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Hernández-Durán M, Colín-Castro CA, Fernández-Rodríguez D, Delgado G, Morales-Espinosa R, Martínez-Zavaleta MG, Shekhar C, Ortíz-Álvarez J, García-Contreras R, Franco-Cendejas R, López-Jácome LE. Inside-out, antimicrobial resistance mediated by efflux pumps in clinical strains of Acinetobacter baumannii isolated from burn wound infections. Braz J Microbiol 2024; 55:3629-3641. [PMID: 39044104 PMCID: PMC11711420 DOI: 10.1007/s42770-024-01461-4] [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: 02/27/2024] [Accepted: 07/11/2024] [Indexed: 07/25/2024] Open
Abstract
Acinetobacter baumannii belongs to the ESKAPE group. It is classified as a critical priority group by the World Health Organization and a global concern on account of its capacity to acquire and develop resistance mechanisms to multiple antibiotics. Data from the United States indicates 500 deaths annually. Resistance mechanisms of this bacterium include enzymatic pathways such as ß-lactamases, carbapenemases, and aminoglycoside-modifying enzymes, decreased permeability, and overexpression of efflux pumps. A. baumannii has been demonstrated to possess efflux pumps, which are classified as members of the MATE family, RND and MFS superfamilies, and SMR transporters. The aim of our work was to assess the distribution of efflux pumps and their regulatory gene expression in clinical strains of A. baumannii isolated from burned patients. METHODS: From the Clinical Microbiology Laboratory at the Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra collection in Mexico, 199 strains were selected. Antibiotics susceptibilities were performed by broth microdilutions to determine minimal inhibitory concentrations. Phenotypic assays with efflux pump inhibitors were conducted using carbonyl cyanide 3-chlorophenylhydrazone (CCCP) and phenylalanine-arginine ß-naphthylamide (PAßN) in conjunction with amikacin, ceftazidime, imipenem, meropenem and levofloxacin. A search was conducted for structural genes that are linked to efflux pumps, and the relative expression of the adeR, adeS, and adeL genes was analyzed. RESULTS: Among a total of 199 strains, 186 exhibited multidrug resistance (MDR). Fluoroquinolones demonstrated the highest resistance rates, while minocycline and amikacin displayed comparatively reduced resistance rates (1.5 and 28.1, respectively). The efflux activity of fluorquinolones exhibited the highest phenotypic detection (from 85 to 100%), while IMP demonstrated the lowest activity of 27% with PAßN and 43.3% with CCCP. Overexpression was observed in adeS and adeL, with adeR exhibiting overexpression. Concluding that clinical strains of A. baumannii from our institution exhibited efflux pumps as one of the resistance mechanisms.
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Affiliation(s)
- Melissa Hernández-Durán
- Laboratorio de Microbiología Clínica, División de Infectología, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Mexico City, Mexico
| | - Claudia Adriana Colín-Castro
- Laboratorio de Microbiología Clínica, División de Infectología, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Mexico City, Mexico
| | - Diana Fernández-Rodríguez
- Laboratorio de Microbiología Clínica, División de Infectología, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Mexico City, Mexico
- Plan de Estudios Combinados en Medicina (PECEM) MD/PhD, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Gabriela Delgado
- Laboratorio de Genómica Bacteriana, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Rosario Morales-Espinosa
- Laboratorio de Genómica Bacteriana, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - María Guadalupe Martínez-Zavaleta
- Laboratorio de Microbiología Clínica, División de Infectología, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Mexico City, Mexico
| | - Chandra Shekhar
- College of Medicine, The University of Tennessee Health Science Center, Memphis, USA
| | - Jossue Ortíz-Álvarez
- Ciencias y Tecnologías (CONAHCYT), Programa "Investigadoras E Investigadores Por México". Consejo Nacional de Humanidades, Mexico City, Mexico
| | - Rodolfo García-Contreras
- Laboratorio de Bacteriología, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Rafael Franco-Cendejas
- Biomedical Research Subdirection, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Mexico City, Mexico
| | - Luis Esaú López-Jácome
- Laboratorio de Microbiología Clínica, División de Infectología, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Mexico City, Mexico.
- Departamento de Biología. Facultad de Química, Universidad Nacional Autónoma de México, Mexico City, Mexico.
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Schechner V, Cohen A, Carmeli Y. Tailoring Interventions for Control of Endemic Carbapenem-Resistant Acinetobacter baumannii: An Interrupted Time Series Analysis. Open Forum Infect Dis 2024; 11:ofae301. [PMID: 38872846 PMCID: PMC11170493 DOI: 10.1093/ofid/ofae301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Accepted: 05/26/2024] [Indexed: 06/15/2024] Open
Abstract
Background We examined temporal trends in carbapenem-resistant Acinetobacter baumannii (CRAB) infections in a hospital with hyperendemic CRAB and assessed the efficacy of varied infection control strategies in different ward types. Methods We retrospectively analyzed all CRAB clinical samples from 2006 to 2019 and categorized infections as hospital-onset (HO) or community-onset. We used interrupted time series analysis to assess the impact of interventions on the incidence of all HO-CRAB infections and bloodstream infections (BSIs) at the hospital and ward group levels. Results Over 14 years, 4009 CRAB infections were identified (89.7% HO), with 813 CRAB BSI (93.2% HO). The incidence per 100 000 patient-days of CRAB infections peaked in 2008 at 79.1, and that of CRAB BSI peaked in 2010 at 16.2. These rates decreased by two-thirds by 2019. In the general intensive care unit (ICU), hand hygiene and environmental cleaning interventions were followed by a significant reduction in the level of HO-CRAB infections, with an additional decrease in the slope after the introduction of active surveillance and 2% chlorhexidine bathing. In the surgical ICU and surgical department, a reduction in slope or level of CRAB infection was observed after moving ventilated patients to single rooms. In medical wards, a multimodal intervention was followed by a reduction in the slope of HO-CRAB infections and BSIs. In wards where CRAB infections were uncommon, the incidence of HO-CRAB infections decreased throughout the study period. Conclusions Ward-specific variables determine the success of interventions in reducing CRAB infections; therefore, interventions should be tailored to each setting.
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Affiliation(s)
- Vered Schechner
- National Institute for Antibiotic Resistance and Infection Control, Ministry of Health, Tel Aviv, Israel
- School of Public Health, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Adi Cohen
- National Institute for Antibiotic Resistance and Infection Control, Ministry of Health, Tel Aviv, Israel
| | - Yehuda Carmeli
- National Institute for Antibiotic Resistance and Infection Control, Ministry of Health, Tel Aviv, Israel
- School of Public Health, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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Yang X, Wei R, Liu H, Wei T, Zeng P, Cheung YC, Heng H, Chan EW, Li X, Chen S. Discovery of a Monoclonal Antibody That Targets Cell-Surface Pseudaminic Acid of Acinetobacter baumannii with Direct Bactericidal Effect. ACS CENTRAL SCIENCE 2024; 10:439-446. [PMID: 38435534 PMCID: PMC10906240 DOI: 10.1021/acscentsci.3c01507] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Revised: 01/18/2024] [Accepted: 01/19/2024] [Indexed: 03/05/2024]
Abstract
The therapeutic effects of antibodies include neutralization of pathogens, activation of the host complement system, and facilitation of phagocytosis of pathogens. However, antibody alone has never been shown to exhibit bactericidal activity. In this study, we developed a monoclonal antibody that targets the bacterial cell surface component Pseudaminic acid (Pse). This monoclonal antibody, Pse-MAB1, exhibited direct bactericidal activity on Acinetobacter baumannii strains, even in the absence of the host complements or other immune factors, and was able to confer a protective effect against A. baumannii infections in mice. This study provides new insight into the potential of developing monoclonal antibody-based antimicrobial therapy of multidrug resistant bacterial infections, especially those which occurred among immunocompromised patients.
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Affiliation(s)
- Xuemei Yang
- State
Key Lab of Chemical Biology and Drug Discovery and the Department
of Food Science and Nutrition, The Hong
Kong Polytechnic University, Hung Hom 999077, Hong Kong SAR
- Shenzhen
Key lab for Food Biological Safety Control, The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen 518000, China
| | - Ruohan Wei
- Department
of Chemistry, the State Key Laboratory of Synthetic Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong 999077, Hong Kong SAR
| | - Han Liu
- Department
of Chemistry, the State Key Laboratory of Synthetic Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong 999077, Hong Kong SAR
| | - Tongyao Wei
- Department
of Chemistry, the State Key Laboratory of Synthetic Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong 999077, Hong Kong SAR
| | - Ping Zeng
- School
of Pharmacy, Faculty of Medicine, The Chinese
University of Hong Kong, Shatin 999077, Hong Kong
SAR
| | - Yan Chu Cheung
- State
Key Lab of Chemical Biology and Drug Discovery and the Department
of Food Science and Nutrition, The Hong
Kong Polytechnic University, Hung Hom 999077, Hong Kong SAR
- Department
of Infectious Diseases and Public Health, Jockey Club College of Veterinary
Medicine and Life Sciences, City University
of Hong Kong, Kowloon
Tong 999077, Hong Kong SAR
| | - Heng Heng
- State
Key Lab of Chemical Biology and Drug Discovery and the Department
of Food Science and Nutrition, The Hong
Kong Polytechnic University, Hung Hom 999077, Hong Kong SAR
- Department
of Infectious Diseases and Public Health, Jockey Club College of Veterinary
Medicine and Life Sciences, City University
of Hong Kong, Kowloon
Tong 999077, Hong Kong SAR
| | - Edward Waichi Chan
- Shenzhen
Key lab for Food Biological Safety Control, The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen 518000, China
| | - Xuechen Li
- Department
of Chemistry, the State Key Laboratory of Synthetic Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong 999077, Hong Kong SAR
| | - Sheng Chen
- State
Key Lab of Chemical Biology and Drug Discovery and the Department
of Food Science and Nutrition, The Hong
Kong Polytechnic University, Hung Hom 999077, Hong Kong SAR
- Shenzhen
Key lab for Food Biological Safety Control, The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen 518000, China
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Osanloo L, Zeighami H, Haghi F, Shapouri R, Shokri R. Molecular Typing of Multidrug-Resistant Acinetobacter baumannii Isolates from Clinical Specimens by ERIC-PCR and MLVA. Curr Microbiol 2023; 80:355. [PMID: 37752362 DOI: 10.1007/s00284-023-03459-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Accepted: 08/26/2023] [Indexed: 09/28/2023]
Abstract
Acinetobacter baumannii, a Gram-negative and oxidase-negative bacterium, is a major cause of nosocomial infections, leading to high mortality rates in hospitalized patients. The use of 2 prominent molecular typing methods (i.e., enterobacterial repetitive intergenic consensus-polymerase chain reaction [ERIC-PCR] and multiple-locus variable-number tandem repeat [VNTR] analysis [MLVA]) for genotyping A. baumannii isolates has proven to be an effective approach in assessing the clonal relation of these isolates and managing their outbreaks. A total of 100 A. baumannii isolates were collected from immunocompromised patients hospitalized in the intensive care unit (ICU) of a hospital in Zanjan City, Iran. Their antibiotic resistance ability (especially aminoglycoside resistance) was studied by disc diffusion tests. The genetic typing of A. baumannii was studied using ERIC-PCR and MLVA methods. All isolates were resistant to 3 or more antibiotics and regarded as multidrug-resistant (MDR). Additionally, 32% of the isolates were resistant to all antibiotics tested, and 91% were extensively drug-resistant (XDR). The increased rate of aminoglycoside-resistant A. baumannii in ICU patients, with an increased incidence of aminoglycoside-modifying enzymes of aac (6')-Ib, ant (3″)-I, and aph (2″)-Id. ERIC-PCR has likewise shown an increased level of diversity in A. baumannii isolates. According to the ERIC-PCR patterns, isolates were classified as 4 clusters, while according to the MLVA patterns, isolates were classified as 9 distinct clusters. ERIC-PCR and MLVA assays serve as useful genotyping methods to assess the genetic variety or clonal relatedness of A. baumannii isolates.
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Affiliation(s)
- Leili Osanloo
- Department of Microbiology, Biology Research Center, Zanjan Branch, Islamic Azad University, Zanjan, Iran
| | - Habib Zeighami
- Department of Microbiology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
| | - Fakhri Haghi
- Department of Microbiology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Reza Shapouri
- Department of Microbiology, Biology Research Center, Zanjan Branch, Islamic Azad University, Zanjan, Iran
| | - Rasoul Shokri
- Department of Microbiology, Biology Research Center, Zanjan Branch, Islamic Azad University, Zanjan, Iran
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Ebrahimi A, Ergün T, Kaygusuz İzgördü Ö, Darcan C, Avci H, Öztürk B, Güner HR, Ghorbanpoor H, Doğan Güzel F. Revealing the single-channel characteristics of OprD (OccAB1) porins from hospital strains of Acinetobacter baumannii. EUROPEAN BIOPHYSICS JOURNAL : EBJ 2023:10.1007/s00249-023-01651-2. [PMID: 37052656 DOI: 10.1007/s00249-023-01651-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 03/28/2023] [Accepted: 04/07/2023] [Indexed: 04/14/2023]
Abstract
Nowadays, reports of antimicrobial resistance (AMR) against many antibiotics are increasing because of their misapplication. With this rise, there is a serious decrease in the discovery and development of new types of antibiotics amid an increase in multi-drug resistance. Unfermented Acinetobacter baumannii from gram-negative bacteria, which is one of the main causes of nosocomial infections and multi-drug resistance, has 4 main kinds of antibiotic resistance mechanism: inactivating antibiotics by enzymes, reduced numbers of porins and changing of their target or cellular functions due to mutations, and efflux pumps. In this study, characterization of the possible mutations in OprD (OccAB1) porins from hospital strains of A. baumannii were investigated using single channel electrophysiology and compared with the standard OprD isolated from wild type ATCC 19,606. For this aim, 5 A. baumannii bacteria samples were obtained from patients infected with A. baumannii, after which OprD porins were isolated from these A. baumannii strains. OprD porins were then inserted in an artificial lipid bilayer and the current-voltage curves were obtained using electrical recordings through a pair of Ag/AgCl electrodes. We observed that each porin has a characteristic conductance and single channel recording, which then leads to differences in channel diameter. Finally, the single channel data have been compared with the gene sequences of each porin. It was interesting to find out that each porin isolated has a unique porin diameter and decreased anion selectivity compared to the wild type.
