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Therapeutic Methods and Therapies TCIM
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1.
Clin Infect Dis ; 78(1): 27-30, 2024 01 25.
Article in English | MEDLINE | ID: mdl-37584360

ABSTRACT

In a propensity-score-weighted cohort of 183 adults with carbapenem-resistant Enterobacterales bacteremia at 24 US hospitals, patients receiving short courses of active therapy (7-10 days, median 9 days) experienced similar odds of recurrent bacteremia or death within 30 days as those receiving prolonged courses of active therapy (14-21 days, median 14 days).


Subject(s)
Bacteremia , Sepsis , Adult , Humans , Bacteremia/drug therapy , Hospitals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Carbapenems/pharmacology , Carbapenems/therapeutic use , Microbial Sensitivity Tests , Drug Combinations , Ceftazidime
2.
Clin Infect Dis ; 75(1): 47-54, 2022 08 24.
Article in English | MEDLINE | ID: mdl-34618008

ABSTRACT

BACKGROUND: As cefiderocol is increasingly being prescribed in clinical practice, it is critical that we understand key mechanisms contributing to acquired resistance to this agent. METHODS: We describe a patient with acute lymphoblastic leukemia and a New Delhi metallo-ß-lactamase (NDM)-5-producing Escherichia coli intra-abdominal infection in whom resistance to cefiderocol evolved approximately 2 weeks after the start of treatment. Through whole-genome sequencing (WGS), messenger RNA expression studies, and ethylenediaminetetraacetic acid inhibition analysis, we investigated the role of increased NDM-5 production and genetic mutations contributing to the development of cefiderocol resistance, using 5 sequential clinical E. coli isolates obtained from the patient. RESULTS: In all 5 isolates, blaNDM-5 genes were identified. The minimum inhibitory concentrations for cefiderocol were 2, 4, and >32 µg/mL for isolates 1-2, 3, and 4-5, respectively. WGS showed that isolates 1-3 contained a single copy of the blaNDM-5 gene, whereas isolates 4 and 5 had 5 and 10 copies of the blaNDM-5 gene, respectively, on an IncFIA/FIB/IncFII plasmid. These findings were correlated with those of blaNDM-5 messenger RNA expression analysis, in which isolates 4 and 5 expressed blaNDM-5 1.7- and 2.8-fold, respectively, compared to, isolate 1. Synergy testing with the combination of ceftazidime-avibactam and aztreonam demonstrated expansion of the zone of inhibition between the disks for all isolates. The patient was successfully treated with this combination and remained infection free 1 year later. CONCLUSIONS: The findings in our patient suggest that increased copy numbers of blaNDM genes through translocation events are used by Enterobacterales to evade cefiderocol-mediated cell death. The frequency of increased blaNDM-5 expression in contributing to cefiderocol resistance needs investigation.


Subject(s)
Escherichia coli Infections , Escherichia coli , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Cephalosporins , DNA Copy Number Variations , Drug Resistance, Multiple, Bacterial/genetics , Escherichia coli/genetics , Escherichia coli Infections/drug therapy , Gene Expression , Humans , Microbial Sensitivity Tests , Plasmids , RNA, Messenger , beta-Lactamases/genetics , Cefiderocol
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