Vancomycin Monitoring Research Articles

A retrospective study to estimate serum vancomycin trough concentrations in pediatric patients with current recommended dosing regimen

Background: Vancomycin is widely prescribed to treat infections caused by methicillin-resistant Staphylococcus aureus (MRSA). According to the Infectious Disease Society of America 2011 MRSA guidelines for adults, trough concentrations of 15–20 μg/ml were recommended with vancomycin 15–20 mg/kg/dose every 8–12 h not to exceed 2 g per dose in patients with normal renal function. As the data for dosage and monitoring of vancomycin in children are still controversial, physicians often follow the guidelines established for adults. To evaluate serum vancomycin trough concentrations in pediatric patients with currently recommended dosing regimen, we evaluated clinical data. Methods: This retrospective observational study collected pediatric patients aged <18 years for whom vancomycin was administered at a single medical center between 2009 and 2015. Results: Fifty pediatric patients were analyzed. Two groups were identified according to the vancomycin dosage. Fourteen (28%) patients underwent vancomycin at 60 mg/kg/day (high dose) and 36 (72%) patients at 40 mg/kg/day (low dose). The average serum vancomycin trough concentrations of the two groups were 13.12 μg/ml (high-dose group) and 9.02 μg/ml (low dose group), respectively. In addition, 71% (high-dose group) and 91% (low-dose group) of patients could not reach the target trough concentrations 15–20 μg/ml, set by the Infectious Disease Society of America. Conclusion: This investigation revealed that the current recommended vancomycin dosing regimens in children (40–60 mg/kg/day) mostly brought out trough concentrations <10 μg/ml in this research population.

The Pharmacokinetics, Optimal Dose and Therapeutic Monitoring of Vancomycin in Severe Burn Patients

The Pharmacokinetics, Optimal Dose and Therapeutic Monitoring of Vancomycin in Severe Burn Patients

Impact of vancomycin monitoring on patient safety outcome

Impact of vancomycin monitoring on patient safety outcome

Bioanalytical Method Optimization for the Therapeutic Drug Monitoring of Vancomycin

Chemometric optimization and validation of a method based on High Performance Liquid Chromatography (HPLC) using core – shell particles for the determination of Vancomycin (VMC) in human plasma is reported. The combination of the efficiency of the core-shell particles and the benefits of the design of experiments allowed the successful determination of VCM, even in presence of several interferents. Selectivity, linearity, accuracy and precision were accomplished according to the European Medicines Agency (EMA) guideline, within the concentration range of 1.00 – 60.0 μg/mL of VCM. It is noteworthy that this method requires small amount of sample and solvents, and the sample treatment is simple and no time-consuming. Thus, this method becomes a simple and high-throughput alternative to therapeutic drug monitoring in treated patients, as well as an analytical procedure that conforms to the principles of the green chemistry.

Interventions Targeting the Prescribing and Monitoring of Vancomycin for Hospitalized Patients: A Systematic Review Protocol.

IntroductionVancomycin remains one of our essential antibiotics after fifty years of treating serious infections such as methicillin-resistant Staphylococcus aureus. Vancomycin, unlike many other antibiotic agents, requires individualized dosing and monitoring of serum drug levels to ensure it is efficacious, to minimize toxicity, and to limit the development of antibiotic resistance. These issues have led to numerous vancomycin clinical practice guidelines being published in recent years including several key national guidelines. Significant resources are invested during the development of such guidelines; however, there is often little or no information about how such guidelines or other vancomycin practice improvement initiatives should be implemented. The aim of this systematic review is to identify and evaluate the effect of interventions using education, guideline implementation, and dissemination of educational resources that have sought to improve therapeutic drug monitoring and dosing of vancomycin.MethodsA systematic review of the literature will be conducted for RCTs and observational studies where a vancomycin guideline or practice improvement initiative has been implemented. Electronic databases to be searched are PubMed, Medline, CINAHL, EMBASE and the Cochrane Library of Systematic Reviews. The population will be patients who have had intravenous vancomycin prescribed and monitored in hospital. The interventions will be education, implementation of guidelines or protocols, dissemination of educational materials (printed or electronic) or multifaceted interventions of the above. The comparator will be patients who have had standard-care prescribing and monitoring of vancomycin. Outcomes will be changes in prescribing and ordering of vancomycin serum tests, and serum levels attained in patients as well as reported nephrotoxicity. Two reviewers will be involved in the quality assessment and extraction of data. The Scottish Intercollegiate Guidelines Network checklist for RCTs will be used. Studies that are not randomized will be assessed for quality using the validated ROBINS-I (risk of bias in non-randomized studies of interventions) tool.DiscussionThis systematic review will identify interventions that have been used to implement guidelines and clinical practice initiatives for vancomycin. The findings of this review may be informative to those involved with the implementation of vancomycin clinical practice guidelines. Systematic review registration: PROSPERO: CRD42016049147.Electronic supplementary materialThe online version of this article (doi:10.1007/s40121-017-0177-7) contains supplementary material, which is available to authorized users.