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Affiliation(s)
- Aliakbar Ebrahimi
- Faculty of Engineering and Natural Sciences, Department of Biomedical Engineering, Ankara Yildirim Beyazit University, Ankara, Turkey
- Cellular Therapy and Stem Cell Research Center and Translational Medicine Research and Clinical Center (ESTEM), Eskisehir Osmangazi University, Eskisehir, Turkey
| | - Tuğçe Ergün
- Faculty of Engineering and Natural Sciences, Department of Biomedical Engineering, Ankara Yildirim Beyazit University, Ankara, Turkey
- Department of Biotechnology and Biosafety, Eskisehir Osmangazi University, Eskisehir, Turkey
| | - Özge Kaygusuz İzgördü
- Biotechnology Application and Research Center, Bilecik Şeyh Edebali University, Bilecik, Turkey
| | - Cihan Darcan
- Faculty of Science and Literature, Department of Molecular Biology and Genetics, Bilecik Seyh Edebali University, Bilecik, Turkey
| | - Hüseyin Avci
- Cellular Therapy and Stem Cell Research Center and Translational Medicine Research and Clinical Center (ESTEM), Eskisehir Osmangazi University, Eskisehir, Turkey
- Faculty of Engineering and Architecture, Department of Metallurgical and Material Engineering, Eskisehir Osmangazi University, Eskisehir, Turkey
- Department of Stem Cell, Institute of Health Sciences, Eskisehir Osmangazi University, Eskisehir, Turkey
- Translational Medicine Research and Clinical Center (TATUM), Eskisehir Osmangazi University, Eskisehir, Turkey
| | - Barçin Öztürk
- Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology, Adnan Menderes University, Aydin, Turkey
| | - Hatice Rahmet Güner
- Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology, Ankara Yildirim Beyazit University, Ankara, Turkey
| | - Hamed Ghorbanpoor
- Cellular Therapy and Stem Cell Research Center and Translational Medicine Research and Clinical Center (ESTEM), Eskisehir Osmangazi University, Eskisehir, Turkey
- Department of Biomedical Engineering, Eskisehir Osmangazi University, Eskisehir, Turkey
| | - Fatma Doğan Güzel
- Faculty of Engineering and Natural Sciences, Department of Biomedical Engineering, Ankara Yildirim Beyazit University, Ankara, Turkey.
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Min EK, Yim SH, Choi MC, Lee JG, Joo DJ, Kim MS, Kim DG. Incidence, mortality, and risk factors associated with carbapenem-resistant Acinetobacter baumannii bacteremia within 30 days after liver transplantation. Clin Transplant 2023; 37:e14956. [PMID: 36860160 DOI: 10.1111/ctr.14956] [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: 11/29/2022] [Revised: 01/10/2023] [Accepted: 02/26/2023] [Indexed: 03/03/2023]
Abstract
Carbapenem-resistant Acinetobacter baumannii bacteremia (CRAB-B) is a fatal infectious complication of liver transplantation (LT). This study investigated the incidence, effects, and risk factors associated with CRAB-B during the early post-LT period. Among 1051 eligible LT recipients, 29 patients experienced CRAB-B within 30 days of LT with a cumulative incidence of 2.7%. In the patients with CRAB-B (n = 29) and matched controls (n = 145) by nested-case control design, the cumulative incidence of death on days 5, 10, and 30 from the index date was 58.6%, 65.5%, and 65.5%, and 2.1%, 2.8%, and 4.2%, respectively (p < .001). Pre-transplant MELD (OR 1.11, 95% confidence interval [CI] 1.04-1.19, p = .002), severe encephalopathy (OR 4.62, 95% CI 1.24-18.61, p = .025), donor body mass index (OR .57, 95% CI .41-.75, p < .001), and reoperation (OR 6.40, 95% CI 1.19-36.82, p = .032) were independent risk factors for 30-day CRAB-B. CRAB-B showed extremely high mortality within 30 days after LT, especially within 5 days after its occurrence. Therefore, assessment of risk factors and early detection of CRAB, followed by proper treatment, are necessary to control CRAB-B after LT.
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Affiliation(s)
- Eun-Ki Min
- Department of Surgery, The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, South Korea
| | - Seung Hyuk Yim
- Department of Surgery, The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, South Korea
| | - Mun Chae Choi
- Department of Surgery, The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, South Korea
| | - Jae Geun Lee
- Department of Surgery, The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, South Korea
| | - Dong Jin Joo
- Department of Surgery, The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, South Korea
| | - Myoung Soo Kim
- Department of Surgery, The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, South Korea
| | - Deok-Gie Kim
- Department of Surgery, The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, South Korea
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Deshwal PR, Fathima R, Aggarwal M, Reddy NS, Tiwari P. A systematic review and meta-analysis for risk factor profiles in patients with resistant Acinetobacter baumannii infection relative to control patients. INTERNATIONAL JOURNAL OF RISK & SAFETY IN MEDICINE 2023; 34:337-355. [PMID: 37154184 DOI: 10.3233/jrs-220037] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/10/2023]
Abstract
BACKGROUND Acinetobacter baumannii is a major cause of nosocomial infections and high mortality rates. Evaluation of risk factors for such resistant infections may aid surveillance and diagnostic initiatives, as well as, can be crucial in early and appropriate antibiotic therapy. OBJECTIVE To identify the risk factors in patients with resistant A. baumannii infection with respect to controls. METHODS Prospective or retrospective cohort and case-control studies reporting the risk factors for resistant A. baumannii infection were collected through two data sources, MEDLINE/PubMed and OVID/Embase. Studies published in the English language were included while animal studies were excluded. The Newcastle-Ottawa Scale was used to assess the quality of studies. The odds ratio of developing antibiotic resistance in patients with A. baumannii infection was pooled using a random-effect model. RESULTS The results are based on 38 studies with 60878 participants (6394 cases and 54484 controls). A total of 28, 14, 25, and 11 risk factors were identified for multi-drug resistant (MDRAB), extensive-drug resistant (XDRAB), carbapenem-resistant (CRAB) and imipenem resistant A. baumannii infection (IRAB), respectively. In the MDRAB infection group, exposure to carbapenem (OR 5.51; 95% CI: 3.88-7.81) and tracheostomy (OR 5.01; 95% CI: 2.12-11.84) were identified with maximal pool odd's ratio. While previous use of amikacin (OR 4.94; 95% CI: 1.89-12.90) and exposure to carbapenem (OR 4.91; 95% CI: 2.65-9.10) were the foremost factors associated with developing CRAB infection. Further analysis revealed, mechanical ventilation (OR 7.21; 95% CI: 3.79-13.71) and ICU stay (OR 5.88; 95% CI: 3.27-10.57) as the most significant factors for XDRAB infection. CONCLUSION The exposure of carbapenem, amikacin (previous) and mechanical ventilation were the most significant risk factors for multidrug, extensive-drug, and carbapenem resistance in patients with A. baumannii infection respectively. These findings may guide to control and prevent resistant infections by identifying the patients at higher risk of developing resistance.
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Affiliation(s)
- Prity Rani Deshwal
- Department of Pharmacy Practice, National Institute of Pharmaceutical Education and Research (NIPER), Punjab, India
| | - Raisa Fathima
- Department of Pharmacy Practice, National Institute of Pharmaceutical Education and Research (NIPER), Punjab, India
| | - Muskan Aggarwal
- Department of Pharmacy Practice, National Institute of Pharmaceutical Education and Research (NIPER), Punjab, India
| | - Nalla Surender Reddy
- Department of Pharmacy Practice, National Institute of Pharmaceutical Education and Research (NIPER), Punjab, India
| | - Pramil Tiwari
- Department of Pharmacy Practice, National Institute of Pharmaceutical Education and Research (NIPER), Punjab, India
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A bioinformatics approach to introduce novel multi-epitope vaccines against Acinetobacter baumannii retrieved from immunogenic extracellular loops of outer membrane proteins. INFORMATICS IN MEDICINE UNLOCKED 2022. [DOI: 10.1016/j.imu.2022.100989] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
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9
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Genetic Resistance Determinants in Clinical Acinetobacter pittii Genomes. Antibiotics (Basel) 2022; 11:antibiotics11050676. [PMID: 35625320 PMCID: PMC9137642 DOI: 10.3390/antibiotics11050676] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 05/10/2022] [Accepted: 05/16/2022] [Indexed: 12/14/2022] Open
Abstract
Antimicrobial-resistant pathogenic bacteria are an increasing problem in public health, especially in the healthcare environment, where nosocomial infection microorganisms find their niche. Among these bacteria, the genus Acinetobacter which belongs to the ESKAPE pathogenic group harbors different multi-drug resistant (MDR) species that cause human nosocomial infections. Although A. baumannii has always attracted more interest, the close-related species A. pittii is the object of more study due to the increase in its isolation and MDR strains. In this work, we present the genomic analysis of five clinically isolated A. pittii strains from a Spanish hospital, with special attention to their genetic resistance determinants and plasmid structures. All the strains harbored different genes related to β-lactam resistance, as well as different MDR efflux pumps. We also found and described, for the first time in this species, point mutations that seem linked with colistin resistance, which highlights the relevance of this comparative analysis among the pathogenic species isolates.
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Gülbüz M, Saral Sariyer A. Combined in silico approach and whole genome sequencing: Acinetobacter baumannii ST218 isolate harboring ADC-73 β-lactamase which has a similar C-loop with ADC-56 and ADC-68 β-lactamase. J Mol Graph Model 2022; 114:108195. [DOI: 10.1016/j.jmgm.2022.108195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Revised: 04/07/2022] [Accepted: 04/11/2022] [Indexed: 11/28/2022]
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Mills JP, Marchaim D. Multidrug-Resistant Gram-Negative Bacteria: Infection Prevention and Control Update. Infect Dis Clin North Am 2021; 35:969-994. [PMID: 34752228 DOI: 10.1016/j.idc.2021.08.001] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Multidrug-resistant gram-negative bacteria (MDR-GNB) pose one of the greatest challenges to health care today because of their propensity for human-to-human transmission and lack of therapeutic options. Containing the spread of MDR-GNB is challenging, and the application of multifaceted infection control bundles during an evolving outbreak makes it difficult to measure the relative impact of each measure. This article will review the utility of various infection control measures in containing the spread of various MDR-GNB and will provide the supporting evidence for these interventions.
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Affiliation(s)
- John P Mills
- Division of Infectious Diseases, University of Michigan Medical School, F4177 University Hospital South, 1500 E. Medical Center Dr, Ann Arbor, MI 48109-5226, USA.
| | - Dror Marchaim
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Division of Infectious Diseases, Shamir (Assaf Harofeh) Medical Center, Zerifin, Israel
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Khaled JM, Alharbi NS, Siddiqi MZ, Alobaidi AS, Nauman K, Alahmedi S, Almazyed AO, Almosallam MA, Al Jurayyan AN. A synergic action of colistin, imipenem, and silver nanoparticles against pandrug-resistant Acinetobacter baumannii isolated from patients. J Infect Public Health 2021; 14:1679-1685. [PMID: 34627065 DOI: 10.1016/j.jiph.2021.09.015] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Revised: 09/07/2021] [Accepted: 09/16/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND The upgrowth and rapid prevalence of pandrug-resistant Acinetobacter baumannii strains that have a pathogenic activity to cause several infections are of considerable influence on the health of communities worldwide. No infections by these bacterial strains were recorded before 1998, and currently, the numbers are on the rise. METHODS The A. baumannii strains were isolated from male and female patients in Medical Microbiology Department, King Fahd Medical City (KFMC) in Riyadh, Saudi Arabia between 1/1/2020 to 29/12/2020. The statistical analysis was performed base on sex, age, source of samples, and response to commercially available antibiotics. The A. baumannii strains that resisted all the antibiotics including colistin and imipenem were selected for the synergic test. RESULTS The data showed that 62.28%, 77.07% of 342 A. baumannii strains were isolated from males and patients over 35 years of age. A. baumannii strains (pandrug-A. baumannii) that can resist all tested antibiotics were 8.19%. The major source of the A. baumannii isolates was the respiratory system (>50%). Among all isolates (N = 342), azidothymidine-resistant A. baumannii strains were more than 85%. There is a statistically significant difference (P < 0.05) in the number of colistin-resistant A. baumannii strains isolated from males comparing with the female. The combinations of colistin and silver nanoparticles or imipenem and silver nanoparticles resulted in synergistic action led to reduction of MICs of colistin, imipenem, and silver nanoparticles (more than four-fold reduction). Also, the combinations of colistin and imipenem had high synergistic action. CONCLUSION The pandrug-resistant A. baumannii strains may represent a current and future threat that must be fought, and the synergy action of antibiotics and nanoparticles may be one of the available, rapid, and easy strategies to confront this global problem.
