Vancomycin Serum Trough Concentrations Research Articles

Association between trough serum vancomycin concentration and vancomycin-associated acute kidney injury and 30-day mortality in critically ill elderly adults

BackgroundVancomycin-associated acute kidney injury (VA-AKI) is the most clinically relevant side effect of vancomycin. The objective of this study was to investigate the association between VTC and VA-AKI as well as 30-day mortality in critically ill elderly adults.MethodElderly patients with trough serum vancomycin concentration records(VTC) in the Medical Information Mart-IV (MIMIC-IV) and eICU databases were retrospectively studied.ResultsA total of 3,146 critically ill elderly adults were finally enrolled. The incidence of VA-AKI in the elderly population was 76.5%. Logistic regression analysis revealed significant relationships between VA-AKI and various factors, including VTC, comorbidities, and laboratory indicators, and SOFA, and GCS score. For each mg/L increase, the OR for VA-AKI increased by 2.5%. The association between VTC and 30-day mortality was found to be statistically significant (odds ratio (OR): 1.021, 95% CI: 1.010–1.031), P < 0.001). The Restricted cubic splines (RCS) curves revealed that VTC ranged of 19.67 to 35.72 mg/l for AKI and 19.17 to 42.86 mg/l for 30-day mortality exhibit OR with 95% CI above 1, indicating statistically significant associations with an increased risk of AKI and 30-day mortality, respectively. In the subgroup analysis, VTC was identified as a risk factor for VA-AKI in specific patient groups, including white individuals, female patients, those with shock, patients with SOFA > 6, patients with baseline creatinine > 1.2 mg/dl and patients with or without exposed to other nephrotoxic medications.ConclusionThis study found the significant association between VTC and the incidence of VA-AKI and 30-day mortality in critically ill elderly adults. The RCS curves indicated concentration ranges for AKI (19.67–35.72 mg/L) and 30-day mortality (19.17–42.86 mg/L), signifying increased risk.

Epidemiology of Vancomycin in Combination With Piperacillin/Tazobactam-Associated Acute Kidney Injury in Children: A Systematic Review and Meta-analysis.

Several studies have shown that vancomycin combined with piperacillin/tazobactam (VPT) increased the risk of acute kidney injury (AKI) compared with other antibiotics in children. However, the epidemiology of VPT-associated AKI in children is unknown. To evaluate the incidence and risk factors of VPT-associated AKI in children. Literature databases of PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, WanFang Database, and China Biology Medicine Disc were searched from inception to November 2023. References of included studies were also manually checked. Two independent reviewers selected studies, extracted data, and quality assessment. Meta-analyses were performed to quantify the incidence and risk factors of VPT-associated AKI in children. Sixteen cohort studies were identified. Overall, the incidence of VPT-associated AKI in children was 24.3% (95% CI: 17.9%-30.6%). The incidence of VPT-associated AKI in critically ill children (26.6%) was higher than that in noncritically ill children (10.9%). Moreover, higher serum vancomycin trough concentration (>15 mg/L), use of vasopressors, combination of nephrotoxins and intensive care unit admission were risk factors for VPT-associated AKI in children (P < 0.05). Identifying high-risk groups and determining safer treatments is critical to reducing the incidence of VPT-associated AKI in children. The incidence of VPT-associated AKI in children is high, especially in critically ill children. Medication regimens should be personalized based on the presence of individual risk factors. Moreover, renal function was regularly assessed throughout treatment with VPT.

A descriptive study of vancomycin use at Red Cross War Memorial Children's Hospital, Cape Town.

