Vancomycin Trough Levels Research Articles

Evaluating the safety and effectiveness of a nurse-led outpatient virtual IV vancomycin monitoring clinic: a retrospective cohort study.

BackgroundOutpatient parenteral antimicrobial therapy (OPAT) with vancomycin is a common treatment modality for certain Gram-positive infections. Data regarding the safety of various models of delivery are limited.ObjectivesTo review outcomes of a nurse-led OPAT vancomycin monitoring service.MethodsThis was a retrospective cohort study of consecutive patients referred to a nurse-led OPAT vancomycin clinic from December 2015 to March 2018. Patients were administered IV vancomycin in the home with active laboratory monitoring of vancomycin trough levels, renal function and complete blood count using an integrated electronic database linked with community laboratories (virtual vancomycin clinic, VVC). Monitoring was coordinated by nurses with physician approval of recommended dosing changes. Data were extracted from the electronic medical record. Demographics; clinical indication; microbial aetiology; culture source; antimicrobial regimen(s); serum creatinine and vancomycin trough values; initiation, discharge and completion dates; hospitalizations; adverse events; and outcomes were all evaluated.ResultsTwo hundred and seventy-five patients underwent a total of 301 courses of OPAT with vancomycin; 285 courses were completed. The rate of treatment discontinuation due to adverse effects was 33/301 (11.0%), with 15/33 (45.5%) being due to renal adverse effects (15/301 [5.0%] of episodes). Two of 15 (18.2%) patients developed stage 2 acute kidney injury (AKI), and no patients had stage 3 AKI or required haemodialysis. Nine of 301 (3.0%) required readmission for treatment failure. Nursing costs associated with monitoring were $63.93 CAD/patient ($48.43 USD).ConclusionsA nurse-led VVC was a safe, effective and inexpensive modality for administering outpatient vancomycin.

The impact of Vancomycin loading dose on the emergency department in Saudi Arabia: a multicenter cohort study

Background: The emergency department (ED) is a crowded area with complex workflow. Broad spectrum antibiotics given within the first hour of recognizing sepsis have proven to lower the mortality rate. Initiating optimal dose of Vancomycin to attain targeted serum level is an important role of emergency physicians and pharmacists. Objective: To evaluate the efficacy and safety of Vancomycin loading dose (VLD) (25-35 mg/kg) in reaching the targeted Vancomycin serum trough level compared to regular dose (15-20 mg/kg) in ED. Study design and settings: A multicenter, retrospective, cohort study. Methods: The study was carried out in four hospitals in Saudi Arabia; patients who received VLD were matched in a 1:1 fashion based on age category and diagnosis suspected in the ED. Inclusion criteria were age ≥14 years, diagnosed with serious infections caused by methicillin-resistant Staphylococcus aureus (MRSA), and microbiology culture confirmed MRSA. Exclusion criteria were missing weight, SCr, or Vancomycin trough level, patient on dialysis therapy/continuous renal replacement therapies, and concomitant use of nephrotoxic drugs at ED. Results: Over the 1-year study period, a total of 3,746 patients were prescribed Vancomycin in the ED. 232 patients received VLD matched to 232 patients received regular dose. Mean dose were 25.3 mg/kg (±4.3) and 13.7 mg/ kg (±2.6) for VLD and regular dose groups, respectively. The targeted Vancomycin trough level was significantly reached with the VLD group within 24 hours post-initial dose vs regular dose [18.7 (±3.2) vs. 11.6 (±4.3), respectively, p < 0.0001]. No difference in SCr value was noted post-Vancomycin initial dose between VLD and regular dose groups [1.5 (± 1.5) vs. 1.4 (± 1.8), respectively, p = 0.735]. Nephrotoxicity incident was higher with VDL (33, 14.2%) compared to regular dose, but the difference was not significant (22, 9.5%, p = 0.117). Conclusion: VLD has a rapid effect in reaching the targeted Vancomycin serum trough level compared to regular dose with a low rate of nephrotoxicity effect. The finding supports the use of VLD in patients admitted to ED who were suspected to have serious infections caused by MRSA.