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Affiliation(s)
- Jamal M Khaled
- Department of Botany and Microbiology, College of Science, King Saud University, PO Box 4255, Riyadh 11451, Saudi Arabia.
| | - Naiyf S Alharbi
- Department of Botany and Microbiology, College of Science, King Saud University, PO Box 4255, Riyadh 11451, Saudi Arabia
| | - Muhammad Z Siddiqi
- Department of Biotechnology, Hankyong National University, 327 Jungang-ro Anseong-Si, Gyeonggi-do 17579, South Korea
| | - Ahmed S Alobaidi
- Department of Botany and Microbiology, College of Science, King Saud University, PO Box 4255, Riyadh 11451, Saudi Arabia
| | - Khaled Nauman
- Department of Botany and Microbiology, College of Science, King Saud University, PO Box 4255, Riyadh 11451, Saudi Arabia
| | - Salah Alahmedi
- Department of Botany and Microbiology, College of Science, King Saud University, PO Box 4255, Riyadh 11451, Saudi Arabia
| | - Abeer O Almazyed
- Microbiology Department, King Fahd Medical City, Riyadh, Saudi Arabia
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Longjam LA, Tsering DC, Das D. A Microbiological Study of Acinetobacter calcoaceticus baumannii with Special Reference to Multidrug Resistance. J Lab Physicians 2021; 14:169-174. [PMID: 35982877 PMCID: PMC9381315 DOI: 10.1055/s-0041-1735583] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Introduction
The outbreak of
Acinetobacter calcoaceticus baumannii
(
ACB
) is mainly reported to be a notorious pathogens at health-care settings. It is the major problem on the health-care system with high morbidity and mortality rates because of the broad range of antibiotic resistance and lack of understanding the mechanism of developing new antibiotic resistance rapidly. It emphasizes the importance of local surveillance in describing or understanding and predicting microbial resistance patterns so that there will be limited use of antibiotics by developing strategies to control the extensive use of antimicrobial chemotherapy in clinical environment, which is still considered as one of the factors in the emergence of multidrug resistance microorganisms.
Objectives
The study aims to detect the occurrence rate of
ACB
infections from various clinical samples, identify the resistance levels to different groups of antimicrobial agents, and the occurrence rate of multidrug resistant (MDR)
ACB
clinical isolates from a tertiary hospital in Durgapur, West Bengal, India.
Material and Methods
The study was performed in the Department of Microbiology of the IQ City Medical College and Hospital, Durgapur, West Bengal, India, for the 24 months duration, that is, from January 1, 2018 to December 31, 2019. Altogether 15,800 clinical samples consisting of endotracheal tube aspirates, sputum, pus, blood, catheter tips, urine, tissue, and other body fluids were studied.
ACB
from clinical samples were identified by its characteristic colonies (nonlactose fermenting, glistening, small mucoid colonies), Gram-staining pattern (Gram-negative coccobacillus), and standard biochemical reactions. It was further confirmed in the Department of Microbiology of the Healthworld Hospital, Durgapur, West Bengal, India, by Vitek2 compact system (bioMerieux, Inc., Durham, North Carolina, United States). Antibiotic susceptibility testing was performed using automated broth microdilutions by Vitek2 compact system (bioMerieux, Inc.) and Kirby-Bauer disk diffusion test on Mueller-Hinton Agar (HiMedia).
Results
Nonrepetitive 289
ACB
were isolated from various clinical samples. A total of 277 (96%) isolates of
ACB
were MDR strains.
Conclusion
ACB
was mostly isolated from the intensive care unit department and was found to be the most MDR type in the tertiary care hospital by this study.
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Affiliation(s)
- Langamba Angom Longjam
- Department of Microbiology, Sikkim Manipal Institute of Medical Sciences, Gangtok, Sikkim, India
| | - Dechen Chomu Tsering
- Department of Microbiology, Sikkim Manipal Institute of Medical Sciences, Gangtok, Sikkim, India
| | - Dipmala Das
- Department of Microbiology, IQ City Medical College and Hospital, Durgapur, West Bengal, India
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Singla A, Sharma P, Gupta A, Iqbal N, Rani C, Singh TP, Sharma S. Biophysical Characterization of Type III Pantothenate Kinase (PanK) from Acinetobacter baumannii. Protein Pept Lett 2021; 28:450-458. [PMID: 32798368 DOI: 10.2174/0929866527666200813202445] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 06/11/2020] [Accepted: 06/12/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Type-III Pantothenate kinase from the multi drug resistant bacteria, Acinetobacter baumannii (AbPanK) catalyzes the first step of the essential Coenzyme A biosynthesis pathway. AbPanK is an attractive drug target against the bacteria since it is an essential enzyme and its structure is significantly different from the human PanK. METHODS AbPanK was cloned, expressed, purified and crystallized. A good quality single crystal was used for X-ray intensity data collection. Dynamic light scattering was done for calculating the hydrodynamic radii and its oligomeric nature in the solution. Binding studies of this protein with its two substrates, Pantothenate and ATP were done using spectrofluorometer. RESULTS Our results indicated that AbPanK shows a strong affinity with pantothenate with dissociation constant of 1.2 x 10- 8 M and moderate affinity towards ATP of 3.7x 10-3 M. This fact was further substantiated by the calculations of Km of both substrates using kinase assay kit. Dynamic light scattering studies have shown that it exists as homogenous solution with hydrodynamic radii corresponding to the molecular weight of 29.55 kDa. A low-resolution X-ray intensity data set was collected, which shows that AbPank crystallizes in P2 space group with cell dimensions of a= 165 Å, b= 260 Å, and, c= 197 Å and α= 90.0, β= 113.60, γ= 90.0. DISCUSSION Recombinant Pantothenate kinase from Acinetobacter baumannii was purified to homogeneity and crystallized. The enzyme exhibits very low sequence identity (28%) to other corresponding enzymes. CONCLUSION The recombinant enzyme was active and its binding affinities with its substrates pantothenate and ATP have been studied. This information would be very useful while designing the inhibitors of this enzyme in order to fight bacterial infections associated to this pathogen.
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Affiliation(s)
- Ankita Singla
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi-110029, India
| | - Pradeep Sharma
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi-110029, India
| | - Akshita Gupta
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi-110029, India
| | - Naseer Iqbal
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi-110029, India
| | - Chitra Rani
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi-110029, India
| | - T P Singh
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi-110029, India
| | - Sujata Sharma
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi-110029, India
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Vahhabi A, Hasani A, Rezaee MA, Baradaran B, Hasani A, Samadi Kafil H, Abbaszadeh F, Dehghani L. A plethora of carbapenem resistance in Acinetobacter baumannii: no end to a long insidious genetic journey. J Chemother 2021; 33:137-155. [PMID: 33243098 DOI: 10.1080/1120009x.2020.1847421] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 10/23/2020] [Accepted: 11/02/2020] [Indexed: 01/21/2023]
Abstract
Acinetobacter baumannii, notorious for causing nosocomial infections especially in patients admitted to intensive care unit (ICU) and burn units, is best at displaying resistance to all existing antibiotic classes. Consequences of high potential for antibiotic resistance has resulted in extensive drug or even pan drug resistant A. baumannii. Carbapenems, mainly imipenem and meropenem, the last resort for the treatment of A. baumannii infections have fallen short due to the emergence of carbapenem resistant A. baumannii (CRAB). Though enzymatic degradation by production of class D β-lactamases (Oxacillinases) and class B β-lactamases (Metallo β-lactamases) is the core mechanism of carbapenem resistance in A. baumannii; however over-expression of efflux pumps such as resistance-nodulation cell division (RND) family and variant form of porin proteins such as CarO have been implicated for CRAB inception. Transduction and outer membrane vesicles-mediated transfer play a role in carbapenemase determinants spread. Colistin, considered as the most promising antibacterial agent, nevertheless faces adverse effects flaws. Cefiderocol, eravacycline, new β-lactam antibiotics, non-β-lactam-β-lactamase inhibitors, polymyxin B-derived molecules and bacteriophages are some other new treatment options streamlined.
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Affiliation(s)
- Abolfazl Vahhabi
- Immunology Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, I.R. Iran
- Department of Bacteriology and Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, I.R. Iran
| | - Alka Hasani
- Immunology Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, I.R. Iran
- Department of Bacteriology and Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, I.R. Iran
- Clinical Research Development Unit, Sina Educational, Research and Treatment Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, I.R. Iran
| | - Mohammad Ahangarzadeh Rezaee
- Immunology Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, I.R. Iran
- Department of Bacteriology and Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, I.R. Iran
| | - Behzad Baradaran
- Immunology Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, I.R. Iran
| | - Akbar Hasani
- Department of Clinical Biochemistry and Laboratory Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, I. R. Iran
| | - Hossein Samadi Kafil
- Department of Bacteriology and Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, I.R. Iran
| | - Faeze Abbaszadeh
- Department of Bacteriology and Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, I.R. Iran
| | - Leila Dehghani
- Clinical Research Development Unit, Sina Educational, Research and Treatment Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, I.R. Iran
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Nocera FP, Attili AR, De Martino L. Acinetobacter baumannii: Its Clinical Significance in Human and Veterinary Medicine. Pathogens 2021; 10:pathogens10020127. [PMID: 33513701 PMCID: PMC7911418 DOI: 10.3390/pathogens10020127] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 01/13/2021] [Accepted: 01/24/2021] [Indexed: 02/06/2023] Open
Abstract
Acinetobacter baumannii is a Gram-negative, opportunistic pathogen, causing severe infections difficult to treat. The A. baumannii infection rate has increased year by year in human medicine and it is also considered as a major cause of nosocomial infections worldwide. This bacterium, also well known for its ability to form biofilms, has a strong environmental adaptability and the characteristics of multi-drug resistance. Indeed, strains showing fully resistant profiles represent a worrisome problem in clinical therapeutic treatment. Furthermore, A. baumannii-associated veterinary nosocomial infections has been reported in recent literature. Particularly, carbapenem-resistant A. baumannii can be considered an emerging opportunistic pathogen in human medicine as well as in veterinary medicine.
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Affiliation(s)
- Francesca Paola Nocera
- Department of Veterinary Medicine and Animal Production, University of Naples “Federico II”, 80137 Naples, Italy;
| | - Anna-Rita Attili
- School of Biosciences and Veterinary Medicine, University of Camerino, 62024 Matelica, Italy;
| | - Luisa De Martino
- Department of Veterinary Medicine and Animal Production, University of Naples “Federico II”, 80137 Naples, Italy;
- Correspondence:
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17
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Zhang H, Zhao Y, Zheng Y, Kong Q, Lv N, Liu Y, Zhao D, Li J, Ye Y. Development and Validation of a Model for Predicting the Risk of Death in Patients with Acinetobacter baumannii Infection: A Retrospective Study. Infect Drug Resist 2020; 13:2761-2772. [PMID: 32848426 PMCID: PMC7428379 DOI: 10.2147/idr.s253143] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Accepted: 07/10/2020] [Indexed: 11/23/2022] Open
Abstract
Purpose This study aimed to develop and validate a personalized prediction model of death risk in patients with Acinetobacter baumannii (A. baumannii) infection and thus guide clinical research and support clinical decision-making. Patients and Methods The development group is comprised of 350 patients with A. baumannii infection admitted between January 2013 and December 2015 in The First Affiliated Hospital of Anhui Medical University. Further, 272 patients in the validation group were admitted between January 2016 and December 2018. The univariate and multivariate logistic regression analyses were used to determine the independent risk factors for death with A. baumannii infection. The nomogram prediction model was established based on the regression coefficients. The discrimination of the proposed prediction model was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC) curves and decision curve analysis (DCA). The calibration diagram was used to evaluate the calibration degree of this model. Results The infectious source, carbapenem-resistant A. baumannii (CRAB), hypoalbuminemia, Charlson comorbidity index (CCI), and mechanical ventilation (MV) were independent risk factors for death. The AUC of the ROC curve of the two groups was 0.768 and 0.792, respectively. The net income was higher when the probability was between 30% and 80%, showing a strong discrimination capacity of the proposed model. The calibration curve swung around the 45° oblique line, indicating a high degree of calibration. Conclusion The proposed model helped predict the risk of death from A. baumannii infection, improve the early identification of patients with a higher risk of death, and guide clinical treatment. ![]()
Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/iftqW0bPElE
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Affiliation(s)
- Hui Zhang
- Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People's Republic of China
| | - Yayun Zhao
- Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People's Republic of China
| | - Yahong Zheng
- Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People's Republic of China
| | - Qinxiang Kong
- Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People's Republic of China.,Department of Infectious Diseases, The Chaohu Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People's Republic of China
| | - Na Lv
- Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People's Republic of China
| | - Yanyan Liu
- Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People's Republic of China.,Anhui Center for Surveillance of Bacterial Resistance, Hefei, Anhui, People's Republic of China.,Institute of Bacterial Resistance, Anhui Medical University, Hefei, Anhui, People's Republic of China
| | - Dongmei Zhao
- Department of Infectious Disease, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People's Republic of China
| | - Jiabin Li
- Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People's Republic of China.,Department of Infectious Diseases, The Chaohu Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People's Republic of China.,Anhui Center for Surveillance of Bacterial Resistance, Hefei, Anhui, People's Republic of China.,Institute of Bacterial Resistance, Anhui Medical University, Hefei, Anhui, People's Republic of China
| | - Ying Ye
- Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People's Republic of China
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18
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High mortality in an outbreak of multidrug resistant Acinetobacter baumannii infection introduced to an oncological hospital by a patient transferred from a general hospital. PLoS One 2020; 15:e0234684. [PMID: 32702006 PMCID: PMC7377454 DOI: 10.1371/journal.pone.0234684] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2019] [Accepted: 06/01/2020] [Indexed: 02/08/2023] Open
Abstract
OBJECTIVE To describe the clinical features, outcomes, and molecular epidemiology of an outbreak of multidrug resistant (MDR) A. baumannii. METHODS We performed a retrospective analysis of all MDR A. baumannii isolates recovered during an outbreak from 2011 to 2015 in a tertiary care cancer hospital. Cases were classified as colonized or infected. We determined sequence types following the Bartual scheme and plasmid profiles. RESULTS There were 106 strains of A. baumannii isolated during the study period. Sixty-six (62.3%) were considered as infection and 40 (37.7%) as colonization. The index case, identified by molecular epidemiology, was a patient with a drain transferred from a hospital outside Mexico City. Ninety-eight additional cases had the same MultiLocus Sequence Typing (MLST) 758, of which 94 also had the same plasmid profile, two had an extra plasmid, and two had a different plasmid. The remaining seven isolates belonged to different MLSTs. Fifty-three patients (50%) died within 30 days of A. baumanniii isolation: 28 (20%) in colonized and 45 (68.2%) in those classified as infection (p<0.001). In multivariate regression analysis, clinical infection and patients with hematologic neoplasm, predicted 30-day mortality. The molecular epidemiology of this outbreak showed the threat posed by the introduction of MDR strains from other institutions in a hospital of immunosuppressed patients and highlights the importance of adhering to preventive measures, including contact isolation, when admitting patients with draining wounds who have been hospitalized in other institutions.
