Abstract. Carbapenem-resistant Pseudomonas aeruginosa (CRPA), a World Health Organization high-priority pathogen, represents a major clinical threat due to

Carbapenem-resistant Klebsiella pneumoniae (CRKP), a WHO’s critical priority pathogen, continuously evolves to generate health-threatening high-risk (sub)lineages. Here, we conducted a 10-year surveillance of nosocomial CRKP infections, collecting and whole-genome sequencing 1513 clinical isolates, accompanied by clinical data. We applied fine-scale genome analysis for 60,724 non-local public-available K. pneumoniae genomes. We identified a predominant ST11-KL64 sublineage widely-disseminated across China and internationally-distributed. Isolates of this sublineage were more frequently recovered during seasonal influenza peaks and harbored plasmids encoding ‘hypervirulence’ factors but caused no increase in patient mortality. Instead, they exhibited enhanced invasiveness and translocation capacity. Mechanistically, this suggested highly invasive CRKP (hiCRKP) sublineage showed elevated resistance to macrophage-mediated phagocytosis, partly due to the virulence-encoding plasmid and the

Antimicrobial resistance (AMR) is one of the major global public health threats. In recent decades, Acinetobacter baumannii has become one of the most significant multidrug-resistant (MDR) bacteria in hospital settings (1, 2). Since 2017, the World Health Organization has classified carbapenem-resistant A. baumannii as a critical-priority pathogen, a status that remains in the most recent update in 2024, which reflects the urgent need for new antibiotics against this bacterium (3, 4). A. baumannii is a frequent cause of nosocomial infections, primarily affecting patients in intensive care units (ICUs), immunocompromised individuals, patients using medical devices (such as catheters), and those with underlying diseases (5).

New data from the PETERPEN trial suggest that piperacillintazobactam may be noninferior to meropenem for early clinical outcomes in select patients with ESBL bloodstream infections, but carbapenems re...

Patients with bloodstream infections with antimicrobial resistant bacteria often receive ineffective empirical therapy. The implications are still uncertain.MethodsWe performed a retrospective, multicenter, study of patients with bloodstream infections caused by Extended-Spectrum Beta-Lactamase-producing gram-negative bacteria in southern Sweden from 2013 to 2022. Patients were categorized based on time to effective therapy: ≤24 h (effective empirical therapy) and >24 h (ineffective empirical therapy). Therapy was considered effective if the agent was active in susceptibility testing and administered intravenously at an appropriate dose.The primary outcome was 30-day mortality. Secondary outcomes were ICU admission and hospital length of stay.ResultsA total of 289/644 (44.9%) patients received ineffective empirical therapy within the first 24 hours after the index blood culture collection. No significant impact of ineffective empirical therapy on 30-day mortality was found in univariable (Hazard ratio 0.66; P=0.15) or multivariable Cox regression analysis (Hazard ratio 0.64; P=0.13). Patients receiving effective empirical therapy were more likely to receive intensive care (Odds ratio 0.38; P=0.008), but the association was non-significant after adjusting for severity of illness and comorbidities.Ineffective empirical therapy was not associated with a longer hospital stay in Fine–Gray competing risks regression analysis (univariable: sHR 1.15; P=0.082; multivariable: sHR 1.11; P=0.20).ConclusionIneffective empirical therapy was not associated with 30-day mortality, in patients with bloodstream infections with Extended-Spectrum Beta-Lactamase-producing Enterobacterales. If confirmed in prospective studies, our findings could support antimicrobial stewardship efforts by reducing unnecessary empirical carbapenem use without compromising short-term clinical outcomes, particularly in low-prevalence settings

This study aimed to monitor clinical isolate susceptibility to antimicrobial agents in healthcare facilities in 31 provinces or cities of China in 2024. Antimicrobial susceptibility of clinical…

This systematic review with bayesian meta-analysis of randomized clinical trials examined the association of cefepime with all-cause mortality compared with other β-lactam antibiotics.

Links for you. Science: Pennsylvania’s Measles Outbreak Is Enormous. The two latest deaths suggest that the true number of infections is much larger than reported. Study suggests carbapenem-resistant Acinetobacter may spread through the air Three wild dogs have traveled farther than any African mammal The South Can’t Shake This Record-Breaking Heat. Here’s Why Few people with the flu isolate for the recommended period…

Non-carbapenemase-producing Enterobacterales with isolated ertapenem resistance (ETP-mono-R) may represent an early stage in the evolution toward broader carbapenem resistance, but whether further resistance induction occurs and its underlying mechanisms remain poorly understood.MethodsResistance induction was assessed in three Escherichia coli, four Klebsiella pneumoniae, and two Enterobacter cloacae isolates through serial exposure to subinhibitory concentrations of meropenem (MEM), imipenem, ceftazidime-avibactam, or colistin (COL), with antibiotic-free passaging for reversion. Resistance induction under MEM+COL was evaluated separately. Whole-genome sequencing (WGS), targeted porin-gene Sanger sequencing, and transcriptional analysis were used to characterize resistance mechanisms across induction stages.ResultsSubinhibitory MEM exposure rapidly selected for carbapenem resistance through porin-associated alterations in a species-specific manner. E. coli accumulated loop-region mutations in ompC, while K. pneumoniae predominantly developed disruptive mutations in ompK36, both accompanied by marked transcriptional downregulation. In contrast, E. cloacae retained wild-type porins but showed increased MEM MICs, suggesting a non-porin-mediated mechanism. Subinhibitory exposure to COL alone rapidly induced colistin resistance but was associated with decreased carbapenem MICs. Co-exposure to MEM and COL significantly delayed resistance development and reduced MIC increases (all P < 0.05). Targeted sequencing of 26 non-carbapenemase-producing K. pneumoniae isolates resistant to all carbapenems revealed widespread disruptive ompK36 alterations, including the S337P substitution identified experimentally, consistent with a shared permeability-loss pathway.ConclusionsIn ETP-mono-R Enterobacterales, subinhibitory carbapenem exposure promotes carbapenem resistance, with porin-associated mechanisms predominating in E. coli and K. pneumoniae. Co-exposure to COL attenuates this process, suggesting a potential strategy to delay the emergence of carbapenem resistance.