Comparison of trough concentration and area under the curve of vancomycin associated with the incidence of nephrotoxicity and predictors of a high trough level

PurposeA high vancomycin trough concentration during therapy is associated with increased nephrotoxicity, and the recent guidelines for therapeutic monitoring of vancomycin recommend target of the ratio of area under the curve (AUC) to minimum inhibitory concentration. We aimed to determine vancomycin trough concentration and AUC that induce nephrotoxicity and evaluate predictive factors associated with a high serum vancomycin trough level according to the initial dosing strategy. MethodsWe conducted a retrospective cohort study in patients administered intravenous vancomycin from June 2013 to February 2017. Totally, 346 patients were included. Results38 experienced nephrotoxicity during therapy. The both trough level and AUC were significant risk factors for the occurrence of vancomycin induced-nephrotoxicity (p < 0.001, p = 0.001). The exposure–response analysis revealed that the trough level of 15 μg/mL was associated with 12.0% nephrotoxicity incidence and AUC of 600 was associated with 12.9% nephrotoxicity incidence. During the treatment, 90 patients had an initial trough concentration of ≥15 μg/mL, and 124 patients had AUC of ≥600 μg h/mL. The multiple logistic regression analysis revealed body weight (p = 0.001), serum creatinine level (p = 0.028), daily vancomycin dose (p = 0.001), and ICU (p = 0.015) were independent predictive factors for a high trough concentration. And same factors were selected for the high AUC. ConclusionThe risk factors for vancomycin induced nephrotoxicity were comparable in both trough concentration and AUC. The incidence of nephrotoxicity can be reduced by controlling vancomycin trough concentration similarly AUC and promoting antimicrobial stewardship.

Lower vancomycin trough levels in adults undergoing unrelated cord blood transplantation

Vancomycin (VCM) is frequently used for neutropenic patients undergoing cord blood transplantation (CBT). We retrospectively examined the relationship between VCM trough levels and the efficacy and toxicity in 122 adult patients undergoing CBT in our institute. The median initial dose of VCM based on body weight was 9.1 mg/kg/dose (range, 6.0–22.6 mg/kg/dose). The median initial trough level of VCM for all patients was 4.50 µg/mL (range, 1.20–24.05 µg/mL), at a median of 3 days (range, 2–6 days) after VCM administration. The cumulative incidence of acute kidney injury (AKI) was 19% at 30 days after VCM administration. A higher median trough level of VCM during the first 7 days was significantly associated with the development of AKI in the multivariate analysis (Hazard ratio: 1.28, p = .026). These data suggest that a lower VCM trough level may be safe in adult patients undergoing CBT under therapy with nephrotoxic drugs.

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.

Association of Initial Trough Concentrations of Vancomycin with Outcomes in Pediatric Patients with Gram-Positive Bacterial Infection.

Vancomycin is a glycopeptide antibiotic used for the treatment of Gram-positive infections. For adult patients, treatment with vancomycin requires effective therapeutic drug-monitoring (TDM) to achieve clinical outcomes and reduce the incidence of adverse effects. However, it remains still unclear whether the TDM with vancomycin is beneficial in yielding better clinical outcomes in pediatrics. The objective of our study was to evaluate whether the clinical response to treatment was associated with initial trough concentrations of vancomycin in pediatric patients. A retrospective observation study of 60 patients (age: 1 month-15 years) who had completed and qualified for analysis was conducted at Kyoto University Hospital. The response to treatment was assessed by the time to resolution of fever and time to 50% decline in C-reactive protein (CRP). In addition, we explored whether vancomycin trough level was associated with the baseline characteristics. Trend analysis showed that there were significant correlations between vancomycin trough level and age, body weight, estimated glomerular filtration rate, and serum albumin levels. The time to resolution of fever of the patients with higher initial trough level (≥ 5 µg/mL) was significantly lower than that of the patients with lower trough level (< 5 µg/mL). The higher vancomycin concentration tended to be associated with the shorter time to 50% decline in CRP. The findings suggest that initial trough concentration is important in achieving better outcomes with vancomycin treatment in pediatrics.

