1. Int J Antimicrob Agents. 2013 May;41(5):439-46. doi:
10.1016/j.ijantimicag.2013.01.009. Epub 2013 Mar 22.

Implementation of a protocol for administration of vancomycin by continuous
infusion: pharmacokinetic, pharmacodynamic and toxicological aspects.

Ampe E, Delaere B, Hecq JD, Tulkens PM, Glupczynski Y.

Pharmacologie cellulaire et moléculaire et Centre de pharmacie clinique, Louvain 
Drug Research Institute, Université catholique de Louvain, Brussels, Belgium;
Laboratoire de microbiologie, Service d'infectiologie et Département de
pharmacie, CHU Mont-Godinne, Yvoir, Belgium.

Optimising antibiotic administration is critical when dealing with pathogens with
reduced susceptibility. Vancomycin activity is dependent on the area under the
concentration-time curve over 24h at steady-state divided by the minimum
inhibitory concentration (AUC/MIC), making continuous infusion (CI) or
conventional twice daily administration pharmacodynamically equipotent. Because
CI facilitates drug administration and serum level monitoring, we have
implemented a protocol for CI of vancomycin by: (i) examining whether maintaining
stable serum concentrations (set at 25-30mg/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 20mg/kg; infusion of
2.57g/24h adjusted for creatinine clearance) for up to 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>1mg/L. Nephrotoxicity potentially related to vancomycin was observed in 10%
of patients, but treatment had to be discontinued in only two of them.

Copyright © 2013 Elsevier B.V. and the International Society of Chemotherapy. All
rights reserved.

PMID: 23523733  [PubMed - in process]