Vancomycin Serum Trough Concentrations Research Articles

The Impact of Serum Vancomycin Levels and Minimum Inhibitory Concentrations of Methicillin‐Resistant Staphylococcus aureus on Mortality in Patients with Nosocomial Pneumonia

Vancomycin is the treatment of choice for methicillin-resistant Staphylococcus aureus (MRSA) infections; however, treatment failure is not uncommon, even when the minimum inhibitory concentration (MIC) of the MRSA strain is within the susceptible range for vancomycin. To describe the relationship between molecular markers such as the mecA and agrII genes, serum vancomycin levels and vancomycin MICs, and the 30-day mortality rate of patients with nosocomial MRSA pneumonia in an intensive care unit (ICU). The present study was a prospective cohort study including all patients with MRSA hospital-acquired pneumonia or ventilator-associated pneumonia who were admitted to the ICU of a tertiary care hospital between June 2009 and December 2011. The MIC for vancomycin was determined using the E-test and broth microdilution methods. Variables analyzed included age, sex, comorbid conditions, serum vancomycin trough concentration, the Acute Physiology and Chronic Health Evaluation II (APACHE) score and the presence of the agrII gene. The primary outcome was mortality at 30 days. Thirty-six (42.4%) patients died within 30 days of the index MRSA culture. A multiple regression analysis that included the variables of MIC (determined using the E-test or broth microdilution methods), APACHE II score, serum vancomycin level and the presence of agrII revealed that only the APACHE II score was related to the 30-day mortality rate (P=0.03). Seven patients (9.0%) with isolates exhibiting an MIC ≥1.5 μg/mL according to the E-test method died, and nine patients (11.6%) survived (P=0.76). Of the patients for whom MICs were determined using the broth microdilution method, 11 (14.1%) patients with MICs of 1.0 μg/mL died, and 16 (20.5%) survived (P=0.92). The median APACHE II score of survivors was 22.5, and the median score of nonsurvivors was 25.0 (P=0.03). The presence of the agrII gene was not related to the 30-day mortality rate. Patients with severe hospital-acquired pneumonia presented with MRSA isolates with low to intermediate vancomycin MICs in the ICU setting. At the Hospital de Clínicas de Porto Alegre (Porto Alegre, Brazil), the 30-day mortality rate was high, and was similar among patients with severe hospital-acquired pneumonia infected with MRSA isolates that exhibited MICs of ≤1.5 μg/mL determined using the E-test method and ≤1.0 μg/mL determined using the broth microdilution method in those who achieved optimal serum vancomycin levels. The APACHE II scores which provides an overall estimate of ICU mortality were independently associated with mortality in the present study, regardless of the MICs determined. Molecular markers, such as the agrII gene, were not associated with higher mortality in the present study.

Acute kidney injury after myeloablative cord blood transplantation in adults: the efficacy of strict monitoring of vancomycin serum trough concentrations

Acute kidney injury (AKI) is a common medical complication after myeloablative allogeneic stem cell transplantation (SCT). We have previously performed a retrospective analysis of AKI after cord blood transplantation (CBT) in adults, and found that the maximum of vancomycin (VCM) trough levels were significantly higher in patients with AKI. Following these results, we have monitored VCM serum trough concentrations more strictly, to not exceed 10.0mg/L, since 2008. In this report, we performed an analysis of AKI in a new group of 38 adult patients with hematological malignancies treated with unrelated CBT after myeloablative conditioning between January 2008 and July 2011. Cumulative incidence of AKI at day 100 after CBT was 34% (95% confidence interval 19-50). The median of the maximum value of VCM trough was 8.8 (4.5-12.2) mg/L. In multivariate analysis, no factor was associated with the incidence of AKI. No transplant-related mortality was observed. The probability of disease-free survival at 2years was 83%. These findings suggest that strict monitoring of VCM serum trough concentrations has a beneficial effect on outcomes of CBT.

