Piperacillin-tazobactam dosing in anuric acute kidney injury patients receiving continuous renal replacement therapy.

INTRODUCTION: To determine appropriate dosing of piperacillin-tazobactam in critically ill patients receiving continuous renal replacement therapy (CRRT). METHODS: The databases of PubMed, Embase, and ScienceDirect were searched. We used the Medical Subject Headings of "piperacillin-tazobactam," "CRRT," and "pharmacokinetics" or related terms or synonym to identify the studies for reviews. A one-compartment pharmacokinetic model was conducted to predict piperacillin levels for the initial 48 h of therapy. The pharmacodynamic target was 50% of free drug level above the minimum inhibitory concentration (MIC) and 4 times of the MIC. The dose that achieved at least 90% of the probability of target attainment was defined as an optimal dose. RESULTS: Our simulation study reveals that the dosing regimen of piperacillin-tazobactam 12 g/day is appropriate for treating Pseudomonal infection with KDIGO recommended effluent rate of 25-35 mL/kg/h. The MIC values of each setting were an important factor to design piperacillin-tazobactam dosing regimens. CONCLUSION: The Monte Carlo simulation can be a useful tool to evaluate drug dosing in critically ill acute kidney injury patients receiving CRRT when limited pharmacokinetic data are a concern. Clinical validation of these results is needed.

Optimal levofloxacin dosing regimens in critically ill patients with acute kidney injury receiving continuous renal replacement therapy.

PURPOSES: To determine appropriate dosing of levofloxacin in critically ill patients receiving continuous renal replacement therapy (CRRT). METHODS: All necessary pharmacokinetic and pharmacodynamic parameters from critically ill patients were obtained to develop mathematical models with first order elimination. Levofloxacin concentration-time profiles were calculated to determine the efficacy based on the probability of target attainment (PTA) of AUC24h/MIC ≥50 for Gram-positive and AUC24h/MIC ≥125 for Gram-negative infections. A group of 5000 virtual patients was simulated and tested using Monte Carlo simulations for each dose in the models. The optimal dosing regimens were defined as the dose achieved target PTA at least 90% of the virtual patients. RESULTS: No conventional, FDA approved regimens achieved at least 90% of PTA for Gram-negative infection with Pseudomonas aeruginosa at MIC of 2 mg/L. The successful dose (1750 mg on day 1, then 1500 mg q 24 h) was far exceeded the maximum FDA-approved doses. For Gram-positive infections, a levofloxacin 750 mg q 24 h was sufficient to attain PTA target of ~90% at the MIC of 2 mg/L for Streptococcus pneumoniae. CONCLUSIONS: Levofloxacin cannot be recommended as an empiric monotherapy for serious Gram-negative infections in patients receiving CRRT due to suboptimal efficacy.

Meropenem dosing recommendations for critically ill patients receiving continuous renal replacement therapy.

PURPOSES: To gather available meropenem pharmacokinetics and define drug dosing regimens for Asian critically ill patients receiving CRRT. METHODS: All necessary pharmacokinetic and pharmacodynamic data from Asian population were gathered to develop mathematic models with first order elimination. Meropenem concentration-time profiles were calculated to evaluate efficacy based on the probability of target attainment (PTA) of 40%fT>4MIC. A group of 5000 virtual patients was created and tested using Monte Carlo simulations for each dose in the models. The optimal dosing regimens were defined as the doses achieved at least 90% of the PTA. RESULTS: The recommended meropenem dosing regimen for Asian critically ill patients receiving CRRT with standard (20-25 mL/kg/h) and high (35 mL/kg/h) effluent rates was 750 mg q 8 h to manage Gram negative infections with expected MIC < 2 mg/L in virtual Asian patients. Some meropenem dosages from available clinical resources could not achieve the aforementioned target. The volume of distribution, body weights and nonrenal clearance significantly contributed to drug dosing adaptation especially in the specific population. CONCLUSIONS: A meropenem regimen of 750 mg q 8 h was recommended for Asian critically ill patients receiving 2 different CRRT modalities with standard and high effluent rates. Clinical validation of these results is needed.

Clinical outcomes of patients infected with carbapenem-resistant Acinetobacter baumannii treated with single or combination antibiotic therapy.

OBJECTIVE: To evaluate treatment outcomes in patients with carbapenem-resistant Acinetobacter baumannii (CRAB) nosocomial infections treated with antimicrobial agent either alone or in combination. MATERIAL AND METHOD: Clinical data were retrospectively evaluated in patients with CRAB nosocomial infections admitted to Songklanagarind Hospital, Songkhla, Thailand from January-December 2008. RESULTS: One hundred ten patients with CRAB nosocomial infections were identified. Most patients (57.3%) had site of infection in the lower respiratory tract and the majority of them (61.8%) received a single antimicrobial agent. Crude mortality was 30%. The presumptive success rate was 60.3% (41/68) for patients given monotherapy and 81.0% (34/42) for patients given combination therapy (p = 0.024). Patients given combination therapy were more likely to have been given at least one antibiotic to which the organism was susceptible (p = 0.004). In multivariate analysis, renal impairment, bloodstream infection, and inappropriate antimicrobial regimen were independent predictors of treatment failure. CONCLUSION: The combination therapy regimen yielded more presumptive treatment success by increasing the likelihood of an appropriate antimicrobial therapy. Additionally, inappropriate antimicrobial treatment, renal impairment, and bloodstream infection were associated with poor treatment outcomes in patients with CRAB nosocomial infections.