tigecycline and Acinetobacter-Infections

During an island-wide PCR-based surveillance study of beta-lactam resistance in multidrug-resistant (MDR) Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter calcoaceticus-baumannii complex isolates obtained from 17 different hospitals, 10 KPC-positive Acinetobacter isolates were identified. DNA sequencing of the bla(KPC) gene identified KPC-2, -3, and -4 and a novel variant, KPC-10. This is the first report of a KPC-type beta-lactamase identified in Acinetobacter species.

Topics: Acinetobacter; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; beta-Lactam Resistance; beta-Lactamases; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Population Surveillance; Puerto Rico

The genetic structure of beta-lactamases in Acinetobacter genospecies 3 (AG3) isolates in Taiwan was studied to analyze their high rates of resistance to beta-lactams, including carbapenems (57.9%). bla(IMP-1) and bla(IMP-8) were located in a class 1 integron. bla(OXA-58) was bracketed by ISAba3. A novel TnpF-like integrase gene was identified upstream of bla(VEB-3). Adjacent to the 5' sequence of the bla(ADC) gene, folE was identified. Four new Acinetobacter-derived cephalosporinase (ADC) enzymes were found, which clustered phylogenetically with published AG3 ADC proteins.

Topics: Acinetobacter; Acinetobacter Infections; beta-Lactam Resistance; beta-Lactamases; Cephalosporinase; Gene Transfer, Horizontal; Genes, Bacterial; Humans; In Vitro Techniques; Integrons; Microbial Sensitivity Tests; Molecular Epidemiology; Molecular Sequence Data; Phylogeny; Taiwan

Thirteen clinical isolates of multidrug-resistant Acinetobacter baumannii resistant to carbapenems (MRAB-C) with tigecycline nonsusceptibility were collected from individual patients in this study. None of the 13 isolates shared the same strain characteristics in molecular typing. All of them showed increased adeB transcription, as predicted. However, none of these tigecycline-nonsusceptible MRAB-C isolates were found to possess previously known adeRS mutations. Upregulation of adeB transcription may result from cross stimulation by other mechanisms.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Aged, 80 and over; Bacterial Proteins; Carbapenems; Drug Resistance, Bacterial; Female; Humans; Male; Membrane Transport Proteins; Middle Aged; Minocycline; Molecular Sequence Data; Mutagenesis, Insertional; Reverse Transcriptase Polymerase Chain Reaction; Tigecycline

The mechanism of stepwise acquired multidrug resistance in Acinetobacter baumannii isolates from a hospitalized patient was investigated. Thirteen consecutive multidrug-resistant isolates were recovered from the same patient over a 2-month period. The Vitek 2 system identified the isolates as meropenem-sensitive Acinetobacter lwoffii; however, molecular identification showed that the isolates were A. baumannii. Etest revealed that the isolates were meropenem resistant. The presence of oxacillinase (OXA)-type enzymes were investigated by sequencing. The clonal relatedness of isolates was assessed by pulsed-field gel electrophoresis (PFGE). Expression of the genes encoding the efflux pumps AdeB and AdeJ was performed by semiquantitative real-time reverse transcription-PCR (qRT-PCR). The adeRS two-component system was sequenced. All isolates had identical PFGE fingerprints, suggesting clonal identity. The first six isolates were positive for the novel bla(OXA-164) gene. The following seven isolates, recovered after treatment with a combination of meropenem, amikacin, ciprofloxacin, and co-trimoxazole showed an increase of >7-fold in adeB mRNA transcripts and a missense mutation in bla(OXA-164), converting it to bla(OXA-58). Sequencing revealed a novel mutation in adeR. These data illustrate how A. baumannii can adapt during antimicrobial therapy, leading to increased antimicrobial resistance.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Bacterial Proteins; Carbapenems; Drug Resistance, Bacterial; Fatal Outcome; Humans; Male; Middle Aged; Molecular Sequence Data; Mutation, Missense; Reverse Transcriptase Polymerase Chain Reaction

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Minocycline; Tigecycline

Acinetobacter baumannii strains resistant to all beta-lactams, aminoglycosides, and fluoroquinolones have emerged in many medical centers. Potential mechanisms contributing to antimicrobial resistance were investigated in 40 clinical isolates endemic to New York City. The isolates were examined for the presence of various beta-lactamases, aminoglycoside-modifying enzymes, and mutations in gyrA and parC. Expression of the genes encoding the beta-lactamase AmpC, the efflux systems AdeABC and AbeM, and the OmpA-like porin was also examined by real-time reverse transcription-PCR. No VIM, IMP, KPC, OXA-23-type, OXA-24-type, or OXA-58 beta-lactamases were detected, although several isolates had acquired bla(SHV-5). Most cephalosporin-resistant isolates had increased levels of expression of ampC and/or had acquired bla(SHV-5); however, isolates without these features still had reduced susceptibility to cefepime that was mediated by the AdeABC efflux system. Although most isolates with ISAba1 upstream of the bla(OXA-51)-like carbapenemase gene were resistant to meropenem, several remained susceptible to imipenem. The presence of aminoglycoside-modifying enzymes and gyrase mutations accounted for aminoglycoside and fluoroquinolone resistance, respectively. The increased expression of adeABC was not an important contributor to aminoglycoside or fluoroquinolone resistance but did correlate with reduced susceptibility to tigecycline. The expression of abeM and ompA and phenotypic changes in OmpA did not correlate with antimicrobial resistance. A. baumannii has become a well-equipped nosocomial pathogen; defining the relative contribution of these and other mechanisms of antimicrobial resistance will require further investigation.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Outer Membrane Proteins; Bacterial Proteins; beta-Lactamases; Drug Resistance, Bacterial; Endemic Diseases; Humans; Microbial Sensitivity Tests; Molecular Sequence Data; New York City; Sequence Analysis, DNA

Topics: Acinetobacter baumannii; Acinetobacter Infections; Belgium; beta-Lactam Resistance; beta-Lactamases; Carbapenems; DNA Transposable Elements; Genes, Bacterial; Humans

The susceptibilities of 142 Acinetobacter baumannii-calcoaceticus complex isolates (95 from wounded U.S. soldiers deployed overseas) to 13 antimicrobial agents were determined by broth microdilution. The most active antimicrobial agents (> or =95% of isolates susceptible) were colistin, polymyxin B, and minocycline.

Topics: Acinetobacter; Acinetobacter Infections; Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Military Personnel; Minocycline; Polymyxin B; United States; Warfare