Projects per year
Abstract
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 (MICpiperacillin 4 mg/L, MICtobramycin 0.5 mg/L) and CR380 (MICpiperacillin 32 mg/L, MICtobramycin 1 mg/L), simulating the pharmacokinetics of: (A) tobramycin 7 mg/kg q24 h (0.5 h-infusions, t1/2 = 3.1 h); (B) piperacillin 4 g q4 h (0.5 h-infusions, t1/2 = 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 log10 CFU/mL killing, followed by regrowth close to initial inoculum by 96 h for Pa1281, and suppressed growth to <4 log10 CFU/mL for CR380. A and A + B initially suppressed counts of both isolates to <1 log10 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 log10 CFU/mL) of Pa1281 and CR380, and suppressed re-growth to <2 and <4 log10 CFU/mL, respectively, and resistance emergence over 120 h. The shape of the concentration–time curve was important for synergy of the combination.
Original language | English |
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Article number | 101 |
Number of pages | 13 |
Journal | Antibiotics |
Volume | 11 |
Issue number | 1 |
DOIs | |
Publication status | Published - Jan 2022 |
Keywords
- Dynamic infection model
- Pharmacodynamics
- Pharmacokinetics
- Pseudomonas aeruginosa
Projects
- 3 Finished
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Developing an integrated approach to precision medicine targeting antimicrobial resistance of bacterial 'superbugs'
Landersdorfer, C. (Primary Chief Investigator (PCI)), Oliver, A. (Chief Investigator (CI)) & Nation, R. (Chief Investigator (CI))
NHMRC - National Health and Medical Research Council (Australia)
1/01/20 → 31/12/24
Project: Research
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Overcoming multidrug-resistant hypermutable Pseudomonas aeruginosa via antibiotic combinations
Landersdorfer, C. (Primary Chief Investigator (PCI)), Oliver, A. (Chief Investigator (CI)), Harper, M. (Chief Investigator (CI)) & Nation, R. (Chief Investigator (CI))
NHMRC - National Health and Medical Research Council (Australia)
1/01/19 → 31/12/23
Project: Research
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Centre for REdefining antibiotic use to reDUce resistanCE and prolong the lives of antibiotics (REDUCE)
Roberts, J. A. (Primary Chief Investigator (PCI)), Lipman, J. (Chief Investigator (CI)), Peake, S. (Chief Investigator (CI)), Turnidge, J. D. (Chief Investigator (CI)), Slavin, M. A. (Chief Investigator (CI)), Hopkins, P. M. A. (Chief Investigator (CI)), Landersdorfer, C. (Chief Investigator (CI)), Paul, S. K. (Chief Investigator (CI)), De Waele, J. (Chief Investigator (CI)), Joynt, G. (Chief Investigator (CI)) & Udy, A. (Associate Investigator (AI))
1/12/15 → 30/11/20
Project: Research