Vancomycin Trough Research Articles

Outcomes and Nephrotoxicity Associated with Vancomycin Treatment in Patients 80 Years and Older.

PurposeThis retrospective observational study investigated the efficacy and safety of vancomycin to treat patients aged 80 years and older. In particular, the associations between vancomycin trough concentration (VTC) and treatment outcomes or nephrotoxicity were explored.Patients and MethodsPatients aged ≥80 years had received ≥3 vancomycin treatments and ≥1 detection of VTC. Treatment outcomes were defined as success or failure. Nephrotoxicity was considered an increase in serum creatinine ≥ 44.2 mmol/L, or 50% above baseline, for ≥2 consecutive days. Univariate and multivariate analyses were performed to identify risk factors for treatment failure and nephrotoxicity.ResultsOf 349 patients, 120 (34.4%) experienced treatment failure. For patients with VTCs at <10, 10–15, 15–20, and ≥20 µg/mL, the clinical response rates were, respectively, 77.8, 77.0, 80.5, and 61.0%; the 30-day mortality rates were 2.8, 15.0, 15.3, and 37.8%; and the rates of persistent bacteremia were 16.7, 12.4, 11.9, and 11.0%. The multivariate analysis indicated that blood urea nitrogen ≥11 g/dL and heart failure were independently associated with treatment failure; but not VTC (P = 0.004, 0.016, 0.828, respectively). During vancomycin treatment, 42 (12.0%) patients experienced nephrotoxicity with recovery time 7.5 ± 4.5 days. Fewer than half of patients with nephrotoxicity recovered after suspending vancomycin application. The variables found independently associated with increased nephrotoxicity were: VTC ≥15 µg/mL; treatment duration ≥15 d; and concomitant aminoglycosides administration (P = 0.024, 0.035, 0.029).ConclusionIn patients aged 80 years and older, elevated VTC level was not associated with favorable treatment outcomes. Patients with VTC ≥20 µg/mL appear to suggest a worsened prognosis compared with lower VTCs. The risk of nephrotoxicity increases with elevated VTC, longer treatment time, and concomitant aminoglycoside administration.

Optimizing outcomes using vancomycin therapeutic drug monitoring in patients with MRSA bacteremia: trough concentrations or area under the curve?

BackgroundVancomycin therapeutic drug monitoring is routinely performed but the specific measure used in practice is variable. ObjectiveTo evaluate the relationship between the first measured vancomycin trough, area-under-the-curve (AUC), and failure in patients with MRSA bacteremia. MethodsThis retrospective, cohort study included adult non-neutropenic patients with MRSA bacteremia who received vancomycin. The primary outcome was treatment failure. Initial trough and AUC values were compared between the failure and success groups. Classification and regression tree analysis was used to identify thresholds associated with failure. Multivariate analysis was performed to control for identified confounders. ResultsThere were 89 patients. Failure occurred in 23 (26%). Trough and AUC values associated with failure were < 10.6 mg/L (39% vs. 13%; P = 0.006) and AUC < 410mg*h/L (40% vs. 17%; P = 0.014). Both remained significant after controlling covariates (trough < 10.6 mg/L, OR [95% CI] = 4.91 [1.6–15]; AUC<410mg*h/L, OR [95% CI] = 3.13 [1.14–8.62]). Only AUC was predictive of nephrotoxicity. ConclusionFailure was more common with troughs < 10.6 mg/L or AUC < 410 mg*h/L. Supratherapeutic AUCs, but not trough, were associated with nephrotoxicity.

Pediatric Antibiotic Stewardship: Optimization of Vancomycin Therapy Based on Individual Pharmacokinetics.

