Might real-time pharmacokinetic/pharmacodynamic optimisation of high-dose continuous-infusion meropenem improve clinical cure in infections caused by KPC-producing Klebsiella pneumoniae?

The effect of real-time pharmacokinetic/pharmacodynamic (PK/PD) optimisation of high-dose continuousinfusion meropenem on the clinical outcome of patients receiving combination antimicrobial therapy for treatment of KPC-producing Klebsiella pneumoniae (KPC-Kp) infections was retrospectively assessed. Data for all patients with KPC-Kp-related infections who received antimicrobial combination therapy containing high-dose continuous-infusion meropenem optimised by means of therapeutic drug monitoring (TDM) were retrieved. Optimal PK/PD exposure was considered a steady-state concentration to minimum inhibitory concentration ratio (C-ss/MIC) of 1-4. Univariate binary logistic regression analysis was performed to identify independent predictors of clinical outcome. Among the 30 eligible patients, 53.3% had infections caused by meropenem-resistant KPC-Kp (MIC >= 16 mg/L). Tigecycline and colistin were the two antimicrobials most frequently combined with meropenem. Mean doses of continuousinfusion meropenem ranged from 1.7 to 13.2 g/daily. The C-ss/MIC ratio was >= 1 in 73.3% of cases and >= 4 in 50.0%. Clinical outcome was successful in 73.3% of cases after a median treatment length of 14.0 days. In univariate analysis, a significant correlation with successful clinical outcome was found for a C-ss/MIC ratio >= 1 (OR = 10.556, 95% CI 1.612-69.122; P = 0.014), a C-ss/MIC ratio >= 4 (OR = 12.250, 95% CI 1.268-118.361; P = 0.030) and a Charlson co-morbidity index of >= 4 (OR = 0.158, 95% CI 0.025-0.999; P = 0.05). High-dose continuous-infusion meropenem optimised by means of real-time TDM may represent a valuable tool in improving clinical outcome when dealing with the treatment of infections caused by KPC-Kp with a meropenem MIC <= 64 mg/L. (C) 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.