Abstract
Optimal early vancomycin target exposure remains controversial. To clarify the therapeutic exposure range, we investigated the association between vancomycin exposure and treatment outcomes or nephrotoxicity in patients with methicillin-resistant Staphylococcus aureus (MRSA) infection. This retrospective study reviewed clinical data obtained from 131 patients with MRSA infections between January 2017 and September 2019. Clinical outcomes included treatment failure, 30-day mortality, microbiological failure, and acute kidney injury. We measured serum vancomycin levels after the first dose to 48 h and estimated vancomycin exposure using the Bayesian theorem. The minimum inhibitory concentration (MIC) of antimicrobial agents was determined using the broth microdilution method. Classification and Regression Tree analyses identified day 1 and 2 exposure thresholds associated with an increased risk of failure and nephrotoxicity. Treatment failure (27.9% vs. 33.3%) and 30-day mortality (26.6% vs. 31.74%) were numerically but not significantly reduced in patients with the area under the curve (AUC)24–48h/MICBMD ≥ 698. Patients with AUCss/MICBMD ≥ 679 exhibited a significantly increased risk of acute kidney injury (27.9% vs. 10.9%, p = 0.041). These findings indicate that AUCss/MICBMD ratios > 600 may cause nephrotoxicity. AUC/MICBMD at days 1 and 2 do not appear to be significantly associated with particular clinical outcomes, but further studies are needed.
Highlights
Methicillin-resistant Staphylococcus aureus (MRSA) is the most common cause of nosocomial infections
A previous study showed that intensive care unit (ICU) patients had a volume of distribution (Vd) nearly twice as high as that of healthy patients [3]
The number of patients with acute kidney injury (AKI) was 17, and was significantly higher in the high vancomycin exposure exposure groups ss/MICBMD 679 (27.9% vs. 10.9%, p = 0.041)) (Figure 1)
Summary
Methicillin-resistant Staphylococcus aureus (MRSA) is the most common cause of nosocomial infections. The Asian Network for Surveillance of Resistant Pathogens (ANSORP) study reported that. Glycopeptide antibiotic vancomycin remains the treatment of choice for MRSA infections. Patient conditions can be affected by complex vancomycin pharmacokinetics (PK) and variable serum concentrations. The early phase of sepsis is a hypermetabolic condition that leads to increased renal blood flow and renal elimination of antibiotics, which is a phenomenon termed augmented renal clearance (ARC). ARC is strongly associated with subtherapeutic vancomycin serum concentrations during the first three days of treatment [4]. Standard dosing might lead to insufficient vancomycin exposure and therapeutic failure in these patients [2,3,4,5]
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