Bactericidal action of ampicillin/sulbactam against intracellular mycobacteria

The resistance of mycobacteria to beta-lactam antibiotics is attributed to their ability to synthesize beta-lactamase. In our previous studies, beta-l actam/beta-lactamase-inhibitor combinations suppressed the growth of severa l mycobacteria in axenic cultures and ampicillin/sulbactam was bactericidal to Mycobacterium tuberculosis H37Rv in vitro, and to Mycobacterium leprae multiplying in mouse foot-pads. Since both these organisms multiply in phag ocytic cells in the host, it is important to know whether the drug combinat ion is active against mycobacteria multiplying in macrophages. We tested th e action of ampicillin/sulbactam against four potentially pathogenic (to hu mans or to animals) mycobacteria, M. simiae, M. haemophilum, M. avium, M. m icroti, when phagocytosed by mouse macrophages. Bacteria were exposed to mo nolayers of peritoneal macrophages harvested from BALB/c mice. Unphagocytos ed bacilli were removed and three concentrations of ampicillin/sulbactam we re tested. Optimum activity was observed at 100 mg/l which killed 58-97% of the mycobacteria within macrophages, as determined by the CFU. beta-lactam /beta-lactamase-inhibitors, especially ampicillin/sulbactam, might provide an effective alternative therapy against infections caused by mycobacteria resistant to other drugs. (C) 1999 Elsevier Science B.V. and International Society of Chemotherapy. All rights reserved.