The pharmacokinetics and pharmacodynamics of two multiple-dose regimens of piperacillin-tazobactam (3.375 g every 6 h and 4.5 g every 8 h) were evaluated at steady state for 12 healthy adult volunteers. Inhibitory and bactericidal activities for the two regimens were determined with five American Type Culture Collection (ATCC) organisms (Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Bacteroides fragilis). The percentage of time that plasma concentrations remained above the MIC (T > MIC) for each organism and dosage regimen was calculated. Areas under the inhibitory (AUIC 0-24 ) and bactericidal activity (AUBC 0-24 ) curves were calculated with the trapezoidal rule by using the reciprocal of the inhibitory and bactericidal titers determined for each dosage regimen. In order to assess the validity of predicted measures of bactericidal (AUC 0-24 /MBC) and inhibitory (AUC 0-24 /MIC) activity to determine bacteriological response to ␤-lactam antimicrobial agents, AUC 0-24 /MBC and AUC 0-24 /MIC values were compared with measured AUBC 0-24 and AUIC 0-24 values. Total body clearance values were equivalent for piperacillin (183.96 ؎ 22.66 versus 181.72 ؎ 19.54 ml/min/1.73 m 2 , P > 0.05) and tazobactam (184.71 ؎ 19.89 versus 184.87 ؎ 18.35 ml/min/1.73 m 2 , P > 0.05) following the administration of the 3.375-g-every-6-h and 4.5-gevery-8-h dosages, respectively. Comparison of area under the plasma concentration-time curve (AUC 0-24 ) for piperacillin (967.74 ؎ 135.56 g ⅐ h/ml versus 978.88 ؎ 140.96 g ⅐ h/ml) and tazobactam (120.14 ؎ 15.78 g ⅐ h/ml versus 120.01 ؎ 16.22 g ⅐ h/ml) revealed no significant differences (P > 0.05) between the 3.375-g-every-6-h and 4.5-g-every-8-h regimens, respectively. Both regimens provided T > MIC values of > 60% for all organisms tested. Measured values of bactericidal (AUBC) and inhibitory (AUIC) activity were significantly different (P < 0.05) from predicted values (AUC 0-24 /MBC and AUC 0-24 /MIC) for all organisms studied with the exception of the bactericidal activity for P. aeruginosa and S. aureus. Additionally, ATCC organisms possessing the same MICs and MBCs exhibited great differences in measured AUBC 0-24 and AUIC 0-24 values. Reasons for this difference may be inherent differences in organism specific susceptibility.

The combination of tazobactam with piperacillin results in an antimicrobial agent with enhanced activity against most beta-lactamase-producing organisms. Preliminary data indicate that piperacillin/tazobactam has proven clinical efficacy in the treatment of a variety of infections, especially polymicrobic infections.

A retrospective review of urine cultures obtained from patients at the University of Illinois Hospital revealed that the frequency of isolation of non-albicans Candida species increased significantly from 1990 to 1991 (p = 0.0003), while the frequency of isolation of Candida albicans species decreased significantly (p = 0.0006). Patients with urine cultures positive for non-albicans Candida species of Torulopsis glabrata during 1991 were identified for review. Sixty-seven patients were eligible for evaluation. Non-albicans candiduria developed in an average of 12 days. Identical fungal species were isolated from the blood following a positive urine culture in only two patients. Twenty patients were treated; candiduria persisted in 9 (45%), while resolution occurred in 11 (55%). The remaining 47 patients were not treated. Non-albicans candiduria persisted in 30 (64%) of these patients and resolved in 15 (32%); in the remaining two patients (4%) the microbiologic outcome was undetermined. The difference in microbiologic outcomes between treated and untreated patients was not significant using the Chi-square test (p = 0.170). Non-albicans candiduria developed rapidly, frequently persisted whether treated or untreated, and rarely progressed to candidemia.

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