Evolution of carbapenem resistance in Acinetobacter baumannii: an 18-year longitudinal study from a medical center in northern Taiwan.

Carbapenem-resistant Acinetobacter baumannii has emerged as an important cause of nosocomial infections with high morbidity and mortality. The carbapenemases, especially class D carbapenem-hydrolyzing oxacillinases (CHDLs), play an important role, but the relationship between their prevalence trend and carbapenem resistance remains unclear. Between 1995 and 2012, we collected 667 isolates of A. baumannii from a single medical center in northern Taiwan. Pulsed-field gel electrophoresis (PFGE) was used to determine clonality. Antimicrobial susceptibility was determined. Carbapenemase genes and associated genetic structures were detected by polymerase chain reaction. Isolates were heterogeneous on PFGE. Susceptibility to carbapenem decreased steadily over the study period from 88.1% (2001-2003) to <25% (2010-2012), whereas the isolates remained susceptible to colistin (nearly 100%) and partially susceptible to tigecycline (80%). Starting in 2001, isolates carrying the ISAba1-blaOXA-51-like allele were consistently identified. Isolates containing the transposons Tn2006 or Tn2008 first appeared in 2007 with increasing carriage rates from 17.5% (2007-2009) to 50.0% (2010-2012). The IS1008-ΔISAba3-blaOXA-58-like, blaOXA-72 and metallo-β-lactamase genes were detected only sporadically. Isolates carrying CHDL genes were resistant to multiple drugs, including carbapenem, but remained susceptible to colistin (100.0%). Increased carbapenem resistance in A. baumannii may be caused by the increased prevalence of isolates containing the ISAba1-blaOXA-51-like allele and the transposons Tn2006 and Tn2008.

Ku WW ，Kung CH ，Lee CH ，Tseng CP ，Wu PF ，Kuo SC ，Chen TL ，Lee YT ，Wang FD ，Fung CP ... -  《-》

Dissemination of multidrug-resistant Acinetobacter baumannii carrying BlaOxA-23 from hospitals in central Taiwan.

Imipenem-resistant Acinetobacter baumannii (IRAB) poses a great threat to healthcare systems. Production of carbapenem-hydrolyzing class D β-lactamases (CHDLs) is the major mechanism for imipenem resistance. In this study, we found a high prevalence of IRAB carrying a gene encoding CHDL, bla(OxA-23), in central Taiwan and elucidated the molecular characteristics and possible mechanisms of the spread of these isolates. During 2007, we collected 291 nonrepetitive A baumannii isolates from 10 teaching hospitals in Taiwan. The antimicrobial susceptibility of the isolates was determined by agar dilution or Etest. The genes encoding carbapenemase and related structure were detected by polymerase chain reaction mapping and sequencing, and the clonal relationship of the isolates was analyzed by pulsed-field gel electrophoresis. Plasmid localization of bla(OxA-23) was determined by extraction of plasmid with commercial kit and Southern blot analysis. Among 142 IRAB isolates, 30 harbored the bla(OxA-23). The prevalence of IRAB with bla(OxA-23) was highest in central Taiwan compared to other areas [24.8% (27/109) vs. 1.6% (3/182); p < 0.001]. These IRAB with bla(OxA-23) were also resistant to other antimicrobial agents, except colistin. The PCR methods showed the presence of bla(OxA-51) in all isolates. We could exclude clonal spreading due to the diversity of the pulsotype. The bla(OxA-23) gene was detected in the plasmids of 6 isolates. Tn2006 was present in 22 (73.3%) isolates, and Tn2008, in 6 other isolates (26.7%). Two strains had bla(oxa-23)-ΔATPase but lacked upstream ISAba1. The high prevalence of bla(OxA-23)-harboring IRAB in central Taiwan might be attributed to the transposition event of Tn2006.

Lee MH ，Chen TL ，Lee YT ，Huang L ，Kuo SC ，Yu KW ，Hsueh PR ，Dou HY ，Su IJ ，Fung CP ... -  《-》

Genetic diversity and clonal evolution of carbapenem-resistant Acinetobacter baumannii isolates from Portugal and the dissemination of ST118.

In this study, 116 multidrug-resistant Acinetobacter baumannii (MDR-Ab) isolates recovered in various regions of Portugal were studied. All isolates were non-susceptible to tigecycline; one isolate was also non-susceptible to colistin, making it a step closer to pandrug resistance. Among 72 isolates tested by PFGE, 98.6% carried bla(OXA-66), 1.4% bla(OXA-104), 77.8% bla(OXA-23), 23.6% bla(OXA-24), 18.1% bla(TEM-1) and 1.4% bla(CTX-M-15-like) genes. No OXA-58 or metallo-β-lactamase-encoding genes were detected. ISAba1 was found in 58/72 isolates (80.6%). Among these, ISAba1 was found upstream of bla(OXA-51-like) in 54 isolates. All but two of these isolates also carried ISAba1-bla(OXA-23), highlighting the coexistence of ISAba1-bla(OXA-51-like) and ISAba1-bla(OXA-23) genetic platforms, emphasising the importance of mobile genetic elements in the dissemination of carbapenem-hydrolysing class D β-lactamase genes. Tn2006-like and Tn2008-like, found within ST92 and ST118, may reflect either multiple genetic structures in the origin of bla(OXA-23) acquisition or interclonal complex evolution. These results indicate that there may exist different genetic origins for carbapenem resistance among MDR-Ab isolates. Six PFGE profiles were associated with three major sequence types, with ST118 (OXA-23- or OXA-24-producer) being widely disseminated since 2009. ST98 (described so far as endemic in Portugal) and ST92 (which co-existed with ST98 before 2009) appeared to have been gradually replaced by ST118. The new ST188 (OXA-104-producer) was detected for the first time in this country. Identification of an extensively drug-resistant ST118 and carbapenem-resistant ST92, ST98 and ST118 isolates, both in community and healthcare facilities, demonstrates the menace of A. baumannii-associated infections.

