title: The risk of seizures among the carbapenems: a meta-analysis.
abstract: OBJECTIVE
  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.affiliation: Pharmacy Services, Hines VA Hospital, Hines, IL, USA.
authors.forename: Joan P
authors.initials: JP
authors.lastname: Cannon
authors.affiliation: Department of Pharmacy Systems, Outcomes and Policy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Todd A
authors.initials: TA
authors.lastname: Lee
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Loyola University Chicago, Maywood, IL, USA.
authors.forename: Nina M
authors.initials: NM
authors.lastname: Clark
authors.affiliation: Baxter Healthcare, Deerfield, IL, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Setlak
authors.affiliation: 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.
authors.forename: Shellee A
authors.initials: SA
authors.lastname: Grim
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015780:Carbapenems / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D015377:Cilastatin / Q000009:adverse effects / Q000627:therapeutic use; D000077728:Cilastatin, Imipenem Drug Combination; D000077726:Doripenem; D004338:Drug Combinations; D000077727:Ertapenem; D006801:Humans; D015378:Imipenem / Q000009:adverse effects / Q000627:therapeutic use; D000077731:Meropenem; D012306:Risk; D012640:Seizures / Q000139:chemically induced* / Q000453:epidemiology*; D013845:Thienamycins / Q000009:adverse effects; D047090:beta-Lactams / Q000009:adverse effects
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D004338:Drug Combinations; D013845:Thienamycins; D047090:beta-Lactams; D015377:Cilastatin; D015378:Imipenem; D000077728:Cilastatin, Imipenem Drug Combination; D000077726:Doripenem; D000077731:Meropenem; D000077727:Ertapenem
keywords: doripenem; epileptogenic; ertapenem; imipenem; meropenem