1533. Is Cation-Adjusted Mueller–Hinton Broth (CAMHB) Appropriate for Metallo-β-lactamase (MBL) Susceptibility Testing? Novel Insights in In Vitro–In Vivo Discordance Among MBL-Producing Enterobacteriaceae
Abstract
Abstract Background MBLs, which require Zn for catalytic activity, are a major contributor to high-level β-lactam resistance when tested using conventional CAMHB. We have previously reported marked reductions in meropenem (MEM) MICs in Zn-depleted media (Chelex-CAMHB and EDTA-CAMHB; Zn [C] 64, ≤0.0625 to 0.5, and ≤ 0.0625 to 0.5 mg/L, respectively. LVX MICs ranged from ≤ 0.0625 – > 64 mg/L. Neutropenic lung-infected ICR mice received a MEM HSR of 2g q8h [1.5 hours infusion], 2 lower MEM exposures or LVX 750 mg q24h HSR. Zn [C] were determined in the epithelial lining fluid (ELF) of infected mice. Results LVX displayed predictable in vivo efficacy consistent with its phenotypic profile irrespective of the media utilized for MIC testing (figure). Despite attaining zero %T> MIC using values generated in CAMHB, MEM HSR produced marked bacterial reductions against all MBL-producing isolates (figure). Reductions in MEM exposures produced bacterial killing concordant with its pharmacodynamic profile using Zn-depleted CAMHB MIC values. Zn [C] in infected murine ELF were undetectable, i.e., <0.002 mg/L. Conclusion Our results indicate that MEM in vivo efficacy is best represented by the pharmacodynamic profile generated using MICs determined in Zn-depleted media for MBL-producing Enterobacteriaceae. These observations are consistent with the case reports describing positive outcomes in MBL-infected patients following treatment with carbapenems (Infection 2018;46:1–13). Our…
Read the paper
Related studies
- Penicillins for Treatment of Pneumococcal Pneumonia: Does In Vitro Resistance Really Matter?
- Thiophenes—Naturally Occurring Plant Metabolites: Biological Activities and In Silico Evaluation of Their Potential as Cathepsin D Inhibitors
- Inhalable Mannosylated Rifampicin–Curcumin Co-Loaded Nanomicelles with Enhanced In Vitro Antimicrobial Efficacy for an Optimized Pulmonary Tuberculosis Therapy
- Development and validation of microbial bioassay for quantification of Levofloxacin in pharmaceutical preparations
- GC-MS Analysis and Biomedical Therapy of Oil from n-Hexane Fraction of Scutellaria edelbergii Rech. f.: In Vitro, In Vivo, and In Silico Approach
- Propranolol, chlorpromazine and diclofenac restore susceptibility of extensively drug-resistant (XDR)-Acinetobacter baumannii to fluoroquinolones
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.