Vancomycin has been a first-line treatment for Gram-positive infections for decades. However, strategies for therapeutic drug monitoring (TDM) and dose-optimization in pediatrics remain controversial. In this study, we analyzed the impact of specific antibiotic stewardship interventions on efficacy and safety of vancomycin therapy. From September 2014 to May 2017, we conducted a prospective study to compare a control and a TDM intervention group in our tertiary care center. As part of an antibiotic stewardship program, we implemented internal guidelines on correct vancomycin dosing, TDM timing, as well as targeted trough level range and installed a pharmacokinetic (PK) consultation service to adapt vancomycin dosing to individually calculated PK parameters. As primary clinical outcomes, the percentage of patients with sustained therapeutic vancomycin trough levels and treatment days with therapeutic vancomycin trough levels, that is, 10-15 mg/L were analyzed. Secondary outcomes included nephrotoxicity, readmission rate and mortality. Median daily dose required to achieve therapeutic trough levels was examined. Clinical outcomes for 90 control patients were compared with outcomes for 19 patients guided by a PK consultation service. Percentage of patients with sustained therapeutic vancomycin trough levels increased from 17.8% to 94.7% (P < 0.001) and percentage of treatment days with therapeutic vancomycin trough levels increased from 18.4% (117/637) to 665% (155/233, P < 0.001). Readmission rate decreased from 24.4% to 5.3% (P = 0.07). No differences in nephrotoxicity or mortality rate were observed between groups. A median daily dose of 72 mg/kg/d was required to achieve therapeutic trough levels. Our data demonstrate that implementation of internal guidelines and a PK consultation service was associated with a profound improvement of vancomycin therapy and, therefore, patient safety.

Causes of vancomycin dosing error; problem detection and practical solutions; a retrospective, single-center, cross-sectional study

Vancomycindosing error and inappropriate monitoring is a common problem in hospital daily practice. In King Abdulaziz Medical City (KAMC) in Jeddah, a high percentage of abnormal vancomycin trough levels is still detected despite using the recommended dose. Therefore, the current research objective is to study the major causes of vancomycin dosing errors. This retrospective, single-center, cross-sectional study was carried out at KAMC hospital in Jeddah from January 1st until December 31st 2019. All adult patients (≥15 years) who received vancomycin and had an initial abnormal trough level at the measured steady-state were included in this study. 472 patients have met the study inclusion criteria.The current study evaluated the factors that play a role in causing vancomycin trough level abnormalities such as sampling time, vancomycin dosing, and patient’s pharmacokinetic and pharmacodynamic variations.In this study, we found that pharmacokinetic and pharmacodynamic variability was attributed to 65% of vancomycin's abnormal trough level. Also, the result showed a significantly increased odds of the low trough in the non-elderly group (OR 6, 95% CI 2.48 – 14.9, P < 0.001) and febrile neutropenic patients (OR 2.21, 95% CI 1.119 – 4.365, P < 0.05). However, the odds of high trough levels were significantly elevated among patients who have CrCl < 50 ml/min (OR 5, 95% CI 1.262–20.539, P < 0.05). In addition, the present investigation revealed that the occurrence of abnormal vancomycin levels was not affected by daily duty time or working days (p > 0.05). The current study indicated that vancomycin dosing errors were common in KAMC patients; thus, there is an unmet need to evaluate the causes of vancomycin abnormal trough level and optimize a strategy that would enhance the therapeutic effectiveness and minimize the potential toxicity.

An evaluation on the association of vancomycin trough concentration with mortality in critically ill patients: A multicenter retrospective study.

