In-vitro activity of ofloxacin against Mycobacterium tuberculosis and its clinical efficacy in multiply resistant pulmonary tuberculosis

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Abstract
The in-vitro susceptibilities to ofloxacin of 159 clinical sputum isolates of Mycobacterium tuberculosis, comprising 95 isolates sensitive to all drugs, 31 isolates resistant to streptomycin or isoniazid or both, 27 isolates resistant to streptomycin, isoniazid and rifampicin and six isolates resistant to rifampicin (and in three cases to other drugs) were determined. Favourable MICs of ofloxacin (0.63–1.25 mg/l) were demonstrated for 147 isolates (92%). Twenty-two patients with resistant strains (including one patient with rifampicin intolerance) were studied: ten were given 300 mg ofloxacin and ten were given 800 mg ofloxacin, once daily in both cases, together with second-line accompanying drugs, for nine months to one year. Two received 800 mg of ofloxacin once daily alone for similar periods. In the 300 mg-ofloxacin group and the 800 mg-ofloxacin group, five and eight patients, respectively, achieved culture conversion; the rest failed. In the former group, the peak serum ofloxacin concentrations were 3.71–8.08 mg/l and the mean sputum/serum ratio was 0–85. In the latter group, the corresponding values were 10–18.7 mg/l, and 0.76, respectively. All patients tolerated the drugs well. Analysing only patients with accompanying drugs, those on ofloxacin 800 mg once daily had more rapid sputum culture conversion than those on ofloxacin 300 mg once daily (Mann-Whitney Wilcoxon Rank Sum Test P < (0.05), indicating more rapid bacteriolysis and implying the definite efficacy of ofloxacin when used together with second-line accompanying drugs in the management of resistant tuberculosis.