Antimicrobial stewardship principles guide the clinical use of antimicrobials, including vancomycin, but paediatric vancomycin prescribing practices have not been evaluated in South Africa. To document the use, prescribing practices and monitoring of intravenous vancomycin and the spectrum of bacteria isolated on microbiological culture in children treated with intravenous vancomycin during a 12-month period at Red Cross War Memorial Children's Hospital (RCWMCH). A retrospective audit of intravenous vancomycin use in children admitted to RCWMCH during 2019 was performed. All 158 vancomycin prescription episodes for 143 children were included. Overall usage of intravenous vancomycin was 63 days of therapy per 1000 patient days (interquartile range [IQR]: 38-72). The median starting dose was 15 mg/kg per dose (IQR: 14-15) and median daily dose was 45 mg/kg per day (IQR: 43-60). Vancomycin was prescribed as empiric (127/158, 80%) and directed (31/158, 20%) treatment. The median duration of treatment for the directed group (7 days) was longer than the empiric group (4 days) (p = 0.001). Vancomycin serum trough concentrations were performed in 65/98 (66%) episodes where vancomycin treatment exceeded 3 days, with only 16/65 (25%) of these samples obtained before the fourth dose. Prolonged antibiotic treatment of 14 days or more was not associated with Gram-positive bacteria on culture (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 0.17-4.2). Dosing errors, prolonged empiric treatment and inappropriate vancomycin monitoring were problems associated with vancomycin prescriptions. The study identified multiple opportunities for improved vancomycin prescribing and monitoring. Further research and implementation of improved prescribing practices could contribute to the preservation of vancomycin as an effective antibiotic.

Predicting vancomycin trough serum concentration in augmented renal clearance patients through an artificial neural network model

PurposeArtificial neural network (ANN) model has been developed in prediction of serum drug concentration. The aim of this study was verifying the accuracy of ANN model in predicting vancomycin trough serum concentration in ARC adult patients. MethodsA total of 162 ARC patients (258 observations) who received vancomycin treatment (500–2000 ​mg) at the First Affiliated Hospital of China Medical University between Jan 2017 and Nov 2020 were included. The performance and accuracy of the ANN model was evaluated by mean absolute deviation (MAD), mean absolute percent error (MAPE), mean square error (MSE), and root mean squared error (RMSE). In addition, the vancomycin calculator and multivariable linear regressions were compared with the ANN model in predicting vancomycin concentration. ResultsFrom results of linear regression analyses, dosage, dosage interval, age, creatinine clearance, sex, weight, total bilirubin (T-Bil), haemoglobin (HGB) and total protein (TP) were used as input variables to develop an ANN model for predicting vancomycin concentration in ARC patients. The MAPE, MSE, RMSE, MAD and R2 were 14.81%, 2.47%, 0.44%, 1.40% and 0.88%, respectively.The ANN model might be an useful tool to predict vancomycin concentration and help modify the dosing regimen accurately and in a timely manner to improve the clinical efficacy in ARC patients. In the future, ANN model could be developed to predict serum concentration and modify dosing regimens for more types of therapeutic drugs and patients with more complex diseases.

Relationship between vancomycin-induced nephrotoxicity and vancomycin trough concentration in older adults: A retrospective observational study.

The objective of the study is to investigate the risk factors of vancomycin-induced renal toxicity in older adults, especially in those with chronic kidney disease (CKD) Stages 3-5. In this retrospective observational study, serum vancomycin trough concentrations (VTCs) in patients aged g65 years treated with vancomycin were analyzed, and independent risk factors of vancomycin-induced nephrotoxicity (VIN) were determined by logistic regression analysis. In total, 321 patients were included in this study. Serum VTC was an independent risk factor for vancomycin-induced renal toxicity in total cohort (odds ratio [OR], 1.07; P = 0.004) as well as in the cohort with CKD Stages 3-5 (OR, 1.09; P = 0.010). A daily dose of vancomycin and Charlson comorbidity index was an independent risk factor for vancomycin-induced renal toxicity in total cohort (OR, 3.63; P = 0.006) and in the cohort with CKD Stage 3-5 (OR, 1.83; P = 0.002), respectively. In older adults with CKD Stages 3a and 3b-5, the VTCs associated with higher risk for vancomycin-induced renal toxicity were 21.5 mg/L and 16.5 mg/L, respectively. In older adults, serum VTC is an independent risk factor for VIN. VTCs over 21.5 mg/L and 16.5 mg/L are associated with increased risk of VIN in this population with CKD Stage 3a and 3b-5, respectively.

