Treatment of Carbapenem-Resistant Multidrug-Resistant Gram-Negative Bacilli with Intracerebroventricular Injection of Polymyxin B: A Retrospective Study

Abstract

Purpose

We evaluated the efficacy and administration time of intraventricular (IVT) polymyxin B in the treatment of carbapenem-resistant and multidrug-resistant/extensively drug-resistant (MDR/XDR) Gram-negative bacilli in central nervous system (CNS) infections and investigated prognostic factors.

Patients and Methods

This retrospective analysis comprised 41 post-surgical carbapenem-resistant CNS infections from October 2016 to October 2021. All patients were treated with effective intravenous antibiotics and IVT polymyxin B. Patient characteristics, therapeutic procedure, symptoms, cerebrospinal fluid (CSF) examination, laboratory tests, and complications were recorded. The effectiveness of IVT polymyxin B was evaluated using temperature, Glasgow Coma Scale, CSF contents, bacterial clearance rate, cure rate, and mortality. Mortality between early (7 days) and late administration of IVT polymyxin B was compared. Prognostic factors were evaluated using the pupillary light reflex and multiloculated hydrocephalus.

Results

The 41 patients acquired carbapenem-resistant MDR/XDR bacteria, including 24 Klebsiella pneumoniae, 15 Acinetobacter baumannii, 3 Pseudomonas aeruginosa, and 1 Enterobacter cloacae. The bacterial clearance rate was 32/41 (78.0%), and 9 patients (22.0%) with uncured bacterial infections died. Adverse events included 1 case of skin pigmentation. Among the 32 cured patients, 31 received a ventriculoperitoneal shunt, and 1 patient had an extraventricular drainage tube removed. Mortality in the late (>7 days) group was higher (39.1% vs 0%, P < 0.05). The group without pupillary light reflex showed a higher death rate (41.2% vs 8.3%; P < 0.05). The multiloculated hydrocephalus group had a higher mortality rate than that of the normal group (34.8% vs 5.6%, P < 0.05). All 32 cured patients were followed up for 9 to 66 months, and all survived without recurrent infections.

Conclusion

Intraventricular polymyxin B is an effective treatment for carbapenem-resistant MDR/XDR Gram-negative bacilli, with a 78% cure rate and significant mortality reduction if administered within 7 days of bacterial identification. Multiloculated hydrocephalus and the pupillary light reflex may be used as prognostic indicators of mortality.

Keywords:

• polymyxin B
• intracerebroventricular injection
• central nervous system infections
• cerebrospinal fluid
• prognosis

Abbreviations

CNS, central nervous system; CSF, cerebrospinal fluid; DP, delay period; GCS, Glasgow Coma Scale; IDSA, Infectious Diseases Society of America; ITH, intrathecal; IV, intravenous; IVT, intraventricular; MDR/XDR, multidrug-resistant/extensively drug-resistant.

Ethical Statement

The study protocol was approved by Aviation General Hospital Medical Ethics Committee. (Protocol Number: KY2022-073-02). The study was conducted in accordance with the revised Helsinki Declaration in 2013. Written informed consent was obtained from patients or guardians of patients with coma, a parent or legal guardian of patients under 18 years of age. Written informed consent was obtained from the patient or guardian to have the case details and any accompanying images published.

Acknowledgments

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis, and interpretation, or in all these areas; took part in drafting, revising, or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The author reports no conflicts of interest in this work.