A Rapid and Simple HPLC Method for Therapeutic Monitoring of Vancomycin.

Therapeutic monitoring of the antibiotic vancomycin is important to achieve specific plasma concentration and prevent toxic effects. Several assays have been described for vancomycin determination in clinical practice, but high-performance liquid chromatography is still considered the gold standard for the quantification of vancomycin. In this study, we developed a new and rapid high-performance liquid chromatography method requiring 50 μL of plasma for the quantification of vancomycin. Acetonitrile was used for processing plasma by protein precipitation (1:2.5). Isocratic chromatographic analysis was carried out on a C18 silica-based (2.7 μm) column with the mobile phase containing 20 mM ammonium acetate/formic acid buffer (pH 4.0):methanol 88:12 (v/v). A diode array detector was used for UV detection at 240 nm. This method was validated according to the Brazilian Health Surveillance Agency legislation and International Conference on Harmonization guidelines. The measurement range was 1-100 μg/mL, analysis time was 8 min, and intermediate precision was <12%, supporting the present method as a fast, simple, and effective alternative for therapeutic monitoring of vancomycin.

Impact of Vancomycin Serum Trough Concentrations and Vancomycin AUC/MIC on Vancomycin Response, In-Hospital Outcomes and Acute Kidney Injury in Pediatric Staphylococcus aureus Pneumonia

BackgroundVancomycin AUC/MIC > 400 was initially shown to be beneficial in adults with staphylococcal pneumonia. Current practice guidelines recommend targeting serum vancomycin trough concentrations (VTC) of 15–20 µg/ml in adults with severe MRSA infection to approximate these AUC/MIC goals. Small studies have shown no benefit to VTC > 15 µg/ml in children with osteomyelitis or bacteremia. We describe the impact of VTC and AUC/MIC on outcomes of pediatric S. aureuspneumonia.MethodsCases of S. aureuspneumonia from January 1, 2011 to December 31, 2016 were reviewed. Patients treated with vancomycin <48 hours were excluded. Suboptimal vancomycin response (SVR) was considered any combination of duration of fever, bacteremia or ICU stay > 75%-tile, need for re-operation, or mortality. The highest VTC and AUC obtained in the first 96 hours of therapy was used in analyses. Vancomycin MIC was determined with the E-test. Acute kidney injury (AKI) was defined as a doubling of the baseline serum creatinine.ResultsThirty-six patients were identified meeting inclusion criteria with a median age of 0.74 years. 75% of isolates were MRSA and 70.4% were USA300. 80.6% of patients were admitted to the ICU and 52.8% were intubated. No benefit was observed in terms of duration of fever, bacteremia, ICU stay, ventilator or hospital days or rates of SVR between patients with VTC > or <15 µg/ml. There were substantial increases in rates of AKI with higher VTC (66.7 vs. 24.2%, P < 0.001). Among 23 patients for whom AUC/MIC determinations were possible, none achieved an AUC/MIC >400; the median AUC/MIC = 42 (IQR: 32–51). Eighty-eight% of isolates had an MIC ≥1.5 µg/ml. There was no correlation between values of AUC/MIC and length of ICU or hospital stay or SVR (AUROC 0.45).ConclusionWhile the sample size is limiting, VTC >15 µg/ml did not provide clinical benefit to children with S. aureus pneumonia compared with lower VTC levels while at the same time predisposing to nephrotoxicity. AUC/MIC > 400 is rarely achieved in children with S. aureus pneumonia and may not be a realistic goal in this infection given the rarity with which this occurs, the frequency of high MICs and the very young age of the typical patient. Large multicenter studies are required to understand optimal vancomycin dosing and monitoring in children with invasive MRSA infections.Disclosures J. McNeil, NIAID, NIH: Grant Investigator, Grant recipient; S. L. Kaplan, Allergan: Grant Investigator, Grant recipient and This grant pertains to unrelated research

