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Beig M, Parvizi E, Navidifar T, Bostanghadiri N, Mofid M, Golab N, Sholeh M. Geographical mapping and temporal trends of Acinetobacter baumannii carbapenem resistance: A comprehensive meta-analysis. PLoS One 2024; 19:e0311124. [PMID: 39680587 DOI: 10.1371/journal.pone.0311124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Accepted: 09/04/2024] [Indexed: 12/18/2024] Open
Abstract
BACKGROUND Carbapenem-resistant Acinetobacter baumannii (CRAB) is of critical concern in healthcare settings, leading to limited treatment options. In this study, we conducted a comprehensive meta-analysis to assess the prevalence of CRAB by examining temporal, geographic, and bias-related variations. METHODS We systematically searched prominent databases, including Scopus, PubMed, Web of Science, and EMBASE. Quality assessment was performed using the JBI checklist. Subgroup analyses were performed based on the COVID-19 timeframes, years, countries, continents, and bias levels, antimicrobial susceptivity test method and guidelines. RESULTS Our comprehensive meta-analysis, which included 795 studies across 80 countries from 1995 to 2023, revealed a surge in carbapenem resistance among A. baumannii, imipenem (76.1%), meropenem (73.5%), doripenem (73.0%), ertapenem (83.7%), and carbapenems (74.3%). Temporally, 2020-2023 witnessed significant peaks, particularly in carbapenems (81.0%) and meropenem (80.7%), as confirmed by meta-regression, indicating a steady upward trend. CONCLUSION This meta-analysis revealed an alarmingly high resistance rate to CRAB as a global challenge, emphasizing the urgent need for tailored interventions. Transparency, standardized methodologies, and collaboration are crucial for the accurate assessment and maintenance of carbapenem efficacy.
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Affiliation(s)
- Masoumeh Beig
- Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran
| | - Elnaz Parvizi
- Department of Microbiology, Science and Research Branch, Islamic Azad University, Fars, Iran
| | - Tahereh Navidifar
- Shoushtar Faculty of Medical Sciences, Department of Basic Sciences, Shoushtar, Iran
| | - Narjes Bostanghadiri
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Maryam Mofid
- School of Medicine, Hamadan University of Medical Science, Hamadan, Iran
| | - Narges Golab
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Sholeh
- Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran
- Student Research Committee, Pasteur Institute of Iran, Tehran, Iran
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Acinetobacter baumannii from Samples of Commercially Reared Turkeys: Genomic Relationships, Antimicrobial and Biocide Susceptibility. Microorganisms 2023; 11:microorganisms11030759. [PMID: 36985332 PMCID: PMC10052703 DOI: 10.3390/microorganisms11030759] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 03/05/2023] [Accepted: 03/07/2023] [Indexed: 03/18/2023] Open
Abstract
Acinetobacter baumannii is especially known as a cause of nosocomial infections worldwide. It shows intrinsic and acquired resistances to numerous antimicrobial agents, which can render the treatment difficult. In contrast to the situation in human medicine, there are only few studies focusing on A. baumannii among livestock. In this study, we have examined 643 samples from turkeys reared for meat production, including 250 environmental and 393 diagnostic samples, for the presence of A. baumannii. In total, 99 isolates were identified, confirmed to species level via MALDI-TOF-MS and characterised with pulsed-field gel electrophoresis. Antimicrobial and biocide susceptibility was tested by broth microdilution methods. Based on the results, 26 representative isolates were selected and subjected to whole-genome sequencing (WGS). In general, A. baumannii was detected at a very low prevalence, except for a high prevalence of 79.7% in chick-box-papers (n = 118) of one-day-old turkey chicks. The distributions of the minimal inhibitory concentration values were unimodal for the four biocides and for most of the antimicrobial agents tested. WGS revealed 16 Pasteur and 18 Oxford sequence types, including new ones. Core genome MLST highlighted the diversity of most isolates. In conclusion, the isolates detected were highly diverse and still susceptible to many antimicrobial agents.
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Vuillemenot JB, Bour M, Beyrouthy R, Bonnet R, Laaberki MH, Charpentier X, Ruimy R, Plésiat P, Potron A. Genomic analysis of CTX-M-115 and OXA-23/-72 co-producing Acinetobacter baumannii, and their potential to spread resistance genes by natural transformation. J Antimicrob Chemother 2022; 77:1542-1552. [PMID: 35412620 DOI: 10.1093/jac/dkac099] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 02/16/2022] [Indexed: 11/15/2022] Open
Abstract
OBJECTIVES To characterize Acinetobacter baumannii strains co-producing the ESBL CTX-M-115 and carbapenem-hydrolysing class D β-lactamases (CHDLs), and to assess the potential diffusion of their resistance genes by horizontal transfer. METHODS Nineteen CTX-M-115/CHDL-positive A. baumannii were collected between 2015 and 2019 from patients hospitalized in France. Their whole-genome sequences were determined on Illumina and Oxford Nanopore platforms and were compared through core-genome MLST (cgMLST) and SNP analyses. Transferability of resistance genes was investigated by natural transformation assays. RESULTS Eighteen strains were found to harbour CHDL OXA-72, and another one CHDL OXA-23, in addition to CTX-M-115, narrow-spectrum β-lactamases and aminoglycoside resistance determinants including ArmA. cgMLST typing, as well as Oxford Scheme ST and K locus typing, confirmed that 17 out of the 18 CTX-M-115/OXA-72 isolates belonged to new subclades within clonal complex 78 (CC78). The chromosomal region carrying the blaCTX-M-115 gene appeared to vary greatly both in gene content and in length (from 20 to 79 kb) among the strains, likely because of IS26-mediated DNA rearrangements. The blaOXA-72 gene was localized on closely related plasmids showing structural variations that occurred between pdif sites. Transfer of all the β-lactamase genes, as well as aminoglycoside resistance determinants to a drug-susceptible A. baumannii recipient, was easily obtained in vitro by natural transformation. CONCLUSIONS This work highlights the propensity of CC78 isolates to collect multiple antibiotic resistance genes, to rearrange and to pass them to other A. baumannii strains via natural transformation. This process, along with mobile genetic elements, likely contributes to the considerable genomic plasticity of clinical strains, and to the diversity of molecular mechanisms sustaining their multidrug resistance.
