Vancomycin Dosing Practices among Critical Care Pharmacists: A Survey of Society of Critical Care Medicine Pharmacists
ABSTRACT: Introduction: Critically ill patients and their pharmacokinetics present complexities often not considered by consensus guidelines from the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Prior surveys have suggested discordance between certain guideline recommendations and reported infectious disease pharmacist practice. Vancomycin dosing practices, including institutional considerations, have not previously been well described in the critically ill patient population. Objectives: To evaluate critical care pharmacists’ self-reported vancomycin practices in comparison to the 2009 guideline recommendations and other best practices identified by the study investigators. Methods: An online survey developed by the Research and Scholarship Committee of the Clinical Pharmacy and Pharmacology (CPP) Section of the Society of Critical Care Medicine (SCCM) was sent to pharmacist members of the SCCM CPP Section practicing in adult intensive care units in the spring of 2017. This survey queried pharmacists’ self-reported practices regarding vancomycin dosing and monitoring in critically ill adults. Results: Three-hundred and sixty-four responses were received for an estimated response rate of 26%. Critical care pharmacists self-reported largely following the 2009 vancomycin dosing and monitoring guidelines. The largest deviations in guideline recommendation compliance involve consistent use of a loading dose, dosing weight in obese patients, and quality improvement efforts related to systematically monitoring vancomycin-associated nephrotoxicity. Variation exists regarding pharmacist protocols and other practices of vancomycin use in critically ill patients. Conclusion: Among critical care pharmacists, reported vancomycin practices are largely consistent with the 2009 guideline recommendations. Variations in vancomycin dosing and monitoring protocols are identified, and rationale for guideline non-adherence with loading doses elucidated.
Project description:AIMS:Vancomycin is frequently used in critically ill children in whom the drug pharmacokinetics are significantly altered as a result of changes in renal clearance and volume of distribution. Therapeutic drug monitoring (TDM) is recommended to achieve vancomycin trough concentrations between 10 and 20 mg/L. In this study we reviewed vancomycin dosing, TDM and treatment outcomes in paediatric and neonatal intensive care unit patients. METHODS:We reviewed the medical records of all patients receiving intravenous vancomycin in a tertiary paediatric and neonatal intensive care unit over a 10-month period. Demographic, vancomycin dosing, TDM and drug-related adverse effects data were collected. RESULTS:In total, 115 children received 126 courses of vancomycin and had at least 1 TDM blood sample taken at steady state. In only 38/126 (30%) courses was the target concentration (10-20 mg/L) achieved at the initial steady state trough sample. Of the 88 courses that had initial trough concentrations outside the target range, the dose was adjusted in only 49 (56%). Overall, minimum doses of 30 mg/kg/day in neonates with a corrected gestational age of <35 weeks, and 50 mg/kg/day in older children, were required to achieve target vancomycin concentrations. Vancomycin-attributable nephrotoxicity occurred in 10/126 (8%) courses and there were no episodes of red man syndrome. CONCLUSION:In critically ill children, individualised dosing is needed. In the absence of Bayesian model-based dosing, in children with normal renal function, empiric vancomycin doses of at least 30 mg/kg/day in neonates of <35 weeks corrected gestational age, and 50 mg/kg/day in older children, should be considered. Optimisation of TDM practices through the development of protocols, ideally built into electronic medical records, should be considered.
Project description:PURPOSE:This Position Paper aims to review and discuss the available data on therapeutic drug monitoring (TDM) of antibacterials, antifungals and antivirals in critically ill adult patients in the intensive care unit (ICU). This Position Paper also provides a practical guide on how TDM can be applied in routine clinical practice to improve therapeutic outcomes in critically ill adult patients. METHODS:Literature review and analysis were performed by Panel Members nominated by the endorsing organisations, European Society of Intensive Care Medicine (ESICM), Pharmacokinetic/Pharmacodynamic and Critically Ill Patient Study Groups of European Society of Clinical Microbiology and Infectious Diseases (ESCMID), International Association for Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT) and International Society of Antimicrobial Chemotherapy (ISAC). Panel members made recommendations for whether TDM should be applied clinically for different antimicrobials/classes. RESULTS:TDM-guided dosing has been shown to be clinically beneficial for aminoglycosides, voriconazole and ribavirin. For most common antibiotics and antifungals in the ICU, a clear therapeutic range has been established, and for these agents, routine TDM in critically ill patients appears meritorious. For the antivirals, research is needed to identify therapeutic targets and determine whether antiviral TDM is indeed meritorious in this patient population. The Panel Members recommend routine TDM to be performed for aminoglycosides, beta-lactam antibiotics, linezolid, teicoplanin, vancomycin and voriconazole in critically ill patients. CONCLUSION:Although TDM should be the standard of care for most antimicrobials in every ICU, important barriers need to be addressed before routine TDM can be widely employed worldwide.