Optimization of therapeutic drug monitoring of vancomycin in patients with chronic hemodialysis .

To validate a simplified vancomycin monitoring algorithm in patients on chronic hemodialysis who required intravenous vancomycin for at least 3 weeks. In this prospective study, all hemodialysis patients who were admitted between April 1, 2013, and March 31, 2015, in our unit for suspected or confirmed methicillin-resistant <italic>Staphylococcus aureus </italic>infection that required vancomycin were enrolled. All patients were categorized into two groups. In group 1 (standard vancomycin dosing algorithm), the maintenance doses of vancomycin were adjusted according to the pre-hemodialysis vancomycin concentrations determined before each hemodialysis session. In group 2 (simplified vancomycin dosing algorithm), pre-dialysis vancomycin trough levels were taken before the 2^nd and the 6^thsession of hemodialysis. Maintenance doses were adjusted according to the residual concentrations of vancomycin. A total of 101 blood samples were collected, the average plasma concentration of vancomycin was 13.1 ± 3.8 µg/mL. 64 (63.4%) levels fell out of the therapeutic range. Seven (6.9%) of these exceeded the therapeutic range and 30 (29.7%) were lower. After the loading dose, the average plasma concentration was 11.2 ± 3.4 µg/mL. There were no statistically significant differences between the two groups with respect to the average plasma concentration of vancomycin and the proportion of vancomycin trough levels in the target range. The vancomycin dosing algorithm using limited concentration monitoring for hemodialysis patients achieved drug concentrations comparable to those found with more frequent monitoring and resulted in significant cost savings. .

Therapeutic drug monitoring of vancomycin and voriconazole by liquid chromatography-tandem mass spectrometric method

A reliable liquid chromatography-tandem mass spectrometric(LC-MS/MS) method was developed and validated for the simultaneous determination of vancomycin and voriconazole in human plasma. The analytes and internal standard 10-hydroxycarbazepine were separated at a flow rate of 0.9 mL/min using a Zorbax SB-C18 column (50 mm×4.6 mm, 2.7 μm). Positive ion electrospray ionization was used to detect vancomycin, voriconazole and intrenal standard(IS) 10-hydroxycarbazepine followed by multiple reaction monitoring(MRM) of the transition at m/z 725.5→144.2, 350.3→281.0 and 253.1→208.0, respectively. The total run time for both vancomycin and voriconazole samples was 5 min; 0.30 μg/mL was the lower limit of quantification. The precision of intraday and interday was no more than 12.4%. The method was successfully and resoundingly applied in therapeutic drug monitoring of 156 patients treated with vancomycin and voriconazole.

Vancomycin levels are frequently subtherapeutic in critically ill patients: a prospective observational study.

BackgroundAppropriate utilization of vancomycin is important to attain therapeutic targets while avoiding clinical failure and the development of antimicrobial resistance. Our aim was to observe the use of vancomycin in an intensive care population, with the main focus on achievement of therapeutic serum concentrations (15–20 mg/l) and to evaluate how this was influenced by dose regimens, use of guidelines and therapeutic drug monitoring.MethodsA prospective observational study was carried out in the intensive care units at two tertiary hospitals in Norway. Data were collected from 83 patients who received vancomycin therapy, half of these received continuous renal replacement therapy. Patients were followed for 72 h after initiation of therapy. Blood samples were drawn for analysis of trough serum concentrations. Urine was collected for calculations of creatinine clearance. Information was gathered from medical records and electronic health records.ResultsLess than 40% of the patients attained therapeutic trough serum concentrations during the first 3 days of therapy. Patients with augmented renal clearance had lower serum trough concentrations despite receiving higher maintenance doses and more loading doses. When trough serum concentrations were outside of therapeutic range, dose adjustments in accordance to therapeutic drug monitoring were made to less than half.ConclusionThe present study reveals significant challenges in the utilization of vancomycin in critically ill patients. There is a need for clearer guidelines regarding dosing and therapeutic drug monitoring of vancomycin for patient subgroups.