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Amera GM, Khan RJ, Pathak A, Jha RK, Jain M, Muthukumaran J, Singh AK. Structure based drug designing and discovery of promising lead molecules against UDP-N-acetylenolpyruvoylglucosamine reductase (MurB): A potential drug target in multi-drug resistant Acinetobacter baumannii. J Mol Graph Model 2020; 100:107675. [PMID: 32731183 DOI: 10.1016/j.jmgm.2020.107675] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Revised: 06/27/2020] [Accepted: 06/29/2020] [Indexed: 11/28/2022]
Abstract
According to the world health organization (WHO) reports, Acinetobacter baumannii was considered as one of the significant and first-line priority pathogens, which causes hospital-acquired nosocomial infections in human. The enzymes involved in the peptidoglycan biosynthetic pathway are critical for the survival of this bacterium. Therefore, these enzymes are ideal drug target since they are conserved among most of the species and non-homologous to human. Here, we utilized the structure-based virtual screening (SBVS) technique to identify the promising lead molecules against MurB (UDP-N-acetylenolpyruvoylglucosamine reductase) protein using computational approaches. Initially, the three-dimensional structure of MurB was predicted based on MurB from P. aeruginosa (PDB ID: 4JAY), which is used as a structural template for homology modeling. During the High-throughput Virtual screening (HTVS) analysis, we started with 30,792 molecules against MurB model, among these; only 5238 molecules could be considered suitable for further step. Finally, only twenty molecules were able to pass Lipinski's and ADMET properties. After a thorough examination of interaction analysis, higher ΔG and Ki values, we had chosen five promising molecules (ZINC IDs: ZINC12530134, ZINC15675540, ZINC15675762, ZINC15675624 and ZINC15707270) and three control molecules (PubChem IDs: 54682555, 729933 and 39964628) for Molecular dynamics (MD) simulation to understand the effect of ligands towards the structural stability, structural integrity and structural compactness of MurB protein. Further, the MM/PBSA binding free energy analysis was performed for eight ligands bound MurB structures. Together the results obtained from global dynamics, essential dynamics and MM-PBSA binding free energy analysis, we concluded that apart from the control molecules, ZINC12530134 should be considered as one of the most promising ones and it could be the potent inhibitor against A baumannii and provide valuable insight for further experimental studies.
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Affiliation(s)
- Gizachew Muluneh Amera
- Department of Biotechnology, School of Engineering and Technology, Sharda University, P.C. 201310, Greater Noida, U.P., India
| | - Rameez Jabeer Khan
- Department of Biotechnology, School of Engineering and Technology, Sharda University, P.C. 201310, Greater Noida, U.P., India
| | - Amita Pathak
- Department of Chemistry, Indian Institute of Technology, Hauz Khas, New Delhi, 110016, India
| | - Rajat Kumar Jha
- Department of Biotechnology, School of Engineering and Technology, Sharda University, P.C. 201310, Greater Noida, U.P., India
| | - Monika Jain
- Department of Biotechnology, School of Engineering and Technology, Sharda University, P.C. 201310, Greater Noida, U.P., India
| | - Jayaraman Muthukumaran
- Department of Biotechnology, School of Engineering and Technology, Sharda University, P.C. 201310, Greater Noida, U.P., India
| | - Amit Kumar Singh
- Department of Biotechnology, School of Engineering and Technology, Sharda University, P.C. 201310, Greater Noida, U.P., India.
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Tawfick MM, Rady HF, El-Borhamy MI, Maraqa AD. Dissemination of Plasmid-Mediated Aminoglycoside-Modifying Enzymes Among MDR Acinetobacter baumannii Isolates from a Tertiary Care Egyptian Hospital. Open Microbiol J 2020. [DOI: 10.2174/1874285802014010098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Background:
Acinetobacter baumannii is one of the most challenging multidrug-resistant (MDR) nosocomial pathogens worldwide. Aminoglycosides are used for the treatment of A. baumannii infections, however, resistance to aminoglycosides is currently emerging, limiting therapeutic choices.
Objective:
In this study, the prevalence of aminoglycoside resistance and plasmid-mediated mechanisms of aminoglycoside resistance were investigated in A. baumannii clinical isolates collected from ICU patients at a tertiary care hospital in Egypt.
Methods:
The automated Vitek 2 system was used to identify A. baumannii species and determination of the antimicrobial susceptibility pattern. The identification of A. baumannii was confirmed by the detection of the blaOXA-51-like gene intrinsic to this species. Minimum Inhibitory Concentration (MIC) of gentamicin was determined using E-test following the CLSI breakpoints. Isolates were screened for the prevalence and diversity of the plasmid-carried aminoglycoside-modifying enzymes encoding genes aacC1, aadA1, aadB and aphA6. For genetic diversity analysis, the ERIC-PCR method was performed.
Results:
All A. baumannii isolates were MDR with high resistance rates to tested antimicrobials. The resistance rate to gentamicin was 92.9% with elevated MICs (≥ 32 μg/mL). The gentamicin-resistant isolates harboured one or more of the studied genes with the prevalence of aphA6 (81%). ERIC-based genotyping revealed that there was no evidence of A. baumannii clonal dissemination among isolates.
Conclusion:
The study concluded that MDR A. baumannii isolates were highly resistant to gentamicin. The plasmid-carried aminoglycoside-modifying enzymes encoding genes were disseminated among isolates with the AphA6 gene, which was the most prevalent one. The acquisition of more than one aminoglycoside resistance gene was associated with an elevated MIC of gentamicin. Thus, regular surveillance studies of the emerging resistance to antimicrobials and strict measures to control the dissemination of resistance determinants genes are warranted.
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Detection of Antimicrobial Resistance Genes Associated with Carbapenem Resistance from the Whole-Genome Sequence of Acinetobacter baumannii Isolates from Malaysia. CANADIAN JOURNAL OF INFECTIOUS DISEASES & MEDICAL MICROBIOLOGY 2020; 2020:5021064. [PMID: 32318127 PMCID: PMC7154965 DOI: 10.1155/2020/5021064] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Revised: 12/20/2019] [Accepted: 01/09/2020] [Indexed: 12/20/2022]
Abstract
Background The spread of carbapenem-resistant A. baumannii (CrAb) is gaining worldwide attention. The spread of this pathogen is largely due to its ability to acquire various resistance genes of intrinsic and extrinsic origins that confer unpredictable susceptibility to β-lactams. The aim of this study was to analyze β-lactamase genetic compositions of CrAb in Malaysia. Methods Whole-genome sequencing (WGS) was carried out on 13 CrAb isolates from clinical samples in Malaysia from 2011 to 2016. Results Endotracheal aspirate was the dominant clinical sample source (n = 6), and only one isolate was obtained from wound swab. A total of 6 sequence types (STs) of the Oxford scheme were identified, including 4 reported STs and 2 novel STs. Eleven isolates were classified into clonal complex 92 (CC92/ICII), among which ST195 and ST208 were the most prevalent STs. All 13 CrAb isolates harbored multiple β-lactamase genes. blaOXA-23 (n = 13) and blaOXA-66 (n = 11) were the dominant carbapenemase gene families found in these isolates. All isolates harbor blaADC, blaOXA-51-like, and blaOXA-23-like genes. blaTEM (n = 7), blaNDM-1 (n = 3), blaCARB-8 (n = 1), and blaPER-3 (n = 1) are amongst other β-lactamase genes found in this study. ISAba1 was found upstream to blaOXA-23 (n = 13), blaOXA-66 (n = 1), and blaADC (n = 11). All blaNDM-1 isolates had ISAba125 (mobile genetic element) upstream to the genes. All isolates were positive for Tn2006/2008 and Tn2009 but were negative for Tn2007. Conclusion Most of the isolates were grouped under the CC92 clonal complex which belongs to international clonal lineage 2. These findings predict that carriage of carbapenem-resistant genes possibly constitutes the underlying basis of high level of international clone II prevalence. Therefore, molecular surveillance and antimicrobial stewardship are essential in implementing policies to prevent and control the spread of CrAb in hospital settings.
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Hood-Pishchany MI, Pham L, Wijers CD, Burns WJ, Boyd KL, Palmer LD, Skaar EP, Noto MJ. Broad-spectrum suppression of bacterial pneumonia by aminoglycoside-propagated Acinetobacter baumannii. PLoS Pathog 2020; 16:e1008374. [PMID: 32168364 PMCID: PMC7094866 DOI: 10.1371/journal.ppat.1008374] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2019] [Revised: 03/25/2020] [Accepted: 01/31/2020] [Indexed: 12/29/2022] Open
Abstract
Antimicrobial resistance is increasing in pathogenic bacteria. Yet, the effect of antibiotic exposure on resistant bacteria has been underexplored and may affect pathogenesis. Here we describe the discovery that propagation of the human pathogen Acinetobacter baumannii in an aminoglycoside antibiotic results in alterations to the bacterium that interact with lung innate immunity resulting in enhanced bacterial clearance. Co-inoculation of mice with A. baumannii grown in the presence and absence of the aminoglycoside, kanamycin, induces enhanced clearance of a non-kanamycin-propagated strain. This finding can be replicated when kanamycin-propagated A. baumannii is killed prior to co-inoculation of mice, indicating the enhanced bacterial clearance results from interactions with innate host defenses in the lung. Infection with kanamycin-propagated A. baumannii alters the kinetics of phagocyte recruitment to the lung and reduces pro- and anti-inflammatory cytokine and chemokine production in the lung and blood. This culminates in reduced histopathologic evidence of lung injury during infection despite enhanced bacterial clearance. Further, the antibacterial response induced by killed aminoglycoside-propagated A. baumannii enhances the clearance of multiple clinically relevant Gram-negative pathogens from the lungs of infected mice. Together, these findings exemplify cooperation between antibiotics and the host immune system that affords protection against multiple antibiotic-resistant bacterial pathogens. Further, these findings highlight the potential for the development of a broad-spectrum therapeutic that exploits a similar mechanism to that described here and acts as an innate immunity modulator.
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Affiliation(s)
- M. Indriati Hood-Pishchany
- Department of Pediatrics, Division of Infectious Diseases, Boston Children’s Hospital, Boston, Massachusetts, United States of America
| | - Ly Pham
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America
- Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America
| | - Christiaan D. Wijers
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America
- Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America
| | - William J. Burns
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America
| | - Kelli L. Boyd
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America
- Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America
| | - Lauren D. Palmer
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America
- Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America
| | - Eric P. Skaar
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America
- Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America
- Tennessee Valley Healthcare System, US Department of Veterans Affairs, Nashville, Tennessee, United States of America
| | - Michael J. Noto
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America
- Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America
- Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America
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Subramaniyan JS, Sundaram JM. Occurrence of bla genes encoding carbapenem-resistant Pseudomonas aeruginosa and Acinetobacter baumannii from Intensive Care Unit in a tertiary care hospital. J Lab Physicians 2020; 10:208-213. [PMID: 29692589 PMCID: PMC5896190 DOI: 10.4103/jlp.jlp_108_17] [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] [Indexed: 12/04/2022] Open
Abstract
CONTEXT: ICU shows increasing incidence of infection associated with the use of invasive procedures for the diagnostic purpose as well as the indiscriminate use of antibiotics. Pseudomonas aeruginosa and Acinetobacter species are “very successful” pathogen and the emergence of the Metallo-β-Lactamases (MBL) is becoming a therapeutic challenge. AIMS: To isolate the Nonfermenting Gram negative bacilli from the ICU samples. To identify the metallo betalactamase producers and to detect the bla gene presence among the Pseudomonas aeruginosa and Acinetobacter baumannii. SETTINGS AND DESIGN: The Nonfermenting Gram negative bacilli isolates from the ICU samples were taken over for 5 years (2009-2014) in a tertiary care hospital. METHODS AND MATERIALS: The isolates of Pseudomonas species and Acinetobacter species were confirmed by API analyser and processed according to standard procedures. Detection of the MBL producers were done by E strip method and subjected for bla gene detection by PCR method. RESULTS: In our study a total of 195 isolates of NFGNB were obtained from various ICU. Of these MBL producers, 26 % were Pseudomonas aeruginosa and 25 % were Acinetobacter baumannii. The subtypes of blaVIM MBL producing P.aeruginosa were 26%. The predominant gene coding for MBL activity in A.baumannii were found to be blaOXA gene 11.9%. The gene accession numbers were KF975367, KF975372. CONCLUSIONS: We have to control the development and dissemination of these superbugs among the ICU's.
