Utilizing Ceftazidime/Avibactam Therapeutic Drug Monitoring in the Treatment of Neurosurgical Meningitis Caused by Difficult-to-Treat Resistant Pseudomonas aeruginosa and KPC-Producing Enterobacterales

Mohamad Yasmin, Amir Nutman, Lu Wang, Steven Marshall, Ke Chen, Jiping Wang, Dafna Yahav, Liad Lupinsky, Andrea M. Hujer, Adarsh Bhimraj, David van Duin, Jian Li, Robert A. Bonomo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background. Central nervous system (CNS) infections caused by Klebsiella pneumoniae carbapenemase (KPC)–producing Enterobacterales and difficult-to-treat resistant (DTR) Pseudomonas aeruginosa represent a formidable clinical challenge. Antimicrobial regimens that efficiently penetrate the cerebrospinal fluid (CSF) and achieve sufficient concentrations associated with microbiologic and clinical cure are limited. We evaluated therapy with ceftazidime-avibactam (CAZ-AVI) in order to guide precise dosing in the treatment of CNS infections. Methods. Therapeutic drug monitoring (TDM) was performed in 3 patients with health care–associated ventriculitis and meningitis (HAVM) using CAZ-AVI 2.5 g infused intravenously every 8 hours as standard and extended infusion. Simultaneous CSF and plasma samples were obtained throughout the dosing interval in each patient. Concentrations of CAZ and AVI were determined by liquid chromatography/mass spectrometry. Results. Bacterial identification revealed KPC-producing Klebsiella pneumoniae (KPC-Kp), DTR Pseudomonas aeruginosa, and KPC-producing Enterobacter cloacae (KPC-Ent.c). All isolates were resistant to carbapenems. The minimum inhibitory concentrations (MICs) of CAZ-AVI were 0.25/4, 4/4, and 0.25/4 μg/mL, respectively. CAZ and AVI concentrations were determined in CSF samples ranging from 29.0 to 15.0 µg/mL (CAZ component) and 4.20 to 0.92 µg/mL (AVI component), respectively. AVI achieved concentrations ≥1 µg/mL in 11 out of 12 CSF samples collected throughout the dosing interval. Clinical and microbiologic cure were attained in all patients. Conclusions. Postinfusion concentrations of CAZ-AVI were measured in plasma and CSF samples obtained from 3 patients with complicated CNS infections caused by antimicrobial-resistant isolates. The measured concentrations revealed that standard CAZ and AVI exposures sufficiently attained values correlating to 50% fT > MIC, which are associated with efficient bacterial killing.

Original languageEnglish
Article numberofad507
JournalOpen Forum Infectious Diseases
Volume10
Issue number11
DOIs
StatePublished - 1 Nov 2023

Keywords

  • Klebsiella pneumoniae carbapenemase
  • Pseudomonas aeruginosa
  • ceftazidime-avibactam
  • central nervous system infection
  • therapeutic drug monitoring

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