Dose Of Intravenous Vancomycin Research Articles

Vancomycin Hypersensitivity: Case Reports of Successful Vancomycin Desensitization

Background: Vancomycin infusion reaction (VIR, previously known as “red man syndrome”) and anaphylaxis are two vancomycin hypersensitivity reactions with identical and clinically indistinguishable clinical presentations. Method: This was a retrospective study where vancomycin hypersensitivity cases who underwent vancomycin desensitization in the past two years were recruited. Results: Two vancomycin hypersensitivity cases were labeled as allergic to vancomycin in their previous hospitalizations before being admitted to our hospitals. The first case developed facial and lips swelling, while the second case developed transient hypotension; both occurred after the first dose of intravenous vancomycin, and hence were labelled as allergies without continuation of vancomycin in the previous hospitalizations. During current hospital admissions, both patients required vancomycin to treat infections. After weighing the risks and benefits, rapid vancomycin desensitization was conducted in both patients because of budget constraints in the public hospitals for alternative antibiotics. The desensitization was successfully conducted with no recurrence of previous reactions, and both cases completed intravenous vancomycin treatment for their infections. Conclusion: Clinical presentations in VIR and anaphylaxis might be identical and indistinguishable, especially the reactions that have happened in the past and confirmatory allergy test is not available. Our study reported that vancomycin desensitization could be conducted in cases where VIR or anaphylaxis are uncertain, with the past reactions not life-threatening, and if no other alternative antibiotic can be used to treat infections.

A Free Open-Source Bayesian Vancomycin Dosing App for Adults: Design and Evaluation Study.

BackgroundIt has been suggested that Bayesian dosing apps can assist in the therapeutic drug monitoring of patients receiving vancomycin. Unfortunately, Bayesian dosing tools are often unaffordable to resource-limited hospitals. Our aim was to improve vancomycin dosing in adults. We created a free and open-source dose adjustment app, VancoCalc, which uses Bayesian inference to aid clinicians in dosing and monitoring of vancomycin.ObjectiveThe aim of this paper is to describe the design, development, usability, and evaluation of a free open-source Bayesian vancomycin dosing app, VancoCalc.MethodsThe app build and model fitting process were described. Previously published pharmacokinetic models were used as priors. The ability of the app to predict vancomycin concentrations was performed using a small data set comprising of 52 patients, aged 18 years and over, who received at least 1 dose of intravenous vancomycin and had at least 2 vancomycin concentrations drawn between July 2018 and January 2021 at Lakeridge Health Corporation Ontario, Canada. With these estimated and actual concentrations, median prediction error (bias), median absolute error (accuracy), and root mean square error (precision) were calculated to evaluate the accuracy of the Bayesian estimated pharmacokinetic parameters.ResultsA total of 52 unique patients’ initial vancomycin concentrations were used to predict subsequent concentration; 104 total vancomycin concentrations were assessed. The median prediction error was –0.600 ug/mL (IQR –3.06, 2.95), the median absolute error was 3.05 ug/mL (IQR 1.44, 4.50), and the root mean square error was 5.34.ConclusionsWe described a free, open-source Bayesian vancomycin dosing calculator based on revisions of currently available calculators. Based on this small retrospective preliminary sample of patients, the app offers reasonable accuracy and bias, which may be used in everyday practice. By offering this free, open-source app, further prospective validation could be implemented in the near future.

A Multicenter Retrospective Study of Vancomycin Dosing by Weight Measures in Children.

Vancomycin carries risks of treatment failure and emergent resistance with underexposure and renal toxicity with overexposure. Children with overweight or obesity may have altered pharmacokinetics. We aimed to examine how body weight metrics influence vancomycin serum concentrations and to evaluate alternative dosing strategies. This was a multicenter retrospective cohort study across 3 large, academic hospitals. Patients aged 2 to 18 years old who received ≥3 doses of intravenous vancomycin were included. Weight metrics included total body weight, adjusted body weight, ideal body weight, body surface area, and allometric weight. Outcomes included vancomycin concentration and ratios of area under the curve (AUC) to minimum inhibitory concentration (MIC). Regression analyses were used to examine which body-weight identifier predicted outcomes. Of the 1099 children, 45% were girls, mean age was 9.0 (SD = 5.4) years, 14% had overweight, and 17% had obesity. Seventy-five percent of children had vancomycin concentrations in the subtherapeutic range by trough <10 µg/mL, and 63% had a ratio of AUC to MIC <400 μg-hr/mL. Three percent had a supratherapeutic initial trough >20 µg/mL or ratio of AUC to MIC >600 μg-hr/mL. Serum vancomycin concentrations were higher in children with overweight or obesity compared with children who were at a normal weight or underweight; the mean ratio of AUC to MIC also trended higher in the groups with overweight or obesity. Most children received vancomycin regimens that produced suboptimal trough levels. Children with overweight or obesity experienced higher vancomycin trough levels than children of normal weight despite receiving lower total body weight dosing. Using the ratio of AUC to MIC was a better measure of drug exposure.