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Affiliation(s)
- Jean-Baptiste Vuillemenot
- Centre National de Référence de la Résistance aux Antibiotiques, Centre Hospitalier Universitaire de Besançon, France.,Laboratoire de Bactériologie, UMR 6249 Chrono-Environnement, UFR Santé, Université Bourgogne Franche-Comté, Besançon, France
| | - Maxime Bour
- Centre National de Référence de la Résistance aux Antibiotiques, Centre Hospitalier Universitaire de Besançon, France
| | - Racha Beyrouthy
- UMR INSERM 1071 USC INRA2018, Université Clermont Auvergne, Clermont-Ferrand, France.,Laboratoire associé Centre National de Référence de la Résistance aux Antibiotiques, Centre Hospitalier Universitaire de Clermont-Ferrand, France
| | - Richard Bonnet
- UMR INSERM 1071 USC INRA2018, Université Clermont Auvergne, Clermont-Ferrand, France.,Laboratoire associé Centre National de Référence de la Résistance aux Antibiotiques, Centre Hospitalier Universitaire de Clermont-Ferrand, France
| | - Maria-Halima Laaberki
- CIRI, Centre International de Recherche en Infectiologie, INSERM U1111, Université Claude Bernard Lyon 1, Villeurbanne, France
| | - Xavier Charpentier
- CIRI, Centre International de Recherche en Infectiologie, INSERM U1111, Université Claude Bernard Lyon 1, Villeurbanne, France
| | - Raymond Ruimy
- Laboratoire de Bactériologie, Centre Hospitalier Universitaire de Nice, UMR INSERM C3M, Université Côte d'Azur, Nice, France
| | - Patrick Plésiat
- Centre National de Référence de la Résistance aux Antibiotiques, Centre Hospitalier Universitaire de Besançon, France.,Laboratoire de Bactériologie, UMR 6249 Chrono-Environnement, UFR Santé, Université Bourgogne Franche-Comté, Besançon, France
| | - Anaïs Potron
- Centre National de Référence de la Résistance aux Antibiotiques, Centre Hospitalier Universitaire de Besançon, France.,Laboratoire de Bactériologie, UMR 6249 Chrono-Environnement, UFR Santé, Université Bourgogne Franche-Comté, Besançon, France
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4
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Arakawa Y. Systematic research to overcome newly emerged multidrug-resistant bacteria. Microbiol Immunol 2020; 64:231-251. [PMID: 32068266 DOI: 10.1111/1348-0421.12781] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2019] [Revised: 01/05/2020] [Accepted: 02/08/2020] [Indexed: 11/30/2022]
Abstract
In the 1980s, I found that the chromosomal β-lactamase of Klebsiella pneumoniae LEN-1 showed a very high similarity to the R-plasmid-mediated penicillinase TEM-1 on the amino acid sequence level, and this strongly suggested the origination of TEM-1 from the chromosomal penicillinases of K. pneumoniae or related bacteria. Moreover, the chromosomal K1 β-lactamase (KOXY) of Klebsiella oxytoca was found to belong to the class A β-lactamases that include LEN-1 and TEM-1, although KOXY can hydrolyze cefoperazone (CPZ) like the chromosomal AmpC-type cephalosporinases of various Enterobacteriaceae that can hydrolyze several cephalosporins including CPZ. Furthermore, my collaborators and I found plural novel serine-type β-lactamases, such as MOX-1, SHV-24, TEM-91, CTX-M-64, CMY-9, CMY-19, GES-3, GES-4, and TLA-3, mediated by plasmids. Besides these serine-type β-lactamases, we also first identified exogenously acquired metallo-β-lactamases (MBLs), IMP-1 and SMB-1, in imipenem-resistant Serratia marcescens, and the IMP-1-producing S. marcescens TN9106 became the index case for carbapenemase-producing Enterobacteriaceae. I developed the sodium mercaptoacetic acid (SMA)-disk test for the simple identification of MBL-producing bacteria. We were also the first to identify a variety of plasmid-mediated 16S ribosomal RNA methyltransferases, RmtA, RmtB, RmtC, and NpmA, from various Gram-negative bacteria that showed very high levels of resistance to a wide range of aminoglycosides. Furthermore, we first found plasmid-mediated quinolone efflux pump (QepA) and fosfomycin-inactivating enzymes (FosA3 and FosK). We also first characterized penicillin reduced susceptible Streptococcus agalactiae, macrolide-resistant Mycoplasma pneumoniae, as well as Campylobacter jejuni, and Helicobacter pylori, together with carbapenem-resistant Haemophilus influenzae. We constructed a PCR-based open reading frame typing method for rapid identification of Acinetobacter baumannii international clones.
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Affiliation(s)
- Yoshichika Arakawa
- Department of Bacteriology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan
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5
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Abd El-Baky RM, Farhan SM, Ibrahim RA, Mahran KM, Hetta HF. Antimicrobial resistance pattern and molecular epidemiology of ESBL and MBL producing Acinetobacter baumannii isolated from hospitals in Minia, Egypt. ALEXANDRIA JOURNAL OF MEDICINE 2020. [DOI: 10.1080/20905068.2019.1707350] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Affiliation(s)
- Rehab M. Abd El-Baky
- Department of Microbiology and Immunology, Faculty of Pharmacy, Minia University, Minia, Egypt
- Department of Microbiology & Immunology, Faculty of Pharmacy, Deraya University, Minia, Egypt
| | - Sara M. Farhan
- Department of Microbiology & Immunology, Faculty of Pharmacy, Deraya University, Minia, Egypt
| | - Reham A. Ibrahim
- Department of Microbiology and Immunology, Faculty of Pharmacy, Minia University, Minia, Egypt
| | - Khaled M. Mahran
- General Surgery and Laparoscopic surgery, Faculty of Medicine, Minia University, Minia, Egypt
| | - Helal F. Hetta
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt
- Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA
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6
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Mlynarcik P, Bardon J, Htoutou Sedlakova M, Prochazkova P, Kolar M. Identification of novel OXA-134-like β-lactamases in Acinetobacter lwoffii and Acinetobacter schindleri isolated from chicken litter. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2019; 163:141-146. [DOI: 10.5507/bp.2018.037] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2018] [Accepted: 06/22/2018] [Indexed: 11/23/2022] Open
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7
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Jamal S, Al Atrouni A, Rafei R, Dabboussi F, Hamze M, Osman M. Molecular mechanisms of antimicrobial resistance in Acinetobacter baumannii, with a special focus on its epidemiology in Lebanon. J Glob Antimicrob Resist 2018; 15:154-163. [PMID: 29859266 DOI: 10.1016/j.jgar.2018.05.022] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2017] [Revised: 02/24/2018] [Accepted: 05/22/2018] [Indexed: 10/16/2022] Open
Abstract
Acinetobacter baumannii is an opportunistic bacterium involved in several types of infection with high mortality and morbidity, especially in intensive care units. Treatment of these infections remains a challenge due to the worldwide emergence of broad-spectrum resistance to many antibiotics. Following the implementation of molecular techniques to study A. baumannii outbreaks, it has been shown that they are mainly caused by specific clones such as international clones I, II and III. The present work aims to review the available data on the mechanisms underlying antimicrobial resistance in A. baumannii, with a special focus on the molecular epidemiology of this species in Lebanon.
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Affiliation(s)
- Sabah Jamal
- Laboratoire Microbiologie Santé et Environnement (LMSE), Ecole Doctorale des Sciences et de Technologie, Faculté de Santé Publique, Université Libanaise, Tripoli, Lebanon
| | - Ahmad Al Atrouni
- Laboratoire Microbiologie Santé et Environnement (LMSE), Ecole Doctorale des Sciences et de Technologie, Faculté de Santé Publique, Université Libanaise, Tripoli, Lebanon
| | - Rayane Rafei
- Laboratoire Microbiologie Santé et Environnement (LMSE), Ecole Doctorale des Sciences et de Technologie, Faculté de Santé Publique, Université Libanaise, Tripoli, Lebanon
| | - Fouad Dabboussi
- Laboratoire Microbiologie Santé et Environnement (LMSE), Ecole Doctorale des Sciences et de Technologie, Faculté de Santé Publique, Université Libanaise, Tripoli, Lebanon
| | - Monzer Hamze
- Laboratoire Microbiologie Santé et Environnement (LMSE), Ecole Doctorale des Sciences et de Technologie, Faculté de Santé Publique, Université Libanaise, Tripoli, Lebanon.
| | - Marwan Osman
- Laboratoire Microbiologie Santé et Environnement (LMSE), Ecole Doctorale des Sciences et de Technologie, Faculté de Santé Publique, Université Libanaise, Tripoli, Lebanon
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8
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Smiline A, Vijayashree JP, Paramasivam A. Molecular characterization of plasmid-encoded blaTEM, blaSHV and blaCTX-M among extended spectrum β-lactamases [ESBLs] producing Acinetobacter baumannii. Br J Biomed Sci 2018; 75:200-202. [PMID: 29962277 DOI: 10.1080/09674845.2018.1492207] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Affiliation(s)
- Asg Smiline
- a Department of Microbiology , Saveetha Dental College and Hospitals, [SIMATS] , Chennai , India
| | - J P Vijayashree
- b BRULAC-DRC , Saveetha Dental College and Hospitals, [SIMATS] , Chennai , India
| | - A Paramasivam
- c Centre for cellular and Molecular Biology , Hyderabad , India
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9
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ESBL-producing Escherichia coli
and Its Rapid Rise among Healthy People. Food Saf (Tokyo) 2017; 5:122-150. [PMID: 32231938 DOI: 10.14252/foodsafetyfscj.2017011] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2017] [Accepted: 12/11/2017] [Indexed: 02/06/2023] Open
Abstract
Since around the 2000s, Escherichia coli (E. coli) resistant to both oxyimino-cephalosporins and fluoroquinolones has remarkably increased worldwide in clinical settings. The kind of E. coli is also identified in patients suffering from community-onset infectious diseases such as urinary tract infections. Moreover, recoveries of multi-drug resistant E. coli from the feces of healthy people have been increasingly documented in recent years, although the actual state remains uncertain. These E. coli isolates usually produce extended-spectrum β-lactamase (ESBL), as well as acquisition of amino acid substitutions in the quinolone-resistance determining regions (QRDRs) of GyrA and/or ParC, together with plasmid-mediated quinolone resistance determinants such as Qnr, AAC(6')-Ib-cr, and QepA. The actual state of ESBL-producing E. coli in hospitalized patients has been carefully investigated in many countries, while that in healthy people still remains uncertain, although high fecal carriage rates of ESBL producers in healthy people have been reported especially in Asian and South American countries. The issues regarding the ESBL producers have become very complicated and chaotic due to rapid increase of both ESBL variants and plasmids mediating ESBL genes, together with the emergence of various "epidemic strains" or "international clones" of E. coli and Klebsiella pneumoniae harboring transferable-plasmids carrying multiple antimicrobial resistance genes. Thus, the current state of ESBL producers outside hospital settings was overviewed together with the relation among those recovered from livestock, foods, pets, environments and wildlife from the viewpoint of molecular epidemiology. This mini review may contribute to better understanding about ESBL producers among people who are not familiar with the antimicrobial resistance (AMR) threatening rising globally.