Population pharmacokinetics of vancomycin in very low birth weight neonates.

Vancomycin dosing in very low birth weight (VLBW) neonates is challenging. Compared with the general neonatal population, VLBW neonates are less likely to achieve the vancomycin therapeutic targets. Current dosing recommendations are based on studies of the general neonatal population, as only a very limited number of studies have evaluated vancomycin pharmacokinetics in VLBW neonates. The main aim of this study was to develop a vancomycin population pharmacokinetic model to optimize vancomycin dosing in VLBW neonates. This multicenter study was conducted at six major hospitals in Saudi Arabia. The study included VLBW neonates who received vancomycin and had at least one vancomycin serum trough concentration measurement at a steady state. We developed a pharmacokinetic model and performed Monte Carlo simulations to develop an optimized dosing regimen for VLBW infants. We evaluated two different targets: AUC0-24 of 400-600 or 400-800 µg. h/mL. We also estimated the probability of trough concentrations >15 and 20 µg/mL. In total, we included 236 neonates, 162 in the training dataset, and 74 in the validation dataset. A one-compartment model was used, and the distribution volume was significantly associated only with weight, whereas clearance was significantly associated with weight, postmenstrual age (PMA), and serum creatinine (Scr). We developed dosing regimens for VLBW neonates, considering the probability of achieving vancomycin therapeutic targets, as well as different toxicity thresholds. The dosing regimens were classified according to PMA and Scr. These dosing regimens can be used to optimize the initial dose of vancomycin in VLBW neonates.

Evaluation of Vancomycin Accumulation in Patients With Obesity

BackgroundCurrent vancomycin guidelines recommend early and frequent area-under-the-curve monitoring in patients with obesity. Vancomycin's volume of distribution is likely altered in patients with obesity, which may result in lower serum concentrations initially but lead to accumulation with continued use. The objective of this study was to evaluate the incidence of vancomycin accumulation in patients with obesity and identify potential factors associated with accumulation.MethodsThis was a single-center, retrospective, observational study at a tertiary academic medical center. Adult patients with a body mass index (BMI) ≥ 30 kg/m2 and ≥ 2 vancomycin serum trough concentrations drawn in 2019 were screened for inclusion. The major endpoint was the incidence of vancomycin accumulation defined as ≥ 20% increase in trough concentration within the first 10 days of therapy. Key minor endpoints included incidence of acute kidney injury (AKI) and factors associated with accumulation.ResultsOf the 443 patients screened, 162 were included. The median age was 56.5 years (interquartile range [IQR], 43–65.3), and 62.3% were male. The median weight was 112.7 kg (IQR, 99.8–122.6) and the median BMI was 36.8 kg/m2 (IQR, 33.1–41). The total daily dose median at initiation was 28.7 mg/kg per day (IQR, 25.4–31.2). Accumulation occurred in 99 of 162 patients (61.1%) and AKI occurred in 20 of 140 patients (14.3%). No specific factors were found to be associated with accumulation.ConclusionsPatients with obesity are likely to experience vancomycin accumulation within the first 10 days of therapy. Clinicians should use frequent monitoring of vancomycin and use caution when interpreting early concentrations in patients with obesity.

Relationship between Vancomycin Trough Serum Concentrations and Clinical Outcomes in Children: a Systematic Review and Meta-Analysis.

