Combined effect of pyrazinamide and ofloxacin within the human macrophage

Setting: Recent reports of outbreaks of multidrug resistant tuberculosis have raised questions as to the most appropriate therapeutic response for those exposed to such organisms, A recent Centers for Disease Control National Action Plan suggests the combination of pyrazinamide (PZA) and a quinolone as a potential preventive therapy regimen. Objective: Prior studies in the ex-vivo human macrophage model have shown PZA to have only a bacteriostatic effect and, in addition, to diminish the bactericidal effect of rifampin, This study was designed to quantify the intramacrophage antimycobacterial effect of PZA when combined with a quinolone (ofloxacin). Design: Forty mu g/ml of PZA was combined with varying concentrations of ofloxacin and administered to human macrophages infected with virulent tubercle bacilli; drug sequencing was also studied. Results: A clinically achievable level of PZA enhances the antimycobacterial effect of low non-bactericidal levels of ofloxacin and does not impede the bactericidal effect of a higher clinically effective level of ofloxacin, Unlike the combination of PZA and rifampin, these interactive effects are not affected by the sequence of drug administration. Conclusions: Findings support the use of these agents as a potentially effective preventive therapy combination for individuals exposed to multidrug resistant tuberculous organisms.