - Simone Ambretti
- Operative Unit of Clinical Microbiology, Policlinico Sant'Orsola Malpighi, University of Bologna, Bologna, Italy
| | - Tommaso Lupia
- Department of Medical Sciences, Infectious Diseases, University of Turin, Turin, Italy
| | - Cristina Costa
- Department of Public Health and Pediatrics, Laboratory of Microbiology and Virology, Città della Salute e della Scienza Hospital, University of Turin, Turin, Italy
| | - Anna Marchese
- Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Genoa, Italy.,Microbiology Unit, Ospedale Policlinico San Martino-IRCCS, Genoa, Italy
| | | | - Matteo Bassetti
- Infectious Diseases Unit, Ospedale Policlinico San Martino-IRCCS, Genoa, Italy
| | - Claudio Viscoli
- Infectious Diseases Unit, Ospedale Policlinico San Martino-IRCCS, Genoa, Italy
| | - Michele Bartoletti
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Massarenti 11, 40137, Bologna, Italy
| | - Maddalena Giannella
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Massarenti 11, 40137, Bologna, Italy
| | - Pierluigi Viale
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Massarenti 11, 40137, Bologna, Italy
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14
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Álvarez-Marín R, López-Cerero L, Guerrero-Sánchez F, Palop-Borras B, Rojo-Martín MD, Ruiz-Sancho A, Herrero-Rodríguez C, García MV, Lazo-Torres AM, López I, Martín-Hita L, Nuño-Álvarez E, Sánchez-Yebra W, Galán-Sánchez F, Reguera-Iglesias JM, Lepe JA, Peñalva G, Pascual Á, Cisneros JM. Do specific antimicrobial stewardship interventions have an impact on carbapenem resistance in Gram-negative bacilli? A multicentre quasi-experimental ecological study: time-trend analysis and characterization of carbapenemases. J Antimicrob Chemother 2021; 76:1928-1936. [PMID: 33769481 DOI: 10.1093/jac/dkab073] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Accepted: 02/17/2021] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Carbapenem-resistant Gram-negative bacilli (CR-GNB) are among the most threatening microorganisms worldwide and carbapenem use facilitates their spread. Antimicrobial stewardship programmes (ASPs) can help to optimize the use of antibiotics. This study evaluates the impact of a multifaceted educational ASP on carbapenem use and on the epidemiology of CR-GNB. METHODS We conducted a quasi-experimental, time-series study in seven hospitals, from January 2014 to September 2018. The key intervention was composed of educational interviews promoting the appropriate use of carbapenems. The primary endpoints were carbapenem consumption and incidence density (ID) of CR-GNB. All non-duplicated CR-GNB clinical isolates were tested using phenotypic assays and PCR for the presence of carbapenemases. Joinpoint regression and interrupted time-series analyses were used to determine trends. RESULTS A decrease in carbapenem consumption throughout the study period [average quarterly percentage change (AQPC) -1.5%, P < 0.001] and a -8.170 (-16.064 to -0.277) level change following the intervention were observed. The ID of CR-Acinetobacter baumannii decreased (AQPC -3.5%, P = 0.02) and the overall ID of CR-GNB remained stable (AQPC -0.4%, P = 0.52). CR-GNB, CR-Pseudomonas aeruginosa and CR-A. baumannii IDs per hospital correlated with the local consumption of carbapenems. The most prevalent carbapenem resistance mechanisms were OXA-23 for CR-A. baumannii (76.1%), OXA-48 for CR-Klebsiella pneumoniae (66%) and no carbapenemases for CR-P. aeruginosa (91.7%). The epidemiology of carbapenemases was heterogeneous throughout the study, especially for carbapenemase-producing Enterobacteriaceae. CONCLUSIONS In conclusion, a multifaceted, educational interview-based ASP targeting carbapenem prescribing reduced carbapenem use and the ID of CR-A. baumannii.
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Affiliation(s)
- Rocío Álvarez-Marín
- Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, University Hospital Virgen del Rocio/CSIC/University of Seville/Institute of Biomedicine of Seville (IBiS), Seville, Spain
| | - Lorena López-Cerero
- Unit of Infectious Diseases, Microbiology and Preventive Medicine, University Hospital Virgen Macarena, Department of Microbiology, University of Seville, Institute of Biomedicine of Seville (IBiS), Seville, Spain
| | | | - Begoña Palop-Borras
- Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedical Research of Malaga (IBIMA), Regional University Hospital of Malaga, Malaga, Spain
| | | | - Andrés Ruiz-Sancho
- Clinical Unit of Infectious Diseases, Hospital San Cecilio, Granada, Spain
| | | | | | - Ana María Lazo-Torres
- Clinical Unit of Internal Medicine, Department of Infectious Diseases, Hospital Torrecardenas, Almeria, Spain
| | - Inmaculada López
- Unit of Infectious Diseases, Microbiology and Preventive Medicine, University Hospital Virgen Macarena, Department of Microbiology, University of Seville, Institute of Biomedicine of Seville (IBiS), Seville, Spain
| | - Lina Martín-Hita
- Department of Microbiology, Hospital Complex of Jaen, Jaen, Spain
| | - Enrique Nuño-Álvarez
- Clinical Unit of Infectious Diseases, Hospital Virgen de la Victoria, Malaga, Spain
| | | | | | - José María Reguera-Iglesias
- Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedical Research of Malaga (IBIMA), Regional University Hospital of Malaga, Malaga, Spain
| | - José Antonio Lepe
- Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, University Hospital Virgen del Rocio/CSIC/University of Seville/Institute of Biomedicine of Seville (IBiS), Seville, Spain
| | - Germán Peñalva
- Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, University Hospital Virgen del Rocio/CSIC/University of Seville/Institute of Biomedicine of Seville (IBiS), Seville, Spain
| | - Álvaro Pascual
- Unit of Infectious Diseases, Microbiology and Preventive Medicine, University Hospital Virgen Macarena, Department of Microbiology, University of Seville, Institute of Biomedicine of Seville (IBiS), Seville, Spain
| | - José Miguel Cisneros
- Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, University Hospital Virgen del Rocio/CSIC/University of Seville/Institute of Biomedicine of Seville (IBiS), Seville, Spain
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Kousovista R, Athanasiou C, Liaskonis K, Ivopoulou O, Ismailos G, Karalis V. Correlation between Acinetobacter baumannii Resistance and Hospital Use of Meropenem, Cefepime, and Ciprofloxacin: Time Series Analysis and Dynamic Regression Models. Pathogens 2021; 10:pathogens10040480. [PMID: 33920945 PMCID: PMC8071258 DOI: 10.3390/pathogens10040480] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 04/06/2021] [Accepted: 04/09/2021] [Indexed: 12/02/2022] Open
Abstract
Acinetobacter baumannii is one of the most difficult-to-treat pathogens worldwide, due to developed resistance. The aim of this study was to evaluate the use of widely prescribed antimicrobials and the respective resistance rates of A. baumannii, and to explore the relationship between antimicrobial use and the emergence of A. baumannii resistance in a tertiary care hospital. Monthly data on A. baumannii susceptibility rates and antimicrobial use, between January 2014 and December 2017, were analyzed using time series analysis (Autoregressive Integrated Moving Average (ARIMA) models) and dynamic regression models. Temporal correlations between meropenem, cefepime, and ciprofloxacin use and the corresponding rates of A. baumannii resistance were documented. The results of ARIMA models showed statistically significant correlation between meropenem use and the detection rate of meropenem-resistant A. baumannii with a lag of two months (p = 0.024). A positive association, with one month lag, was identified between cefepime use and cefepime-resistant A. baumannii (p = 0.028), as well as between ciprofloxacin use and its resistance (p < 0.001). The dynamic regression models offered explanation of variance for the resistance rates (R2 > 0.60). The magnitude of the effect on resistance for each antimicrobial agent differed significantly.
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Affiliation(s)
- Rania Kousovista
- Department of Mathematics, University of Crete, Heraklion, 70013 Crete, Greece;
| | - Christos Athanasiou
- Pharmacy Department, General Military Hospital of Athens, 11525 Athens, Greece;
| | - Konstantinos Liaskonis
- Department of Medical Biopathology, General Military Hospital of Athens, 11525 Athens, Greece; (K.L.); (O.I.)
| | - Olga Ivopoulou
- Department of Medical Biopathology, General Military Hospital of Athens, 11525 Athens, Greece; (K.L.); (O.I.)
| | - George Ismailos
- Experimental-Research Center ELPEN, ELPEN Pharmaceuticals, Pikermi, 19009 Attika, Greece;
| | - Vangelis Karalis
- Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, 15784 Athens, Greece
- Correspondence: ; Tel.: +30-210-727-4267
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16
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Association of Antibiotic Use with the Resistance Epidemiology of Pseudomonas aeruginosa in a Hospital Setting: A Four-Year Retrospective Time Series Analysis. Sci Pharm 2021. [DOI: 10.3390/scipharm89010013] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Background: Even though, Pseudomonas aeruginosa is a common cause of hospital-acquired infections, treatment is challenging because of decreasing rates of susceptibility to many broad-spectrum antibiotics. Methods: Consumption data of eight broad spectrum antimicrobial agents and resistance rates of P. aeruginosa were collected for 48 consecutive months. Autoregressive integrated moving average (ARIMA) and transfer functions models were used to develop relationships between antibiotic use and resistance. Results: Positive correlations between P. aeruginosa resistance and uses of ciprofloxacin (p < 0.001), meropenem (p < 0.001), and cefepime (p = 0.005) were identified. Transfer function models showed the quantified effect of each of these antibiotics on resistance. Regarding levofloxacin, ceftazidime, piperacillin/tazobactam and imipenem, no significant relationships were found. For ceftazidime and levofloxacin, this was probably due to their low consumption, while for imipenem the reason can possibly be ascribed to the already high established P. aeruginosa resistance in the hospital. Conclusion: In the hospital setting, the effect of antimicrobial agents’ consumption on the susceptibility epidemiology of P. aeruginosa differs significantly for each one of them. In this study, the role of precedent use of meropenem, cefepime and ciprofloxacin was quantified in the development of P. aeruginosa resistance.