Impact of a Pharmacist-driven Methicillin-resistant Staphylococcus aureus Polymerase Chain Reaction Nasal Swab Protocol on the De-escalation of Empiric Vancomycin in Patients with Pneumonia in a Rural Healthcare Setting.

IntroductionPneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) carries a high rate of morbidity and mortality. Many clinicians empirically treat those at risk of developing MRSA pneumonia with vancomycin. Several studies have identified a high negative predictive value of the MRSA polymerase chain reaction (PCR) nasal swab test in lower respiratory tract infections, suggesting it can be used to guide the de-escalation of empiric anti-MRSA therapy.ObjectiveTo evaluate the impact of a pharmacist-driven MRSA PCR nasal swab protocol on the de-escalation of empiric vancomycin in patients with pneumonia in a rural healthcare setting. Secondarily, to assess the rate of hospital length of stay, the rate of vancomycin-associated acute kidney injury, and in-hospital mortality after pharmacist-driven de-escalation of empiric vancomycin in patients with pneumonia. MethodsA retrospective, single-center, pre-post cohort study was conducted in patients after the implementation of a pharmacist-driven protocol allowing pharmacists to obtain nasal swabs and PCR testing for MRSA in those on empiric vancomycin therapy for suspected MRSA pneumonia. Based on negative test results, pharmacists recommended a de-escalation of empiric vancomycin to the physician. Patients were included if they were adults at least 18 years of age, had a physician diagnosis of suspected or confirmed pneumonia, and initiated on at least one dose of intravenous vancomycin within 48 hours of admission.ResultsA total of 79 patients were identified for inclusion in the pre-protocol group (n=32) or post-protocol group (n= 47). The mean duration of vancomycin therapy in the pre-protocol group was 3.1 days as compared to 1.7 days in the post-protocol group for a 1.4 days reduction (p=0.044). There was no significant impact on the number of vancomycin cases de-escalated within 24 hours (p=0.14) but there was a significant reduction at 48 hours (p=0.01). Protocol implementation was associated with a reduction in the average length of hospitalization (8 versus 5.20 days, p=0.006). Neither group had a vancomycin-associated acute kidney injury or in-hospital mortality.ConclusionAmong patients with suspected MRSA pneumonia, a pharmacist-driven MRSA PCR nasal swab protocol resulted in a significant reduction of empiric vancomycin duration of therapy without an adverse impact on clinical outcomes in a rural healthcare setting.

Appropriateness of vancomycin therapeutic drug monitoring and its outcomes among non-dialysis patients in a tertiary hospitalin Singapore.

Background Vancomycin therapeutic drug monitoring (TDM) is commonly performed to ensure safe and effective use of the antibiotic. Aim of Study To evaluate appropriateness of vancomycin TDM and its outcomes in Singapore General Hospital. Method A retrospective, cross-sectional study was conducted between 1 January 2014 and 28 February 2014 involving patients who received ≥ 1 dose of intravenous vancomycin with TDM. Patient demographics and relevant vancomycin TDM data were collected from medical records. Results Of 746 vancomycin troughs measured among 234 patients, 459 troughs (61.5%) were taken inappropriately, with a median time of 2.6h (interquartile range 1.1-4.3) before the next scheduled dose. Inappropriate interpretation of vancomycin troughs resulted in 41 unnecessary dose suspensions, 24 dose changes, and 102 unchanged vancomycin doses. The cost incurred due to inappropriate interpretation and measurement after discontinuation of treatment was US$7286. No differences in rates of vancomycin related nephrotoxicity, ototoxicity, recurrent infection, development of infection secondary to vancomycin resistant microorganism and mortality were observed (p > 0.05). Conclusion This study highlighted a high incidence of inappropriate vancomycin TDM which has led to increased healthcare cost.

