Initial Vancomycin Trough Levels Research Articles

Augmented Renal Clearance of Vancomycin in Suspected Sepsis: Single-Center, Retrospective Pediatric Cohort.

To identify associations between augmented renal clearance (ARC) in pediatric patients treated for suspected sepsis and vancomycin pharmacokinetics. ARC has been associated with lower serum drug levels in both adult and pediatric cohorts for multiple drugs. We hypothesize that presence of ARC is associated with subtherapeutic initial vancomycin trough level (VTL). Retrospective study, with patients divided into two groups based on the presence of ARC (estimated glomerular filtration rate [eGFR] above 130 mL/min/1.73 m2) in comparison with VTL. Multivariable logistic regression analysis was performed to evaluate the association between eGFR and subtherapeutic VTL. Tertiary children's hospital. Hospitalized children (0-18 yr) initiated on empiric vancomycin therapy for suspected sepsis. Retrospective measurement of VTL, eGFR, and clinical variables. Seventy-three patients were treated with empiric vancomycin for sepsis. ARC was present in 32 patients (44%). Subtherapeutic first VTL was present in 40 patients (55%). Higher eGFR was independently associated with subtherapeutic VTL in the multivariable logistic regression analysis. Subtherapeutic VTL is associated with ARC in our single-center retrospective cohort of children with suspected sepsis. This problem may present a potential risk of treatment failure in Gram-positive sepsis or longer time to clinical response. Prospective studies to investigate the clinical significance and effect of optimizing vancomycin dose in patients with ARC are recommended.

Optimizing Treatment of Hand Infections: Is MRSA Coverage Always Necessary?

Background:Multiple publications have highlighted the prevalence of methicillin resistant Staphylococcus aureus (MRSA) as a cause of hand infections. We hypothesized that these publications have shifted the empiric treatment of hand infections. The aim of this study was to identify the current standard of care, the most common causative bacteria, and factors leading to extended length of stay for hand infection patients at a suburban hospital to improve treatment and establish an optimized care protocol.Methods:Retrospective cohort analysis was conducted to identify all patients admitted for hand infections over an 8-year period. A comprehensive chart review of each patient’s hospital course was completed.Results:A total of 70 patients were included. Maximum white blood cell count ≥ 12 was associated with a significantly longer hospital length of stay (9.1 days versus 5.4 days) compared to WBC values < 12 (P < 0.05). Also, 11 out of 23 (47.8%) underwent two or more incision and drainages (I&D’s), compared with patients with maximum WBC < 12. Vancomycin use as an empiric antibiotic was widespread (68 patients, 97.1%), despite only 14 (20%) having MRSA positive cultures. Univariate analysis identified a significant increased likelihood for increased length of stay (P < 0.05) and rise in creatinine (P < 0.05) in patients with an initial vancomycin trough level > 20.Conclusions:This analysis of hand infection treatment in a suburban hospital demonstrates the incidence of MRSA hand infections may not be universally high across institutions. Each hospital should review its own data to optimize hand infection treatment and its associated costs.

Impact of a computerised clinical decision support system on vancomycin loading and the risk of nephrotoxicity

BackgroundA vancomycin loading dose is recommended for the treatment of serious methicillin-resistant Staphylococcus aureus (MRSA) infections. However, clinicians often do not adhere to these recommendations, mainly due to nephrotoxicity risk, unfamiliarity with the guideline, or complexity of calculating an individual dose. Therefore, we introduced a computerised clinical decision support system (CDSS) for vancomycin loading (hereafter Vancomycin CDSS) to promote the use of vancomycin loading dose. MethodsWe describe a quasi-experimental study spanning 6 months before and 18 months after the deployment of a Vancomycin CDSS. The Vancomycin CDSS was integrated into the hospital’s electronic medical record system in the form of a vancomycin order set. Our primary endpoint was the incidence of nephrotoxicity; the secondary endpoint was mean initial vancomycin trough levels. We also conducted a survey to evaluate the reasons why clinicians opted not to utilise a vancomycin loading dose. ResultsAfter implementation of Vancomycin CDSS, 363 out of 746 patients (49 %) who were first administered vancomycin received a loading dose. We did not find significant differences in nephrotoxicity between the pre- and post-intervention groups, nor between the loading- and non-loading groups. In the pre-intervention group, the mean initial vancomycin trough level was 7.10 mg/L, which was significantly lower than that in the post-intervention group of 11.11 mg/L. In the vancomycin loading group, the mean initial trough level was 11.95 mg/L, compared to 7.55 mg/L in the non-loading group. The main reason stated for not prescribing a vancomycin loading dose was concern about nephrotoxicity. ConclusionIntroduction of the Vancomycin CDSS did not increase nephrotoxicity and increased the mean initial dose and trough level of vancomycin.