Evaluation of a pediatric continuous-infusion vancomycin therapy guideline

An institutional guideline for converting pediatric patients to continuous-infusion vancomycin (CIV) therapy if therapeutic targets are not achieved with intermittent i.v. dosing was evaluated. All patients within a specified age range (>6 months but <19 years) who were converted to CIV therapy for pneumonia or osteomyelitis during the 2 years after guideline implementation were included in the evaluation. The guideline calls for conversion to CIV therapy if goals for trough serum vancomycin concentration (SVC) are not attained with escalating intermittent-infusion vancomycin (IIV) dosing. Primary outcome measures included the rate of attainment of the goal steady-state trough SVC (15-20 mg/L), preferably within 24-48 hours, the adequacy of an empirical dosing strategy, and adverse events. Secondary study outcomes included final vancomycin doses and the time to attainment of therapeutic SVCs. Within 24-48 hours after conversion to CIV therapy, the mean initial plateau SVC in the evaluated cases (n = 15) was 20.2 mg/L; the mean of all SVCs was 19.1 mg/L. The range of dosages required to achieve a plateau SVC of 15 mg/L was 23.8-65.4 mg/kg/day (median, 41 mg/kg/day). The mean ± S.D. vancomycin dosage at the end of CIV therapy was 44.3 ± 12.8 mg/kg/day. Monitoring of serum creatinine, urine output, and glomerular filtration rate indicated that no patients developed nephrotoxicity during CIV therapy. Conversion from IIV to CIV therapy in selected pediatric patients appeared to be safe and well tolerated, with few adverse effects noted. Using the institutional CIV dosing guideline, goal plateau SVC values were attained in most patients within 24-48 hours.

The Relationship of Nephrotoxicity to Vancomycin Trough Serum Concentrations in a Veteran's Population: A Retrospective Analysis

The risk of vancomycin-associated nephrotoxicity varies greatly depending on the trough concentration. Recent guidelines suggest target vancomycin trough concentrations of 15-20 mg/L as a predictor of efficacy in the treatment of severe gram-positive infections. Limited data exist quantifying the risk for nephrotoxicity with various ranges of vancomycin troughs. To determine the occurrence of nephrotoxicity during vancomycin therapy and up to 72 hours after its completion, in relation to the maximum trough concentration value, and identify risk factors that impact nephrotoxicity associated with vancomycin use. We reviewed the medical records of veterans with a baseline serum creatinine less than 2 mg/dL who received 48 or more hours of vancomycin therapy and had 1 or more vancomycin trough samples obtained within 96 hours of therapy initiation from January 1, 2006, to November 1, 2008, to determine the occurrence of nephrotoxicity (as defined by RIFLE [Risk, Injury, Failure, Loss, and End-stage renal disease] criteria). Thirty-four (12.6%) patients developed nephrotoxicity. In multiple logistic regression analysis, maximum trough concentrations (OR 1.14; 95% CI 1.09 to 1.20), documented hypotension (OR 4.7; 95% CI 1.3 to 16.4), and weight (OR 1.02; 95% CI 1.0 to 1.03) were found to be significantly associated with the occurrence of nephrotoxicity. Once stratified into ranges of 5-10 mg/L (4.9%), 10.1-15 mg/L (3.1%), 15.1-20 mg/L (10.6%), 20.1-35 mg/L (23.6%), and greater than 35 mg/L (81.8%), increasing trough ranges were associated with a subsequently higher risk of nephrotoxicity. In the population evaluated, hypotension and trough concentrations were predictors of nephrotoxicity; elevated vancomycin trough concentration had the highest odds of association. These data reinforce the close therapeutic monitoring guidelines for vancomycin trough concentrations, especially when targeting troughs of 15-20 mg/L.

