Efficacy of ceftazidime-avibactam for the treatment of central nervous system infection caused by carbapenem-resistant Klebsiella pneumoniae after neurosurgery

TL;DR

This study shows that ceftazidime-avibactam combined with other antibiotics can effectively treat dangerous brain infections caused by drug-resistant bacteria after neurosurgery.

Contribution

The study demonstrates the efficacy of ceftazidime-avibactam in treating CNS infections caused by CRKP, a treatment previously unproven for this specific condition.

Findings

88.9% of patients treated with ceftazidime-avibactam achieved clinical and etiological cure.

Combination therapy with intracerebroventricular or intrathecal antibiotics showed promising results in resolving CNS infections.

Most patients showed neurological improvement, including recovery from a comatose state.

Abstract

Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections of the central nervous system (CNS) are associated with high mortality rates. These infections are particularly challenging to treat due to both bacterial resistance and the protective blood–brain barrier. This study aims to evaluate treatment outcomes for CRKP-induced CNS infections and provide insights into effective therapeutic strategies for similar cases.

A retrospective analysis was conducted on patients with CRKP-positive cerebrospinal fluid (CSF) samples admitted to the CSF Neurosurgery Department of the Aviation General Hospital between August 2019 and November 2021. Data collected included patient demographics, medical history, laboratory results, etiological findings, and antibiotic treatments. Nine patients with CRKP-induced CNS infections who were treated with Ceftazidime-avibactam (CAZ-AVI) were included in the analysis. The study assessed clinical features, treatment courses, and patient outcomes.

Of the nine patients, 88.9% (8/9) achieved both clinical and etiological cure. One patient experienced relapse 20 days after initial CSF culture negativity, with the family opting for discontinuation of further treatment. Following infection resolution, patients exhibited varying degrees of neurological improvement, including one case of complete recovery from a comatose state (GCS 6 to GCS 15). Treatment-related adverse effects included transient liver dysfunction in one patient and diarrhea in three, which resolved with symptomatic management. CSF drainage tubes were removed in three patients following treatment, while five required shunt surgery due to hydrocephalus. No relapses were reported in treated patients during a follow-up period of 3–12 months.

Intravenous CAZ-AVI combined with intracerebroventricular or intrathecal polymyxin B or amikacin demonstrated promising efficacy as a treatment regimen for CRKP-induced CNS infections.