Pharmacodynamics of vancomycin in elderly patients aged 75 years or older with methicillin-resistant Staphylococcus aureus hospital-acquired pneumonia

Abstract

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) infections are associated with significant mortality and health care costs. To improve treatment outcomes for MRSA, a better understanding of the pharmacokinetic/pharmacodynamic parameters of vancomycin is required to develop optimal dosing strategies, particularly in elderly patients (≥75 years of age) with limited renal function. The purpose of this study was to determine whether pharmacokinetic indices for vancomycin are associated with mortality from MRSA hospital-acquired pneumonia in elderly patients.MethodsWe conducted a retrospective observational study with 28-day mortality as the primary outcome for 94 patients with MRSA hospital-acquired pneumonia who had been treated with vancomycin from January 2006 through December 2012. Our most recent sampling of MRSA isolates had a minimum inhibitory concentration (MIC) for vancomycin of 1 μg/mL (86%), indicating that the area under the curve (AUC) was equal to the AUC/MIC in these isolates. The primary data from 28-day survivors and nonsurvivors were compared.ResultsAmong 94 elderly patients, the mean age was 82 (75–99) years. Multivariate analyses revealed that, among the factors examined, only the nonoptimal AUC (<250, >450 μg*h/mL) was an independent predictor of 28-day mortality in elderly patients (odds ratio 23.156, 95% confidence interval 6.814–78.687, P < 0.001). We detected a significant difference for increasing nephrotoxicity in nonsurvivors (nine of 32 patients [28%]) compared with survivors (three of 62 patients [4.8%], P = 0.003).ConclusionThis finding indicates that patients with potentially poor renal function are likely to have increased AUC values and a poor prognosis. Consideration of the pharmacokinetics/pharmacodynamics of vancomycin and targeting an AUC/MIC value of 250–450 μg*h/mL may result in improved treatment outcomes for elderly patients with MRSA hospital-acquired pneumonia.

Intravenous Vancomycin Dosing in the Elderly: A Focus on Clinical Issues and Practical Application

“…Furthermore, elderly patients with MRSA pneumonia also have the potential to have worse clinical outcomes despite adequate vancomycin therapy, in part due to low albumin [19]. Therefore, if practicing at an institution that utilizes loading doses, consider a lower empiric maintenance dose to account for the serum accumulation over time, while still adjusting further maintenance dosing by utilizing serum concentrations or calculated AUC/MIC ratio of vancomycin [29, 68, 73]. …”

“…Alternatively, equation-based monitoring can be programmed into the electronic medical system to automatically calculate the patient’s daily vancomycin AUC. Additionally, new evidence suggests that specific AUC/MIC goals may be better clinical markers of therapeutic efficacy [73]. In the general adult population, AUC/MIC ratio of >400 μg h/mL is targeted to provide effective therapy should the MRSA isolate have a vancomycin MIC ≤1 [9]; alternatively, the new proposed AUC/MIC targets of ≥521 on day 1 and ≥650 on day 2 should be sufficient for a 80–85% clinical success rate [36].…”

“…In the general adult population, AUC/MIC ratio of >400 μg h/mL is targeted to provide effective therapy should the MRSA isolate have a vancomycin MIC ≤1 [9]; alternatively, the new proposed AUC/MIC targets of ≥521 on day 1 and ≥650 on day 2 should be sufficient for a 80–85% clinical success rate [36]. In the elderly population, a targeted AUC/MIC of 250–450 μg h/mL may provide improved efficacy while limiting toxicity [73]. Ultimately, the decision on how to monitor vancomycin and adjust doses lies with the clinician.…”

Efficacy and safety of linezolid versus teicoplanin for the treatment of MRSA infections: a meta-analysis

“…In the present meta-analysis, several studies focused on elderly patients with nosocomial pneumonia and reported linezolid was associated with better efficacy compared with teicoplanin in elderly patients [27,29,[32][33][34]. We believe that higher clinical cure rate may contribute to better outcomes in elderly patients with nosocomial pneumonia because the immune system and organ function are often affected by aging and underlying diseases [41]. In contrast, teicoplanin have significant drawbacks which compromise their clinical usefulness for the treatment of serious MRSA infections.…”

Antimicrobial treatment of bacterial infections in frail elderly patients: the difficult balance between efficacy, safety and tolerability

“…Several antimicrobials used for the treatment of bacterial infections are excreted by the kidney, and this means that appropriate dosage adjustments should be applied whenever using these antimicrobials in elderly patients with CKD [7,8]. Dosage adjustments is required when creatinine clearance is lower than 50-60 ml/min [7 ,8], especially for those antimicrobials which may cause severe toxicity due to overexposure, namely aminoglycosides [37], vancomycin [38], levofloxacin [39] and cefepime [40]. Although reduced glomerular filtration rate (GFR) is often due to the combination of aging and chronic nephropathy damage [36], however the clinician should be aware that the finding of serum creatinine levels in the upper part of the normal range (i.e., 1.2 mg/dL) in an elderly patient may conceal moderate renal impairment (i.e., CLCr < 60 ml/min) [41].…”