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Quorum quenching by 2-Hydroxyanisole extracted from Solanum torvum on Pseudomonas aeruginosa and its inhibitory action upon LasR protein. GENE REPORTS 2020. [DOI: 10.1016/j.genrep.2020.100802] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
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18
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Kula BE, Hudson D, Sligl WI. Pseudomonas aeruginosa infection in intensive care: Epidemiology, outcomes, and antimicrobial susceptibilities. JOURNAL OF THE ASSOCIATION OF MEDICAL MICROBIOLOGY AND INFECTIOUS DISEASE CANADA = JOURNAL OFFICIEL DE L'ASSOCIATION POUR LA MICROBIOLOGIE MEDICALE ET L'INFECTIOLOGIE CANADA 2020; 5:130-138. [PMID: 36341317 PMCID: PMC9608728 DOI: 10.3138/jammi-2020-0003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/11/2020] [Accepted: 06/05/2020] [Indexed: 06/16/2023]
Abstract
BACKGROUND Pseudomonas aeruginosa (PA) infection in the intensive care unit (ICU) contributes to substantial mortality. In this study, we describe the epidemiology, antimicrobial susceptibilities, and outcomes of ICU patients with pseudomonal infection. METHODS ICU patients with PA were identified and classified as colonized or infected. Infected patients were reviewed for source, patient characteristics, antimicrobial susceptibilities, appropriateness of empiric antimicrobial therapy, and 30-day mortality. Independent predictors of mortality were identified using multivariable logistic regression. RESULTS One hundred forty (71%) patients with PA were infected. Mean patient age was 55 (SD 18) years; 62% were male. Admission categories included medical (71%), surgical (20%), and trauma or neurological (9%). Mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 19 (SD 10). One hundred twenty-six (90%) patients were mechanically ventilated, 102 (73%) required vasopressors, and 27 (19%) received renal replacement; 32 (23%) died within 30 days. Infection was nosocomial in 101 (72%) cases. Sources were respiratory (66%), skin-soft tissue (11%), urinary (10%), blood (5%), surgical (5%), gastrointestinal (2%), or unknown (1%). Twenty (14%) isolates were multi-drug resistant; 6 (4%) were extensively drug resistant. Empiric antimicrobial therapy was effective in 97 (69%) cases. Liver disease (adjusted OR [aOR] 6.2, 95% CI 1.5 to 25.7; p = 0.01), malignancy (aOR 5.0, 95% CI 1.5 to 17.3; p = 0.01), and higher APACHE II score (aOR 1.1, 95% CI 1.0 to 1.1; p = 0.02) were independently associated with 30-day mortality. CONCLUSIONS PA infection in ICU is most commonly respiratory and associated with substantial mortality. Existing malignancy, liver disease, and higher APACHE II score were independently associated with mortality.
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Affiliation(s)
- Brittany E Kula
- Division of Internal Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
| | - Darren Hudson
- Department of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
| | - Wendy I Sligl
- Department of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
- Division of Infectious Diseases, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
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19
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Abstract
Multidrug-resistant bacteria are among the most important current threats to public health. Typically, they are associated with nosocomial infections. However, some have become prevalent causes of community-acquired infections, such as Neisseria gonorrhoeae, Shigella, Salmonella, and Streptococcus pneumoniae. The community spread of multidrug-resistant bacteria is also a crucial development. An important global threat on the horizon is represented by production of carbapenemases by community-acquired hypervirulent Klebsiella pneumoniae. Such strains have already been found in Asia, Europe, and North America. Prevention of further community spread of multidrug-resistant bacteria is of the utmost importance, and will require a multidisciplinary approach involving all stakeholders.
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20
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Chen Q, Lu W, Zhou D, Zheng G, Liu H, Qian C, Zhou W, Lu J, Ni L, Bao Q, Li A, Xu T, Xu H. Characterization of Two Macrolide Resistance-Related Genes in Multidrug-Resistant Pseudomonas aeruginosa Isolates. Pol J Microbiol 2020; 69:349-356. [PMID: 33574864 PMCID: PMC7810118 DOI: 10.33073/pjm-2020-038] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Revised: 07/31/2020] [Accepted: 08/15/2020] [Indexed: 11/05/2022] Open
Abstract
In analyzing the drug resistance phenotype and mechanism of resistance to macrolide antibiotics of clinical Pseudomonas aeruginosa isolates, the agar dilution method was used to determine the minimum inhibitory concentrations (MICs), and PCR (polymerase chain reaction) was applied to screen for macrolide antibiotics resistance genes. The macrolide antibiotics resistance genes were cloned, and their functions were identified. Of the 13 antibiotics tested, P. aeruginosa strains showed high resistance rates (ranging from 69.5-82.1%), and MIC levels (MIC90 > 256 μg/ml) to macrolide antibiotics. Of the 131 known macrolide resistance genes, only two genes, mphE and msrE, were identified in 262 clinical P. aeruginosa isolates. Four strains (1.53%, 4/262) carried both the msrE and mphE genes, and an additional three strains (1.15%, 3/262) harbored the mphE gene alone. The cloned msrE and mphE genes conferred higher resistance levels to three second-generation macrolides compared to two first-generation ones. Analysis of MsrE and MphE protein polymorphisms revealed that they are highly conserved, with only 1-3 amino acids differences between the proteins of the same type. It can be concluded that even though the strains showed high resistance levels to macrolides, known macrolide resistance genes are seldom present in clinical P. aeruginosa strains, demonstrating that a mechanism other than this warranted by the mphE and msrE genes may play a more critical role in the bacteria's resistance to macrolides.
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Affiliation(s)
- Qing Chen
- The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, China
| | - Wei Lu
- School of Laboratory Medicine and Life Science, Institute of Biomedical Informatics, Wenzhou Medical University, Wenzhou, China
| | - Danying Zhou
- School of Laboratory Medicine and Life Science, Institute of Biomedical Informatics, Wenzhou Medical University, Wenzhou, China
| | - Guotong Zheng
- The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, China
| | - Hongmao Liu
- The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, China
| | - Changrui Qian
- School of Laboratory Medicine and Life Science, Institute of Biomedical Informatics, Wenzhou Medical University, Wenzhou, China
| | - Wangxiao Zhou
- School of Laboratory Medicine and Life Science, Institute of Biomedical Informatics, Wenzhou Medical University, Wenzhou, China
| | - Junwan Lu
- School of Laboratory Medicine and Life Science, Institute of Biomedical Informatics, Wenzhou Medical University, Wenzhou, China
| | - Liyan Ni
- The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, China
| | - Qiyu Bao
- School of Laboratory Medicine and Life Science, Institute of Biomedical Informatics, Wenzhou Medical University, Wenzhou, China
| | - Aifang Li
- The Fifth Affiliated Hospital, Wenzhou Medical University, Lishui, Zhejiang, China
| | - Teng Xu
- Institute of Translational Medicine, Baotou Central Hospital, Baotou, China
| | - Haili Xu
- The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, China
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21
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Gebremariam T, Zhang L, Alkhazraji S, Gu Y, Youssef EG, Tong Z, Kish-Trier E, Bajji A, de Araujo CV, Rich B, French SW, Li DY, Mueller AL, Odelberg SJ, Zhu W, Ibrahim AS. Preserving Vascular Integrity Protects Mice against Multidrug-Resistant Gram-Negative Bacterial Infection. Antimicrob Agents Chemother 2020; 64:e00303-20. [PMID: 32393494 PMCID: PMC7526831 DOI: 10.1128/aac.00303-20] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2020] [Accepted: 05/01/2020] [Indexed: 12/29/2022] Open
Abstract
The rise in multidrug-resistant (MDR) organisms portends a serious global threat to the health care system with nearly untreatable infectious diseases, including pneumonia and its often fatal sequelae, acute respiratory distress syndrome (ARDS) and sepsis. Gram-negative bacteria (GNB), including Acinetobacter baumannii, Pseudomonas aeruginosa, and carbapenemase-producing Klebsiella pneumoniae (CPKP), are among the World Health Organization's and National Institutes of Health's high-priority MDR pathogens for targeted development of new therapies. Here, we show that stabilizing the host's vasculature by genetic deletion or pharmacological inhibition of the small GTPase ADP-ribosylation factor 6 (ARF6) increases survival rates of mice infected with A. baumannii, P. aeruginosa, and CPKP. We show that the pharmacological inhibition of ARF6-GTP phenocopies endothelium-specific Arf6 disruption in enhancing the survival of mice with A. baumannii pneumonia, suggesting that inhibition is on target. Finally, we show that the mechanism of protection elicited by these small-molecule inhibitors acts by the restoration of vascular integrity disrupted by GNB lipopolysaccharide (LPS) activation of the TLR4/MyD88/ARNO/ARF6 pathway. By targeting the host's vasculature with small-molecule inhibitors of ARF6 activation, we circumvent microbial drug resistance and provide a potential alternative/adjunctive treatment for emerging and reemerging pathogens.
