Relationship between day 1 and day 2 Vancomycin area under the curve values and emergence of heterogeneous Vancomycin-intermediate Staphylococcus aureus (hVISA) by Etest\xae macromethod among patients with MRSA bloodstream infections: a pilot study

Dmitriy M Martirosov,R E Mendes,Corey Faragon,Manjunath P Pai,Thomas P Lodise,Louise-Anne Mcnutt,R N Jones,M Malik,Marc H Scheetz,Susan L Rosenkranz,Monique R Bidell

doi:10.1186/s12879-017-2609-0

Abstract

BackgroundIn vitro data suggests that suboptimal initial vancomycin exposure may select for heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) infections. However, no clinical studies have evaluated the relationship between initial vancomycin exposure and emergence of hVISA. This pilot study seeks to assess the relationship between day 1 and day 2 vancomycin area under the curve (AUC) and emergence of hVISA bloodstream infections (BSIs) by Etest® macromethod among patients with a non-hVISA BSI at baseline.MethodsThis was a retrospective cohort study of patients with methicillin-resistant Staphylococcus aureus (MRSA) BSIs at Albany Medical Center Hospital (AMCH) between January 2005 and June 2009. The vancomycin AUC exposure variables on day 1 (AUC0-24h) and day 2 (AUC24-48h) were estimated using the maximal a posteriori probability (MAP) procedure in ADAPT 5.ResultsThere were 238 unique episodes of MRSA BSIs during the study period, 119 of which met inclusion criteria. Overall, hVISA emerged in 7/119 (5.9%) of patients. All 7 cases of hVISA involved patients who did not achieve area under the curve over broth microdilution minimum inhibitory concentration (AUC0-24h/MICBMD) ratio of 521 or an AUC24-48h/MICBMD ratio of 650. No associations between other day 1 and day 2 AUC variables and emergence of hVISA were noted.ConclusionsAlthough more data are needed to draw definitive conclusions, these findings suggest that hVISA emergence among patients with non-hVISA MRSA BSIs at baseline may be partially explained by suboptimal exposure to vancomycin in the first 1 to 2 days of therapy. At a minimum, these findings support further study of the relationship between initial vancomycin exposure and hVISA emergence among patients with MRSA BSIs in a well-powered, multi-center, prospective trial.

Highlights

In vitro data suggests that suboptimal initial vancomycin exposure may select for heterogeneous vancomycin-intermediate Staphylococcus aureus infections
Patients were included if they met the following criteria: (1) age ≥ 18 years; (2) absolute neutrophil count ≥1000 cells/mm3; (3) not receiving renal replacement therapy; (4) methicillin-resistant Staphylococcus aureus (MRSA) blood culture met the Centers for Disease Control and Prevention (CDC) criteria for bloodstream infections (BSIs) [5]; (5) index and at least 1 subsequent MRSA bloodstream isolates were available for phenotypic characterization; (6) index MRSA isolate was negative for heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) by Etest® macromethod [6]; (7) received vancomycin within 48 h of index blood culture; (8) received at least 2 days of vancomycin; and (9) had at least one vancomycin level collected within 5 days of starting treatment
Most hVISA isolates emerged during vancomycin treatment and 4 of 7 appeared within 15 days of the index MRSA blood culture (Table 1)

Summary

Introduction

In vitro data suggests that suboptimal initial vancomycin exposure may select for heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) infections. This in vitro finding is concerning as data suggest that patients with hVISA infections are less responsive to vancomycin [4] Despite this potential association between suboptimal exposure to vancomycin and hVISA emergence, clinical studies evaluating the relationship between initial vancomycin exposure and emergence of hVISA are largely nonexistent. This pilot study seeks to assess the relationship between day 1 and day 2 vancomycin area under the curve (AUC) and emergence of hVISA bloodstream infections (BSIs) by Etest® macromethod among patients with a nonhVISA BSI at baseline. The Bayesian approach used to estimate exposure profiles in this study has recently been validated as a method to estimate vancomycin exposure values with low bias and high precision in situations where trough-only PK data are available

Methods

Results

Discussion

Conclusion