Vancomycin in ICU Patients with Gram-Positive Infections: Initial Trough Levels and Mortality.

BackgroundVancomycin is one of the most common therapeutic agents for treating gram-positive infections, particularly in critically ill patients. The aim of this study was to identify factors associated with initial therapeutic vancomycin trough levels and mortality in a tertiary-care intensive care unit (ICU).MethodsThis retrospective study evaluated 301 adult ICU patients admitted to King Abdulaziz Medical City in Riyadh between October 1, 2017 and December 31, 2018 with confirmed gram-positive infections and received intravenous vancomycin. Vancomycin trough levels of 15–20 mg/L for severe infections and 10–15 mg/L for less severe infections were considered therapeutic.ResultsThe patients were relatively older with a mean age of 60 (SD ±20) years. Initial vancomycin trough levels were therapeutic in 168 (55.8%). Factors associated with initial therapeutic vancomycin trough levels were female gender (adjusted odds ratio [aOR]=2.575), older age (aOR=1.024), receiving a loading dose (aOR=2.445), having bacteremia (aOR=2.061), and high platelet count (aOR=1.003). On the other hand, the increase of estimated glomerular filtration rate (eGFR) (aOR=0.993) and albumin levels (aOR=0.944) were associated with lower odds of initial therapeutic vancomycin trough levels. Factors associated with higher mortality were female gender (adjusted hazard ratio [aHR]=2.630), increased body weight (aHR=1.021), cancer (aHR=3.451), and high APACHE II score (aHR=1.068).ConclusionThe study identified several factors associated with achieving initial therapeutic vancomycin trough levels (i.e. older age, female gender, receiving a loading dose, bacteremia, high platelets count, low eGFR and albumin level). These factors should be considered in the dosing of vancomycin in critically ill patients with gram-positive infections.

Assessment of initial vancomycin trough levels and risk factors of vancomycin-induced nephrotoxicity in neonates

ObjectivesVancomycin is a glycopeptide antibiotic commonly used in neonatal intensive care units (NICUs) to treat late onset sepsis. It is recommended that vancomycin trough levels at steady state following intermittent...

Evaluation of a modified vancomycin nomogram for obese adults.

The purpose of this study was to compare therapeutic vancomycin trough levels in obese adults when using an original nomogram (phase I) versus a modified nomogram (phase II). This study compared a vancomycin nomogram with a modified vancomycin nomogram for obese adults over 100kg. The primary endpoint compared the percentage of sub-therapeutic, therapeutic, and supra-therapeutic vancomycin trough concentrations between the nomograms. Patients were included if they were at least 18years of age, had a total body weight of 100-299kg, and had an initial vancomycin trough level collected. Patients were excluded if they had end-stage renal disease or were on continuous renal replacement therapy. Therapeutic trough levels occurred in 85 out of 171 patients (50%) in phase I and 98 out of 149 patients (66%) in phase II. The incidence of both sub-therapeutic and supra-therapeutic troughs was less in phase II (p = 0.013). In the subgroup of adults aged 18 to 49 with a normalized creatinine clearance of greater than 90mL/min, there was a trend in more therapeutic levels with the modified nomogram and less chance of sub-therapeutic levels (p = 0.088). In the subgroup of adults with a normalized creatinine clearance of 60-90mL/min, there was significant improvement in therapeutic levels and a decrease in supra-therapeutic levels without increasing the percent of sub-therapeutic levels (p = 0.001). The modified vancomycin nomogram at Cone Health showed significant improvement in therapeutic trough concentrations while reducing the rates of under and over dosing obese adults. The Cone Health-modified vancomycin nomogram could be a useful tool for initial dosing of vancomycin in the obese population.