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Affiliation(s)
- Teclegiorgis Gebremariam
- The Lundquist Institute for Biomedical Innovations at Harbor-University of California Los Angeles (UCLA) Medical Center, Torrance, California, USA
| | - Lina Zhang
- The Lundquist Institute for Biomedical Innovations at Harbor-University of California Los Angeles (UCLA) Medical Center, Torrance, California, USA
- College of Wildlife Resources, Northeast Forestry University, Harbin, China
| | - Sondus Alkhazraji
- The Lundquist Institute for Biomedical Innovations at Harbor-University of California Los Angeles (UCLA) Medical Center, Torrance, California, USA
| | - Yiyou Gu
- The Lundquist Institute for Biomedical Innovations at Harbor-University of California Los Angeles (UCLA) Medical Center, Torrance, California, USA
| | - Eman G Youssef
- The Lundquist Institute for Biomedical Innovations at Harbor-University of California Los Angeles (UCLA) Medical Center, Torrance, California, USA
- Faculty of Postgraduate Studies for Advanced Sciences, Beni-Suef University, Beni-Suef, Egypt
| | | | | | - Ashok Bajji
- A6 Pharmaceuticals, Salt Lake City, Utah, USA
| | - Claudia V de Araujo
- Department of Internal Medicine, University of Utah, Salt Lake City, Utah, USA
| | - Bianca Rich
- Department of Internal Medicine, University of Utah, Salt Lake City, Utah, USA
| | - Samuel W French
- The Lundquist Institute for Biomedical Innovations at Harbor-University of California Los Angeles (UCLA) Medical Center, Torrance, California, USA
- David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Dean Y Li
- A6 Pharmaceuticals, Salt Lake City, Utah, USA
- Department of Internal Medicine, University of Utah, Salt Lake City, Utah, USA
- Department of Human Genetics, University of Utah, Salt Lake City, Utah, USA
- Department of Oncological Sciences, University of Utah, Salt Lake City, Utah, USA
| | | | - Shannon J Odelberg
- Department of Internal Medicine, University of Utah, Salt Lake City, Utah, USA
| | - Weiquan Zhu
- Department of Internal Medicine, University of Utah, Salt Lake City, Utah, USA
| | - Ashraf S Ibrahim
- The Lundquist Institute for Biomedical Innovations at Harbor-University of California Los Angeles (UCLA) Medical Center, Torrance, California, USA
- David Geffen School of Medicine at UCLA, Los Angeles, California, USA
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22
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Gong Z, Li J, Luo H, Zhan D, Liu X, Gao C, Huang J, Qian Y, Song Y, Quan W, An S, Tian Y, Hu Z, Sun J, Yuan H, Jiang R. Low-temperature laminar flow ward for the treatment of multidrug resistance Acinetobacter baumannii pneumonia. Eur J Clin Microbiol Infect Dis 2020; 39:877-887. [PMID: 31898800 PMCID: PMC7223702 DOI: 10.1007/s10096-019-03790-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2019] [Accepted: 12/04/2019] [Indexed: 01/17/2023]
Abstract
This study was designed to investigate the effect of low-temperature laminar flow ward (LTLFW) on the Acinetobacter baumannii pneumonia (MDR-ABP) in neurosurgical intensive care unit (NICU) patients. We evaluated whether patients in a LTLFW had significantly improved clinical outcomes as compared to those in nonconstant-temperature NICU (room temperature). The association of temperature with the prevalence of ABP and A. baumannii isolates (ABI) found in NICU patients was specifically investigated. In vitro microbiological experiments were conducted to measure the proliferation, antibiotic sensitivity, and genomic profiles of A. baumannii (AB) that grew in variable temperatures. MDR-ABP patients in LTLFW had significantly improved outcomes than those in the room temperature NICU. In addition, the numbers of ABI were positively associated with mean ambient outdoor temperatures (P = 0.002), with the incidence of ABP and average numbers of ABI among NICU patients being substantially lower in the winter as compared to other seasons. However, there were no significant seasonal variations in the other strains of the top five bacteria. Consistent with these clinical observations, AB growing at 20°C and 25°C had significantly reduced viability and antibiotic resistance compared to those growing at 35°C. The expression of genes related to AB survival ability, drug resistance, and virulence also differed between AB growing at 20°C and those at 35°C. LTLFW is effective in promoting the recovery of MDR-ABP patients because low temperatures reduced the density and virulence of AB and enhanced the efficacy of antibiotics, likely at the genetic level.
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Affiliation(s)
- Zhitao Gong
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 300052, China
- Tianjin Neurological Institute, Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, 300052, China
| | | | - Hongliang Luo
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 300052, China
- Tianjin Neurological Institute, Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, 300052, China
| | - Daqiang Zhan
- Tianjin Neurological Institute, Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, 300052, China
- Department of Pharmacy, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, 300052, China
| | - Xuanhui Liu
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 300052, China
- Tianjin Neurological Institute, Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, 300052, China
| | - Chuang Gao
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 300052, China
- Tianjin Neurological Institute, Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, 300052, China
| | - Jinhao Huang
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 300052, China
- Tianjin Neurological Institute, Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, 300052, China
| | - Yu Qian
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 300052, China
- Tianjin Neurological Institute, Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, 300052, China
| | - Yiming Song
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 300052, China
- Tianjin Neurological Institute, Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, 300052, China
| | - Wei Quan
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 300052, China
- Tianjin Neurological Institute, Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, 300052, China
| | - Shuo An
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 300052, China
- Tianjin Neurological Institute, Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, 300052, China
| | - Ye Tian
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 300052, China
- Tianjin Neurological Institute, Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, 300052, China
| | - Zhidong Hu
- Department of clinical laboratories, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, 300052, China
| | - Jian Sun
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 300052, China
- Tianjin Neurological Institute, Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, 300052, China
| | - Hengjie Yuan
- Tianjin Neurological Institute, Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, 300052, China.
- Department of Pharmacy, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, 300052, China.
| | - Rongcai Jiang
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 300052, China.
- Tianjin Neurological Institute, Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, 300052, China.
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23
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Propolis Extract: A Possible Antiseptic Oral Care against Multidrug-Resistant Non-Fermenting Bacteria Isolated from Non-Ventilator Hospital-Acquired Pneumonia. JOURNAL OF PURE AND APPLIED MICROBIOLOGY 2020. [DOI: 10.22207/jpam.14.1.13] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
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24
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Khan MI, Xu S, Ali MM, Ali R, Kazmi A, Akhtar N, Bilal M, Hu Y, Li F. Assessment of multidrug resistance in bacterial isolates from urinary tract-infected patients. JOURNAL OF RADIATION RESEARCH AND APPLIED SCIENCES 2020. [DOI: 10.1080/16878507.2020.1730579] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Affiliation(s)
- Muhammad Imran Khan
- Hefei National Lab for Physical Sciences at the Microscale and the Centers for Biomedical Engineering, University of Science and Technology of China, Hefei, Anhui, China
- Pathology Department, Rawalpindi Medical University, Rawalpindi, Pakistan
| | - Surui Xu
- Hefei National Lab for Physical Sciences at the Microscale and the Centers for Biomedical Engineering, University of Science and Technology of China, Hefei, Anhui, China
| | - Malik Mubashar Ali
- Pathology Department, Rawalpindi Medical University, Rawalpindi, Pakistan
| | - Rizwan Ali
- Hefei National Lab for Physical Sciences at the Microscale and the Centers for Biomedical Engineering, University of Science and Technology of China, Hefei, Anhui, China
| | - Ahsan Kazmi
- Pathology Department, Al-Nafees Medical College and Hospital, Isra University, Islamabad, Pakistan
| | - Naeem Akhtar
- Pathology Department, Rawalpindi Medical University, Rawalpindi, Pakistan
| | - Muhammad Bilal
- School of Life Science and Food Engineering, Huaiyin Institute of Technology, Huaian, China
| | - Yi Hu
- Hefei National Lab for Physical Sciences at the Microscale and the Centers for Biomedical Engineering, University of Science and Technology of China, Hefei, Anhui, China
| | - Fenfen Li
- Hefei National Lab for Physical Sciences at the Microscale and the Centers for Biomedical Engineering, University of Science and Technology of China, Hefei, Anhui, China
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25
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Kamali M, Manshouri S, Bagheri Y, Rostami M, Karkhaneh Mahmoudi M, Moradnejad P, Seif F. Prevalence and antibiotic resistance of Acinetobacter baumannii among patients in postcardiac surgery intensive care units of Rajaei Hospital, Tehran. Med J Islam Repub Iran 2020; 34:4. [PMID: 32284928 PMCID: PMC7139260 DOI: 10.34171/mjiri.34.4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Indexed: 12/30/2022] Open
Abstract
Background: Acinetobacter baumannii is an opportunistic, aerobic, nonfermentative, Gram-negative bacterium that can cause major nosocomial infections, especially in patients hospitalized in intensive care units (ICU). Recently, A. baumannii strains have been resistant to a variety of antibiotics. Thus, it was aimed to evaluate the prevalence of A. baumannii and their resistance to the antibiotics in the patients hospitalized in postcardiac surgery ICU. Methods: This retrospective cross sectional study was performed in Rajaei hospital between March 2014 and February 2016. A. baumannii strains were isolated from blood cultures, catheter cultures, sputum cultures, and wound smear cultures. Then, isolates were characterized using standard morphological, cultural, and biochemical properties according to CLSI 2016. The frequency of A. baumannii species were reported as percent. Results: Among 27 167 patients were admitted to the ICU, 113 individuals, including 55 males and 58 females, were identified as A. baumannii-infected and the prevalence rate was 0.42%. The highest rates of antibiotic sensitivity were related to Meropenem 20 (17.7%) and Colistin 16 (14.1%). The shortest length of stay (LOS) for patients with A. baumanniiin the ICU was 3 days, while the longest LOS was 98 days. Conclusion: The findings indicated that A. baumannii strains isolated from postcardiac surgery ICUs had a high prevalence and were sensitive to Meropenem and Colistin. However, new molecular-based techniques are needed to monitor nosocomial infections. Therefore, the treatment of the patients may be feasible by appropriate antibiotic therapy, and infection control policies will be improved by adopting precise disinfection strategies.
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Affiliation(s)
- Monireh Kamali
- Rajaei Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Shirin Manshouri
- Rajaei Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Yasser Bagheri
- Immunology Research Center, Institute of Immunology and infectious Diseases, Iran University of Medical Sciences, Tehran, Iran.,Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Masoumeh Rostami
- Rajaei Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Mahdi Karkhaneh Mahmoudi
- Rajaei Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Pardis Moradnejad
- Rajaei Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Farhad Seif
- Neuroscience Research Center, Iran University of Medical Sciences, Tehran, Iran.,Academic Center for Education, Culture, and Research, Tehran, Iran
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26
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Santajit S, Seesuay W, Mahasongkram K, Sookrung N, Ampawong S, Reamtong O, Diraphat P, Chaicumpa W, Indrawattana N. Human single-chain antibodies that neutralize Pseudomonas aeruginosa-exotoxin A-mediated cellular apoptosis. Sci Rep 2019; 9:14928. [PMID: 31624289 PMCID: PMC6797803 DOI: 10.1038/s41598-019-51089-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2019] [Accepted: 09/23/2019] [Indexed: 01/20/2023] Open
Abstract
Targeting bacterial virulence factors directly provides a new paradigm for the intervention and treatment of bacterial diseases. Pseudomonas aeruginosa produces a myriad of virulence factors to cause fatal diseases in humans. In this study, human single-chain antibodies (HuscFvs) that bound to P. aeruginosa exotoxin A (ETA) were generated by phage display technology using recombinant ETA, ETA-subdomains and the synthetic peptide of the ETA-catalytic site as baits for selecting ETA-bound-phages from the human-scFv phage display library. ETA-bound HuscFvs derived from three phage-transfected E. coli clones neutralized the ETA-induced mammalian cell apoptosis. Computerized simulation demonstrated that these HuscFvs used several residues in their complementarity-determining regions (CDRs) to form contact interfaces with the critical residues in ETA-catalytic domain essential for ADP-ribosylation of eukaryotic elongation factor 2, which should consequently rescue ETA-exposed-cells from apoptosis. The HuscFv-treated ETA-exposed cells also showed decremented apoptosis-related genes, i.e., cas3 and p53. The effective HuscFvs have high potential for future evaluation in animal models and clinical trials as a safe, novel remedy for the amelioration of exotoxin A-mediated pathogenesis. HuscFvs may be used either singly or in combination with the HuscFv cognates that target other P. aeruginosa virulence factors as an alternative therapeutic regime for difficult-to-treat infections.
