Clinical and microbiological efficacy of continuous versus intermittent administration of vancomycin in critical care patients

Introduction

Vancomycin is known to induce postantibiotic effect but some data suggest that bactericidal activity is time dependent. Presently, the optimal dosing regimen for administration of vancomycin remains unknown. The aim of this open prospective randomized study was to compare clinical and microbiological efficacy of continuous infusion versus intermittent administration of vancomycin in critically ill patients.

Methods

Patients admitted to the interdisciplinary ICU suffering from infection indicated to vancomycin administration with predicted duration of treatment of at least 4 days were randomized to receive either a 15 mg/kg intravenous loading dose of vancomycin followed by a daily 15 mg/kg continuous infusion (continuous group) or intermittent administration of 15 mg/kg vancomycin intravenously every 12 hours (intermittent group). Antibiotic therapy was stopped at improvement of clinical state and laboratory signs of subsidence of infection. Failure of antimicrobial therapy was defined as persistence or progression of signs and symptoms of infection, development of new clinical findings consistent with active infection or death from infection. The age, APACHE II score, type of infection, length of ICU stay, length of mechanical ventilation, mortality, clinical and microbiological failure and length of vancomycin therapy and total dose of vancomycin were assessed. The Sequential Organ Failure Assessment score, white blood count, C-reactive protein and renal function at the beginning and at the end of therapy were evaluated. The Mann–Whitney test, unpaired t test and chi-squared test were used accordingly; P < 0.05 was considered statistically significant.

Results

A total of 65 patients were enrolled and randomized in the continuous (n = 33) and intermittent (n = 32) groups. No significant differences between both groups in all assessed parameters were found. Clinically evaluated failure of therapy in the continuous versus intermittent groups was in 12 (36%) patients versus eight (25%) patients, and microbiological failure in seven (21%) patients versus eight (25%) patients.

Conclusion

Continuous infusion and intermittent administration of vancomycin in critically ill patients provided equivalent clinical and microbiological outcome.