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Affiliation(s)
| | - Jeya Meenakshi Sundaram
- Department of Microbiology, Chettinad Hospital and Research Institute, Kanchipuram, Tamil Nadu, India
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Wang J, Ning Y, Li S, Wang Y, Liang J, Jin C, Yan H, Huang Y. Multidrug-resistant Acinetobacter baumannii strains with NDM-1: Molecular characterization and in vitro efficacy of meropenem-based combinations. Exp Ther Med 2019; 18:2924-2932. [PMID: 31572535 PMCID: PMC6755477 DOI: 10.3892/etm.2019.7927] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2018] [Accepted: 12/31/2018] [Indexed: 11/24/2022] Open
Abstract
Acinetobacter baumannii is an important cause of hospital-acquired, multidrug-resistant (MDR) infections occurring worldwide. Anti-microbial combination regimens may be the only feasible treatment option for affected patients. In the present study, the efficacy of the combined therapy of meropenem with colistin, ampicillin-sulbactam, tazobactam and vancomycin against clinical strains of MDR A. baumannii was determined. Anti-microbial susceptibility testing was performed and resistance genes were characterized by a multiplex polymerase chain reaction (PCR)-reverse line blot assay. The genetic background of New Delhi metallo-β-lactamase 1 (NDM-1) was analysed by primer walking. The presence of NDM-1 was detected using the modified Hodge test and the EDTA-combined disk test. To screen for synergistic drug effects, the fractional inhibitory concentration index was calculated using a checkerboard assay. The results of the PCR as well as the sequence analyses suggested that NDM-1 was located downstream of the ISAba125 element. In addition, a synergistic effect was determined for meropenem + vancomycin, meropenem + tazobactam and meropenem + ampicillin + sulbactam in two strains each, and in four strains for meropenem + colistin. A total of five A. baumannii strains with resistance to numerous antibiotics and carrying numerous resistance genes were identified. In the strains of A. baumannii, the NDM-1 gene was integrated in a transposon structure with a copy of the ISAba125 insertion sequence. However, the genetic background was not identical among the different species and strains. The genetic variability of NDM-1 may facilitate the rapid dissemination of this gene. In conclusion, meropenem may enhance the efficacy of antibiotics in A. baumannii strains with NDM-1-associated MDR.
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Affiliation(s)
- Jingjing Wang
- Department of Laboratory Medicine, The Second Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan 471000, P.R. China
| | - Yongzhong Ning
- Department of Laboratory Medicine, Beijing ChuiYangLiu Hospital Affiliated to Tsinghua University, Beijing 100022, P.R. China
| | - Shu Li
- Department of Laboratory Medicine, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, P.R. China
| | - Yun Wang
- Department of Laboratory Medicine, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, P.R. China
| | - Jinhua Liang
- Department of Laboratory Medicine, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, P.R. China
| | - Chunming Jin
- Department of Laboratory Medicine, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, P.R. China
| | - Hairun Yan
- Department of Laboratory Medicine, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, P.R. China
| | - Yongcun Huang
- Department of Laboratory Medicine, The Second Affiliated Hospital of Mudanjiang Medical College, Mudanjiang, Heilongjiang 157001, P.R. China
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26
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Yagnik KJ, Kalyatanda G, Cannella AP, Archibald LK. Outbreak of Acinetobacter baumannii associated with extrinsic contamination of ultrasound gel in a tertiary centre burn unit. Infect Prev Pract 2019; 1:100009. [PMID: 34368675 PMCID: PMC8336045 DOI: 10.1016/j.infpip.2019.100009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Accepted: 06/20/2019] [Indexed: 11/28/2022] Open
Abstract
Background During 2011 and 2012, an increase in occurrence of multidrug-resistant Acinetobacter baumannii infections was recorded in the Shands Hospital Burn Intensive Care Unit (BICU). An epidemic curve together with strain typing was consistent with an intermittent common source outbreak. An investigation was therefore initiated. Aim To identify risk factors for A. baumannii infection, characterize the source of the pathogen, implement control measures to terminate the outbreak, and institute preventive measures. Methods We conducted a retrospective case-control study; reviewed BICU infection control policies, practices and procedures, and patient exposure to healthcare workers (HCWs), and obtained epidemiologically-directed environmental cultures. Findings Eleven patients met the case definition. On multivariate analysis, case-patients were more likely to have undergone an ultrasound procedure in the BICU (adjusted odds ratio [AOR]: 19.5; confidence interval [CI]: 2.4-435) or have a FlexiSeal™ device (AOR: 11.9, CI:1.3-276). Epidemiologically-directed cultures of the environment, ultrasound equipment, and ultrasound gel from opened containers on the ultrasound trolley and in the Ultrasound Department were negative for the outbreak pathogen. Culture of an open ultrasound gel dispenser stored in the Ultrasound Department yielded an A. baumannii strain with DNA banding patterns identical to the outbreak strain. Conclusions Based on data from our epidemiologic, microbiologic, and observational studies, we believe that inadvertent extrinsic contamination of the gel dispenser occurred in the Ultrasound Department. Contaminated gel was then dispensed into multiuse vials of gel stored on the mobile carts. The outbreak was stemmed by instituting changes in practices in the Ultrasound Department, including introduction of single-use ultrasound vials and storage of ultrasound gel.
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Affiliation(s)
- Kruti J Yagnik
- University of Florida College of Medicine, Department of Medicine, Gainesville, FL, USA
| | - Gautam Kalyatanda
- University of Florida College of Medicine, Department of Medicine, Division of Infectious Diseases & Global Medicine, Gainesville, FL, USA
| | - Anthony P Cannella
- University of Florida College of Medicine, Department of Medicine, Division of Infectious Diseases & Global Medicine, Gainesville, FL, USA.,Malcolm Randall Veterans Health Administration Medical Centre, Gainesville, FL, USA.,University of Florida College of Medicine, Department of Molecular Genetics & Microbiology, Gainesville, FL, USA.,University of Florida College of Medicine, Emerging Pathogens Institute, Gainesville, FL, USA
| | - Lennox K Archibald
- University of Florida College of Medicine, Department of Medicine, Division of Infectious Diseases & Global Medicine, Gainesville, FL, USA.,Malcolm Randall Veterans Health Administration Medical Centre, Gainesville, FL, USA
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27
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Oh DH, Kim YC, Kim EJ, Jung IY, Jeong SJ, Kim SY, Park MS, Kim A, Lee JG, Paik HC. Multidrug-resistant Acinetobacter baumannii infection in lung transplant recipients: risk factors and prognosis. Infect Dis (Lond) 2019; 51:493-501. [PMID: 31081415 DOI: 10.1080/23744235.2018.1556400] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/26/2022] Open
Abstract
Backgrounds: Infectious complication is an important cause of poor outcome of lung transplantation (LT). Infections with Acinetobacter baumannii (A. baumannii) are problematic, because of limited therapeutic option due to increasing resistance to antibiotics. However, there are few studies on A. baumannii infection in lung transplant recipients. Thus, we aimed to investigate epidemiology and risk factors for infection with A. baumannii in lung transplant recipients. Methods: Lung transplant recipients ≥18 years of age in a university hospital were enrolled in this retrospective cohort study. Risk factors for infection with multidrug resistant A. baumannii and 90-day mortality were analysed. Results: Fifty-one of 96 lung transplant recipients experienced A. baumannii infection. Infected patients had a significantly higher 90-day mortality rate than uninfected (19.6% vs. 2.2%, p = .009). High blood urea nitrogen (BUN) before transplantation (odds ratio [OR] 1.16; p = .008), long duration of surgery (OR 1.16; p = .029) and hypoalbuminemia before transplantation (OR 4.01; p = .037) were independent risk factors for infection with multidrug resistant A. baumannii. On multivariate analysis, severe thrombocytopenia (OR 28.69; p = .005), high serum creatinine (OR 1.48; p = .042) and infection with multidrug resistant A. baumannii (OR 22.58; p = .031) were independent risk factors for 90-day mortality. Conclusions: Prolonged surgery, high BUN and hypoalbuminemia before LT were significant risk factors for infection with multidrug resistant A. baumannii. Severe thrombocytopenia, high serum creatinine and infection with multidrug resistant A. baumannii infection were independent risk factors for 90-day mortality.
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Affiliation(s)
- Dong Hyun Oh
- a Department of Internal Medicine, Division of Infectious Disease , Seoul Medical Center , Seoul , South Korea
| | - Yong Chan Kim
- b Department of Internal Medicine, Division of Infectious Disease , Yonsei University College of Medicine , Seoul , South Korea
| | - Eun Jin Kim
- b Department of Internal Medicine, Division of Infectious Disease , Yonsei University College of Medicine , Seoul , South Korea
| | - In Young Jung
- b Department of Internal Medicine, Division of Infectious Disease , Yonsei University College of Medicine , Seoul , South Korea
| | - Su Jin Jeong
- b Department of Internal Medicine, Division of Infectious Disease , Yonsei University College of Medicine , Seoul , South Korea
| | - Song Yee Kim
- c Department of Internal Medicine, Division of Pulmonology , Institute of Chest Diseases, Yonsei University College of Medicine , Seoul , South Korea
| | - Moo Suk Park
- c Department of Internal Medicine, Division of Pulmonology , Institute of Chest Diseases, Yonsei University College of Medicine , Seoul , South Korea
| | - Anes Kim
- d Department of Thoracic and Cardiovascular Surgery , Yonsei University College of Medicine , Seoul , South Korea
| | - Jin Gu Lee
- d Department of Thoracic and Cardiovascular Surgery , Yonsei University College of Medicine , Seoul , South Korea
| | - Hyo Chae Paik
- d Department of Thoracic and Cardiovascular Surgery , Yonsei University College of Medicine , Seoul , South Korea
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28
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Kamischke C, Fan J, Bergeron J, Kulasekara HD, Dalebroux ZD, Burrell A, Kollman JM, Miller SI. The Acinetobacter baumannii Mla system and glycerophospholipid transport to the outer membrane. eLife 2019; 8:e40171. [PMID: 30638443 PMCID: PMC6365058 DOI: 10.7554/elife.40171] [Citation(s) in RCA: 71] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Accepted: 01/11/2019] [Indexed: 01/14/2023] Open
Abstract
The outer membrane (OM) of Gram-negative bacteria serves as a selective permeability barrier that allows entry of essential nutrients while excluding toxic compounds, including antibiotics. The OM is asymmetric and contains an outer leaflet of lipopolysaccharides (LPS) or lipooligosaccharides (LOS) and an inner leaflet of glycerophospholipids (GPL). We screened Acinetobacter baumannii transposon mutants and identified a number of mutants with OM defects, including an ABC transporter system homologous to the Mla system in E. coli. We further show that this opportunistic, antibiotic-resistant pathogen uses this multicomponent protein complex and ATP hydrolysis at the inner membrane to promote GPL export to the OM. The broad conservation of the Mla system in Gram-negative bacteria suggests the system may play a conserved role in OM biogenesis. The importance of the Mla system to Acinetobacter baumannii OM integrity and antibiotic sensitivity suggests that its components may serve as new antimicrobial therapeutic targets.