Relationship Between Initial Vancomycin Trough Levels and Early-Onset Vancomycin-Associated Nephrotoxicity in Critically Ill Patients.

Appropriate initial dosing of vancomycin (VCM) is important in improving survival and in preventing nephrotoxicity in critically ill patients, but the potential relationship between initial VCM trough levels and early-onset nephrotoxicity remains unclear. We examined the relationship between initial VCM trough levels and early-onset VCM-associated nephrotoxicity. We performed a retrospective study of patients who had therapeutic drug monitoring of VCM with initial trough levels within 4 days after the beginning of VCM administration. We excluded patients who received renal replacement therapy from 2 days before to 7 days after the beginning of VCM administration, were younger than 18 years, or had renal dysfunction before the beginning of VCM administration. Early-onset VCM-associated nephrotoxicity was defined as an increase in serum creatinine level of ≥0.5 mg/dL (44.2 μmol/L) or 50% above baseline for 2 or more consecutive days within 7 days after the beginning of VCM administration. Among 109 enrolled patients, 13 patients had early-onset VCM-associated nephrotoxicity. Its incidence rate was 31.3% in patients with initial trough levels of ≥20g/mL, which was significantly higher than 6.3% in patients with initial trough levels of <10 mg/L. Multiple logistic regression analysis demonstrated that early-onset VCM-associated nephrotoxicity was associated with initial trough levels of ≥20 mg/L (odds ratio, 5.0; 95% confidence interval, 1.3-19.1) and with vasopressor use (odds ratio, 5.0; 95% confidence interval, 1.3-19.1). Kaplan-Meier analysis showed that the probability of nonnephrotoxicity for patients with initial VCM trough levels of ≥20 mg/L was lower compared with patients with trough levels of <15 mg/L. Initial trough levels of ≥20 mg/L but not ≥15 mg/L were associated with early-onset VCM-associated nephrotoxicity in critically ill patients. Future prospective studies are needed to examine outcomes in critically ill patients achieving initial VCM trough levels of 15-20 mg/L.

Relationship between initial vancomycin trough levels and early-onset vancomycin-associated nephrotoxicity in critically ill patients

Relationship between initial vancomycin trough levels and early-onset vancomycin-associated nephrotoxicity in critically ill patients

Currently used dosage regimens of vancomycin fail to achieve therapeutic levels in approximately 40% of intensive care unit patients.

ObjectiveThis study aimed to assess whether currently used dosages of vancomycin for treatment of serious gram-positive bacterial infections in intensive care unit patients provided initial therapeutic vancomycin trough levels and to examine possible factors associated with the presence of adequate initial vancomycin trough levels in these patients.MethodsA prospective descriptive study with convenience sampling was performed. Nursing note and medical record data were collected from September 2013 to July 2014 for patients who met inclusion criteria. Eighty-three patients were included. Initial vancomycin trough levels were obtained immediately before vancomycin fourth dose. Acute kidney injury was defined as an increase of at least 0.3mg/dL in serum creatinine within 48 hours.ResultsConsidering vancomycin trough levels recommended for serious gram-positive infection treatment (15 - 20µg/mL), patients were categorized as presenting with low, adequate, and high vancomycin trough levels (35 [42.2%], 18 [21.7%], and 30 [36.1%] patients, respectively). Acute kidney injury patients had significantly greater vancomycin trough levels (p = 0.0055, with significance for a trend, p = 0.0023).ConclusionSurprisingly, more than 40% of the patients did not reach an effective initial vancomycin trough level. Studies on pharmacokinetic and dosage regimens of vancomycin in intensive care unit patients are necessary to circumvent this high proportion of failures to obtain adequate initial vancomycin trough levels. Vancomycin use without trough serum level monitoring in critically ill patients should be discouraged.

