Activity of Carbapenems Combined with Clavulanate against Murine Tuberculosis

Abstract

ABSTRACTAlthough beta-lactam antibiotics are not considered as antituberculous drugs, it has been recently shown that the combination of carbapenems and clavulanate is bactericidalin vitro. We evaluated in a murine model of tuberculosis the activity of carbapenems alone and combined with clavulanate againstMycobacterium tuberculosis. Swiss mice infected intravenously with 3 × 105M. tuberculosisH37Rv 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 withM. tuberculosisand should be further evaluated.