Impact of Malignancy Category on Vancomycin Dosage Requirements in Pediatric Oncology Patients

Objectives: To determine the dosage of vancomycin in milligrams/kilogram/day (mg/kg/day) required to achieve a trough value of 10 to 20 micrograms/milliliter (mcg/mL) in pediatric patients with differing types of malignancies. Methods: Retrospective review of pediatric patients with hematologic malignancy, solid tumor, or status post autologous or allogeneic hematopoietic stem cell transplantation (HSCT) receiving at least two doses of intravenous vancomycin with at least one evaluable trough concentration. Primary outcome was the dosage of vancomycin required to achieve first therapeutic trough value. Secondary endpoints included dosage requirement by age, proportion of patients achieving goal, incidence of supratherapeutic trough values and nephrotoxicity. Results: Mean dosage requirements were 72.5 [± 2.3] mg/kg/day among patients with hematologic malignancies, 66.5 [± 3.3] mg/kg/day in patients with solid tumors, and 77.3 [± 4.1] mg/kg/day in HSCT patients (p=0.12). Younger patients required significantly increased daily dosages in order to meet their trough goals in the hematologic malignancy and solid tumor groups (p<0.05). The proportion of patients achieving trough goals was also similar between groups (p=0.5). Supratherapeutic trough values were more common in the solid tumor groups (p<0.05). Nephrotoxicity occurred more frequently in the HSCT group (p<0.05). Conclusion: Vancomycin dosage requirements are similar between pediatric patients with differing categories of malignancies. Patients with solid tumors and HSCT appear to be at higher risk for supratherapeutic trough values, and HSCT patients appear to be at an increased risk for nephrotoxicity.

Achievement of Therapeutic Vancomycin Trough Serum Concentrations with Empiric Dosing in Neonatal Intensive Care Unit Patients.

The recommended goal serum trough concentration for vancomycin has increased to 10 to 20 mcg/mL, with a higher range of 15 to 20 mcg/mL for serious infections due to methicillin-resistant Staphylococcus aureus in children and adults. Although neonatal references have also recommended these higher target concentrations, dosing recommendations remained unchanged. The objective of this study was to assess the percentage of neonates and young infants achieving a serum trough concentration between 10 and 20 mcg/mL with empiric vancomycin dosing based on Neofax® in a neonatal intensive care unit (NICU) population. A multi-institutional retrospective chart review was conducted to identify NICU patients who received a minimum of three doses of intravenous vancomycin and had at least one appropriately drawn trough. Additional outcomes included the duration of vancomycin therapy, number of dose adjustments required to attain goal trough concentrations, time to goal trough, and incidence of nephrotoxicity and ototoxicity. Of the 171 vancomycin serum trough concentrations included in the primary outcome, only 25.1% achieved a goal trough of 10 to 20 mcg/mL with empiric dosing. Only 44.6% of patients achieved the goal trough of 10 to 20 mcg/mL at any time during their vancomycin therapy. The average gestational age was 28.2 ± 4.1 weeks, average postnatal age at start of vancomycin was 34.1 ± 34.6 days, and average weight of the patients at start of vancomycin was 1602 ± 1014.5 g. The average and median total daily dose in those patients who achieved an initial vancomycin trough of 10-20 mcg/mL were 32.4 mg/kg/day and 30 mg/kg/day, respectively. Dosing of vancomycin based on Neofax® in NICU patients is insufficient in yielding serum trough concentrations of 10 to 20 mcg/mL. Further studies are needed to evaluate the optimal dosing regimen to achieve higher trough concentrations in this patient population.