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Affiliation(s)
- Sirijan Santajit
- Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Watee Seesuay
- Center of Research Excellence on Therapeutic Proteins and Antibody Engineering, Department of Parasitology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Kodchakorn Mahasongkram
- Center of Research Excellence on Therapeutic Proteins and Antibody Engineering, Department of Parasitology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Nitat Sookrung
- Center of Research Excellence on Therapeutic Proteins and Antibody Engineering, Department of Parasitology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
- Biomedical Research Incubator Unit, Department of Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Sumate Ampawong
- Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Onrapak Reamtong
- Department of Tropical Molecular Biology and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Pornphan Diraphat
- Department of Microbiology, Faculty of Public Health, Mahidol University, Bangkok, Thailand
| | - Wanpen Chaicumpa
- Center of Research Excellence on Therapeutic Proteins and Antibody Engineering, Department of Parasitology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Nitaya Indrawattana
- Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
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27
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Pourakbari B, Movahedi Z, Mahmoudi S, Sabouni F, Ashtiani MTH, Sadeghi RH, Mamishi S. Genotypic characteristics of Pseudomonas aeruginosa strains circulating in the tertiary referral Children's Medical Hospital in Tehran, Iran. Br J Biomed Sci 2019. [DOI: 10.1080/09674845.2012.12069147] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Affiliation(s)
- B. Pourakbari
- Pediatrics Infectious Diseases Research Center, Tehran University of Medical Sciences
| | - Z. Movahedi
- Department of Infectious Disease, School of Medicine, Qom University of Medical Sciences
| | - S. Mahmoudi
- Pediatrics Infectious Diseases Research Center, Tehran University of Medical Sciences
| | - F. Sabouni
- Department of Pediatric Infectious Disease, School of Medicine Tehran University of Medical Sciences
| | - M. T. H. Ashtiani
- Department of Pathology, School of Medicine, Tehran University of Medical Sciences, Iran
| | - R. H. Sadeghi
- Pediatrics Infectious Diseases Research Center, Tehran University of Medical Sciences
| | - S. Mamishi
- Pediatrics Infectious Diseases Research Center, Tehran University of Medical Sciences
- Department of Pediatric Infectious Disease, School of Medicine Tehran University of Medical Sciences
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28
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Saurav K, Macho M, Kust A, Delawská K, Hájek J, Hrouzek P. Antimicrobial activity and bioactive profiling of heterocytous cyanobacterial strains using MS/MS-based molecular networking. Folia Microbiol (Praha) 2019; 64:645-654. [PMID: 31385159 DOI: 10.1007/s12223-019-00737-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Accepted: 07/15/2019] [Indexed: 12/11/2022]
Abstract
The rapid emergence of resistance in pathogenic bacteria together with a steep decline in economic incentives has rendered a new wave in the drug development by the pharmaceutical industry and researchers. Since cyanobacteria are recognized as wide producers of pharmaceutically important compounds, we investigated thirty-four cyanobacterial extracts prepared by solvents of different polarities for their antimicrobial potential. Almost all tested cyanobacterial strains exhibited some degree of antimicrobial bioactivity, with more general effect on fungal strains compared with bacteria. Surprisingly ~50% of cyanobacterial extracts exhibited specific activity against one or few bacterial indicator strains with Gram-positive bacteria being more affected. Extracts of two most promising strains were subjected to activity-guided fractionation and determination of the minimum inhibitory concentration (MIC) against selected bacterial and fungal isolates. Multiple fractions were responsible for their antimicrobial effect with MIC reaching low-micromolar concentrations and in some of them high level of specificity was recorded. Twenty-six bioactive fractions analyzed on LC-HRMS/MS and Global Natural Product Social Molecular Networking (GNPS) online workflow using dereplication resulted in identification of only forty-nine peptide spectrum matches (PSMs) with eleven unique metabolites spectrum matches (MSMs). Interestingly, only three fractions from Nostoc calcicola Lukešová 3/97 and four fractions from Desmonostoc sp. Cc2 showed the presence of unique MSMs suggesting the presence of unknown antimicrobial metabolites among majority of bioactive fractions from both the strains. Our results highlight potential for isolation and discovery of potential antimicrobial bioactive lead molecules from cyanobacterial extracts.
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Affiliation(s)
- Kumar Saurav
- Laboratory of Algal Biotechnology-Centre Algatech, Institute of Microbiology of the Czech Academy of Sciences, Opatovický mlýn, Novohradská 237, 379 81, Třeboň, Czech Republic
| | - Markéta Macho
- Laboratory of Algal Biotechnology-Centre Algatech, Institute of Microbiology of the Czech Academy of Sciences, Opatovický mlýn, Novohradská 237, 379 81, Třeboň, Czech Republic
| | - Andreja Kust
- Laboratory of Algal Biotechnology-Centre Algatech, Institute of Microbiology of the Czech Academy of Sciences, Opatovický mlýn, Novohradská 237, 379 81, Třeboň, Czech Republic.,The Czech Academy of Sciences, Biology Centre, Institute of Hydrobiology, Na Sádkách 702/7, 370 05, České Budějovice, Czech Republic
| | - Kateřina Delawská
- Laboratory of Algal Biotechnology-Centre Algatech, Institute of Microbiology of the Czech Academy of Sciences, Opatovický mlýn, Novohradská 237, 379 81, Třeboň, Czech Republic
| | - Jan Hájek
- Laboratory of Algal Biotechnology-Centre Algatech, Institute of Microbiology of the Czech Academy of Sciences, Opatovický mlýn, Novohradská 237, 379 81, Třeboň, Czech Republic
| | - Pavel Hrouzek
- Laboratory of Algal Biotechnology-Centre Algatech, Institute of Microbiology of the Czech Academy of Sciences, Opatovický mlýn, Novohradská 237, 379 81, Třeboň, Czech Republic.
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29
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Peri AM, Doi Y, Potoski BA, Harris PNA, Paterson DL, Righi E. Antimicrobial treatment challenges in the era of carbapenem resistance. Diagn Microbiol Infect Dis 2019; 94:413-425. [PMID: 30905487 DOI: 10.1016/j.diagmicrobio.2019.01.020] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2017] [Revised: 01/14/2019] [Accepted: 01/28/2019] [Indexed: 12/22/2022]
Abstract
Infections due to carbapenem-resistant Gram-negative bacteria are burdened by high mortality and represent an urgent threat to address. Clinicians are currently at a dawn of a new era in which antibiotic resistance in Gram-negative bacilli is being dealt with by the availability of the first new antibiotics in this field for many years. Although new antibiotics have shown promising results in clinical trials, there is still uncertainty over whether their use will improve clinical outcomes in real world practice. Some observational studies have reported a survival benefit in carbapenem-resistant Enterobacteriaceae bloodstream infections using combination therapy, often including "old" antibiotics such as colistin, aminoglycosides, tigecycline, and carbapenems. These regimens, however, are linked to increased risk of antimicrobial resistance, and their efficacy has yet to be compared to new antimicrobial options. While awaiting more definitive evidence, antibiotic stewards need clear direction on how to optimize the use of old and novel antibiotic options. Furthermore, carbapenem-sparing regimens should be carefully considered as a potential tool to reduce selective antimicrobial pressure.
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Affiliation(s)
- Anna Maria Peri
- Infectious Diseases Unit, Department of Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Italy; The University of Queensland Centre for Clinical Research (UQCCR), Royal Brisbane and Women's Hospital, Herston, QLD, Australia
| | - Yohei Doi
- Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Brian A Potoski
- Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, PA, USA
| | - Patrick N A Harris
- The University of Queensland Centre for Clinical Research (UQCCR), Royal Brisbane and Women's Hospital, Herston, QLD, Australia
| | - David L Paterson
- The University of Queensland Centre for Clinical Research (UQCCR), Royal Brisbane and Women's Hospital, Herston, QLD, Australia
| | - Elda Righi
- The University of Queensland Centre for Clinical Research (UQCCR), Royal Brisbane and Women's Hospital, Herston, QLD, Australia; Infectious Diseases, Department of Diagnostics and Public Health, University of Verona, Italy.