To determine the impact of initial vancomycin trough concentration (VTC) on mortality in adult patients in the intensive care unit (ICU) undergoing vancomycin therapy. During their first ICU stay, patients with initial VTC records after vancomycin treatment were recruited from the eICU Collaborative Research Database to this multicenter retrospective cohort study, and classified into four groups according to VTC: less than 10, 10–15, 15–20, and greater than 20 mg/L. Multivariable logistic regression and sensitivity analyses were performed to explore the association of VTC, as a continuous and categorical variable, with mortality. This study enrolled 7220 patients from 335 different ICUs at 208 hospitals. Multivariable logistic regression models indicated that VTC was positively correlated with ICU (odds ratio [OR], 1.028, 95% confidence interval [CI], 1.019–1.037) and hospital (OR 1.028, 95% CI, 1.020–1.036) mortalities. Moreover, compared with VTC less than 10 mg/L, VTCs of 10–15, 15–20, and greater than 20 mg/L were associated with a higher risk of ICU mortality (OR, 1.330, 95% CI, 1.070–1.653; OR, 1.596, 95% CI, 1.265–2.015; abd OR, 1.875, 95% CI, 1.491–2.357, respectively), and VTCs of 15–20 and greater than 20 mg/L were also correlated with increased hospital mortality (OR, 1.482, 95% CI, 1.225–1.793; and OR, 1.831, 95% CI, 1.517–2.210, respectively). Similar results persisted in patients with different Acute Physiology and Chronic Health Evaluation Ⅳ scores, creatinine clearance levels, ages, and body mass indexes. Our findings indicated a potential relationship of initial VTC with ICU and hospital mortalities in patients in the ICU. However, due to the retrospective nature of this study, future prospective studies or randomized controlled trials are needed to validate those results.

Correlates and Outcomes of Early Acute Kidney Injury after Hematopoietic Cell Transplantation

BackgroundPatients undergoing hematopoietic cell transplantation (HCT) are at high risk for acute kidney injury (AKI). The etiology of AKI is often multifactorial and includes exposure to antibiotics and calcineurin inhibitors (CNI) for prevention of graft versus host disease. MethodsThis is a retrospective, single center study which evaluated patients undergoing inpatient HCT at Froedtert Memorial Hospital, Milwaukee, Wisconsin from Jan 1 to Dec 31, 2016. AKI was defined as an increase in serum creatinine > 0.3 mg/dL from baseline value. ResultsThe total number of patients included in the study was 280, 64 had AKI and 216 were in the non-AKI group. AKI was noted in 23% patients. Exposure to CNI or vancomycin accounted for the majority of the cases (82%). The median pre-AKI vancomycin trough was elevated in the AKI group at 21.3 mcg/mL (range: 17.4–24.4 mcg/mL) while the pre-AKI CNI trough was lower in the AKI group at 12.3 ng/mL (range: 8.7–14.7 ng/mL).There were also a higher number of ICU transfers (19%) and higher 100 day mortality (15.6%) in the AKI group. ConclusionAKI is a frequent complication following HCT and is associated with a higher risk of ICU transfer and higher mortality post HCT. While a higher vancomycin trough level may be indicative of a higher risk of AKI, the risk following CNI exposure may not be related to trough levels alone. There may be underlying pharmacogenetic factors which may alter the risk of AKI with CNI use.

An Ensemble Model for Prediction of Vancomycin Trough Concentrations in Pediatric Patients.

PurposeThis study aimed to establish an optimal model to predict vancomycin trough concentrations by using machine learning.Patients and MethodsWe enrolled 407 pediatric patients (age < 18 years) who received vancomycin intravenously and underwent therapeutic drug monitoring from June 2013 to April 2020 at Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine. The median (interquartile range) age and weight of the patients were 2 (0.63–5) years and 12 (7.8–19) kg. Vancomycin trough concentrations were considered as the target variable, and eight different algorithms were used for predictive performance comparison. The whole dataset (407 cases) was divided into training group and testing group at the ratio of 80%: 20%, which were 325 and 82 cases, respectively.ResultsUltimately, five algorithms (XGBoost, GBRT, Bagging, ExtraTree and decision tree) with high R2 (0.657, 0.514, 0.468, 0.425 and 0.450, respectively) were selected and further ensembled to establish the final model and achieve an optimal result. For missing data, through filling the missing values and model ensemble, we obtained R2=0.614, MAE=3.32, MSE=24.39, RMSE=4.94 and a prediction accuracy of 51.22% (predicted trough concentration within ±30% of the actual trough concentration). In comparison with the pharmacokinetic models (R2=0.3), the machine learning model works better in model fitting and has better prediction accuracy.ConclusionTherefore, the ensemble model is useful for the vancomycin concentration prediction, especially in the population of children with great individual variation. As machine learning methods evolve, the clinical value of the ensemble model will be demonstrated in the clinical practice.