A higher dose of vancomycin is needed in critically ill patients with augmented renal clearance.

BackgroundUsing standard vancomycin dosage in critically ill patients might lead to therapy failure and worse patient outcomes, augmented renal clearance (ARC) may be the leading risk factor. In this study, we comprehensively investigated the pharmacokinetics-pharmacodynamics (PK-PD) of vancomycin in critically ill patients with ARC, hoping to explore the precise and accurate dose adjustment method for vancomycin.MethodsAll critically ill patients tested for steady-state trough vancomycin serum concentrations during the recent 6 years in a tertiary level hospital were collected retrospectively and divided into ARC and non-ARC groups, respectively, according to creatinine clearance (CLcr). Serum vancomycin concentrations were measured by the fluorescence polarization immunoassay method. PK-PD parameters of vancomycin were recorded or calculated. The desired daily dose successful in achieving the lower target trough levels (10 mg/L) of vancomycin were investigated correspondingly.ResultsA total of 280 vancomycin concentrations were eligible for analysis. The ARC group (n=139) contained more male patients (64.7%) with average age and CLcr of 40 years old (P<0.05) and 180.8 mL/min (P<0.001), respectively. Those patients exhibited higher clearance (CL) and lower trough serum concentrations than the non-ARC patients under comparable daily doses of vancomycin. All the ICU patients demonstrated lower AUC24h values than the target level of 400 µg·h/mL, and this value showed a lower trend in the ARC group than the non-ARC group (232.9 vs. 316.2 µg·h/mL). Subtherapeutic trough concentrations of vancomycin (<10.0 mg/L) were observed in 77.7% and 68.8% of the ARC and non-ARC patients (P<0.05). The proportion of patients with a trough concentration of 10–15 and 15–20 mg/L was 17.9% and 4.3%, respectively, in the ARC group and 24.8% and 2.8%, respectively, in the non-ARC group., a daily dose of 46.0 and 35.5 mg/kg of vancomycin is needed, respectively, in the ARC and non-ARC group to achieve a target trough concentration of 10 mg/L.ConclusionsA higher dose of vancomycin is needed in critically ill patients, especially those with ARC, and appropriate TDM-guided dose adjustment should be considered to achieve the targeted therapeutic range and to provide dosing guidance for this: patient population.

Vancomycin prophylaxis in paediatric patients following cardiac surgery: aretrospective evaluation of trough levels and associated variables.

Therapeutic drug monitoring during vancomycin administration is recommended. However, little information is available in case of paediatric vancomycin prophylaxis. The aim of this study was to analyse vancomycin trough levels on postoperative day (POD) 2 and 3 after paediatric cardio-surgery to assess the clinical predictors and outcomes associated with vancomycin concentrations and to evaluate whether adjustments are effective to target optimal levels. A retrospective study was conducted in paediatric patients receiving vancomycin prophylaxis after elective cardio-surgery. Adjustments were made if levels between 20 and 30 (halving subsequent dose) or ˃30 mg/l (dose withheld) were found. Vancomycin doses of the 100 examined children (3.7-6.4 years) were 12.8 (2.5), 9.4 (5.4) and 9.7 (4.5) mg/kg, on POD1, 2 and 3, respectively (P = 0.0001). The 200 vancomycin trough levels decreased from 16.9 (11.4) on POD2 to 14.6 (8.5) on POD3 (P = 0.003). Overall, 66 troughs were sub-target, 68 reached the optimal target and 66 were supra-target. On POD2 and 3, 32 and 27 dose adjustments were required, leading to a reduced number of patients with supra-target troughs. Neonates showed a higher number of supra-target levels with respect to non-neonatal patients on both POD2 (P = 0.003) and 3 (P = 0.0001). At multivariable regression analysis, vancomycin levels showed independent association with weight and creatinine levels on both POD2 and 3. Vancomycin levels correlated with ventilation days (P = 0.31, P = 0.039), but not with methicillin-resistant Staphylococcus aureus positivity (P = 0.69). Vancomycin prophylaxis in paediatric cardio-surgery requires strict therapeutic drug monitoring and several dosage adjustments. Supra-target troughs are frequent and neonatal age, weight and creatinine levels significantly affect vancomycin concentrations.