Project description:OBJECTIVES:The aims of this study were, first, to compare the predicted (calculated) energy requirements based on standard equations with target energy requirement based on indirect calorimetry (IC) in critically ill, obese mechanically ventilated patients; and second, to compare actual energy intake to target energy requirements. METHODS:We conducted a prospective cohort study of mechanically ventilated critically ill patients with body mass index ?30.0 kg/m2 for whom enteral feeding was planned. Clinical and demographic data were prospectively collected. Resting energy expenditure was measured by open-circuit IC. American Society of Parenteral and Enteral Nutrition (APSPEN)/Society of Critical Care Medicine (SCCM) 2016 equations were used to determine predicted (calculated) energy requirements. Target energy requirements were set at 65% to 70% of measured resting energy expenditure as recommended by ASPEN/SCCM. Nitrogen balance was determined via simultaneous measurement of 24-h urinary nitrogen concentration and protein intake. RESULTS:Twenty-five patients (mean age: 64.5 ± 11.8 y, mean body mass index: 35.2 ± 3.6 kg/m2) underwent IC. The mean predicted energy requirement was 1227 kcal/d compared with mean measured target energy requirement of 1691 kcal/d. Predicted (calculated) energy requirements derived from ASPEN/SCCM equations were less than the target energy requirements in most cases. Actual energy intake from enteral nutrition met 57% of target energy requirements. Protein intake met 25% of target protein requirement and the mean nitrogen balance was -2.3 ± 5.1 g/d. CONCLUSIONS:Predictive equations underestimated target energy needs in this population. Further, we found that feeding to goal was often delayed resulting in failure to meet both protein and energy intake goals.
Project description:BACKGROUND:Pharmacokinetics (PK) are severely altered in critically ill patients due to changes in volume of distribution (Vd) and/or drug clearance (Cl). This affects the target attainment of antibiotics in critically ill children. We aimed to identify gaps in current knowledge and to compare published PK parameters and target attainment of antibiotics in critically ill children to healthy children and critically ill adults. METHODS:Systematic literature search in PubMed, EMBASE and Web of Science. Articles were labelled as relevant when they included information on PK of antibiotics in critically ill, non-neonatal, pediatric patients. Extracted PK-parameters included Vd, Cl, (trough) concentrations, AUC, probability of target attainment, and elimination half-life. RESULTS:50 relevant articles were identified. Studies focusing on vancomycin were most prevalent (17/50). Other studies included data on penicillins, cephalosporins, carbapenems and aminoglycosides, but data on ceftriaxone, ceftazidime, penicillin and metronidazole could not be found. Critically ill children generally show a higher Cl and larger Vd than healthy children and critically ill adults. Reduced target-attainment was described in critically ill children for multiple antibiotics, including amoxicillin, piperacillin, cefotaxime, vancomycin, gentamicin, teicoplanin, amikacin and daptomycin. 38/50 articles included information on both Vd and Cl, but a dosing advice was given in only 22 articles. CONCLUSION:The majority of studies focus on agents where TDM is applied, while other antibiotics lack data altogether. The larger Vd and higher Cl in critically ill children might warrant a higher dose or extended infusions of antibiotics in this patient population to increase target-attainment. Studies frequently fail to provide a dosing advice for this patient population, even if the necessary information is available. Our study shows gaps in current knowledge and encourages future researchers to provide dosing advice for special populations whenever possible.
Project description:BACKGROUND:Broad-spectrum antibiotics are commonly prescribed in critically ill patients. While it is commonly believed that only patients with impaired renal function need dose adjustment, augmented renal clearance (ARC) is a phenomenon that warrants dose adjustment as well. In critically ill patients ARC is often undetectable because it is associated with a normal or decreased serum creatinine concentration (SCr). This study's objective was to assess pharmacists' knowledge about ARC identification, risk factors, affected antimicrobials, and dosing of antibiotics in patients with ARC. METHODS:In January 2020, we carried out a cross-sectional study by sending out an online survey to the Saudi Pharmaceutical Society, Kuwait Pharmaceutical Association, and Oman Pharmaceutical Society. Due to the expected low response rate, we administered an electronic questionnaire to pharmacists attending Dubai International Pharmaceuticals and Technologies Conference and Exhibition 2020 (DUPHAT). RESULTS:Data were collected from 288 respondents. However, only 134 were included in the final analysis following the exclusion of incomplete responses, no experience working in in-patient settings, and respondents who chose "no" universal ARC definition. Those who chose "yes" or "I do not know" regarding the universal definition of ARC were asked about SCr status in ARC. Elevation in SCr was chosen by 67/134 (50%) compared to those who chose decreased or normal (48/134, 35.8%). Regarding risk factors, only 1/134 (0.7%) respondent selected all risk factors. Two/134 (1.4%) respondents chose all hydrophilic antibiotics that are likely to be affected by ARC. Concerning the appropriate dose and frequency of piperacillin-tazobactam and meropenem, they were selected by 60.4% and 30.5%, respectively. CONCLUSION:Pharmacists' knowledge about ARC was limited. Implementation of educational programs targeting hospital pharmacists, especially those practicing in critical care settings, and developing antimicrobial institutional guidelines are important.