Vancomycin concentrations during cardiopulmonary bypass in pediatric cardiac surgery: a prospective study.

Few data are available regarding intraoperative plasma concentrations of vancomycin administered as prophylaxis in pediatric cardiac surgery. The aims of this study were to investigate during pediatric cardiac surgery with cardiopulmonary bypass(CPB) the attainment of the area-under-the-curve of the vancomycin serum concentrations versus time over surgery to minimum inhibitory concentration ratio(AUCintra/MIC) of 400 (mg × h)/l and/or a target concentration of 15-20 mg/l. In a prospective study, 40 patients divided into four subgroups (neonates, infants, children <10 years-old, ⩾10 years-old) undergoing cardiac surgery with cardiopulmonary bypass (CPB) were enrolled. A slow vancomycin bolus of 20 mg/kg, up to a maximum dose of 1000 mg was administered before skin incision and a further dose of 10 mg/kg (up to 500 mg) at CPB start. Vancomycin samples were collected intraoperatively at four time points. The median (interquartile range) age was 241.5 days (47-3898) and the median weight was 7.1 kg (3.1-37). The median AUCintra/MIC was 254.73 (165.89-508.06). In 11 patients the AUCintra/MIC target was not reached. Neonates displayed the lowest AUCintra/MIC values, and these were significantly lower than those of children ⩾10 years old (p = 0.02). Vancomycin concentrations were above the maximal target of 20 mg/l in 82.5% and 80% of patients at surgery and CPB start, respectively. At CPB and surgery end, 42.5% of patients showed vancomycin concentrations above 20 mg/l and 42.5% below 15 mg/l. Patients⩾10 years old showed the highest peak values whereas neonates were those with the lowest troughs. AUCintra/MIC correlated with age(r:0.36, p = 0.02), weight(r:0.35, p = 0.03), intraoperative protein value(r:0.40, p = 0.01), CPB priming volume/kg(r:-0.33, p = 0.04), CPB duration(r:0.36, p = 0.02) and vancomycin troughs(r:0.35, p = 0.04). An AUCintra/MIC ⩾400 target was not reached in one-quarter of children undergoing heart surgery. Vancomycin peaked before the start of surgery and neonates were those with the lowest troughs. Vancomycin concentrations are affected by CPB hemodilution and by patients' age and weight.

#50: Vancomycin Doses and Trough Concentrations in Pediatric Patients

Abstract Background Vancomycin serum trough concentrations are monitored to reduce nephrotoxicity and optimize therapeutic efficacy. Vancomycin pharmacokinetics and trough levels used in pediatric patients are extrapolated from the adult population. The pediatric dosing strategies are empirical and there is limited evidence to suggest that these doses result in the recommended steady-state trough concentrations. The objective of the study was to determine the association between vancomycin dosing regimens and trough concentrations levels of 10 to 20 μg/mL in pediatric patients with complicated infections. Methods Retrospective cohort, 505 trough vancomycin serum concentrations of patients of 1 month to 18 years from hospital wards and the Intensive Care Unit of the Instituto Nacional de Salud del Niño San Borja during December 2015 to April 2019. It included only the first vancomycin trough level measured 30 minutes before the fourth doses and serum trough concentrations of 10 to 20 μg/mL were considered as therapeutic levels. A multinomial logistic regression model to estimate the relative risk ratio (RRR) with a 95% confidence interval was used, the comparator group was therapeutic vancomycin levels and it was adjusted by glomerular filtration rate, age group, hospital room, dose interval, and weight. Results Five hundred and five vancomycin dosages were analyzed. Infants and children were 43.12% and 39.22%, respectively, 45.17% were women. 56.77% had a high glomerular filtration rate and only 28.02% of the patients obtained therapeutic trough levels of vancomycin. The RRR of having sub-therapeutic levels in patients with low glomerular filtration rates compared with normal filtration rates was 0.31 (P = 0.049) and the RRR of having sub-therapeutic levels in patients from 2 to 12 years compared with patients under 2 years old was 2.38 (P = 0.007). There was no difference in having therapeutic levels using doses equal or greater than 60 mg/kg/day vs. less than 40 mg/kg/day comparing sub-therapeutic levels (P = 0.655) and supratherapeutic levels (P = 0.264). Conclusions The empirical vancomycin regimens used in pediatric patients did not reach the recommended therapeutic trough levels of 10 to 20 μg/mL. Patients of 2 to 12 years and low glomerular filtration rates were associated to have sub-therapeutic trough levels.

