Acta Microbiologica Hellenica

Introduction: Ventilator-associated pneumonia (VAP) is associated with increased morbidity and mortality. Early-onset (EOVAP) and late-onset (LOVAP) VAP differ in risk factors, microbiology, and outcomes. Methods: A retrospective cohort study of adult ICU patients admitted to a tertiary hospital between May 2020 and May 2022 compared EOVAP and LOVAP. Results: 194 patients were included (73.7% male), with a median age of 61 years. A total of 70.6% were admitted to the ICU for infection-related respiratory failure, predominantly due to COVID-19 (59.3%). EOVAP represented 21% and LOVAP 79% of cases, with median days to diagnosis of 4 and 11, respectively. Empirical antibiotic therapy was adequate in both groups; de-escalation was possible in 26.8%, and escalation due to treatment failure was required in 13.4%. The most commonly prescribed initial antibiotic was piperacillin–tazobactam (45%). Broad-spectrum antibiotic use did not differ between groups. Amoxicillin–clavulanate resistance was high in both groups (LOVAP 62.1%; EOVAP 48.8%), and piperacillin–tazobactam resistance was more frequent in LOVAP (41.2%). Follow-up cultures showed a high persistence rate (73.2%), with no significant change in resistance patterns. Conclusions: VAP remains common in the ICU, and the COVID-19 pandemic significantly impacted the already complex epidemiology of VAP. High resistance rates to amoxicillin–clavulanate and frequent isolation of MDR pathogens challenge empirical treatment based on onset timing, supporting empiric antibiotic selection guided by local microbiological ecology.

The rising prevalence of multidrug-resistant (MDR) Enterobacterales poses a major challenge for the empirical treatment of urinary tract infections (UTIs). We evaluated the in vitro activity of mecillinam against urinary Escherichia coli and Klebsiella pneumoniae isolates, including extended-spectrum β-lactamase (ESBL)-producing and non-ESBL-producing isolates. In this prospective, single-center study conducted in Spain (December 2020–March 2021), urinary isolates of E. coli and K. pneumoniae from patients with suspected UTIs were tested for susceptibility to mecillinam and other commonly used antibiotics. A total of 503 isolates were analyzed, including 285 non-ESBL-producing and 218 ESBL-producing isolates. Overall susceptibility was 96.2% (95% CI, 94.2–97.7%) for mecillinam and 98.2% for ertapenem. Mecillinam susceptibility was 96.5% (95% CI, 93.6–98.3%) among non-ESBL-producing isolates and 95.9% (95% CI, 92.3–98.1%) among ESBL-producing isolates, with MIC₅₀ values of 0.5 mg/L and 1 mg/L, respectively. Among ESBL-producing isolates, susceptibility to fosfomycin and trimethoprim–sulfamethoxazole was 72.9% and 44.0%, respectively. These findings demonstrate high in vitro activity of mecillinam against urinary E. coli and K. pneumoniae isolates, including both ESBL-producing and non-ESBL-producing isolates, and provide microbiological evidence supporting further clinical evaluation of pivmecillinam as an oral treatment option for UTIs.

Carbapenem-resistant Enterobacterales (CRE) are a major public health concern, yet genomic data from Bulgaria remain limited. We investigated the genomic epidemiology and genomic characteristics of clinically significant CRE recovered at University Hospital “Lozenetz”, Sofia, between 2022 and 2025. Antimicrobial susceptibility testing, phenotypic carbapenemase characterization, and PCR were combined with whole-genome sequencing of 23 purposively selected isolates chosen to capture temporal, species, carbapenemase, specimen, ward, and resistance-phenotype diversity. The proportion of CRE among all Enterobacterales remained broadly stable over the study period, and Klebsiella pneumoniae was the predominant species throughout. NDM-type carbapenemases were the most frequent overall, although VIM-, KPC-, and OXA-48-like enzymes were also detected. Among the sequenced isolates K. pneumoniae ST6260 (n = 16) was predominant. The remaining isolates included single K. pneumoniae isolates belonging to ST11, ST101, and ST258; two Enterobacter hormaechei ST114; one Proteus mirabilis ST93; and one Providencia stuartii ST46. All ST6260 isolates carried chromosomal blaNDM-5 within a conserved multidrug-resistance module with variable downstream regions, whereas blaOXA-232 was situated on a small ColKP3 plasmid within a defined subcluster. Overall, the data indicate that ST6260 is an emerging hospital-associated multidrug-resistant lineage.