Manageiro V ，Jones-Dias D ，Ferreira E ，Louro D ，Antimicrobial Resistance Surveillance Program in Portugal ，Caniça M ... -  《-》

Wide spread of Tn2006 in an AbaR4-type resistance island among carbapenem-resistant Acinetobacter baumannii clinical isolates in Taiwan.

Carbapenem resistance in Acinetobacter baumannii is a global problem. The purpose of this study was to elucidate current resistance mechanisms of imipenem-resistant A. baumannii (IRAB) in Taiwan and their correlation with patient outcomes. Acinetobacter baumannii clinical isolates from two teaching hospitals in Taiwan were collected in 2009 and were examined by Etest for determination of the minimum inhibitory concentrations (MICs) of imipenem, ceftazidime and ceftriaxone. Primers specific for carbapenemase genes and upstream regions were designed for PCR amplification. Bacterial isolates were genotyped by pulsed-field gel electrophoresis (PFGE). Clinical presentations of patients were analysed retrospectively. Upstream insertion sequence ISAba1 was found in 34 isolates that carried bla(OXA-23), including 28 with transposon Tn2006 (ISAba1-bla(OXA-23)-ISAba1) in an AbaR4-type resistance island and 6 with Tn2008 (ISAba1-bla(OXA-23)), as well as in 8 isolates carrying ISAba1-bla(OXA-51-like). All of these isolates expressed full resistance to imipenem (MIC>32 mg/L). Forty-one different PFGE genotypes were found among 62 isolates. Tn2006 was found in 19 genotypes (46.3%), which is more common than ISAba1-bla(OXA-51-like) (12.2%) (P=0.001). Prior use of carbapenems or extended-spectrum cephalosporins for ≥5 days was the only independent risk factor significantly associated with IRAB infection (odds ratio=361.175). Higher mortality was significantly associated with infection caused by IRAB and ISAba1-bla(OXA-23)-carrying strains compared with infection caused by imipenem-susceptible A. baumannii and ISAba1-bla(OXA-51-like)-carrying strains (P=0.009 and 0.027, respectively). Tn2006 is currently the most common imipenem resistance determinant, which showed a higher ability to spread among A. baumannii and was associated with a higher mortality in IRAB-infected patients.

Lee HY ，Chang RC ，Su LH ，Liu SY ，Wu SR ，Chuang CH ，Chen CL ，Chiu CH ... -  《-》

Outbreak of imipenem-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii complex harboring different carbapenemase gene-associated genetic structures in an intensive care unit.

To investigate the clinical and molecular epidemiology of the imipenem-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii (IRAcb) complex during an outbreak in an intensive care unit (ICU). Forty-six clinical and 11 environmental isolates of the IRAcb complex were collected from the ICU of Taipei Veterans General Hospital, Taiwan between December 2003 and March 2004. These isolates were genotyped using pulsed-field gel electrophoresis (PFGE). Carbapenemase genes and their associated genetic structures were analyzed using PCR. Clinical data obtained from the patients were also reviewed and analyzed. The isolates were identified at the genomic species level as A. baumannii (42 clinical and five environmental isolates) and Acinetobacter genomic species 13TU (four clinical and six environmental isolates). Both species were comprised of two pulsotypes, but those of A. baumannii were closely related (83% similar). IS1008-ΔISAba3-bla(OXA-58-like) and ISAba1-bla(OXA-51-like) were identified in 22 and 21 clinical isolates of A. baumannii, respectively (one isolate contained both). The ISAba3-bracketed bla(OXA-58-like) gene was detected in all isolates of Acinetobacter genomic species 13TU. Patient transfers between different sections of the ICU were important factors that contributed to the spread of the two pulsotypes of A. baumannii. However, among the A. baumannii isolates identified, only those carrying IS1008-ΔISAba3-bla(OXA-58-like) could be found in the environment, indicating an additional route of transmission. The prior use of carbapenem or cefepime was associated with the subsequent infection with A. baumannii carrying the ISAba1-bla(OXA-51-like) gene, while prior piperacillin/tazobactam use was associated with the subsequent infection with A. baumannii carrying the IS1008-ΔISAba3-bla(OXA-58-like) gene. A. baumannii isolates carrying different carbapenemase genes and their associated genetic structures might be transmitted or selected in different ways.

Lee YT ，Fung CP ，Wang FD ，Chen CP ，Chen TL ，Cho WL ... -  《-》