Optimal Empiric Treatment for Klebsiella pneumoniae Infections in Short-Stay ICU Patients During Continuous Renal Replacement Therapy: Results from a Population Pharmacokinetic/Pharmacodynamic Analysis

Abstract

Yuhong Jin,1 Haiyan Mao,1 Bingyang Liu,1 Fen Zhou,1 Junjie Yang,1 Lei Xu,1 Jingtao Tong,2 Chen Huang,3 Yi Ding1 1Department of Intensive Care, Lihuili Hospital, Ningbo Medical Center, Ningbo, People’s Republic of China; 2Department of Radiotherapy, Lihuili Hospital, Ningbo Medical Center, Ningbo, People’s Republic of China; 3Department of Respiratory Medicine, Lihuili Hospital, Ningbo Medical Center, Ningbo, People’s Republic of ChinaCorrespondence: Chen HuangDepartment of Respiratory Medicine, Lihuili Hospital, Ningbo Medical Center, Ningbo 315000, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected] DingDepartment of Intensive Care, Lihuili Hospital, Ningbo Medical Center, Ningbo 315000, People’s Republic of ChinaTel [phone]Email [email protected]: 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

Keywords

• klebsiella pneumoniae infection
• pharmacokinetic/pharmacodynamic
• continuous renal replacement therapy
• intensive care unit.