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Infections caused by extensively drug-resistant (XDR) Acinetobacter nosocomialis have become a challenging problem. The frequent use of colistin as the last resort drug for XDR bacteria has led to the emergence of colistin-resistant A. nosocomialis (ColRAN) in hospitals. The mechanism of colistin resistance in A. nosocomialis remains unclear. This study aimed to investigate the mechanisms underlying colistin resistance in clinical ColRAN isolates. We collected 36 A. nosocomialis isolates from clinical blood cultures, including 24 ColRAN and 12 colistin-susceptible A. nosocomialis (ColSAN). The 24 ColRAN isolates clustered with ST1272 (13), ST433 (eight), ST1275 (two), and ST410 (one) by multilocus sequence typing. There was a positive relationship between pmrCAB operon expression and colistin resistance. Further analysis showed that colistin resistance was related to an amino acid substitution, Ser253Leu in PmrB. By introducing a series of recombinant PmrB constructs into a PmrB knockout strain and protein structural model analyses, we demonstrated that the association between Ser253Leu and Leu244 in PmrB was coupled with colistin resistance in ColRAN. To the best of our knowledge, this is the first study demonstrating that the key amino acid Ser253Leu in PmrB is associated with overexpression of the pmrCAB operon and hence colistin resistance. This study provides insight into the mechanism of colistin resistance in A. nosocomialis .

Introduction. Outbreaks of carbapenem-resistant A. baumannii and A. nosocomialis have occurred worldwide in healthcare settings. Rapid and reliable molecular typing of bacterial isolates is vital for the effective surveillance of institutional outbreaks. The Pan-PCR and OXA-PCR assays are two multiplex PCR-based assays for the molecular typing of Acinetobacter species. Gap statement. However, few studies have investigated the discriminatory power of two multiplex PCR assays in in the genotyping of Acinetobacter species. Aim. We aimed to evaluate the efficacies of the Pan-PCR and OXA-PCR assays for molecular typing of A. baumannii and A. nosocomialis . Methodology. A total of 105 carbapenem-resistant A. baumannii isolates (CRABs) and 93 carbapenem-resistant A. nosocomialis isolates (CRANs) obtained from blood cultures were used for molecular typing by the Pan-PCR and OXA-PCR assays and two multilocus sequence typing (MLST) schemes. Results. The isolates were individually divided into 12 and 21 different sequence types via the Pasteur and Oxford MLST schemes, respectively. Additionally, these isolates were distinguished into 18 different types by the Pan-PCR and OXA-PCR assays. The results of the Pan-PCR and OXA-PCR assays distinguished CRABs and CRANs with a sensitivity of 98.13 % and a specificity of 100 %. Conclusion. The Pan-PCR and OXA-PCR assays are promising alternative methods for rapid molecular typing of CRABs and CRANs in a routine laboratory setting.