Persistent Staphylococcus aureus Bacteremia

Persistent Staphylococcus aureus bacteremia (SAB) that fails to respond to appropriate antibiotic therapy is associated with poor outcomes. Comprehensive prospective studies on risk factors and outcomes of persistent bacteremia are limited. We investigated outcomes and risk factors encompassing clinical, pharmacokinetic, microbiologic, and genotypic characteristics associated with persistent bacteremia using a case-control study nested in a prospective cohort of patients with SAB at a tertiary-care hospital from August 2008 through September 2010. We compared the clinical characteristics, management, and outcomes of patients with persistent bacteremia (≥7 d) with controls with resolving bacteremia (<3 d). To detect associations between microbiologic and genotypic characteristics of methicillin-resistant S. aureus (MRSA) isolates and persistent bacteremia, we determined the heteroresistance phenotype, SCCmec type, agr genotype and functionality, multilocus sequence typing, and presence of 41 virulence genes. Our cohort consisted of 483 patients; 76 (15.7%) had persistent bacteremia, 212 (43.5%) had resolving bacteremia. In the multivariate analysis, independent risk factors associated with persistent bacteremia were community-onset bacteremia (odds ratio [OR], 2.91; 95% confidence interval [CI], 1.24–6.87), bone and joint infection (OR, 5.26; 95% CI, 1.45–19.03), central venous catheter-related infection (OR, 3.36; 95% CI, 1.47–7.65), metastatic infection (OR, 36.22; 95% CI, 12.71–103.23), and methicillin resistance (OR, 16.99; 95% CI, 5.53–52.15). For patients with eradicable foci, delay (>3 d) in the removal of the infection focus was significantly associated with persistent bacteremia (OR, 2.18; 95% CI, 1.05–4.55). There were no significant associations of persistent bacteremia with high vancomycin minimal inhibitory concentration, vancomycin heteroresistance, and microbiologic/genotypic characteristics of MRSA isolates. However, initial vancomycin trough level <15 mg/L was an independent risk factor for persistent MRSA bacteremia (OR, 4.25; 95% CI, 1.51–11.96) in the multivariate analysis. Clinical outcomes were significantly worse for patients with persistent bacteremia. Relapse of bacteremia and attributable mortality within 12 weeks after SAB were significantly higher in patients with persistent bacteremia than in those with resolving bacteremia (9.2% [7/76] vs. 2.4% [5/212], p = 0.02 and 21.1% [16/76] vs. 9.4% [20/212], p = 0.009, respectively).In conclusion, patients with SAB should be given early aggressive treatment strategies, including early source control and maintenance of a vancomycin trough level ≥15 mg/L, to reduce the risk of persistent bacteremia.

Effects of Targeting Higher Vancomycin Trough Levels on Clinical Outcomes and Costs in a Matched Patient Cohort