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30
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Petrova AP, Stanimirova ID, Ivanov IN, Petrov MM, Miteva-Katrandzhieva TM, Grivnev VI, Kardjeva VS, Kantardzhiev TV, Murdjeva MA. Carbapenemase Production of Clinical Isolates Acinetobacter baumannii and Pseudomonas aeruginosa from a Bulgarian University Hospital. Folia Med (Plovdiv) 2019; 59:413-422. [PMID: 29341954 DOI: 10.1515/folmed-2017-0060] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2017] [Accepted: 05/23/2017] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND Production of Bla OXA-23, OXA-24, OXA-58 and hyperexpression of OXA-51 due to ISAba1 insertion sequence are the leading causes of carbapenem resistance in Acinetobacter baumannii. The loss of OprD transmembrane protein and the overexpression of some effl ux pumps are considered to be the main factors for carbapenem resistance in Pseudomonas aeruginosa whereas metallo-enzymes' production has a secondary role. AIM Тo examine the carbapenem resistance due to carbapenemase production among clinically signifi cant Gram-negative non-fermenters from St George University hospital, Plovdiv: A. baumannii and P. aeruginosa. MATERIALS AND METHODS Forty three A. baumannii and 43 P. aeruginosa isolates, resistant or with intermediate resistance to imipenem and/or meropenem were included in the study. They were collected from patients admitted in 14 various hospital wards between 2010 and 2014. Both phenotypic and genetic methods were used for identifi cation and antimicrobial susceptibility testing. RESULTS All A. baumannii demonstrated carbapenemase production determined by a modifi ed Hodge test whereas P. aeruginosa isolates did not show this phenomenon. OXA-23 genes were determined in 97.7% (42 out of 43) of A. baumannii isolates indistinguishable from the sequence of the classical ARI-1 gene. OXA-24, OXA-58 and overexpression of OXA-51 were not registered in any of the isolates. All P. aeruginosa were negative for blaVIM and blaIMP genes. CONCLUSION The leading cause of carbapenem resistance in A. baumannii isolates from our hospital is the carbapenemase production due to the expression of OXA- 23 gene, whereas in P. aeruginosa - the loss of transmembrane OprD protein and the effl ux pumps' hyperexpression are suspected to be the main mechanisms.
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Affiliation(s)
- Atanaska P Petrova
- Department of Microbiology and Immunology, Faculty of Pharmacy, Medical University of Plovdiv, Plovdiv, Bulgaria.,Laboratory of Microbiology, St George University Hospital, Plovdiv, Bulgaria,Technology Center of Emergency Medicine, Plovdiv, Bulgaria
| | - Irina D Stanimirova
- Department of Microbiology and Immunology, Faculty of Pharmacy, Medical University of Plovdiv, Plovdiv, Bulgaria.,Laboratory of Microbiology, St George University Hospital, Plovdiv, Bulgaria
| | - Ivan N Ivanov
- National Reference Laboratory for Control and Monitoring of Antimicrobial Resistance, National Center of Infectious and Parasitic Diseases, Sofia, Bulgaria
| | - Michael M Petrov
- Department of Microbiology and Immunology, Faculty of Pharmacy, Medical University of Plovdiv, Plovdiv, Bulgaria
| | - Tsonka M Miteva-Katrandzhieva
- Deparment of Social Medicine and Public Health, Faculty of Public Health, Medical University of Plovdiv, Plovdiv, Bulgaria
| | - Vasil I Grivnev
- Department of Microbiology and Immunology, Faculty of Pharmacy, Medical University of Plovdiv, Plovdiv, Bulgaria
| | | | - Todor V Kantardzhiev
- National Reference Laboratory for Control and Monitoring of Antimicrobial Resistance, National Center of Infectious and Parasitic Diseases, Sofia, Bulgaria
| | - Mariana A Murdjeva
- Department of Microbiology and Immunology, Faculty of Pharmacy, Medical University of Plovdiv, Plovdiv, Bulgaria.,Laboratory of Microbiology, St George University Hospital, Plovdiv, Bulgaria,Technology Center of Emergency Medicine, Plovdiv, Bulgaria
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Ahmad H, Sadiq A, Bhatti HW, Bhatti AA, Tameez-Ud-Din A, Ibrahim A, Chaudhary NA. Bacteriological Profile and Antibiogram of Cultures Isolated from Tracheal Secretions. Cureus 2019; 11:e4965. [PMID: 31453037 PMCID: PMC6701908 DOI: 10.7759/cureus.4965] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Background Respiratory infections are associated with high morbidity and mortality, especially in critically ill patients. The excessive use of broad-spectrum antibiotics has led to the development of drug resistance, thus resulting in the emergence of pathogens which are difficult to treat. The aim of this study was to identify common pathogens in tracheal secretions and to study the patterns of their sensitivity and resistance to various antibiotics. Materials and methods This descriptive cross-sectional study was conducted in the Department of Pathology and Microbiology, Holy Family Hospital, Rawalpindi, Pakistan, from August 2017 to December 2017, using the convenient sampling technique. Tracheal secretions from patients in the intensive care unit (ICU), tested in the Pathology and Microbiology Department of Holy Family Hospital, were included in the study. The culture was done on blood and MacConkey agar and the sensitivity pattern was performed on Muller Hinton agar. Data were analyzed using SPSS v.23.0. Results Out of the bacteria isolated from positive growth cultures, Acinetobacter (45; 53.6%) was the most common isolate followed by Klebsiella (11; 13.1%). Acinetobacter was most sensitive to tigecycline (94.7%), and gram-negative bacteria such as Acinetobacter, Klebsiella, and Pseudomonas showed resistance to higher generation cephalosporins. Conclusion Acinetobacter was the most common gram-negative bacilli isolated. Tigecycline was found to be effective against Acinetobacter.
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Affiliation(s)
- Hassaan Ahmad
- Miscellaneous, Rawalpindi Medical University, Rawalpindi, PAK
| | | | | | - Awais A Bhatti
- Medicine, Rawalpindi Medical University, Rawalpindi, PAK
| | | | - Ahmed Ibrahim
- Internal Medicine, Rawalpindi Medical University, Rawalpindi, PAK
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Muntean D, Licker M, Horhat F, Dumitrașcu V, Săndesc D, Bedreag O, Dugăeșescu D, Coșniță DA, Krasta A, Bădițoiu L. Extensively drug-resistant Acinetobacter baumannii and Proteeae association in a Romanian intensive care unit: risk factors for acquisition. Infect Drug Resist 2018; 11:2187-2197. [PMID: 30519056 PMCID: PMC6233948 DOI: 10.2147/idr.s171288] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Purpose The purpose of this study was to identify risk factors for extensively drug-resistant (XDR) Acinetobacter baumannii (AB) and XDR Proteeae association in the largest intensive care unit (ICU) in Western Romania. Materials and methods This retrospective case-controlled study was conducted between January 2016 and December 2016 in the ICU of the “Pius Brînzeu” County Emergency Clinical Hospital of Timi oara. Data were collected, in strict confidentiality, from the electronic database of the Microbiology Laboratory and the hospital’s electronic medical records. Risk factors were ș investigated by logistic regression. Independent variables with P≤0.05 and OR >1 (95% CI >1) in the univariate analysis were entered into multivariate sequenced analysis. Findings The incidence density of coinfection with XDR AB and XDR Proteeae was 5.31 cases per 1,000 patient-days. Independent risk factors for the association of XDR AB and XDR Proteeae were represented by the presence of tracheostomy and naso-/orogastric nutrition ≥ 8 days. In addition, pressure ulcers were independent predictive factors for infections with all three infection types. Previous antibiotic therapy was an independent risk factor for the acquisition of XDR-AB strains, alone or in association, while the prolonged hospitalization in the ICU, blood transfusion, and hemodialysis appear as independent risk factors for single infections. Conclusion This association of XDR AB and XDR Proteeae may well not be limited to our hospital or our geographical area.
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Affiliation(s)
- Delia Muntean
- Victor Babeș University of Medicine and Pharmacy, Timisoara, Romania, .,Pius Brînzeu Emergency Clinical County Hospital, Timisoara, Romania,
| | - Monica Licker
- Victor Babeș University of Medicine and Pharmacy, Timisoara, Romania, .,Pius Brînzeu Emergency Clinical County Hospital, Timisoara, Romania,
| | - Florin Horhat
- Victor Babeș University of Medicine and Pharmacy, Timisoara, Romania,
| | - Victor Dumitrașcu
- Victor Babeș University of Medicine and Pharmacy, Timisoara, Romania,
| | - Dorel Săndesc
- Victor Babeș University of Medicine and Pharmacy, Timisoara, Romania, .,Pius Brînzeu Emergency Clinical County Hospital, Timisoara, Romania,
| | - Ovidiu Bedreag
- Victor Babeș University of Medicine and Pharmacy, Timisoara, Romania, .,Pius Brînzeu Emergency Clinical County Hospital, Timisoara, Romania,
| | - Dorina Dugăeșescu
- Victor Babeș University of Medicine and Pharmacy, Timisoara, Romania,
| | - Dan A Coșniță
- Victor Babeș University of Medicine and Pharmacy, Timisoara, Romania,
| | - Anca Krasta
- Pius Brînzeu Emergency Clinical County Hospital, Timisoara, Romania,
| | - Luminița Bădițoiu
- Victor Babeș University of Medicine and Pharmacy, Timisoara, Romania,
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Chatani B, Garcia J, Biaggi C, Beduschi T, Tekin A, Vianna R, Arheart K, Gonzalez IA. Comparison in outcome with tailored antibiotic prophylaxis postoperatively in pediatric intestinal transplant population. Pediatr Transplant 2018; 22:e13277. [PMID: 30091217 DOI: 10.1111/petr.13277] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2018] [Accepted: 07/16/2018] [Indexed: 12/23/2022]
Abstract
BIs are ubiquitous among the pediatric intestinal transplant patient population. Personalizing postoperative prophylaxis antibiotic regimens may improve outcomes in this population. A retrospective analysis of all pediatric patients who underwent intestinal transplantation was evaluated to compare standardized and tailored regimens of antibiotics provided as prophylaxis postoperatively. Patients in the standard group have both shorter time to and higher rate of BIs, which was statistically significant (P < 0.001). Of the children who developed a BI, there was no statistical difference in average times to the development of a second BI (293 vs 119 days, P = 0.211). The tailored group had prolonged times until the development of a MDRO (52.6 vs 63.9 days, P = 0.677). Although not statistically significant, the tailored group had a propensity to present with gram-negative pathogens after transplant as compared to the standard regimen group, which presented with gram-positive pathogens (P = 0.103). Children with a history of an MDRO held a 7.3 (P < 0.01) times more likelihood of death within a year of transplant. A tailored prophylactic antibiotic regimen in the post-transplant period appears to prolong the time to the first BI. Although the data do not show differences in mortality, further study may prove the impact of a tailored antibiotic regimen on morbidity and mortality rates.
