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Liao J, Li C, Li L. Optimizing meropenem therapy in critical infections: a review of pharmacokinetics/pharmacodynamics research and clinical practice. Expert Rev Clin Pharmacol 2025; 18:151-163. [PMID: 39930721 DOI: 10.1080/17512433.2025.2465427] [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: 11/13/2024] [Revised: 02/03/2025] [Accepted: 02/06/2025] [Indexed: 02/18/2025]
Abstract
INTRODUCTION Meropenem is a first-line antibiotic used in the treatment of severe infections. However, patients with critical infections often exhibit a notably low pharmacokinetic/pharmacodynamic (PK/PD) compliance rate, especially in cases involving multidrug-resistant gram-negative bacteria and in specific patient populations. AREAS COVERED This article reviews the relevant literature on the use of meropenem in treating severe infections, with data primarily sourced from PubMed, Web of Science, Embase, and Cochrane databases before July 2024. The primary analysis focuses on determining the optimal clinical efficacy target value for meropenem in treating multidrug-resistant Gram-negative bacteria infection, exploring PK/PD research, individualizing drug regiments for special populations, and evaluating safety. EXPERT OPINION Based on the PK/PD properties of meropenem across different special populations such as children and elderly patients, as well as its efficacy against severe infections and multidrug-resistant Gram-negative infections, prolonged and continuous infusion regimens of meropenem have already shown some clinical benefit. Personalized dosing of meropenem for critical infections should be guided by real-time therapeutic drug monitoring (TDM). However, there is a notable lack of sufficient data, highlighting the necessity for large-scale, multi-center clinical trials to validate the safety and effectiveness of meropenem in treating severe infections.
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Affiliation(s)
- Jingli Liao
- Department of Pharmacy, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Department of Pharmacy, Dalian Medical University, Dalian, Liaoning Province, China
| | - Chao Li
- Department of Pharmacy, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Lixia Li
- Department of Pharmacy, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- China Hospital Development Institute, Shanghai Jiao Tong University, China
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Bandić Pavlović D, Pospišil M, Nađ M, Vrbanović Mijatović V, Luxner J, Zarfel G, Grisold A, Tonković D, Dobrić M, Bedenić B. Multidrug-Resistant Bacteria in Surgical Intensive Care Units: Antibiotic Susceptibility and β-Lactamase Characterization. Pathogens 2024; 13:411. [PMID: 38787264 PMCID: PMC11124292 DOI: 10.3390/pathogens13050411] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2024] [Revised: 05/08/2024] [Accepted: 05/14/2024] [Indexed: 05/25/2024] Open
Abstract
Multidrug-resistant (MDR) bacteria of the utmost importance are extended-spectrum β-lactamase (ESBL) and carbapenemase-producing Enterobacterales (CRE), carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA), methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus spp. (VRE). In this study, an evaluation of MDR bacteria in surgical intensive care units in a tertiary referral hospital was conducted. The study aimed to characterize β-lactamases and other resistance traits of Gram-negative bacteria isolated in surgical intensive care units (ICUs). Disk diffusion and the broth dilution method were used for antibiotic susceptibility testing, whereas ESBL screening was performed through a double disk synergy test and an inhibitor-based test with clavulanic acid. A total of 119 MDR bacterial isolates were analysed. ESBL production was observed in half of the Proteus mirabilis, 90% of the Klebsiella pneumoniae and all of the Enterobacter cloacae and Escherichia coli isolates. OXA-48 carbapenemase, carried by the L plasmid, was detected in 34 K. pneumoniae and one E. coli and Enterobacter cloacae complex isolates, whereas NDM occurred sporadically and was identified in three K. pneumoniae isolates. OXA-48 positive isolates coharboured ESBLs belonging to the CTX-M family in all but one isolate. OXA-23 carbapenemase was confirmed in all A. baumannii isolates. The findings of this study provide valuable insight of resistance determinants of Enterobacterales and A. baumannii which will enhance surveillance and intervention strategies that are necessary to curb the ever-growing carbapenem resistance rates.
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Affiliation(s)
- Daniela Bandić Pavlović
- Department of Anesthesiology and Intensive Care, University of Zagreb School of Medicine, University Hospital Centre Zagreb, 10000 Zagreb, Croatia; (D.B.P.); (V.V.M.); (D.T.)
| | - Mladen Pospišil
- Department of Emergency Medicine, University Hospital Centre Zagreb, 10000 Zagreb, Croatia;
| | - Marina Nađ
- University of Zagreb School of Medicine, 10000 Zagreb, Croatia;
| | - Vilena Vrbanović Mijatović
- Department of Anesthesiology and Intensive Care, University of Zagreb School of Medicine, University Hospital Centre Zagreb, 10000 Zagreb, Croatia; (D.B.P.); (V.V.M.); (D.T.)
| | - Josefa Luxner
- Institute for Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, 8010 Graz, Austria; (J.L.); (G.Z.); (A.G.)
| | - Gernot Zarfel
- Institute for Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, 8010 Graz, Austria; (J.L.); (G.Z.); (A.G.)
| | - Andrea Grisold
- Institute for Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, 8010 Graz, Austria; (J.L.); (G.Z.); (A.G.)
| | - Dinko Tonković
- Department of Anesthesiology and Intensive Care, University of Zagreb School of Medicine, University Hospital Centre Zagreb, 10000 Zagreb, Croatia; (D.B.P.); (V.V.M.); (D.T.)
| | - Mirela Dobrić
- Department of Anesthesiology, Intensive Medicine and Pain Management, University Hospital Centre Sestre Milosrdnice, 10000 Zagreb, Croatia;
| | - Branka Bedenić
- Biomedical Research Center Šalata—BIMIS, Department for Clinical Microbiology and Infection Prevention and Control, University of Zagreb School of Medicine, University Hospital Centre Zagreb, 10000 Zagreb, Croatia
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Peykov S, Strateva T. Whole-Genome Sequencing-Based Resistome Analysis of Nosocomial Multidrug-Resistant Non-Fermenting Gram-Negative Pathogens from the Balkans. Microorganisms 2023; 11:microorganisms11030651. [PMID: 36985224 PMCID: PMC10051916 DOI: 10.3390/microorganisms11030651] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 02/28/2023] [Accepted: 03/01/2023] [Indexed: 03/06/2023] Open
Abstract
Non-fermenting Gram-negative bacilli (NFGNB), such as Pseudomonas aeruginosa and Acinetobacter baumannii, are among the major opportunistic pathogens involved in the global antibiotic resistance epidemic. They are designated as urgent/serious threats by the Centers for Disease Control and Prevention and are part of the World Health Organization’s list of critical priority pathogens. Also, Stenotrophomonas maltophilia is increasingly recognized as an emerging cause for healthcare-associated infections in intensive care units, life-threatening diseases in immunocompromised patients, and severe pulmonary infections in cystic fibrosis and COVID-19 individuals. The last annual report of the ECDC showed drastic differences in the proportions of NFGNB with resistance towards key antibiotics in different European Union/European Economic Area countries. The data for the Balkans are of particular concern, indicating more than 80% and 30% of invasive Acinetobacter spp. and P. aeruginosa isolates, respectively, to be carbapenem-resistant. Moreover, multidrug-resistant and extensively drug-resistant S. maltophilia from the region have been recently reported. The current situation in the Balkans includes a migrant crisis and reshaping of the Schengen Area border. This results in collision of diverse human populations subjected to different protocols for antimicrobial stewardship and infection control. The present review article summarizes the findings of whole-genome sequencing-based resistome analyses of nosocomial multidrug-resistant NFGNBs in the Balkan countries.
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Affiliation(s)
- Slavil Peykov
- Department of Genetics, Faculty of Biology, Sofia University “St. Kliment Ohridski”, 8, Dragan Tzankov Blvd., 1164 Sofia, Bulgaria
- Department of Medical Microbiology, Faculty of Medicine, Medical University of Sofia, 2, Zdrave Str., 1431 Sofia, Bulgaria
- BioInfoTech Laboratory, Sofia Tech Park, 111, Tsarigradsko Shosse Blvd., 1784 Sofia, Bulgaria
- Correspondence: (S.P.); (T.S.); Tel.: +359-87-6454492 (S.P.); +359-2-9172750 (T.S.)
| | - Tanya Strateva
- Department of Medical Microbiology, Faculty of Medicine, Medical University of Sofia, 2, Zdrave Str., 1431 Sofia, Bulgaria
- Correspondence: (S.P.); (T.S.); Tel.: +359-87-6454492 (S.P.); +359-2-9172750 (T.S.)
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Multidrug-Resistant Bacteria in a COVID-19 Hospital in Zagreb. Pathogens 2023; 12:pathogens12010117. [PMID: 36678465 PMCID: PMC9863123 DOI: 10.3390/pathogens12010117] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Revised: 01/05/2023] [Accepted: 01/06/2023] [Indexed: 01/13/2023] Open
Abstract
During November to December 2020, a high rate of COVID-19-associated pneumonia with bacterial superinfections due to multidrug-resistant (MDR) pathogens was recorded in a COVID-19 hospital in Zagreb. This study analyzed the causative agents of bacterial superinfections among patients with serious forms of COVID-19. In total, 118 patients were hospitalized in the intensive care unit (ICU) of the COVID-19 hospital. Forty-six out of 118 patients (39%) developed serious bacterial infection (VAP or BSI or both) during their stay in ICU. The total mortality rate was 83/118 (70%). The mortality rate due to bacterial infection or a combination of ARDS with bacterial superinfection was 33% (40/118). Six patients had MDR organisms and 34 had XDR (extensively drug-resistant). The dominant species was Acinetobacter baumannii with all isolates (34) being carbapenem-resistant (CRAB) and positive for carbapenem-hydrolyzing oxacillinases (CHDL). One Escherichia coli causing pneumonia harboured the blaCTX-M-15 gene. It appears that the dominant resistance determinants of causative agents depend on the local epidemiology in the particular COVID center. Acinetobacter baumannii seems to easily spread in overcrowded ICUs. Croatia belongs to the 15 countries in the world with the highest mortality rate among COVID-19 patients, which could be in part attributable to the high prevalence of bacterial infections in local ICUs.
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Potentiate the activity of current antibiotics by naringin dihydrochalcone targeting the AdeABC efflux pump of multidrug-resistant Acinetobacter baumannii. Int J Biol Macromol 2022; 217:592-605. [PMID: 35841965 DOI: 10.1016/j.ijbiomac.2022.07.065] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Revised: 07/07/2022] [Accepted: 07/08/2022] [Indexed: 11/23/2022]
Abstract
Acinetobacter baumannii is an ESKAPE pathogen responsible for severe nosocomial infections. Among all the mechanisms contributing to multidrug resistance, efflux pumps have gained significant attention due to their widespread distribution among bacterial species and broad substrate specificity. This study has investigated the diverse roles of efflux pumps present in carbapenem-resistant A. baumannii (CRAB) and screen an efflux pump inhibitor. The result showed the presence of AdeABC, AdeFGH, AdeIJK, and AbeM efflux pumps in CRAB, and experimental studies using gene mutants demonstrated the significant role of AdeABC in carbapenem resistance, biofilm formation, surface motility, pathogenesis, bacterial adherence, and invasion to the host cells. The structure-based ligand screening, molecular mechanics, molecular dynamics simulation, and experimental validation using efflux pump mutants and antibiotic accumulation assay identified naringin dihydrochalcone (NDC) as the lead against AdeB. This lead was selected as a capping agent for silver nanoparticles. The NDC-capped silver nanoparticles (NDC-AgNPs) were characterized by UV-spectroscopy, Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and scanning electron microscopy (SEM). The investigated molecular mechanism showed that the NDC-AgNPs possessed multiple mechanisms of action. In addition to efflux inhibitory activity, it also generates reactive oxygen and nitrogen species as well as causes change in the electrochemical gradient in CRAB. The proton gradient is important for the function of AdeABC; hence altering the electrochemical gradient also disrupts its efflux activity. Moreover, A. baumannii did not develop any resistance against NDC-AgNPs till several generations which were investigated. The NDC-AgNPs were also found to be effective against carbapenem-resistant clinical isolates of A. baumannii. Therefore, the present study provided an insight into the efflux pump mediated carbapenem resistance and possible inhibitor NDC-AgNPs to combat AdeABC efflux pump mediated resistance.
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Kumar S, Anwer R, Azzi A. Virulence Potential and Treatment Options of Multidrug-Resistant (MDR) Acinetobacter baumannii. Microorganisms 2021; 9:microorganisms9102104. [PMID: 34683425 PMCID: PMC8541637 DOI: 10.3390/microorganisms9102104] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 09/18/2021] [Accepted: 09/21/2021] [Indexed: 12/12/2022] Open
Abstract
Acinetobacter baumannii is an opportunistic pathogen which is undoubtedly known for a high rate of morbidity and mortality in hospital-acquired infections. A. baumannii causes life-threatening infections, including; ventilator-associated pneumonia (VAP), meningitis, bacteremia, and wound and urinary tract infections (UTI). In 2017, the World Health Organization listed A. baumannii as a priority-1 pathogen. The prevalence of A. baumannii infections and outbreaks emphasizes the direct need for the use of effective therapeutic agents for treating such infections. Available antimicrobials, such as; carbapenems, tigecycline, and colistins have insufficient effectiveness due to the appearance of multidrug-resistant strains, accentuating the need for alternative and novel therapeutic remedies. To understand and overcome this menace, the knowledge of recent discoveries on the virulence factors of A. baumannii is needed. Herein, we summarized the role of various virulence factors, including; outer membrane proteins, efflux pumps, biofilm, penicillin-binding proteins, and siderophores/iron acquisition systems. We reviewed the recent scientific literature on different A. baumannii virulence factors and the effective antimicrobial agents for the treatment and management of bacterial infections.