Project description:BACKGROUND:Older adults with chronic kidney disease (CKD) are at heightened risk for polypharmacy. We examined potentially inappropriate prescribing in this population and whether introducing pharmacists into the ambulatory kidney care model was associated with improved prescribing practices. METHODS:Retrospective cohort study using linked administrative databases. We included patients with an eGFR ?30 mL/min/1.73 m2 ?66 years of age followed in multidisciplinary kidney clinics in Ontario, Canada (n = 25,016 from 28 centres). The primary outcome was the absence of a statin prescription or the receipt of a potentially inappropriate prescription defined by the American Geriatric Society Beers Criteria® and a modified Delphi panel that identified key drugs of concern in CKD. We calculated the crude cumulative incidence and incidence rate for the primary outcome and used change-point regression to determine if a change occurred following pharmacist introduction. RESULTS:There were 6,007 (24%) and 16,497 patients (66%) not prescribed a statin and with ?1 potentially inappropriate prescription, respectively. The rate of potentially inappropriate prescribing was 125.6 per 100 person-years and was higher in more recent years. The change-point regression analysis included 2,275 patients from two centres. No immediate change was detected at pharmacist introduction, but potentially inappropriate prescribing was increasing pre-pharmacist introduction, and this rising trend was reversed post-pharmacist introduction. The incidence of potentially inappropriate prescribing still remained high post-pharmacist introduction. CONCLUSIONS:Potentially inappropriate prescribing practices were common. Incorporating pharmacists into the kidney care model may improve prescribing practices. The role of pharmacists in the ambulatory kidney care team warrants further investigation in a randomized controlled trial.
Project description:Objectives:Prolonged intermittent renal replacement therapy is an increasingly popular treatment for acute kidney injury in critically ill patients that runs at different flow rates and durations than conventional hemodialysis or continuous renal replacement therapies. Pharmacokinetic studies conducted in patients receiving prolonged intermittent renal replacement therapy are scarce; consequently, clinicians are challenged to dose antibiotics effectively. The purpose of this study was to develop vancomycin dosing recommendations for patients receiving prolonged intermittent renal replacement therapy. Methods:Monte Carlo simulations were performed in thousands of virtual patients derived from previously published demographic, pharmacokinetic, and dialytic information derived from critically ill patients receiving vancomycin and other forms of renal replacement therapy. We conducted "in silico" vancomycin pharmacokinetic/pharmacodynamics analyses in these patients receiving prolonged intermittent renal replacement therapy to determine what vancomycin dose would achieve vancomycin 24-h area under the curve (AUC24h) of 400-700?mg·h/L, a target associated with positive clinical outcomes. Nine different vancomycin dosing regimens were tested using four different, commonly used prolonged intermittent renal replacement therapy modalities. A dosing nomogram based on serum concentration data achieved after the third dose was developed to individualize vancomycin therapy. Results:An initial vancomycin dose of 15 or 20?mg/kg immediately followed by 15?mg/kg after subsequent prolonged intermittent renal replacement therapy treatments achieved AUC24h of ?400?mg·h/L for ?90% of patients regardless of prolonged intermittent renal replacement therapy duration, modality, or time of vancomycin dose relative to prolonged intermittent renal replacement therapy. Many patients experienced AUC24h of ?700?mg·h/L, but once the dosing nomogram was applied to serum concentrations obtained after the third vancomycin dose, 67%-88% of patients achieved AUC24h of 400-700?mg·h/L. Conclusion:An initial loading dose of 15-20?mg/kg followed by a maintenance regimen of 15?mg/kg after every prolonged intermittent renal replacement therapy session coupled with serum concentration monitoring should be used to individualize vancomycin dosing. These predictions need clinical verification.
