Is a standard vancomycin dosing protocol appropriate to achieve therapeutic trough levels in adult neutropenic patients?

Purpose:   Neutropenia is a condition defined as an absolute neutrophil count (ANC) less than 1000 cells/mm³, at which point a patient's risk increases for opportunistic infections.  Bacteremia cases often involve drug resistant organisms, such as methicillin-resistant Staphylococcus aureus (MRSA).  Vancomycin is used to treat MRSA infections and serum concentrations must remain above the minimum inhibitory concentration (MIC) to be effective.   Improper dosing can delay therapy, which can be life-threatening in neutropenic patients.  NMCSD uses a standard vancomycin protocol to target trough concentrations between 10-20mcg/ml, which correlate to better clinical outcomes in systemic infections.  This protocol doses vancomycin at 15-20mg/kg/dose and administration times are determined by patient renal function.  The aim of this study is to explore if vancomycin pharmacokinetics are altered in neutropenic adult patients. 

Methods: This retrospective study reviewed neutropenic, adult patients treated with vancomycin from January 2006-August 2011.  A chart review was performed and demographic information was collected.  Data included initial vancomycin dosing and administration details.  The primary outcome was evaluated by collecting corresponding trough concentrations and results were divided into subtherapeutic (<15mcg/ml), therapeutic (15-20mcg/ml) or supratherapeutic (>20mcg/ml).  Patient demographics were evaluated for effect on achieving therapeutic trough concentrations. 

Results: 198 patients met inclusion criteria.  107 (54%) patients followed vancomycin dosing and interval recommendations per the protocol.  Across all interval groups, 25.3% (p<0.001) of patients achieved therapeutic trough concentrations.  Comparing the higher frequency group (n=42) to the recommended frequency group (n=107), there was no significant improvement in achieving therapeutic concentrations.  Age, sex and renal function had no significant impact on the ability to achieve therapeutic concentrations. 

Conclusions:   Study confirms that vancomycin pharmacokinetics is altered in adult neutropenic patients.  The pharmacy department is recommending the use of a loading dose for adult patients with an ANC <1000cells/mm3.  Future studies evaluating use of loading dose and clinical outcomes are needed.