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Affiliation(s)
- Cassandra Kamischke
- Department of Microbiology, University of Washington, Seattle, United States
| | - Junping Fan
- Department of Microbiology, University of Washington, Seattle, United States
| | - Julien Bergeron
- Department of Biochemistry, University of Washington, Seattle, United States
- Department of Molecular Biology and Biotechnology, The University of Sheffield, Sheffield, United Kingdom
| | | | - Zachary D Dalebroux
- Department of Microbiology, University of Washington, Seattle, United States
| | - Anika Burrell
- Department of Biochemistry, University of Washington, Seattle, United States
| | - Justin M Kollman
- Department of Biochemistry, University of Washington, Seattle, United States
| | - Samuel I Miller
- Department of Microbiology, University of Washington, Seattle, United States
- Department of Genome Sciences, University of Washington, Seattle, United States
- Department of Medicine, University of Washington, Seattle, United States
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29
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Linz B, Mukhtar N, Shabbir MZ, Rivera I, Ivanov YV, Tahir Z, Yaqub T, Harvill ET. Virulent Epidemic Pneumonia in Sheep Caused by the Human Pathogen Acinetobacter baumannii. Front Microbiol 2018; 9:2616. [PMID: 30459734 PMCID: PMC6232368 DOI: 10.3389/fmicb.2018.02616] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Accepted: 10/12/2018] [Indexed: 01/12/2023] Open
Abstract
The human pathogen Acinetobacter baumannii has emerged as a frequent cause of hospital-acquired infections, but infection of animals has rarely been observed. Here we analyzed an outbreak of epidemic pneumonia killing hundreds of sheep on a farm in Pakistan and identified A. baumannii as the infecting agent. A pure culture of strain AbPK1 isolated from lungs of sick animals was inoculated into healthy sheep, which subsequently developed similar disease symptoms. Bacteria re-isolated from the infected animals were shown to be identical to the inoculum, fulfilling Koch’s postulates. Comparison of the AbPK1 genome against 2283 A. baumannii genomes from the NCBI database revealed that AbPK1 carries genes for unusual surface structures, including a unique composition of iron acquisition genes, genes for O-antigen synthesis and sialic acid-specific acetylases of cell-surface carbohydrates that could enable immune evasion. Several of these unusual and otherwise rarely present genes were also identified in genomes of phylogenetically unrelated A. baumannii isolates from combat-wounded US military from Afghanistan indicating a common gene pool in this geographical region. Based on core genome MLST this virulent isolate represents a newly emerging lineage of Global Clone 2, suggesting a human source for this disease outbreak. The observed epidemic, direct transmission from sheep to sheep, which is highly unusual for A. baumannii, has important consequences for human and animal health. First, direct animal-to-animal transmission facilitates fast spread of pathogen and disease in the flock. Second, it may establish a stable ecological niche and subsequent spread in a new host. And third, it constitutes a serious risk of transmission of this hyper-virulent clone from sheep back to humans, which may result in emergence of contagious disease amongst humans.
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Affiliation(s)
- Bodo Linz
- Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, United States.,Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, United States
| | - Nadia Mukhtar
- Quality Operations Laboratory, University of Veterinary and Animal Sciences, Lahore, Pakistan
| | - Muhammad Zubair Shabbir
- Quality Operations Laboratory, University of Veterinary and Animal Sciences, Lahore, Pakistan
| | - Israel Rivera
- Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, United States.,Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, United States
| | - Yury V Ivanov
- Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, United States
| | - Zarfishan Tahir
- Quality Operations Laboratory, University of Veterinary and Animal Sciences, Lahore, Pakistan
| | - Tahir Yaqub
- Quality Operations Laboratory, University of Veterinary and Animal Sciences, Lahore, Pakistan
| | - Eric T Harvill
- Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, United States.,Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, United States
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Rebic V, Masic N, Teskeredzic S, Aljicevic M, Abduzaimovic A, Rebic D. The Importance of Acinetobacter Species in the Hospital Environment. Med Arch 2018; 72:325-329. [PMID: 30524162 PMCID: PMC6282909 DOI: 10.5455/medarh.2018.72.330-334] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2018] [Accepted: 09/25/2018] [Indexed: 11/03/2022] Open
Abstract
INTRODUCTION Acinetobacter species is associated with health care associated infections especially in patients on respiratory therapy equipment and indwelling catheters. They are becoming increasingly drug resistant. The knowledge of the prevalence and pattern of antimicrobial susceptibility pattern of Acinetobacter spp. is important. AIMS The study is undertaken to estimate the prevalence rate, risk factors and antimicrobial resistance pattern of isolates. in Acinetobacter spp. from various clinical samples. MATERIAL AND METHODS The isolates of Acinetobacter species obtained from various clinical specimen. Specimens were processed by standard microbiological techniques. Antimicrobial sensitivity tests of the Acinetobacter isolates were done by modified Kirby-Bauer disc diffusion method. RESULTS Out of 622 isolates, 399 isolates were from inpatients (62,18%) and 223 were from outpatients (37,82%). More than 90% of isolates displayed resistance to ampicillin, amoxicillin-clavulanic acid, ceftazidime, caftriaxon and amikacin. Resistance to gentamicin, co-trimoxazole and ciprofloxacin were also common. Least resistance was seen to piperacillin-tazobactam and imipenem. A total of 125 Acinetobacter isolates were analyzed, out of which 78.4 % were multi-drug resistant (MDR). Of these MDR isolates, 17.24% were pan-resistant. A. baumannii was the most common species responsible for wound infection (84,8%), pneumonia(96,15%), abscess (72.7%), urinary tract infection (85,7%) and septicemia(89,5%). CONCLUSION Multi-drug resistant Acinetobacter has emerged as an important nosocomial pathogen. Antibiotic susceptibility testing is critical in the treatment of infections caused by Acinetobacter. Continued surveillance of prevalent organisms in ICUs, combined with preventive measures remains absolutely essential in efforts to prevent or limit the spread of Acinetobacter infection.
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Affiliation(s)
- Velma Rebic
- Institute of Microbiology, Faculty of Medicine, University of Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - Nejra Masic
- Public Health Center, Donji Vakuf, Bosnia and Herzegovina
| | - Sanela Teskeredzic
- Department of Microbiology, Public Hospital Travnik, Travnik, Bosnia and Herzegovina
| | - Mufida Aljicevic
- Institute of Microbiology, Faculty of Medicine, University of Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - Amila Abduzaimovic
- Institute of Microbiology, Faculty of Medicine, University of Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - Damir Rebic
- Clinical for Nephrology, Clinical Center of Sarajevo University, Sarajevo, Bosnia and Herzegovina
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31
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Jiang L, Lin J, Taggart CC, Bengoechea JA, Scott CJ. Nanodelivery strategies for the treatment of multidrug-resistant bacterial infections. JOURNAL OF INTERDISCIPLINARY NANOMEDICINE 2018; 3:111-121. [PMID: 30443410 PMCID: PMC6220773 DOI: 10.1002/jin2.48] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/17/2018] [Revised: 06/27/2018] [Accepted: 07/10/2018] [Indexed: 12/15/2022]
Abstract
One of the most important health concerns in society is the development of nosocomial infections caused by multidrug-resistant pathogens. The purpose of this review is to discuss the issues in current antibiotic therapies and the ongoing progress of developing new strategies for the treatment of ESKAPE pathogen infections, which is acronymized for Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species. We not only examine the current issues caused by multidrug resistance but we also examine the barrier effects such as biofilm and intracellular localization exploited by these pathogens to avoid antibiotic exposure. Recent innovations in nanomedicine approaches and antibody antibiotic conjugates are reviewed as potential novel approaches for the treatment of bacterial infection, which ultimately may expand the useful life span of current antibiotics.
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Affiliation(s)
- Lai Jiang
- Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical SciencesQueen's University BelfastBelfastUK
| | - Jia Lin
- School of PharmacyQueen's University BelfastBelfastUK
| | - Clifford C. Taggart
- Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical SciencesQueen's University BelfastBelfastUK
| | - José A. Bengoechea
- Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical SciencesQueen's University BelfastBelfastUK
| | - Christopher J. Scott
- Centre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical SciencesQueen's University BelfastBelfastUK
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32
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Lin SY, Huang ZH, Chen HC, Chang DM, Lu CC. Multidrug-resistance Acinetobacter baumannii pneumonia in a rheumatoid arthritis patient receiving tumor necrosis factor inhibitor: A case report. Medicine (Baltimore) 2018; 97:e11730. [PMID: 30113458 PMCID: PMC6113047 DOI: 10.1097/md.0000000000011730] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
Abstract
INTRODUCTION Multidrug-resistant Acinetobacter baumannii (MDRAB) pneumonia with severe sepsis in a patient with rheumatoid arthritis (RA), who is predisposed after treatment with tumor necrosis factor inhibitor (TNFI), is a rare severe infection and can be successfully treated with prompt antibiotics. CASE PRESENTATION A 75-year-old woman was diagnosed with RA >30 years previously. After inadequate treatment responses to conventional disease-modifying antirheumatic drugs (DMARDs), she developed progressive RA, including swollen joints in both hands, and had a high disease activity score of 4.96 when presenting at our rheumatology clinic. She had started taking the TNFI, golimumab (50 mg/month), 3 years before and developed a productive cough 4 weeks before this admission. One week after admission, she developed fever, dyspnea, hypoxemia, tachycardia, and increased serum C-reactive protein level. DIAGNOSIS Chest plain film (CxR) and computed tomography of the chest showed hospital-acquired pneumonia; microbial examination of the sputum showed the presence of MDRAB. THERAPEUTICS She was prescribed a full course of antibiotics with cefoperazone sulbactam. OUTCOMES CxR showed complete remission of pneumonia. CONCLUSION Biological DMARDs, such as TNFI, act as a double-edged sword: these drugs are used to treat autoimmune diseases, but they increase the risk of infection. The trend toward antibiotic resistance and persistent environmental survival of MDRAB is an emerging problem in countries with high rates of antibiotic abuse. TNFI may affect intestinal immunity by inducing dysbiosis, which affects T helper 17-mediated mucosal immunity and can contribute to A baumannii colonization and the development of MDRAB in frequently hospitalized patients.
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Affiliation(s)
- Shu-Yi Lin
- Division of Rheumatology/Immunology and Allergy, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei
| | - Zheng-Hao Huang
- Division of Rheumatology/Immunology and Allergy, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei
- Division of Rheumatology/Immunology and Allergy, Department of Medicine, Kaohsiung Armed Forces General Hospital, Kaohsiung
| | - Hsiang-Cheng Chen
- Division of Rheumatology/Immunology and Allergy, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei
| | - Deh-Ming Chang
- Division of Rheumatology/Immunology and Allergy, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taipei Veteran General Hospital, Taipei, Taiwan
| | - Chun-Chi Lu
- Division of Rheumatology/Immunology and Allergy, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei
- Department of Pathology, University of Washington, WA
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Multidrug-Resistant Acinetobacter baumannii Chloramphenicol Resistance Requires an Inner Membrane Permease. Antimicrob Agents Chemother 2018; 62:AAC.00513-18. [PMID: 29891596 DOI: 10.1128/aac.00513-18] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2018] [Accepted: 06/04/2018] [Indexed: 11/20/2022] Open
Abstract
Acinetobacter baumannii is a Gram-negative organism that is a cause of hospital-acquired multidrug-resistant (MDR) infections. A. baumannii has a unique cell surface compared to those of many other Gram-negative pathogens in that it can live without lipopolysaccharide (LPS) and it has a high content of cardiolipin in the outer membrane. Therefore, to better understand the cell envelope and mechanisms of MDR A. baumannii, we screened a transposon library for mutants with defective permeability barrier function, defined as a deficiency in the ability to exclude the phosphatase chromogenic substrate 5-bromo-4-chloro-3-indolylphosphate (XP). We identified multiple mutants with mutations in the ABUW_0982 gene, predicted to encode a permease broadly present in A. baumannii isolates with increased susceptibility to the ribosome-targeting antibiotic chloramphenicol (CHL). Moreover, compared to other known CHL resistance genes, such as chloramphenicol acyltransferase genes, we found that ABUW_0982 is the primary determinant of intrinsic CHL resistance in A. baumannii strain 5075 (Ab5075), an important isolate responsible for severe MDR infections in humans. Finally, studies measuring the efflux of chloramphenicol and expression of ABUW_0982 in CHL-susceptible Escherichia coli support the conclusion that ABUW_0982 encodes a single-component efflux protein with specificity for small, hydrophobic molecules, including CHL.
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Acinetobacter baumannii Gastrointestinal Colonization Is Facilitated by Secretory IgA Which Is Reductively Dissociated by Bacterial Thioredoxin A. mBio 2018; 9:mBio.01298-18. [PMID: 29991584 PMCID: PMC6050963 DOI: 10.1128/mbio.01298-18] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Multidrug-resistant Acinetobacter baumannii is among the most common causes of infectious complications associated with combat-related trauma in military personnel serving overseas. However, little is currently known about its pathogenesis. While the gastrointestinal (GI) tract has been found to be a major reservoir for A. baumannii, as well as to potentially contribute to development of multidrug resistance, no studies have addressed the mechanisms involved in gut colonization. In this study, we address this critical gap in knowledge by first assessing the interaction between secretory IgA (SIgA), the principal humoral immune defense on mucosal surfaces, and the A. baumannii clinical isolate Ci79. Surprisingly, SIgA appeared to enhance A. baumannii GI tract colonization, in a process mediated by bacterial thioredoxin A (TrxA), as evidenced by reduction of bacterial attachment in the presence of TrxA inhibitors. Additionally, a trxA targeted deletion mutant (ΔtrxA) showed reduced bacterial burdens within the GI tract 24 h after oral challenge by in vivo live imaging, along with loss of thiol-reductase activity. Surprisingly, not only was GI tract colonization greatly reduced but the associated 50% lethal dose (LD50) of the ΔtrxA mutant was increased nearly 100-fold in an intraperitoneal sepsis model. These data suggest that TrxA not only mediates A. baumannii GI tract colonization but also may contribute to pathogenesis in A. baumannii sepsis following escape from the GI tract under conditions when the intestinal barrier is compromised, as occurs with cases of severe shock and trauma. Acinetobacter baumannii is an emerging bacterial pathogen recently classified as a serious threat to U.S. and global health by both the Centers for Disease Control and Prevention and the World Health Organization. It also is one of the leading causes of combat-related infections associated with injured military personnel serving overseas. Little is known regarding mechanisms of gastrointestinal tract colonization despite this site being shown to serve as a reservoir for multidrug-resistant (MDR) A. baumannii isolates. Here, we establish that secretory IgA, the major immunoglobulin of mucosal surfaces, promotes A. baumannii GI tract colonization via bacterial thioredoxin A as evidenced through significant reduction in colonization in IgA-deficient animals. Additionally, bacterial colonization and mortality were significantly reduced in animals challenged with a thioredoxin A-deficient A. baumannii mutant. Combined, these data suggest that thioredoxin A is a novel virulence factor, for which antithioredoxin therapies could be developed, for this important multidrug-resistant pathogen.