ABSTRACTTo systematically evaluate the relationships between vancomycin trough serum concentrations and clinical outcomes in children using meta-analysis. Several databases, including PubMed, Elsevier, Web of Science, EMBASE, Medline, clinicaltrials.gov, the Cochrane Library, and three Chinese databases (Wanfang Data, China National Knowledge Infrastructure, and SINOMED), were comprehensively searched to obtain research articles on vancomycin use in children from inception through December 2021. All studies were screened and evaluated using the Cochrane systematic review method. Then, the feature information was extracted for meta-analysis. The evaluated results included clinical efficacy, vancomycin-associated nephrotoxicity, hepatotoxicity, ototoxicity, mortality, and microbial clearance. A total of 35 studies involving 4820 children were included in the analysis. The meta-analysis showed that compared with children with vancomycin trough concentrations <10 μg/mL, those with vancomycin trough concentrations ≥10 μg/mL had a higher clinical efficacy rate [OR: 2.23, 95% CI: 1.29 to 3.84, P = 0.004] and higher incidences of nephrotoxicity [OR: 2.76, 95% CI: 1.51 to 5.07, P = 0.001], ototoxicity [OR: 1.87, 95% CI: 1.08 to 3.23, P = 0.02] and microbial clearance [OR: 2.36, 95% CI: 1.53 to 3.64, P = 0.0001]. All-cause mortality [OR: 1.07, 95% CI: 0.45 to 2.53, P = 0.88] and hepatotoxicity [OR: 0.84, 95% CI: 0.46 to 1.53, P = 0.57] were similar between the two groups. Subgroup analysis showed that compared with children with vancomycin trough concentrations of 10 to 15 μg/mL, those with vancomycin trough concentrations >15 μg/mL had a higher incidence of nephrotoxicity [OR: 2.64, 95% CI: 1.28 to 5.43, P = 0.008], but there was no significant difference in clinical efficacy [OR: 0.85, 95% CI: 0.30 to 2.44, P = 0.76]. A vancomycin trough concentration of 10 to 15 μg/mL can improve clinical efficacy in children. Additionally, avoidance of trough concentrations >15 μg/mL can reduce the incidence of adverse reactions.

Mortality and Factors Related in Pediatric Intensive Care Unit Patients Treated with Vancomycin

Abstract There is limited information available regarding clinical outcome and rate of mortality in relation to invasive methicillin-resistant Staphylococcus aureus (MRSA) infection in pediatric intensive care unit (PICU) patients treated with vancomycin in this tertiary hospital in northern Thailand. Therapeutic drug monitoring (TDM) is recommended vancomycin prescription; however, it is important to investigate the outcome of this monitoring in PICU patients. This study aims to evaluate the mortality and factors related to these in PICU patients treated with vancomycin. A retrospective study was conducted in PICU patients given vancomycin from April 2018 to April 2019. The following variables were included: age, sex, underlying disease, diagnosis, length of stay (LOS) in PICU, Pediatric Index of Mortality 2 (PIM 2) score, mechanical ventilator use, renal replacement therapy (RRT), laboratory data, vancomycin dose, trough serum vancomycin concentration (Ctrough) and mortality rate. One hundred and sixty pediatric patients were enrolled into the study (median age 12 months, range 2-180 months, 69.4% male). Ctrough of vancomycin (10–20 mg/L) was recorded in 32.5% (n = 52) of cases. Septic shock was the most common diagnosis (49.3%) and the mortality rate was 39.4%. Results indicated that children who had a vancomycin Ctrough outside the therapeutic range, mechanical ventilator use and RRT use were statistically significantly associated with higher mortality rate (adjusted OR 3.29, 95% CI, 1.41-7.69; P &lt;0.05), (adjusted OR 6.22, 95% CI, 1.67-23.16; P &lt; 0.05) and (adjusted OR 10.41, 95% CI, 2.62-41.37; P &lt; 0.05). These factors were related to mortality and further studies are needed to determine if this outcome can be improved. Keywords: Vancomycin, Vancomycin trough concentration, Pediatric patients, Intensive care, Mortality, Factors related to mortality

Comparison of single trough-based area under the concentration–time curve versus trough concentration for the incidence of vancomycin-associated nephrotoxicity