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Affiliation(s)
- Sunil Kumar
- Department of Biotechnology, Maharishi Markandeshwar (Deemed to Be University), Mullana, Ambala 133207, India;
| | - Razique Anwer
- Department of Pathology, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 13317-4233, Saudi Arabia;
| | - Arezki Azzi
- Department of Biochemistry, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 13317-4233, Saudi Arabia
- Correspondence:
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Mechanisms of Resistance in Gram-Negative Urinary Pathogens: From Country-Specific Molecular Insights to Global Clinical Relevance. Diagnostics (Basel) 2021; 11:diagnostics11050800. [PMID: 33925181 PMCID: PMC8146862 DOI: 10.3390/diagnostics11050800] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 04/20/2021] [Accepted: 04/26/2021] [Indexed: 12/12/2022] Open
Abstract
Urinary tract infections (UTIs) are the most frequent hospital infections and among the most commonly observed community acquired infections. Alongside their clinical importance, they are notorious because the pathogens that cause them are prone to acquiring various resistance determinants, including extended-spectrum beta-lactamases (ESBL); plasmid-encoded AmpC β-lactamases (p-AmpC); carbapenemases belonging to class A, B, and D; qnr genes encoding reduced susceptibility to fluoroquinolones; as well as genes encoding enzymes that hydrolyse aminoglycosides. In Escherichia coli and Klebsiella pneumoniae, the dominant resistance mechanisms are ESBLs belonging to the CTX-M, TEM, and SHV families; p-AmpC; and (more recently) carbapenemases belonging to classes A, B, and D. Urinary Pseudomonas aeruginosa isolates harbour metallo-beta-lactamases (MBLs) and ESBLs belonging to PER and GES families, while carbapenemases of class D are found in urinary Acinetobacter baumannii isolates. The identification of resistance mechanisms in routine diagnostic practice is primarily based on phenotypic tests for the detection of beta-lactamases, such as the double-disk synergy test or Hodge test, while polymerase chain reaction (PCR) for the detection of resistance genes is mostly pursued in reference laboratories for research purposes. As the emergence of drug-resistant bacterial strains poses serious challenges in the management of UTIs, this review aimed to appraise mechanisms of resistance in relevant Gram-negative urinary pathogens, to provide a detailed map of resistance determinants in Croatia and the world, and to discuss the implications of these resistance traits on diagnostic approaches. We summarized a sundry of different resistance mechanisms among urinary isolates and showed how their prevalence highly depends on the local epidemiological context, highlighting the need for tailored interventions in the field of antimicrobial stewardship.
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Grisold AJ, Luxner J, Bedenić B, Diab-Elschahawi M, Berktold M, Wechsler-Fördös A, Zarfel GE. Diversity of Oxacillinases and Sequence Types in Carbapenem-Resistant Acinetobacter baumannii from Austria. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18042171. [PMID: 33672170 PMCID: PMC7926329 DOI: 10.3390/ijerph18042171] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 02/17/2021] [Accepted: 02/18/2021] [Indexed: 12/20/2022]
Abstract
Carbapenem-resistant Acinetobacter baumannii is a significant health problem worldwide. A multicenter study on A. baumannii was performed to investigate the molecular epidemiology and genetic background of carbapenem resistance of A. baumannii isolates collected from 2014–2017 in Austria. In total, 117 non-repetitive Acinetobacter spp. assigned to A. baumannii (n = 114) and A. pittii (n = 3) were collected from four centers in Austria. The isolates were uniformly resistant to piperacillin/tazobactam, ceftazidime, and carbapenems, and resistance to imipenem and meropenem was 97.4% and 98.2%, respectively. The most prominent OXA-types were OXA-58-like (46.5%) and OXA-23-like (41.2%), followed by OXA-24-like (10.5%), with notable regional differences. Carbapenem-hydrolyzing class D carbapenemases (CHDLs) were the only carbapenemases found in A.baumannii isolates in Austria since no metallo-β-lactamases (MBLs) nor KPC or GES carbapenemases were detected in any of the isolates. One-third of the isolates harbored multiple CHDLs. The population structure of A. baumannii isolates from Austria was found to be very diverse, while a total of twenty-three different sequence types (STs) were identified. The most frequent was ST195 found in 15.8%, followed by ST218 and ST231 equally found in 11.4% of isolates. Two new ST types, ST2025 and ST2026, were detected. In one A. pittii isolate, blaOXA-143-like was detected for the first time in Austria.
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Affiliation(s)
- Andrea J. Grisold
- D&R Institute of Hygiene, Microbiology and Environmental Medicine, Medical University Graz, Neue Stiftingtalstrasse 6, A-8010 Graz, Austria; (J.L.); (G.E.Z.)
- Correspondence: ; Tel.: +43-316-385-73630
| | - Josefa Luxner
- D&R Institute of Hygiene, Microbiology and Environmental Medicine, Medical University Graz, Neue Stiftingtalstrasse 6, A-8010 Graz, Austria; (J.L.); (G.E.Z.)
| | - Branka Bedenić
- Department of Microbiology, University Hospital Center Zagreb, 10000 Zagreb, Croatia;
| | - Magda Diab-Elschahawi
- Department of Infection Control and Hospital Epidemiology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria;
| | - Michael Berktold
- Institute of Hygiene and Microbiology, Medical University Innsbruck, Schöpfstrasse 41, A-6020 Innsbruck, Austria;
| | | | - Gernot E. Zarfel
- D&R Institute of Hygiene, Microbiology and Environmental Medicine, Medical University Graz, Neue Stiftingtalstrasse 6, A-8010 Graz, Austria; (J.L.); (G.E.Z.)
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Verma P, Tiwari M, Tiwari V. Efflux pumps in multidrug-resistant Acinetobacter baumannii: Current status and challenges in the discovery of efflux pumps inhibitors. Microb Pathog 2021; 152:104766. [PMID: 33545327 DOI: 10.1016/j.micpath.2021.104766] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 01/13/2021] [Accepted: 01/22/2021] [Indexed: 12/14/2022]
Abstract
Acinetobacter baumannii is an ESKAPE pathogen known to cause fatal nosocomial infections. With the surge of multidrug resistance (MDR) in the bacterial system, effective treatment measures have become very limited. The MDR in A. baumannii is contributed by various factors out of which efflux pumps have gained major attention due to their broad substrate specificity and wide distribution among bacterial species. The efflux pumps are involved in the MDR as well as contribute to other physiological processes in bacteria, therefore, it is critically important to inhibit efflux pumps in order to combat emerging resistance. The present review provides insight about the different efflux pump systems in A. baumannii and their role in multidrug resistance. A major focus has been put on the different strategies and alternate therapeutics to inhibit the efflux system. This includes use of different efflux pump inhibitors-natural, synthetic or combinatorial therapy. The use of phage therapy and nanoparticles for inhibiting efflux pumps have also been discussed here. Moreover, the present review provides the knowledge of barriers in development of efflux pump inhibitors (EPIs) and their approval for commercialization. Here, different prospectives have been discussed to improve the therapeutic development process and make it more compatible for clinical use.
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Affiliation(s)
- Privita Verma
- Department of Biochemistry, Central University of Rajasthan, Bandarsindri, Ajmer, 305817, India
| | - Monalisa Tiwari
- Department of Biochemistry, Central University of Rajasthan, Bandarsindri, Ajmer, 305817, India
| | - Vishvanath Tiwari
- Department of Biochemistry, Central University of Rajasthan, Bandarsindri, Ajmer, 305817, India.
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Overexpression of bla OXA-58 Gene Driven by IS Aba3 Is Associated with Imipenem Resistance in a Clinical Acinetobacter baumannii Isolate from Vietnam. BIOMED RESEARCH INTERNATIONAL 2020; 2020:7213429. [PMID: 32802871 PMCID: PMC7420922 DOI: 10.1155/2020/7213429] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Revised: 06/02/2020] [Accepted: 06/29/2020] [Indexed: 02/06/2023]
Abstract
The aim of this study was to investigate genetic structures and expression of blaOXA-58 gene in five Acinetobacter baumannii clinical isolates recovered from two hospitals in southern Vietnam during 2012-2014. A. baumannii isolates were identified by automated microbiology systems and confirmed by PCR. All isolates were characterized as multidrug resistant by antimicrobial testing using the disk diffusion method. Four imipenem susceptible and one nonsusceptible isolates (MIC > 32 μg·ml−1) were identified by E-test. PCR amplification of blaOXA-58 gene upstream and downstream sequences revealed the presence of ISAba3 at both locations in one multidrug-resistant isolate. Semiquantitation of blaOXA-51 and blaOXA-58 gene expression was performed by the 2-ΔΔCt method. The blaOXA-51 gene expression of five isolates showed little difference, but the isolate bearing ISAba3-blaOXA-58-ISAba3 exhibited significantly higher blaOXA-58 mRNA level. Higher β-lactamases activity in periplasmic than cytoplasmic fraction was found in most isolates. The isolate overexpressing blaOXA-58 gene possessed very high periplasmic enzyme activity. In conclusion, the A. baumannii isolate bearing ISAba3-blaOXA-58 gene exhibited high resistance to imipenem, corresponding to an overexpression of blaOXA-58 gene and very high periplasmic β-lactamase activity.
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Bandić-Pavlović D, Zah-Bogović T, Žižek M, Bielen L, Bratić V, Hrabač P, Slačanac D, Mihaljević S, Bedenić B. Gram-negative bacteria as causative agents of ventilator-associated pneumonia and their respective resistance mechanisms. J Chemother 2020; 32:344-358. [PMID: 32729399 DOI: 10.1080/1120009x.2020.1793594] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Ventilator-associated pneumonia (VAP) is a serious and common complication in patients admitted to intensive care unit (ICU) and contributes to mortality. Multidrug Gram-negative bacteria such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae are frequently associated with VAP in ICU. A prospective study was set up in three ICUs of the University Hospital Center Zagreb and one ICU in General Hospital Pula from September 2017 to March 2018. Antibiotic susceptibility was determined by broth microdilution method. Production of extended-spectrum β-lactamases (ESBLs) was determined by double-disk synergy test and carbapenemases by Hodge and carbapenem inactivation method (CIM). The genes encoding ESBLs, carbapenemases of class A, B and D and qnr genes were determined by PCR. In total 97 Gram-negative bacteria isolates were analyzed. P. aeruginosa demonstrated high resistance rates for imipenem and meropenem with 74% and 68% of resistant strains, respectively. Moderate resistance rates were observed for ceftazidime andpiperacillin/tazobactam, ciprofloxacin and gentamicin (44%). All except three A. baumannii isolates, were resistant to carbapenems and to all other antibiotics apart from colistin and amikacin. Eight A. baumannii isolates were positive for blaOXA-23 and 12 for blaOXA-24 genes. Four K. pneumoniae and two E. cloacae strains were ESBL positive and harboured group 1 of CTX-M β-lactamases. Three P. mirabilis strains were positive for plasmid-mediated ampC β-lactamase of CMY family. Two carbapenem-resistant K. pneumoniae harboured OXA-48 and one carbapenem-resistant E. cloacae VIM-1. A high proportion of multidrug-resistant P. aeruginosa, K. pneumoniae and extensively resistant A. baumannii was reported. Acquired resistance mechanisms, mainly production of carbapenemases and ESBLs were dominant in A. baumannii and K. pneumoniae, respectively. Resistance of P. aeruginosa isolates was more likely due to upregulation of efflux pumps or porin loss. A marked diversity of β-lactamases was identified in Enterobacteriaceae.
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Affiliation(s)
- Daniela Bandić-Pavlović
- Department of Anesthesiology, School of Medicine, University of Zagreb, Zagreb, Croatia.,Clinic for Anesthesiology, University Hospital Center Zagreb, Zagreb, Croatia
| | - Tajana Zah-Bogović
- Department of Anesthesiology, School of Medicine, University of Zagreb, Zagreb, Croatia.,Clinic for Anesthesiology, University Hospital Center Zagreb, Zagreb, Croatia
| | - Marta Žižek
- Faculty of Sciences, University of Zagreb, Zagreb, Croatia
| | - Luka Bielen
- Department of Internal Medicine, School of Medicine, University of Zagreb, Zagreb, Croatia.,Department of Internal Medicine, Intensive Care Unit, University Hospital Center Zagreb, Zagreb, Croatia
| | - Vesna Bratić
- Clinic for Anesthesiology, University Hospital Center Zagreb, Zagreb, Croatia
| | - Pero Hrabač
- Department of Informatics, School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Domagoj Slačanac
- Department of Microbiology, School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Slobodan Mihaljević
- Department of Anesthesiology, School of Medicine, University of Zagreb, Zagreb, Croatia.,Clinic for Anesthesiology, University Hospital Center Zagreb, Zagreb, Croatia
| | - Branka Bedenić
- Department of Microbiology, School of Medicine, University of Zagreb, Zagreb, Croatia.,Clinical Department for Clinical and Molecular Microbiology, University Hospital Center Zagreb, Zagreb, Croatia
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Molecular typing of Acinetobacter baumannii clinical strains by enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR). GENE REPORTS 2020. [DOI: 10.1016/j.genrep.2019.100542] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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Khazaal SS, Al-Kadmy IM, Aziz SN. Mechanism of pathogenesis in multidrug resistant Acinetobacter baumannii isolated from intensive care unit. GENE REPORTS 2020. [DOI: 10.1016/j.genrep.2019.100557] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
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14
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Kakuta N, Nakano R, Nakano A, Suzuki Y, Tanouchi A, Masui T, Horiuchi S, Endo S, Kakuta R, Ono Y, Yano H. A Novel Mismatched PCR-Restriction Fragment Length Polymorphism Assay for Rapid Detection of gyrA and parC Mutations Associated With Fluoroquinolone Resistance in Acinetobacter baumannii. Ann Lab Med 2020; 40:27-32. [PMID: 31432636 PMCID: PMC6713654 DOI: 10.3343/alm.2020.40.1.27] [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: 02/15/2019] [Revised: 03/31/2019] [Accepted: 07/26/2019] [Indexed: 12/05/2022] Open
Abstract
Background Mutations in the quinolone resistance-determining regions (QRDRs) of Acinetobacter baumannii DNA gyrase (gyrA) and topoisomerase IV (parC) are linked to fluoroquinolone (FQ) resistance. We developed a mismatched PCR-restriction fragment length polymorphism (RFLP) assay to detect mutations in the gyrA and parC QRDRs associated with FQ resistance in A. baumannii. Methods Based on the conserved sequences of A. baumanniigyrA and parC, two primer sets were designed for mismatched PCR-RFLP to detect mutations in gyrA (codons 83 and 87) and parC (codons 80 and 84) by introducing an artificial restriction enzyme cleavage site into the PCR products. This assay was evaluated using 58 A. baumannii strains and 37 other Acinetobacter strains that have been identified by RNA polymerase β-subunit gene sequence analysis. Results PCR amplification of gyrA and parC was successful for all A. baumannii strains. In 11 FQ -susceptible strains, the gyrA and parC PCR products were digested by the selected restriction enzymes at the site containing gyrA (codons 83 and 87) and parC (codons 80 and 84). PCR products from 47 FQ-resistant strains containing mutations in gyrA and parC were not digested by the restriction enzymes at the site containing the mutation. As for the non-baumanniiAcinetobacter strains, although amplification products for gyrA were obtained for 28 strains, no parC amplification product was obtained for any strain. Conclusions This assay specifically amplified gyrA and parC from A. baumannii and detected A. baumanniigyrA and parC mutations with FQ resistance.