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Antimicrobial Susceptibility Pattern and Prevalence of Extended-Spectrum β-Lactamase Genotypes among Clinical Isolates of Acinetobacter baumanii in Tabriz, North-West of Iran. Jundishapur J Microbiol 2017. [DOI: 10.5812/jjm.13368] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
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11
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Dou Y, Song F, Guo F, Zhou Z, Zhu C, Xiang J, Huan J. Acinetobacter baumannii quorum-sensing signalling molecule induces the expression of drug-resistance genes. Mol Med Rep 2017; 15:4061-4068. [PMID: 28487993 PMCID: PMC5436197 DOI: 10.3892/mmr.2017.6528] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2016] [Accepted: 03/13/2017] [Indexed: 01/23/2023] Open
Abstract
Quorum-sensing signalling molecules such as N-acyl homoserine lactones (AHLs) enable certain Gram-negative bacteria to respond to environmental changes through behaviours, such as biofilm formation and flagellar movement. The present study aimed to identify Acinetobacter baumannii AHLs and assess their influence on antibiotic resistance. A clinical isolate of A. baumannii strain S (AbS) was collected from the wound of a burn patient and high-performance liquid chromatography and tandem quadrupole or quadrupole time-of-flight high-resolution mass spectrometry was used to identify AbS AHLs. Antibiotic sensitivity was assessed in an AHL-deficient AbS mutant (AbS-M), and the expression of drug-resistance genes in the presence of meropenem in AbS, AbS-M and AbS-M treated with the AHL N-3-hydroxy-dodecanoyl-homoserine lactone (N-3-OH-C12-HSL). AbS-M was more sensitive to meropenem and piperacillin than wild-type AbS, but resistance was restored by supplementation with N-3-OH-C12-HSL. In addition, meropenem-treated AbS-M expressed lower levels of the drug-resistance genes oxacillinase 51, AmpC, AdeA and AdeB; treatment with N-3-OH-C12-HSL also restored the expression of these genes. Overall, the results of the present study indicate that N-3-OH-C12-HSL may be involved in regulating the expression of drug-resistance genes in A. baumannii. Therefore, this quorum-sensing signalling molecule may be an important target for treating multidrug-resistant A. baumannii infections.
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Affiliation(s)
- Yi Dou
- Department of Burns and Plastic Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China
| | - Fei Song
- Department of Burns and Plastic Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China
| | - Feng Guo
- Department of Burns and Plastic Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China
| | - Zengding Zhou
- Department of Burns and Plastic Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China
| | - Cailian Zhu
- The Ninth People's Hospital, School of Stomatology, Shanghai Jiaotong University, Shanghai Research Institute of Stomatology, Shanghai 200011, P.R. China
| | - Jun Xiang
- Department of Burns and Plastic Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China
| | - Jingning Huan
- Department of Burns and Plastic Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China
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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: 549] [Impact Index Per Article: 68.6] [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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PER-8, a Novel Extended-Spectrum β-Lactamase PER Variant, from an Acinetobacter baumannii Clinical Isolate in Nepal. Antimicrob Agents Chemother 2017; 61:AAC.02300-16. [PMID: 28031203 DOI: 10.1128/aac.02300-16] [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] [Received: 11/01/2016] [Accepted: 12/17/2016] [Indexed: 01/29/2023] Open
Abstract
A novel PER-type extended-spectrum β-lactamase, PER-8, was identified in an Acinetobacter baumannii clinical isolate obtained in Nepal. The amino acid sequence of PER-8 has a substitution at position 39 (Gly to Glu) compared with that of PER-7. The kcat/Km ratio of PER-8 for aztreonam was lower than that of PER-7, while the kcat/Km ratio of PER-8 for imipenem was higher than that of PER-7. The genomic environment surrounding blaPER-8 was intI1 blaPSE-1qacEDI sulI ISCR1-blaPER-8gts sulI orfX on a 100-kb plasmid.
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14
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Esterly JS, Richardson CL, Eltoukhy NS, Qi C, Scheetz MH. Genetic Mechanisms of Antimicrobial Resistance of Acinetobacter baumannii. Ann Pharmacother 2015; 45:218-28. [PMID: 21304033 DOI: 10.1345/aph.1p084] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVE To summarize published data identifying known genetic mechanisms of antibiotic resistance in Acinetobacter baumannii and the correlating phenotypic expression of antibiotic resistance. DATA SOURCES MEDLINE databases (1966-July 15, 2010) were searched to identify original reports of genetic mechanisms of antibiotic resistance in A. baumannii. DATA SYNTHESIS Numerous genetic mechanisms of resistance to multiple classes of antibiotics are known to exist in A. baumannii, a gram-negative bacterium increasingly implicated in nosocomial infections. Mechanisms may be constitutive or acquired via plasmids, integrons, and transposons. Methods of resistance include enzymatic modification of antibiotic molecules, modification of antibiotic target sites, expression of efflux pumps, and downregulation of cell membrane porin channel expression. Resistance to β-lactams appears to be primarily caused by β-lactamase production, including extended spectrum β-lactamases (b/aTEM, blaSHV, b/aTX-M,b/aKPC), metallo-β-lactamases (blaMP, blaVIM, bla, SIM), and most commonly, oxacillinases (blaOXA). Antibiotic target site alterations confer resistance to fluoroquinolones (gyrA, parC) and aminoglycosides (arm, rmt), and to a much lesser extent, β-lactams. Efflux pumps (tet, ade, abe) contribute to resistance against β-lactams, tetracyclines, fluoroquinolones, and aminoglycosides. Finally, porin channel deletion (carO, oprD) appears to contribute to β-lactam resistance and may contribute to rarely seen polymyxin resistance. Of note, efflux pumps and porin deletions as solitary mechanisms may not render clinical resistance to A. baumannii. CONCLUSIONS A. baumannii possesses copious genetic resistance mechanisms. Knowledge of local genotypes and expressed phenotypes for A. baumannii may aid clinicians more than phenotypic susceptibilities reported in large epidemiologic studies.
