Turbidimetric and microscopic analysis of Bacteroides fragilis exposed to tazobactam and piperacillin alone and in combination.
Tazobactam, a non-amino penicillanic acid sulfone, is a new beta-lactamase inhibitor and acts synergistically with piperacillin against clinical isolates of beta-lactamase-producing Bacteroides fragilis. The effectiveness of this inhibitor has been demonstrated by reduction of piperacillin MIC values and growth curves in two combinations (ratio 8:1 and 4:1). Tazobactam has an intrinsic activity against B. fragilis (MIC = 4-8 micrograms/ml). Phase contrast microscopy of treated cells showed cell-wall-deficient bacteria, predominantly filaments for piperacillin and spheric bodies for tazobactam. The combination of these two drugs induced large bulging filaments. This would suggest that with this organism, tazobactam binds to PBP2 while piperacillin binds to PBP3. The growth curves obtained with the MS-2 system showed: (1) a significant deviation (lower OD value) from the control curve with piperacillin at 1/4 MIC and numerous irregularities as compared to the control, due to the presence of filament clusters; (2) a deviation from the control curves without irregularities, quite different than these observed with piperacillin while using tazobactam at 1/8 MIC, and (3) a deviation from the control curve for lower piperacillin values in piperacillin-tazobactam combinations (8:1-4:1). In conclusion, the synergistic efficiencies of piperacillin/tazobactam against B. fragilis act in two ways, inhibition of beta-lactamase and a probable competition of PBPs.
Yourassowsky
E
E
Brugmann University Hospital, Brussels, Belgium.
Van der Linden
M P
MP
Lismont
M J
MJ
Crokaert
F
F
D001441:Bacteroides fragilis / Q000187:drug effects* / Q000254:growth & development; D004352:Drug Resistance, Microbial; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000494:pharmacology; D006801:Humans; D009391:Nephelometry and Turbidimetry / Q000379:methods; D010397:Penicillanic Acid / Q000494:pharmacology*; D010878:Piperacillin / Q000494:pharmacology*; D000078142:Tazobactam
D010397:Penicillanic Acid; D000078142:Tazobactam; D010878:Piperacillin