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Affiliation(s)
| | - Jennifer Garcia
- Pediatric Gastroenterology, University of Miami Miller School of Medicine, Miami, Florida
| | - Chiara Biaggi
- Pediatric Gastroenterology, University of Miami Miller School of Medicine, Miami, Florida
| | | | - Akin Tekin
- Miami Transplant Institute, Miami, Florida
| | | | - Kristopher Arheart
- Biostatistics, University of Miami Miller School of Medicine, Miami, Florida
| | - Ivan A Gonzalez
- Pediatric Infectious Diseases, University of Miami Miller School of Medicine, Miami, Florida
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Lépesová K, Kraková L, Pangallo D, Medveďová A, Olejníková P, Mackuľak T, Tichý J, Grabic R, Birošová L. Prevalence of antibiotic-resistant coliform bacteria, Enterococcus spp. and Staphylococcus spp. in wastewater sewerage biofilm. J Glob Antimicrob Resist 2018; 14:145-151. [DOI: 10.1016/j.jgar.2018.03.008] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2017] [Revised: 03/19/2018] [Accepted: 03/21/2018] [Indexed: 11/28/2022] Open
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Zhu Y, Zhang Q, Xu J, Qu Q, Lu T, Du B, Ke M, Zhang M, Qian H. Changes in bacterial community structure and antibiotic resistance genes in soil in the vicinity of a pharmaceutical factory. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2018; 158:87-93. [PMID: 29660617 DOI: 10.1016/j.ecoenv.2018.04.016] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/18/2018] [Revised: 04/04/2018] [Accepted: 04/06/2018] [Indexed: 06/08/2023]
Abstract
China is the largest global producer of antibiotics. With the demand for antibiotics increasing every year, it is necessary to assess potential environmental risks and the spread of antibiotic resistance genes (ARGs) associated with antibiotic production. Here, we investigated the occurrence and distribution of ARGs in soil in the vicinity of a pharmaceutical factory. The results showed that antibiotic concentrations were under the detection limit; however, ARGs were present in soil and tended to be enriched near the factory. A significant correlation between the relative abundance of intI-1 and tetracycline ARGs implied that horizontal gene transfer might play an important role in the spread of ARGs. The occurrence of these ARGs could be the results of previous antibiotic contamination. However, the soil bacterial community structure seemed to be more affected by nutrients or other factors than by antibiotics. Overall, this study supports the viewpoint that long-term pharmaceutical activity might have a negative effect on environmental health, thus, underscoring the need to regulate antibiotic production and management.
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Affiliation(s)
- Youchao Zhu
- College of Environment, Zhejiang University of Technology, Hangzhou 310032, PR of China
| | - Qi Zhang
- College of Environment, Zhejiang University of Technology, Hangzhou 310032, PR of China
| | - Jiahui Xu
- College of Environment, Zhejiang University of Technology, Hangzhou 310032, PR of China
| | - Qian Qu
- College of Environment, Zhejiang University of Technology, Hangzhou 310032, PR of China
| | - Tao Lu
- College of Environment, Zhejiang University of Technology, Hangzhou 310032, PR of China
| | - Benben Du
- College of Environment, Zhejiang University of Technology, Hangzhou 310032, PR of China
| | - Mingjing Ke
- College of Environment, Zhejiang University of Technology, Hangzhou 310032, PR of China
| | - Meng Zhang
- College of Environment, Zhejiang University of Technology, Hangzhou 310032, PR of China
| | - Haifeng Qian
- College of Environment, Zhejiang University of Technology, Hangzhou 310032, PR of China.
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Zhao J, Cheng W, He X, Liu Y, Li J, Sun J, Li J, Wang F, Gao Y. Association of furanone C-30 with biofilm formation & antibiotic resistance in Pseudomonas aeruginosa. Indian J Med Res 2018; 147:400-406. [PMID: 29998876 PMCID: PMC6057246 DOI: 10.4103/ijmr.ijmr_2010_16] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Background & objectives Pseudomonas aeruginosa is an opportunistic pathogen that can cause nosocomial bloodstream infections in humans. This study was aimed to explore the association of furanone C-30 with biofilm formation, quorum sensing (QS) system and antibiotic resistance in P. aeruginosa. Methods An in vitro model of P. aeruginosa bacterial biofilm was established using the standard P. aeruginosa strain (PAO-1). After treatment with 2.5 and 5 μg/ml of furanone C-30, the change of biofilm morphology of PAO-1 was observed, and the expression levels of QS-regulated virulence genes (lasB, rhlA and phzA2), QS receptor genes (lasR, rhlR and pqsR) as well as QS signal molecule synthase genes (lasI, rhlI, pqsE and pqsH) were determined. Besides, the AmpC expression was quantified in planktonic and mature biofilm induced by antibiotics. Results Furanone C-30 treatment significantly inhibited biofilm formation in a dose-dependent manner. With the increase of furanone C-30 concentration, the expression levels of lasB, rhlA, phzA2, pqsR, lasI, rhlI pqsE and pqsH significantly decreased in mature biofilm bacteria while the expression levels of lasR and rhlR markedly increased. The AmpC expression was significantly decreased in both planktonic and biofilm bacteria induced by imipenem and ceftazidime. Interpretation & conclusions Furanone C-30 may inhibit biofilm formation and antibiotic resistance in P. aeruginosa through regulating QS genes. The inhibitory effect of furanone C-30 on las system appeared to be stronger than that on rhl system. Further studies need to be done with different strains of P. aeruginosa to confirm our findings.
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Affiliation(s)
- Jingming Zhao
- Department of Respiratory Medicine, The Affiliated Hospital of Qingdao University, Qingdao, PR China
| | - Wei Cheng
- Department of Respiratory Medicine, The Affiliated Hospital of Qingdao University, Qingdao, PR China
| | - Xigang He
- Department of Respiratory Medicine, People's Hospital of Rizhao Lanshan, Rizhao, PR China
| | - Yanli Liu
- Department of Respiratory Medicine, The Affiliated Hospital of Qingdao University, Qingdao, PR China
| | - Ji Li
- Department of Pharmacy, Qilu Hospital of Shandong University, Qingdao, PR China
| | - Jiaxing Sun
- Department of Respiratory Medicine, The Affiliated Hospital of Qingdao University, Qingdao, PR China
| | - Jinfeng Li
- Department of Respiratory Medicine, The Affiliated Hospital of Qingdao University, Qingdao, PR China
| | - Fangfang Wang
- Department of Respiratory Medicine, The Affiliated Hospital of Qingdao University, Qingdao, PR China
| | - Yufang Gao
- Department of President's Office, The Affiliated Hospital of Qingdao University, Qingdao, PR China
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Pinto MN, Martinez-Gonzalez J, Chakraborty I, Mascharak PK. Incorporation of a Theranostic “Two-Tone” Luminescent Silver Complex into Biocompatible Agar Hydrogel Composite for the Eradication of ESKAPE Pathogens in a Skin and Soft Tissue Infection Model. Inorg Chem 2018; 57:6692-6701. [DOI: 10.1021/acs.inorgchem.8b00901] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Affiliation(s)
- Miguel N. Pinto
- Contribution from Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, United States
| | - Jorge Martinez-Gonzalez
- Contribution from Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, United States
| | - Indranil Chakraborty
- Contribution from Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, United States
| | - Pradip K. Mascharak
- Contribution from Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, United States
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Ramalingam K, Lee VA. Antibiofilm activity of an EDTA-containing nanoemulsion on multidrug-resistant Acinetobacter baumannii. ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY 2018; 46:737-743. [PMID: 29719996 DOI: 10.1080/21691401.2018.1468771] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
Acinetobacter baumannii have evolved as an exceedingly troublesome pathogenic microorganisms and prevention and controlling this pathogen is considered to be a public health problem. Nanoemulsions (NE) are a distinctive type of decontaminator produced by integration of immiscible oil phase with aqueous phase under extreme shear forces. The effectiveness of NEs and their components was determined against four stains of A. baumannii by MBC, adherence assay, biofilm assay and SEM studies. NE dilutions ranging from 125 to 225 reduced adhesion by from 61.8 to 99.9% in NE-treated groups (p<.05) as determined by MBC. Four-day-old A. baumannii biofilms were treated with NE; LIVE/DEAD staining showed dead cell intensity of 56.2-92.0% in NE-treated groups. After NE treatment and observation by SEM, cell surfaces appeared to be remarkably disintegrated. Irregular boundaries were observed and margins of cell walls were unclear. The anti-adherence, anti-biofilm and morphological disruption effects of NE suggest that this material could be useful for the development of promising antimicrobial agents.
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Affiliation(s)
- Karthikeyan Ramalingam
- a School of Life Sciences , B.S. Abdur Rahman Crescent Institute of Science and Technology , Chennai , India
| | - Valerie A Lee
- b University of Texas Health Science Center at San Antonio , San Antonio , TX , USA
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Uppuluri P, Lin L, Alqarihi A, Luo G, Youssef EG, Alkhazraji S, Yount NY, Ibrahim BA, Bolaris MA, Edwards JE, Swidergall M, Filler SG, Yeaman MR, Ibrahim AS. The Hyr1 protein from the fungus Candida albicans is a cross kingdom immunotherapeutic target for Acinetobacter bacterial infection. PLoS Pathog 2018; 14:e1007056. [PMID: 29746596 PMCID: PMC5963808 DOI: 10.1371/journal.ppat.1007056] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Revised: 05/22/2018] [Accepted: 04/26/2018] [Indexed: 11/21/2022] Open
Abstract
Different pathogens share similar medical settings and rely on similar virulence strategies to cause infections. We have previously applied 3-D computational modeling and bioinformatics to discover novel antigens that target more than one human pathogen. Active and passive immunization with the recombinant N-terminus of Candida albicans Hyr1 (rHyr1p-N) protect mice against lethal candidemia. Here we determine that Hyr1p shares homology with cell surface proteins of the multidrug resistant Gram negative bacterium, Acinetobacter baumannii including hemagglutinin (FhaB) and outer membrane protein A (OmpA). The A. baumannii OmpA binds to C. albicans Hyr1p, leading to a mixed species biofilm. Deletion of HYR1, or blocking of Hyr1p using polyclonal antibodies, significantly reduce A. baumannii binding to C. albicans hyphae. Furthermore, active vaccination with rHyr1p-N or passive immunization with polyclonal antibodies raised against specific peptide motifs of rHyr1p-N markedly improve survival of diabetic or neutropenic mice infected with A. baumannii bacteremia or pneumonia. Antibody raised against one particular peptide of the rHyr1p-N sequence (peptide 5) confers majority of the protection through blocking A. baumannii invasion of host cells and inducing death of the bacterium by a putative iron starvation mechanism. Anti-Hyr1 peptide 5 antibodies also mitigate A. baumannii /C. albicans mixed biofilm formation in vitro. Consistent with our bioinformatic analysis and structural modeling of Hyr1p, anti-Hyr1p peptide 5 antibodies bound to A. baumannii FhaB, OmpA, and an outer membrane siderophore binding protein. Our studies highlight the concept of cross-kingdom vaccine protection against high priority human pathogens such as A. baumannii and C. albicans that share similar ecological niches in immunocompromised patients.