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Affiliation(s)
- John S Esterly
- John S Esterly PharmD BCPS, at time of writing, Infectious Diseases Pharmacotherapy Fellow, Department of Pharmacy Practice, College of Pharmacy, Midwestern University Chicago, Downers Grove, IL; now, Assistant Professor of Pharmacy Practice, College of Pharmacy, Chicago State University, Chicago, IL; Infectious Diseases Pharmacist, Northwestern Memorial Hospital, Chicago
| | - Chad L Richardson
- Chad L Richardson PharmD, at time of writing, Infectious Diseases Pharmacotherapy Resident, Department of Pharmacy Practice, College of Pharmacy, Midwestern University Chicago; now, Solid Organ Transplant Pharmacist, Northwestern Memorial Hospital
| | - Noha S Eltoukhy
- Noha S Eltoukhy PharmD BCPS, at time of writing, Infectious Diseases Pharmacy Resident, Department of Pharmacy Practice, College of Pharmacy, Midwestern University Chicago; Rush University Medical Center, Chicago; now, Infectious DIseases Clinical Pharmacy Specialist, St. Mary Medical Center, Langhorne, PA
| | - Chao Qi
- Chao Qi PhD, Assistant Professor of Pathology, Feinberg School of Medicine, Northwestern University; Assistant Director, Clinical Microbiology Laboratory, Northwestern Memorial Hospital, Chicago
| | - Marc H Scheetz
- Marc H Scheetz PharmD MSc BCPS, Assistant Professor of Pharmacy Practice, College of Pharmacy, Midwestern University Chicago; Infectious Diseases Pharmacist, Northwestern Memorial Hospital
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Miranda C, de Filippis I, Pinto L, Coelho-Souza T, Bianco K, Cacci L, Picão R, Clementino M. Genotypic characteristics of multidrug-resistant Pseudomonas aeruginosa
from hospital wastewater treatment plant in Rio de Janeiro, Brazil. J Appl Microbiol 2015; 118:1276-86. [DOI: 10.1111/jam.12792] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2014] [Revised: 01/16/2015] [Accepted: 02/24/2015] [Indexed: 11/27/2022]
Affiliation(s)
- C.C. Miranda
- Instituto Nacional de Controle de Qualidade em Saúde; FIOCRUZ; Rio de Janeiro Brazil
| | - I. de Filippis
- Instituto Nacional de Controle de Qualidade em Saúde; FIOCRUZ; Rio de Janeiro Brazil
| | - L.H. Pinto
- Departamento de Bioquímica; Instituto de Biologia Roberto Alcântara Gomes; Universidade do Estado do Rio de Janeiro; Rio de Janeiro Brazil
| | - T. Coelho-Souza
- Instituto Nacional de Controle de Qualidade em Saúde; FIOCRUZ; Rio de Janeiro Brazil
| | - K. Bianco
- Instituto Nacional de Controle de Qualidade em Saúde; FIOCRUZ; Rio de Janeiro Brazil
| | - L.C. Cacci
- Instituto de Microbiologia Paulo de Góes; Universidade Federal do Rio de Janeiro; Rio de Janeiro Brazil
| | - R.C. Picão
- Instituto de Microbiologia Paulo de Góes; Universidade Federal do Rio de Janeiro; Rio de Janeiro Brazil
| | - M.M. Clementino
- Instituto Nacional de Controle de Qualidade em Saúde; FIOCRUZ; Rio de Janeiro Brazil
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Potron A, Poirel L, Nordmann P. Emerging broad-spectrum resistance in Pseudomonas aeruginosa and Acinetobacter baumannii: Mechanisms and epidemiology. Int J Antimicrob Agents 2015; 45:568-85. [PMID: 25857949 DOI: 10.1016/j.ijantimicag.2015.03.001] [Citation(s) in RCA: 476] [Impact Index Per Article: 47.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2015] [Accepted: 03/05/2015] [Indexed: 02/07/2023]
Abstract
Multidrug resistance is quite common among non-fermenting Gram-negative rods, in particular among clinically relevant species including Pseudomonas aeruginosa and Acinetobacter baumannii. These bacterial species, which are mainly nosocomial pathogens, possess a diversity of resistance mechanisms that may lead to multidrug or even pandrug resistance. Extended-spectrum β-lactamases (ESBLs) conferring resistance to broad-spectrum cephalosporins, carbapenemases conferring resistance to carbapenems, and 16S rRNA methylases conferring resistance to all clinically relevant aminoglycosides are the most important causes of concern. Concomitant resistance to fluoroquinolones, polymyxins (colistin) and tigecycline may lead to pandrug resistance. The most important mechanisms of resistance in P. aeruginosa and A. baumannii and their most recent dissemination worldwide are detailed here.
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Affiliation(s)
- Anaïs Potron
- Laboratoire de Bactériologie, Faculté de Médecine-Pharmacie, Centre Hospitalier Régional Universitaire, Université de Franche-Comté, Besançon, France
| | - Laurent Poirel
- Emerging Antibiotic Resistance Medical and Molecular Microbiology Unit, Department of Medicine, Faculty of Science, University of Fribourg, Fribourg, Switzerland.
| | - Patrice Nordmann
- Emerging Antibiotic Resistance Medical and Molecular Microbiology Unit, Department of Medicine, Faculty of Science, University of Fribourg, Fribourg, Switzerland; HFR - Hôpital Cantonal de Fribourg, Fribourg, Switzerland
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17
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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: 237] [Impact Index Per Article: 21.5] [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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Kjeldsen TSB, Overgaard M, Nielsen SS, Bortolaia V, Jelsbak L, Sommer M, Guardabassi L, Olsen JE. CTX-M-1 β-lactamase expression in Escherichia coli is dependent on cefotaxime concentration, growth phase and gene location. J Antimicrob Chemother 2014; 70:62-70. [DOI: 10.1093/jac/dku332] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
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19
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Durante-Mangoni E, Utili R, Zarrilli R. Combination therapy in severe Acinetobacter baumannii infections: an update on the evidence to date. Future Microbiol 2014; 9:773-89. [DOI: 10.2217/fmb.14.34] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
ABSTRACT: Acinetobacter baumannii is a drug-resistant Gram-negative pathogen increasingly causing hospital-acquired infections in critically ill patients. In this review, we summarize the current mechanisms of antimicrobial resistance in A. baumannii and describe in detail recent in vitro and in vivo experimental data on the activity of antimicrobial combinations against this microorganism. We then introduce the rationale for the use of combination antibiotic therapy in resistant A. baumannii infections. Finally, we present and critically discuss both uncontrolled clinical studies and the few randomized clinical trials of combination antimicrobial therapy for these infections, with a special focus on ongoing multinational trials and optimal approach to future research in this field.
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Affiliation(s)
- Emanuele Durante-Mangoni
- Internal Medicine, University of Naples S.U.N. & AORN dei Colli, Monaldi Hospital, Via L. Bianchi, Naples, Italy
| | - Riccardo Utili
- Internal Medicine, University of Naples S.U.N. & AORN dei Colli, Monaldi Hospital, Via L. Bianchi, Naples, Italy
| | - Raffaele Zarrilli
- Department of Public Health, University of Naples Federico II, Naples, Italy
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Singla P, Sikka R, Deeep A, Gagneja D, Chaudhary U. Co-production of ESBL and AmpC β-Lactamases in Clinical Isolates of A. baumannii and A. lwoffii in a Tertiary Care Hospital From Northern India. J Clin Diagn Res 2014; 8:DC16-9. [PMID: 24959443 DOI: 10.7860/jcdr/2014/8008.4289] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2013] [Accepted: 01/20/2014] [Indexed: 11/24/2022]
Abstract
BACKGROUND Acinetobacter baumannii is an important cause of health care associated infections which are difficult to control and treat, because of widespread antimicrobial resistance which is possessed by this organism. AIMS The aim of the present study was to know the prevalence of ESBLs and AmpC β-lactamases in clinical isolates of Acinetobacter spp. which were cultured from various clinical specimens by using different phenotypic methods. SETTINGS AND DESIGN Study was conducted over a period of one year at the Microbiology Department of a tertiary care teaching hospital. A total of 100 consecutive, non-duplicate strains of Acinetobacter species which were isolated from various clinical samples were included. MATERIALS AND METHODS All the isolates were identified by standard microbiological procedures and antimicrobial susceptibility testing was done by Kirby-Bauer disc diffusion technique. Isolates which showed reduced susceptibilities to third generation cephalosporins were tested for ESBL production by CLSI double disc synergy method and also by using sulbactam as an inhibitory agent. Isolates which showed reduced susceptibilities to cefoxitin were tested for AmpC detection by doing AmpC disc test. STATISTICAL ANALYSIS SPSS, version 17 was used to calculate p-value. If the p-value was <0.05, it was considered to be significant. RESULTS Out of 100 isolates, 82 were Acinetobacter baumannii and 18 were Acinetobacter lwoffii. ESBL were mentioned in 4% of the Acinetobacter isolates and in 77% of the isolates by using clavulanic acid and sulbactam as inhibitory agents respectively. AmpC β-lactamase production was detected in 60% isolates of Acinetobacter spp. Co-production of both ESBL and AmpC enzymes were seen in 29% of the Acinetobacter strains. CONCLUSION Failure in detecting β-lactamases contributes to their uncontrolled spread and therapeutic failures. Hence, these β-lactamases should be detected routinely and they should be reported to clinicians in time, so that inappropriate use of antibiotics can be stopped in time.
