Risk Factors Associated With Nephrotoxicity During Outpatient Intravenous Vancomycin Administration

Background: Many studies have described an association between intravenous vancomycin and nephrotoxicity; however, the majority have evaluated incidence and risk factors among hospitalized patients. Outpatient administration of intravenous antibiotics is a growing practice and presents its own set of unique challenges. Objective: The aim of this study was to identify risk factors for vancomycin-associated nephrotoxicity in the outpatient setting. Methods: A case-control study of patients who received intravenous vancomycin through an Outpatient Parenteral Antimicrobial Therapy (OPAT) program was conducted. Patients were identified who developed an acute kidney injury (AKI) during treatment. The primary outcome was the incidence of AKI during treatment. Results: A total of 37 out of 130 patients (28.5%) met the criteria for AKI. AKI was more likely to occur in patients with a longer duration of therapy, higher maximum trough concentration, co-administration of a fluoroquinolone or metronidazole, and those who received another potentially nephrotoxic medication. Co-administration of a fluoroquinolone (OR = 5.96, P = 0.009, [CI: 1.59, 24.38]), any nephrotoxic medication (OR = 11.17, P < 0.001, [CI 3.14, 51.23]), and a higher maximum vancomycin trough (OR = 1.29, P < 0.001, [CI 1.17, 1.44]) were all indicative of a higher odds of an AKI. Conclusion: In this cohort, vancomycin-associated nephrotoxicity was common during outpatient intravenous antibiotic therapy. Co-administration of a fluoroquinolone, any nephrotoxic medication, and a higher maximum vancomycin trough were associated with AKI development. Further study is needed to determine how this impacts long-term clinical outcomes and what measures can be taken to reduce nephrotoxicity risk.

Association of vancomycin trough concentration on the treatment outcome of patients with bacteremia caused by Enterococcus species

Background Pharmacokinetic-pharmacodynamic (PK/PD) targets of vancomycin therapy have been recognized for methicillin-resistant Staphylococcus aureus infections but not for other gram-positive bacterial infections. Therefore, we investigated whether vancomycin concentration targets such as the trough level and ratio of the area under the curve to minimum inhibitory concentration (AUC/MIC) are associated with the treatment outcome in enterococcal bacteremia. Methods A retrospective cohort analysis enrolled patients with bacteremia caused by vancomycin-susceptible Enterococcus faecium and Enterococcus faecalis who were treated with vancomycin from January 2007 to December 2017 at a tertiary hospital located in Seoul, South Korea. Patients without vancomycin concentrations were excluded from the study. The primary outcome was 28-day all-cause mortality. Results A total of 37 patients were enrolled—26 with E. faecium infection and 11 with E. faecalis infection. The 28-day all-cause mortality rate was 21.6 %. In univariate analysis, vancomycin trough level (≤ 15 µg/mL; p = 0.042), age (p = 0.044), and septic shock (p = 0.049) were associated with 28-day mortality but not AUC24/MIC (> 389; p = 0.479). In multivariate analysis, vancomycin trough concentration (≤ 15 µg/mL; p = 0.041) and younger age (p = 0.031) were associated with 28-day mortality in patients with enterococcal bacteremia. Conclusions In this study, a vancomycin trough level of 15 µg/mL or lower was associated with 28-day mortality in enterococcal bacteremia. However, relatively large prospective studies are needed to examine the efficacy of vancomycin PK/PD parameters in patients with enterococcal bacteremia.

Acute kidney injury associated with area under the curve versus trough monitoring of vancomycin in obese patients.

Vancomycin is a first-line agent used in the treatment of methicillin-resistant Staphylococcus aureus ; however, vancomycin is associated with acute kidney injury (AKI). Previous literature demonstrates decreased incidence of AKI using 24-hour area under the concentration-time curve (AUC 24 ) monitoring, but its safety is unknown in obese populations. Patients ≥18 years, with Body Mass Indices (BMI) ≥30 kg/m 2 , admitted between August 2015-July 2017 or October 2017-September 2019, who received vancomycin for ≥72 hours and had level(s) drawn within 96 hours of initiation were included. The primary outcome was incidence of AKI. Secondary outcomes included inpatient mortality rate, median inpatient length of stay, median vancomycin trough concentration, and median vancomycin AUC 24 . AKI was identified using the highest serum creatinine value compared to the value immediately prior to vancomycin initiation based on Kidney Disease Improving Global Outcomes (KDIGO) criteria. Overall, 1024 patients met inclusion criteria, with 142 out of 626 patients in the trough group and 65 out of 398 patients in the AUC 24 group meeting criteria for AKI (22.7% vs. 16.3%, p=0.008). Logistic regression of the data to account for confounding factors maintained significance for the reduction in incidence of AKI with AUC 24 monitoring compared to trough monitoring (p=0.010). Monitoring of vancomycin with AUC 24 was associated with a decreased risk of AKI when compared with trough monitoring in obese patients.

