Combined effect of pyrazinamide and ofloxacin within the human macrophage.
METHODS
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).


METHODS
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.
Sbarbaro
J A
JA
Department of Medicine/Division General Internal Medicine, School of Medicine, University of Colorado Health Sciences Center, Denver 80262, USA.
Iseman
M D
MD
Crowle
A J
AJ
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008264:Macrophages / Q000382:microbiology*; D008297:Male; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development; D015242:Ofloxacin / Q000494:pharmacology*; D011718:Pyrazinamide / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D011718:Pyrazinamide; D015242:Ofloxacin