P01 An evaluation of vancomycin therapy in paediatric patients post guideline change

AimTo evaluate the prescribed dose of vancomycin as per local guideline and review the achieved therapeutic drug levels.MethodRetrospective data was collected from paediatric inpatients that were prescribed vancomycin for more than 24 hours during the audit period. Data was obtained from the Trust’s electronic prescribing system, LastWord. Measured standards included initial vancomycin dose, dose prescribed for renal impairment, time to first trough level and any required dose adjustments as per local guidance. The dose bands for each age group were1; birth - 6 months 15 mg/g 8 hourly; &gt;6 months -12 months 20 mg/kg 8 hourly; &gt;12 months – 12 years 25 mg/kg 8 hourly; &gt;12 years 20 mg/kg 8 hourly. The number of patients achieving therapeutic vancomycin trough levels was recorded. Safety data was collected, including reported adverse effects, infusion related reactions and renal impairment. Renal impairment was defined as an increase in creatinine by 50%. Data was collected from April 2018 for 6 months. Relevant data with regards to patient demographics, dosing and drug levels were collected and analysed using Microsoft Excel.Results12 patients received 15 doses of vancomycin over 6 months. 67% of initial vancomycin doses were prescribed as per local guideline, 60% of therapeutic trough levels were taken at the right time and 71% of patients that were prescribed the correct dose and had levels taken at the right time achieved therapeutic trough levels. 12 patients required dose adjustments. One patient with renal impairment was not prescribed the recommended dose as per local guidance. One patient reported an infusion related reaction, which was overcome by increasing the infusion time. Two patients who received therapy for &gt;7 days accumulated vancomycin and recorded high trough levels, with no adverse events. One patient reported an increase in creatinine by 50% over the treatment period.ConclusionsVancomycin has the potential to induce nephrotoxicity and ototoxicity when consistently at high serum drug levels. Due to its narrow therapeutic index, drug levels should be monitored to ensure the drug does not accumulate. The licensed dose and dose listed in the BNF for Children 2 3 has historically under dosed patients at our trust, leading to the risk of ineffective therapy and bacterial resistance. It is unclear from research what the optimal dose is for paediatric patients.More research is needed to determine the correct paediatric dose of vancomycin. Higher doses than currently recommended as per licence resulted in three quarters of patients achieving therapeutic levels, however 12 patients still required dose adjustment. No patients suffered irreversible adverse effects or toxicity, suggesting that higher doses are safe to use in the paediatric population. Further education is required for those involved in the prescribing, administering and monitoring of Vancomycin in paediatric patients to ensure its safe use. Additional monitoring is required for those receiving higher doses &gt;7 days to prevent drug accumulation, alternatively a loading dose followed by lower maintenance dose may be a more suitable dosing regimen.ReferencesHughes S, Crook J, Ross J. Vancomycin intravenous dosing guideline - paediatrics. Chelsea and Westminster Hospital; 2017.Stockman C, Sammons H, Stakey E, et al. Unanswered Questions Regarding Optimal Pediatric Vancomycin Use. Therapeutic Drug Monitoring 2016; 38:491–420.National Institute for Health and Care Excellence. Vancomycin. Available from https://bnfc.nice.org.uk/drug/vancomycin.html [Accessed 10th Oct 2018]

Drug Utilization in Critically Ill Adults with Augmented Renal Clearance Compared to Normal Renal Clearance: Implications for use of Antimicrobials with Predominant Renal Excretion.

