title: Activity of carbapenems combined with clavulanate against murine tuberculosis.
abstract: Although beta-lactam antibiotics are not considered as antituberculous drugs, it has been recently shown that the combination of carbapenems and clavulanate is bactericidal in vitro. We evaluated in a murine model of tuberculosis the activity of carbapenems alone and combined with clavulanate against Mycobacterium tuberculosis. Swiss mice infected intravenously with 3 x 10⁵ M. tuberculosis H37Rv were treated for 4 weeks with clavulanate alone or imipenem, meropenem, and ertapenem alone or combined with clavulanate, whereas a positive control group was treated with isoniazid, and a negative control group was held without treatment. The combination of imipenem or meropenem plus clavulanate significantly improved survival. Among groups of mice with 100% survival, only isoniazid reduced lung CFU counts; the carbapenem-clavulanate combinations did not prevent bacterial growth. Although less active than isoniazid, the combinations of imipenem or meropenem plus clavulanate improved the survival of mice infected with M. tuberculosis and should be further evaluated.
authors.affiliation: Laboratoire de Bactériologie, Faculté de Médecine Pitié-Salpêtrière, 91 Boulevard de l'Hôpital, 75634 Paris Cedex 13, France. nicolas.veziris@upmc.fr
authors.forename: Nicolas
authors.initials: N
authors.lastname: Veziris
authors.forename: Chantal
authors.initials: C
authors.lastname: Truffot
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Mainardi
authors.forename: Vincent
authors.initials: V
authors.lastname: Jarlier
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D058491:Bacterial Load; D015780:Carbapenems / Q000008:administration & dosage*; D019818:Clavulanic Acid / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D008168:Lung / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008826:Microbial Sensitivity Tests; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D019818:Clavulanic Acid