We aimed to describe the increased rate of Acinetobacter baumannii infections during the COVID-19 pandemic and define its significance within the last five years. This study was performed in a tertiary hospital with 280 beds and included all patients infected with A. baumannii in the intensive care unit between January 1, 2018, and June 30, 2022. A. baumannii-infected patients in the intensive care unit 27 months before the pandemic and 27 months during the pandemic were included. Pulsed-field gel electrophoresis was performed to assess clonal relatedness. The infection control measures were specified based on the findings and targeted elimination. In total, 5718 patients were admitted to the intensive care unit from January 1st, 2018, to June 30th, 2022. A. baumannii infection was detected in 81 patients. Compared to the pre-pandemic era, the rate of A. baumannii infection during the pandemic was 1.90 times higher (OR: 1.90, 95% CI: [1.197, 3.033]). Clonality assessment of multidrug-resistant A. baumannii samples revealed eight clusters with one main cluster comprising 14/27 isolates between 2021 and 2022. The case fatality rate of the pre-pandemic and pandemic era was not different statistically (83.33% vs. 81.48%, p = 0.835). Univariate analysis revealed the association of mechanical ventilation (p = 0.002) and bacterial growth in tracheal aspirate (p = 0.001) with fatality. During the COVID-19 pandemic, potential deficits in infection control measures may lead to persistent nosocomial outbreaks. In this study, the introduction of enhanced and customized infection control measures has resulted in the containment of an A. baumannii outbreak.

Background: In the era of rising carbapenem resistance, we aimed to investigate the change in mortality rate and positivity of carbapenemase genes in Acinetobacter baumannii. Methods: Preferred Reporting Items for Systematic Review (PRISMA) guidelines were adopted in this systematic review. Our literature search included the Cochrane Library, Pubmed, Scopus, Web of Science, Medline, Tubitak TR Dizin, and Harman databases for studies dating back from 2003 to 2023 reporting bloodstream A. baumannii infections in Türkiye. A simple linear regression model was used to determine the association between resistance, mortality, and time. Results: A total of 1717 studies were identified through a literature search, and 21 articles were selected based on the availability of the data regarding mortality and resistance rate (four articles) or the molecular epidemiology of carbapenem-resistant A. baumannii (17 articles) in Türkiye. From 2007 to 2018, the carbapenem resistance rate increased (p = 0.025). The OXA-23 and OXA-58 positivities were inversely correlated (p = 0.025). Conclusions: Despite the emergence of carbapenem resistance, mortality did not increase in parallel, which may be due to improved medical advancements or the fitness cost of bacteria upon prolonged antimicrobial exposure. Therefore, we suggest further global research with the foresight to assess clonal relatedness that might affect the carbapenem resistance rate.

Multidrug-resistant Acinetobacter baumannii remains a global concern with its ability to adhere, disperse and sustain in areas involving suboptimal infection control measures, particularly in war areas. In this study we aimed to evaluate the susceptibility profiles, molecular epidemiology and pathogenesis of A. baumannii isolates from conflict zones in Ukraine. A. baumannii wound isolates (n=46) were tested to comparatively assess antimicrobial resistance, molecular epidemiology, pathogenesis and infectivity. Briefly, antimicrobial susceptibility testing, whole genome sequencing, biofilm and capsule formation, as well as serum survival and bacterial viability in G. mellonella and a mouse infection model were performed. Dominating sequence types were ST2, ST19, ST78 and ST400 while 65.21% of isolates were from international clones. All isolates were multidrug resistant (MDR), and 7 isolates were extensively drug resistant (XDR). ST19 isolates had higher encapsulation, lower serum survival and missing T6SS, omp33-36 and biofilm production associated genes. However, bacteria expressed higher virulence and lethality during early infection compared to later stages in vivo. We report the first results characterizing the pathogenesis and infectivity of the emerging A. baumannii ST19. High MDR and XDR rates alongside clonally related isolates are concerning and highlight the importance of infection prevention and control measures in conflict zones.

