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

    Author(s)
    Heffernan, Aaron James
    Sime, Fekade Bruck
    Sun, Jing
    Lipman, Prof Jeffrey
    Kumar, Anand
    Andrews, Katherine
    Ellwood, David
    Grimwood, Keith
    Roberts, Prof Jason
    Griffith University Author(s)
    Sun, Jing
    Ellwood, David A.
    Grimwood, Keith
    Andrews, Katherine T.
    Year published
    2019
    Metadata
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    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 ...
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    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.
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    Journal Title
    International Journal of Antimicrobial Agents
    Volume
    55
    Issue
    3
    DOI
    https://doi.org/10.1016/j.ijantimicag.2019.10.020
    Subject
    Medical microbiology
    Pharmacology and pharmaceutical sciences
    Science & Technology
    Life Sciences & Biomedicine
    Infectious Diseases
    Microbiology
    Pharmacology & Pharmacy
    Publication URI
    http://hdl.handle.net/10072/394093
    Collection
    • Journal articles

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