The risk of seizures among the carbapenems: a meta-analysis Journal Article

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Authors: Cannon, J. P.; Lee, T. A.; Clark, N. M.; Setlak, P.; Grim, S. A.
Article Title: The risk of seizures among the carbapenems: a meta-analysis
Abstract: OBJECTIVES: A consensus exists among clinicians that imipenem/cilastatin is the most epileptogenic carbapenem, despite inconsistencies in the literature. METHODS: We conducted a meta-analysis of all randomized controlled trials comparing carbapenems with each other or with non-carbapenem antibiotics to assess the risk of seizures for imipenem, meropenem, ertapenem and doripenem. RESULTS: In the risk difference (RD) analysis, there were increased patients with seizure (2 per 1000 persons, 95% CI 0.001, 0.004) among recipients of carbapenems versus non-carbapenem antibiotics. This difference was largely attributed to imipenem as its use was associated with an additional 4 patients per 1000 with seizure (95% CI 0.002, 0.007) compared with non-carbapenem antibiotics, whereas none of the other carbapenems was associated with increased seizure. Similarly, in the pooled OR analysis, carbapenems were associated with a significant increase in the risk of seizures relative to non-carbapenem comparator antibiotics (OR 1.87, 95% CI 1.35, 2.59). The ORs for risk of seizures from imipenem, meropenem, ertapenem and doripenem compared with other antibiotics were 3.50 (95% CI 2.23, 5.49), 1.04 (95% CI 0.61, 1.77), 1.32 (95% CI 0.22, 7.74) and 0.44 (95% CI 0.13, 1.53), respectively. In studies directly comparing imipenem and meropenem, there was no difference in epileptogenicity in either RD or pooled OR analyses. CONCLUSIONS: The absolute risk of seizures with carbapenems was low, albeit higher than with non-carbapenem antibiotics. Although imipenem was more epileptogenic than non-carbapenem antibiotics, there was no statistically significant difference in the imipenem versus meropenem head-to-head comparison.
Journal Title: The Journal of antimicrobial chemotherapy
Volume: 69
Issue: 8
ISSN: 1460-2091; 0305-7453
Publisher: . Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy  
Date Published: 2014
Start Page: 2043
End Page: 2055
Language: ENG
DOI/URL:

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Notes: CI: (c) The Author 2014; JID: 7513617; OTO: NOTNLM; 2014/04/16 [aheadofprint]; ppublish