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Affiliation(s)
- Pooja Singla
- Demonstrator, Department of Microbiology, PT. B.D. Sharma PGIMS Rohtak, India
| | - Rama Sikka
- Professor, Department of Microbiology, PT. B.D. Sharma PGIMS Rohtak, India
| | - Antariksh Deeep
- Associate Professor, Department of Microbiology, PT. B.D. Sharma PGIMS Rohtak, India
| | - Deep Gagneja
- Medical Officer, General Hospital , Sirsa, India
| | - Uma Chaudhary
- Sr. Professor and Head, Department of Microbiology, PT. B.D. Sharma PGIMS Rohtak, India
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21
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Briceño DF, Quinn JP, Villegas MV. Treatment options for multidrug-resistant nonfermenters. Expert Rev Anti Infect Ther 2014; 8:303-15. [DOI: 10.1586/eri.09.125] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
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22
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Zavascki AP, Carvalhaes CG, Picão RC, Gales AC. Multidrug-resistantPseudomonas aeruginosaandAcinetobacter baumannii: resistance mechanisms and implications for therapy. Expert Rev Anti Infect Ther 2014; 8:71-93. [DOI: 10.1586/eri.09.108] [Citation(s) in RCA: 203] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
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23
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Bonnin RA, Nordmann P, Poirel L. Screening and deciphering antibiotic resistance inAcinetobacter baumannii: a state of the art. Expert Rev Anti Infect Ther 2014; 11:571-83. [DOI: 10.1586/eri.13.38] [Citation(s) in RCA: 73] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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24
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Joshi SG, Litake GM. Acinetobacter baumannii: An emerging pathogenic threat to public health. World J Clin Infect Dis 2013; 3:25-36. [DOI: 10.5495/wjcid.v3.i3.25] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2013] [Accepted: 08/06/2013] [Indexed: 02/06/2023] Open
Abstract
Over the last three decades, Acinetobacter has gained importance as a leading nosocomial pathogen, partly due to its impressive genetic capabilities to acquire resistance and partly due to high selective pressure, especially in critical care units. This low-virulence organism has turned into a multidrug resistant pathogen and now alarming healthcare providers worldwide. Acinetobacter baumannii (A. baumannii) is a major species, contributing about 80% of all Acinetobacter hospital-acquired infections. It disseminates antibiotic resistance by virtue of its extraordinary ability to accept or donate resistance plasmids. The procedures for breaking the route of transmission are still proper hand washing and personal hygiene (both the patient and the healthcare professional), reducing patient’s biofilm burden from skin, and judicious use of antimicrobial agents. The increasing incidence of extended-spectrum beta-lactamases and carbapenemases in A. baumannii leaves almost no cure for these “bad bugs”. To control hospital outbreaks of multidrug resistant-Acinetobacter infection, we need to contain their dissemination or require new drugs or a rational combination therapy. The optimal treatment for multidrug-resistant A. baumannii infection has not been clearly established, and empirical therapy continues to require knowledge of susceptibility patterns of isolates from one’s own institution. This review mainly focused on general features and introduction to A. baumannii and its epidemiological status, potential sources of infection, risk factors, and strategies to control infection to minimize spread.
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25
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Abstract
Production of extended-spectrum β-lactamases (ESBLs) is the principal mechanism of resistance to oxyimino-cephalosporins evolved by members of the family Enterobacteriaceae. Among the several ESBLs emerged among clinical pathogens, the CTX-M-type enzymes have proved the most successful in terms of promiscuity and diffusion in different epidemiological settings, where they have largely replaced and outnumbered other types of ESBLs. Originated by the capture and mobilization of chromosomal β-lactamase genes of strains of Kluyvera species, the blaCTX-M genes have become associated with a variety of mobile genetic elements that have mediated rapid and efficient inter-replicon and cell-to-cell dissemination involving highly successful enterobacterial lineages (e.g. Escherichia coli ST131 and ST405, or Klebsiella pneumoniae CC11 and ST147) to yield high-risk multiresistant clones that have spread on a global scale. The CTX-Mβ-lactamase lineage exhibits a striking plasticity, with a large number of allelic variants belonging in several sublineages, which can be associated with functional heterogeneity of clinical relevance. This review article provides an update on CTX-M-type ESBLs, with focus on structural and functional diversity, epidemiology and clinical significance.
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26
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Fehlberg LC, Xavier DE, Peraro PP, Marra AR, Edmond MB, Gales AC. Beta-Lactam Resistance Mechanisms inPseudomonas aeruginosaStrains Causing Bloodstream Infections: Comparative Results Between Brazilian and American Isolates. Microb Drug Resist 2012; 18:402-7. [DOI: 10.1089/mdr.2011.0174] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Affiliation(s)
- Lorena C.C. Fehlberg
- Division of Infectious Diseases, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Danilo E. Xavier
- Division of Infectious Diseases, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Paula P. Peraro
- Division of Infectious Diseases, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Alexandre R. Marra
- Division of Infectious Diseases, Universidade Federal de São Paulo, São Paulo, Brazil
- Intensive Care Unit, Hospital Israelita Albert Einstein, São Paulo, Brazil
| | - Michael B. Edmond
- Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia
| | - Ana C. Gales
- Division of Infectious Diseases, Universidade Federal de São Paulo, São Paulo, Brazil
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Poirel L, Bonnin RA, Nordmann P. Genetic support and diversity of acquired extended-spectrum β-lactamases in Gram-negative rods. INFECTION GENETICS AND EVOLUTION 2012; 12:883-93. [DOI: 10.1016/j.meegid.2012.02.008] [Citation(s) in RCA: 98] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/24/2011] [Revised: 02/14/2012] [Accepted: 02/15/2012] [Indexed: 02/01/2023]
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Zhao WH, Hu ZQ. Epidemiology and genetics of CTX-M extended-spectrum β-lactamases in Gram-negative bacteria. Crit Rev Microbiol 2012; 39:79-101. [PMID: 22697133 PMCID: PMC4086240 DOI: 10.3109/1040841x.2012.691460] [Citation(s) in RCA: 206] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
CTX-M enzymes, the plasmid-mediated cefotaximases, constitute a rapidly growing family of extended-spectrum β-lactamases (ESBLs) with significant clinical impact. CTX-Ms are found in at least 26 bacterial species, particularly in Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis. At least 109 members in CTX-M family are identified and can be divided into seven clusters based on their phylogeny. CTX-M-15 and CTX-M-14 are the most dominant variants. Chromosome-encoded intrinsic cefotaximases in Kluyvera spp. are proposed to be the progenitors of CTX-Ms, while ISEcp1, ISCR1 and plasmid are closely associated with their mobilization and dissemination.
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Affiliation(s)
- Wei-Hua Zhao
- Department of Microbiology and Immunology, Showa University School of Medicine, Tokyo, Japan.
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29
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Roca I, Espinal P, Vila-Farrés X, Vila J. The Acinetobacter baumannii Oxymoron: Commensal Hospital Dweller Turned Pan-Drug-Resistant Menace. Front Microbiol 2012; 3:148. [PMID: 22536199 PMCID: PMC3333477 DOI: 10.3389/fmicb.2012.00148] [Citation(s) in RCA: 251] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2011] [Accepted: 03/28/2012] [Indexed: 12/28/2022] Open
Abstract
During the past few decades Acinetobacter baumannii has evolved from being a commensal dweller of health-care facilities to constitute one of the most annoying pathogens responsible for hospitalary outbreaks and it is currently considered one of the most important nosocomial pathogens. In a prevalence study of infections in intensive care units conducted among 75 countries of the five continents, this microorganism was found to be the fifth most common pathogen. Two main features contribute to the success of A. baumannii: (i) A. baumannii exhibits an outstanding ability to accumulate a great variety of resistance mechanisms acquired by different mechanisms, either mutations or acquisition of genetic elements such as plasmids, integrons, transposons, or resistant islands, making this microorganism multi- or pan-drug-resistant and (ii) The ability to survive in the environment during prolonged periods of time which, combined with its innate resistance to desiccation and disinfectants, makes A. baumannii almost impossible to eradicate from the clinical setting. In addition, its ability to produce biofilm greatly contributes to both persistence and resistance. In this review, the pathogenesis of the infections caused by this microorganism as well as the molecular bases of antibacterial resistance and clinical aspects such as treatment and potential future therapeutic strategies are discussed in depth.
