Interaction of increased pressures of oxygen and sulfonamides on the in vitro and in vivo growth of pathogenic bacteria.

The objective of these experiments was to determine whether synergism will occur between increased oxygen tensions and PABA-folic acid inhibitors in vitro and in vivo. Initial in vitro experiments indicated that PO2 greater than or equal to 2.2 ATA alone exerts marked growth-inhibitory (static) effects. Oxygen at 2.2 ATA decreased the minimal inhibitory concentrations (MIC) of sodium sulfisoxazole (NaS) fivefold and trimethoprim (TMP), a sulfonamide potentiator, twofold. At 3.2 ATA O2, there was a twenty-fivefold decrease in MIC of NaS and a tenfold decrease for TMP: cidal effects were also obtained. There is a PO2 dependent increase in effectiveness of the combination of NaS + TMP, including cidal effects, in situations where static effects were noted in absence of increased oxygen levels. Similar effects were not obtained with air pressure controls. In goldfish infected with Vibrio anquillarum, 3.2 ATA O2 in combination with NaS increased survival from 20% to 75%. Similar results were not obtained with air pressure controls. Trimethoprim was toxic to goldfish. We conclude that increased oxygen tensions synergize with NaS or TMP, or both, in vitro to decrease their MIC and to produce bactericidal effects where bacteriostatic effects are normally found: oxygen also synergizes with NaS in vivo to markedly increase survival of goldfish.