Evaluation of a vancomycin dosing nomogram in achieving high target trough concentrations in Taiwanese patients

The use of a vancomycin dosing nomogram is an alternative and more cost-effective method to conventional dosing; it reliably allows the achievement of trough vancomycin serum concentrations of 5-15 mg/l, with a successful clinical response. Recent guidelines have further recommended that the trough concentration be maintained at 15-20mg/l for complicated infections. However, to date no published nomogram has been constructed to achieve the optimal trough of 15-20mg/l in an Asian population. This study aimed to develop two vancomycin nomograms for the achievement of trough concentrations of 5-15 mg/l and 15-20mg/l in the Taiwanese population, and to ensure the clinical efficacy and safety of such nomograms. The estimated concentrations and the real concentrations in our patient population were compared between six pharmacokinetic models to see which was the most precise. As the Ambrose method was the best at predicting the trough, this was used to create two nomograms, one for a target trough at 5-15 mg/l and the other for a target trough at 15-20mg/l. We then evaluated the nomograms by analyzing the number of patients with the target vancomycin trough concentration, clinical and microbiological outcomes, and safety. More patients who had dosing according to the nomogram had a vancomycin trough concentration within the desired target range than patients who had conventional dosing (65.1% vs. 32.1%, p = 0.001). These patients also had a higher rate of 'cure' as the clinical response (35.7% vs. 27.1%) and 'eradication' as the microbiological response (46.4% vs. 29.2%), and a lower rate of nephrotoxicity (14.3% vs. 22.9%). For the patients with a complicated infection, more had a trough between 15 and 20mg/l when vancomycin was dosed with the nomogram than when dosed conventionally (41.2% vs. 12.1%, p = 0.019). We found that when dosing vancomycin with these nomograms, patients tended to have vancomycin trough concentrations within the target range and also to have a better outcome with regard to clinical efficacy and the safety profile.

The relationship between trough concentration of vancomycin and effect on methicillin-resistant Staphylococcus aureus in critically ill patients

The incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections in intensive care units in Malaysia is significant. Invasive MRSA infections are commonly treated with vancomycin. In clinical practice, the serum vancomycin trough concentration is used as a surrogate marker of vancomycin efficacy. A low concentration of vancomycin may result in less effective therapy and increase the risk of bacterial resistance. We evaluated the relationship between the resolution of MRSA infections and trough concentrations of vancomycin. A total of 76 patients admitted between January 2005 and February 2011 were included in the study. Serum vancomycin trough concentration data were collected from the microbiology records. The clinical response was evaluated on the basis of clinical notes and culture test results. A total of 262 appropriate trough concentration data were included, with a median of 3 trough concentrations per patient. Fifty-four patients responded to vancomycin therapy. The initial trough concentration did not differ between responders and non-responders (p=0.135) but the corrected trough concentration was higher among responders than among non-responders (11.64±1.50 mg/l and 9.25±1.59 mg/l, respectively; p=0.036). The average total daily dose of vancomycin was significantly higher among the responders (p=0.008). In this critically ill population, a vancomycin dose of 15 mg/kg/day was found sufficient to produce optimal trough concentrations to eradicate the MRSA infection. This study demonstrated the significant relationship between response to treatment of MRSA infection and serum vancomycin trough concentrations.

Vancomycin: evaluating dosing and therapeutic drug monitoring on the neonatal unit

ObjectiveThe aim of this audit was to evaluate the effectiveness of our dosing schedule of 15 mg/kg, at varying intervals depending on corrected age, at achieving trough serum vancomycin concentrations...

Evaluation of the vancomycin dosage regimen based on serum creatinine used in the neonatal intensive care unit

Vancomycin is frequently used for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections; however, determining the optimal dosage for neonates is difficult because of their immature renal function. Serum creatinine-based dosing was introduced in Kumamoto City Hospital Neonatal Medical Center. Serum trough concentration and therapeutic efficacy of vancomycin were evaluated before and after the introduction of the creatinine-based dosing. When the therapeutic range of serum trough concentration of vancomycin at steady state was set to 5-15 µg/mL, 20 trough concentrations (48.8%) were within the therapeutic range and 21 trough concentrations were outside the therapeutic range before the introduction of the serum creatinine-based dosing. After the introduction of serum creatinine-based dosing, 18 trough concentrations (81.8%) were within the therapeutic range and 4 trough concentrations were not, and there was an increase in the number of patients with trough concentrations in the therapeutic range (P= 0.01; Fisher's exact test). The serum creatinine-based dosing of vancomycin is useful in maintaining the appropriate serum level of vancomycin in neonates.