Outcomes of a pharmacist-driven vancomycin monitoring initiative in a community hospital.

Vancomycin, an antibiotic commonly used to treat MRSA infections, can be nephrotoxic. Administering vancomycin requires close monitoring of serum vancomycin levels and appropriate dosing based on patients' renal function, underlying infection type and serum concentration levels. This article discusses the results and implications of a pharmacist-driven vancomycin monitoring initiative, which was implemented at Mercy Catholic Medical Center's Philadelphia Campus (MPC) in July 2016. MPC pharmacists were trained on how to give appropriate vancomycin dosing recommendations based on patients' vancomycin trough levels, renal function and underlying infection. This retrospective observational study consisted of patients who presented to MPC and were administered vancomycin over a 3-month period in 2015 for pre-implementation cohort and over a 3-month period in 2018 for post-implementation cohort. Patients with age ≥18 and receiving vancomycin for a minimum of 48 hours were included, whereas ESRD patients were excluded. Primary goal evaluated whether the incidence of AKI decreased with the pharmacist-driven initiative. Secondary goal assessed whether vancomycin level monitoring and achievement of goal serum levels improved with the initiative. A total of 214 patients were included in the final data analysis, with 110 patients in the pre-implementation cohort and 104 patients in the post-implementation cohort. Although not statistically significant, a higher incidence of AKI was observed in the post-implementation cohort. However, compared to pre-implementation cohort, post-implementation group had higher percentage of patients with underlying comorbidities (such as CKD), higher number of cases of severe sepsis and septic shock, and greater number of patients with concomitant exposure to CT contrast and piperacillin-tazobactam-all of which were confounding factors that likely increased the AKI incidence in post-implementation cohort. With the initiative, there was a significant increase in the number of patients with appropriate vancomycin trough level monitoring (27.3% vs 55.8%, p value < 0.001) in the post-implementation cohort and a decrease in the number of patients with no trough level monitoring (30% vs. 7.6%, p value < 0.001). Pharmacist-driven vancomycin monitoring significantly improved the monitoring compliance of vancomycin trough levels. In patients who developed AKI during their hospital course, pharmacist interventions improved the total percentage of patients attaining desired trough goals and helped reduce further renal insult from supratherapeutic vancomycin level. Incorporation of AUC-guided dosing and monitoring has the potential to further optimize vancomycin efficacy and safety.

Low vancomycin trough concentration in neonates and young infants.

Vancomycin (VCM) is useful for treating methicillin-resistant Staphylococcus aureus. In infants, calibrating the initial VCM dose is difficult, and many regimens have been proposed. For instance, our center uses the VCM regimen recommended for infants in the 2012-13 Nelson's Pediatric Antimicrobial Therapy. Nonetheless, our experience has shown that the initial VCM trough concentrations were frequently off target. We therefore analyzed the data on the initial VCM trough concentration in infant patients at our center. The study subjects were inborn infants born between July 2014 and June 2019 who were given VCM at earlier than day 60 in the neonatal intensive care unit. The primary outcome was the initial VCM trough concentration. The patients were divided into three groups by VCM trough concentration: <10, 10-15, and >15mg/L. We also estimated VCM trough concentration by one method using Monte Carlo simulation, based on Nelson regimen dosage. Thirty-three patients were analyzed. The number of patients with <10, 10-15, and >15mg/L was 24, 4, and 5, respectively. There was no significant difference in clinical characteristics between <10 versus 10-15 and 10-15 versus >15mg/L. The numbers of patients with <10, 10-15, and >15mg/L in the simulation were 26, 6, and 1, respectively. Most initial VCM trough concentrations were below the target. We could not find any significant clinical characteristics, which affected VCM trough concentration. Increasing the VCM dosage of the Nelson regimen with simulation should therefore be considered.