To compare clinical outcomes and costs in patients treated with the new vancomycin guidelines recommending goal serum trough concentrations of 15-20 mg/L versus patients treated with vancomycin doses targeting trough concentrations 5-20 mg/L prior to the new guidelines. Retrospective quasi-experimental study. Urban level I trauma center. A total of 200 patients treated with vancomycin for at least 72 hours for confirmed, complicated methicillin-resistant Staphylococcus aureus (MRSA) bacteremia during one of two study phases relative to the implementation of the vancomycin dosing guidelines targeting serum trough concentrations of 15-20 mg/L: 2005-2007 (preperiod phase) and 2008-2010 (postperiod phase). One hundred patients in each phase were matched in a 1:1 ratio according to diagnosis, any concomitant nephrotoxic agents (e.g., aminoglycosides, colistin, acyclovir), and age ± 5 years. Patients in the preperiod had significantly lower success rates with vancomycin than those in the postperiod (45% vs 60%, p=0.034). Median length of stay (LOS) was not significantly higher in patients in the preperiod versus postperiod (15 days vs 13.5 days; p=0.28), and patients in the preperiod received a longer median duration of vancomycin versus those in the postperiod (13 days vs 8.5 days; p<0.001). No statistically significant difference was noted in total hospital costs for patients treated with vancomycin during the preperiod versus the postperiod ($32,754 vs $27,709, p=0.147). However, total drug and monitoring costs of vancomycin were significantly higher for patients in the postperiod. Initial vancomycin trough levels were significantly lower in patients in the preperiod versus postperiod (12.3 mg/L vs 15.8 mg/L, p=0.02). Patients in the preperiod had lower rates of nephrotoxicity than those in the postperiod, although this difference was not statistically significant (15% vs 18%; p=0.85). Median (interquartile range) LOS was significantly longer in patients who developed nephrotoxicity compared with patients who did not develop nephrotoxicity (17 days [11.5-36.5 days] vs 14 days [9-24 days], p=0.017). Costs associated with measurement of serum creatinine concentrations and vancomycin trough levels as well as labor were significantly higher in patients who developed nephrotoxicity. Higher vancomycin trough concentrations improved outcomes in patients with complicated MRSA bacteremia. In addition, more aggressive dosing was shown to significantly decrease overall duration of vancomycin therapy, which may affect total hospital LOS and cost. Patients who experienced nephrotoxicity had a significantly longer hospital LOS. Additional studies evaluating optimal therapy for MRSA bacteremia in a larger cohort of matched patients are warranted.

Incidence of Nephrotoxicity and Association With Vancomycin Use in Intensive Care Unit Patients With Pneumonia: Retrospective Analysis of the IMPACT-HAP Database

BackgroundThe 2005 guidelines from the American Thoracic Society and the Infectious Diseases Society of America recommend vancomycin trough levels of 15 to 20 mg/L for the therapy of hospital-acquired (HAP), ventilator-associated (VAP), and health care–associated (HCAP) pneumonia. ObjectiveThe goal of this article was to report the incidence of nephrotoxicity and associated risk factors in intensive care unit patients who received vancomycin for the treatment of HAP, VAP, and HCAP. MethodsThis was a retrospective analysis of data from a multicenter, observational study of pneumonia patients. Antibiotic-associated nephrotoxicity was defined as either an increase in serum creatinine ≥0.5 mg/dL or 50% above baseline, from initiation of vancomycin to 72 hours after completion of therapy. Univariate and multivariate logistic regression analyses were performed to identify risk factors for development of renal dysfunction. ResultsOf the 449 patients in the database, 240 received at least one dose of vancomycin and 188 had sufficient data for analysis. In these 188 patients, 63% were male. Mean (SD) age was 58.5 (17.2) years, and the mean Acute Physiology and Chronic Health Evaluation II score was 19.4 (6.4). Nephrotoxicity occurred in 29 of 188 (15.4%) vancomycin-treated patients. In multivariate analysis, initial vancomycin trough levels ≥15 mg/L (odds ratio [OR], 5.2 [95% CI, 1.9–13.9]; P = 0.001), concomitant aminoglycoside use (OR, 2.67 [95% CI, 1.09–6.54]; P = 0.03), and duration of vancomycin therapy (OR for each additional treatment day, 1.12 [95% CI, 1.02–1.23]; P = 0.02) were independently associated with nephrotoxicity. The incidence of nephrotoxicity increased as a function of the initial vancomycin trough level, rising from 7% at a trough <10 mg/L to 34% at >20 mg/L (P = 0.001). The mean time to nephrotoxicity decreased from 8.8 days at vancomycin trough levels <15 mg/L to 7.4 days at >20 mg/L (Kaplan-Meier analysis, P = 0.0003). ConclusionsNephrotoxicity may be common among intensive care unit patients with pneumonia treated with broad-spectrum antibiotic therapy that includes vancomycin. The finding that an initial vancomycin trough level ≥15 mg/L may be an independent risk factor for nephrotoxicity highlights the need for additional studies to assess current recommendations for vancomycin dosing for ICU patients with pneumonia.

