The Whole Price of Vancomycin: Toxicities, Troughs, and Time

Abstract

Vancomycin is a glycopeptide antibiotic that is active against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. Nephrotoxicity, which is usually reversible, is the most serious common adverse effect of vancomycin. Vancomycin-associated nephrotoxicity prolongs hospital stays, imposes a need for additional antibiotics and, in rare circumstances, dialysis treatment, and increases medical costs and mortality. Risk factors for nephrotoxicity include the dose and duration of vancomycin treatment, serum trough concentration, patient characteristics, and concomitant receipt of nephrotoxins. Contemporary guidelines recommend targeting vancomycin trough concentrations of ≥10 mg/L to prevent resistance and trough concentrations of 15-20 mg/L to optimize outcomes. There is significant correlation between vancomycin trough serum concentrations and the incidence of vancomycin-associated nephrotoxicity; however, evidence of an association between trough concentrations and efficacy is less convincing. Routine monitoring of serum vancomycin concentrations consumes time and limited healthcare resources and may not be cost effective. The use of alternative antibacterial agents that do not require monitoring would free up pharmacy resources. This time could then be devoted to initiatives such as pharmacist-led antibiotic stewardship programs that are known to reduce antibiotic use and promote improved patient outcomes.

Fig. 1

Risk factors for vancomycin-associated nephrotoxicity. Abrupt (within 48 h) reduction in kidney function signified by an absolute increase in SCr of ≥0.3 mg/L, an increase in SCr. AKI acute kidney injury, AKIN acute kidney injury network, AMG aminoglycoside, APACHE II Acute Physiology and Chronic Health Evaluation II, BUN:SCr >20 ratio of blood urea nitrogen to serum creatinine >20, CrCl creatinine clearance, HAP hospital-acquired pneumonia, HCAP healthcare-associated pneumonia, ICU intensive care unit, IV intravenous, LOS length of stay, NR not reported, SCr serum creatinine, tr trough, VAN vancomycin-associated nephrotoxicity, VAP ventilator-associated pneumonia. ¹In addition, data from 45 patients who received linezolid were included as a control group. Data from this group are not included in the table. ²Mortality at 28 days; p = 0.48. ³Median LOS; p = 0.06. ⁴Continuous variable (per day)