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Affiliation(s)
- Naoki Kakuta
- Department of Microbiology and Infectious Diseases, Nara Medical University, Nara, Japan
| | - Ryuichi Nakano
- Department of Microbiology and Infectious Diseases, Nara Medical University, Nara, Japan.
| | - Akiyo Nakano
- Department of Microbiology and Infectious Diseases, Nara Medical University, Nara, Japan
| | - Yuki Suzuki
- Department of Microbiology and Infectious Diseases, Nara Medical University, Nara, Japan
| | - Ayako Tanouchi
- Department of Microbiology and Infectious Diseases, Nara Medical University, Nara, Japan
| | - Takashi Masui
- Department of Microbiology and Infectious Diseases, Nara Medical University, Nara, Japan.,Department of Otolaryngology-Head and Neck Surgery, Nara Medical University, Nara, Japan
| | - Saori Horiuchi
- Department of Microbiology and Infectious Diseases, Nara Medical University, Nara, Japan
| | - Shiro Endo
- International University of Health and Welfare, Shioya Hospital, Tochigi, Japan
| | - Risako Kakuta
- Department of Otolaryngology-Head and Neck Surgery, Tohoku University Graduate School of Medicine, Miyagi, Japan
| | - Yasuo Ono
- Department of Microbiology and Immunology, Teikyo University School of Medicine, Tokyo, Japan
| | - Hisakazu Yano
- Department of Microbiology and Infectious Diseases, Nara Medical University, Nara, Japan
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15
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Lukić-Grlić A, Kos M, Žižek M, Luxner J, Grisold A, Zarfel G, Bedenić B. Emergence of Carbapenem-Hydrolyzing Oxacillinases in Acinetobacter baumannii in Children from Croatia. Chemotherapy 2019; 64:167-172. [PMID: 31707391 DOI: 10.1159/000503746] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2019] [Accepted: 09/26/2019] [Indexed: 11/19/2022]
Abstract
INTRODUCTION Carbapenem resistance in Acinetobacter baumannii can be mediated by carbapenemases of class A, class B metallo-β-lactamases (MBLs), and class D carbapenem-hydrolyzing oxacillinases (CHDL). The aim of the study was to investigate the antimicrobial susceptibility and β-lactamase production of carbapenem-resistant A. baumannii isolates (CRAB) from the Children's Hospital Zagreb, Croatia. METHODS A total of 12 A. baumannii isolates collected between August 2016 and March 2018 were analyzed. Antibiotic susceptibility was determined by the broth microdilution method. The presence of MBLs was explored by combined disk test with EDTA. The presence of carbapenemases of class A, B, and D was explored by PCR. The occurrence of the ISAba1 upstream of the blaOXA-51-like or blaOXA-23-like was determined by PCR mapping. Epidemiological typing was performed by determination of sequence groups (SG). Genotyping was performed by SG determination, rep-PCR, and MLST. RESULTS All CRAB were resistant to piperacillin/tazobactam, ceftazidime, cefotaxime, ceftriaxone, cefepime, imipenem, meropenem, gentamicin, and ciprofloxacin. Moderate resistance rates were observed for ampicillin/sulbactam (67%) and tigecycline (42%). The isolates were uniformly susceptible to colistin. PCR revealed the presence of genes encoding OXA-24-like CHDL in nine and OXA-23-like CHDL in three isolates. blaOXA-51 genes were preceded by ISAba1. PCR for the common MBLs in Acinetobacter was negative. All isolates belonged to SG 1 corresponding to ICL (International Clonal Lineage) II. Rep-PCR identified four major clones. CONCLUSIONS The study found OXA-24-like β-lactamase to be the dominant CHDL among children'sCRAB. The predominant spread of OXA-24-like is in contrast with the recent global dissemination of OXA-23 reported all over the world. In contrast to the previous studies in which emergency of OXA-24-like positive isolates was monoclonal, we found considerable genetic diversity of the isolates.
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Affiliation(s)
- Amarela Lukić-Grlić
- School of Medicine, University of Zagreb, Zagreb, Croatia, .,Children's Hospital Zagreb, Zagreb, Croatia,
| | - Matea Kos
- Children's Hospital Zagreb, Zagreb, Croatia
| | - Marta Žižek
- Faculty of Health Sciences, University of Zagreb, Zagreb, Croatia
| | - Josefa Luxner
- Institute of Microbiology, Hygiene and Environmental Medicine, Medical University of Graz, Graz, Austria
| | - Andrea Grisold
- Institute of Microbiology, Hygiene and Environmental Medicine, Medical University of Graz, Graz, Austria
| | - Gernot Zarfel
- Institute of Microbiology, Hygiene and Environmental Medicine, Medical University of Graz, Graz, Austria
| | - Branka Bedenić
- School of Medicine, University of Zagreb, Zagreb, Croatia.,University Hospital Center, Zagreb, Croatia
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Iovene MR, Pota V, Galdiero M, Corvino G, Lella FMD, Stelitano D, Passavanti MB, Pace MC, Alfieri A, Franco SD, Aurilio C, Sansone P, Niyas VKM, Fiore M. First Italian outbreak of VIM-producing Serratia marcescensin an adult polyvalent intensive care unit, August-October 2018: A case report and literature review. World J Clin Cases 2019. [DOI: 10.12998/wjcc.v7.i21.3518] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
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17
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Iovene MR, Pota V, Galdiero M, Corvino G, Di Lella FM, Stelitano D, Passavanti MB, Pace MC, Alfieri A, Di Franco S, Aurilio C, Sansone P, Niyas VKM, Fiore M. First Italian outbreak of VIM-producing Serratia marcescens in an adult polyvalent intensive care unit, August-October 2018: A case report and literature review. World J Clin Cases 2019; 7:3535-3548. [PMID: 31750335 PMCID: PMC6854422 DOI: 10.12998/wjcc.v7.i21.3535] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2019] [Revised: 05/15/2019] [Accepted: 07/27/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Carbapenem-resistant Enterobacteriaceae has become a significant public health concern as hospital outbreaks are now being frequently reported and these organisms are becoming difficult to treat with the available antibiotics. CASE SUMMARY An outbreak of VIM-producing Serratia marcescens occurred over a period of 11 wk (August, 1 to October, 18) in patients admitted to the adult polyvalent intensive care unit of the University of Campania "Luigi Vanvitelli" located in Naples. Four episodes occurred in three patients (two patients infected, and one patient colonized). All the strains revealed the production of VIM. CONCLUSION After three decades of carbapenem antibiotics use, the emergence of carbapenem-resistance in Enterobacteriaceae has become a significant concern and a stricter control to preserve its clinical application is mandatory. This is, to our knowledge, the first outbreak of VIM-producing Serratia marcescens in Europe. Surveillance policies must be implemented to avoid future outbreaks.
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Affiliation(s)
- Maria Rosaria Iovene
- Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Vincenzo Pota
- Department of Women, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Massimiliano Galdiero
- Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Giusy Corvino
- Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Federica Maria Di Lella
- Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Debora Stelitano
- Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Maria Beatrice Passavanti
- Department of Women, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Maria Caterina Pace
- Department of Women, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Aniello Alfieri
- Department of Women, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Sveva Di Franco
- Department of Women, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Caterina Aurilio
- Department of Women, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Pasquale Sansone
- Department of Women, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | | | - Marco Fiore
- Department of Women, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples 80138, Italy
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18
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Bedenić B, Siroglavić M, Slade M, Šijak D, Dekić S, Musić MŠ, Godan-Hauptman A, Hrenović J. Comparison of clinical and sewage isolates of Acinetobacter baumannii from two long-term care facilities in Zagreb; mechanisms and routes of spread. Arch Microbiol 2019; 202:361-368. [DOI: 10.1007/s00203-019-01750-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2019] [Revised: 10/09/2019] [Accepted: 10/15/2019] [Indexed: 10/25/2022]
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19
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Nasiri MJ, Zamani S, Fardsanei F, Arshadi M, Bigverdi R, Hajikhani B, Goudarzi H, Tabarsi P, Dabiri H, Feizabadi MM. Prevalence and Mechanisms of Carbapenem Resistance in Acinetobacter baumannii: A Comprehensive Systematic Review of Cross-Sectional Studies from Iran. Microb Drug Resist 2019; 26:270-283. [PMID: 30822197 DOI: 10.1089/mdr.2018.0435] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Introduction: Carbapenem-resistant Acinetobacter baumannii (CRAB) is recognized to be among the most difficult antimicrobial-resistant gram-negative bacilli to control and treat. An understanding of the epidemiology of CRAB and the mechanisms of resistance to carbapenems is necessary to develop strategies to curtail their spread. Methods: Electronic databases were searched from January 1995 to December 2017 for all studies, which: (1) provide data on the frequency and antibiotic resistance profile of the isolated A. baumannii and (2) describe the mechanisms of carbapenem resistance in detail. Results: Sixty-eight studies were found referring to mechanisms of carbapenem resistance in clinical isolates of A. baumannii, and 56 studies were found referring to the frequency of CRAB. The pooled frequency of carbapenem resistance was 85.1% (95% confidence interval [CI]: 82.2-88.1) in 8,067 clinical isolates of A. baumannii. Resistances due to blaOXA23 (55.3%), blaOXA24 (41.4%), and blaOXA58 (5.2%) genes were the most prevalent reported mechanisms of resistance to carbapenem, respectively. Conclusions: Our data warn that CRAB will rise if the current situation remains uncontrolled. Better control infection strategies and antibiotic managements, particularly in the health care systems, are needed to limit the spread of this pathogen.
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Affiliation(s)
- Mohammad Javad Nasiri
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Samin Zamani
- Infectious Diseases Research Center, Golestan University of Medical Sciences, Gorgan, Iran.,Department of Microbiology, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran
| | - Fatemeh Fardsanei
- Division of Microbiology, Department of Pathobiology, School of Public Health, Tehran University of Medical Science, Tehran, Iran
| | - Mania Arshadi
- Department of Medical Laboratory Sciences, Faculty of Para Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Reza Bigverdi
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Bahareh Hajikhani
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hossein Goudarzi
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Payam Tabarsi
- Clinical TB and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hossein Dabiri
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Mehdi Feizabadi
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
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20
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Bedenić B, Cavrić G, Vranić-Ladavac M, Barišić N, Karčić N, Tot T, Presečki-Stanko A, Lukić-Grlić A, Frančula-Zaninović S, Sreter KB. COMPARISON OF TWO DIFFERENT METHODS FOR TIGECYCLINE SUSCEPTIBILITY TESTING IN ACINETOBACTER BAUMANNII. Acta Clin Croat 2018; 57:618-623. [PMID: 31168197 PMCID: PMC6544113 DOI: 10.20471/acc.2018.57.04.02] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
SUMMARY – Tigecycline susceptibility testing (TST) presents a tremendous challenge for clinical microbiologists. Previous studies have shown that the Epsilometer test (E-test) and Vitek 2 automated system significantly overestimate the minimum inhibitory concentrations for tigecycline resistance compared to the broth microdilution method (BMM). This leads to very major errors or false susceptibility (i.e. the isolate is called susceptible when it is actually resistant). The aim of this study was to compare E-test against BMM for TST in carbapenem-resistant and carbapenem-susceptible Acinetobacter (A.) baumannii and to analyze changes in tigecycline susceptibility between two time periods (2009-2012 and 2013-2014), with BMM as the gold standard. Using the EUCAST criteria, the rate of resistance to tigecycline for the OXA-23 MBL-positive, OXA-23 MBL-negative and carbapenemase-negative strains for BMM was 54.5% (6/11), 29.4% (5/17) and 2.7% (1/37), respectively; the OXA-24/40 and OXA-58 producing organisms did not exhibit any resistance. With E-test, all OXA-23 MBL-positive organisms (11/11), 23.5% (4/17) of OXA-23 MBL-negative, and 4.1% of OXA-24/40 (3/74) strains displayed tigecycline resistance; there were no resistant strains among the OXA-58 and carbapenemase-negative isolates. Resistance emerged in the bacterial isolates from 2013 to 2014. Although tigecycline does not display cross-resistance, the highest rates of resistant A. baumannii isolates were observed among those producing VIM MBL, regardless of the testing method. These findings suggest that the commercial E-test does not provide reliable results for TST of A. baumannii. Further confirmation with the dilution method should be recommended, particularly in cases of serious infections.