Simple approach to improving vancomycin dosing in intensive care: a standardised loading dose results in earlier therapeutic levels

Patients in the Intensive Care Unit (ICU) often have sub-therapeutic vancomycin levels in the initial stages of therapy. Loading doses have been demonstrated to overcome this problem. The aim of this study was to determine the impact of a standardised loading dose and increased clinician awareness of under-dosing on the achievement of early therapeutic vancomycin trough concentrations in the ICU. A pre- and post-intervention observational study was conducted in the ICU following the introduction of a 2-g vancomycin loading dose and demonstration of local under-dosing. All initial vancomycin trough levels were examined, except those from neurosurgical patients. Primary outcome measures were the proportion of patients achieving therapeutic vancomycin levels and mean trough concentrations. A year after introduction, a review was conducted to further assess the impact and sustainability of the intervention. There were 31 courses of vancomycin in the pre-intervention period (no loading doses given) and 21 courses in the post-intervention period, of which 11 had a loading dose. In the pre-intervention group, 13% of courses achieved therapeutic concentrations. This increased to 33% in the post-intervention group (P= 0.08). A statistically significant increase in mean trough concentration, from 9.8 ± 6.6 mg/L to 14.9 ± 6.3 mg/L (P= 0.01), between the pre- and post-intervention groups was observed. During the follow-up period, results were similar to the post-intervention audit. A standardised loading dose is a simple and sustainable intervention that may improve early achievement of therapeutic vancomycin levels in critically ill patients. The clinical significance of this requires further study.

Impact of a Hospitalwide Increase in Empiric Pediatric Vancomycin Dosing on Initial Trough Concentrations

To evaluate the impact of a hospitalwide increase in the recommended vancomycin starting dose from 45 to 60 mg/kg/day on initial vancomycin trough concentrations in children suspected of having an invasive methicillin-resistant Staphylococcus aureus (MRSA) infection. Retrospective medical record review. Dedicated children's hospital located in a tertiary care, academic medical center. A total of 182 children aged 1 month-12 years with normal renal function who had suspected MRSA infections treated with vancomycin during two different starting dose recommendation periods: 45 mg/kg/day divided every 8 hours during July 2006-June 2007 (low-dose group [88 children]) and 60 mg/kg/day divided every 6 hours during July 2008-June 2009 (high-dose group [94 children]). Data on patient demographics, vancomycin doses, and initial vancomycin trough concentrations were collected. No significant demographic differences were noted between patients in the low-dose and high-dose groups. The mean ± SD initial vancomycin trough level increased from 7 ± 5 μg/ml in the low-dose group to 9 ± 5 μg/ml in the high-dose group (p<0.001). The percentage of patients with an initial trough level less than 5 μg/ml declined from 38% (33/88 children) in the low-dose group to 17% (16/94 children) in the high-dose group (p<0.001), whereas the percentage of patients with an initial trough concentration in the potentially adverse range (> 20 μg/ml) did not change between the two groups (2% vs 2%, p=0.9). Less than 14% (13/94 children) achieved a trough level in the range of 15-20 μg/ml in the high-dose group. An increase in the recommended vancomycin starting dose to 60 mg/kg/day decreased the likelihood of an initial low vancomycin trough level (< 5 μg/ml), with no increase in the proportion of patients with trough levels in a potentially toxic range. The 60-mg/kg/day dose did not consistently achieve a vancomycin trough of 15-20 μg/ml, a goal suggested by some experts for adults. Comparative effectiveness studies are needed to directly evaluate vancomycin dosing regimens and clinical outcomes for children with invasive MRSA infections.