Defining Risk Factors for Red Man Syndrome in Children and Adults

Red man syndrome (RMS) is a well-known adverse reaction that occurs in pediatric patients receiving vancomycin, yet reported prevalence is varied, and characteristics and risk factors are not well understood. Our objective was to determine the prevalence, characteristics and risk factors for RMS in pediatric patients receiving vancomycin, including contributing genetic factors. A multicenter retrospective study of 546 subjects (0.5-21 years) who received at least 1 dose of intravenous vancomycin was conducted. Demographic and symptom data were collected through chart review and parent/nurse report. Genotype analysis included 10 single nucleotide polymorphisms in the histamine pathway. RMS was observed in 77 (14%) subjects receiving vancomycin. Forty percent of subjects with RMS symptoms developed rash, pruritis and flushing, without hypotension. Antecedent antihistamine use was identified as a risk factor for RMS (P < 0.001). Multivariate regression analysis identified age > 2 years (P = 0.008), previous RMS (P < 0.001), vancomycin dose (P = 0.02) and vancomycin concentration (P = 0.017) as RMS risk factors, whereas African American race was protective (P = 0.011). We observed an apparent association between RMS and a single nucleotide polymorphism in the diamine oxidasegene (P = 0.044); however, no associations were revealed by multifactor dimensionality reduction analysis. RMS is a common adverse event in children receiving vancomycin. Identified risk factors are Caucasian ethnicity, age ≥ 2 years, previous RMS history, vancomycin dose ≥ 10 mg/kg, vancomycin concentration ≥ 5 mg/mL and antecedent antihistamine use. Known genetic variants in histamine metabolism or receptors do not appear to be substantial contributors to risk of RMS.

Fulminant Supraglottitis fromNeisseria meningitidis

Fulminant Supraglottitis from<i>Neisseria meningitidis</i>

Vancomycin Heteroresistance in Methicillin-resistantStaphylococcus aureus, Taiwan

Vancomycin Heteroresistance in Methicillin-resistant<i>Staphylococcus aureus</i>, Taiwan

Impact of Monitoring Vancomycin Peak and Trough Concentrations versus Trough Concentrations Alone on Dose Adjustments: An Outcomes Analysis

Objective: To determine whether monitoring both steady-state peak and trough serum vancomycin concentrations or steady-state trough serum vancomycin concentrations alone resulted in differences between two groups of patients in terms of dose adjustment, clinical outcome, and toxicity. Design: The study was a retrospective chart review of patients treated with vancomycin during two time periods. Group 1 represented patients hospitalized between July 1, 1996, and January 31, 1997. These patients routinely had vancomycin peak and trough concentrations measured. Group 2 represented patients hospitalized from July 1, 1997, to January 31, 1998, who were monitored with trough vancomycin concentrations only. Setting: A university teaching hospital. Patients: Adults at least 18 years of age who received a constant dose of intravenous vancomycin for at least three consecutive days were eligible for inclusion in the study. Patients were selected from lists generated by the Microbiology Department. The lists contained vancomycin serum concentrations measured during those time frames. Main Outcome Measures: The main outcome measure was to assess whether dose adjustments by prescribers were influenced by both vancomycin peak and trough concentrations or by the trough concentration alone. Results: Forty-nine and 37 patients met the criteria for inclusion into group 1 and group 2, respectively. The mean duration of therapy in group 1 (15 ± 10 d) was not statistically different from that of group 2 (14 ± 12 d). Patients in both groups received a mean daily vancomycin dose of approximately 1,500 mg. In analyzing treatment decisions, trough concentration was the only significant factor influencing a change in total daily dose of vancomycin (p = 0.038). Furthermore, although the method of vancomycin serum concentration monitoring varied between the two groups, the mean clinical outcome parameters were comparable. Conclusions: Prescribers tended to adjust vancomycin regimens based only on trough serum concentrations; monitoring peak serum vancomycin concentrations did not enhance patient care. Mean outcome parameters in the two groups were comparable.

Trough serum vancomycin levels predict the relapse of gram-positive peritonitis in peritoneal dialysis patients