Critically ill adults have Augmented Renal Clearance, (ARC) decreasing the systemic circulation of drugs with predominant renal elimination. The phenomenon of ARC is crucial for antimicrobial drugs as it hinders the therapeutic response and aids the development of antimicrobial resistance. The present study was conducted to assess the impact of ARC on an Intensive Care Unit (ICU) of a tertiary care hospital. This was a prospective observational study carried out in critically ill patients with normal serum creatinine without any history of renal disease. Details on their demographic characteristics, clinical diagnoses, laboratory parameters including trough levels of vancomycin and gentamicin, ICU length of stay, and clinical outcomes (discharged alive/death) were obtained. Creatinine clearance (Crcl) was estimated from 24-hour urine creatinine. Monte Carlo simulation test with 100000 iterations was used for predicting serum vancomycin trough levels with the observed Crcl. Eighty patients were recruited in the study of which 52.5% had ARC. Patients in younger age and body weight were observed with a trend to have ARC. No significant differences were observed in any of the drug classes prescribed between patients with and without ARC, including the systemic antimicrobials. Although the observed serum trough levels of vancomycin in patients with ARC did not differ significantly from those without ARC, Monte Carlo simulation predicted that 90% of patients with ARC were likely to have trough levels between 5.63 and 7.85 mg/dl, while those without ARC may have it between 7.75 to 9.82 mg/dl. A significant proportion of critically ill adults exhibit ARC and such patients are more likely to achieve lower trough concentrations of vancomycin than recommended. All critically ill adults with normal serum creatinine have to be screened for ARC using urine creatinine as soon as possible for appropriate adjustment in the dosage regimen of antimicrobials with predominant renal elimination.

Risk Factors for Low Vancomycin Trough Level in Adult General Ward Inpatients: a Retrospective Cohort Study

Risk Factors for Low Vancomycin Trough Level in Adult General Ward Inpatients: a Retrospective Cohort Study

Factors increasing the risk of inappropriate vancomycin therapy in ICU patients: A prospective observational study.

Vancomycin trough levels are frequently subtherapeutic in intensive care unit (ICU) patients. The aim of this study was to identify patients at risk of therapeutic failure defined as vancomycin area-under-the-curve0-24 /minimum inhibitory concentration (AUC0-24 /MIC) <400, and to examine possible effects of different MICs, the variability in renal clearance and continuous renal replacement therapy (CRRT), and the relevance of vancomycin therapy. A prospective observational study of ICU patients 18years at initiation of vancomycin therapy was conducted from May 2013 to October 2015. The patients were divided into four groups according to renal function and CRRT-mode as follows: normal- or augmented renal clearance and continuous venovenous hemodialysis or -hemofiltration. Vancomycin peak and trough levels were measured at 24, 48, and 72hours after therapy initiation. Relevance of vancomycin therapy was retrospectively evaluated based on microbiological results. Eighty-three patients were included, median age 54.5years, 74.5% male, SAPS II score 46, and 90day mortality 28%. Vancomycin therapy was initiated on ICU-day 8 (IQR, 5-12), with a median treatment time of 7.5 (IQR, 5-12) days. AUC0-24 /MIC>400 was reached in 81% and 8% with MIC=1 and 2mg/L respectively. The CRRT groups had higher AUC0-24 /MIC-ratios than the non-CRRT groups (P<.001). Augmented renal clearance increased the risk of AUC0-24 /MIC<400, independent of MIC-value. Initiation of vancomycin therapy was retrospectively considered relevant in 28 patients (34%). A MIC-value >1mg/L and augmented renal clearance, were factors increasing the risk of therapeutic failure. Vancomycin treatments could have been omitted or shortened in most of these patients.