Relationships between vancomycin minimum inhibitory concentration, dosing strategies, and outcomes in methicillin-resistant Staphylococcus aureus bacteremia

Retrospective study aimed to examine outcomes of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia in relationship to vancomycin minimum inhibitory concentration (VAN MIC) and serum trough concentrations among subjects who had ≥1 blood culture positive for MRSA between April 2008 and August 2009. Treatment failure occurred in 7/24 (29%) subjects with VAN MIC = 2 mg/L versus 20/94 (21%) subjects with VAN MIC ≤1.5 mg/L (adjusted OR 1.11, 95% confidence interval [CI] 0.24–5.14). Among subjects who had documented VAN serum trough concentrations, treatment failure occurred in 5/26 (19%) subjects with concentrations <15 mg/L versus 18/68 (27%) subjects with concentrations ≥15 mg/L (adjusted OR 0.91, 95% CI 0.21–3.84). In conclusion, treatment outcomes were similar regardless of VAN MIC, although there was a non–statistically significant trend towards decreased clinical efficacy among patients with VAN MIC = 2 mg/L. Optimization of VAN pharmacokinetic indices did not appear to correlate with clinical responses.

Validation of the Effectiveness of a Vancomycin Nomogram in Achieving Target Trough Concentrations of 15–20 mg/L Suggested by the Vancomycin Consensus Guidelines

To assess and validate the effectiveness of a newly constructed vancomycin dosing nomogram in achieving target trough serum concentrations of 15-20 mg/L. Prospective multicenter study. Five tertiary care teaching hospitals. A total of 200 adults who required vancomycin dosages targeted to attain recommended trough vancomycin serum concentrations of 15-20 mg/L. The new nomogram, which based dosing on weight and renal function, was used to calculate patients' initial vancomycin dosages. Serum trough concentrations were measured before the fourth or fifth dose, and dosages were adjusted as needed. Median patient age was 56 years (interquartile range [IQR] 49-65 yrs), median weight was 71.2 kg (IQR 63-85 kg), and median creatinine clearance was 66.5 ml/minute (IQR 52-82 ml/min). The median initial vancomycin trough concentration achieved was 17.5 mg/L (IQR 15.0-20.0 mg/L), with 116 patients (58%) achieving the initial target trough of 15-20 mg/L. The median percent error was 13.6%, and the mean ± SD error for predicted versus actual serum trough concentrations was -0.50 ± 0.021 mg/L. One hundred fifty-four patients (77%) eventually achieved the trough target concentration within a median of 2 days. One hundred forty patients (70%) achieved initial troughs of 14-21 mg/L and 160 (80%) achieved troughs of 13-22 mg/L. Nine patients (4.5%) experienced nephrotoxicity while receiving vancomycin, which occurred after a median of 8 days of therapy. The median initial vancomycin trough concentration for these patients was 18.5 mg/L (IQR 15.3-19.3 mg/L), with eight of the nine patients having trough concentrations of 15 mg/L or greater. Fifty-eight percent of patients achieved the target trough of 15-20 mg/L (median 17.5 mg/L). The performance of the nomogram improved to 80% when the trough range was adjusted to 13-22 mg/L. Caution should be applied when using this nomogram. The nomogram should not replace clinical judgment, and dosage adjustments should be based on pharmacokinetic-pharmacodynamic targets and clinical response.

Vancomycin Dosing in Obese Pediatric Patients

Data are lacking to guide antimicrobial dosing for overweight children. The authors hypothesized that obese children would have increased vancomycin serum trough concentrations compared with nonobese children. A matched study design was employed to compare retrospectively vancomycin trough concentrations. Among 24 matched pairs, obese patients received 14.1 ± 1.5 mg per kilogram and nonobese children 14.9 ± 0.9 mg per kilogram of vancomycin per kilogram of vancomycin (P = .03). There was a trend toward higher vancomycin serum concentrations in obese (6.9 ± 4.30 μg/mL) versus nonobese children (4.8 ± 3.08 μg/mL; P = .052). Mean half-life in obese patients was 2.9 ± 0.29 hours and volume of distribution was 0.35 ± 0.15 L/kg. Since obesity did not alter vancomycin trough concentrations, overweight children should receive vancomycin based on actual body weight. However, since vancomycin troughs were substantially lower than those recommended for adults, further studies of vancomycin metabolism in children are needed.