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Labib JR, Ibrahim SK, Salem MR, Youssef MRL, Meligy B. Infection with gram-negative bacteria among children in a tertiary pediatric hospital in Egypt. Am J Infect Control 2018; 46:798-801. [PMID: 29429556 DOI: 10.1016/j.ajic.2017.12.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2017] [Revised: 12/11/2017] [Accepted: 12/12/2017] [Indexed: 12/29/2022]
Abstract
BACKGROUND Patients in pediatric intensive care units (PICUs) are susceptible to infections with gram-negative bacteria (GNB). METHODS A prospective observational study was conducted in 2 PICUs at Cairo University Hospitals to determine the incidence and outcome of GNB infections over 1 year. Variables of interest included age, gender, isolated organism, susceptibility to antibiotics, and final outcome. RESULTS During the study period, 1420 patients were admitted to the PICU; of these, 291 developed GNB infections. The median age of the studied GNB patients was 50 months (interquartile range [IQR], 22-80 months). The mortality rate was 37.1%. Organisms were isolated from blood in the majority (86.6%) of patients, with Klebsiella (36.0%) being the most frequently isolated organism. Among patients with GNB infection, 235 patients, one had a multidrug-resistant (MDR) infection. The length of hospital stay was statistically significantly longer in the MDR group (25 days; IQR, 20-30) than in the non-MDR group (15 days; IQR, 10-20) (P < .01). Mortality was similar in both groups (37.4% vs 35.7% in the MDR and non-MDR groups, respectively; P = .88). CONCLUSION This study highlights high rates of pediatric MDR-GNB infections and emphasizes the need for a continuous surveillance system in the management of these critically ill children.
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Jiménez-Guerra G, Heras-Cañas V, Gutiérrez-Soto M, Del Pilar Aznarte-Padial M, Expósito-Ruiz M, Navarro-Marí JM, Gutiérrez-Fernández J. Urinary tract infection by Acinetobacter baumannii and Pseudomonas aeruginosa: evolution of antimicrobial resistance and therapeutic alternatives. J Med Microbiol 2018; 67:790-797. [PMID: 29693543 DOI: 10.1099/jmm.0.000742] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Purpose. Acinetobacter baumannii and Pseudomonas aeruginosa are responsible for numerous nosocomial infections. The objective of this study was to determine the development of their susceptibility to ten antibiotics and the antibiotic consumption of patients with suspicion of urinary tract infection (UTI).Methodology. A retrospective study was conducted on the susceptibility profiles of A. baumannii and P. aeruginosa isolates from 749 urine samples gathered between January 2013 and December 2016, and on the consumption of imipenem, meropenem and piperacillin-tazobactam between 2014 and 2016.Results. Hospital patients were the source of 82 (91.1 %) of the 90 A. baumannii isolates detected and 555 (84.2 %) of the 659 P. aeruginosa isolates. Globally, the lowest percentage susceptibility values were found for fosfomycin, aztreonam and ciprofloxacin, while colistin continued to be the most active antibiotic in vitro. In 2016, the susceptibility of A. baumannii to carbapenem and piperacillin-tazobactam decreased to very low values, while the susceptibility of P. aeruginosa to carbapenem remained stable but its susceptibility to piperacillin-tazobactam decreased. There was a marked increase in the consumption of piperacillin-tazobactam.Conclusion. In our setting, it is no longer possible to use carbapenems and piperacillin-tazobactam for empirical treatment of UTI due to A. baumannii or to use piperacillin-tazobactam for empirical treatment of UTI due to P. aeruginosa. Colistin was found to be the most active antibiotic in vitro. There was a marked increase in the consumption of piperacillin-tazobactam.
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Affiliation(s)
- Gemma Jiménez-Guerra
- Laboratorio de Microbiología, Hospital Virgen de las Nieves-Instituto de Investigación Biosanitaria de Granada, Granada, Spain
| | - Victor Heras-Cañas
- Laboratorio de Microbiología, Hospital Virgen de las Nieves-Instituto de Investigación Biosanitaria de Granada, Granada, Spain
| | | | | | - Manuela Expósito-Ruiz
- Unidad de Metodología de la Investigación y Bioestadística. Hospital Virgen de las Nieves-Instituto de Investigación Biosanitaria de Granada, Granada, Spain
| | - José María Navarro-Marí
- Laboratorio de Microbiología, Hospital Virgen de las Nieves-Instituto de Investigación Biosanitaria de Granada, Granada, Spain
| | - José Gutiérrez-Fernández
- Laboratorio de Microbiología, Hospital Virgen de las Nieves-Instituto de Investigación Biosanitaria de Granada, Granada, Spain.,Departamento de Microbiología, Facultad de Medicina, Universidad de Granada-Instituto de Investigación Biosanitaria de Granada, Granada, Spain
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Kim Y, Kim S, Lee Y, Choi H, Choi J, Yoon S, You YK, Kim DG. Carbapenem-resistant Acinetobacter baumannii Bacteremia in Liver Transplant Recipients. Transplant Proc 2018; 50:1132-1135. [DOI: 10.1016/j.transproceed.2018.01.043] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2017] [Accepted: 01/22/2018] [Indexed: 12/29/2022]
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Study of the Role of Efflux Pumps in Amikacin-Resistant Acinetobacter Isolates from Teaching Hospitals of Mashhad, Iran. Jundishapur J Microbiol 2018. [DOI: 10.5812/jjm.12754] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
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Neethu S, Midhun SJ, Radhakrishnan E, Jyothis M. Green synthesized silver nanoparticles by marine endophytic fungus Penicillium polonicum and its antibacterial efficacy against biofilm forming, multidrug-resistant Acinetobacter baumanii. Microb Pathog 2018; 116:263-272. [DOI: 10.1016/j.micpath.2018.01.033] [Citation(s) in RCA: 91] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2017] [Revised: 01/19/2018] [Accepted: 01/19/2018] [Indexed: 11/15/2022]
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Almasaudi SB. Acinetobacter spp. as nosocomial pathogens: Epidemiology and resistance features. Saudi J Biol Sci 2018; 25:586-596. [PMID: 29686523 PMCID: PMC5910652 DOI: 10.1016/j.sjbs.2016.02.009] [Citation(s) in RCA: 172] [Impact Index Per Article: 24.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2015] [Revised: 02/05/2016] [Accepted: 02/07/2016] [Indexed: 11/14/2022] Open
Abstract
The genus Acinetobacter is a major cause of nosocomial infections; it is increasingly being associated with various epidemics and has become a widespread concern in a variety of hospitals worldwide. Multi-antibiotic resistant Acinetobacter baumannii, is now recognized to be of great clinical significance. Numerous reports relay to the spread of A. baumannii in the hospital settings which leads to enhanced nosocomial outbreaks associated with high death rates. However, many other Acinetobacter spp. also can cause nosocomial infections. This review focused on the role of Acinetobacter spp. as nosocomial pathogens in addition to their persistence, antimicrobial resistance patterns and epidemiology.
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Affiliation(s)
- Saad B. Almasaudi
- Biology Department, Faculty of Science, King Abdulaziz University (KAU), P.O. Box 80203, Jeddah 21589, Saudi Arabia
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Multidrug-Resistant Acinetobacter baumannii: An Emerging Health Threat in Aseer Region, Kingdom of Saudi Arabia. CANADIAN JOURNAL OF INFECTIOUS DISEASES & MEDICAL MICROBIOLOGY 2018; 2018:9182747. [PMID: 29623140 PMCID: PMC5829427 DOI: 10.1155/2018/9182747] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/25/2017] [Revised: 10/31/2017] [Accepted: 12/14/2017] [Indexed: 12/05/2022]
Abstract
Objective The study aims to determine the prevalence of multidrug-resistant A. baumannii in Aseer Region, Kingdom of Saudi Arabia. Methods This study evaluated the antibiotic susceptibility of ninety-four (n = 94) clinical isolates of A. baumannii. The isolates were collected from the south region of Saudi Arabia, and notably Aseer Region, during the period from 15 October 2014 to 15 January 2015. The isolates were tentatively identified as A. baumannii by routine bench tests and were confirmed by using VITEK® 2 Compact. The latest instrument was used to identify antibiotic susceptibility of these isolates. Results Antibiotic susceptibility in this study showed that 69% of these isolates were multidrug-resistant strains. Moreover, they were highly resistant to carbapenem drugs. Several strains of these isolates were found to be extremely resistant to test antibiotics and were only sensitive to one or two of them. Conclusion High rate of multidrug-resistant A. baumannii bacteraemia has emerged in the south region of Saudi Arabia as an important health problem. Therefore, it is considered as a new threat in hospitals, which requires a tremendous effort to stop its escalation and spread.
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Chatterjee S, Mondal A, Mitra S, Basu S. Acinetobacter baumannii transfers the blaNDM-1 gene via outer membrane vesicles. J Antimicrob Chemother 2018; 72:2201-2207. [PMID: 28505330 DOI: 10.1093/jac/dkx131] [Citation(s) in RCA: 101] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2016] [Accepted: 04/07/2017] [Indexed: 01/05/2023] Open
Abstract
Objectives To investigate the transmission of the gene encoding New Delhi metallo-β-lactamase-1 ( bla NDM-1 ) through outer membrane vesicles (OMVs) released from an Acinetobacter baumannii strain (A_115). Methods Isolation and purification of OMVs by density gradient from a carbapenem-resistant clinical strain of A. baumannii harbouring plasmid-mediated bla NDM-1 and aac(6')-Ib-cr genes was performed. DNA was purified from the OMVs and used for PCR and dot-blot analysis. Vesicles treated with DNase I and proteinase K were used to transform A. baumannii ATCC 19606 and Escherichia coli JM109 strains. MIC values for the transformants were determined, followed by PCR and restriction digestion of plasmids. PFGE was done for A_115 and transformants of ATCC 19606 and JM109. Results The A. baumannii strain (ST 1462) released vesicles (25-100 nm) during in vitro growth at late log phase. PCR and dot-blot analysis confirmed the presence of bla NDM-1 and aac(6')-Ib-cr genes in intravesicular DNA. bla NDM-1 and aac(6')-Ib-cr genes were transferred to both the A. baumannii ATCC 19606 and E. coli JM109 recipient cells. The transformation frequency of the purified OMVs was in the range of 10 -5 -10 -6 and gradually reduced with storage of OMVs. The sizes of the plasmids in the transformants and their restriction digestion patterns were identical to the plasmid in A_115. The transformants showed elevated MIC values of the β-lactam group of antibiotics, which confirmed the presence of a bla NDM-1 -harbouring plasmid. Conclusions This is the first experimental evidence of intra- and inter-species transfer of a plasmid harbouring a bla NDM-1 gene in A. baumannii via OMVs with high transformation frequency.
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Affiliation(s)
- Somdatta Chatterjee
- Division of Bacteriology, National Institute of Cholera and Enteric Diseases, P33, CIT Road, Scheme XM, Beliaghata, Kolkata 700010, India
| | - Ayan Mondal
- Division of Pathophysiology, National Institute of Cholera and Enteric Diseases, P33, CIT Road, Scheme XM, Beliaghata, Kolkata 700010, India
| | - Shravani Mitra
- Division of Bacteriology, National Institute of Cholera and Enteric Diseases, P33, CIT Road, Scheme XM, Beliaghata, Kolkata 700010, India
| | - Sulagna Basu
- Division of Bacteriology, National Institute of Cholera and Enteric Diseases, P33, CIT Road, Scheme XM, Beliaghata, Kolkata 700010, India
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Multi-drug resistant Acinetobacter species: a seven-year experience from a tertiary care center in Lebanon. Antimicrob Resist Infect Control 2018; 7:9. [PMID: 29387343 PMCID: PMC5778738 DOI: 10.1186/s13756-017-0297-6] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2017] [Accepted: 12/26/2017] [Indexed: 11/10/2022] Open
Abstract
Background Acinetobacter species have become increasingly common in the intensive care units (ICU) over the past two decades, causing serious infections. At the American University of Beirut Medical Center, the incidence of multi-drug resistant Acinetobacter baumannii (MDR-Ab) infections in the ICU increased sharply in 2007 by around 120%, and these infections have continued to cause a serious problem to this day. Methods We conducted a seven-year prospective cohort study between 2007 and 2014 in the ICU. Early in the epidemic, a case-control study was performed that included MDR-Ab cases diagnosed between 2007 and 2008 and uninfected controls admitted to the ICU during the same time. Results The total number of patients with MDR-Ab infections diagnosed between 2007 and 2014 was 128. There were also 99 patients with MDR-Ab colonization without evidence of active infection between 2011 and 2014. The incidence of MDR-Ab transmission was 315.4 cases/1000 ICU patient-days. The majority of infections were considered hospital-acquired (84%) and most consisted of respiratory infections (53.1%). The mortality rate of patients with MDR-Ab ranged from 52% to 66%. Conclusion MDR-Ab infections mostly consisted of ventilator-associated pneumonia and were associated with a very high mortality rate. Infection control measures should be reinforced to control the transmission of these organisms in the ICU.