Background: Colistin resistance in Acinetobacter baumannii is an emerging problem that limits antimicrobial therapy options. Materials & methods: We isolated two pairs of colistin susceptible and colistin-resistant A. baumannii (K1007/K1006 and K408/K409) from two patients diagnosed with carbapenem-resistant A. baumannii infection. Colistin susceptible isolates were exposed to in vitro colistin induction for 50 generations. The selected cell populations were subjected to DNA and RNA sequencing and phenotypic assays. Results: In the in vitro induction assay, K408 gained colistin resistance on the corresponding day of clinical resistance (K408-G25) and got resensitized to colistin in the consecutive generation (K408-G26). A significant upregulation of ompW, ata, adeFGH genes on K408-G25 was followed by a downregulation upon resensitization to colistin (G26). Despite the upregulation of the ompW gene in transcriptomic analysis, the ompW protein disappeared on K408-G25 and recovered in the resensitized generation (G26). In parallel, disrupted cell membrane integrity recovered in K408-G26. In the K408-G25, downregulation of pbpG and upregulation of pbp1a/pbp3 genes decreased serum-resistance which was reversed in the resensitized generation (G26). The K1007 did not gain colistin resistance amongst 50-generations, however, the generation corresponding to clinical resistance day (K1007-G9) had a similar trend with K408-G25. The clinical colistin-resistant K409 and K1006 had SNPs on pmrA and pmrB genes. Conclusion: In this study, we observed that A. baumannii regulates adhesion, efflux pumps and serum-resistance associated genes as an early response to colistin stress. Besides, the ompW protein disappears in the cell membrane of colistin resistant cells which recovers after resensitization to colistin. The lack of ompW protein in colistin-resistant cells should be taken into consideration for escape mutants in development of antivirulence vaccination or treatment options.

Background: Escalating resistance among Gram-negative pathogens limits β-lactam options. Cefepime/enmetazobactam combines a fourth-generation cephalosporin with a class A β-lactamase inhibitor. We evaluated its activity against multidrug, extensive and pandrug-resistant war-wound isolates from Ukraine. Materials and methods: We tested 215 clinical samples (2022–2023) isolated from wounded patients in Ukraine by broth microdilution. Paired comparisons of cefepime monotherapy versus cefepime/enmetazobactam was done to evaluate enmetazobactam. Whole-genome sequencing (n = 83) identified β-lactamases, sequence types and outer-membrane protein alterations. Results: Across Enterobacterales, resistance decreased from 60.5% (26/43) with cefepime to 27.9% (12/43) with the cefepime/enmetazobactam combination. In K. pneumoniae, resistance declined from 92.6% (75/81) to 74% (60/81) and in P. mirabilis, from 88.9% (8/9) to 11.1% (1/9), respectively. P. aeruginosa showed a modest change [77.8% (23/36) to 58.3% (32/36)], while A. baumannii remained non-susceptible to both cefepime and cefepime/enmetazobactam with the rates of 91.3% (42/46) to 82.6% (36/46), respectively. Genotype–phenotype correlation revealed that in K. pneumoniae, reduced activity was associated with OmpK36 loop-3 insertions, OmpK35 loss and metallo-β-lactamases, whereas selected sequence types lacking these changes were more susceptible. In A. baumannii, OXA-type carbapenemases and blaADC beta-lactamases predominated; isolates lacking type VI secretion, omp33-36 and adhesin genes (ata/bap) demonstrated relatively higher susceptibility to cefepime/enmetazobactam. Conclusions: Cefepime/enmetazobactam improved susceptibility relative to cefepime, most notably in Enterobacterales, but activity was constrained by permeability defects and non-target β-lactamases. Combination therapy with agents that does not get hydrolysed by MBLs and integrated β-lactamase detection with practical permeability indicators may optimize the clinical use of this combination in high-resistance settings.