Systematic Review of Beta-Lactam vs. Beta-Lactam plus Aminoglycoside Combination Therapy in Neutropenic Cancer Patients

Author:

Ishikawa Kazuhiro1ORCID,Nakamura Tomoaki2,Kawai Fujimi3ORCID,Ota Erika45,Mori Nobuyoshi1ORCID

Affiliation:

1. Department of Infectious Diseases, St. Luke’s International Hospital, Tokyo 104-8560, Japan

2. Department of Pulmonary Medicine, Thoracic Center, St. Luke’s International Hospital, Tokyo 104-8560, Japan

3. Library, Department of Academic Resources, St. Luke’s International University, Tokyo 104-0044, Japan

4. Global Health Nursing, Graduate School of Nursing Sciences, St. Luke’s International University, Tokyo 104-0044, Japan

5. Tokyo Foundation for Policy Research, Tokyo 106-0032, Japan

Abstract

We performed a systematic review of studies that compared beta-lactams vs. beta-lactams plus aminoglycosides for the treatment of febrile neutropenia in cancer patients. Method: We searched CENTRAL, MEDLINE, and Embase for studies published up to October 2023, and randomized controlled trials (RCTs) that compared anti-Pseudomonas aeruginosa beta-lactam monotherapy with any combination of an anti-Pseudomonas aeruginosa beta-lactam and an aminoglycoside were included. Result: The all-cause mortality rate of combination therapy showed no significant differences compared with that of monotherapy (RR 0.99, 95% CI 0.84 to 1.16, high certainty of evidence). Infection-related mortality rates showed that combination therapy had a small positive impact compared with the intervention with monotherapy (RR 0.83, 95% CI 0.66 to 1.05, high certainty of evidence). Regarding treatment failure, combination therapy showed no significant differences compared with monotherapy (RR 0.99, 95% CI 0.94 to 1.03, moderate certainty of evidence). In the sensitivity analysis, the treatment failure data published between 2010 and 2019 showed better outcomes in the same beta-lactam group (RR 1.10 [95% CI, 1.01–1.19]). Renal failure was more frequent with combination therapy of any daily dosing regimen (RR 0.46, 95% CI 0.36 to 0.60, high certainty of evidence). Conclusions: We found combining aminoglycosides with a narrow-spectrum beta-lactam did not spare the use of broad-spectrum antibiotics. Few studies included antibiotic-resistant bacteria and a detailed investigation of aminoglycoside serum levels, and studies that combined the same beta-lactams showed only a minimal impact with the combination therapy. In the future, studies that include the profile of antibiotic-resistant bacteria and the monitoring of serum aminoglycoside levels will be required.

Publisher

MDPI AG

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