![]() Multivariable regression analyses were then performed to examine the independent association between loading dose and composite failure as well as loading dose and nephrotoxicity. Categorical variables were compared using the χ 2 or Fisher’s exact test while continuous variables were compared using the Student’s t test or Mann–Whitney U test. In the primary analysis, a series of bivariate analyses were performed to compare outcomes between exposure groups, determine factors associated with the primary outcome of composite failure, and determine factors associated with nephrotoxicity. All statistical analyses were performed using SPSS v.24.0 (Armonk, NY, USA). For all analyses, a P value ≤ 0.05 was considered statistically significant. Concomitant nephrotoxins assessed included aminoglycosides, colistin, acyclovir, intravenous (IV) contrast dye, amphotericin, tacrolimus, loop diuretics, non-steroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers.Ī sample size of 272 patients, 136 matched pairs, was required to detect a 15% difference in the primary endpoint using an alpha of 0.05 and power of 80%. Vancomycin trough concentration assessment included only initial trough concentrations drawn at steady-state of the maintenance regimen (prior to the 4th or 5th dose). Baseline SCr was the creatinine value immediately preceding the first dose of vancomycin. Nephrotoxicity was defined as an increase in serum creatinine (SCr) of greater than 0.5 mg/dL or at least a 50% increase from baseline on two consecutive measurements as per the vancomycin dosing and monitoring guidelines, and was assessed starting from the first dose of vancomycin to 72 h after the final dose. Secondary outcomes included duration of bacteremia, length of stay post-bacteremia onset, and nephrotoxicity. Patients not meeting criteria for composite failure were considered to be a treatment success. ![]() The primary outcome of this study was composite treatment failure defined as the presence of at least one of the following: 30-day mortality (from index culture), bacteremia duration ≥ 7 days after vancomycin initiation, persistent signs and symptoms of infection ≥ 7 days after vancomycin initiation, or switch to an alternative anti-MRSA antimicrobial agent due to treatment failure as determined by treating physician documentation. The primary objective of this study was to evaluate the effect of administering a one-time, weight-based vancomycin loading dose on clinical outcomes in patients with MRSA bacteremia. ĭue to the relative paucity of evidence demonstrating advantages to vancomycin loading doses, combined with the concern for increasing the risk for toxic events, continued evaluation of this practice is necessary. However, this is likely due to resultant supratherapeutic vancomycin exposures in these patients, and there are currently few data to demonstrate an association between vancomycin loading doses and nephrotoxicity. Conversely, given previous findings of higher total daily doses being correlated with higher incidence of nephrotoxicity, hypothetical concerns of increased vancomycin-associated nephrotoxicity persist with the weight-based loading dose approach, especially in obese patients. Although published data demonstrate that achievement of PD targets during the first 48 h of infection improves outcomes, clinical data showing a direct benefit of vancomycin loading doses are lacking. By increasing the likelihood of pharmacokinetic/pharmacodynamic (PK/PD) target attainment early in therapy, this would theoretically improve outcomes in those patients at highest risk of mortality. To facilitate rapid attainment of goal concentrations, the guidelines recommend a one-time loading dose of 25–30 mg/kg based off total body weight (TBW) for seriously ill patients. ![]() The vancomycin guidelines recommend targeting trough concentrations of 15–20 mg/L for patients with Staphylococcus aureus bacteremia, endocarditis, osteomyelitis, meningitis, or hospital-acquired pneumonia and dosing regimens are designed to achieve these target serum exposures at steady-state.ĭepending on a patient’s renal function, it may take anywhere from 24 to 72 h, or longer, to reach steady-state. Various guidelines have suggested different vancomycin dosing and monitoring strategies and it was not until 2009 that the first consensus guideline for the therapeutic monitoring of vancomycin was published.
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