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Molecular epidemiology of sequential outbreaks of Acinetobacter baumannii in an intensive care unit shows the emergence of carbapenem resistance.

ABSTRACT: The molecular epidemiology of multidrug-resistant Acinetobacter baumannii was investigated in the medical-surgical intensive care unit (ICU) of a university hospital in Italy during two window periods in which two sequential A. baumannii epidemics occurred. Genotype analysis by pulsed-field gel electrophoresis (PFGE) of A. baumannii isolates from 131 patients identified nine distinct PFGE patterns. Of these, PFGE clones B and I predominated and occurred sequentially during the two epidemics. A. baumannii epidemic clones showed a multidrug-resistant antibiotype, being clone B resistant to all antimicrobials tested except the carbapenems and clone I resistant to all antimicrobials except ampicillin-sulbactam and gentamicin. Type 1 integrons of 2.5 and 2.2 kb were amplified from the chromosomal DNA of epidemic PFGE clones B and I, respectively, but not from the chromosomal DNA of the nonepidemic clones. Nucleotide analysis of clone B integron identified four gene cassettes: aacC1, which confers resistance to gentamicin; two open reading frames (ORFs) coding for unknown products; and aadA1a, which confers resistance to spectinomycin and streptomycin. The integron of clone I contained three gene cassettes: aacA4, which confers resistance to amikacin, netilmicin, and tobramycin; an unknown ORF; and bla(OXA-20), which codes for a class D beta-lactamase that confers resistance to amoxicillin, ticarcillin, oxacillin, and cloxacillin. Also, the bla(IMP) allele was amplified from chromosomal DNA of A. baumannii strains of PFGE type I. Class 1 integrons carrying antimicrobial resistance genes and bla(IMP) allele in A. baumannii epidemic strains correlated with the high use rates of broad-spectrum cephalosporins, carbapenems, and aminoglycosides in the ICU during the study period.

SUBMITTER: Zarrilli R

PROVIDER: S-EPMC356829 | biostudies-literature | 2004 Mar

REPOSITORIES: biostudies-literature

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Molecular epidemiology of sequential outbreaks of Acinetobacter baumannii in an intensive care unit shows the emergence of carbapenem resistance.

Zarrilli Raffaele R Crispino Margherita M Bagattini Maria M Barretta Elena E Di Popolo Anna A Triassi Maria M Villari Paolo P

Journal of clinical microbiology 20040301 3

The molecular epidemiology of multidrug-resistant Acinetobacter baumannii was investigated in the medical-surgical intensive care unit (ICU) of a university hospital in Italy during two window periods in which two sequential A. baumannii epidemics occurred. Genotype analysis by pulsed-field gel electrophoresis (PFGE) of A. baumannii isolates from 131 patients identified nine distinct PFGE patterns. Of these, PFGE clones B and I predominated and occurred sequentially during the two epidemics. A. ...[more]

PMID: 15004037

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Project description:Acinetobacter baumannii is a common cause of healthcare-associated infections (HAI) worldwide, mostly occurring in intensive care units (ICUs). Extended-spectrum beta lactamases (ESBL)-positive A. baumannii strains have emerged as highly resistant to most currently used antimicrobial agents, including carbapenems. The most common mechanism for carbapenem resistance in this species is β-lactamase-mediated resistance. Carbapenem-hydrolyzing class D oxacillinases are widespread among multidrug-resistant (MDR) A. baumannii strains. The present study was conducted to determine the presence and distribution of blaOXA genes among multidrug-resistant A. baumannii isolated from ICU patients and genes encoding insertion sequence (IS-1) in these isolates. Additionally, the plasmid DNA profiles of these isolates were determined. A total of 120 clinical isolates of A. baumannii from various ICU clinical specimens of four main Jordanian hospitals were collected. Bacterial isolate identification was confirmed by biochemical testing and antibiotic sensitivity was then assessed. PCR amplification and automated sequencing were carried out to detect the presence of blaOXA-51, blaOXA-23, blaOXA-24, and blaOXA-58 genes, and ISAba1 insertion sequence. Out of the 120 A. baumannii isolates, 95% of the isolates were resistant to three or more classes of the antibiotics tested and were identified as MDR. The most frequent resistance of the isolates was against piperacillin (96.7%), cephalosporins (97.5%), and β-lactam/β-lactamase inhibitor combinations antibiotics (95.8%). There were 24 (20%) ESBL-producing isolates. A co-existence of blaOXA-51 gene and ISAba1 in all the 24 ESBL-producing isolates was determined. In addition, in the 24 ESBL-producing isolates, 21 (87.5%) carried blaOXA-51 and blaOXA-23 genes, 1 (4.2%) carried blaOXA-51 and blaOXA-24, but all were negative for the blaOXA-58 gene. Plasmid DNA profile A and profile B were the most common (29%) in ESBL-positive MDR A. baumannii isolates while plasmid DNA profile A was the most common in the ESBL-negative isolates. In conclusion, there was an increase in prevalence of MDR-A. baumannii in ICU wards in Jordanian hospitals, especially those having an ESBL phenotype. Thus, identification of ESBL genes is necessary for the surveillance of their transmission in hospitals.

Project description:Carbapenem-resistant Acinetobacter baumannii (CRAB) infections are associated with poor outcomes depending on patient's conditions, clinical severity and type of infection, and treatment is challenging given the limited therapeutic options available. The aim of this study was to describe the clinical and microbiological characteristics of two outbreaks caused by CRAB in an intensive care unit (ICU). In addition, the mechanisms of resistance detected in these strains and the treatment chosen according to the available therapeutic options were analyzed. Overall, 28 patients were included. Ten patients (35.71%) had ventilator-associated pneumonia (VAP), ten (35.71%) had a bloodstream infection (BSI), and eight (28.57%) were only colonized. Recurrent infection occurred in 25% (5/20) of infected patients. Two different strains of A. baumannii were isolated from the index patient of the first outbreak. The first strain belonged to the ST85 and carried the blaNDM-1 carbapenemase gene, while the second belonged to the ST2 and carried blaOXA-23, and blaOXA-66 carbapenemase genes. The phylogenetic analysis revealed that the ST2 strain was the cause of the major outbreak, and mutations in the AmpC gene were related to progressive increasing minimum inhibitory concentration (MIC) and finally, cefiderocol-resistance in one strain. The CRAB isolates from the second outbreak were also identified as ST2. Cefiderocol-resistant strains tests identified by the disc diffusion method were involved in 24% (6/25) of nosocomial infections. Using broth microdilution (BMD) ComASP® only, 33.3% (2/6) of these strains were cefiderocol-resistant. All-cause ICU mortality was 21.4%. Conclusions: Cefiderocol is the first approved siderophore cephalosporin for the treatment of CRAB infections. Cefiderocol-resistant strains were related with blaNDM-1 carbapenemase and mutations in the AmpC gene. Cefiderocol-resistant strains or that cannot be properly interpreted by disk diffusion, should be retested using BMD for definitive categorization.

Dataset Information

Molecular epidemiology of sequential outbreaks of Acinetobacter baumannii in an intensive care unit shows the emergence of carbapenem resistance.

Publications

Molecular epidemiology of sequential outbreaks of Acinetobacter baumannii in an intensive care unit shows the emergence of carbapenem resistance.

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