Author(s): Sbarbaro JA, Iseman MD, Crowle AJ
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Abstract 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 micrograms/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.
This article was published in Tuber Lung Dis
and referenced in Air & Water Borne Diseases