Increasing Vancomycin Serum Trough Concentrations and Incidence of Nephrotoxicity

Background Conflicting evidence regarding the association of vancomycin serum concentrations with efficacy and toxicity has resulted in controversy regarding optimal target concentrations. Recent publications recommend attaining higher vancomycin trough concentrations of 15 to 20 mg/L for target infections, yet limited research is available assessing the correlation of vancomycin serum concentrations with toxicity. The aim of this study was to evaluate the association between vancomycin serum trough concentrations and nephrotoxicity. Methods A 2-phase retrospective analysis was completed. Phase 1 evaluated 2493 courses of vancomycin completed between January 2003 and December 2007. The analysis describes a 5-year trend in vancomycin prescribing practices and assesses the association of nephrotoxicity with baseline serum creatinine, vancomycin serum trough concentrations, and duration of vancomycin therapy. Phase 2 examined patients receiving vancomycin therapy during 2007 to evaluate specific risk factors for development of nephrotoxicity. Results The proportion of vancomycin serum trough concentrations ≥15 mg/L and ≥20 mg/L increased significantly over time. Statistical analysis identified vancomycin serum trough concentrations ≥14 mg/L, duration of vancomycin therapy ≥7 days, and baseline serum creatinine levels ≥1.7 mg/dL as independent predictors of nephrotoxicity. Phase 2 analysis again implicated mean vancomycin serum trough concentration as a significant predictor of nephrotoxicity. Nephrotoxicity resolved in 81% (17/21) of cases evaluated. Conclusions A higher vancomycin serum trough concentration and prolonged vancomycin therapy are associated with an increased risk of nephrotoxicity. The decision to target increased vancomycin trough concentrations should be based on an assessment of the severity of the infection and must consider the nephrotoxicity risk associated with increased vancomycin levels.

Predictors of persistent methicillin-resistant Staphylococcus aureus bacteraemia in patients treated with vancomycin

The high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) coupled with an increase in vancomycin use have induced vancomycin tolerance in MRSA, adversely affecting the outcome of MRSA bacteraemia. This study aimed to identify predictors of persistent MRSA bacteraemia (PMRSAB) in patients treated with vancomycin. A retrospective, case-control study was performed at a university hospital in Korea from January 2006 to February 2009. Subjects included 96 patients who had MRSA bacteraemia and received vancomycin under therapeutic drug monitoring. We compared the clinical characteristics, management and outcomes of cases with PMRSAB (>or=7 days, n = 31) with controls with non-PMRSAB (<or=3 days, n = 32). Vancomycin MICs were determined by the Vitek 2 system. Of 96 patients with MRSA bacteraemia, MRSA isolates from 21 patients (21.9%) showed a vancomycin MIC of 2 mg/L. Independent predictors of PMRSAB were: retention of implicated medical devices [odds ratio (OR), 10.35; 95% confidence interval (CI), 1.03-104.55]; MRSA infection of at least two sites (OR, 10.24; 95% CI, 1.72-61.01); and vancomycin MIC of 2 mg/L (OR, 6.34; 95% CI, 1.21-33.09). The frequency of side effects and mean trough serum vancomycin concentrations were not significantly different between the two groups. Sixteen patients with PMRSAB subsequently received teicoplanin +/- arbekacin, linezolid or quinupristin/dalfopristin, due to vancomycin failure or intolerance. To minimize the risk of PMRSAB, early removal of implicated devices and evaluation for metastatic infections should be encouraged. Alternative antibiotic therapy is warranted for infections due to isolates with elevated vancomycin MICs, as well as for the high rates of side effects.