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Affiliation(s)
- Ignasi Roca
- Department of Clinical Microbiology, School of Medicine, IDIBAPS and Barcelona Centre for International Health Research, Hospital Clínic-Universitat de Barcelona Barcelona, Spain
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Decré D. Acinetobacter baumannii et résistance aux antibiotiques: Un modèle d’adaptation. ACTA ACUST UNITED AC 2012. [DOI: 10.1016/s1773-035x(12)71412-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Lee Y, Bae IK, Kim J, Jeong SH, Lee K. Dissemination of ceftazidime-resistant Acinetobacter baumannii clonal complex 92 in Korea. J Appl Microbiol 2012; 112:1207-11. [PMID: 22404202 DOI: 10.1111/j.1365-2672.2012.05283.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
AIMS This study was performed to describe the epidemiological traits of ceftazidime-resistant Acinetobacter baumannii clinical isolates from Korea. METHODS AND RESULTS Antimicrobial susceptibilities were determined by disk diffusion assay. PCR experiments were performed to detect genes encoding extended-spectrum β-lactamases and metallo-β-lactamases. Detection of ISAba1 upstream of the bla(ADC) gene was also performed by PCR amplification. The genetic organization of the bla(PER-1) gene was investigated by PCR mapping and sequencing of the regions surrounding the gene. Multilocus sequence typing was performed using seven housekeeping genes. A. baumannii isolates of clonal complex (CC) 92 exhibited a higher resistance rate (286/289, 99%) against ceftazidime compared to A. baumannii isolates of non-CC92 (7/87, 8%). Amongst 286 ceftazidime-resistant isolates of CC92, 100 (35%) isolates carried the bla(PER-1) gene, while none of the 87 isolates of non-CC92 carried the gene. The bla(ADC) gene associated with an ISAba1 element was detected in 98% (281/286) of ceftazidime-resistant isolates of CC92 and in all seven ceftazidime-resistant isolates of non-CC92. The bla(PER-1) gene was located on a transposon, Tn1213 (ISPa12-bla(PER-1) -Δgst-ISPa13), in 95 isolates and on a complex class 1 integron (orf513-bla(PER-1) -putative ABC transporter gene) in five isolates. Southern blot experiments confirmed the chromosomal location of the bla(PER-1) gene. CONCLUSIONS Acinetobacter baumannii CC92 which has acquired ceftazidime resistance by the production of PER-1 extended-spectrum β-lactamases and/or the overproduction of Acinetobacter-derived cephalosporinase is widely disseminated in Korea. SIGNIFICANCE AND IMPACT OF THE STUDY This study shows the mechanisms of acquiring ceftazidime resistance in A. baumannii and the epidemiological traits of ceftazidime-resistant A. baumannii isolates from Korea.
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Affiliation(s)
- Y Lee
- Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea
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Ramírez MS, Merkier AK, Quiroga MP, Centrón D. Acinetobacter baumannii is able to gain and maintain a plasmid harbouring In35 found in Enterobacteriaceae isolates from Argentina. Curr Microbiol 2011; 64:211-3. [PMID: 22119898 DOI: 10.1007/s00284-011-0052-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2011] [Accepted: 10/28/2011] [Indexed: 10/15/2022]
Abstract
The aim of this study was to determine the presence of bla (CTX-M-2) in our A. baumannii population and their putative role as an alternative mechanism of resistance to third-generation cephalosporins in this species. The bla (CTX-M-2) gene is widespread among the Enterobacteriaceae isolates from our country; however, it was not found in 76 isolates A. baumannii non-epidemiologically related clinical isolates resistant to third-generation cephalosporins isolated since 1982 in hospitals from Buenos Aires City. A plasmid isolated from Proteus mirabilis that possesses the complex class 1 integron In35::ISCR1::bla (CTX-M-2) was used to transform the natural competent A. baumannii clinical strain A118. PCR, plasmid extraction, DNA restriction, and susceptibility test confirmed that A118 could gain and maintain the plasmid possessing In35::ISCR1::bla (CTX-M-2), the genetic platform where the bla (CTX-M-2) gene is dispersing in Argentina.
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Affiliation(s)
- María Soledad Ramírez
- Laboratorio de Investigaciones de los Mecanismos de Resistencia a Antibióticos, Facultad de Medicina, Departamento de Microbiología, Parasitología e Inmunología, Universidad de Buenos Aires, Paraguay, Buenos Aires, Argentina
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Abstract
Innate resistance and remarkable ability to acquire additional resistance determinants underline the clinical importance of Acinetobacter. Over 210 β-lactamases belonging to 16 families have been identified in the genus, mostly in clinical isolates of A. baumannii. In this review, we update the current taxonomy of the genus Acinetobacter and summarize the β-lactamases detected in Acinetobacter spp. with an emphasis on Acinetobacter-derived cephalosporinases (ADCs) and carbapenem-hydrolysing class D β-lactamases (CHDLs). We also discuss the roles of integrons and insertion sequence (IS) elements in the expression and dissemination of such resistance determinants.
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Affiliation(s)
- Wei-Hua Zhao
- Department of Microbiology and Immunology, Showa University School of Medicine, Tokyo, Japan.
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34
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Poirel L, Bonnin RA, Nordmann P. Genetic basis of antibiotic resistance in pathogenic Acinetobacter species. IUBMB Life 2011; 63:1061-7. [DOI: 10.1002/iub.532] [Citation(s) in RCA: 111] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2011] [Accepted: 06/09/2011] [Indexed: 01/23/2023]
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35
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Durante-Mangoni E, Zarrilli R. Global spread of drug-resistant Acinetobacter baumannii: molecular epidemiology and management of antimicrobial resistance. Future Microbiol 2011; 6:407-22. [PMID: 21526942 DOI: 10.2217/fmb.11.23] [Citation(s) in RCA: 112] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Acinetobacter baumannii is an opportunistic Gram-negative pathogen with increasing relevance in a variety of hospital-acquired infections especially among intensive care unit patients. Resistance to antimicrobial agents is the main reason for A. baumannii spread. A. baumannii outbreaks described worldwide are caused by a limited number of genotypic clusters of multidrug-resistant strains that successfully spread among hospitals of different cities and countries. In this article, we will focus on the mechanisms responsible for resistance to antimicrobials and disinfectants in A. baumannii and the epidemiology of drug-resistant A. baumannii in healthcare facilities. We will also discuss the therapeutic and infection control strategies for management of drug-resistant A. baumannii epidemics.
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Affiliation(s)
- Emanuele Durante-Mangoni
- Chair of Internal Medicine & Unit of Transplant Medicine, Second University of Naples, Monaldi Hospital, Naples, Italy
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36
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Genetic features of CTX-M-15-producing Acinetobacter baumannii from Haiti. Antimicrob Agents Chemother 2011; 55:5946-8. [PMID: 21930877 DOI: 10.1128/aac.05124-11] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Acinetobacter baumannii isolates T23, W35, and H1 were isolated from three patients who had been injured in the Haiti earthquake in January 2010. Those isolates, corresponding to two distinct clones, were identified as extended-spectrum β-lactamase (ESBL) producers and found to be bla(CTX-M-15)-positive. That ESBL gene was associated with ISEcp1, involved in its acquisition by a one-ended transposition mechanism. In all isolates, the ISEcp1-bla(CTX-M-15) compound transposon was apparently chromosomally located.
