Continuous infusion of vancomycin in non-ICU patients : why, how and what's the benefit?

Therapeutic Drug Monitoring (TDM) of vancomycin is widely recommended yet its performance in routine practice is rarely assessed. In the first part of the PhD thesis we performed a combined observational and qualitative study in order to assess routine TDM performance and adherence to local hospital TDM guidelines for vancomycin and to evaluate the impact of continuous infusion on the quality of TDM services. Baseline: 4 months observational study (vanncomycin BID, 46 patients, 132 samples). Intervention: switch to continuous infusion [CI] with centralised drug preparation (1 year, 92 patients, 224 samples). Process indicators: (i) correct sample timing; (ii) implementation of TDM dosage readjustment recommendations; (iii) prescribed daily dose in accordance to hospital guidelines; (iv) proportion of serum levels values within the recommended ranges. Qualitative studies: focus groups and structured interviews with ward and laboratory personnel to identify difficulties and barriers in TDM performance at baseline and assess satisfaction/dissatisfaction with the intervention. TDM performance was poor at baseline (BID) with only 53% of peak and 66% of trough samples collected within 30 min from scheduled time, 13% of peak levels and 48% of trough levels within recommended therapeutic ranges [84% too low], 32% implementation of dosage re-adjustment recommendation, and 83% incorrect prescribed daily doses (average: 20% lower). Insufficient knowledge and training of HCPs, and organisational issues were the main reasons for poor adherence and perceived as critical barriers. Implementation of CI was associated with significant improvement (p<0.0001) for correct sample timing (97.0%), drug levels within recommended range (66.8%); implementation of dosage re-adjustment recommendations (94.4%) and correct daily doses (86%). Centralised preparation, CI and TDM were perceived by ward personnel as reliable and contributing to the quality of care. Implementation of CI of vancomycin was effective for improving its TDM performance in routine practice in non-ICU wards. In the second part of the PhD thesis we evaluated the pharmacokinetics, pharmacodynamics and toxicity of vancomycin continuous infusion in non-ICU patients by: (i) examining whether maintaining stable serum concentrations (set at 25–30 mg/L based on local susceptibility data of Gram-positive target organisms) can be achieved in patients suffering from difficult-to-treat infections; (ii) assessing toxicity (n = 94) and overall efficacy (n = 59); and (iii) examining the correlation between AUC/MIC and the clinical outcome in patients for whom vancomycin was the only active agent against a single causative pathogen (n = 20). Stable serum levels at the expected target were obtained at the population level (loading dose 20 mg/kg; infusion of 2.57 g/24 h adjusted for creatinine clearance) for upto 44 days, but large intrapatient variations required frequent dose re-adjustments (increase in 57% and decrease in 16% of the total population). Recursive partitioning analysis of AUC/MIC ratios versus success or failure suggested threshold values of 667 (total serum level) and 451 (free serum level), corresponding to organisms with a MIC > 1 mg/L. Nephrotoxicity potentially related to vancomycin was observed in 10% of patients, but treatment had to be discontinued in only two of them.