Vancomycin during the Last Hour of the Hemodialysis Session: A Pharmacokinetic Analysis

Background: Vancomycin is usually administered after the dialysis sessions to patients undergoing hemodialysis. Administration of vancomycin during (as opposed to after) sessions would save time, and would be more acceptable to patients and staff, but may lead to vancomycin underexposure. The aim of this study was to propose a new dosing regimen of vancomycin taking into account the dialysis-related losses of vancomycin when administered during dialysis. Methods: In this monocentric prospective study, vancomycin was infused to dialyzed patients during the last hour of the dialysis session at increased doses. Monitoring of vancomycin was performed using repeated blood samples by pharmacokinetics modeling. Patients were treated according to our protocol and guidelines. Results: Twenty patients were included. Vancomycin protocol was efficient: 17 of 20 (85%) patients were cured, 1 needed additional vancomycin treatment, and 2 died (sepsis n = 1, multiple organ failure n = 1). Median pre-dialysis concentration was adequate (16.2 [10.2-24.4] µg/mL), and there was no emergence of resistant bacteria. Infusion of vancomycin during dialysis therefore decreased the exposure to vancomycin by 25% compared to infusion of vancomycin after dialysis. For a typical patient, the dose of vancomycin to be administered during dialysis would be 1.4 g. Conclusion: Administration of vancomycin during the last hour of dialysis session is safe, efficacious with regards to infection control, achieved recommended vancomycin concentrations despite the use of high-flux membranes, and improved patients' quality of life.

Monitoring of vancomycin in human plasma via portable microchip electrophoresis with contactless conductivity detector and multi-stacking strategy

A portable microchip electrophoresis (MCE) coupled with on-chip contactless conductivity detection (C4D) system was evaluated for the determination of vancomycin in human plasma. In order to enhance the detection sensitivity, a new online multi-stacking preconcentration technique based on field-enhanced sample injection (FESI) and micelle-to-solvent stacking (MSS) was developed and implemented in MCE-C4D system equipped with a commercially available double T-junction glass chip. The cationic analytes from the two sample reservoirs were injected under FESI conditions and subsequently focused by MSS within the sample-loading channel. The proposed multi-stacking strategy was verified under a fluorescence microscope using Rhodamine 6G as the model analyte and a sensitivity enhancement factor (SEF) of up to 217 was achieved. The developed approach was subsequently implemented in the aqueous-based MCE, coupled to C4D in order to monitor the targeted antibiotic (in this case, vancomycin) present in human plasma samples. The multi-stacking and analysis time for vancomycin were 50s and 250s respectively, with SEF of approximately 83 when compared to typical gated injection. The detection limit of the method for vancomycin was 1.2μg/mL, with intraday and interday repeatability RSDs of 2.6% and 4.3%, respectively. Recoveries in spiked human plasma were 99.0%–99.2%.

Is vancomycin monitoring of real value in pediatric cancer patients?