Vancomycin: the need to suit serum concentrations in hemodialysis patients

The vancomycin dose for hemodialysis (HD) patients should be adjusted by monitoring drug serum concentrations. However, this procedure is not available in most health services in Brazil, which usually adopts protocols based on published studies. The trials available are controversial, and several have not been conducted with current dialyzers. This study aimed at assessing the suitability of vancomycin serum concentrations in HD patients at a public hospital. Blood samples of HD patients were collected from November 2006 to May 2007, at time intervals of 48, 96, 120, or 168 hours after vancomycin administration. Drug measurement was performed with polarized light immunofluorescence. Approximately 86% of trough vancomycin serum concentrations were below the recommended value, indicating exposure to subtherapeutic doses and a higher risk for selecting resistant microorganisms.

Clinical outcomes and nephrotoxicity associated with vancomycin trough concentrations during treatment of deep-seated infections

Objective: Higher vancomycin concentrations are thought necessary for treatment of deep-seated methicillin-resistant Staphylococcus aureus (MRSA) infection, yet this may result in greater risk of nephrotoxicity. We evaluated the relationship of serum vancomycin trough concentration with clinical outcomes and nephrotoxicity for patients with deep-seated MRSA infection.Methods: A retrospective cohort study evaluated adults with MRSA pneumonia, endocarditis or osteomyelitis who received vancomycin for ≥ 5 days from June 2005 to June 2007. Patients were stratified by mean vancomycin trough level [low (< 15 mg/l), high (≥ 15 mg/l)]. Outcomes were clinical response, mortality, length of stay (LOS) and nephrotoxicity. Three definitions of nephrotoxicity were used: i) rise in serum creatinine (SCr) ≥ 0.5 mg/dl; ii) 50% increase in SCr; and iii) 25% decrease in estimated creatinine clearance.Results: Fifty-five patients experiencing MRSA pneumonia (n = 28), endocarditis (n = 9), osteomyelitis (n = 20) and multiple infections (n = 2) were stratified into low (n = 39) and high (n = 16) groups. High group patients were more likely to be septic (p = 0.01) and have a higher APACHE II score (p = 0.01). After adjustment for APACHE II score, clinical response rates among survivors did not differ significantly. Risk of death was not significantly different between the high (19%) and low (5%) group patients (p = 0.1). LOS did not differ significantly between groups (p = 0.7). Nephrotoxicity occurred in the low and high groups, respectively, for 10 and 31% (p = 0.04) with definition 1, 10 and 31% (p = 0.04) with definition 2, and 13 and 25% (p = 0.1) with definition 3. After adjustment for APACHE II score, odds of nephrotoxicity based on definitions 1 or 2 were increased among the high versus low groups (OR = 3.27, 95% CI: 0.7 – 15.25, p = 0.1), although not statistically significant.Conclusions: Clinical outcomes did not differ significantly between high and low trough groups for deep-seated MRSA infections. Nephrotoxicity was consistently higher in the high trough group, regardless of the definition used.

Optimizing Vancomycin Dosing through Pharmacodynamic Assessment Targeting Area under the Concentration-Time Curve/Minimum Inhibitory Concentration

Because of its activity against multidrug resistant gram-positive organisms, vancomycin is one of the antimicrobials most utilized in health care systems worldwide. Despite its widespread use, application of the pharmacodynamic principles governing vancomycin efficacy are not frequently considered in contemporary clinical practice. Although the vancomycin trough serum concentration has been used historically to assess the adequacy of a prescribed dose, data validating that this practice leads to improved patient outcomes do not exist. Alternatively, both in vitro and clinical outcomes data demonstrate improved results when an area under the concentration-time curve/minimum inhibitory concentration (AUC/MIC) of 400 mcg•h/mL or greater is achieved. This article describes the process through which individualized vancomycin dosing regimens targeting an AUC/MIC of 400 mcg•h/mL or greater, rather than trough serum concentration, at the beside can be derived. The equations, methodology, thought processes, benefits, potential pitfalls, and practical applicability of this method are specifically examined. Obtaining the actual MIC value—not an interpretation—from the microbiology laboratory and/or the MIC distribution for Staphylococcus aureus within one's own institution is essential for implementation of this method. Although vancomycin dosing recommendations suggested in contemporary practice guidelines are likely adequate for most patients, using the methods described here may lead to improved clinical outcomes for nonstandard conditions in patients who are critically ill and would benefit from an individualized dosing approach.