We reviewed 31 episodes of gram-positive peritonitis that occurred in our peritoneal dialysis population between 1990 and 1993 in an attempt to identify the risk factor(s) for peritonitis relapse. All patients were treated with 4 weekly doses of intravenous vancomycin. Vancomycin doses no. 1 and 2 were based on body weight (15 mg/kg with a 1-g minimum); vancomycin doses no. 3 and 4 were adjusted in an attempt to maintain the trough serum vancomycin level at greater than 12 mg/L. Nine peritonitis episodes complicated by a relapse were identified. Peritonitis episodes preceding a relapse were similar to relapse-free episodes with respect to patient age, diabetes, peritoneal dialysis modality, duration of peritoneal dialysis treatment, residual urea clearance, peritoneal fluid cell count, causative organism, and weekly vancomycin dose. However, cumulative 4-week mean trough vancomycin levels were consistently lower during peritonitis episodes preceding a relapse (7.8 ± 0.6 mg/L during relapse-prone episodes v 13.7 ± 0.9 mg/L during relapse-free episodes; P = 0.0004). Furthermore, relapses developed during nine of 14 peritonitis episodes demonstrating a 4-week mean trough vancomycin level less than 12 mg/L compared with zero of 17 episodes with a 4-week trough level greater than 12 mg/L ( P < 0.05). The detection of a low initial 7-day trough vancomycin level also was a useful marker for subsequent peritonitis relapse. In 13 peritonitis episodes associated with an initial trough level less than 9 mg/L, nine were complicated by a relapse. The mean trough vancomycin level persisted below 9 mg/L over the final 3 weeks of therapy in all nine relapse-prone episodes as opposed to only one of four relapse-free episodes. All peritonitis relapses were treated successfully with 4 weeks of intravenous vancomycin therapy. This coincided with a significantly higher 4-week mean trough vancomycin level during treatment of the relapses (14.7 ± 0.7 mg/L during the relapse v 7.8 ± 0.6 mg/L immediately preceding the relapse; P < 0.05) despite similar mean weekly vancomycin dosages during both periods (19.4 ± 1.0 mg/kg during the relapse v 17.8 ± 1.2 mg/kg prior to the relapse; P = NS). In patients with uncomplicated peritoneal dialysis-related gram-positive peritonitis treated with weekly intravenous vancomycin, we conclude that (1) a suboptimal trough serum vancomycin level (cumulative 4-week trough serum vancomycin level <12 mg/L or an initial 7-day trough serum level <9 mg/L) is the only clinical parameter that identified peritonitis episodes at risk for relapse, and that (2) on detection of a suboptimal initial trough level (<9 mg/L), prevention of a subsequent peritonitis relapse may be possible if adequate trough vancomycin levels (>9 mg/L and preferably >12 mg/L) can be maintained for the remainder of therapy.

Pharmacokinetics and Cerebrospinal Fluid (CSF) Concentrations of Vancomycin in Pediatric Patients Undergoing CSF Shunt Placement

Staphylococcus epidermidis has been established as the common pathogen causing cerebrospinal fluid shunt infections. In addition, clinical isolates of S. epidermidis from infected shunts are typically resistant to methicillin. Vancomycin is often used for neurosurgical prophylaxis due to its excellent in vitro activity against methicillin-resistant staphylococci. Limited data are available about the pharmacokinetics and cerebrospinal fluid concentrations of vancomycin in pediatric patients intraoperatively. The objectives of this study were to characterize the pharmacokinetics and determine the cerebrospinal fluid concentrations of vancomycin. Eight patients (mean age 8.3 +/- 7.0 years) received three doses of intravenous vancomycin, 15 mg/kg every 6 h. The first dose was administered 1 h prior to surgery. Blood samples were collected at 0, 0.5, 1, 2, 4, and 5 h after the end of the infusion. A cerebrospinal fluid sample was collected at the time of shunt insertion. Urine samples were collected over a 24-hour period. Vancomycin was measured with a fluorescence polarization immunoassay. The peak serum concentrations ranged from 15.6 to 33.7 micrograms/ml; cerebrospinal fluid concentrations ranged from less than 0.6 to 0.8 microgram/ml. The mean total clearance, renal clearance, apparent volume of distribution, and elimination half-life were 0.11 +/- 0.05 l/h/kg, 0.07 +/- 0.02 l/h/kg, 0.54 +/- 0.15 l/kg, and 4.8 +/- 4.0 h, respectively. Approximately 70% of total vancomycin dose was excreted in the urine. A 2- to 5-fold variation in total clearance and a 2.5-fold variability in renal clearance were observed. Low cerebrospinal fluid concentrations of vancomycin were present at the time of shunt insertion in these pediatric patients.(ABSTRACT TRUNCATED AT 250 WORDS)