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Published on: February 23, 2021
Combined effect of pyrazinamide and ofloxacin within the human macrophage
J A Sbarbaro1, M D Iseman, A J Crowle
1Department of Medicine/Division General Internal Medicine, School of Medicine, University of Colorado Health Sciences Center, Denver 80262, USA.
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.
