Cefiderocol is a parenteral siderophore cephalosporin, with a catechol-containing 3′ substituent. We evaluated its MICs against gram-negative bacteria, using iron-depleted Mueller-Hinton broth. The panel comprised 305 Enterobacterales, 111 P. aeruginosa and 99 A. baumannii, all selected for carbapenem resistance and multi-resistance to other agents. At 2 and 4 μg/ml cefiderocol inhibited 78.7% and 92.1% respectively of all Enterobacterales tested, with rates of 80-100% for isolates with all modes of carbapenem resistance except NDM enzymes (41.0% inhibited at 2 μg/ml, 72.1% at 4 μg/ml) or combinations of ESBL and porin-loss (61.5% inhibited at 2 μg/ml, 88.5% at 4 μg/ml). Cefiderocol also inhibited 81.1% and 86.5% of all P. aeruginosa at 2 and 4 μg/ml respectively, with rates of 80-100% for isolates with VIM, IMP, GES or VEB β-lactamases and slightly lower rates for those with NDM (45.5% at 2 μg/ml and 72.7% at 4 μg/ml) and PER (66.7% at 2 μg/ml and 73.3% at 4 μg/ml) enzymes; 63.3% of P. aeruginosa were inhibited at the FDA's 1 μg/ml breakpoint. Lastly, cefiderocol 2 and 4 μg/ml inhibited 80.8% and 88.9% of the A. baumannii isolates respectively, with rates >85% for isolates with OXA-51-like, -23, -24, or -58 enzymes and 50% at 2 μg/ml and 80% at 4 μg/ml for those with NDM carbapenemases. Dipicolinic acid and avibactam weakly potentiated cefiderocol against Enterobacterales with MBLs and serine carbapenemase respectively, indicating incomplete β-lactamase stability.
Zidebactam represents a second triple-action DBO following RG6080, with lower MICs for Enterobacteriaceae and P. aeruginosa . Clinical evaluation of cefepime/zidebactam must critically evaluate the reliance that can be placed on this direct antibacterial activity and on the enhancer effect as well as β-lactamase inhibition.
Asymptomatic carriage of methicillin-resistant Staphylococcus aureus (MRSA) can predispose the host to a wide range of infections. To inform public health strategies, this study sought to determine the prevalence and the phenotypic and genotypic characteristics of MRSA from nasal swabs of health care workers (HCWs) and other healthy individuals in Jordan. Overall, 716 nasal swabs were collected from 297 HCWs, 141 adults and 278 children in the community. MRSA was recovered from 56 (7.8%) nasal swabs, which represented carriage rates of 10.1%, 4.3% and 7.2% among HCWs, adults and children, respectively. The MRSA isolates were resistant to oxacillin (100%), erythromycin (42.8%), tetracycline (37.5%), clindamycin (5.3%), fucidin (5.3%), and ciprofloxacin (3.5%). A total of 17 different spa types belonging to eight different clonal complexes (CCs) were identified. All isolates were mecA positive, and mecC-MRSA was not detected. Analysis of the staphylococcal cassette chromosome mec (SCCmec) elements revealed that the majority (54; 96.4%) of the samples harbored the smaller type IV and V elements (the most common were SCCmec IVa or IVc, and there were two each of the IVg and V elements), and two were nontypable. The genes for Panton-Valentine leukocidin (luk-PV) were detected in 5.4% of the study isolates. A tst-positive, CC22-MRSA-SCCmecIVa clone (spa type t223) was identified as the dominant MRSA lineage among the nasal carriage isolates from both HCWs and other individuals (adults and children) in the community. These findings provide important information for public health personnel for the formulation of effective infection prevention and control strategies. Studies to further our understanding of the distribution, pathogenicity, transmissibility and fitness of this lineage would be prudent.
Reduced susceptibility to trimethoprim of DHFR enzymes carrying substitutions L(41)F, F(99)S, F(99)Y and H(150)R appears to result from structural changes that reduce trimethoprim binding to the enzyme. However, the mutations conferring trimethoprim resistance are not associated with fitness costs in vitro, suggesting that the survival of trimethoprim-resistant strains emerging in the clinic may not be subject to a fitness disadvantage.
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