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Affiliation(s)
- Branka Bedenić
- 1Department of Microbiology, School of Medicine, University of Zagreb, Zagreb, Croatia; 2Department of Clinical and Molecular Microbiology, Zagreb University Hospital Centre, Zagreb, Croatia; 3Department of Intensive Care, Merkur University Hospital, Zagreb, Croatia; 4Department of Microbiology, Public Health Institute of Istria County, Pula, Croatia; 5Department of Microbiology, Karlovac General Hospital, Karlovac, Croatia; 6Department of Clinical Microbiology, Zagreb Children's Hospital, Zagreb, Croatia; 7Zagreb Health Centre, Zagreb, Croatia; 8Department of Clinical Immunology, Pulmonology and Rheumatology, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia
| | - Gordana Cavrić
- 1Department of Microbiology, School of Medicine, University of Zagreb, Zagreb, Croatia; 2Department of Clinical and Molecular Microbiology, Zagreb University Hospital Centre, Zagreb, Croatia; 3Department of Intensive Care, Merkur University Hospital, Zagreb, Croatia; 4Department of Microbiology, Public Health Institute of Istria County, Pula, Croatia; 5Department of Microbiology, Karlovac General Hospital, Karlovac, Croatia; 6Department of Clinical Microbiology, Zagreb Children's Hospital, Zagreb, Croatia; 7Zagreb Health Centre, Zagreb, Croatia; 8Department of Clinical Immunology, Pulmonology and Rheumatology, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia
| | - Mirna Vranić-Ladavac
- 1Department of Microbiology, School of Medicine, University of Zagreb, Zagreb, Croatia; 2Department of Clinical and Molecular Microbiology, Zagreb University Hospital Centre, Zagreb, Croatia; 3Department of Intensive Care, Merkur University Hospital, Zagreb, Croatia; 4Department of Microbiology, Public Health Institute of Istria County, Pula, Croatia; 5Department of Microbiology, Karlovac General Hospital, Karlovac, Croatia; 6Department of Clinical Microbiology, Zagreb Children's Hospital, Zagreb, Croatia; 7Zagreb Health Centre, Zagreb, Croatia; 8Department of Clinical Immunology, Pulmonology and Rheumatology, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia
| | - Nada Barišić
- 1Department of Microbiology, School of Medicine, University of Zagreb, Zagreb, Croatia; 2Department of Clinical and Molecular Microbiology, Zagreb University Hospital Centre, Zagreb, Croatia; 3Department of Intensive Care, Merkur University Hospital, Zagreb, Croatia; 4Department of Microbiology, Public Health Institute of Istria County, Pula, Croatia; 5Department of Microbiology, Karlovac General Hospital, Karlovac, Croatia; 6Department of Clinical Microbiology, Zagreb Children's Hospital, Zagreb, Croatia; 7Zagreb Health Centre, Zagreb, Croatia; 8Department of Clinical Immunology, Pulmonology and Rheumatology, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia
| | - Natalie Karčić
- 1Department of Microbiology, School of Medicine, University of Zagreb, Zagreb, Croatia; 2Department of Clinical and Molecular Microbiology, Zagreb University Hospital Centre, Zagreb, Croatia; 3Department of Intensive Care, Merkur University Hospital, Zagreb, Croatia; 4Department of Microbiology, Public Health Institute of Istria County, Pula, Croatia; 5Department of Microbiology, Karlovac General Hospital, Karlovac, Croatia; 6Department of Clinical Microbiology, Zagreb Children's Hospital, Zagreb, Croatia; 7Zagreb Health Centre, Zagreb, Croatia; 8Department of Clinical Immunology, Pulmonology and Rheumatology, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia
| | - Tatjana Tot
- 1Department of Microbiology, School of Medicine, University of Zagreb, Zagreb, Croatia; 2Department of Clinical and Molecular Microbiology, Zagreb University Hospital Centre, Zagreb, Croatia; 3Department of Intensive Care, Merkur University Hospital, Zagreb, Croatia; 4Department of Microbiology, Public Health Institute of Istria County, Pula, Croatia; 5Department of Microbiology, Karlovac General Hospital, Karlovac, Croatia; 6Department of Clinical Microbiology, Zagreb Children's Hospital, Zagreb, Croatia; 7Zagreb Health Centre, Zagreb, Croatia; 8Department of Clinical Immunology, Pulmonology and Rheumatology, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia
| | - Aleksandra Presečki-Stanko
- 1Department of Microbiology, School of Medicine, University of Zagreb, Zagreb, Croatia; 2Department of Clinical and Molecular Microbiology, Zagreb University Hospital Centre, Zagreb, Croatia; 3Department of Intensive Care, Merkur University Hospital, Zagreb, Croatia; 4Department of Microbiology, Public Health Institute of Istria County, Pula, Croatia; 5Department of Microbiology, Karlovac General Hospital, Karlovac, Croatia; 6Department of Clinical Microbiology, Zagreb Children's Hospital, Zagreb, Croatia; 7Zagreb Health Centre, Zagreb, Croatia; 8Department of Clinical Immunology, Pulmonology and Rheumatology, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia
| | - Amarela Lukić-Grlić
- 1Department of Microbiology, School of Medicine, University of Zagreb, Zagreb, Croatia; 2Department of Clinical and Molecular Microbiology, Zagreb University Hospital Centre, Zagreb, Croatia; 3Department of Intensive Care, Merkur University Hospital, Zagreb, Croatia; 4Department of Microbiology, Public Health Institute of Istria County, Pula, Croatia; 5Department of Microbiology, Karlovac General Hospital, Karlovac, Croatia; 6Department of Clinical Microbiology, Zagreb Children's Hospital, Zagreb, Croatia; 7Zagreb Health Centre, Zagreb, Croatia; 8Department of Clinical Immunology, Pulmonology and Rheumatology, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia
| | - Sonja Frančula-Zaninović
- 1Department of Microbiology, School of Medicine, University of Zagreb, Zagreb, Croatia; 2Department of Clinical and Molecular Microbiology, Zagreb University Hospital Centre, Zagreb, Croatia; 3Department of Intensive Care, Merkur University Hospital, Zagreb, Croatia; 4Department of Microbiology, Public Health Institute of Istria County, Pula, Croatia; 5Department of Microbiology, Karlovac General Hospital, Karlovac, Croatia; 6Department of Clinical Microbiology, Zagreb Children's Hospital, Zagreb, Croatia; 7Zagreb Health Centre, Zagreb, Croatia; 8Department of Clinical Immunology, Pulmonology and Rheumatology, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia
| | - Katherina Bernadette Sreter
- 1Department of Microbiology, School of Medicine, University of Zagreb, Zagreb, Croatia; 2Department of Clinical and Molecular Microbiology, Zagreb University Hospital Centre, Zagreb, Croatia; 3Department of Intensive Care, Merkur University Hospital, Zagreb, Croatia; 4Department of Microbiology, Public Health Institute of Istria County, Pula, Croatia; 5Department of Microbiology, Karlovac General Hospital, Karlovac, Croatia; 6Department of Clinical Microbiology, Zagreb Children's Hospital, Zagreb, Croatia; 7Zagreb Health Centre, Zagreb, Croatia; 8Department of Clinical Immunology, Pulmonology and Rheumatology, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia
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Petrović T, Uzunović S, Barišić I, Luxner J, Grisold A, Zarfel G, Ibrahimagić A, Jakovac S, Slaćanac D, Bedenić B. Arrival of carbapenem-hydrolyzing-oxacillinases in Acinetobacter baumannii in Bosnia and Herzegovina. INFECTION, GENETICS AND EVOLUTION : JOURNAL OF MOLECULAR EPIDEMIOLOGY AND EVOLUTIONARY GENETICS IN INFECTIOUS DISEASES 2018; 58:192-198. [PMID: 29277554 DOI: 10.1016/j.meegid.2017.12.021] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/08/2017] [Revised: 12/05/2017] [Accepted: 12/20/2017] [Indexed: 02/08/2023]
Affiliation(s)
| | - Selma Uzunović
- Department for Laboratory Diagnostics, Cantonal Public Health Institute Zenica, Bosnia and Herzegovina.
| | - Ivan Barišić
- IT, Austrian Institute for Technology, Molecular Diagnostic, Vienna, Austria.
| | - Josefa Luxner
- Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Neue Stiftingtalstrasse Graz, Austria.
| | - Andrea Grisold
- Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Neue Stiftingtalstrasse Graz, Austria.
| | - Gernot Zarfel
- Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Neue Stiftingtalstrasse Graz, Austria.
| | - Amir Ibrahimagić
- Department for Laboratory Diagnostics, Cantonal Public Health Institute Zenica, Bosnia and Herzegovina.
| | | | - Domagoj Slaćanac
- Department of Microbiology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia.
| | - Branka Bedenić
- Department of Microbiology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia; Department of Clinical and Molecular Microbiology, University Hospital Center Zagreb, Zagreb, Croatia.
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22
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Hundeshagen G, Herndon DN, Capek KD, Branski LK, Voigt CD, Killion EA, Cambiaso-Daniel J, Sljivich M, De Crescenzo A, Mlcak RP, Kinsky MP, Finnerty CC, Norbury WB. Co-administration of vancomycin and piperacillin-tazobactam is associated with increased renal dysfunction in adult and pediatric burn patients. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2017; 21:318. [PMID: 29262848 PMCID: PMC5738705 DOI: 10.1186/s13054-017-1899-3] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/08/2017] [Accepted: 11/28/2017] [Indexed: 02/07/2023]
Abstract
Background Burn patients are prone to infections which often necessitate broad antibiotic coverage. Vancomycin is a common antibiotic after burn injury and is administered alone (V), or in combination with imipenem-cilastin (V/IC) or piperacillin-tazobactam (V/PT). Sparse reports indicate that the combination V/PT is associated with increased renal dysfunction. The purpose of this study was to evaluate the short-term impact of the three antibiotic administration types on renal dysfunction. Methods All pediatric and adult patients admitted to our centers between 2004 and 2016 with a burn injury were included in this retrospective review if they met the criteria of exposition to either V, V/IC, or V/PT for at least 48 h, had normal baseline creatinine, and no pre-existing renal dysfunction. Creatinine was monitored for 7 days after initial exposure; the absolute and relative increase was calculated, and patient renal outcomes were classified according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria depending on creatinine increases and estimated creatinine clearance. Secondary endpoints (demographic and clinical data, incidences of septicemia, and renal replacement therapy) were analyzed. Antibiotic doses were modeled in logistic and linear multivariable regression models to predict categorical KDIGO events and relative creatinine increase. Results Out of 1449 patients who were screened, 718 met the inclusion criteria, 246 were adults, and 472 were children. Between the study cohorts V, V/IC, and V/PT, patient characteristics at admission were comparable. V/PT administration was associated with a statistically higher serum creatinine, and lower creatinine clearance compared to patients receiving V alone or V/IC in adults and children after burn injury. The incidence of KDIGO stages 1, 2, and 3 was higher after V/PT treatment. In children, the incidence of KDIGO stage 3 following administration of V/PT was greater than after V/IC. In adults, the incidence of renal replacement therapy was higher after V/PT compared with V or V/IC. Multivariate modeling demonstrated that V/PT is an independent predictor of renal dysfunction. Conclusion Co-administration of vancomycin and piperacillin-tazobactam is associated with increased renal dysfunction in pediatric and adult burn patients when compared to vancomycin alone or vancomycin plus imipenem-cilastin. The mechanism of this increased nephrotoxicity remains elusive and warrants further scientific evaluation. Electronic supplementary material The online version of this article (doi:10.1186/s13054-017-1899-3) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Gabriel Hundeshagen
- Department of Surgery, University of Texas Medical Branch, 301 University Blvd., Galveston, TX, 77555, USA. .,Shriners Hospitals for Children, 815 Market St., Galveston, TX, 77550, USA. .,Department of Hand, Plastic and Reconstructive Surgery, Burn Trauma Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Ludwig-Guttmann-Str. 13, 67071, Ludwigshafen, Germany.
| | - David N Herndon
- Department of Surgery, University of Texas Medical Branch, 301 University Blvd., Galveston, TX, 77555, USA.,Shriners Hospitals for Children, 815 Market St., Galveston, TX, 77550, USA
| | - Karel D Capek
- Department of Surgery, University of Texas Medical Branch, 301 University Blvd., Galveston, TX, 77555, USA.,Shriners Hospitals for Children, 815 Market St., Galveston, TX, 77550, USA
| | - Ludwik K Branski
- Department of Surgery, University of Texas Medical Branch, 301 University Blvd., Galveston, TX, 77555, USA.,Shriners Hospitals for Children, 815 Market St., Galveston, TX, 77550, USA.,Department of Plastic Surgery, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, 77030, USA
| | - Charles D Voigt
- Department of Surgery, University of Texas Medical Branch, 301 University Blvd., Galveston, TX, 77555, USA.,Shriners Hospitals for Children, 815 Market St., Galveston, TX, 77550, USA
| | - Elizabeth A Killion
- Department of Plastic Surgery, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, 77030, USA
| | - Janos Cambiaso-Daniel
- Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, Graz, Austria
| | - Michaela Sljivich
- Department of Surgery, University of Texas Medical Branch, 301 University Blvd., Galveston, TX, 77555, USA.,Shriners Hospitals for Children, 815 Market St., Galveston, TX, 77550, USA
| | - Andrew De Crescenzo
- Department of Surgery, University of Texas Medical Branch, 301 University Blvd., Galveston, TX, 77555, USA.,Shriners Hospitals for Children, 815 Market St., Galveston, TX, 77550, USA
| | - Ronald P Mlcak
- Department of Surgery, University of Texas Medical Branch, 301 University Blvd., Galveston, TX, 77555, USA.,Shriners Hospitals for Children, 815 Market St., Galveston, TX, 77550, USA
| | - Michael P Kinsky
- Department of Anesthesiology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX, 77555, USA
| | - Celeste C Finnerty
- Department of Surgery, University of Texas Medical Branch, 301 University Blvd., Galveston, TX, 77555, USA.,Shriners Hospitals for Children, 815 Market St., Galveston, TX, 77550, USA
| | - William B Norbury
- Department of Surgery, University of Texas Medical Branch, 301 University Blvd., Galveston, TX, 77555, USA.,Shriners Hospitals for Children, 815 Market St., Galveston, TX, 77550, USA
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Nowak J, Zander E, Stefanik D, Higgins PG, Roca I, Vila J, McConnell MJ, Cisneros JM, Seifert H, MagicBullet Working Group WP4. High incidence of pandrug-resistant Acinetobacter baumannii isolates collected from patients with ventilator-associated pneumonia in Greece, Italy and Spain as part of the MagicBullet clinical trial. J Antimicrob Chemother 2017; 72:3277-3282. [PMID: 28961773 PMCID: PMC5890771 DOI: 10.1093/jac/dkx322] [Citation(s) in RCA: 143] [Impact Index Per Article: 17.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2017] [Revised: 08/01/2017] [Accepted: 08/01/2017] [Indexed: 01/05/2023] Open
Abstract
OBJECTIVES To investigate the molecular epidemiology, antimicrobial susceptibility and carbapenem resistance determinants of Acinetobacter baumannii isolates from respiratory tract samples of patients diagnosed with ventilator-associated pneumonia (VAP) who were enrolled in the MagicBullet clinical trial. METHODS A. baumannii isolates were prospectively cultured from respiratory tract samples from 65 patients from 15 hospitals in Greece, Italy and Spain. Susceptibility testing was performed by broth microdilution. Carbapenem resistance determinants were identified by PCR and sequencing. Molecular epidemiology was investigated using rep-PCR (DiversiLab) and international clones (IC) were identified using our in-house database. RESULTS Of 65 isolates, all but two isolates (97%) were resistant to imipenem and these were always associated with an acquired carbapenemase, OXA-23 (80%), OXA-40 (4.6%), OXA-58 (1.5%) or OXA-23/58 (1.5%). Resistance to colistin was 47.7%. Twenty-two isolates were XDR, and 20 isolates were pandrug-resistant (PDR). The majority of isolates clustered with IC2 (n = 54) with one major subtype comprising isolates from 12 hospitals in the three countries, which included 19 XDR and 16 PDR isolates. CONCLUSIONS Carbapenem resistance rates were very high in A. baumannii recovered from patients with VAP. Almost half of the isolates were colistin resistant, and 42 (64.6%) isolates were XDR or PDR. Rep-PCR confirmed IC2 is the predominant clonal lineage in Europe and suggests the presence of an epidemic XDR/PDR A. baumannii clone that has spread in Greece, Italy and Spain. These data highlight the difficulty in empirical treatment of patients with A. baumannii VAP in centres with a high prevalence of carbapenem-resistant A. baumannii.
