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Effect of Different Piperacillin-Tazobactam Dosage Regimens on Synergy of the Combination with Tobramycin against Pseudomonas aeruginosa for the Pharmacokinetics of Critically Ill Patients in a Dynamic Infection Model
| Content Provider | MDPI |
|---|---|
| Author | Tait, Jessica R. Bilal, Hajira Rogers, Kate E. Lang, Yinzhi Kim, Tae-Hwan Zhou, Jieqiang Wallis, Steven C. Bulitta, Jürgen B. Kirkpatrick, Carl M. J. Paterson, David L. Lipman, Jeffrey Bergen, Phillip J. Roberts, Jason A. Landersdorfer, Cornelia B. |
| Copyright Year | 2022 |
| Description | We evaluated piperacillin-tazobactam and tobramycin regimens against Pseudomonas aeruginosa isolates from critically ill patients. Static-concentration time-kill studies (SCTK) assessed piperacillin-tazobactam and tobramycin monotherapies and combinations against four isolates over 72 h. A 120 h-dynamic in vitro infection model (IVM) investigated isolates Pa1281 $(MIC_{piperacillin}$ 4 mg/L, $MIC_{tobramycin}$ 0.5 mg/L) and CR380 $(MIC_{piperacillin}$ 32 mg/L, $MIC_{tobramycin}$ 1 mg/L), simulating the pharmacokinetics of: (A) tobramycin 7 mg/kg q24 h (0.5 h-infusions, $t_{1/2}$ = 3.1 h); (B) piperacillin 4 g q4 h (0.5 h-infusions, $t_{1/2}$ = 1.5 h); (C) piperacillin 24 g/day, continuous infusion; A + B; A + C. Total and less-susceptible bacteria were determined. SCTK demonstrated synergy of the combination for all isolates. In the IVM, regimens A and B provided initial killing, followed by extensive regrowth by 72 h for both isolates. C provided >4 $log_{10}$ CFU/mL killing, followed by regrowth close to initial inoculum by 96 h for Pa1281, and suppressed growth to <4 $log_{10}$ CFU/mL for CR380. A and A + B initially suppressed counts of both isolates to <1 $log_{10}$ CFU/mL, before regrowth to control or starting inoculum and resistance emergence by 72 h. Overall, the combination including intermittent piperacillin-tazobactam did not provide a benefit over tobramycin monotherapy. A + C, the combination regimen with continuous infusion of piperacillin-tazobactam, provided synergistic killing (counts <1 $log_{10}$ CFU/mL) of Pa1281 and CR380, and suppressed regrowth to <2 and <4 $log_{10}$ CFU/mL, respectively, and resistance emergence over 120 h. The shape of the concentration–time curve was important for synergy of the combination. |
| Starting Page | 101 |
| e-ISSN | 20796382 |
| DOI | 10.3390/antibiotics11010101 |
| Journal | Antibiotics |
| Issue Number | 1 |
| Volume Number | 11 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2022-01-13 |
| Access Restriction | Open |
| Subject Keyword | Antibiotics Pharmacology and Pharmacy Dynamic Infection Model Pseudomonas Aeruginosa Pharmacokinetics Pharmacodynamics |
| Content Type | Text |
| Resource Type | Article |