IntroductionWhile the revised 2020 consensus guideline recommends the use of area under the concentration–time curve (AUC)-guided vancomycin monitoring, collecting multiple vancomycin serum samples to calculate the AUC may cause clinical complications. The aim of the present retrospective study was to evaluate whether AUC-guided vancomycin monitoring, in which AUC was calculated based on a single trough concentration, is a better predictor of nephrotoxicity than trough-guided monitoring in patients receiving vancomycin therapy. MethodsA single-center, retrospective cohort study was conducted at the 614-bed Gifu University Hospital in Japan. Patients who received intravenous vancomycin for a documented or suspected infection and had their serum vancomycin trough concentration monitored between October 1, 2016 and September 30, 2020 were enrolled in the present study. ResultsMultivariate Cox proportional hazard analysis indicated that AUC (>600 μg•h/mL) was a significant risk factor for the incidence of acute kidney injury (AKI), while trough concentration (≥15 μg/mL) was not. Moreover, the AUC (>600 μg•h/mL) showed higher specificity and similar sensitivity to the trough concentration (≥15 μg/mL). Kaplan-Meier plots of the cumulative incidence of the AKI-free rate in patients indicated that the onset of AKI was significantly longer in patients with AUC ≤600 μg•h/mL than in patients with AUC >600 μg•h/mL (HR, 16.1; 95% CI, 6.3–41.2; p < 0.001). ConclusionAUC based on a single trough concentration was a better predictor of nephrotoxicity than trough concentration.

The Thirty-Day Mortality Rate and Nephrotoxicity Associated With Trough Serum Vancomycin Concentrations During Treatment of Enterococcal Infections: A Propensity Score Matching Analysis.

The objective of this study was to evaluate the relationship between vancomycin trough levels in patients with documented enterococcal infections and mortality, clinical outcomes, microbiological outcomes, and nephrotoxicity. We conducted a retrospective cohort study of patients with enterococcus infections who were prescribed vancomycin with therapeutic drug monitoring during January 2010 and December 2019 at Chiang Mai University Hospital (CMUH). The study enrolled 300 participants who met the inclusion criteria and were prescribed vancomycin with therapeutic drug monitoring. The results of this study showed that, after propensity score matching, a vancomycin trough of ≥15 mg/L was associated with significant differences in 30-days mortality compared to a vancomycin trough of <15 mg/L (aHR: 0.41, 95% CI: 0.21–0.82; p = 0.011). Likewise, a vancomycin trough of ≥15 mg/L was associated with significant differences in the clinical response (aHR: 0.49, 95% CI: 0.26–0.94; p = 0.032), microbiological response (aHR: 0.32, 95% CI: 0.12–0.87; p = 0.025) and nephrotoxicity (aHR: 3.17, 95% CI: 1.39–7.23; p = 0.006), compared with a vancomycin trough of <15 mg/L. However, sub-group analysis found that very high trough levels (>20 mg/L) were also associated with a high rate of nephrotoxicity (aHR: 3.55, 95% CI 1.57–8.07, p = 0.002), when compared with a vancomycin trough of <15 mg/L. The target vancomycin trough concentration was ≥15 mg/L and this target can be an optimal alternative to the use of area under the curve (AUC) values for monitoring the treatment of enterococcal infection.

1102. Evaluation of Vancomycin Accumulation in Patients with Obesity

BackgroundCurrent vancomycin guidelines recommend using actual body weight for dosing. However, in patients with obesity, this may result in lower initial vancomycin concentrations that can accumulate with continued doses due to differences in volume of distribution. The objective of this study is to evaluate the incidence of vancomycin accumulation in patients with obesity and identify potential factors associated with accumulation.MethodsThis is a single-center, retrospective, observational study at a tertiary academic medical center. Adult patients with a BMI ≥ 30 kg/m2 and with ≥ 2 vancomycin serum trough concentrations within the same encounter in 2019 were screened. Patients were excluded if they were pregnant, had unstable renal function or severe renal impairment, received < 3 doses before a concentration was drawn, or had inconsistent dosing prior to a concentration draw. Linear kinetics were used to correct for differences in timing of concentration or dose changes. The major endpoint was the incidence of vancomycin accumulation, defined as a 20% increase in trough concentration between the first and any subsequent trough concentrations within the first 10 days of therapy. Minor endpoints included the percentage of supratherapeutic concentrations and the incidence of acute kidney injury (AKI). Descriptive statistics were used to evaluate endpoints and multivariable logistic regression was used to evaluate factors associated with accumulation.ResultsWe screened 543 patients, and 162 were included in our analysis. The median age was 56.5 years (interquartile range [IQR] 43 - 65.3), and 62.3% were male. The median weight was 112.7 kg (IQR 99.8 - 122.6) and the median BMI was 36.8 kg/m2 (IQR 33.1 - 41). The median total daily vancomycin dose at initiation was 28.7 mg/kg/day (IQR 25.4 - 31.2). Vancomycin accumulation occurred in 99 patients (61.1%) within the first 10 days of therapy and AKI occurred in 21 patients (14.9%). No factors studied, including age, gender, obesity class, initial dose, SCr, or frequency were associated with accumulation.ConclusionMost patients with obesity experienced vancomycin accumulation within the first 10 days of therapy. Providers should be cautious when assessing a vancomycin concentration early in the treatment course.Disclosures All Authors: No reported disclosures