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Phenotypic and molecular characterization of Acinetobacter clinical isolates obtained from inmates of California correctional facilities. J Clin Microbiol 2011; 49:2121-31. [PMID: 21450955 DOI: 10.1128/jcm.02373-10] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
Acinetobacter spp. increasingly have been wreaking havoc in hospitals and communities worldwide. Although much has been reported regarding Acinetobacter isolates responsible for nosocomial infections, little is known about these organisms in correctional facilities. In this study, we performed species identification, examined the antibiotic resistance profiles, and determined the mechanisms of resistance and clonal relationships of 123 Acinetobacter isolates obtained from inmates of 20 California correctional facilities (CCFs). We found that 57.7% of the isolates belong to A. baumannii, followed by isolates of Acinetobacter genomic species 3 (gen. sp. 3; 23.6%) and of Acinetobacter gen. sp. 13TU (10.6%). Multidrug-resistant (MDR) CCF isolates were found in only six CCFs. Additionally, DNA sequences of gyrA and parC genes were consistent with fluoroquinolone (FQ) susceptibility phenotypes. Furthermore, the presence of class 1 integrons was detected in 15 CCF isolates, all of which are MDR. Integron-associated gene cassettes encode several aminoglycoside modification enzymes, which correlate with most of the aminoglycoside-resistant phenotypes. Antimicrobial susceptibility testing in the presence of Phe-Arg-β-naphthylamide dihydrochloride and 1-(1-naphthylmethyl)-piperazine indicated the involvement of efflux pumps in the FQ resistance of only a few CCF isolates. Finally, genetic profiling showed that there was no evidence of A. baumannii outbreaks in CCFs. Instead, our analyses revealed only limited clonal dissemination of mostly non-MDR A. baumannii strains in a few facilities. This study represents the first report to characterize phenotypic and molecular features of Acinetobacter isolates in correctional facilities, which provides a baseline for monitoring the antimicrobial resistance changes and dissemination patterns of these organisms in such specialized institutions.
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PER-7, an extended-spectrum beta-lactamase with increased activity toward broad-spectrum cephalosporins in Acinetobacter baumannii. Antimicrob Agents Chemother 2011; 55:2424-7. [PMID: 21383087 DOI: 10.1128/aac.01795-10] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Acinetobacter baumannii isolate AP2 was recovered from a bronchial lavage sample of a patient hospitalized in Paris, France. A. baumannii AP2 was resistant to all β-lactams, including carbapenems, and expressed the extended-spectrum β-lactamase (ESBL) PER-7, which differs from PER-1 by 4 amino acid substitutions. Compared to PER-1, PER-7 possessed higher-level hydrolytic activities against cephalosporins and aztreonam. The blaPER-7 gene was chromosomally located and associated with a mosaic class 1 integron structure. Additionally, isolate AP2 expressed the carbapenem-hydrolyzing oxacillinase OXA-23 and the 16S RNA methylase ArmA, conferring high-level resistance to aminoglycosides.
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Diversity of clavulanic acid-inhibited extended-spectrum β-lactamases in Aeromonas spp. from the Seine River, Paris, France. Antimicrob Agents Chemother 2010; 55:1256-61. [PMID: 21149627 DOI: 10.1128/aac.00921-10] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Environmental Aeromonas sp. isolates resistant to ceftazidime were recovered during an environmental survey performed with water samples from the Seine River, in Paris, France, in November 2009. Selected isolates were identified by sequencing of the 16S rRNA and rpoB genes. PCR and cloning experiments were used to identify broad-spectrum-β-lactamase-encoding genes and their genetic context. Clavulanic acid-inhibited extended-spectrum-β-lactamase (ESBL) genes were identified in 71% of the Aeromonas sp. isolates. A variety of ESBL genes were detected, including bla(VEB-1a), bla(SHV-12), bla(PER-1), bla(PER-6), bla(TLA-2), and bla(GES-7), suggesting an aquatic reservoir of those ESBL genes. Moreover, the repeated elements and different insertion sequences were identified in association with the bla(PER-6) and the bla(VEB-1a) genes, respectively, indicating a wide diversity of mobilization events, making Aeromonas spp. a vehicle for ESBL dissemination.
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Vila J, Marco F. Lectura interpretada del antibiograma de bacilos gramnegativos no fermentadores. Enferm Infecc Microbiol Clin 2010; 28:726-36. [DOI: 10.1016/j.eimc.2010.05.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2010] [Accepted: 05/05/2010] [Indexed: 12/18/2022]
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Samonis G, Maraki S, Rafailidis PI, Kapaskelis A, Kastoris AC, Falagas ME. Antimicrobial susceptibility of Gram-negative nonurinary bacteria to fosfomycin and other antimicrobials. Future Microbiol 2010; 5:961-70. [PMID: 20521939 DOI: 10.2217/fmb.10.47] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND Fosfomycin is an antimicrobial commonly used in uncomplicated urinary tract infections. The microbiological effectiveness of fosfomycin against nonurinary Gram-negative isolates has not been widely investigated. The aim of this study was to evaluate the in vitro activity of fosfomycin against Gram-negative nonurinary isolates in a region of Greece where considerable antimicrobial resistance has been detected. METHODS Data were retrieved from the microbiological library of the University Hospital of Heraklion, Crete. We retrospectively examined the susceptibility of all Gram-negative nonurinary isolates to fosfomycin, collected over 1 year (January-December 2008). RESULTS A total of 594 nonurinary Gram-negative isolates were examined. Susceptibility testing was performed for 270 (45.4%) Enterobacteriaceae, 209 (35.2%) Gram-negative nonfermentative bacilli and 115 (19.4%) other Gram-negative bacteria. In total, 385 (64.8%) were susceptible to fosfomycin. Specifically, all Escherichia coli, Proteus mirabilis and Salmonella species isolates were susceptible. Additionally, 73 out of 94 (77.7%) Klebsiella pneumoniae (including carbapenem-resistant strains), 22 out of 32 (68.8%) Enterobacter species and 51 out of 79 (64.5%) Pseudomonas aeruginosa isolates were susceptible to fosfomycin. Susceptibility was highest amongst isolates (45 of 61; 73.8%) taken from outpatients and lowest for intensive care unit isolates (78 of 161; 48.4%). Isolates originating from the pediatric wards exhibited higher susceptibility (45 of 63; 71.4%) than isolates originating from other departments (340 of 531; 64%). CONCLUSION In a region with relatively high levels of antimicrobial resistance, fosfomycin seems to exhibit good levels of in vitro activity against Gram-negative nonurinary isolates. These data justify further evaluation of its potential clinical effectiveness.
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Affiliation(s)
- George Samonis
- Department of Medicine, University Hospital of Heraklion, Heraklion, Crete, Greece
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Kawamura-Sato K, Wachino JI, Kondo T, Ito H, Arakawa Y. Correlation between reduced susceptibility to disinfectants and multidrug resistance among clinical isolates of Acinetobacter species. J Antimicrob Chemother 2010; 65:1975-83. [DOI: 10.1093/jac/dkq227] [Citation(s) in RCA: 55] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
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Multidrug-resistant Acinetobacter baumannii: mechanisms of virulence and resistance. Int J Antimicrob Agents 2010; 35:219-26. [PMID: 20047818 DOI: 10.1016/j.ijantimicag.2009.10.024] [Citation(s) in RCA: 235] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2009] [Accepted: 10/21/2009] [Indexed: 02/06/2023]
Abstract
Infection due to Acinetobacter baumannii has become a significant challenge to modern healthcare systems. The organism shows a formidable capacity to develop antimicrobial resistance, yet the clinical impact of A. baumannii infection remains unclear. Much is known about the processes involved in multidrug resistance, but those underlying the pathogenicity and virulence potential of the organism are only beginning to be elucidated. In this article, we provide an overview of current knowledge, focusing on mechanisms of pathogenesis, the molecular basis of resistance and options for treatment in the absence of novel therapeutic agents.
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Cheng J, Wang Q, Chen Y, Ye Y, Li H, Li X, Li JB. Phenotypic and molecular characterization of a novel beta-lactamase carried by Klebsiella pneumoniae, CTX-M-72, derived from CTX-M-3. J GEN APPL MICROBIOL 2009; 55:207-16. [PMID: 19590148 DOI: 10.2323/jgam.55.207] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
This study reports phenotypic and molecular characterization of a novel CTX-M beta-lactamase carried by two Klebsiella pneumoniae isolates collected from two hospitals in China. Conjugation experiment, Southern hybridization, susceptibility testing, isoelectric focusing, PCR, and sequencing techniques as well as clone, expression, purification and kinetics were carried out to describe the characterization of the novel CTX-M-type enzyme. The analyses of plasmid profiling and pulsed-field gel electrophoresis of the novel enzyme were performed to investigate epidemiology. The PCR products had 967 nucleotides and a novel CTX-M enzyme with a pI of 8.5 was implicated in this resistance: CTX-M-72. Two strains exhibited a clavulanic acid-inhibited substrate profile that included extended-spectrum cephalosporins. The amino acid sequence of the CTX-M-72 beta-lactamase differed from that of the CTX-M-3 beta-lactamase by the Arg-->Gly change at position 164. The novel enzyme was susceptible to ceftazidime, the same response being observed for other CTX-M enzymes. The substrates of the beta-lactamase were also characterized. Furthermore, two resistant genes of clinical strains were closely related. The emergence of a novel CTX-M-type extended-spectrum beta-lactamase was rarely described in other areas. This study illustrated the importance of molecular surveillance in tracking CTX-M-producing strains in large teaching hospitals, suggested the horizontal transfer of plasmid-borne bla(CTX-M) genes contributed to the dissemination of CTX-M enzymes in hospital environments, and emphasized the need for epidemiological monitoring.