Project description:Late-onset sepsis in neonates can lead to significant morbidity and mortality, especially in preterm infants. Vancomycin is commonly prescribed for the treatment of Gram-positive organisms, particularly methicillin-resistant Staphylococcus aureus (MRSA), coagulase-negative staphylococci, and ampicillin-resistant Enterococcus species in adult and pediatric patients. Currently, there is no consensus on optimal dosing and monitoring of vancomycin in neonates. Different vancomycin dosing regimens exist for neonates, but with many of these regimens, obtaining therapeutic trough concentrations can be difficult. In 2011, the Infectious Diseases Society of America recommended vancomycin trough concentrations of 15 to 20 mg/L or an AUC/MIC ratio of ?400 for severe invasive diseases (e.g., MRSA) in adult and pediatric patients. Owing to recent reports of increased risk of nephrotoxicity associated with vancomycin trough concentrations of 15 to 20 mg/L and AUC/MIC of ?400, a revised consensus guideline, recently published in 2020, no longer recommends monitoring vancomycin trough concentrations in adult patients. The guideline recommends an AUC/MIC of 400 to 600, which has been found to achieve clinical efficacy while reducing nephrotoxicity. However, these recommendations were derived solely from adult literature, as there are limited clinical outcomes data in pediatric and neonatal patients. Furthermore, owing to the variation of vancomycin pharmacokinetic parameters among the neonatal population, these recommendations for achieving vancomycin AUC/MIC of 400 to 600 in neonates require further investigation. This review will discuss the challenges of achieving optimal vancomycin dosing and monitoring in neonatal patients.
Project description:<h4>Background</h4>Pharmacists in the Regina Qu'Appelle Health Region (RQHR), Saskatchewan, independently dose, monitor, and adjust vancomycin therapy. No framework exists for ongoing competency assessment of pharmacists.<h4>Objectives</h4>The primary objective was to determine pharmacists' overall level of competency for all components of the vancomycin prescribing procedure. The secondary objectives were to determine competency for individual prescribing phases, to stratify overall competency in relation to pharmacist and patient factors, and to identify the 3 most frequent errors.<h4>Methods</h4>A retrospective chart audit was performed of patients who received a prescription for vancomycin between November 1, 2015, and January 31, 2016. Patients were included if they received pharmacist-prescribed vancomycin as an inpatient or outpatient of an RQHR facility. Patients under the care of a pediatrician, those receiving vancomycin for surgical prophylaxis or via any route other than the IV route, and those whose vancomycin was prescribed by a current pharmacy resident were excluded. A rubric was created that assigned a numeric value for the appropriate completion of various procedure criteria.<h4>Results</h4>A total of 326 patients received vancomycin during the study period, of whom 200 met the inclusion criteria, representing 511 discrete episodes of prescribing by 42 pharmacists. The median overall competency rate, for all phases of prescribing, was 100% (interquartile range [IQR] 90.1%-100%). The median competency rates for the empiric therapy and monitoring phases were 94.4% (IQR 88.9%-100%) and 100% (IQR 87.5%-100%), respectively. No statistically significant differences were found in relation to pharmacists' experience or postbaccalaureate education, patients' level of acuity, or timing of prescribing. The competency score was significantly higher among pharmacists prescribing for patients with normal renal function than among those prescribing for patients with reduced renal function (<i>p</i> = 0.008). The 3 most common errors were failure to document risk factors for nephrotoxicity, failure to document requirement to obtain future trough levels, and failure to document that samples for trough levels had been drawn correctly.<h4>Conclusions</h4>During the study period, pharmacists at RQHR showed competency in all phases of vancomycin prescribing using the approved procedure. Documentation of clinical plans and assessments was identified as an area for improvement.
Project description:The polymyxin antibiotics colistin (polymyxin E) and polymyxin B became available in the 1950s and thus did not undergo contemporary drug development procedures. Their clinical use has recently resurged, assuming an important role as salvage therapy for otherwise untreatable gram-negative infections. Since their reintroduction into the clinic, significant confusion remains due to the existence of several different conventions used to describe doses of the polymyxins, differences in their formulations, outdated product information, and uncertainties about susceptibility testing that has led to lack of clarity on how to optimally utilize and dose colistin and polymyxin B. We report consensus therapeutic guidelines for agent selection and dosing of the polymyxin antibiotics for optimal use in adult patients, as endorsed by the American College of Clinical Pharmacy (ACCP), Infectious Diseases Society of America (IDSA), International Society of Anti-Infective Pharmacology (ISAP), Society for Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP). The European Society for Clinical Microbiology and Infectious Diseases (ESCMID) endorses this document as a consensus statement. The overall conclusions in the document are endorsed by the European Committee on Antimicrobial Susceptibility Testing (EUCAST). We established a diverse international expert panel to make therapeutic recommendations regarding the pharmacokinetic and pharmacodynamic properties of the drugs and pharmacokinetic targets, polymyxin agent selection, dosing, dosage adjustment and monitoring of colistin and polymyxin B, use of polymyxin-based combination therapy, intrathecal therapy, inhalation therapy, toxicity, and prevention of renal failure. The treatment guidelines provide the first ever consensus recommendations for colistin and polymyxin B therapy that are intended to guide optimal clinical use.