Vancomycin is not nephrotoxic by itself but many patients using it with other nephrotoxic agents show nephrotoxicity to some extent. Whether to monitor or not to monitor vancomycin needs further study. The aim of the present study was to investigate the significance of monitoring vancomycin serum levels in pediatric patients treated from different malignancies. 150 newly diagnosed pediatric patients, with various types of malignancy treated with different nephrotoxic agents including vancomycin, were recruited in the study. All patients had normal renal functions at the start of the study and were divided into three groups; Group I included 50 (21 females) patients received vancomycin without monitoring (VWOM group); Group II included 50 (19 females) patients received vancomycin with monitoring (VWM group); Group III (Control group) included 50 (23 females) patients received vancomycin-free antimicrobial agents (VF group). Vancomycin trough level was determined only for VWM group. The effectiveness of monitoring was estimated by the ability to achieve more rapid response, decrease hospital stay and nephrotoxicity and its effect on total dose of vancomycin. There was a significant decrease in nephrotoxicity in VWM and VF groups, 9 subjects (18%), compared to 15 subjects (30%) in VWOM group (p=0.016). The time needed to show a response achievement was significantly decreased in VWM group compared to VWOM group with mean (SD) of 6.5 (2.5) and 8.7 (3.6) days, respectively (p=0.015). That led to shorter hospital stay in VWM group compared to VWOM group with mean (SD) of 10.1 (3.4) and 12.4 (4.2) days, respectively (p=0.003). Monitoring vancomycin level was important in the examined high risk groups of pediatric cancer patients studied.

An Educational Intervention to Improve the Use and Monitoring of Vancomycin in Pediatric Patients

An Educational Intervention to Improve the Use and Monitoring of Vancomycin in Pediatric Patients

Pharmacist-managed dose adjustment feedback using therapeutic drug monitoring of vancomycin was useful for patients with methicillin-resistant Staphylococcus aureus infections: a single institution experience.

BackgroundVancomycin (VCM) requires dose adjustment based on therapeutic drug monitoring. At Aomori Prefectural Central Hospital, physicians carried out VCM therapeutic drug monitoring based on their experience, because pharmacists did not participate in the dose adjustment. We evaluated the impact of an Antimicrobial Stewardship Program (ASP) on attaining target VCM trough concentrations and pharmacokinetics (PK)/pharmacodynamics (PD) parameters in patients with methicillin-resistant Staphylococcus aureus (MRSA) infections.Materials and methodsThe ASP was introduced in April 2012. We implemented a prospective audit of prescribed VCM dosages and provided feedback based on measured VCM trough concentrations. In a retrospective pre- and postcomparison study from April 2007 to December 2011 (preimplementation) and from April 2012 to December 2014 (postimplementation), 79 patients were treated for MRSA infection with VCM, and trough concentrations were monitored (pre, n=28; post, n=51). In 65 patients (pre, n=15; post, n=50), 24-hour area under the concentration–time curve (AUC 0–24 h)/minimum inhibitory concentration (MIC) ratios were calculated.ResultsPharmacist feedback, which included recommendations for changing dose or using alternative anti-MRSA antibiotics, was highly accepted during postimplementation (88%, 29/33). The number of patients with serum VCM concentrations within the therapeutic range (10–20 μg/mL) was significantly higher during postimplementation (84%, 43/51) than during preimplementation (39%, 11/28) (P<0.01). The percentage of patients who attained target PK/PD parameters (AUC 0–24 h/MIC >400) was significantly higher during postimplementation (84%, 42/50) than during preimplementation (53%, 8/15; P=0.013). There were no significant differences in nephrotoxicity or mortality rate.ConclusionOur ASP increased the percentage of patients that attained optimal VCM trough concentrations and PK/PD parameters, which contributed to the appropriate use of VCM in patients with MRSA infections.

Impact of a Pharmacist-Initiated Vancomycin Monitoring Program.

Evaluate the clinical impact of pharmacist-initiated vancomycin monitoring and dosing in a long-term care setting. Single-center, pretest, post-test design. Rutland Nursing Home, Brooklyn, New York. Nursing facility residents treated with intravenous vancomycin (N = 198). The primary objective is to determine the incidence of acute kidney injury (AKI) a year before and a year after implementation of a pharmacist-initiated vancomycin-monitoring protocol. The secondary objectives are percentage of serum drug levels in therapeutic range and compliance with laboratory testing for monitoring of nephrotoxicity. The overall incidence of AKI decreased from 16.3% (8/49) to 4.7% (7/149) (P = 0.013). Compliance with weekly monitoring for nephrotoxicity via serum creatinine and blood urea nitrogen improved from 76% (37/49) to 95% (141/149) (P ≤ 0.001). Compliance with weekly vancomycin level monitoring improved from 71% (35/49) to 85% (126/149) (P = 0.041). Percentage of vancomycin trough levels in the therapeutic range of 10-20 mcg/mL were shown to have no difference between two groups, but vancomycin levels > 20 mcg/mL decreased from 31% (15/49) to 17% (26/149) (P = 0.048). Implementation of pharmacist-driven vancomycin monitoring significantly improved monitoring compliance of vancomycin serum levels and kidney function as well as reduced the incidence of AKI in the long-term care setting.

