An in vitro study compared cefepime-zidebactam, aztreonam-avibactam and other recently developed agents against carbapenem-resistant hypervirulent Klebsiella pneumoniae. The susceptibility rates of CR-hvKP to cefepime/zidebactam and aztreonam/avibactam all exceeded 90%, with rates of 98.1% and 99.1%, respectively. CR-hvKP exhibited susceptibility rates of 57.5% and 65.1% to imipenem/relebactam and meropenem/vaborbactam, respectively. Several novel combinations retained activity against isolates carrying complex resistance determinants, supporting their potential role against this emerging high-risk pathogen.

A 3-year ICU study investigated the emergence and transmission of ceftazidime/avibactam-resistant (CZA-R) K. pneumoniae. Among patients receiving CZA, 9% tested positive for CZA-R strains. While in vivo evolution accounted for most resistant isolates (71.4%), 28.6% resulted from horizontal transmission, involving three distinct outbreaks. Eight KPC variants were identified, including the novel KPC-295, and 76.2% of CZA-R isolates were also resistant to cefiderocol (FDC). The findings highlight the potential contribution of hospital transmission to CZA resistance and support strengthened microbiological surveillance and infection-control measures in ICU settings.

A multicentre retrospective study evaluated cefiderocol use in 28 patients with haematological malignancies, 57.1% of whom were colonized with MDR organisms. Microbiological documentation was available in 85.7% of patients, with MDR pathogens identified in 75% and P. aeruginosa being the most frequent isolate (46.4%). While clinical responses were observed and no safety signals emerged, cefiderocol resistance was documented, including on-treatment resistance development in a P. aeruginosa infection. Overall 30-day mortality was 35.7%. These findings highlight the need for further research to optimize cefiderocol use and address emerging resistance in severely immunocompromised patients.

LINK: https://pubmed.ncbi.nlm.nih.gov/42264071

A multicentre Italian study evaluated cefepime/enmetazobactam (FEP/META) in 32 patients with documented Enterobacterales infections, predominantly caused by E. coli (50.0%) and K. pneumoniae (40.6%). ESBL production was detected in 90.6% of isolates. Clinical cure was achieved in 100% of patients, with 78.1% microbiological eradication and no in-hospital deaths. FEP/META was well tolerated, supporting its potential role as a carbapenem-sparing option for selected Enterobacterales infections, while larger studies are needed to confirm these real-world findings.

An in vitro study evaluated delafloxacin (DLX) and comparator fluoroquinolones against Enterococcus faecalis and E. faecium. Against E. faecalis, DLX showed greater activity than levofloxacin and moxifloxacin (MIC₅₀ 0.06 mg/L; 16- and 4-fold lower, respectively), with activity further enhanced under acidic conditions (3-log₂ MIC₅₀ reduction from pH 7.2 to pH 5), while comparator activity decreased. None of the agents showed relevant activity against E. faecium. These findings suggest a potential role for DLX in male E. faecalis UTIs, warranting further preclinical and clinical investigation.

A population PK analysis of 23 patients receiving oritavancin (249 samples) evaluated TDM-guided redosing strategies over extended intervals. Repeated dosing resulted in predictable accumulation, while 24-h concentrations strongly predicted AUC₇₂ (R²=0.93) and Day-7 concentrations helped identify appropriate 1-, 2-, or 3-week dosing intervals. Weekly and biweekly regimens achieved 100% Probability for target attainment (PTA) for the AUC₇₂ target at steady state, whereas <5% of patients were predicted to maintain trough targets with 4-week dosing. These findings support TDM-guided individualized redosing; without TDM, weekly dosing provided the highest probability of achieving PK/PD targets.

An experimental study identified a transient survival phenotype under dalbavancin exposure across genetically diverse S. aureus strains, including vancomycin-susceptible and -intermediate isolates. Multi-omics and imaging analyses linked delayed killing to metabolic adaptation and cell-envelope remodelling, including altered peptidoglycan biosynthesis and heterogeneous cell-wall thickening. Disruption of peptidoglycan assembly reduced survival, supporting an adaptive and reversible mechanism rather than stable genetic resistance. These findings provide a potential mechanistic explanation for dalbavancin treatment failure in the absence of measurable resistance.

A retrospective study evaluated 25 patients with prosthetic vascular graft infection (PVGI) receiving suppressive antimicrobial therapy (SAT). Infection control during SAT was achieved in 40%, while 10 patients discontinued therapy and 60% remained relapse-free for >6 months. Long-acting antibiotics were used in 24% (6/25) of patients, with successful discontinuation in 3 cases. These findings support SAT as a potential option for selected high-risk PVGI patients and suggest a possible role for long-acting antibiotics, while further studies are needed to define optimal treatment duration.