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Affiliation(s)
- Priya Uppuluri
- Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-University of California at Los Angeles (UCLA) Medical Center, Torrance, California, United States of America
- Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America
| | - Lin Lin
- Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-University of California at Los Angeles (UCLA) Medical Center, Torrance, California, United States of America
- Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America
| | - Abdullah Alqarihi
- Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-University of California at Los Angeles (UCLA) Medical Center, Torrance, California, United States of America
| | - Guanpingsheng Luo
- Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-University of California at Los Angeles (UCLA) Medical Center, Torrance, California, United States of America
| | - Eman G. Youssef
- Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-University of California at Los Angeles (UCLA) Medical Center, Torrance, California, United States of America
- Department of Biotechnology and Life Sciences, Faculty of Postgraduate Studies for Advanced Sciences (PSAS), Beni-Suef University, Beni-Suef, Egypt
| | - Sondus Alkhazraji
- Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-University of California at Los Angeles (UCLA) Medical Center, Torrance, California, United States of America
| | - Nannette Y. Yount
- Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-University of California at Los Angeles (UCLA) Medical Center, Torrance, California, United States of America
| | - Belal A. Ibrahim
- Portola High School, Irvine, California, United States of America
| | - Michael Anthony Bolaris
- Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-University of California at Los Angeles (UCLA) Medical Center, Torrance, California, United States of America
| | - John E. Edwards
- Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-University of California at Los Angeles (UCLA) Medical Center, Torrance, California, United States of America
- Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America
| | - Marc Swidergall
- Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-University of California at Los Angeles (UCLA) Medical Center, Torrance, California, United States of America
| | - Scott G. Filler
- Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-University of California at Los Angeles (UCLA) Medical Center, Torrance, California, United States of America
- Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America
| | - Michael R. Yeaman
- Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-University of California at Los Angeles (UCLA) Medical Center, Torrance, California, United States of America
- Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America
| | - Ashraf S. Ibrahim
- Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-University of California at Los Angeles (UCLA) Medical Center, Torrance, California, United States of America
- Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America
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Danilovich ME, Sánchez LA, Acosta F, Delgado OD. Antarctic bioprospecting: in pursuit of microorganisms producing new antimicrobials and enzymes. Polar Biol 2018. [DOI: 10.1007/s00300-018-2295-4] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Sala A, Cabassi CS, Santospirito D, Polverini E, Flisi S, Cavirani S, Taddei S. Novel Naja atra cardiotoxin 1 (CTX-1) derived antimicrobial peptides with broad spectrum activity. PLoS One 2018; 13:e0190778. [PMID: 29364903 PMCID: PMC5783354 DOI: 10.1371/journal.pone.0190778] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2017] [Accepted: 12/20/2017] [Indexed: 11/20/2022] Open
Abstract
Naja atra subsp. atra cardiotoxin 1 (CTX-1), produced by Chinese cobra snakes, belonging to Elapidae family, is included in the three-finger toxin family and exerts high cytotoxicity and antimicrobial activity too. Using as template mainly the tip and the subsequent β-strand of the first "finger" of this toxin, different sequences of 20 amino acids linear peptides have been designed in order to avoid toxic effects but to maintain or even strengthen the partial antimicrobial activity already seen for the complete toxin. As a result, the sequence NCP-0 (Naja Cardiotoxin Peptide-0) was designed as ancestor and subsequently 4 other variant sequences of NCP-0 were developed. These synthesized variant sequences have shown microbicidal activity towards a panel of reference and field strains of Gram-positive and Gram-negative bacteria. The sequence named NCP-3, and its variants NCP-3a and NCP-3b, have shown the best antimicrobial activity, together with low cytotoxicity against eukaryotic cells and low hemolytic activity. Bactericidal activity has been demonstrated by minimum bactericidal concentration (MBC) assay at values below 10 μg/ml for most of the tested bacterial strains. This potent antimicrobial activity was confirmed even for unicellular fungi Candida albicans, Candida glabrata and Malassezia pachydermatis (MBC 50-6.3 μg/ml), and against the fast-growing mycobacteria Mycobacterium smegmatis and Mycobacterium fortuitum. Moreover, NCP-3 has shown virucidal activity on Bovine Herpesvirus 1 (BoHV1) belonging to Herpesviridae family. The bactericidal activity is maintained even in a high salt concentration medium (125 and 250 mM NaCl) and phosphate buffer with 20% Mueller Hinton (MH) medium against E. coli, methicillin resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa reference strains. Considering these in vitro obtained data, the search for active sequences within proteins presenting an intrinsic microbicidal activity could provide a new way for discovering a large number of novel and promising antimicrobial peptides families.
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Affiliation(s)
- Andrea Sala
- Department of Veterinary Science, University of Parma, Parma, Italy
| | | | | | - Eugenia Polverini
- Department of Mathematical, Physical and Computer Sciences, University of Parma, Parma, Italy
| | - Sara Flisi
- Department of Veterinary Science, University of Parma, Parma, Italy
| | - Sandro Cavirani
- Department of Veterinary Science, University of Parma, Parma, Italy
| | - Simone Taddei
- Department of Veterinary Science, University of Parma, Parma, Italy
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42
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Samanta S, Singh BR, Adholeya A. Intracellular Synthesis of Gold Nanoparticles Using an Ectomycorrhizal Strain EM-1083 of Laccaria fraterna and Its Nanoanti-quorum Sensing Potential Against Pseudomonas aeruginosa. Indian J Microbiol 2017; 57:448-460. [PMID: 29151646 PMCID: PMC5671422 DOI: 10.1007/s12088-017-0662-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2017] [Accepted: 07/14/2017] [Indexed: 10/18/2022] Open
Abstract
In this research work different shapes and sizes of gold nanoparticles (AuNPs) were synthesized through an intracellular biogenic approach, exploiting the chloroauric acid reducing and Au0 stabilizing potential of Laccaria fraterna EM-1083 mycelia. The intracellularly synthesized AuNPs exhibits anti-quorum sensing inhibitory potential against Pseudomonas aeruginosa. The synthesized AuNPs were characterized using UV-visible spectroscopy; transmission electron microscopy, X-ray diffraction, energy dispersive X-ray spectroscopy, and Fourier transform infrared spectroscopy. The characterization proved that the successful synthesis of highly stable crystalline AuNPs with various shapes. Here we tested inhibitory activity of AuNPs on QS-regulated biofilm development and pyocyanin production traits of P. aeruginosa. The qualitative and quantitative data demonstrated that AuNPs significantly inhibited the biofilm formation and pyocyanin production. In summary, our results signify the future use of intracellularly synthesized AuNPs in P. aeruginosa mediated diseases.
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Affiliation(s)
- Sreeparna Samanta
- TERI-Deakin Nano Biotechnology Centre, The Energy and Resources Institute (TERI), Teri Gram, Gwal Pahari, Gurgoan, 122001 India
| | - Braj Raj Singh
- TERI-Deakin Nano Biotechnology Centre, The Energy and Resources Institute (TERI), Teri Gram, Gwal Pahari, Gurgoan, 122001 India
| | - Alok Adholeya
- TERI-Deakin Nano Biotechnology Centre, The Energy and Resources Institute (TERI), Teri Gram, Gwal Pahari, Gurgoan, 122001 India
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43
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van Duin D, Paterson DL. Multidrug-Resistant Bacteria in the Community: Trends and Lessons Learned. Infect Dis Clin North Am 2017; 30:377-390. [PMID: 27208764 DOI: 10.1016/j.idc.2016.02.004] [Citation(s) in RCA: 356] [Impact Index Per Article: 44.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Multidrug resistant (MDR) bacteria are one of the most important threats to public health. Typically, MDR bacteria are associated with nosocomial infections. However, some MDR bacteria have become prevalent causes of community-acquired infections. The spread of MDR bacteria into the community is a crucial development, and is associated with increased morbidity, mortality, health care costs, and antibiotic use. Factors associated with community dissemination of MDR bacteria overlap but are distinct from those associated with nosocomial spread. Prevention of further community spread of MDR bacteria is of the utmost importance, and requires a multidisciplinary approach involving all stakeholders.
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Affiliation(s)
- David van Duin
- Division of Infectious Diseases, University of North Carolina, CB 7030, 130 Mason Farm Road, Chapel Hill, NC 27599, USA.
| | - David L Paterson
- The University of Queensland, Building 71/918 RBWH, Herston, QLD 4029, Australia
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44
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Marzan LW, Sultana T, Hasan MM, Mina SA, Islam MR, Rakibuzzaman A, Khan MIH. Characterization of furnace oil bioremediation potential of hydrocarbonoclastic bacteria isolated from petroleum contaminated sites of the Sundarbans, Bangladesh. J Genet Eng Biotechnol 2017; 15:103-113. [PMID: 30647647 PMCID: PMC6296641 DOI: 10.1016/j.jgeb.2017.02.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2017] [Revised: 01/22/2017] [Accepted: 02/12/2017] [Indexed: 11/15/2022]
Abstract
Spillage of furnace oil is a more frequent event in recent times. In this study, environmental samples from furnace oil spillage sites of the Shela River, the Sundarbans, Bangladesh, were collected after three weeks of spillage. Serial dilution was applied and total seven bacterial isolates were separated as pure cultures. The oil-degrading potentiality of all seven isolates was further assessed, confirmed and compared with the growth pattern in furnace oil supplemented media, 2, 6-dichlorophenolindophenol test, and gravimetric analysis. After 7 days of incubation, isolates SS3, RW2, and SB degraded 56%, 43%, and 52% of supplemented furnace oil, respectively. The top three hydrocarbonoclastic bacterial isolates were selected as potential and identified as Pseudomonas aeruginosa (SS3), Bacillus sp. (RW2), and Serratia sp. (SB). All three isolates showed significant oil-degrading capacity compared to negative control, when incubated in sterile pond water supplemented with 2% furnace oil, suggesting them as potential bioremediation agents.