Therapeutic drug monitoring of vancomycin: a guideline of the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society.

Guideline development should be based on the quality of evidence, balance of benefits and harms, economic evaluation and patients' views and preferences. Therefore, these factors were considered in the development of a new guideline for therapeutic drug monitoring (TDM) of vancomycin. To develop an evidence-based guideline for vancomycin TDM and to promote standardized vancomycin TDM in clinical practice in China. We referred to the WHO Handbook for Guideline Development and used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to rate the quality of evidence and grade the strength of recommendations, according to economic evaluation and patients' views and preferences. We used the GRADE Grid method to formulate the recommendations. The guideline presents recommendations about who should receive vancomycin TDM, how to monitor vancomycin efficacy and renal safety, therapeutic trough concentrations, time to start initial vancomycin TDM, loading dose and how to administer and adjust the vancomycin dose. We developed an evidence-based guideline for vancomycin TDM, which provides recommendations for clinicians and pharmacists to conduct vancomycin TDM in China.

A protocol for developing a clinical practice guideline for therapeutic drug monitoring of vancomycin.

This study aimed to develop a guideline for therapeutic drug monitoring (TDM) of vancomycin. We adopted the new guideline definition from the Institute of Medicine (IOM), adhered closely to the six domains of the Appraisal of Guidelines for Research & Evaluation II (AGREE II), and made recommendations based on systematic reviews. We established a Guideline Steering Group and a Guideline Development Group, formulated 12 questions in the form of Population, Intervention, Comparison, Outcome (PICO) and completed a literature search. As far as we know, we will develop the first evidenced-based guideline for vancomycin TDM under the framework of the Grade of Recommendations Assessment, Development and Evaluation (GRADE).

The ANTIBIOPERF study: a nationwide cross-sectional survey about practices for β-lactam administration and therapeutic drug monitoring among critically ill patients in France

Our objective was to assess current practices about the administration (intermittent, extended, or continuous infusions) and therapeutic drug monitoring (TDM) of β-lactam antibiotics and vancomycin in France. We conducted a nationwide cross-sectional survey in May–August 2015, using an online questionnaire, sent as an e-mail link to infectious disease specialists and intensive care specialists through national mailing lists. We used clinical vignettes of critically ill patients to assess physicians’ practices about administration and TDM practices for amoxicillin, cloxacillin, piperacillin/tazobactam, cefotaxime, ceftazidime, cefepime, meropenem and vancomycin. In all, 507 physicians participated (507/1200, response rate 42%). TDM was rarely available for β-lactams (from 16.5% (81/490) for cloxacillin to 30% (145/490) for ceftazidime), whereas vancomycin TDM was available in 97% (477/490) of the cases. In the clinical vignettes, ceftazidime and piperacillin/tazobactam were the β-lactams administered most frequently by extended or continuous infusions (76% (336/440) and 57% (252/444), respectively). Gaps in knowledge about the duration of stability of intravenous β-lactams were common (correct answers ranged from 8% (35/432) for cloxacillin to 33% (146/438) for ceftazidime). Most physicians (77%, 339/442) were convinced of the value of extended or continuous infusions for β-lactams in critically ill patients, but 48% (211/442) did not have access to practical guidelines. Our survey found that most infectious disease and intensive care specialists are favourable to optimized administration of β-lactams in critically ill patients. But the lack of guidelines and limited TDM availability for β-lactams in hospitals are potential barriers to its implementation.

The Value of Therapeutic Drug Monitoring of Vancomycin in Treatment in a Tertiary Hospital, Cho Ray Hospital, Viet Nam

The Value of Therapeutic Drug Monitoring of Vancomycin in Treatment in a Tertiary Hospital, Cho Ray Hospital, Viet Nam