Abstract Objectives To determine comparative effectiveness of piperacillin/tazobactam and cefepime for the treatment of bacteremia due to Enterobacterales at moderate risk for clinically significant AmpC production. Methods A retrospective multicentre study was conducted among adults with bacteremia due to Enterobacter cloacae complex, Klebsiella aerogenes, or Citrobacter freundii complex from 2017 to 2025. Treatment-emergent resistance was defined as a ≥4-fold MIC increase or a categorical change in susceptibility within 90 days. Results Seven hundred twenty-eight patients met inclusion criteria. The median (IQR) age was 67 years (55–74), and 35% (252/728) were immunocompromised. Cefepime was used for definitive therapy in 47% (342/728), followed by piperacillin/tazobactam in 18% (129/728) and carbapenems in 16% (115/728). Overall, 30-day mortality was 12% (88/728). Patients receiving piperacillin/tazobactam had a higher median (IQR) Pitt bacteremia score (2 [1–3] versus 1 [0–3], P=0.017) than those receiving cefepime, but rates of 30-day mortality (14% [18/129] versus 11% [37/342], P = 0.345) and relapsed infection between days 5–14 (3% [4/129] versus 2% [5/342], P = 0.266) were similar. After inverse probability of treatment weighting, 30-day mortality rates between patients treated with piperacillin/tazobactam and cefepime were not significantly different (HR 1.05, 95% CI 0.57–1.92). Treatment-emergent resistance to definitive therapy occurred in 1% (5/342), 2% (3/129), and 3% (4/115) of patients treated with cefepime, piperacillin/tazobactam, and carbapenems, respectively. Conclusions In the largest study to date of bacteremia due to E. cloacae complex, K. aerogenes, or C. freundii complex, treatment-emergent resistance was uncommon, and outcomes did not differ significantly between patients treated with piperacillin/tazobactam and cefepime.
Abstract Objectives Extended-spectrum β-lactamase- and carbapenemase-producing Enterobacterales (ESBL-E and CP-E, respectively) are global public health threats, prioritized by the WHO for urgent action. We assessed prevalence, risk factors and genomic context of ESBL-E and CP-E carriage in domestic carnivores on Réunion Island and compared resistant isolates with human isolates to evaluate pets’ role in islandwide antimicrobial resistance transmission. Methods Combining the methods of classical microbiology (selective culture, MS identification, disc-diffusion antimicrobial susceptibility testing) and WGS (using in-house Nanopore technology), we compared 55 ESBL-E isolates originating from 881 domestic carnivores obtained in an island-wide cross-sectional survey with 40 human isolates obtained through an existing ESBL surveillance network and from healthy volunteers. We evaluated the risk factors for ESBL-E carriage in domestic carnivores by fitting multivariate generalized linear models applied to data from anamnestic questionnaires. Results The prevalence of ESBL-E/CP-E carriage was 6% in carnivores (dogs: 8%; cats: 3%). The dominant ESBL gene across hosts (dogs, cats, humans) was blaCTX-M-15, followed by blaCTX-M-27. Three carbapenem-resistant isolates were detected in dogs, including the blaNDM-1 gene. Risk factors for animal ESBL-E/CP-E colonization included intact reproductive status, recent antibiotic therapy and free-roaming behaviour. Animal-originating ESBL-producing Escherichia coli exhibited greater genetic diversity than human-origin isolates, suggesting multiple introduction sources and environmental influences. Conclusions Our findings suggest that domestic carnivores should be routinely included in surveillance networks, as their lifestyle and close contact with humans may allow trends in their enteric antimicrobial-resistant flora to foreshadow trends in the human resistome.
Abstract Introduction Cefepime/zidebactam is a β-lactam/β-lactam enhancer combination with activity against carbapenem-resistant (CR) Gram-negative pathogens, including metallo-β-lactamase (MBL)-producing organisms. Before regulatory approval, cefepime/zidebactam was available through a compassionate-use programme for patients with CR Gram-negative infections who had limited available treatment options. Methods We conducted a retrospective, multi-country analysis of patients who received cefepime/zidebactam through compassionate use between 2022 and 2025. Data included demographics, comorbidities, acute complications, prior antibiotic exposure, infection characteristics, microbiology, treatment details, and investigator-assessed outcomes. Results Eighty-five patients were included (median age 48 years; 57.6% in an intensive care unit at initiation). Primary infections included pneumonia/respiratory infection (30.6%), bone and joint infection (24.7%), and complicated urinary tract infection/pyelonephritis (14.1%). Pseudomonas aeruginosa was the predominant pathogen (77.6%), followed by Klebsiella pneumoniae (14.1%) and Acinetobacter baumannii (11.8%); infections involving at least two Gram-negative pathogens occurred in 10.6%. Among isolates with available genotypic data, MBLs were common and predominantly NDM. The cefepime/zidebactam minimum inhibitory concentration (MIC)50 and MIC90 were 8 and 32 mg/L, respectively. Investigator-assessed clinical success at the end of therapy was achieved in 88.2% of patients (95% CI, 79.7–93.5), and microbiological eradication in 89.4% (95% CI, 81.1–94.3); on-therapy mortality was 10.6% (95% CI, 5.7–18.9). Treatment-emergent adverse events occurred in five patients (5.9%, 95% CI, 2.5–13.0), with one discontinuation. Conclusions In this uncontrolled compassionate-use case series, cefepime/zidebactam treatment was accompanied by high investigator-assessed clinical success and microbiological eradication in patients with severe infections caused by CR Gram-negative pathogens. These observations require confirmation in prospective controlled studies.
Abstract Background Surveillance data for Pseudomonas aeruginosa in the USA are distributed across systems designed for different purposes, potentially limiting standardized national surveillance of high-priority resistant phenotypes. We evaluated whether the Centers for Disease Control and Prevention (CDC) National Notifiable Diseases Surveillance System (NNDSS) can support surveillance of multidrug-resistant (MDR) P. aeruginosa and synthesized available CDC surveillance data to characterize the residual surveillance gap. Methods We reviewed the 2026 NNDSS list of nationally notifiable conditions for P. aeruginosa. Because neither P. aeruginosa infection nor a resistant phenotype was present, NNDSS case counts were unable to be analysed. We therefore conducted a descriptive secondary analysis of CDC National Healthcare Safety Network (NHSN) reports for 2018–21 and the 2022 NHSN Antimicrobial Resistance (AR) Option report. Results In 2018–21 adult NHSN data, 11.9% of tested P. aeruginosa isolates from device-associated infections were MDR, compared with 3.9% from surgical-site infections. Among central-line-associated bloodstream infection isolates, MDR proportions were highest in long-term acute-care hospitals (LTACHs, 25.3%), followed by hospital intensive-care units (14.2%), hospital wards (11.9%) and oncology units (8.5%). Among catheter-associated urinary tract infection isolates, MDR phenotype was observed in 20.8% of LTACH isolates. In the 2022 AR Option report, carbapenem non-susceptibility exceeded 10% among community-onset isolates and approached 20% among hospital-onset isolates. Conclusions NNDSS cannot currently quantify the burden of MDR P. aeruginosa, but substantial resistance surveillance is available through NHSN and the CDC AR Laboratory Network. The principal gap is not an absence of surveillance data but fragmentation across systems with different populations, denominators, objectives and reporting mechanisms.