Cystatin C and/or creatinine-based estimated glomerular filtration rate for prediction of vancomycin clearance in long-stay critically ill patients with persistent inflammation, immunosuppression and catabolism syndrome (PICS): a population pharmacokinetics analysis.

Persistent inflammation, immunosuppression and catabolism syndrome (PICS) in critically ill patients are associated with unreliable creatinine (Cr)-based estimated glomerular filtration rate (eGFR) and alteration in vancomycin clearance (CL) due to ongoing muscle wasting and renal dysfunction (RD). Currently, cystatin C (Cys) is of great interest for eGFR due to its muscle independence. Patients receiving intravenous vancomycin with trough concentration monitoring after intensive care unit stay ≥ 14days were retrospectively enrolled. Those with C-reactive protein > 30.0mg/L, lymphocytes count < 0.80 × 109, albumin < 30mg/L and weight loss > 10% were diagnosed with PICS. Impact of PICS on vancomycin trough achievement was analyzed. Plasma Cys and Cr levels with their eGFRs in RD were compared in patients with and without PICS. Furthermore, the performance of eGFRs in predicting vancomycin CL was quantificationally evaluated by population pharmacokinetics (PPK) analysis using the Phoenix NLME software. Of 69 enrolled patients, 32 (46.4%) were PICS. PICS was predictive of Cr-guided vancomycin supratherapeutic trough concentrations (OR = 5.26, P = 0.013). Significant elevation of Cys, not of Cr, was observed in patients with PICS suffering from RD (P = 0.022), causing substantial differences among eGFRs. Fifty-two and 17 patients were enrolled for the modeling group and validation group, respectively. A one-compartment PPK model with first-order elimination adequately described the data of 126 Ctrough. Prediction of vancomycin CL with Cys and Cr-based eGFR (CKD-EPIcys-cr) significantly reduced the interindividual variability of CL (from 75.6 to 28.5%). External validation with 34 Ctrough showed the robustness and accuracy of this model. This study showed the negative impact of PICS on Cr-guided vancomycin trough achievement. PPK model with CKD-EPIcys-cr can be used to optimize vancomycin dosage in patients with PICS.

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 &gt; 20 mg/L was associated with a six-fold increase in odds of VA-AKI when compared to those with vancomycin levels &lt; 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 &gt; 30 ml/min was 11.7%. Serum vancomycin levels of &gt; 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.

Individualized Vancomycin Dosing with Therapeutic Drug Monitoring and Pharmacokinetic Consultation Service: A Large-Scale Retrospective Observational Study.