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Affiliation(s)
- J Nowak
- Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Goldenfelsstraße 19-21, 50935 Cologne, Germany
| | - E Zander
- Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Goldenfelsstraße 19-21, 50935 Cologne, Germany
| | - D Stefanik
- Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Goldenfelsstraße 19-21, 50935 Cologne, Germany
| | - P G Higgins
- Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Goldenfelsstraße 19-21, 50935 Cologne, Germany
- German Centre for Infection Research (DZIF), partner site Bonn-Cologne, Germany
| | - I Roca
- Department of Clinical Microbiology and ISGlobal, Barcelona Ctr. Int. Health Res. CRESIB, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain
| | - J Vila
- Department of Clinical Microbiology and ISGlobal, Barcelona Ctr. Int. Health Res. CRESIB, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain
| | - M J McConnell
- Clinical Unit of Infectious Diseases, Microbiology, and Preventive Medicine Infectious Diseases Research Group, Institute of Biomedicine of Seville (IBiS), University of Seville/CSIC/University Hospital Virgen del Rocío, Seville, Spain
| | - J M Cisneros
- Clinical Unit of Infectious Diseases, Microbiology, and Preventive Medicine Infectious Diseases Research Group, Institute of Biomedicine of Seville (IBiS), University of Seville/CSIC/University Hospital Virgen del Rocío, Seville, Spain
| | - H Seifert
- Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Goldenfelsstraße 19-21, 50935 Cologne, Germany
- German Centre for Infection Research (DZIF), partner site Bonn-Cologne, Germany
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24
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Lin L, Wang SF, Yang TY, Hung WC, Chan MY, Tseng SP. Antimicrobial resistance and genetic diversity in ceftazidime non-susceptible bacterial pathogens from ready-to-eat street foods in three Taiwanese cities. Sci Rep 2017; 7:15515. [PMID: 29138446 PMCID: PMC5686198 DOI: 10.1038/s41598-017-15627-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2017] [Accepted: 10/30/2017] [Indexed: 11/24/2022] Open
Abstract
Bacterial contamination of ready-to-eat (RTE) street foods is a major concern worldwide. Dissemination of antibiotic resistant pathogens from food is an emerging public-health threat. To investigate the prevalence of antibiotic resistance genes and ceftazidime resistance-associated efflux pumps in foodborne pathogens, 270 RTE street foods samples were collected in three densely populated Taiwanese cities. Among 70 ceftazidime non-susceptible isolates, 21 Stenotrophomonas maltophilia, 12 Pseudomonas spp., 22 Acinetobacter spp., and 15 Enterobacteriaceae isolates were identified. Phylogenetic analyses revealed high levels of genetic diversity between all of the different strains. Multi-drug resistance was observed in 86.4% (19/22) of Acinetobacter spp., 100% (12/12) of Pseudomonas spp., 71.4% (15/21) of S. maltophilia, and 93.3% (14/15) of Enterobacteriaceae. Of 70 ceftazidime non-susceptible isolates, 13 contained ESBLs or plasmid-mediated ampC genes and 23 contained ceftazidime resistance-associated efflux pumps, with Acinetobacter spp. identified as predominant isolate (69.6%; 16/23). AdeIJK pump RNA expression in Acinetobacter isolates was 1.9- to 2-fold higher in active efflux strains. Nine clinically resistant genes were detected: catIII and cmlA (chloramphenicol); aacC1, aacC2, aacC3, and aacC4 (gentamicin); tet(A), tet(C), and tet(D) (tetracycline). The scope and abundance of multidrug-resistant bacteria described in this report underscores the need for ongoing and/or expanded RTE monitoring and control measures.
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Affiliation(s)
- Lin Lin
- Department of Culinary Art, I-Shou University, Kaohsiung, Taiwan
| | - Sheng-Fan Wang
- Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Tsung-Ying Yang
- Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wei-Chun Hung
- Department of Microbiology and Immunology, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Min-Yu Chan
- Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Sung-Pin Tseng
- Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan.
- Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, Taiwan.
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25
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Liu Q, Ren J, Wu X, Wang G, Wang Z, Wu J, Huang J, Lu T, Li J. Shifting trends in bacteriology and antimicrobial resistance among gastrointestinal fistula patients in China: an eight-year review in a tertiary-care hospital. BMC Infect Dis 2017; 17:637. [PMID: 28934938 PMCID: PMC5609055 DOI: 10.1186/s12879-017-2744-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2017] [Accepted: 09/18/2017] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND The purpose of this study was to determine the shifting trends in bacteriology and antimicrobial resistance of infectious specimens isolated from gastrointestinal (GI) fistula patients over eight years in China. METHODS We retrospectively reviewed the microbial records of intra-abdominal specimens at a teaching hospital from 2008 to 2015. Study period was divided into the first half (2008-2011) and the second half (2012-2015). All isolates underwent antibiotic susceptibility testing by the micro dilution method. RESULTS A total of 874 intra-abdominal isolates were consecutively collected from 502 GI fistula patients (mean age, 46.5 years, 71.1% male) during the study period. Patients in the second study period (2012-2015) were older (>65 years) and more likely to have experienced cancer. Over the entire study period, most infections were caused by E. coli (24.2%) and K. pneumonia (14.1%). There was a significant decrease in the proportion E. coli isolates that were extended- spectrum beta-lactamase (ESBL)-positive (P = 0.026). The proportion of E. coli resistant to imipenem increased from 14.3% in 2008-2011 to 25.9% in 2012-2015 (P = 0.037). Imipenem resistance prevalence was higher in ESBL-negative bacteria than ESBL-positive bacteria for both E. coli and K. pneumonia (P < 0.001). In Enterococcus, significant increase in resistance to ampicillin (P = 0.01) and moxifloxacin (P = 0.02) over time were observed. In Staphylococcus and fungi, rates of antibiotic resistance did not significantly change over the study period. CONCLUSIONS Gram-negative bacteria predominated as causative agents of intra-abdominal infections in GI fistula patients, and there was an increase in levels of resistance to certain antibiotics, particularly carbapenems. Infection control and source control are important tools available to surgeons to prevent the emergence of antibiotic-resistant pathogens.
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Affiliation(s)
- Qinjie Liu
- Department of Surgery, Jinling Hospital, Nanjing Medical University, 305 East Zhongshan Road, Nanjing, 210002 People’s Republic of China
| | - Jianan Ren
- Department of Surgery, Jinling Hospital, Nanjing Medical University, 305 East Zhongshan Road, Nanjing, 210002 People’s Republic of China
- Department of Surgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, People’s Republic of China
- Department of Surgery, Jinling Hospital, Medical School of Southeast University, 305 East Zhongshan Road, Nanjing, People’s Republic of China
| | - Xiuwen Wu
- Department of Surgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, People’s Republic of China
| | - Gefei Wang
- Department of Surgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, People’s Republic of China
| | - Zhiwei Wang
- Department of Surgery, Jinling Hospital, Nanjing Medical University, 305 East Zhongshan Road, Nanjing, 210002 People’s Republic of China
| | - Jie Wu
- Department of Surgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, People’s Republic of China
| | - Jinjian Huang
- Department of Surgery, Jinling Hospital, Medical School of Southeast University, 305 East Zhongshan Road, Nanjing, People’s Republic of China
| | - Tianyu Lu
- Department of Surgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, People’s Republic of China
| | - Jieshou Li
- Department of Surgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, People’s Republic of China
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Karampatakis T, Geladari A, Politi L, Antachopoulos C, Iosifidis E, Tsiatsiou O, Karyoti A, Papanikolaou V, Tsakris A, Roilides E. Cluster-distinguishing genotypic and phenotypic diversity of carbapenem-resistant Gram-negative bacteria in solid-organ transplantation patients: a comparative study. J Med Microbiol 2017; 66:1158-1169. [PMID: 28758635 DOI: 10.1099/jmm.0.000541] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Purpose. Solid-organ transplant recipients may display high rates of colonization and/or infection by multidrug-resistant bacteria. We analysed and compared the phenotypic and genotypic diversity of carbapenem-resistant (CR) strains of Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii isolated from patients in the Solid Organ Transplantation department of our hospital.Methodology. Between March 2012 and August 2013, 56 CR strains from various biological fluids underwent antimicrobial susceptibility testing with VITEK 2, molecular analysis by PCR amplification and genotypic analysis with pulsed-field gel electrophoresis (PFGE). They were clustered according to antimicrobial drug susceptibility and genotypic profiles. Diversity analyses were performed by calculating Simpson's diversity index and applying computed rarefaction curves.Results/Key findings. Among K. pneumoniae, KP-producers predominated (57.1 %). VIM and OXA-23 carbapenemases prevailed among P. aeruginosa and A. baumannii (89.4 and 88.9 %, respectively). KPC-producing K. pneumoniae and OXA-23 A. baumannii were assigned in single PFGE pulsotypes. VIM-producing P. aeruginosa generated multiple pulsotypes. CR K. pneumoniae strains displayed phenotypic diversity in tigecycline, colistin (CS), amikacin (AMK), gentamicin (GEN) and co-trimoxazole (SXT) (16 clusters); P. aeruginosa displayed phenotypic diversity in cefepime (FEP), ceftazidime, aztreonam, piperacillin, piperacillin-tazobactam, AMK, GEN and CS (9 clusters); and A. baumannii displayed phenotypic diversity in AMK, GEN, SXT, FEP, tobramycin and rifampicin (8 clusters). The Simpson diversity indices for the interpretative phenotype and PFGE analysis were 0.89 and 0.6, respectively, for K. pneumoniae strains (P<0.001); 0.77 and 0.6 for P. aeruginosa (P=0.22); and 0.86 and 0.19 for A. baumannii (P=0.004).Conclusion. The presence of different antimicrobial susceptibility profiles does not preclude the possibility that two CR K. pneumoniae or A. baumannii isolates are clonally related.
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Affiliation(s)
- Theodoros Karampatakis
- Infectious Disease Unit, 3rd Department of Pediatrics, Medical Faculty, Aristotle University School of Health Sciences, Hippokration General Hospital, Thessaloniki, Greece.,Microbiology Department, Hippokration General Hospital, Thessaloniki, Greece
| | - Anastasia Geladari
- Infectious Disease Unit, 3rd Department of Pediatrics, Medical Faculty, Aristotle University School of Health Sciences, Hippokration General Hospital, Thessaloniki, Greece
| | - Lida Politi
- Microbiology Department, National and Kapodistrian University School of Medicine, Athens, Greece
| | - Charalampos Antachopoulos
- Infectious Disease Unit, 3rd Department of Pediatrics, Medical Faculty, Aristotle University School of Health Sciences, Hippokration General Hospital, Thessaloniki, Greece.,Infection Control Committee, Hippokration General Hospital, Thessaloniki, Greece
| | - Elias Iosifidis
- Infectious Disease Unit, 3rd Department of Pediatrics, Medical Faculty, Aristotle University School of Health Sciences, Hippokration General Hospital, Thessaloniki, Greece.,Infection Control Committee, Hippokration General Hospital, Thessaloniki, Greece
| | - Olga Tsiatsiou
- Infectious Disease Unit, 3rd Department of Pediatrics, Medical Faculty, Aristotle University School of Health Sciences, Hippokration General Hospital, Thessaloniki, Greece.,Infection Control Committee, Hippokration General Hospital, Thessaloniki, Greece
| | - Aggeliki Karyoti
- Microbiology Department, Hippokration General Hospital, Thessaloniki, Greece.,Infection Control Committee, Hippokration General Hospital, Thessaloniki, Greece
| | - Vasileios Papanikolaou
- Solid Organ Transplantation Department, Medical Faculty, Aristotle University School of Health Sciences, Hippokration General Hospital, Thessaloniki, Greece
| | - Athanassios Tsakris
- Microbiology Department, National and Kapodistrian University School of Medicine, Athens, Greece
| | - Emmanuel Roilides
- Infection Control Committee, Hippokration General Hospital, Thessaloniki, Greece.,Infectious Disease Unit, 3rd Department of Pediatrics, Medical Faculty, Aristotle University School of Health Sciences, Hippokration General Hospital, Thessaloniki, Greece
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27
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Karampatakis T, Antachopoulos C, Tsakris A, Roilides E. Molecular epidemiology of carbapenem-resistant Acinetobacter baumannii in Greece: an extended review (2000–2015). Future Microbiol 2017; 12:801-815. [DOI: 10.2217/fmb-2016-0200] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Carbapenem-resistant Acinetobacter baumannii (CRAB) is endemic in Greece. CRAB initially emerged in 2000 and since then, carbapenemases still have a crucial role in CRAB appearance, except for a few cases resulting from efflux pump or outer-membrane protein mechanisms. OXA-type carbapenemases present the highest prevalence worldwide and bla OXA-23-like and bla OXA-58-like are the most important genes found; VIM-yielding CRAB have also been detected, while a single CRAB isolate producing NDM has quite recently emerged in Greece. The predominant OXA-23 producers are associated with multilocus sequence typing Pasteur scheme sequence type 2 clonal strains of the international clone II. The emergence of colistin-resistant CRAB has complicated the treatment of such infections and the interpretation of susceptibility data. Infection control measures and adjusted antimicrobial treatment strategies could confine CRAB spread. The aim of this review is to go through the molecular epidemiology of CRAB, in an endemic area and highlight its potential future evolution.