Comparing Two Equations for Estimation of Kidney Function (Cockcroft-gault and Glomerular Filtration Rate Assessment in Liver Disease) for Vancomycin Dosing in Adult Liver Transplant Recipients: a Pilot, Randomized Clinical Trial

Background: In the setting of impaired liver function, estimation of glomerular filtration rate (GFR) using common creatinine based equations is inaccurate. Recently, Glomerular Filtration Rate Assessment in Liver Disease (GRAIL) model has been introduced for estimating GFR in liver transplantation. This study was conducted to compare vancomycin dose adjustment in liver transplant patients using Cockcroft-Gault (C-G) versus GRAIL method.Methods: In this pilot, randomized clinical trial, adult liver transplant recipients who were candidate to receive intravenous vancomycin were enrolled. GFR and creatinine clearance were estimated using GRAIL model and C-G equation in the intervention and control arms, respectively and vancomycin maintenance doses were adjusted accordingly. At the steady state , peak and trough serum concentrations of vancomycin were collected for pharmacokinetic comparisons.Results: Fifteen patients were enrolled in each arm of the study. Mean daily dose of vancomycin was estimated insignificantly lower for individuals in GRAIL arm than C-G group (1500.00±544.45 versus 1750.00± 389.60mg). The rate of patients who achieved the target vancomycin trough concentration was similar between the two study arms (20%). Compared with C-G group, higher rate of patients in GRAIL arm experienced below-target vancomycin trough concentrations (40% versus 13.3%) and lower rate showed above target trough concentration (40% versus 66.7%), although these differences did not reach statistical significance. Higher rates of patients with at target and above target vancomycin AUC/MIC were seen in the C-G group compared with GRAIL group (40% versus 26.7% and 53.3% versus 26.7%, respectively), while individuals in the GRAIL arm represented significantly higher rate of below target vancomycin AUC/MIC than C-G arm (46.7% versus 6.7%) (P=0.049). No differences in clinical outcomes were observed between the two groups.Conclusion: Using GRAIL model for vancomycin dose selection may result in less percent of patients with at target AUC/MIC exposure compared to C-G method and expose more percent of patients at risk of vancomycin under dosing.

Relationship Between Mean Vancomycin Trough Concentration and Mortality in Critically Ill Patients: A Multicenter Retrospective Study

Background: It remains unclear whether the mean vancomycin trough concentration (VTC) derived from the entire course of therapy is of potential benefit for critically ill patients. This study was conducted to explore the association between mean serum VTC and mortality in intensive care units (ICUs).Methods: 3,603 adult patients with two or more VTC records after receiving vancomycin treatment in the eICU Collaborative Research Database were included in this multicenter retrospective cohort study. Mean VTC was estimated using all measured VTCs and investigated as a continuous and categorical variable. Patients were categorised into four groups according to mean VTC: &lt;10, 10–15, 15–20, and &gt;20 mg/L. Multivariable logistic regression and subgroup analyses were performed to investigate the relationship of mean VTC with mortality.Results: After adjusting for a series of covariates, logistic regression analyses indicated that mean VTC, as a continuous variable, was positively correlated with ICU (odds ratio, 1.038, 95% confidence interval, [1.014–1.063]) and hospital (1.025 [1.005–1.046]) mortalities. As a categorical variable, mean VTC of 10–15 mg/L was not associated with reduced ICU (1.705 [0.975–2.981]) and hospital (1.235 [0.829–1.841]) mortalities. Mean VTC of 15–20 mg/L was not correlated with a lower risk of hospital mortality (1.370 [0.924–2.029]). Moreover, mean VTCs of 15–20 and &gt;20 mg/L were significantly associated with higher ICU mortality (1.924 [1.111–3.332]; 2.428 [1.385–4.258]), and mean VTC of &gt;20 mg/L with higher hospital mortality (1.585 [1.053–2.387]) than mean VTC of &lt;10 mg/L. Similar results were observed in patients with different Acute Physiology and Chronic Health Evaluation IV score, creatinine clearance, age, and body mass index subgroups.Conclusion: Mean VTC was not associated with reduced ICU/hospital related mortality. Our results suggested that VTC monitoring might not guarantee vancomycin efficacy for ICU patients.

Incidence and risk factors of vancomycin-associated acute kidney injury in a single center: Retrospective study

Background: There is enough evidence to suggest that vancomycin increases the risk of acute kidney injury (AKI) but the exact mechanism is not well understood. This study aims to understand the incidence of vancomycin-associated acute kidney injury (VA-AKI) among hospitalized patients and to identify the risk factors for VA-AKI. Methods: Patients aged 18 and above who received a minimum of 24 hours of intravenous vancomycin and who had serial creatinine measurements over a 13-month period were identified through electronic records. Patients with pre-existing AKI, or eGFR of less than 30ml/min, and patients with end stage kidney disease were excluded. Results were analyzed using t-test and Fisher’s test. A logistic regression model was used to identify the predictors for VA-AKI. Results: From the 598 patients who met the inclusion criteria, 70 developed AKI. Compared to those without AKI, patients with VA-AKI had higher mean serum vancomycin trough levels (22.6 mg/L vs. 14.6 mg/L), and a statistically significant longer duration of vancomycin use (6.7 vs. 5.2 days). Multivariate analysis revealed that serum vancomycin level of > 20 mg/L was associated with a six-fold increase in odds of VA-AKI when compared to those with vancomycin levels < 15 mg/L. The presence of hypotension, iodinated contrast use, and concomitant use of piperacillin-tazobactam were all associated with increased odds of VA-AKI. Conclusion: The incidence of VA-AKI in hospitalized patients with eGFR > 30 ml/min was 11.7%. Serum vancomycin levels of > 20 mg/L, hypotension and administration of iodinated contrast significantly increased the risk of VA-AKI. Piperacillin-tazobactam, when used with vancomycin, was noted to be an independent predictor of AKI, regardless of serum vancomycin trough levels, prompting a reevaluation of the safety of this widespread practice as empiric therapy. Close monitoring of kidney function, avoiding high serum vancomycin levels, maintaining hemodynamic stability, and avoiding unnecessary use of iodinated contrast seem to be essential for the prevention of VA-AKI.