Evaluation of association between parameters related to penetration into cerebrospinal fluid and the microbiological efficacy of vancomycin in patients with bacterial meningitis

Vancomycin (VM) is used as empirical therapy for bacterial meningitis (BM). We investigated the relationship of the microbiological efficacy of VM for BM with VM minimum inhibitory concentration (MICVM), serum VM trough concentration (VMser) and cerebrospinal fluid (CSF) protein (P)/serum albumin (SA) ratio, which may reflect the extent of blood–brain barrier (BBB) disruption. Twelve BM patients were enrolled and VM was microbiologically effective in seven (58.3%). VMser, MICVM, and CSF-P/SA ratio were not associated with the microbiological efficacy of VM. The microbiological efficacy of VM was significantly associated with CSF-P/SA ratio multiplied by VMser relative to the MICVM (η = 0.61, p = 0.04). These results indicate that the parameter combining VMser, MICVM, and the extent of BBB disruption could be associated with the microbiological efficacy of VM in BM patients.

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

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

Successful Treatment of Invasive MRSA Infections in Children Using Area Under the Vancomycin Concentration-Time Curve Divided by the Minimum Inhibitory Concentration (AUC/MIC) to Measure Vancomycin Exposure

Background: Vancomycin is the treatment of choice for invasive methicillin-resistant Staphylococcus aureus (MRSA) infections. Previous guidelines issued by the Infectious Diseases Society of America (IDSA) recommended targeting vancomycin serum trough concentrations of 15–20 mg/L; however, troughs &lt;15 mg/L are also associated with increased odds of renal toxicity. To minimize toxicity, recently updated ASHP/IDSA/PIDS vancomycin dosing guidelines recommend the use of an area under the vancomycin concentration-time curve divided by the minimum inhibitory concentration (AUC/MIC) pharmacodynamic index to measure vancomycin exposure, with an AUC/MIC ratio &gt;400 correlating with clinical efficacy. However, data on vancomycin therapeutic drug monitoring (TDM) in children are limited. Our institutional practice since January 2009 has been to use AUC/MIC, rather than serum trough concentrations, to guide vancomycin dosing. In this study, we describe clinical outcomes in vancomycin-treated children with invasive MRSA infections using this dosing method. Methods: We performed a retrospective chart review of children hospitalized with invasive MRSA infections between 2006 and 2019 at Rady Children’s Hospital in San Diego, California. Clinical, microbiologic, and pharmacologic data including the site of MRSA infection, clinical failure or cure, occurrence of acute kidney injury (AKI), vancomycin MIC, vancomycin AUC, and serum trough concentrations were collected. Results: In total, 61 invasive MRSA cases were reviewed: 20 were admitted January 2016 through December 2008, and 41 were admitted January 2009 through June 2019 (Figure 1). Most patients did not have medical comorbidities. The most common types of infections were primary bacteremia (34%) and osteomyelitis (32%). Of 61 children, 50 (82%) had positive clinical outcomes regardless of vancomycin dosing method. Of 20 patients, 8 (40%) admitted prior to January 2009 developed AKI, compared with 5 (12%) of 41 patients admitted after January 2009. Conclusions: In our retrospective review, most patients had clinically successful outcomes regardless of which dosing strategy was used. We found higher rates of renal toxicity in patients who were admitted prior to 2009, with TDM based on measuring peak and trough concentrations, compared with those using AUC/MIC for TDM. Our findings suggest that AUC/MIC TDM for invasive MRSA infections may be associated with lower rates of renal toxicity.Funding: NoDisclosures: None

Impact of the Implementation of a Vancomycin Protocol on Trough Serum Vancomycin Concentrations in a Pediatric Intensive Care Unit.

