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Updated: Nov 25, 2025

Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
Successful de-escalation antibiotic therapy using cephamycins for sepsis caused by extended-spectrum
Tsukasa Kuwana1, Junko Yamaguchi1, Kosaku Kinoshita1
1Division of Emergency and Critical Care Medicine, Department of Acute Medicine, Nihon University School of Medicine, Tokyo, Japan.
Abstract:
Carbapenems are frequently used to treat infections caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E), but carbapenem-resistant Enterobacteriaceae bacteria are a clinical concern. Although cephamycins (cefmetazole; CMZ) have been shown to be effective against mild cases of ESBL-E infection, data on their use for severe ESBL-E infections with sepsis or septic shock remain scarce. Herein, we discuss a de-escalation therapy to CMZ that could be used after empiric antibiotic therapy in ICU patients with sepsis or septic shock caused by ESBL-E bacteremia. A sequence of 25 cases diagnosed with sepsis or septic shock caused by ESBL-E bacteria was evaluated. The attending infectious disease specialist physicians selected the antibiotics and decided the de-escalation timing. The median SOFA (Sequential Organ Failure Assessment) and APACHE II (Acute Physiology and Chronic Health Evaluation II) severity scores were 8 and 30; the rate of septic shock was 60%. Infections originated most frequently with urinary tract infection (UTI) (56%) and Escherichia coli (85%). Eleven patients were de-escalated to CMZ after vital signs were stable, and all survived. No patients died of UTI regardless of with or without de-escalation. The median timing of de-escalation antibiotic therapy after admission was 4 days (range, 3-6 days). At the time of de-escalation, the median SOFA score fell from 8 to 5, the median APACHE II score from 28 to 22, and the rate of septic shock from 55% to 0%. We conclude that for sepsis in UTI caused by ESBL-E bacteremia, de-escalation therapy from broad-spectrum antibiotics to CMZ is a potential treatment option when vital signs are stable.
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