Impact of Vancomycin Serum Trough Concentrations and Vancomycin AUC/MIC on Vancomycin Response, In-Hospital Outcomes and Acute Kidney Injury in Pediatric Staphylococcus aureus Pneumonia

BACKGROUND: Vancomycin AUC/MIC > 400 was initially shown to be beneficial in adults with staphylococcal pneumonia. Current practice guidelines recommend targeting serum vancomycin trough concentrations (VTC) of 15–20 µg/ml in adults with severe MRSA infection to approximate these AUC/MIC goals. Small studies have shown no benefit to VTC > 15 µg/ml in children with osteomyelitis or bacteremia. We describe the impact of VTC and AUC/MIC on outcomes of pediatric S. aureuspneumonia. METHODS: Cases of S. aureuspneumonia from January 1, 2011 to December 31, 2016 were reviewed. Patients treated with vancomycin <48 hours were excluded. Suboptimal vancomycin response (SVR) was considered any combination of duration of fever, bacteremia or ICU stay > 75%-tile, need for re-operation, or mortality. The highest VTC and AUC obtained in the first 96 hours of therapy was used in analyses. Vancomycin MIC was determined with the E-test. Acute kidney injury (AKI) was defined as a doubling of the baseline serum creatinine. RESULTS: Thirty-six patients were identified meeting inclusion criteria with a median age of 0.74 years. 75% of isolates were MRSA and 70.4% were USA300. 80.6% of patients were admitted to the ICU and 52.8% were intubated. No benefit was observed in terms of duration of fever, bacteremia, ICU stay, ventilator or hospital days or rates of SVR between patients with VTC > or <15 µg/ml. There were substantial increases in rates of AKI with higher VTC (66.7 vs. 24.2%, P < 0.001). Among 23 patients for whom AUC/MIC determinations were possible, none achieved an AUC/MIC >400; the median AUC/MIC = 42 (IQR: 32–51). Eighty-eight% of isolates had an MIC ≥1.5 µg/ml. There was no correlation between values of AUC/MIC and length of ICU or hospital stay or SVR (AUROC 0.45). CONCLUSION: While the sample size is limiting, VTC >15 µg/ml did not provide clinical benefit to children with S. aureus pneumonia compared with lower VTC levels while at the same time predisposing to nephrotoxicity. AUC/MIC > 400 is rarely achieved in children with S. aureus pneumonia and may not be a realistic goal in this infection given the rarity with which this occurs, the frequency of high MICs and the very young age of the typical patient. Large multicenter studies are required to understand optimal vancomycin dosing and monitoring in children with invasive MRSA infections. DISCLOSURES: J. McNeil, NIAID, NIH: Grant Investigator, Grant recipient; S. L. Kaplan, Allergan: Grant Investigator, Grant recipient and This grant pertains to unrelated research