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Affiliation(s)
- Theodoros Karampatakis
- Infectious Diseases Unit, 3rd Department of Pediatrics, Medical Faculty, School of Health Sciences, Aristotle University, Hippokration General Hospital, Thessaloniki, Greece
| | - Charalampos Antachopoulos
- Infectious Diseases Unit, 3rd Department of Pediatrics, Medical Faculty, School of Health Sciences, Aristotle University, Hippokration General Hospital, Thessaloniki, Greece
| | - Athanassios Tsakris
- Microbiology Department, National & Kapodistrian University School of Medicine, Athens, Greece
| | - Emmanuel Roilides
- Infectious Diseases Unit, 3rd Department of Pediatrics, Medical Faculty, School of Health Sciences, Aristotle University, Hippokration General Hospital, Thessaloniki, Greece
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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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29
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Lee CR, Lee JH, Park M, Park KS, Bae IK, Kim YB, Cha CJ, Jeong BC, Lee SH. Biology of Acinetobacter baumannii: Pathogenesis, Antibiotic Resistance Mechanisms, and Prospective Treatment Options. Front Cell Infect Microbiol 2017; 7:55. [PMID: 28348979 PMCID: PMC5346588 DOI: 10.3389/fcimb.2017.00055] [Citation(s) in RCA: 585] [Impact Index Per Article: 73.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2016] [Accepted: 02/13/2017] [Indexed: 12/27/2022] Open
Abstract
Acinetobacter baumannii is undoubtedly one of the most successful pathogens responsible for hospital-acquired nosocomial infections in the modern healthcare system. Due to the prevalence of infections and outbreaks caused by multi-drug resistant A. baumannii, few antibiotics are effective for treating infections caused by this pathogen. To overcome this problem, knowledge of the pathogenesis and antibiotic resistance mechanisms of A. baumannii is important. In this review, we summarize current studies on the virulence factors that contribute to A. baumannii pathogenesis, including porins, capsular polysaccharides, lipopolysaccharides, phospholipases, outer membrane vesicles, metal acquisition systems, and protein secretion systems. Mechanisms of antibiotic resistance of this organism, including acquirement of β-lactamases, up-regulation of multidrug efflux pumps, modification of aminoglycosides, permeability defects, and alteration of target sites, are also discussed. Lastly, novel prospective treatment options for infections caused by multi-drug resistant A. baumannii are summarized.
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Affiliation(s)
- Chang-Ro Lee
- National Leading Research Laboratory of Drug Resistance Proteomics, Department of Biological Sciences, Myongji University Yongin, South Korea
| | - Jung Hun Lee
- National Leading Research Laboratory of Drug Resistance Proteomics, Department of Biological Sciences, Myongji University Yongin, South Korea
| | - Moonhee Park
- National Leading Research Laboratory of Drug Resistance Proteomics, Department of Biological Sciences, Myongji UniversityYongin, South Korea; DNA Analysis Division, Seoul Institute, National Forensic ServiceSeoul, South Korea
| | - Kwang Seung Park
- National Leading Research Laboratory of Drug Resistance Proteomics, Department of Biological Sciences, Myongji University Yongin, South Korea
| | - Il Kwon Bae
- Department of Dental Hygiene, College of Health and Welfare, Silla University Busan, South Korea
| | - Young Bae Kim
- Biotechnology Program, North Shore Community College Danvers, MA, USA
| | - Chang-Jun Cha
- Department of Systems Biotechnology, College of Biotechnology and Natural Resources, Chung-Ang University Anseong, South Korea
| | - Byeong Chul Jeong
- National Leading Research Laboratory of Drug Resistance Proteomics, Department of Biological Sciences, Myongji University Yongin, South Korea
| | - Sang Hee Lee
- National Leading Research Laboratory of Drug Resistance Proteomics, Department of Biological Sciences, Myongji University Yongin, South Korea
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Mondal A, Venkataramaiah M, Rajamohan G, Srinivasan VB. Occurrence of Diverse Antimicrobial Resistance Determinants in Genetically Unrelated Biocide Tolerant Klebsiella pneumoniae. PLoS One 2016; 11:e0166730. [PMID: 27870879 PMCID: PMC5117710 DOI: 10.1371/journal.pone.0166730] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2016] [Accepted: 11/02/2016] [Indexed: 11/19/2022] Open
Abstract
Nosocomial infections due to Klebsiella pneumoniae is a significant problem in health care settings worldwide. In this study, we examined the antimicrobial susceptibility, genetic profiles and mechanisms of antibiotic resistance in K. pneumoniae isolates of Indian origin. To our knowledge this is the first report demonstrating the high prevalence of β-lactamases, aminoglycoside modifying enzymes, quinolone resistance genes besides demonstrating the involvement of active efflux in K. pneumoniae Indian isolates. This study has enabled us to correlate the phenotypic and genotypic characteristics in K. pneumoniae, providing an important base for continued monitoring and epidemiological studies of this emerging nosocomial pathogen in Indian hospitals.
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Affiliation(s)
- Amitabha Mondal
- Council of Scientific Industrial Research- Institute of Microbial Technology, Sector 39 A, Chandigarh, 160036, India
| | - Manjunath Venkataramaiah
- Council of Scientific Industrial Research- Institute of Microbial Technology, Sector 39 A, Chandigarh, 160036, India
| | - Govindan Rajamohan
- Council of Scientific Industrial Research- Institute of Microbial Technology, Sector 39 A, Chandigarh, 160036, India
| | - Vijaya Bharathi Srinivasan
- Council of Scientific Industrial Research- Institute of Microbial Technology, Sector 39 A, Chandigarh, 160036, India
- * E-mail:
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Xiao SZ, Chu HQ, Han LZ, Zhang ZM, Li B, Zhao L, Xu L. Resistant mechanisms and molecular epidemiology of imipenem-resistant Acinetobacter baumannii. Mol Med Rep 2016; 14:2483-8. [PMID: 27485638 PMCID: PMC4991767 DOI: 10.3892/mmr.2016.5538] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2016] [Accepted: 07/22/2016] [Indexed: 11/05/2022] Open
Abstract
The aim of the study was to investigate the resistant mechanisms and homology of imipenem-resistant Acinetobacter baumannii (A. baumannii). A total of 46 non-duplicate imipenem‑resistant A. baumannii clinical isolates were collected from three tertiary hospitals between July, 2011 and June, 2012. The minimal inhibitory concentrations (MICs) of antimicrobial agents were determined using the agar dilution method. Phenylalanine‑arginine β-naphthylamide was used to detect the presence of the efflux pump-mediated resistant mechanism. Polymerase chain reaction was employed to amplify genes associated with drug resistance, including β‑lactamase genes, efflux pump genes and outer membrane protein gene CarO. A few amplicons were randomly selected and sequenced. Multilocus sequence analysis (MLST) was employed in typing A. baumanni. A. baumannii was resistant to imipenem, simultaneously showing resistance to several other antimicrobials. In addtition, 13 A. baumannii were found to mediate drug resistance through operation of the efflux pump. Of the various drug resistance genes tested, blaOXA‑51 was present in 46 isolates, blaOXA‑23 gene was present in 44 isolates and blaNDM gene was found in only one strain. Other drug resistant‑associated genes, including blaKPC, blaIMP, blaOXA-24, blaOXA‑58, blaSHV, blaGIM and blaVIM were not detected. Mutation of adeS and outer membrane protein gene CarO were found in a few of the imipenem‑resistant isolates. The MLST analysis revealed that all 46 clinical isolates were clustered into 11 genotypes and the most frequent genotype was ST208. In conclusion, β‑lactamase genes, genes involved in efflux pump and mutation of outer membrane protein encoding gene may be important in mediating imipenem resistance in A. baumannii. Of the 11 different genotypes, ST11 was shared by the majority of A. baumannii, which may be due to horizontal transfer of patients from hospitals.
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Affiliation(s)
- Shu-Zhen Xiao
- Department of Clinical Microbiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China
| | - Hai-Qing Chu
- Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, P.R. China
| | - Li-Zhong Han
- Department of Clinical Microbiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China
| | - Zhe-Min Zhang
- Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, P.R. China
| | - Bing Li
- Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, P.R. China
| | - Lan Zhao
- Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, P.R. China
| | - Liyun Xu
- Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, P.R. China
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Effects of Saline, an Ambient Acidic Environment, and Sodium Salicylate on OXA-Mediated Carbapenem Resistance in Acinetobacter baumannii. Antimicrob Agents Chemother 2016; 60:3415-8. [PMID: 27001819 DOI: 10.1128/aac.03010-15] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2015] [Accepted: 03/13/2016] [Indexed: 01/29/2023] Open
Abstract
Different physiological conditions, such as NaCl, low pH, and sodium salicylate, have been shown to affect antibiotic resistance determinants in Acinetobacter baumannii isolates. Therefore, the aim of this study was to investigate the effects of NaCl, sodium salicylate, and low pH on the susceptibility of A. baumannii to carbapenem. We cloned genes encoding oxacillinases (OXA) of different subclasses, with their associated promoters, from carbapenem-resistant A. baumannii isolates into the same vector and transferred them to the A. baumannii reference strains ATCC 19606 and ATCC 17978. Carbapenem MICs were determined at least in triplicate by agar dilution under standard conditions, as well as in the presence of 200 mM NaCl or 16 mM sodium salicylate, or at pH 5.8. OXA-58-like gene expression was determined by reverse transcription-quantitative PCR (qRT-PCR). Under some experimental conditions, significant MIC reductions were shown for some transformants but not for others. Only in one instance were all transformants harboring the same OXA affected by the same condition: at pH 5.8, the imipenem and meropenem MICs for strains expressing OXA-58-like enzymes decreased from a resistant level (32 to 64 mg/liter) to an intermediate-susceptible level (8 mg/liter). However, blaOXA-58-like gene expression remained the same. MICs for both wild-type reference strains were not affected by the conditions tested. Our results indicate that the effects of the experimental conditions tested on OXA in vivo are mostly strain dependent. MICs were not reduced to wild-type levels, suggesting that the conditions tested do not lead to complete OXA inhibition in the bacterial cell.
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Kim S, Park YJ, Kim J. Inverse PCR for subtyping of Acinetobacter baumannii carrying ISAba1. J Microbiol 2016; 54:376-80. [PMID: 27095456 DOI: 10.1007/s12275-016-6038-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2016] [Revised: 03/14/2016] [Accepted: 03/14/2016] [Indexed: 10/21/2022]
Abstract
Acinetobacter baumannii has been prevalent in nosocomial infections, often causing outbreaks in intensive care units. ISAba1 is an insertion sequence that has been identified only in A. baumannii and its copy number varies among strains. It has been reported that ISAba1 provides a promoter for bla(OXA-51-like), bla(OXA-23-like), and bla(ampC), which are associated with the resistance of A. baumannii to carbapenems and cephalosporins. The main purpose of this study was to develop a novel inverse PCR method capable of typing A. baumannii strains. The method involves three major steps: cutting of genomic DNA with a restriction enzyme, ligation, and PCR. In the first step, bacterial genomic DNA was digested with DpnI. In the second step, the digested genomic DNAs were ligated to form intramolecular circular DNAs. In the last step, the ligated circular DNAs were amplified by PCR with primers specific for ISAba1 and the amplified PCR products were electrophoresed. Twenty-two clinical isolates of A. baumannii were used for the evaluation of the inverse PCR (iPCR) typing method. Dendrogram analysis revealed two major clusters, similar to pulsed-field gel electrophoresis (PFGE) results. Three ISAba1-associated genes--bla(ampC), bla(OXA-66-like), and csuD--were amplified and detected in the clinical isolates. This novel iPCR typing method is comparable to PFGE in its ability to discriminate A. baumannii strains, and is a promising molecular epidemiological tool for investigating A. baumannii carrying ISAba1.
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Affiliation(s)
- Shukho Kim
- Department of Microbiology, Kyungpook National University School of Medicine, Daegu, 41944, Republic of Korea
| | - Yun-Ju Park
- Department of Microbiology, Kyungpook National University School of Medicine, Daegu, 41944, Republic of Korea
| | - Jungmin Kim
- Department of Microbiology, Kyungpook National University School of Medicine, Daegu, 41944, Republic of Korea.