BackgroundTo date, outcome data with a large sample size and data regarding the clinical outcomes of pharmacokinetic-guided (PK) dosing of vancomycin are limited.AimWe evaluated the pharmacokinetic and clinical outcomes of a PK-guided dosing advisory program, pharmacokinetic consultation service (PKCS), in vancomycin treatment.MethodsWe investigated vancomycin therapeutic drug monitoring (TDM) and PKCS use through a retrospective review of patients who had serum vancomycin trough concentration data from October 2017 to November 2018. Among these patients, we selected non-critically ill adult patients satisfying our selection criteria to evaluate the effect of PKCS. Target trough attainment rate, time to target attainment, vancomycin-induced nephrotoxicity (VIN), vancomycin treatment failure rate, and duration of vancomycin therapy were compared between patients whose dosing was adjusted according to PKCS (PKCS group), and those whose dose was adjusted at the discretion of the attending physician (non-PKCS group).ResultsA total of 280 patients met the selection criteria for the VIN analysis (PKCS, n=134; non-PKCS, n=146). The incidence of VIN was similar between the two groups (PKCS, n=5; non-PKCS, n=5); however, the target attainment rate was higher in the PKCS group (75% vs 60%, P = 0.012). The time to target attainment was similar between the two groups. Further exclusions yielded 112 patients for the clinical outcome evaluation (PKCS, n=51; non-PKCS, n=61). The treatment failure rate was similar, and the duration of vancomycin therapy was longer in the PKCS group (12 vs 8 days, P = 0.008).ConclusionIn non-critically ill patients, an increase in target trough achieved by PKCS did not lead to decreased vancomycin treatment failures, shorter vancomycin treatment, or decreased nephrotoxicity in vancomycin treatment. Considering the excessive amount of effort currently put into vancomycin dosing and monitoring, more selective criteria for individualized pharmacokinetic-guided dosing needs to be applied.

Software to predict the right dose for vancomycin in a clinical environment-A commentary on: Personalised dosing of vancomycin: A prospective and retrospective comparative quasi-experimental study by Luqman Vali et al.

Software to predict the right dose for vancomycin in a clinical environment-A commentary on: Personalised dosing of vancomycin: A prospective and retrospective comparative quasi-experimental study by Luqman Vali et al.

The optimal trough-guided monitoring of vancomycin in children: Systematic review and meta-analyses

We carried out a systematic review and meta-analysis exploring the relationship between vancomycin (VCM) trough concentrations and its effectiveness and nephrotoxicity in pediatric patients. We conducted our analysis using MEDLINE, Web of Sciences, and Cochrane Register of Controlled Trials as electronic databases (June 29, 2019). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. We identified 16 studies that were eligible for the meta-analysis. A total of 351 and 3,266 patients were included in the analysis for effectiveness and nephrotoxicity, respectively. Pediatric MRSA infection patients with VCM trough concentrations ≥ 10 μg/mL had significantly lower treatment failure rates (OR 0.54, 95% CI 0.30–0.96). The incidence of nephrotoxicity was significantly higher in trough concentrations ≥ 15 μg/mL than when they were < 15 μg/mL (OR 3.02, 95% CI 2.08–4.38). We identified the optimal VCM trough concentrations associated with effectiveness and nephrotoxicity in pediatric patients with MRSA infection. Further prospective studies are needed to find optimal dosing and monitoring strategy on VCM in pediatric population.

The monitoring of vancomycin: a systematic review and meta-analyses of area under the concentration-time curve-guided dosing and trough-guided dosing

BackgroundThis systematic review and meta-analysis explored the relationship between vancomycin (VCM) monitoring strategies and VCM effectiveness and safety.MethodsWe conducted our analysis using the MEDLINE, Web of Sciences, and Cochrane Register of Controlled Trials electronic databases searched on August 9, 2020. We calculated odds ratios (ORs) and 95% confidence intervals (CIs).ResultsAdult patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia with VCM trough concentrations ≥15 μg/mL had significantly lower treatment failure rates (OR 0.63, 95% CI 0.47–0.85). The incidence of acute kidney injury (AKI) increased with increased trough concentrations and was significantly higher for trough concentrations ≥20 μg/mL compared to those at 15–20 μg/mL (OR 2.39, 95% CI 1.78–3.20). Analysis of the target area under the curve/minimum inhibitory concentration ratios (AUC/MIC) showed significantly lower treatment failure rates for high AUC/MIC (cut-off 400 ± 15%) (OR 0.28, 95% CI 0.18–0.45). The safety analysis revealed that high AUC value (cut-off 600 ± 15%) significantly increased the risk of AKI (OR 2.10, 95% CI 1.13–3.89). Our meta-analysis of differences in monitoring strategies included four studies. The incidence of AKI tended to be lower in AUC-guided monitoring than in trough-guided monitoring (OR 0.54, 95% CI 0.28–1.01); however, it was not significant in the analysis of mortality.ConclusionsWe identified VCM trough concentrations and AUC values that correlated with effectiveness and safety. Furthermore, compared to trough-guided monitoring, AUC-guided monitoring showed potential for decreasing nephrotoxicity.