Influence of cerebrospinal fluid drainage and other variables on the plasma vancomycin trough levels in postoperative neurosurgical patients

Background Therapeutic drug monitoring (TDM) aims to minimise the clinical impact of vancomycin (VCM) pharmacokinetic variability. However, TDM data are limited among specific patient populations, including postoperative neurosurgical populations. The objective of this study was to retrospectively investigate the influence of cerebrospinal fluid (CSF) drainage and other factors on the serum trough concentrations of VCM. Methods We analysed 154 patients who had been hospitalised in the neurosurgical ward and received intravenous infusions of VCM. We compared the daily doses of VCM, serum VCM concentrations, and serum concentration/dose ratio (C/D ratio) between patients who underwent CSF drainage (drainage group) and controls (nondrainage group). In addition, we also elucidated other factors affecting the attainment of target concentrations. Results The patients in the drainage group showed a significantly lower trough concentration of VCM (6.2 ± 4.2 µg/mL) than that shown by the nondrainage group (8.5 ± 6.6 µg/mL, p = 0.03). Furthermore, the patients in the drainage group showed a significantly different trough C/D ratio (3.1 ± 2.1) than that shown by the nondrainage group (4.3 ± 3.4, p = 0.014). The Mann–Whitney U test demonstrated significantly lower VCM trough levels with concomitant use of diuretic than without (p = 0.004). Multivariable logistic regression demonstrated that coadministered diuretic independently predicted subtherapeutic trough levels of <10 µg/mL (p = 0.04). The concomitant use of albumin and other variables exerted no effects on VCM trough levels. Conclusions These data suggest that CSF drainage and diuretics have different effects, but it seems that both lower the VCM concentration in postoperative neurosurgical patients. Our findings strongly suggest that a high dose of VCM is required to maintain optimal serum concentrations of VCM in patients managed with CSF drainage or concomitant use of diuretic.

Relationship of vancomycin trough levels with acute kidney injury risk: an exposure-toxicity meta-analysis.

Nephrotoxicity represents a major complication of vancomycin administration, leading to high rates of morbidity and treatment failure. The aim of this meta-analysis was to evaluate the association between trough levels and risk of renal impairment, by defining an exposure-toxicity relationship and assessing its accuracy in predicting the development of acute kidney injury (AKI). Medline, Scopus, CENTRAL, Clinicaltrials.gov and Google Scholar databases were systematically searched from inception. Studies examining the effects of trough levels on nephrotoxicity risk in adult patients were deemed eligible. The meta-analysis was based on 60 studies, including 13 304 patients. The development of AKI was significantly linked to both higher initial [standardized mean difference (SMD): 0.82; 95% CI: 0.65-0.98] and maximum (SMD: 1.06; 95% CI: 0.82-1.29) trough levels. Dose-response analysis indicated a curvilinear relationship between trough levels and nephrotoxicity risk (χ2 = 127.1; P value < 0.0001). A cut-off of 15 mg/L detected AKI with a sensitivity of 62.6% (95% CI: 55.6-69.2) and a specificity of 65.5% (95% CI: 58.9-71.6), while applying a 20 mg/L threshold resulted in a sensitivity of 42.9% (95% CI: 34-52.2) and a specificity of 82.5% (95% CI: 73.9-88.8). The present findings suggest that the development of vancomycin-induced AKI is significantly associated with higher initial and maximum trough levels. An exposure-response relationship was defined, indicating that increasing trough levels correlate with a significant rise of nephrotoxicity risk. Future studies should verify the effectiveness of individualized pharmacokinetic tools that would enable the attainment of trough level targets and minimize the risk of renal toxicity.

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...

Vancomycin Dosing in Children With Overweight or Obesity: A Systematic Review and Meta-analysis.