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Sen B, Joshi S. Studies on Acinetobacter baumannii
involving multiple mechanisms of carbapenem resistance. J Appl Microbiol 2016; 120:619-29. [DOI: 10.1111/jam.13037] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2015] [Revised: 12/15/2015] [Accepted: 12/17/2015] [Indexed: 01/26/2023]
Affiliation(s)
- B. Sen
- Department of Microbiology and Immunology; Center for Surgical Infections and Biofilms; Drexel University; Philadelphia 19102 PA USA
| | - S.G. Joshi
- Department of Microbiology and Immunology; Center for Surgical Infections and Biofilms; Drexel University; Philadelphia 19102 PA USA
- School of Biomedical Engineering, Science and Health Systems; Center for Surgical Infections and Biofilms; Drexel University; Philadelphia 19102 PA USA
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Meletis G, Chatzidimitriou D, Malisiovas N. Double- and multi-carbapenemase-producers: the excessively armored bacilli of the current decade. Eur J Clin Microbiol Infect Dis 2015; 34:1487-93. [PMID: 25894987 DOI: 10.1007/s10096-015-2379-9] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2015] [Accepted: 03/30/2015] [Indexed: 11/29/2022]
Abstract
Multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative nosocomial pathogens commonly carry one carbapenemase gene conferring resistance to carbapenems and other beta-lactam antibiotics. However, increasing reports show that double-carbapenemase-producing (DCP) and even multi-carbapenemase-producing (MCP) bacteria are emerging in some parts of the world, diminishing further, in some cases, the already limited treatment options. In the present review, the up-to-date reports of DCP and MCP isolates are summarized and concerns regarding their emergence are discussed.
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Affiliation(s)
- G Meletis
- Labnet Laboratories, Agiou Dimitriou str. 161, 53337, Thessaloniki, Greece,
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36
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Bedenić B, Beader N, Godič-Torkar K, Vranić-Ladavac M, Luxner J, Veir Z, Grisold AJ, Zarfel G. Nursing Home as a Reservoir of Carbapenem-ResistantAcinetobacter baumannii. Microb Drug Resist 2015; 21:270-8. [DOI: 10.1089/mdr.2014.0157] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Affiliation(s)
- Branka Bedenić
- Department of Microbiology, School of Medicine, University of Zagreb, Zagreb, Croatia
- Department of Clinical and Molecular Microbiology, Clinical Hospital Center Zagreb, Zagreb, Croatia
| | - Nataša Beader
- Department of Microbiology, School of Medicine, University of Zagreb, Zagreb, Croatia
- Department of Clinical and Molecular Microbiology, Clinical Hospital Center Zagreb, Zagreb, Croatia
| | - Karmen Godič-Torkar
- Department for Sanitary Engineering, Faculty of Health Sciences, University of Ljubljana, Ljubljana, Slovenia
| | - Mirna Vranić-Ladavac
- Department of Microbiology, Public Health Institute of Istria County, Pula, Croatia
| | - Josefa Luxner
- Institute for Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, Austria
| | - Zoran Veir
- Department of Surgery, Clinical Hospital Center Zagreb, Zagreb, Croatia
| | - Andrea J. Grisold
- Institute for Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, Austria
| | - Gernot Zarfel
- Institute for Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, Austria
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Yang YS, Lee YT, Wang YC, Chiu CH, Kuo SC, Sun JR, Yin T, Chen TL, Lin JC, Fung CP, Chang FY. Molecular epidemiology of carbapenem non-susceptible Acinetobacter nosocomialis in a medical center in Taiwan. INFECTION GENETICS AND EVOLUTION 2015; 31:305-11. [PMID: 25724091 DOI: 10.1016/j.meegid.2015.02.017] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/24/2014] [Revised: 02/11/2015] [Accepted: 02/19/2015] [Indexed: 02/07/2023]
Abstract
The mechanism by which carbapenem non-susceptible Acinetobacter nosocomialis (CNSAN) is disseminated is rarely described in the literature. In this study, we delineated the molecular epidemiology of CNSAN isolated from patients in a medical center in Taiwan. Fifty-four non-duplicate bloodstream isolates of CNSAN were collected at the Taipei Veterans General Hospital between 2001 and 2007. Pulsed-field gel electrophoresis (PFGE) was performed to determine their clonal relationship. Carbapenem-resistance genes and associated genetic structures were detected by polymerase chain reaction (PCR) mapping. Southern hybridization was performed to determine the plasmid location of carbapenem-resistance genes. Transmissibility of these genes to Acinetobacterbaumannii was demonstrated by conjugation tests. The overall carbapenem non-susceptibility rate among A. nosocomialis isolates during the study period was 21.6% (54/250). PFGE revealed three major pulsotypes: H (n=23), I (n=10), and K (n=8). The most common carbapenem-resistance gene was blaOXA-58 (43/54, 79.6%), containing an upstream insertion sequence IS1006 and a truncated ISAba3 (IS1006-ΔISAba3-like-blaOXA-58). All isolates belonging to the pulsotypes H, I, and K carried plasmid located IS1006-ΔISAba3-like-blaOXA-58. A common plasmid carrying ISAba1-blaOXA-82 was found in six isolates, which belonged to five pulsotypes. A type 1 integron that carried blaIMP-1 was detected in different plasmids of seven isolates, which belonged to five pulsotypes. Plasmids carrying these carbapenem-resistant determinants were transmissible from A. nosocomialis to A. baumannii via conjugation. In this medical center, CNSAN mainly emerged through clonal dissemination; propagation of plasmids and integrons carrying carbapenem-resistant determinants played a minor role. This study showed that plasmids carrying carbapenem-resistant determinants are transmissible from A. nosocomialis to A. baumannii.
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Affiliation(s)
- Ya-Sung Yang
- Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Yi-Tzu Lee
- Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Emergency Department, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yung-Chih Wang
- Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Chun-Hsiang Chiu
- Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Shu-Chen Kuo
- Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli County, Taiwan
| | - Jun-Ren Sun
- Clinical Microbiology Laboratory Division of Clinical Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Ti Yin
- Department of Nursing, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; School of Nursing, National Yang-Ming University, Taipei, Taiwan
| | - Te-Li Chen
- Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Division of Infectious Diseases, Cheng-Hsin General Hospital, Taipei, Taiwan.
| | - Jung-Chung Lin
- Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chang-Phone Fung
- Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Feng-Yee Chang
- Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
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Tsiatsiou O, Iosifidis Ε, Katragkou A, Dimou V, Sarafidis K, Karampatakis T, Antachopoulos C, Orfanou A, Tsakris A, Drossou-Agakidou V, Roilides E. Successful management of an outbreak due to carbapenem-resistant Acinetobacter baumannii in a neonatal intensive care unit. Eur J Pediatr 2015; 174:65-74. [PMID: 24985124 DOI: 10.1007/s00431-014-2365-8] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2014] [Revised: 06/01/2014] [Accepted: 06/16/2014] [Indexed: 10/25/2022]
Abstract
UNLABELLED The investigation and successful management of a monoclonal Acinetobacter baumannii outbreak in a neonatal intensive care unit are described. Upon the first clustered carbapenem-resistant A. baumannii (CRAB) infections, a bundle of actions were taken, including enhanced infection control, active surveillance (weekly stool samples), case-control study, staff education, daily audits and discontinuation of new admissions. Between September and December 2011, eight neonates developed 10 CRAB infections (five blood, four respiratory and one eye). A total of 216 active surveillance cultures were obtained from 96 neonates (43 % had ≥2 samples). During weeks 12, 16 and 17, active surveillance detected 3, 1 and 2 new CRAB acquisitions, respectively. Prevalence of infections/colonizations decreased, and no event occurred after 20th week. A colonized neonate developed CRAB sepsis and died. All CRAB isolates harboured bla OXA-58 and the intrinsic chromosomal bla OXA-51 carbapenemase genes. CONCLUSION Active surveillance and enhanced infection control measures effectively contained spread of CRAB clone in the neonatal intensive care unit.
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Affiliation(s)
- Olga Tsiatsiou
- Infectious Diseases Unit, 3rd Department of Pediatrics, Aristotle University School of Medicine, Hippokration General Hospital, Konstantinoupoleos 49, 546 42, Thessaloniki, Greece,
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Aksoy MD, Çavuşlu Ş, Tuğrul HM. Investigation of Metallo Beta Lactamases and Oxacilinases in Carbapenem Resistant Acinetobacter baumannii Strains Isolated from Inpatients. Balkan Med J 2015; 32:79-83. [PMID: 25759776 DOI: 10.5152/balkanmedj.2015.15302] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2013] [Accepted: 11/30/2014] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Resistance to beta-lactam antibiotics is widespread among Acinetobacter strains. Plasmid-mediated metallo beta lactamases (MBL) are responsible for carbapenem resistance, as are oxacillinases (OXA). In recent years, MBL producing carbapenem-resistant strains have been reported in the world and in Turkey in increasing rates. In our country, besides the OXA 51-like enzyme which is inherent in A. baumannii strains, OXA 58-like and OXA 23-like carbapenemases producing strains have also been widely detected. In addition, Verona Imipenemase (VIM) and (IMP)-type MBL have been reported in some centers. AIMS The aim of our study was to investigate the presence of carbapenemases in Acinetobacter strains isolated from hospitalized patients in Edirne. STUDY DESIGN Cross-sectional study. METHODS A total of 52 imipenem-resistant A. baumannii strains isolated between January and March 2013 were investigated. The presence of MBL was described phenotypically by the combined disk diffusion test (CDDT), double disk synergy test (DDST), MBL E-test (only performed in 28 strains) and modified Hodge test. blaIMP, blaVIM, blaGIM, blaSIM, blaSPM genes and blaOXA-23, blaOXA-51, blaOXA-40, blaOXA-58 genes were investigated by multiplex polymerase chain reaction (PCR). The blaNDM-1 gene was determined by PCR. RESULTS By modified Hodge test, 50 strains (96%) were found to be MBL positive. Positivity of MBL was 21% by both CDDT (0.1 M EDTA) and DDST. Twenty-four of 28 strains (85.7%) were positive by MBL E-test. OXA 23-like and OXA 51-like carbapenemases were detected in all strains, but OXA 58-like and OXA 40-like carbapenemases-producing A. baumannii were not detected. Also, MBL genes were not detected by genotypic methods. CONCLUSION Only OXA 23-like carbapenemase was responsible for carbapenem resistance in carbapenem-resistant Acinetobacter strains in Edirne. The MBL-producing Acinetobacter strain is not yet a problem in our hospital. MBL resistance was found by phenotyping tests, which must be confirmed by genotypic methods; multiplex PCR tests can be easily used for screening MBL.
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Affiliation(s)
| | - Şaban Çavuşlu
- Department of Medical Microbiology, Trakya University Faculty of Medicine, Edirne, Turkey
| | - H Murat Tuğrul
- Department of Medical Microbiology, Trakya University Faculty of Medicine, Edirne, Turkey
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40
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Mutant prevention concentrations of imipenem and meropenem against Pseudomonas aeruginosa and Acinetobacter baumannii. ScientificWorldJournal 2014; 2014:979648. [PMID: 25610915 PMCID: PMC4293862 DOI: 10.1155/2014/979648] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2014] [Revised: 09/25/2014] [Accepted: 10/22/2014] [Indexed: 11/18/2022] Open
Abstract
The aim of this study was to determine the usefulness of the MPC of carbapenems against clinical isolates of Pseudomonas spp. and Acinetobacter spp. and to assess its possible relationship with mechanisms of resistance. Detection of the mechanisms of resistance was performed using Antibiotic Susceptibility Testing, Double Disk Synergy, disk antagonism, addition of NaCl to the medium, addition of PBA or EDTA to Carbapenem disks, addition of PBA to Cefoxitin disks, and CCCP test for 10 Pseudomonas spp. and Acinetobacter baumannii strains. The MIC and MPC were determined using the broth macrodilution and plate dilution methods, respectively. Four Acinetobacter baumannii strains produced MBL. Two of them produced Oxacillinase and one produced ESBL. Two Pseudomonas spp. isolates produced both KPC and MBL. The resistant Acinetobacter spp. and Pseudomonas spp. strains had higher MPC values than susceptible ones. However, the Mutant Selection Window was found to be dependent on the degree of resistance but not on a particular mechanism of resistance. The usefulness of the MPC was found to be dependent on its value. Based on our data, we recommend determining the MPC for each isolate before using it during treatment. Furthermore, the use of T>MSW instead of T>MIC is suggested.
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Lin MF, Lan CY. Antimicrobial resistance in Acinetobacter baumannii: From bench to bedside. World J Clin Cases 2014; 2:787-814. [PMID: 25516853 PMCID: PMC4266826 DOI: 10.12998/wjcc.v2.i12.787] [Citation(s) in RCA: 241] [Impact Index Per Article: 21.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2014] [Revised: 08/25/2014] [Accepted: 10/27/2014] [Indexed: 02/05/2023] Open
Abstract
Acinetobacter baumannii (A. baumannii) is undoubtedly one of the most successful pathogens in the modern healthcare system. With invasive procedures, antibiotic use and immunocompromised hosts increasing in recent years, A. baumannii has become endemic in hospitals due to its versatile genetic machinery, which allows it to quickly evolve resistance factors, and to its remarkable ability to tolerate harsh environments. Infections and outbreaks caused by multidrug-resistant A. baumannii (MDRAB) are prevalent and have been reported worldwide over the past twenty or more years. To address this problem effectively, knowledge of species identification, typing methods, clinical manifestations, risk factors, and virulence factors is essential. The global epidemiology of MDRAB is monitored by persistent surveillance programs. Because few effective antibiotics are available, clinicians often face serious challenges when treating patients with MDRAB. Therefore, a deep understanding of the resistance mechanisms used by MDRAB can shed light on two possible strategies to combat the dissemination of antimicrobial resistance: stringent infection control and antibiotic treatments, of which colistin-based combination therapy is the mainstream strategy. However, due to the current unsatisfying therapeutic outcomes, there is a great need to develop and evaluate the efficacy of new antibiotics and to understand the role of other potential alternatives, such as antimicrobial peptides, in the treatment of MDRAB infections.