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.

Effects of continuous venovenous hemofiltration on vancomycin trough concentrations in critically ill children.

BackgroundVancomycin trough concentrations are associated with clinical outcomes and drug adverse effects. This study investigates the effects of continuous venovenous hemofiltration (CVVH) on vancomycin trough concentrations in critically ill children with a vancomycin dosage of 40–60 mg/kg/day.MethodsChildren with steady-state vancomycin trough concentrations admitted to the pediatric intensive care unit (PICU) between January 2016 and December 2019 were retrospectively enrolled. Patients were divided into CVVH and non-CVVH groups according to treatment differences and renal function. Vancomycin trough concentrations were then compared between the groups, and risk factors for supratherapeutic trough concentrations (>20 mg/L) were analyzed with logistic regression.ResultsOf the 119 patients included, 35 were enrolled in the CVVH group and 84 in the non-CVVH group. Median vancomycin trough concentrations were significantly higher in the CVVH group than those in the non-CVVH group [14.9 (IQR =9.6–19.6) vs. 9.3 (IQR =7.0–13.4), P<0.001] and the proportion of therapeutic trough concentrations (10–20 mg/L) was similar between CVVH and non-CVVH groups (54.3% vs. 39.3%, P=0.133). However, CVVH therapy patients had a significantly higher proportion of supratherapeutic trough concentrations (20.0% vs. 1.2%, P=0.001) compared to the non-CVVH group. Multivariate analysis demonstrated that the Pediatric Risk of Mortality (PRISM) III score ≥28 (OR =13.7; 95% CI, 1.4–137.0; P=0.026] was an independent risk factor for supratherapeutic trough concentrations in critically ill patients.ConclusionsCVVH therapy affects vancomycin trough concentrations and is associated with supratherapeutic concentrations with a 40–60 mg/kg/day vancomycin dosage. PRISM III scores ≥28 may serve as an independent risk factor for supratherapeutic trough concentrations in children receiving CVVH therapy.

Correlation between vancomycin clearance and cystatin C-based glomerular filtration rate in paediatric patients.

Because of limitations with the serum creatinine-based glomerular filtration rate (GFRcr), estimates of the serum cystatin C-based glomerular filtration rate (GFRcys) are getting attention to predict vancomycin clearance (CLvan). We evaluated the correlations between (i) CLvan and GFRcr, and (ii) CLvan and GFRcys in paediatric patients. We evaluated a retrospective cohort of patients between 1 and 19 years old admitted to a tertiary hospital between 2017 and 2019. CLvan was estimated using measured vancomycin trough concentrations. We conducted Spearman's correlation analyses between CLvan and 1/creatinine, GFRcr, 1/cystatin C and GFRcys. Subgroup analyses were conducted for the young child, child, adolescent subgroups, intensive care unit patients and low body weight (<10th percentile) patients. We analysed 40 patients. GFRcys correlated with CLvan better than GFRcr did (ρ = 0.731, P < 0.001 vs ρ = 0.504, P = 0.001). In the subgroup analyses, the correlation between GFRcys and CLvan was stronger than that between GFRcr and CLvan (child subgroup ρ = 0.712, P = 0.002 vs ρ = 0.282, P = 0.289; intensive care unit patients ρ = 0.772, P < 0.001 vs ρ = 0.540, P = 0.004; low body weight patients ρ = 0.671, P < 0.001 vs ρ = 0.464, P = 0.022). Serum cystatin C-based GFR strongly correlates with vancomycin clearance, suggesting the possibility of better prediction models than creatinine-based GFR. Further prospective studies are required for the validation of the prediction model in a large paediatric population.