Objectives: Acinetobacter seifertii, a new member of the Acinetobacter baumannii group, has emerged as a cause of severe infections in humans. We investigated the clinical and molecular characteristics of A. seifertii., Patients and Methods: This retrospective study enrolled 80 adults with A. seifertii bloodstream infection (BSI) at four medical centres over an 8 year period. Species identification was confirmed by MALDI-TOF MS, rpoB sequencing and WGS. Molecular typing was performed by MLST. Clinical information, antimicrobial susceptibility and the mechanisms of carbapenem and colistin resistance were analysed. Transmissibility of the carbapenem-resistance determinants was examined by conjugation experiments., Results: The main source of A. seifertii BSI was the respiratory tract (46.3%). The 28 day and in-hospital mortality rates of A. seifertii BSI were 18.8% and 30.0%, respectively. High APACHE II scores and immunosuppressant therapy were independent risk factors for 28 day mortality. The most common MLST type was ST553 (58.8%). Most A. seifertii isolates were susceptible to levofloxacin (86.2%), and only 37.5% were susceptible to colistin. Carbapenem resistance was observed in 16.3% of isolates, mostly caused by the plasmid-borne ISAba1-blaOXA-51-like genetic structure. A. seifertii could transfer various carbapenem-resistance determinants to A. baumannii, Acinetobacter nosocomialis and other A. seifertii isolates. Variations of pmrCAB and lpxCAD genes were not associated with colistin resistance of A. seifertii., Conclusions: Levofloxacin and carbapenems, but not colistin, have the potential to be the drug of choice for A. seifertii infections. A. seifertii can transfer carbapenem-resistance determinants to other species of the A. baumannii group and warrants close monitoring., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Colistin remains a last-line antibiotic for the treatment of infections by multidrug-resistant Acinetobacter species. However, mortality rates are high in patients with Acinetobacter infection receiving colistin treatment. This multicentre study evaluated whether colistin susceptibility, additional antimicrobial agents or other prognostic factors influenced the clinical outcomes of patients receiving colistin treatment for Acinetobacter bacteraemia. This retrospective study enrolled 122 adults receiving colistin for monomicrobial Acinetobacter bacteraemia at six medical centres in the ACTION Study Group over an 8-year period. Clinical information, antimicrobial susceptibility and colistin resistance determinants were analysed. The primary outcome measure was 14-day mortality. Among 122 patients, 18 and 104 were infected with colistin-resistant (ColR) isolates [minimum inhibitory concentration (MIC) ≥4 mg/L] and colistin-susceptible (ColS) isolates (MIC ≤2 mg/L), respectively. Patients infected with ColR and ColS isolates did not differ significantly with regard to Charlson comorbidity index, invasive procedures, sources of bacteraemia, disease severity and 14-day mortality rate (44.4% vs. 34.6%; P = 0.592). No specific additional antimicrobial agent was independently associated with higher or lower mortality. Coronary artery disease, higher Acute Physiology and Chronic Health Evaluation (APACHE) II score and bacteraemia caused Acinetobacter baumannii were independent risk factors associated with 14-day mortality. Mechanisms of colistin resistance were associated with amino acid variants in the pmrCAB operon. Finally, previously unreported Acinetobacter nosocomialis amino acid variants related to colistin resistance were identified. In conclusion, colistin susceptibility and colistin combination antimicrobial treatment were not associated with decreased 14-day mortality in patients with Acinetobacter bacteraemia receiving colistin treatment., (Copyright © 2020 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Purpose: Bloodstream infections (BSIs) caused by Acinetobacter species have been extensively reported, however, which majorly focused on respiratory tract infections. The risk of mortality and the effect of early catheter removal on survival in catheter-related BSIs (CRBSIs) caused by Acinetobacter spp. remain unclear. This study aims to investigate that., Methods: This is a retrospective multicentric study conducted in Taiwan from 2012 to 2014. Patients with at least 1 positive blood culture and catheter culture for the same Acinetobacter spp., showing symptoms and signs of CRBSIs, were included (n = 119). Risk factors for 30-day mortality were analyzed using a logistic regression model. The characteristics of patients with early catheter removal (within 48 hours after CRBSIs) were compared to those without removal matching for age, sex, and disease severity., Results: There were no differences in 30-day mortality with regard to causative Acinetobacter spp., catheter type, site, and appropriateness of antimicrobial therapy. Patients with higher Acute Physiologic and Chronic Health Evaluation (APACHE) II scores (odds ratio [OR]: 1.12; 95% confidence interval [CI]: 1.02-1.23; P = .014), shock (OR: 6.43; 95% CI: 1.28-32.33; P = .024), and longer hospitalization before CRBSIs (OR: 1.04; 95% CI: 1.00-1.08; P = .027) had a significantly higher 30-day mortality rate. Early removal of catheters after CRBSIs was not associated with better survival benefits., Conclusion: Higher disease severity (APACHE II score), shock, and longer hospitalization before bacteremia were independently associated with a higher 30-day mortality in CRBSIs caused by Acinetobacter spp. In previous published guidelines, infected catheters were suggested to be removed in CRBSIs caused by gram-negative bacilli. Even though early removal of catheters did not associate with a better survival outcome in current results, it should be judiciously evaluated according to the clinical conditions and risks individually. For better elucidation of these issues, further well-controlled prospective study may be warranted.

