Objective: There is a paucity of published data to evaluate the efficacy and safety of imipenem (IPM) and piperacillin-tazobactam (PT) dosing regimens in the treatment of septic patients acquiring continuous renal replacement therapy (CRRT).
Methods and Materials: Critically-ill patients were grouped into short-stay and long-stay intensive care unit (ICU) patients. Pathogens were isolated from bloodstream infections in these patients. Minimum inhibitory concentration (MIC) value was determined by agar dilution method. Population PK models were introduced in this study, and differences in the likelihood of achieving efficacious and toxic exposures of IPM and PT for critically-ill patients were assessed.
Results: A total of 86 K. pneumoniae  bloodstream infection associated isolates were collected, and the MIC₅₀ and MIC₉₀ for short-stay ICU patients were 0.5/4 mg/L and 32/128 mg/L, respectively. IMP 0.5g q8h reached 90% probability of target attainment (PTA) against isolates with MICs ≤ 2 mg/L and was recommended to empirically treat short-stay ICU patients during CRRT based on the target of 40% ƒT>MIC. However, based on a more aggressive target of 100% ƒT>MIC, all the simulated IMP regimens except for IMP 1g q6h failed to achieve > 80% cumulative fraction of response (CFR) in such patients. Unfortunately, the risk of drug-related toxicity for IMP 1g q6h was relatively high (50– 85%). For PT, even the regimen of 4/0.5g q6h failed to provide sufficient antimicrobial exposure in short-stay ICU patients acquiring CRRT.
Conclusion: No dose adjustment was required for the conventional IMP and PT regimens in the critically-ill population acquiring CRRT. Empirical treatment of IMP 0.5g q8h/q6h, not for PT, may provide sufficient antimicrobial exposure for short-stay ICU patients during CRRT. PT should be used in the knowledge of MIC results.
Keywords: Klebsiella pneumoniae  infection, pharmacokinetic/pharmacodynamic, continuous renal replacement therapy; CRRT, intensive care unit; ICU