β-lactam antibiotic versus combined β-lactam antibiotics and single daily dosing regimens of aminoglycosides for treating serious infections: A meta-analysis

No Thumbnail Available
File version
Author(s)
Heffernan, Aaron James
Sime, Fekade Bruck
Sun, Jing
Lipman, Prof Jeffrey
Kumar, Anand
Andrews, Katherine
Ellwood, David
Grimwood, Keith
Roberts, Prof Jason
Primary Supervisor
Other Supervisors
Editor(s)
Date
2019
Size
File type(s)
Location
License
Abstract

Background: Combining aminoglycosides with β-lactam antibiotics for treating serious infections has not been associated with reduced mortality in previous meta-analyses. However, the multiple daily aminoglycoside dosing regimen principally used in most of the included studies is inconsistent with current practice. Objective: To determine if a combination of an aminoglycoside administered as a single daily dose and a β-lactam antibiotic reduces all-cause mortality in patients compared with β-lactam antibiotic monotherapy. Methods: A systematic review and meta-analysis of clinical studies was performed (Prospero registration number #68506). Studies were included if they compared β-lactam antibiotic monotherapy with combined β-lactam and single daily dose aminoglycoside therapy for treating serious infections. Studies investigating multiple daily dosing aminoglycoside regimens, infective endocarditis and febrile neutropaenia were excluded. Study quality was assessed using the PEDro and Newcastle-Ottawa scoring systems. The end points for outcome analyses were 30-day all-cause mortality, clinical cure and nephrotoxicity. Results: Four randomised controlled trials and five retrospective cohort studies were analysed. Compared with β-lactam antibiotic monotherapy, single daily aminoglycoside dosing in combination with β-lactam antibiotics was not associated with reduced mortality compared with β-lactam antibiotic monotherapy (n = 3686, OR 0.82, 95% CI 0.63–1.08, P = 0.10, I2 42%). A subgroup analysis of cohort studies suggested reduced mortality with combination therapy (n = 3563, OR 0.79, 95% CI 0.64–0.99, P = 0.04, I2 32%). No increased risk of nephrotoxicity was identified (n = 1110, OR 1.31, 95% CI 0.83–2.09, P = 0.40, I2 0%). Conclusions: The existing evidence suggests no added survival benefit from a single daily dosing regimen of an aminoglycoside when combined with β-lactam antibiotics.

Journal Title

International Journal of Antimicrobial Agents

Conference Title
Book Title
Edition
Volume

55

Issue

3

Thesis Type
Degree Program
School
Publisher link
Patent number
Funder(s)
Grant identifier(s)
Rights Statement
Rights Statement
Item Access Status
Note
Access the data
Related item(s)
Subject

Medical microbiology

Pharmacology and pharmaceutical sciences

Microbiology

Science & Technology

Life Sciences & Biomedicine

Infectious Diseases

Microbiology

Pharmacology & Pharmacy

Persistent link to this record
Citation

Heffernan, AJ; Sime, FB; Sun, J; Lipman, PJ; Kumar, A; Andrews, K; Ellwood, D; Grimwood, K; Roberts, PJ, β-lactam antibiotic versus combined β-lactam antibiotics and single daily dosing regimens of aminoglycosides for treating serious infections: A meta-analysis, International Journal of Antimicrobial Agents, 2019, 55 (3)

Collections