Vancomycin is a medication with potential for significant harm with both overdosing and underdosing. Obesity may affect vancomycin pharmacokinetics and is increasingly common among children. We aimed to determine if children with overweight or obesity have increased vancomycin trough concentrations with total body weight (TBW) dosing compared with children with normal weight. We conducted a search of Medline and Medline In-Process & Other Non-Indexed Citations from 1952 (the year vancomycin was discovered) to November 2017. Search terms included vancomycin, body weight, and body composition terms and were limited to children. Studies were reviewed and screened by ≥2 reviewers. The primary outcome was vancomycin level. Data were extracted by 2 reviewers. We performed quality assessment using the Newcastle-Ottawa quality assessment scale. We identified 271 records. After abstract and full-text screening, we identified 7 studies for full review. Six of the 7 studies used a matched case-control design, although there was significant variation in study methodology. Four of the 7 studies were included in a meta-analysis, which revealed a small but significant difference in vancomycin trough levels between children with normal weight and children with overweight or obesity when dosed by using TBW (N = 521; mean difference 2.2 U [95% confidence interval: 1.0-3.4]). High-quality data to guide vancomycin dosing in children with obesity are lacking. More studies evaluating dosing strategies in children with obesity are warranted because using TBW to dose vancomycin may lead to higher vancomycin concentrations and potential toxicity.

Empiric vancomycin dosing in neonates: relationship between initial dose and 24 h area under the curve/minimum inhibitory concentration ratio

Vancomycin is used for treating coagulase-negative staphylococcus infections in neonates. However, concerns about the appropriate empirical dosing required for optimal efficacy, still remain. To assess the relationship between the initial doses of vancomycin used in a Neonatal Intensive Care Unit (NICU) with the possibility of achieving therapeutic target of AUC024h/MIC > 400 µg/h/mL. Retrospective and descriptive study carried out between February 2016 and March 2018. All neonates treated with vancomycin for suspected/proven Gram-positive infection and with at least one trough serum concentration level were included. Probability of target attainment (PTA) was evaluated through resampling of AUC and MIC values. Final dataset included 38 patients and 49 trough vancomycin levels; 94.7% of these cases (n = 36) were confirmed Gram-positive infections. The median AUC/MIC values for the trough values vancomycin < 10 µg/mL group and for the ≥ 10 µg/mL group were 327 (IQR 174-395) and 494 (IQR 318-631) respectively (p = 0.035). Current empirical dosing strategy has a 47.7% PTA (AUC/MIC > 400) when taking institutional MICs into account. It is not possible to assure achieving a AUC/MIC > 400 µg/h/mL when considering institutional sensibilities. Current empiric dosing strategies should be reconsidered and further investigation needs to be done to help determine the appropriate empirical dosing required for optimal efficacy in neonates.

Vancomycin-associated acute kidney injury in Hong Kong in 2012\u20132016

BackgroundTo study the incidence of vancomycin-associated acute kidney injury (VA-AKI) in Hong Kong and identify risk factors for VA-AKI.MethodPatients with vancomycin prescription and blood level measurement in 2012–2016 were identified using the Hong Kong Hospital Authority Clinical Data Analysis and Reporting System. Acute kidney injury was defined using KDIGO criteria. Patients without creatinine measurements, steady-state trough vancomycin level or who had vancomycin treatment < 3 days were excluded. Results were analyzed using SPSS version 22.0. Logistic regression was used to identify the predictors for VA-AKI. Odds ratio and 95% confidence interval were estimated.ResultsOne thousand four hundred fifty patients were identified as VA-AKI from 12,758 records in Hong Kong in 2012–2016. The incidence was respectively 10.6, 10.9, 11.3, 12.2, 11.2% from 2012 to 2016. The incidence of VA-AKI was 16.3, 12.2, 11.3 and 6.2% in patients aged 1–12, 12–60, elderly aged > 60 and newborn and infants, respectively. Baseline creatinine, serum trough vancomycin level, systematic disease history including respiratory failure, hypertension, congestive heart failure, chronic renal failure, anemia and type II diabetes, and concomitant diuretics, piperacillin-tazobactam (PTZ) and meropenem prescription were significantly higher in VA-AKI patients older than 12 years. Logistic regression showed that older age group, higher baseline creatinine, serum trough vancomycin level, respiratory failure, chronic renal failure and congestive heart failure, concomitant diuretics, PTZ and meropenem prescription, and longer hospital stay were all associated with increased risk of VA-AKI.ConclusionThe incidence of VA-AKI in Hong Kong is low but shows no decline. Patients with higher baseline creatinine, multi-organ diseases and multiple drugs administration should have their vancomycin level monitored to decrease the risk of VA-AKI.