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High Proportions of Multidrug-Resistant Acinetobacter spp. Isolates in a District in Western India: A Four-Year Antibiotic Susceptibility Study of Clinical Isolates. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2018; 15:ijerph15010153. [PMID: 29351187 PMCID: PMC5800252 DOI: 10.3390/ijerph15010153] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/09/2017] [Revised: 01/12/2018] [Accepted: 01/17/2018] [Indexed: 12/05/2022]
Abstract
The purpose of the study was to determine the proportions of multidrug-resistant (MDR) Acinetobacter spp. isolates from the district of Nashik in Western India during the period from 2011–2014. Antibacterial susceptibility testing of isolates from inpatients and outpatients was performed using Kirby–Bauer disc diffusion method to determine inhibitory zone diameters. Proportions of non-susceptible isolates were calculated from the antibacterial susceptibility data. MDR was defined as an isolate being non-susceptible to at least one antibacterial agent in at least three antibacterial categories. The change in proportions of MDR isolates; extended-spectrum β-lactamase (ESBL)-producing isolates; and non-susceptible isolates to specific antibacterial categories over calendar time was investigated by logistic regression. The proportions of MDR and ESBL-producing isolates ranged from 89.4% to 95.9% and from 87.9% to 94.0%; respectively. The proportions of non-susceptible isolates to aminoglycosides; carbapenems; antipseudomonal penicillins/β-lactamase inhibitors; cephalosporins; folate pathway inhibitors; or penicillins/β-lactamase inhibitors exceeded 77.5%. Proportions of fluoroquinolone and tetracycline non-susceptible isolates ranged from 65.3% to 83.3% and from 71.3% to 75.9%; respectively. No changes in trends were observed over time; except for a decreasing trend in fluoroquinolone non-susceptible isolates (OR = 0.75 (95% CI, 0.62–0.91)). Significantly higher proportions of non-susceptible; MDR and ESBL-producing isolates were found among isolates from the respiratory system compared to isolates from all other specimen types (p < 0.05). High proportions of MDR Acinetobacter spp. isolates were observed in the period from 2011–2014. Antimicrobial stewardship programmes are needed to prevent the emergence and spread of antibiotic resistance.
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Swe-Han KS, Pillay M, Schnugh D, Mlisana KP, Baba K, Pillay M. Horizontal transfer of OXA-23-carbapenemase-producing Acinetobacterspecies in intensive care units at an academic complex hospital, Durban, KwaZulu-Natal, South Africa. S Afr J Infect Dis 2017. [DOI: 10.1080/23120053.2017.1335482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
Affiliation(s)
- Khine Swe Swe-Han
- Department of Medical Microbiology, National Health Laboratory Service, Durban, South Africa
- Medical Microbiology and Infection Control, School of Laboratory Medicine & Medical Science, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
| | - Melendhran Pillay
- Department of Medical Microbiology, National Health Laboratory Service, Durban, South Africa
| | - Desmond Schnugh
- Infection Control Services Laboratory, Department of Clinical Microbiology and Infectious Diseases, Witwatersrand Medical School, Johannesburg, South Africa
| | - Koleka P Mlisana
- Department of Medical Microbiology, National Health Laboratory Service, Durban, South Africa
- Medical Microbiology and Infection Control, School of Laboratory Medicine & Medical Science, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
| | - Kamaldeen Baba
- Department of Medical Microbiology, National Health Laboratory Service, Universitas Academic Laboratory, University of the Free State, Bloemfontein, South Africa
| | - Manormoney Pillay
- Medical Microbiology and Infection Control, School of Laboratory Medicine & Medical Science, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
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Characterization of Carbapenem-Resistant Acinetobacter baumannii Strains Isolated from Hospitalized Patients in Palestine. Int J Microbiol 2017; 2017:8012104. [PMID: 28814955 PMCID: PMC5549501 DOI: 10.1155/2017/8012104] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2017] [Accepted: 06/18/2017] [Indexed: 12/21/2022] Open
Abstract
The American Centers for Disease Control and Prevention (CDC) recognizes Acinetobacter baumannii as a source of global outbreaks and epidemics especially due to its increasing resistance to commercially available antibiotics. In this study, 69 single patient multidrug resistant isolates collected from all over Palestine, except Gaza, were studied. All the isolates were resistant to all the β–lactam antibiotics including the carbapenems. Of the 69 isolates, 82.6% were positive for blaOXA-23, 14.5% were positive for blaOXA-24, and 3% were positive for blaOXA-58. None were positive for blaOXA-143 and blaOXA-235. In addition, 5.8% and 0% were positive for blaNDM and blaKPC, respectively. Of the 69 isolates, none were positive for the aminoglycoside aphA6 gene while 93% were positive for the aphA1 gene. The acetyltransferases aacC1 and aacA4 genes tested positive in 22% and 13% of the isolates, respectively. The ompA biofilm-producing virulence gene was detected in all isolates. Finally, Multilocus Sequence Typing (MLST) of 13 isolates revealed that more than one strain of A. baumannii was circulating in Palestinian hospitals as results revealed that 7 isolates were of ST208, 2 isolates ST218, 1 isolate ST231, 1 isolate ST348, and 2 new Sequence Types. The detection of these drug resistant pathogens is a reminder of the importance of active surveillance for resistant bacteria in order to prevent their spread in hospital settings.
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Hu YF, Hou CJY, Kuo CF, Wang NY, Wu AYJ, Leung CH, Liu CP, Yeh HI. Emergence of carbapenem-resistant Acinetobacter baumannii ST787 in clinical isolates from blood in a tertiary teaching hospital in Northern Taiwan. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2017; 50:640-645. [PMID: 28711441 DOI: 10.1016/j.jmii.2016.08.025] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/04/2016] [Revised: 08/31/2016] [Accepted: 08/31/2016] [Indexed: 12/01/2022]
Abstract
BACKGROUND/PURPOSE The purpose of this study is to investigate the predominant clones of carbapenem-resistant Acinetobacter baumannii (CRAB) in our hospital in Taiwan by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) technique. METHODS We collected 108 non-duplicate A. baumannii clinical blood isolates from January 2012 to December 2013 in MacKay Memorial Hospital. PFGE and MLST were used for typing the A. baumannii isolates and for investigation of the predominant clones. Bacteria isolates were screened by polymerase chain reaction for the presence of the carbapenemase-encoding genes. RESULTS All 108 isolates were classified as 33 pulsotypes by PFGE. The predominant clones were pulsotype 10 (12.04%) in 2012 and pulsotype 8 (16.67%) in 2013, respectively. The 31 predominant pulsotype isolates were typed by MLST, and ST787 (54.84%) and ST455 (45.16%) were identified. All isolates carried blaOXA-51-like genes, and blaOXA-23-like genes was founded in 101 isolates (93.52%). Other identified resistance genes included blaOXA-24-like and blaOXA-IMP. CONCLUSION To the best of our knowledge, this study is the first to describe the microbiological characteristics of CRAB ST787, which carried high genetic resistance to carbapenem, but remained susceptible to colistin. CRAB ST787 was the predominant clone in our hospital in the study period.
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Affiliation(s)
- Yi-Fan Hu
- Division of Infectious Diseases, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
| | - Charles Jia-Yin Hou
- Division of Cardiology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan; Division of Critical Care Medicine, MacKay Memorial Hospital, Taipei, Taiwan; MacKay Medical College, New Taipei City, Taiwan; MacKay Junior College of Medicine, Nursing and Management, Taipei, Taiwan
| | - Chien-Feng Kuo
- Division of Infectious Diseases, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
| | - Nai-Yu Wang
- Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan
| | - Alice Ying-Jung Wu
- Division of Infectious Diseases, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
| | - Ching-Hsiang Leung
- Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan; MacKay Medical College, New Taipei City, Taiwan
| | - Chang-Pan Liu
- Division of Infectious Diseases, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan; Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan; MacKay Medical College, New Taipei City, Taiwan; MacKay Junior College of Medicine, Nursing and Management, Taipei, Taiwan; Infection Control Committee, MacKay Memorial Hospital, Taipei, Taiwan.
| | - Hung-I Yeh
- Division of Cardiology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan; Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan; MacKay Medical College, New Taipei City, Taiwan; MacKay Junior College of Medicine, Nursing and Management, Taipei, Taiwan; Infection Control Committee, MacKay Memorial Hospital, Taipei, Taiwan.
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Abstract
Acinetobacter species have emerged as one of the most troublesome pathogens for healthcare institutions globally. In more recent times, nosocomial infections involving the central nervous system, skin and soft tissue, and bone have emerged as highly problematic. Acinetobacter species infection is common in intensive care units; however, Acinetobacter baumannii meningitis is rarely reported. Here, we report two cases of Acinetobacter baumannii meningitis which was multidrug resistance and ultimately required the carbapenem group of drugs for the treatment.
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Affiliation(s)
- Ira Shah
- Department of Pediatrics, B. J. Wadia Hospital for Children, Mumbai, Maharashtra, India
| | - Muznah Kapdi
- Department of Pediatrics, B. J. Wadia Hospital for Children, Mumbai, Maharashtra, India
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Cooper TW, Pass SE, Brouse SD, Hall RG. Can Pharmacokinetic and Pharmacodynamic Principles Be Applied to the Treatment of Multidrug-Resistant Acinetobacter? Ann Pharmacother 2017; 45:229-40. [DOI: 10.1345/aph.1p187] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
OBJECTIVE: To discuss treatment options that can be used for treatment of Acinetobacter infections. DATA SOURCES: A MEDLINE search (1966-November 2010) was conducted to identify English-language literature on pharmacotherapy of Acinetobacter and the bibliographies of pertinent articles. Programs and abstracts from infectious diseases meetings were also searched. Search terms included Acinetobacter, multidrug resistance, pharmacokinetics, pharmacodynamics, Monte Carlo simulation, nosocomial pneumonia, carbapenems, polymyxins, sulbactam, aminoglycosides, tetracyclines, tigecycline, rifampin, and fluoroquinolones. DATA SELECTION AND DATA EXTRACTION: All articles were critically evaluated and all pertinent information was included in this review. DATA SYNTHESIS: Multidrug resistant (MDR) Acinetobacter, defined as resistance to 3 or more antimicrobial classes, has increased over the past decade. The incidence of carbapenem-resistant Acinetobacter is also increasing, leading to an increased use of dose optimization techniques and/or alternative antimicrobials, which is driven by local susceptibility patterns. However, Acinetobacter infections that are resistant to all commercially available antibiotics have been reported. General principles are available to guide dose optimization of aminoglycosides, β-lactams, fluoroquinolones, and tigecycline for infections due to gram-negative pathogens. Unfortunately, data specific to patients with Acinetobacter infections are limited. Recent pharmacokinetic-pharmacodynamic information has shed light on colistin dosing. The dilemma with colistin is its concentration-dependent killing, which makes once-daily dosing seem like an attractive option, but its short postantibiotic effect limits a clinician's ability to extend the dosing interval. Localized delivery of antimicrobials is also an attractive option due to the ability to increase drug concentration at the infection site while minimizing systemic adverse events, but more data are needed regarding this approach. CONCLUSIONS: Increased reliance on dosage optimization, combination therapy, and localized delivery of antimicrobials are methods to pursue positive clinical outcomes in MDR Acinetobacter infections since novel antimicrobials will not be available for several years. Well-designed clinical trials with MDR Acinetobacter are needed to define the best treatment options for these patients.
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Marchaim D, Levit D, Zigron R, Gordon M, Lazarovitch T, Carrico JA, Chalifa-Caspi V, Moran-Gilad J. Clinical and molecular epidemiology of Acinetobacter baumannii bloodstream infections in an endemic setting. Future Microbiol 2017; 12:271-283. [PMID: 28287300 DOI: 10.2217/fmb-2016-0158] [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] [Indexed: 01/12/2023] Open
Abstract
AIM The transmission dynamics of Acinetobacter baumannii in endemic settings, and the relation between microbial properties and patients' clinical outcomes, are yet obscure and hampered by insufficient metadata. METHODS & RESULTS Of 20 consecutive patients with A. baumannii bloodstream infection that were thoroughly analyzed at a single center, at least one transmission opportunity was evident for 85% of patients. This implies that patient-to-patient transmission is the major mode of A. baumannii acquisitions in health facilities. Moreover, all patients who died immediately (<24 h of admission) were infected with a single clone (ST457; relative risk = 1.6; p = 0.05). CONCLUSION This preliminary analysis should prompt further investigation by mapping genomic virulence determinants among A. baumannii ST457 lineage compared with other strains.
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Affiliation(s)
- Dror Marchaim
- Unit of Infectious Diseases, Assaf Harofeh Medical Center, Zerifin, Israel.,Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Dana Levit
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Roy Zigron
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Michal Gordon
- NIBN, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Tsillia Lazarovitch
- Clinical Microbiology Laboratory, Assaf Harofeh Medical Center, Zerifin, Israel
| | - Joao A Carrico
- Instituto de Microbiologia & Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
| | | | - Jacob Moran-Gilad
- Public Health Services, Ministry of Health, Jerusalem, Israel.,Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.,ESCMID Study Group for Genomic & Molecular Diagnostics (ESGMD), Basel, Switzerland
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