Joan P Cannon1, Todd A Lee2, Nina M Clark3, Paul Setlak4, Shellee A Grim5. 1. Pharmacy Services, Hines VA Hospital, Hines, IL, USA. 2. Department of Pharmacy Systems, Outcomes and Policy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA. 3. Department of Medicine, Division of Infectious Diseases, Loyola University Chicago, Maywood, IL, USA. 4. Baxter Healthcare, Deerfield, IL, USA. 5. Department of Medicine, Division of Infectious Diseases, Loyola University Chicago, Maywood, IL, USA Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA sgrim@lumc.edu.
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.
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.
Authors: Justin R Lenhard; Jürgen B Bulitta; Terry D Connell; Natalie King-Lyons; Cornelia B Landersdorfer; Soon-Ee Cheah; Visanu Thamlikitkul; Beom Soo Shin; Gauri Rao; Patricia N Holden; Thomas J Walsh; Alan Forrest; Roger L Nation; Jian Li; Brian T Tsuji Journal: J Antimicrob Chemother Date: 2016-09-15 Impact factor: 5.790
Authors: Rajbharan Yadav; Cornelia B Landersdorfer; Roger L Nation; John D Boyce; Jürgen B Bulitta Journal: Antimicrob Agents Chemother Date: 2015-02-02 Impact factor: 5.191
Authors: Rajbharan Yadav; Jürgen B Bulitta; Roger L Nation; Cornelia B Landersdorfer Journal: Antimicrob Agents Chemother Date: 2016-12-27 Impact factor: 5.191