The mechanism by which carbapenem non-susceptible Acinetobacter nosocomialis (CNSAN) is disseminated is rarely described in the literature. In this study, we delineated the molecular epidemiology of CNSAN isolated from patients in a medical center in Taiwan. Fifty-four non-duplicate bloodstream isolates of CNSAN were collected at the Taipei Veterans General Hospital between 2001 and 2007. Pulsed-field gel electrophoresis (PFGE) was performed to determine their clonal relationship. Carbapenem-resistance genes and associated genetic structures were detected by polymerase chain reaction (PCR) mapping. Southern hybridization was performed to determine the plasmid location of carbapenem-resistance genes. Transmissibility of these genes to Acinetobacterbaumannii was demonstrated by conjugation tests. The overall carbapenem non-susceptibility rate among A. nosocomialis isolates during the study period was 21.6% (54/250). PFGE revealed three major pulsotypes: H (n=23), I (n=10), and K (n=8). The most common carbapenem-resistance gene was blaOXA-58 (43/54, 79.6%), containing an upstream insertion sequence IS1006 and a truncated ISAba3 (IS1006-ΔISAba3-like-blaOXA-58). All isolates belonging to the pulsotypes H, I, and K carried plasmid located IS1006-ΔISAba3-like-blaOXA-58. A common plasmid carrying ISAba1-blaOXA-82 was found in six isolates, which belonged to five pulsotypes. A type 1 integron that carried blaIMP-1 was detected in different plasmids of seven isolates, which belonged to five pulsotypes. Plasmids carrying these carbapenem-resistant determinants were transmissible from A. nosocomialis to A. baumannii via conjugation. In this medical center, CNSAN mainly emerged through clonal dissemination; propagation of plasmids and integrons carrying carbapenem-resistant determinants played a minor role. This study showed that plasmids carrying carbapenem-resistant determinants are transmissible from A. nosocomialis to A. baumannii., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: It is unknown whether there are differences between bacteremia caused by carbapenem resistant Acinetobacter baumannii (CRAB) and carbapenem resistant Acinetobacter nosocomialis (CRAN). This study aims to investigate the differences, especially in clinical outcomes, between patients with bacteremia caused by CRAB or CRAN., Methods: This is a 9-year retrospective study comparing the clinical manifestations, antimicrobial susceptibilities, and clinical outcomes of 71 patients with CRAB bacteremia and 64 patients with CRAN bacteremia., Results: Patients with CRAB were more likely to have hematologic malignancies and presented with more shock episodes than those with CRAN. CRAB isolates were more resistant to various classes of antimicrobials except colistin, and therefore the patients with CRAB bacteremia were more likely to receive inappropriate antimicrobial therapies. The 14-day mortality was significantly higher in patients with CRAB (40.8% vs. 14.1%; p = 0.001), and in this study, acquisition of CRAB was identified as an independent risk factor for mortality (odds ratio = 4.003; 95% confidence interval = 1.566-10.231; p = 0.004)., Conclusions: CRAB and CRAN bacteremia are different in clinical characteristics, antimicrobial susceptibilities, and mortality rates. Genomic species identification should be performed in the study of carbapenem resistant Acinetobacters to better delineate the role of different species.

Carbapenem-resistant Acinetobacter nosocomialis (CRAn) is a significant public health concern. Tigecycline non-susceptible CRAn (Tn-CRAn) isolates have emerged worldwide. Tigecycline resistance is mainly related to the overexpression of AdeABC efflux pump controlled by AdeRS two-component system (TCS). Two novel tetracycline derivatives, omadacycline and eravacycline, may present a treatment option for CRAn. This study investigated the in vitro antimicrobial activity of tigecycline, omadacycline and eravacycline against clinical CRAn isolates and the contribution of efflux pumps in their resistance. Eighty-nine clinical CRAn isolates, including 57 Tn-CRAn isolates were evaluated for minimum inhibitory concentrations (MICs) by the broth microdilution. The relationship between the antimicrobial resistance and efflux pump expression was assessed by their responses to the efflux pump inhibitor 1-(1-naphthylmethyl)-piperazine (NMP). The contribution of the AdeABC efflux pump in their resistance was determined by the complementation of the AdeRS two-component system in wild-type, adeRS operon and adeB gene knockout strains. Among the 89 isolates, omadacycline and eravacycline MICs were correlated closely with those of tigecycline. They demonstrated improved potency, based on MIC90 values, by showing a 4 to 8-fold greater potency than tigecycline. The synergetic effects of tigecycline, omadacycline and eravacycline with NMP were observed in 57 (100%), 13 (22.8%), and 51 (89.5%) of Tn-CRAn isolates, respectively. Further analysis showed that the laboratory strain carrying the Type 1 adeRS operon increased the tigecycline, omadacycline and eravacycline MICs by 4–8-folds, respectively. Eravacycline demonstrated improved potency over tigecycline against populations of CRAn, including Tn-CRAn isolates. The over-expression of AdeABC efflux pumps was directly activated by the AdeRS two-component system and simultaneously reduced the susceptibilities of tigecycline, eravacycline, and omadacycline. Omadacycline and eravacycline MICs were correlated closely with those of eravacycline. [ABSTRACT FROM AUTHOR]