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Zhang X, Gu B, Mei Y, Wen Y, Xia W. Increasing resistance rate to carbapenem among blood culture isolates of Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa in a university-affiliated hospital in China, 2004-2011. J Antibiot (Tokyo) 2014; 68:115-20. [PMID: 25182483 DOI: 10.1038/ja.2014.119] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2013] [Revised: 06/01/2014] [Accepted: 07/30/2014] [Indexed: 12/31/2022]
Abstract
The objective of this study is to investigate the profile of antimicrobial resistance of Gram-negative bacteria in blood cultures from 2004-2011. Pathogens from positive blood cultures were subcultured, and identified in the First Affiliated Hospital of Nanjing Medical University from January 2004 to December 2011. The antibiotic resistance pattern was analyzed by WHONET 5.4. A total of 1224 cases of Gram-negative bacterial isolates were documented, accounting for 38.6% of the total pathogens isolated from positive blood cultures in the 8-year period. The isolation rates of Klebsiella pneumoniae and Acinetobacter baumannii increased nearly three times over the same time span. Most Gram-negative bacteria isolates, except the isolates of Pseudomonas aeruginosa, showed a significantly increased resistance rate to cephalosporins (in particular third/fourth generation cephalosporins). Noteworthy, the antimicrobial resistance of K. pneumoniae, A. baumannii and P. aeruginosa isolates to carbapenem (imipenem and meropenem) was significantly increased and the resistant rate to carbapenem was >80.0% in A. baumannii in 2011. The results from PCR detection for carbapenemases were as follows: 82.8% (24/29) isolates of K. pneumoniae carried the kpc-2 gene; only three metallo-beta-lactamase-positive P. aeruginosa isolates were detected; and 93.1% (67/72) A. baumannii isolates were blaOXA-23 positive. The antimicrobial resistance rate of Gram-negative bacteria isolated from blood cultures significantly increased from 2004 to 2011, with significant resistance to the third/fourth generation cephalosporins and carbapenem.
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Affiliation(s)
- Xiaoli Zhang
- 1] Yi Xing People's Hospital, Yixing, Jiangsu, China [2] Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Bing Gu
- Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yaning Mei
- Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yi Wen
- Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Wenying Xia
- Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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Endo S, Yano H, Kanamori H, Inomata S, Aoyagi T, Hatta M, Gu Y, Tokuda K, Kitagawa M, Kaku M. High frequency of Acinetobacter soli among Acinetobacter isolates causing bacteremia at a tertiary hospital in Japan. J Clin Microbiol 2014; 52:911-915. [PMID: 24403303 PMCID: PMC3957750 DOI: 10.1128/jcm.03009-13] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Accepted: 12/29/2013] [Indexed: 12/29/2022] Open
Abstract
Acinetobacter baumannii is generally the most frequently isolated Acinetobacter species. Sequence analysis techniques allow reliable identification of Acinetobacter isolates at the species level. Forty-eight clinical isolates of Acinetobacter spp. were obtained from blood cultures at Tohoku University Hospital. These isolates were identified at the species level by partial sequencing of the RNA polymerase β-subunit (rpoB), 16S rRNA, and gyrB genes. Then further characterization was done by using the PCR for detection of OXA-type β-lactamase gene clusters, metallo-β-lactamases, and carO genes. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing were also performed. The most frequent isolate was Acinetobacter soli (27.1%). Six of the 13 A. soli isolates were carbapenem nonsusceptible, and all of these isolates produced IMP-1. PFGE revealed that the 13 A. soli isolates were divided into 8 clusters. This study demonstrated that A. soli accounted for a high proportion of Acinetobacter isolates causing bacteremia at a Japanese tertiary hospital. Non-A. baumannii species were identified more frequently than A. baumannii and carbapenem-nonsusceptible isolates were found among the non-A. baumannii strains. These results emphasize the importance of performing epidemiological investigations of Acinetobacter species.
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Affiliation(s)
- Shiro Endo
- Department of Infection Control and Laboratory Diagnostics, Internal Medicine, Tohoku University Graduate School of Medicine, Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan
| | - Hisakazu Yano
- Department of Infection Control and Laboratory Diagnostics, Internal Medicine, Tohoku University Graduate School of Medicine, Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan
| | - Hajime Kanamori
- Department of Infection Control and Laboratory Diagnostics, Internal Medicine, Tohoku University Graduate School of Medicine, Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan
| | - Shinya Inomata
- Department of Infection Control and Laboratory Diagnostics, Internal Medicine, Tohoku University Graduate School of Medicine, Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan
| | - Tetsuji Aoyagi
- Department of Infection Control and Laboratory Diagnostics, Internal Medicine, Tohoku University Graduate School of Medicine, Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan
| | - Masumitsu Hatta
- Department of Infection Control and Laboratory Diagnostics, Internal Medicine, Tohoku University Graduate School of Medicine, Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan
| | - Yoshiaki Gu
- Department of Regional Cooperation for Infectious Diseases, Tohoku University Graduate School of Medicine, Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan
| | - Koichi Tokuda
- Department of Infection Control and Laboratory Diagnostics, Internal Medicine, Tohoku University Graduate School of Medicine, Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan
| | - Miho Kitagawa
- Department of Infection Control and Laboratory Diagnostics, Internal Medicine, Tohoku University Graduate School of Medicine, Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan
| | - Mitsuo Kaku
- Department of Infection Control and Laboratory Diagnostics, Internal Medicine, Tohoku University Graduate School of Medicine, Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan
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Gogou V, Meletis G, Tsitouras D. Control of a Multi-Drug-Resistant Acinetobacter baumannii Outbreak after Orthopedics Department Relocation. Microorganisms 2013; 1:158-161. [PMID: 27694769 PMCID: PMC5029489 DOI: 10.3390/microorganisms1010158] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2013] [Revised: 11/13/2013] [Accepted: 11/22/2013] [Indexed: 11/16/2022] Open
Abstract
Acinetobacter baumannii clinical isolates have the ability to survive in the hospital niche for prolonged time periods and to develop resistance against multiple antimicrobial agents. Therefore, A. baumannii has emerged as an important cause of nosocomial outbreaks worldwide, especially in critical-care environments such as intensive care units. In the present communication, we report a multi-drug-resistant A. baumannii outbreak that occurred in an orthopedics department in Greece after the admission of a patient previously hospitalized in the intensive care unit of a Greek tertiary care hospital. Despite the implementation of infection control measures, 29 patients were infected, significantly raising their hospitalization periods and treatment costs. Interestingly, the outbreak was put under control after the department’s previously programmed relocation.
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Affiliation(s)
- Vasiliki Gogou
- Department of Clinical Microbiology, Veroia General Hospital, Veroia 59100, Greece.
| | - Georgios Meletis
- Department of Clinical Microbiology, Veroia General Hospital, Veroia 59100, Greece.
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Growth retardation, reduced invasiveness, and impaired colistin-mediated cell death associated with colistin resistance development in Acinetobacter baumannii. Antimicrob Agents Chemother 2013; 58:828-32. [PMID: 24247145 DOI: 10.1128/aac.01439-13] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
Two colistin-susceptible/colistin-resistant (Col(s)/Col(r)) pairs of Acinetobacter baumannii strains assigned to international clone 2, which is prevalent worldwide, were sequentially recovered from two patients after prolonged colistin administration. Compared with the respective Col(s) isolates (Ab248 and Ab299, both having a colistin MIC of 0.5 μg/ml), both Col(r) isolates (Ab249 and Ab347, with colistin MICs of 128 and 32 μg/ml, respectively) significantly overexpressed pmrCAB genes, had single-amino-acid shifts in the PmrB protein, and exhibited significantly slower growth. The Col(r) isolate Ab347, tested by proteomic analysis in comparison with its Col(s) counterpart Ab299, underexpressed the proteins CsuA/B and C from the csu operon (which is necessary for biofilm formation). This isolate also underexpressed aconitase B and different enzymes involved in the oxidative stress response (KatE catalase, superoxide dismutase, and alkyl hydroperoxide reductase), suggesting a reduced response to reactive oxygen species (ROS) and, consequently, impaired colistin-mediated cell death through hydroxyl radical production. Col(s) isolates that were indistinguishable by macrorestriction analysis from Ab299 caused six sequential bloodstream infections, and isolates indistinguishable from Ab248 caused severe soft tissue infection, while Col(r) isolates indistinguishable from Ab347 and Ab249 were mainly colonizers. In particular, a Col(s) isolate identical to Ab299 was still invading the bloodstream 90 days after the colonization of this patient by Col(r) isolates. These observations indicate considerably lower invasiveness of A. baumannii clinical isolates following the development of colistin resistance.
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Blahova J, Kralikova K, Krcmery V, Babalova M, Menkyna R, Glosova L, Knotkova H, Liskova A, Molokacova M, Vaculikova A, Bruckmayerova D, Rovny I. Four Years of Monitoring Antibiotic Resistance in Microorganisms from Bacteremic Patients. J Chemother 2013; 19:665-9. [DOI: 10.1179/joc.2007.19.6.665] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
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Goic-Barisic I, Bedenic B, Tonkic M, Katic S, Kalenic S, Punda-Polic V. First Report of Molecular Characterization of Carbapenem-ResistantAcinetobacter baumanniiin Different Intensive Care Units in University Hospital Split, Croatia. J Chemother 2013; 19:462-4. [PMID: 17855194 DOI: 10.1179/joc.2007.19.4.462] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
Affiliation(s)
- I Goic-Barisic
- Department of Clinical Microbiology, University Hospital Split, Croatia.
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Abstract
Several studies have reported the isolation of resistant Gram-Negative Bacilli in Lebanon. However, those studies are new and scarce as compared to worldwide data and mostly restricted to single center studies. In this review, we attempt to provide a reliable and comprehensive report describing the current situation and providing prospects for bacterial resistance in Lebanon. Several studies have shown that Extended Spectrum β-Lactamase-producing E. coli and K. pneumoniae strains are being increasingly reported. Moreover, 2.15% of E. coli and 7.84% of K. pneumoniae isolates have shown carbapenem resistance and up to 30% of isolated E. coli strains were found to be Multi-Drug Resistant. Molecular studies showed that the most widespread β-Lactamases in Lebanon are of the CTX-M-15 and SHV types. In addition, K. pneumoniae strains producing metallo-β-Lactamase and Klebsiella pneumoniae Carbapenemase have been reported. Resistant Pseudomonas aeruginosa and Acinetobacter baumannii caused several nosocomial infections and some Acinetobacter baumannii strains were found to produce OXA-58 type ESBL. The few data addressing the rate of antibiotic consumption in Lebanon show a high rate of antibiotic misuse and abuse. In conclusion, there is a need for antibiotic stewardship programs and additional studies that go beyond the scope of single-center studies in Lebanon.
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Affiliation(s)
- S. E. Salem
- Clinical Microbiology, Department of Biomedical Sciences, Faculty of Medicine & Medical Sciences, University of Balamand, P.O. Box 100, Tripoli, Lebanon
| | - E. Dahdouh
- Clinical Microbiology, Department of Biomedical Sciences, Faculty of Medicine & Medical Sciences, University of Balamand, P.O. Box 100, Tripoli, Lebanon
| | - Z. Daoud
- Clinical Microbiology, Department of Biomedical Sciences, Faculty of Medicine & Medical Sciences, University of Balamand, P.O. Box 100, Tripoli, Lebanon
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Virulence of Acinetobacter baumannii Exhibiting Phenotypic Heterogeneous Growth against Meropenem in a Murine Thigh Infection Model. Antibiotics (Basel) 2013; 2:73-82. [PMID: 27029293 PMCID: PMC4790299 DOI: 10.3390/antibiotics2010073] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2013] [Revised: 02/16/2013] [Accepted: 03/01/2013] [Indexed: 11/17/2022] Open
Abstract
Acinetobacter baumannii may exhibit phenotypic heterogeneous growth under exposure to antibiotics. We investigated the in vitro characteristics of A. baumannii isolates grown heterogeneously in the presence of meropenem and their virulence evaluated in experimental infections treated with meropenem. Five clinical A. baumannii isolates and the respective heterogeneously grown subpopulations were tested by agar dilution minimum inhibitory concentration (MIC) testing, pulsed field gel electrophoresis (PFGE), population analysis using meropenem and growth curves. The virulence of isolates and the therapeutic efficacy of three meropenem dosing schemes was evaluated in a neutropenic murine thigh infection model. The clinical isolates were meropenem-susceptible (MICs 1 to 4 mg/liter) and exhibited three distinct PFGE patterns. In all clinical isolates, population analysis yielded heterogeneously grown colonies. After seven subcultures in antibiotic-free media, resistant MIC levels were retained in two isolates (heteroresistant), while three isolates were reversed to susceptible MICs (persisters). Clinical isolates and heterogeneous subpopulations had similar growth rates. The heterogeneously grown A. baumannii subpopulations had reduced virulence, killing considerably fewer animals than the respective clinical isolates without treatment. The meropenem treatment outcome was similar in infections caused by the clinical and the heterogeneous isolates, irrespective to their MICs. In vitro meropenem exposure induces phenotypic heterogeneous growth in A. baumannii. Compared with the parental clinical isolates, the heterogeneously grown subpopulations exhibited lower virulence, killing fewer mice and responding equally to meropenem treatment, despite their higher MICs.
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De Francesco MA, Ravizzola G, Peroni L, Bonfanti C, Manca N. Prevalence of multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa in an Italian hospital. J Infect Public Health 2013; 6:179-85. [PMID: 23668462 DOI: 10.1016/j.jiph.2012.11.006] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2012] [Revised: 11/30/2012] [Accepted: 11/30/2012] [Indexed: 11/25/2022] Open
Abstract
The severity and extent of disease caused by multidrug-resistant organisms (MDROs) varies by the population(s) affected and the institution(s) at which these organisms are found; therefore, preventing and controlling MDROs are extremely important. A retrospective study of patients who were infected with Acinetobacter baumannii or Pseudomonas aeruginosa was performed at the Spedali Civili Hospital in Brescia, Italy, from 2007 to 2010. A total of 167 (0.52%) A. baumannii isolates and 2797 P. aeruginosa (8.7%) isolates were identified among 31,850 isolates. Amikacin and colistin were the most active agents against A. baumannii strains. Multidrug resistance (MDR) was observed in 57 isolates (54%). Most MDR isolates (42 out of 57, 73%) were resistant to four classes of antibiotics. P. aeruginosa was recovered more frequently from the respiratory tract, followed by the skin/soft tissue, urine and blood. Colistin, amikacin and piperacillin/tazobactam were active against 100%, 86% and 75% of P. aeruginosa isolates, respectively. A total of 20% (n=316) of P. aeruginosa isolates were MDR. In summary, A. baumannii was more rare than P. aeruginosa but was more commonly MDR. Epidemiological data will help to implement better infection control strategies, and developing a local antibiogram database will improve the knowledge of antimicrobial resistance patterns in our region.
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