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Affiliation(s)
- Lolo Wal Marzan
- Department of Genetic Engineering and Biotechnology, Faculty of Biological Sciences, University of Chittagong, Chittagong-4331, Bangladesh
| | - Tasrin Sultana
- Department of Genetic Engineering and Biotechnology, Faculty of Biological Sciences, University of Chittagong, Chittagong-4331, Bangladesh
| | - Md. Mahbub Hasan
- Department of Genetic Engineering and Biotechnology, Faculty of Biological Sciences, University of Chittagong, Chittagong-4331, Bangladesh
| | - Sohana Akter Mina
- Department of Genetic Engineering and Biotechnology, Faculty of Biological Sciences, University of Chittagong, Chittagong-4331, Bangladesh
| | - Md. Rafiqul Islam
- Department of Genetic Engineering and Biotechnology, Faculty of Biological Sciences, University of Chittagong, Chittagong-4331, Bangladesh
| | - A.G.M. Rakibuzzaman
- Molecular Research Lab, R&D, Biotechnology Derived Product Facility (BDPF), Incepta Pharmaceuticals Ltd, Zirabo, Savar, Dhaka, Bangladesh
| | - Md. Iqbal Hassan Khan
- Molecular Research Lab, R&D, Biotechnology Derived Product Facility (BDPF), Incepta Pharmaceuticals Ltd, Zirabo, Savar, Dhaka, Bangladesh
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45
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Draft Genome Sequence of a Multidrug-Resistant Pseudomonas aeruginosa Strain Isolated from a Patient with a Urinary Tract Infection in Khartoum, Sudan. GENOME ANNOUNCEMENTS 2017; 5:5/16/e00203-17. [PMID: 28428302 PMCID: PMC5399261 DOI: 10.1128/genomea.00203-17] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Pseudomonas aeruginosa infection is difficult to treat due to the presence of antibiotic resistance determinants. Here, we report the genome sequence of a multidrug-resistant P. aeruginosa strain isolated from a patient with a urinary tract infection in 2015.
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46
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García C. JC, Amaya S, Briceño C. W, Rincón C, Pinzón J. Risk factors for carbapenem-resistant bacterial infection or colonization: A case control study. ACTA ACUST UNITED AC 2017. [DOI: 10.1016/j.acci.2016.11.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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47
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Molecular epidemiology and spatiotemporal analysis of hospital-acquired Acinetobacter baumannii infection in a tertiary care hospital in southern Thailand. J Hosp Infect 2017; 95:53-58. [DOI: 10.1016/j.jhin.2016.10.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2016] [Accepted: 10/03/2016] [Indexed: 12/28/2022]
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48
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Gillard CJ, Al-Dahir S, Brakta F. Observations of resistance through minimum inhibitory concentrations trends for respiratory specimens of commonly isolated organisms. Am J Health Syst Pharm 2016; 73:S42-8. [PMID: 26896525 DOI: 10.2146/sp150032] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
OBJECTIVE The objective of this study was to determine minimum inhibitory concentration (MIC) trends among common bacterial organisms found in respiratory isolates in the trauma intensive care unit setting. METHODS In this retrospective observational study, MIC data was reviewed over a three year period from January 2009 to December 2011 for the three most frequently identified organisms isolated from respiratory specimens in a trauma intensive care unit along with corresponding hospital data. RESULTS The most frequently isolated bacterial species identified were Staphylococcus aureus (229 isolates), Pseudomonas aeruginosa (129 isolates), and Acinetobacter species (87 isolates) in the analysis within our institution from 2009-2011. There was considerable variability among the MIC trends for the analyzed organisms. For Pseudomonas isolates, observed sensitivities were as high as 100% for antibiotics ciprofloxacin and imipenem in 2009, but decreased over the next two years in 2010 and 2011. There was considerable variability among the MIC trends for Acinetobacter over the three year period for the antibiotics tested. The MIC data for most Staphylococcus aureus isolates over the three years were sensitive to vancomycin with little change in the observed MIC data. CONCLUSION The data reported is observational and indicates the need for future studies to establish a valid relationship of the MIC data over time in our institution particularly among our gram negative organisms, to monitor patterns of antimicrobial resistance.
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Affiliation(s)
- Christopher J Gillard
- PGY1 Pharmacy Practice Resident, Xavier University of Louisiana College of Pharmacy/Louisiana State University Interim Hospital; New Orleans, LA
| | - Sara Al-Dahir
- Fulbright Scholar and Clinical Assistant Professor at Xavier University of Louisiana College of Pharmacy and Critical Care Clinical Pharmacist at Louisiana State University Interim Hospital; New Orleans, LA
| | - Fatima Brakta
- Clinical Assistant Professor at Xavier University of Louisiana College of Pharmacy and Infectious Disease Clinical Pharmacist at Louisiana State University Interim Hospital; New Orleans, LA
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49
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Niveshika, Verma E, Mishra AK, Singh AK, Singh VK. Structural Elucidation and Molecular Docking of a Novel Antibiotic Compound from Cyanobacterium Nostoc sp. MGL001. Front Microbiol 2016; 7:1899. [PMID: 27965634 PMCID: PMC5126090 DOI: 10.3389/fmicb.2016.01899] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2016] [Accepted: 11/11/2016] [Indexed: 12/02/2022] Open
Abstract
Cyanobacteria are rich source of array of bioactive compounds. The present study reports a novel antibacterial bioactive compound purified from cyanobacterium Nostoc sp. MGL001 using various chromatographic techniques viz. thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). Further characterization was done using electrospray ionization mass spectroscopy (ESIMS) and nuclear magnetic resonance (NMR) and predicted structure of bioactive compound was 9-Ethyliminomethyl-12-(morpholin - 4 - ylmethoxy) -5, 8, 13, 16–tetraaza–hexacene - 2, 3 dicarboxylic acid (EMTAHDCA). Structure of EMTAHDCA clearly indicated that it is a novel compound that was not reported in literature or natural product database. The compound exhibited growth inhibiting effects mainly against the gram negative bacterial strains and produced maximum zone of inhibition at 150 μg/mL concentration. The compound was evaluated through in silico studies for its ability to bind 30S ribosomal fragment (PDB ID: 1YRJ, 1MWL, 1J7T, and 1LC4) and OmpF porin protein (4GCP, 4GCQ, and 4GCS) which are the common targets of various antibiotic drugs. Comparative molecular docking study revealed that EMTAHDCA has strong binding affinity for these selected targets in comparison to a number of most commonly used antibiotics. The ability of EMTAHDCA to bind the active sites on the proteins and 30S ribosomal fragments where the antibiotic drugs generally bind indicated that it is functionally similar to the commercially available drugs.
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Affiliation(s)
- Niveshika
- Laboratory of Microbial Genetics, Department of Botany, Banaras Hindu University Varanasi, India
| | - Ekta Verma
- Laboratory of Microbial Genetics, Department of Botany, Banaras Hindu University Varanasi, India
| | - Arun K Mishra
- Laboratory of Microbial Genetics, Department of Botany, Banaras Hindu University Varanasi, India
| | - Angad K Singh
- Department of Chemistry, Banaras Hindu University Varanasi, India
| | - Vinay K Singh
- Centre for Bioinformatics, School of Biotechnology, Banaras Hindu University Varanasi, India
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50
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Lee H, Lee H. Clinical and Economic Evaluation of Multidrug-Resistant Acinetobacter baumannii Colonization in the Intensive Care Unit. Infect Chemother 2016; 48:174-180. [PMID: 27659440 PMCID: PMC5047998 DOI: 10.3947/ic.2016.48.3.174] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2016] [Revised: 09/01/2016] [Accepted: 09/01/2016] [Indexed: 12/02/2022] Open
Abstract
Background The clinical and economic impact of multidrug-resistant (MDR) Acinetobacter baumannii colonization remains unclear. This study aimed to estimate and compare the mortality rates, length of stay (LOS), and hospitalization costs in the intensive care unit (ICU) for MDR A. baumannii colonized patients and a matched population. Materials and Methods We performed a retrospective propensity score matched cohort study comparing the outcomes of patients with MDR A. baumannii colonization with those of uncolonized subjects matched at the time they were admitted to the ICU between January 2012 and December 2014. Results During the study period, 375 (7.5%) of the 4,779 patients were colonized with MDR A. baumannii. One hundred and twenty-two MDR A. baumannii colonized patients were compared with 122 uncolonized patients using propensity score matching. MDR A. baumannii colonized patients were likely to have a higher mortality rate compared to uncolonized patients (49.2% vs 32.0%; odds ratio [OR], 3.64). A longer ICU LOS and total admission days were observed in the MDR A. baumannii colonized patient group (4.14 and 4.67 days increase, OR 1.41 and 1.19). MDR A. baumannii colonization patients had an average extra ICU and total admission cost of $1,179 (₩1,261,334) and $1,333 (₩1,422,032) according to a multivariable regression model (OR, 1.27 and 1.17). Multivariable analysis identified the factors affecting ICU cost, which included, MDR A. baumannii colonization (OR = 1.33; P = 0.001), ICU LOS (OR = 1.97; P <0.001), valvular heart disease (OR = 1.12; P = 0.005), invasive devices (OR = 1.15; P = 0.018), and surgery (OR = 1.1; P <0.001). Conclusion MDR A. baumannii colonization was associated with increased mortality, LOS, and costs in the ICU. A strict infection control program including preemptive isolation for high-risk groups would be helpful for reducing the burden of this infection.
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Affiliation(s)
- Hojin Lee
- Division of Infectious Diseases, Department of Internal Medicine, Dong-A University Hospital, Busan, Korea
| | - Hyuck Lee
- Division of Infectious Diseases, Department of Internal Medicine, Dong-A University Hospital, Busan, Korea.
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