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Affiliation(s)
- Jun Cheng
- Department of Infectious Diseases, the First Affiliated Hospital of Anhui Medical University, Hefei, China
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Picão RC, Poirel L, Gales AC, Nordmann P. Diversity of beta-lactamases produced by ceftazidime-resistant Pseudomonas aeruginosa isolates causing bloodstream infections in Brazil. Antimicrob Agents Chemother 2009; 53:3908-13. [PMID: 19596871 PMCID: PMC2737865 DOI: 10.1128/aac.00453-09] [Citation(s) in RCA: 85] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2009] [Revised: 05/02/2009] [Accepted: 07/05/2009] [Indexed: 11/20/2022] Open
Abstract
A retrospective survey was conducted to characterize beta-lactamases in a collection of 43 ceftazidime-resistant Pseudomonas aeruginosa isolates recovered from patients with bloodstream infections hospitalized at a Brazilian teaching hospital between January and December 2005. Resistance rates for carbapenems, aminoglycosides, and quinolones were over 80%, with only colistin remaining active against all isolates. Pulsed-field gel electrophoresis analysis identified seven different genotypes. AmpC overproduction was found to be the sole beta-lactamase-mediated mechanism responsible for ceftazidime resistance in four isolates (9.3%). Nine isolates (20.9%) produced an extended-spectrum beta-lactamase (ESBL), either GES-1 (n = 7, 16.3%) or CTX-M-2 (n = 2, 4.6%). Carbapenemase activity was detected in 30 (70%) additional isolates. Among those isolates, two isolates (4.6%) produced the ESBL GES-5, possessing the ability to hydrolyze imipenem; a single isolate (2.3%) produced the metallo-beta-lactamase (MBL) IMP-1; and 27 isolates produced the MBL SPM-1 (62.8%). None of the isolates coproduced both ESBL and MBL. Insertion sequence elements ISCR4 and ISCR1 were associated with bla(SPM-1) and bla(CTX-M-2) genes, respectively, whereas the bla(GES-1) and bla(GES-5) genes were part of class 1 integron structures. This study underlines the spread of MBL- and ESBL-producing P. aeruginosa isolates as an important source of ceftazidime resistance in Brazil.
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Affiliation(s)
- Renata C Picão
- Service de Bactériologie-Virologie, INSERM U914 Emerging Resistance to Antibiotics, Hôpital de Bicêtre, Assistance Publique/Hôpitaux de Paris, Faculté de Médecine Paris Sud, K.-Bicêtre, France
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Fosfomycin for the treatment of infections caused by multidrug-resistant non-fermenting Gram-negative bacilli: a systematic review of microbiological, animal and clinical studies. Int J Antimicrob Agents 2009; 34:111-20. [DOI: 10.1016/j.ijantimicag.2009.03.009] [Citation(s) in RCA: 128] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2009] [Accepted: 03/10/2009] [Indexed: 11/24/2022]
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Phenotypic and molecular characterization of two novel CTX-M enzymes carried by Klebsiella pneumoniae. Mol Biol Rep 2009; 37:1261-7. [PMID: 19294528 DOI: 10.1007/s11033-009-9499-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2008] [Accepted: 03/02/2009] [Indexed: 10/21/2022]
Abstract
Two clinical strains (Klebsiella pneumoniae 516 and K. pneumoniae 1335) collected in September 2006 from different hospitals in Anhui Province (China) harboured two novel plasmid-mediated bla(CTX-M) genes, designated bla(CTX-M-80) and bla(CTX-M-81), respectively. Both CTX-M-80 with pI of 9.0 and CTX-M-81 with pI of 8.4 were extended-spectrum beta-lactamases (ESBLs). The results of susceptibility testing demonstrated two enzymes were highly activity against broad spectrum beta-lactams, but the level of resistance was reduced with the addition of beta-lactamase inhibitors. The bla(CTX-M-80) gene was detected on a 110-kb plasmid and the bla(CTX-M-81) gene existed on a 120-kb plasmid. The deduced amino acid sequence of CTX-M-80 differed from that of CTX-M-3 by the substitution Ala-27-->Val, and CTX-M-81 possessed the Lys-->Glu, Lys-->Gln, and Asn-->His changes at respective position 82, 98, and 132 in compassion with CTX-M-14. The enzymatic properties showed CTX-M-80 and CTX-M-81 had higher affinities for penicillin G (lower Km values) than for cephalosporins. The activities of novel enzymes against ceftazidime were undetectable or limited, as indicated by MICs data, the same response being observed for many other CTX-M enzymes. This report was evidence of the diversity of CTX-M-type ESBLs in China.
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Lavigne JP, Gaillard JB, Bourg G, Tichit C, Lecaillon E, Sotto A. Étude de souches de Stenotrophomonas maltophilia sécrétrices de BLSE : détection de CTX-M et étude de la virulence. ACTA ACUST UNITED AC 2008; 56:447-53. [DOI: 10.1016/j.patbio.2008.07.013] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2008] [Accepted: 07/03/2008] [Indexed: 11/29/2022]
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Novel chimeric beta-lactamase CTX-M-64, a hybrid of CTX-M-15-like and CTX-M-14 beta-lactamases, found in a Shigella sonnei strain resistant to various oxyimino-cephalosporins, including ceftazidime. Antimicrob Agents Chemother 2008; 53:69-74. [PMID: 18955524 DOI: 10.1128/aac.00227-08] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
The plasmid-mediated novel beta-lactamase CTX-M-64 was first identified in Shigella sonnei strain UIH-1, which exhibited resistance to cefotaxime (MIC, 1,024 microg/ml) and ceftazidime (MIC, 32 microg/ml). The amino acid sequence of CTX-M-64 showed a chimeric structure of a CTX-M-15-like beta-lactamase (N- and C-terminal moieties) and a CTX-M-14-like beta-lactamase (central portion, amino acids 63 to 226), suggesting that it originated by homologous recombination between the corresponding genes. The introduction of a recombinant plasmid carrying bla(CTX-M-64) conferred resistance to cefotaxime in Escherichia coli, and the activities of cefotaxime and ceftazidime were restored in the presence of clavulanic acid. Of note, CTX-M-64 production could also confer consistent resistance to ceftazidime, which differs from the majority of CTX-M-type enzymes, which poorly hydrolyze ceftazidime. These results were consistent with the kinetic parameters determined with the purified CTX-M-64 enzyme. The bla(CTX-M-64) gene was flanked upstream by an ISEcp1 sequence and downstream by an orf477 sequence. The sequence of the 45-bp spacer region between the right inverted repeat (IRR) of ISEcp1 and bla(CTX-M-64) was exactly identical to that of ISEcp1-bla(CTX-M-15-like). Moreover, the presence of a putative IRR of ISEcp1 at the right end of truncated orf477 is indicative of an ISEcp1-mediated transposition event in the bla(CTX-M-64) gene. The emergence of CTX-M-64 by probable homologous recombination would suggest the natural potential of an alternative mechanism for the diversification of CTX-M-type beta-lactamases.
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Abstract
Acinetobacter baumannii has emerged as a highly troublesome pathogen for many institutions globally. As a consequence of its immense ability to acquire or upregulate antibiotic drug resistance determinants, it has justifiably been propelled to the forefront of scientific attention. Apart from its predilection for the seriously ill within intensive care units, A. baumannii has more recently caused a range of infectious syndromes in military personnel injured in the Iraq and Afghanistan conflicts. This review details the significant advances that have been made in our understanding of this remarkable organism over the last 10 years, including current taxonomy and species identification, issues with susceptibility testing, mechanisms of antibiotic resistance, global epidemiology, clinical impact of infection, host-pathogen interactions, and infection control and therapeutic considerations.
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