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Objectives: Individuals infected with extensively-drug-resistant (XDR) Acinetobacter baumannii are difficult to cure and have a high mortality rate. This study compared the genomic and phenotypic differences between XDR and non-multi-drug-resistant (MDR) A. baumannii, and further characterized hypervirulent XDR A. baumannii., Methods: In total, 1403 acinetobacter isolates were collected from patients with bacteraemia between 1997 and 2015. Antimicrobial susceptibility tests were performed to categorize isolates into non-MDR, MDR and XDR groups. The presence of selected virulence-associated genes was determined by polymerase chain reaction. Bacterial phenotypes, including iron acquisition, biofilm formation, capsule production, and virulence to larvae and mice, were determined., Results: Multi-locus sequence typing revealed a high prevalence of sequence type (ST) 2 (81.6%) and ST129 (18.4%) among 49 XDR isolates, and the STs of 18 non-MDR isolates were more diverse. Virulence-associated phenotypic assays showed that XDR isolates had higher iron acquisition ability, greater capsule production, and virulence to Galleria mellonella larvae. However, their ability to form biofilm was lower compared with that of non-MDR isolates. XDR isolates were more likely to have virulence genes (tonB, hemO, abaI and ptk), while non-MDR isolates were more likely to have pld and ompA genes. Twenty-one XDR isolates that had a <20% larvae survival rate after 7 days post-infection were defined as hypervirulent XDR isolates. Among them, isolates 1677 (ST129) and 929-1 (ST2) caused the death of all infected mice within 2 days., Conclusion: Some subpopulations of highly-drug-resistant ST2 isolates exhibit high virulence. As such, it is of utmost importance to continue monitoring the spread of hypervirulent XDR A. baumannii isolates., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To investigate the prevalence of polypharmacy and potential drug-drug interactions (DDIs), and the factors associated with DDIs among people living with human immunodeficiency virus (HIV; PLWH) in the modern era of antiretroviral therapy (ART)., Methods: This cross-sectional study included PLWH who had been on ART for ≥3 months at two designated HIV hospitals in Taiwan. All ART and non-ART prescriptions were collected from the NHI-MediCloud System and screened for DDIs using the University of Liverpool HIV drug interactions database. A case-control analysis was conducted to investigate the factors associated with DDIs., Results: In total, 1007 PLWH were included in this study from June 2021 to August 2022. The median age was 40 (interquartile range 33-49) years, and 96.2% were taking integrase strand transfer inhibitor (INSTI)-based ART. The proportions of PLWH with at least one non-communicable disease and polypharmacy were 50.0% and 18.7%, respectively. Seven (0.7%) PLWH had red-flagged DDIs, and 159 (15.8%) had amber-flagged DDIs. In multi-variable models, the prevalence of DDIs was associated with older age [adjusted odds ratio (aOR) per 1-year increase 1.022), number of co-medications (aOR 1.097), use of boosted INSTI-based ART (vs unboosted INSTI, aOR 8.653), and concomitant medications in the alimentary tract and metabolism category (aOR 11.058) and anti-neoplastic and immunomodulating agents (aOR 14.733)., Conclusions: In the INSTI era, the prevalence of potential DDIs is lower than noted previously, but remains substantial. Clinicians should monitor DDIs routinely, especially in older PLWH, those taking a higher number of co-medications, and those who are taking booster-containing ART or medications from specific categories., (Copyright © 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

This is the first report to show an insidious outbreak of armA- and blaOXA-72-carrying Acinetobacter baumannii sequence type 512 (ST512) at a study hospital in northern Taiwan. Multilocus sequence typing revealed that this was a ST512 clone. All of the isolates with ST512 carried a novel 12,056-bp repGR2 in combination with a repGR12-type plasmid. This plasmid, designated pAB-ML, had one copy of the blaOXA-72 gene that was flanked by XerC/XerD-like sites and conferred resistance to carbapenems., (Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

There have been increasing reports of bla(OXA-23)-carrying strains of carbapenem-resistant Acinetobacter baumannii (CRAB), which has become a significant public health concern in Taiwan. To determine the origin of these CRAB strains, the prevalence of CRAB and bla(OXA-23)-carrying CRAB in a regional hospital was analysed retrospectively. The genome of A. baumannii TYTH-1 was completely sequenced and annotated. Multiple comparative genomics studies, including phylogenetic analysis, functional comparison via the Clusters of Orthologous Groups (COGs) database, and determination of variance in GC profiles in the whole genome and gene arrangements in resistance islands, were performed using 11 completely sequenced A. baumannii genomes. bla(OXA-23)-carrying CRAB isolates became dominant clones in 2007. A comparative genomics analysis revealed a common strain lineage between Taiwanese strains (TYTH-1 and TCDC-AB0715) and Chinese strains (MDR-TJ and MDR-ZJ06). Phylogenetic studies and GC profiles showed that the genome of TYTH-1 was closest to MDR-ZJ06. However, the resistance island of TYTH-1 (RI(TYTH-1)) was nearly identical to that of RI(MDT-TJ). The functional category for COGs was similar in the tested genomes. The results reveal that dissemination of bla(OXA-23)-carrying CRAB in Taiwan may have been mediated by the transfer of people between Taiwan and China during 2007. The global spread of CRAB is now a worldwide public health problem. In Taiwan, the government needs to focus more attention on the importance of identifying and tracing resistant pathogens and issuing notifications of CRAB infections., (Copyright © 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

This study investigated the progression of multidrug resistance upon exposure to imipenem in Acinetobacter baumannii. Eighteen A. baumannii strains, including two reference strains (ATCC 19606 and ATCC 17978), four clinical strains (AB56, AB242, AB273 and AB279) and 12 antibiotic-selected mutant strains, were used in this study. Imipenem-selected mutants were generated from imipenem-susceptible strains (ATCC 19606, ATCC 17978 and AB242) by multistep selection resistance. Amikacin-, ciprofloxacin-, colistin-, meropenem- and ceftazidime-selected mutants were also generated from the two reference strains and were used for comparison. Antibiotic susceptibilities in the absence and presence of the efflux pump inhibitors carbonyl cyanide m-chlorophenylhydrazone (CCCP) and 1-(1-naphthylmethyl)-piperazine (NMP) were examined in the three imipenem-selected mutants and the three clinical multidrug-resistant (MDR) isolates. Expression profiles of the antimicrobial resistance genes in the imipenem-selected mutants and their parental strains were also determined. The results showed that imipenem was more likely, compared with the other antibiotics, to induce a MDR phenotype in the two reference strains. Differences in OXA-51-like carbapenemase, efflux pumps or/and AmpC β-lactamase expression were observed in the three imipenem-selected mutants. Moreover, a reduction in imipenem or amikacin resistance was observed when the imipenem-selected mutants and clinical isolates were exposed to NMP and CCCP. This study concluded that imipenem might be a potent inducer of multidrug resistance in A. baumannii strains. OXA-51-like carbapenemase combined with other resistance mechanisms may contribute to the development of multidrug resistance in A. baumannii. Monitoring the use of carbapenems is required to reduce the spread of MDR A. baumannii in hospitals., (Copyright © 2011 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)