Carbapenems: a potent class of antibiotics.
The purpose of this review is to assess the relative strengths and weaknesses of individual members of the carbapenem class of antibiotics. Clinical trials and review articles were identified from a Medline search (1979 - July 2006), in addition to, reference citations from identified publications, abstracts from the Interscience Conferences on Antimicrobial Agents and Chemotherapy and the 12th International Congress on Infectious Disease, and package inserts. Articles in English were reviewed, with emphasis on those containing efficacy or safety data. Carbapenems bind to critical penicillin-binding proteins, disrupting the growth and structural integrity of bacterial cell walls. They provide enhanced anaerobic and Gram-negative coverage as compared with other beta-lactams and their stability against extended-spectrum beta-lactamases (ESBLs) makes them an effective treatment option. The most common adverse effects are infusion-site complications and gastrointestinal distress. Ertapenem has limited efficacy against non-fermenting, Gram-negative bacteria, restricting its use to community-acquired infections. Imipenem is slightly more effective against Gram-positive organisms and meropenem slightly more effective against Gram-negative organisms. However, both have broad-spectrum activity, including non-fermenting, Gram-negative bacteria. Among non-fermenting, Gram-negatives, resistance to imipenem in particular is increasing. Doripenem is in late-stage clinical development and combines the broad-spectrum coverage of imipenem and meropenem, and more potent activity against Pseudomonas aeruginosa. Due to the increasing challenges represented by ESBLs and multi-drug resistant organisms, the carbapenems are assuming a greater role in the treatment of serious infections. Imipenem and meropenem are presently available and have been shown to be effective against nosocomial infections. Doripenem is an investigational carbapenem that has completed Phase III clinical trials and that has the potential to improve on this efficacy and minimize the emergence of resistance to the carbapenem class.
Nicolau
David P
DP
Hartford Hospital, Center for Anti-Infective Research and Development, 80 Seymour Street, Hartford, Connecticut 06102-5037, USA. dnicola@harthosp.org
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001419:Bacteria / Q000187:drug effects; D015780:Carbapenems / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D000077726:Doripenem; D000077727:Ertapenem; D006801:Humans; D015378:Imipenem / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D000077731:Meropenem; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013845:Thienamycins / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D047090:beta-Lactams / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D013845:Thienamycins; D047090:beta-Lactams; D015378:Imipenem; D000077726:Doripenem; D000077731:Meropenem; D000077727:Ertapenem