A retrospective review of vancomycin dosing in paediatric patients

Background: Vancomycin has antimicrobial activity against most Gram-positive pathogens. Reduced susceptibility of vancomycin to many microbes has necessitated higher target vancomycin trough levels (VTL) of 10-20mg/L. Paediatric dosing algorithms have remained unchanged despite higher VTL targets; increased doses are required. The study outcomes were to assess the impact of new dosing guidelines on VTL, time to target VTL and vancomycin-associated acute kidney injury (vAKI). Methods: A single-centre review assessed 63 vancomycin treatment episodes between Apr-2016 and Feb-2019. Demographic data, treatment duration, daily vancomycin dosing and VTL were collected. Episodes were grouped as high-dose vancomycin (HDV) (≥60mg/kg/day) and low-dose vancomycin (LDV) (&lt;60mg/kg/day). Target VTL was 10-20mg/L. AKI was defined by modified pRIFLE criteria as ≥50% increase in baseline creatinine within 7 days of treatment commencement. The project was registered with the local audit team. Results: Initial VTL were significantly higher in the HDV group (mean 10.4, SD±4.7mg/L; n=20) than LDV (mean 7.9,SD±4.0mg/L;n=43), p=0.0397. Whilst time-taken to reach target VTL was improved in the HDV group (53.5±22.3 hours vs 66.1±37.1hours), this was statistically insignificant (p=0.2675). Paired t-tests revealed no significant changes to baseline creatinine in HDV (p=0.1267) and LDV (p=0.2006). No differences in vAKI incidence between the two groups were noted (p&gt;0.05). Conclusion: Increasing vancomycin dosages improved initial VTL but was insufficient to improve the length of time to reach target VTL. Reassuringly, there was no increase in vAKI incidence with HDV. The study suggests loading doses in paediatrics may be needed to improve time to target VTL.

A simple and validated HPLC method for vancomycin assay in plasma samples: the necessity of TDM center development in Southern Iran.

Background and purpose:Vancomycin is a glycopeptide antibiotic which is the drug of choice against methicillin-resistant Staphylococcus aureus. It has a narrow therapeutic index, and thus therapeutic drug monitoring (TDM), and clinical pharmacokinetic assessment are necessary in order to prevent adverse drug reactions such as nephrotoxicity. In this study, we aimed to develop a simple and validated HPLC method for vancomycin assay in order to establish a TDM center for patients admitted to the ICU of Nemazee Hospital in southern Iran.Experimental approach:In this study, a brief review of different parameters and variables which could affect the sensitivity, selectivity of the validated HPLC method for vancomycin determination were considered. According to the previous studies a simple, fast, and the relatively low-cost method was established for vancomycin determination in plasma samples.Findings/Results:The developed HPLC assay indicated a calibration curve with R-square of > 0.999, acceptable selectivity, the accuracy of 90-105%, CV% of less than 15%, the limit of quantification of 1 μg/mL, and limit of detection of 300 ng/mL. Vancomycin trough level, the area under the curve, renal clearance, the volume of distribution, and elimination constant were measured in patients using this validated method.Conclusion and implications:Validated method for assay of vancomycin plasma levels was used to quantify vancomycin levels of four patients who were admitted to the ICU of Nemazee Hospital. According to the results, two of these patients showed lower levels than recommended therapeutic purposes while one of them showed a toxic level. According to the results, the TDM assessment of vancomycin is strongly recommended for patients who are hospitalized in ICU.