Hoek’s formula, a cystatin C-based prediction formula for determining the glomerular filtration rate, is the most effective method for adjusting the dosage of vancomycin

Some formulas using the serum cystatin C level to estimate the GFR have recently been reported. However, there has been no report of a serum cystatin C-based formula for adjusting the dosage of the drugs cleared by the kidney. In this study, we compared the predictive performance of the serum vancomycin trough concentration predicted using serum cystatin C-based formulas. The data were collected from 158 hospitalized patients. Five formulas have been published to predict the GFR using serum cystatin C. The cystatin C-based formulas were divided into two groups, formulas with or without anthropometric data. We predicted the serum vancomycin trough concentrations using VCM-TDM S_edition ver. 1.00 software. In formulas with anthropometric data, the mean absolute error (MAE) using Hoek's formula was 2.38, the MAE using Grubb's 1 formula was 4.13, the MAE using Sjöström's formula was 2.90, and the MAE using Cockcroft and Gault formula based on creatinine was 4.42. On the other hand, in formulas without an anthropometric data group, the MAE using Larsson's formula was 3.07, and the MAE using Grubb's 2 formula was 3.63. These results suggested that Hoek's formula is the most useful formula for determining the initial dosage settings for vancomycin.

Observations on vancomycin use in U.S. hospitals

Current knowledge and policies regarding vancomycin use and the clinical performance of vancomycin in U.S. hospitals were assessed. A questionnaire was sent to interested hospital pharmacists. An observational study of hospitalized adults who received at least 72 hours of i.v. vancomycin for a culture-confirmed gram-positive infection followed. Hospital antibiograms were obtained for gram-positive susceptibility data. A total of 59 respondents completed the survey. Survey results revealed that vancomycin is rarely restricted. Investigators from 24 hospitals, 16 (67%) of which were teaching facilities, collected retrospective data from the records of 200 patients. Infection sites included blood, lower respiratory tract, and skin and soft tissue. Staphylococcus aureus was isolated from 52% of positive cultures; 75% of these were methicillin-resistant S. aureus (MRSA). Serum vancomycin concentrations were monitored in 95% of patients; results from 22 hospitals were evaluable. Trough serum vancomycin concentrations were higher in teaching versus nonteaching hospitals (p < 0.001). Peak serum vancomycin concentrations were also higher in teaching versus nonteaching hospitals (p < 0.05). Clinical responses from 22 hospitals were evaluable; the mean success rate of 82% did not significantly differ between teaching and nonteaching hospitals. Vancomycin- associated adverse events occurred in 13 patients (6.5%) and were reported more frequently for patients in teaching versus nonteaching hospitals (p = 0.02). Observational data suggest that vancomycin remains an effective antibiotic with infrequent discontinuations due to adverse events, and trough serum vancomycin concentrations are monitored routinely. Antibiogram data revealed that the prevalence of MRSA continues to increase.

