Drug action against intracellularly growingMycobacterium xenopi

Abstract

The intracellular growth kinetics ofMycobacterium xenopi was studied in the murine J-774 macrophage cell line model. During the initial 4 days of infection, the bacilli divided about every 33 h. Electron microscopy of infected macrophages showed that bacteria inside phagosomes were surrounded by a protective electron-transparent zone (ETZ). This model was used for comparing the extracellular and intracellular activities of the following drugs: pristinamycin (PRISTINA), isoniazid (INH), clofazimine (CLOFA), rifabutin (=ansamycin; ANSA), rifampicine (RIFA), streptomycin (SM), ethambutol (EMB), and five fluoroquinolones, namely, ciprofloxacin (CIPRO), ofloxacin (OFLO), pefloxacin (PEFLO), enoxacin (ENOX) and norfloxacin (NORFLO). All the drugs were tested within their obtainable serum level concentrations in man. Under these conditions, CLOFA, SM, CIPRO, and OFLO were highly active against intracellularly growingM. xenopi, INH and RIFA were moderately active, whereas ANSA, PRISTINA, EMB, PEFLO, ENOX, and NORFLO were only growth inhibiting. The comparison of these data with extracellular activities of the same drugs underlined the discrepancies observed in test-tube drug activity evaluation and its correlation with results of chemotherapy in patients in whom the drug has essentially an intracellular bacterial killing role.