Vancomycin is an antibiotic that is widely used in pediatric intensive care, but the safe and effective use of this drug is challenging. This study aimed to assess the impact of a vancomycin protocol on trough serum concentrations. We conducted a retrospective quasiexperimental study in patients aged ≤18 years in intensive care who received vancomycin for at least 5 days. Patients were divided into two groups: before and after a protocol implemented in 2017 that suggested an initial vancomycin dose of 60 mg/kg/day, target serum levels of 15-20 μg/mL, and dose adjustments. We compared patient characteristics, target serum level achievement, and vancomycin levels over time. Each group contained 65 patients; most were male infants with heart disease as the main reason for hospitalization. Only 29.2% of the patients had pretreatment cultures for bacteria identification recorded, with 1.5% identified as methicillin-resistant Staphylococcus aureus. For the first serum levels, 10.8% of patients in the pre-protocol group and 21.5% in the post-protocol group achieved the 15-20 μg/mL target (p = 0.153); during the first 5 days of treatment, this proportion significantly increased from 52.3 to 73.8% (p = 0.018). We observed a difference between the first and fifth levels: 8.9 μg/mL (95% confidence interval [CI] -3.1 to 21) pre-protocol and 0.4 μg/mL (95% CI -6.1 to 6.9) post-protocol (p = 0.175). Reaching adequate trough vancomycin concentrations in critically ill pediatric patients remains a challenge, and clinical practice protocols allow better dose adjustment and control even when monitoring technologies are unavailable.

#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.

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.

Association between Serum Trough Concentration of Vancomycin and Vancomycin-induced Renal Dysfunction Based on the Geriatric Nutritional Risk Index

Association between Serum Trough Concentration of Vancomycin and Vancomycin-induced Renal Dysfunction Based on the Geriatric Nutritional Risk Index

An individualized administration model of vancomycin in elderly patients with sepsis and factors influencing augmented renal clearance.

Vancomycin efficacy is dependent on appropriate dosing, which should aim to achieve a target serum trough level. The purpose of this study was to determine the variables that predicted vancomycin serum trough concentrations in elderly patients with sepsis. This retrospective cohort study, which was conducted in the medical ICU of a university-affiliated teaching hospital in China, included 87 medical patients with sepsis who were enrolled from January 2014 to December 2017. All the patients were at least 60years old (mean age=74.8±8.2years), and 51.7% (n=45) of them were male. The most common primary site of infection was the lungs (67.8%), followed by the abdomen (12.6%). Patients with septic shock accounted for 21.8% (n=19) of the cases. The proportion of patients with vancomycin serum trough concentrations reaching target concentrations (≥15mg/L) was 47.1% (41 cases). Multivariate linear regression showed that the creatinine clearance rate (CCR) and the daily dosage of vancomycin were independent predictors of vancomycin serum trough concentrations (both p's<0.05), and the model for predicting vancomycin trough concentrations should be: serum trough concentration (mg/L)=15.942-0.101×CCR (mL/min)+0.347×vancomycin daily doses (mg/kg/d). Augmented renal clearance (ARC) was present in 13 patients (14.9%), and logistic regression revealed body mass index (OR=1.420, p=.002) and serum creatinine level (OR=0.883, p=.002) were independent predictors of ARC. The CCR and daily dosage of vancomycin were significantly correlated with vancomycin serum trough concentrations in elderly patients with sepsis, and the individualized administration model should be verified through further clinical trials. BMI and serum creatinine level were identified to be independent predictors of ARC in elderly patients.