Predictability of vancomycin pharmacokinetics in neonates

Dear Editor, We read with great interest the paper of Cunha et al. on the cost-ineffectiveness of measuring serum vancomycin trough concentrations in adult hospitalized patients receiving parenteral vancomycin. Based on a retrospective analysis of observations collected in 351 patients, the authors illustrated that vancomycin dosed by creatinine clearance estimations, based on serum creatinine values, was acceptably accurate [1]. We would like to add to the discussion that the conclusions formulated by Cunha et al. in adults might be extrapolated to neonatal populations in whom vancomycin dosed by creatinine clearance estimations is acceptable once serum creatinine values reflect renal function. Since glycopeptides are almost exclusively eliminated according to the glomerular filtration rate (GFR), developmental changes in renal clearing capacity in the neonate have to be taken into account. We therefore would like to report here our recently published data on vancomycin clearance in the first month of life in 214 neonates and compare them with the findings of Cunha et al. [1, 2]. Size explained 49.8%, postmenstrual age 18.2%, and renal function (serum creatinine values) 14.1% of vancomycin clearance variability, resulting in over 80% of explained variability in vancomycin clearance in the first 4 weeks of postnatal life [2]. In children and adults, serum creatinine values serve as a useful and reliable marker of renal clearance. In neonates, however, serum creatinine values at birth mainly reflect the maternal renal function and only turn into a reliable marker of renal clearance after the first week of life [3]. The overall high predictability of vancomycin clearance in this cohort of neonates therefore mainly relates to the fact that this drug is only very rarely administered in the very first days of life when creatinaemia does not yet reflect neonatal GFR and is in contrast to the limited predictability of renal drug clearance at birth [4]. The bactericidal activity of glycopeptide antibiotics is based on the inhibition of bacterial cell-wall synthesis. Glycopeptide antibiotics are the drugs of choice for methicillin-resistant staphylococcal infections and are widely used as empiric treatment for infections related to the central venous line in neonates. These infections are often caused by coagulase-negative staphylococci. Taking these epidemiological factors into account, vancomycin is only rarely administered in the first days of life but is a frequently administered drug in neonates for the abovementioned pathogens [5]. We therefore suggest extrapolating the conclusions formulated by Cunha et al. in adults to all populations in whom vancomycin dosed by creatinine clearance estimations is acceptably accurate hereby excluding the first days of postnatal life in addition to other specific conditions such as extracorporeal membrane oxygenation. Eur J Clin Microbiol Infect Dis (2007) 26:847–848 DOI 10.1007/s10096-007-0367-4

A retrospective analysis of possible renal toxicity associated with vancomycin in patients with health care-associated methicillin-resistant Staphylococcus aureus pneumonia

The goal of this investigation was to determine whether more aggressive vancomycin dosing is associated with greater risk for renal toxicity in patients with health care-associated pneumonia (HCAP) attributed to methicillin-resistant Staphylococcus aureus (MRSA). This was a retrospective, single-center, observational cohort study. The following information was obtained for all study patients from automated hospital, microbiology, and pharmacy databases: age, sex, weight, serial serum creatinine (SCr), age- and sex-adjusted creatinine clearance (CrCl) during receipt of vancomycin, vancomycin serum trough concentrations, duration of vancomycin therapy, and Acute Physiology and Chronic Health Evaluation II scores. Renal toxicity was defined as either a 0.5-mg/dL increase from baseline in SCr or a >or=50% increase in SCr based on serial SCr measurements. Data for patients who met the definition of renal toxicity were compared with data for those who did not. Ninety-four patients (mean [SD]age, 59.0 [15.6] years; 59 [62.8%] men; 73 (77.7%) white; mean baseline CrCl, 70.3 [23.0] mL/min) were identified as having MRSA HCAP. Forty (42.6%) patients developed renal toxicity. Patients who developed renal toxicity were significantly more likely than patients who did not develop renal toxicity to have greater mean vancomycin serum trough concentrations (20.8 [9.9] g/mL vs 14.3 [6.7] g/mL, respectively; P < 0.001), vancomycin serum trough concentrations >or=15 g/mL (67.5% vs 40.7%; P = 0.01), and a prolonged duration (>or=14 days) of vancomycin treatment (45.0% vs 20.4%; P = 0.011). Logistic regression analysis identified a maximum vancomycin serum trough concentration of >or=15 g/mL as being independently associated with renal toxicity (adjusted odds ratio = 2.82; 95% CI, 1.02-7.74; P = 0.045). The overall mean change in CrCl for the study population was -13.5 (-16.0) mL/min (range, 0.0 to -62.6 mL/min). Patients with maximum measured vancomycin serum trough concentrations >or=15 g/mL (n = 49) had significantly greater absolute changes in CrCl compared with patients with maximum measured vancomycin serum trough concentrations <15 g/mL (n = 45) (-18.9 [-17.0] vs -7.6 [-12.5] mL/min, respectively; P < 0.001). The results suggest that aggressive vancomycin dosing and prolonged vancomycin administration may be associated with greater risk for renal toxicity in patients with MRSA HCAP. However, this retrospective study cannot establish causation, and a prospective, randomized, double-blind trial is needed.