Antibiotics

Background/Objectives: Carbapenems remain the standard treatment for infections caused by extended-spectrum β-lactamase–producing Enterobacterales (ESBL-E), but their widespread use contributes to the emergence of carbapenem resistance. Cephamycins have been proposed as carbapenem-sparing alternatives because of their relative stability against ESBL-mediated hydrolysis; however, their clinical effectiveness remains uncertain. We aimed to compare the effectiveness of cephamycins versus carbapenems as definitive treatment for ESBL-E infections. Methods: We searched Scopus, PubMed, and Embase for studies comparing cephamycins with carbapenems for the treatment of ESBL-producing Enterobacterales infections, with the search conducted through January 2026. Observational studies and randomized trials comparing cephamycins (cefmetazole, flomoxef, cefoxitin) with carbapenems in adult patients with microbiologically confirmed ESBL-E infections were included. The primary outcome was all-cause mortality; secondary outcomes were clinical and microbiological cure. Risk of bias was assessed using ROBINS-I, and data were pooled using random-effects models. Results: Ten retrospective cohort studies (n = 653 for mortality) were included. Cephamycins were associated with a non-significant trend toward lower mortality compared with carbapenems (OR 0.48, 95% CI 0.22–1.03). Subgroup analyses suggested a potential benefit in Escherichia coli and urinary-source infections, whereas no advantage was observed in Klebsiella pneumoniae or non-urinary bloodstream infections. No significant differences were found for clinical or microbiological cure. The certainty of evidence was rated as very low. Conclusions: Cephamycins may represent a carbapenem-sparing option in carefully selected patients with low-risk ESBL-E infections, particularly urinary-source infections caused by E. coli. However, the current evidence is limited to retrospective observational studies with very low certainty and should be considered hypothesis-generating rather than practice-changing. Adequately powered randomized controlled trials are needed to confirm these findings.

Objectives: The fourth-generation fluoroquinolone delafloxacin (DFX) is propagated as a novel (oral) treatment option for infections with multidrug-resistant Gram-negatives. To date, efficacy data for Enterobacterales is only available for wild-type isolates but not for those with pre-existing resistance against third-generation fluoroquinolones. Methods: One hundred twenty-nine non-duplicate clinical isolates of Enterobacterales that demonstrated ciprofloxacin resistance in VITEK 2 testing were collected and analyzed for CIP and DFX minimum inhibitory concentrations (MICs) via broth microdilution. Results: DFX MICs ranged from 0.5 to ≥ 16 mg L⁻¹ (median: 4 mg L⁻¹). All Escherichia coli isolates (n = 56; 43% of all isolates), the only species with EUCAST breakpoints, were classified as DFX resistant. All other isolates belonging to species for which EUCAST epidemiological cut-offs (ECOFFs) are available (n = 64; 50% of all isolates) demonstrated MICs above the ECOFF. With a minimum and median MIC of 2 and 8 mg L⁻¹, respectively, the remaining isolates (6%) achieved similar results. A moderate correlation between the MIC values of the two fluoroquinolones was found. For the majority of isolates (64%), other oral options for antibiotic therapy, such as amoxicillin/clavulanic acid and trimethoprim/sulfamethoxazole, were still available. Conclusions: Our data suggests that, compared to CIP, DFX does not demonstrate increased in vitro efficacy against fluoroquinolone-resistant Enterobacterales. Subsequent DFX testing seems to be of limited additional value.

Background/Objectives: Proteus mirabilis is an opportunistic pathogen and a potential reservoir of clinically important antimicrobial resistance genes in animal production. However, mink-derived P. mirabilis remains poorly characterized. This study investigated multidrug-resistant and extended-spectrum β-lactamase (ESBL)-producing isolates from intensive mink farms, focusing on clinically important β-lactamase genes, their genomic backgrounds, and mobile genetic elements (MGEs). Methods:  Among 373 fecal and intestinal-content samples collected from six mink farms in Shandong Province, China, 68 P. mirabilis isolates were recovered. All underwent antimicrobial susceptibility testing, ESBL confirmation, and virulence-associated phenotypic assays. The 39 ESBL-positive isolates underwent whole-genome sequencing, followed by analyses of antimicrobial resistance genes, the pangenome, and MGEs and comparison with 198 publicly available genomes. Results:  Of the 373 sampled mink, 68 (18.2%) were P. mirabilis positive, and 39 (10.5%) carried ESBL-producing isolates. Of the 68 isolates, 63 (92.6%) were multidrug resistant, and 39 (57.4%) were ESBL positive. All exhibited strong biofilm formation and urease activity, while 83.8% showed strong swarming motility. Among the sequenced isolates, bla_CTX-M genes were identified in 32 isolates and bla_NDM-1 in three. Both bla_CTX-M-65- and bla_NDM-1-positive isolates were distributed across multiple genomic lineages, with bla_CTX-M-65 additionally detected in multiple sequence types. This distribution indicates that these genes were not restricted to a single clone but does not demonstrate horizontal gene transfer. MGE-associated features showed same-contig co-occurrence with several resistance genes, notably IS903–bla_CTX-M-65 and ISAba125–bla_NDM-1. The sequenced isolates also exhibited substantial accessory-genome diversity and widely distributed virulence determinants associated with adhesion, motility, iron acquisition, and toxin-related functions. Conclusions:  Mink-derived P. mirabilis exhibited extensive multidrug resistance and carried clinically important β-lactamase genes across diverse genomic backgrounds. These findings support the inclusion of fur-animal production systems in One Health surveillance of antimicrobial-resistant P. mirabilis.