Antimicrobial-resistant (AMR) bacterial infections, including those caused by Acinetobacter baumannii , have emerged as a clinical crisis worldwide. Immunization with AMR determinants has been suggested as a novel approach to combat AMR bacteria, but has not been validated. The present study targeted tigecycline (TGC) resistance determinants in A. baumannii to test the feasibility of this approach. Using bioinformatic tools, four candidates, AdeA, Ade I, AdeK, and TolC, belonging to the resistance-nodulation-division (RND) efflux pump were identified as highly conserved and exposed antigens from 15 A. baumannii genomes. Antisera generated from recombinant proteins showed the capability to reserve Hoechst 33342, a substrate of the efflux pump, in bacterial cells. The rTolC antisera had the highest complement-dependent killing and opsonophagocytosis effect compared to the sera from phosphate-buffered saline immunized mice. Among the antisera, anti-rAdeK-specific antisera decreased the minimal inhibitory concentration of TGC in 26.7% of the tested isolates. Immunization with rAdeK significantly potentiated TGC efficacy in treating TGC-resistant A. baumannii pneumonia in the murine model. The bacterial load (7.5 × 105 vs. 3.8 × 107, p < 0.01) and neutrophil infiltration in the peri-bronchial vasculature region of immunized mice was significantly lower compared to the PBS-immunized mice when TGC was administrated concomitantly. Collectively, these results suggest that active immunization against resistance determinants might be a feasible approach to combat multidrug-resistant pathogens in high risk population. [ABSTRACT FROM AUTHOR]

Background: It is unknown whether there are differences between bacteremia caused by carbapenem resistant Acinetobacter baumannii (CRAB) and carbapenem resistant Acinetobacter nosocomialis (CRAN). This study aims to investigate the differences, especially in clinical outcomes, between patients with bacteremia caused by CRAB or CRAN. Methods: This is a 9-year retrospective study comparing the clinical manifestations, antimicrobial susceptibilities, and clinical outcomes of 71 patients with CRAB bacteremia and 64 patients with CRAN bacteremia. Results: Patients with CRAB were more likely to have hematologic malignancies and presented with more shock episodes than those with CRAN. CRAB isolates were more resistant to various classes of antimicrobials except colistin, and therefore the patients with CRAB bacteremia were more likely to receive inappropriate antimicrobial therapies. The 14-day mortality was significantly higher in patients with CRAB (40.8% vs. 14.1%; p = 0.001), and in this study, acquisition of CRAB was identified as an independent risk factor for mortality (odds ratio = 4.003; 95% confidence interval = 1.566-10.231; p = 0.004). Conclusions: CRAB and CRAN bacteremia are different in clinical characteristics, antimicrobial susceptibilities, and mortality rates. Genomic species identification should be performed in the study of carbapenem resistant Acinetobacters to better delineate the role of different species. [ABSTRACT FROM AUTHOR]

Background: Acinetobacter baumannii hospital-acquired pneumonia (HAP) is associated with a high mortality worldwide. Non-ventilated patients with HAP (NVHAP) caused by nosocomial pathogens are reported to have a more favorable outcome than those with ventilator-associated pneumonia (VAP). The current study was designed to determine whether bacteremic patients with A. baumannii NVHAP also have a lower mortality than those receiving assisted ventilation. Methods: This retrospective 10-year study was conducted at a 2900-bed teaching hospital located in Northern Taiwan. The population consisted of 144 patients with A. baumannii bacteremia and HAP. Of these 96 had VAP and 48 had NVHAP. Charts were reviewed for demographic characteristics, comorbidities, clinical manifestations, antimicrobial susceptibility, and 14-day mortality. Clonal relationships were determined by molecular typing. Results: There were no significant differences between the two groups in comorbidities (Charlson scores). Patients with NVHAP were more likely to have developed bacteremia earlier, outside the ICU and undergone fewer invasive procedures. They had significantly lower APACHE II scores, fewer bilateral pneumonias and lower rates of antimicrobial resistance. No specific clones were identified in either group. The unadjusted (crude) 14-day mortality rates were not significantly different between the groups (NVHAP 43.8% vs. VAP 31.3%, p = 0.196). The adjusted 14-day mortality risk was significantly lower in ventilator-assisted patients (odds ratio = 0.201; 95% confidence interval = 0.075-0.538; p = 0.001). Conclusions: Patients with bacteremic NVHAP and VAP caused by A. baumannii had similar crude mortality rates, but on logistic regression analysis those receiving ventilator assistance had a significantly lower mortality. This may have been due to better airway protection, more intensive monitoring with earlier diagnosis and treatment in patients with VAP, greater innate susceptibility to infection in those with NVHAP and differences in the virulence of A. baumannii. [ABSTRACT FROM AUTHOR]