Vancomycin Dosing Research Articles

Topical Vancomycin for Prevention of Surgical Site Infection in Cranial Surgeries

Background: Surgical site infection (SSI) rates (1–9%) remain high despite the widespread adoption of infection control bundles. Topical vancomycin has emerged as an effective strategy to reduce the rate of SSI in patients undergoing spinal surgery including instrumentation. However, its use and efficiency in cranial neurosurgery is not well established. The aim of this study is to study the efficacy of topical vancomycin in cranial neurosurgery. Methods: A systematic search was performed according to Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Data regarding type of surgery, use of implants, the dose of vancomycin, technique of administration in each study, outcomes, rate of SSI, and the interval between surgery and SSI; possible complications related to antibiotic use were collected. Results: A total of 12 studies were included in the qualitative analysis with 3,446 patients. SSI developed in 1.6% of the patients in the vancomycin group as compared to 5.28% in the control group. The pooled risk ratio was 0.24 with 95% CI: 0.12–0.51 (P-value: <0.00001). The difference between the subgroups was significant (P-value: < 0.00001). The number needed to treat (NNT) was 27.2. The studies showed low heterogeneity with an I 2 of 24%. Meta-regression analysis showed that the number of patients in a study, duration of follow-up, and year of publication did not contribute significantly to effect size. Conclusion: The limited systemic absorption of vancomycin and broad-spectrum led to its widespread applicability in the prevention of SSI in all types of cranial neurosurgery. Cases with implantable pulse generators, cranioplasty, and cerebrospinal fluid (CSF) diversion procedures have all demonstrated their unequivocal effectiveness.

Using population pharmacokinetics to optimize initial vancomycin dosing guidelines for neonates to treat sepsis caused by coagulase-negative staphylococcus.

Vancomycin dosing tailored for newborns is challenging due to the significant influence of maturation and organ function on pharmacokinetics. Population pharmacokinetic (popPK) models can be used to improve target attainment in neonates. The primary objective was to derive and evaluate a popPK model of intravenous vancomycin for neonates. Second, the predictive performance of this popPK model was compared with published popPK models. This is a retrospective cohort study of neonates admitted to the neonatal intensive care unit receiving intravenous vancomycin. A popPK model was derived with 70% of the dataset using a nonlinear mixed effects modeling method. The predictive performance of the current popPK model was validated and compared with 22 published popPK models using the remaining 30% of the dataset. Monte Carlo simulations (MCS) were performed to derive optimal dosing regimens to treat neonatal sepsis caused by coagulase-negative staphylococci (CoNS). Among 655 vancomycin courses from 448 neonates, 78% of vancomycin trough concentrations were outside target range (10-15 mg/L) for central nervous system infections and 43% were outside target range (5-12 mg/L) for other infections using the institution's vancomycin dosing. A one-compartment model best described the observed data with a mean clearance of 0.11 ± 0.03 L/kg/h and volume of distribution (V) of 1.02 ± 0.08 L/kg. Body weight (WT), postmenstrual age (PMA), and serum creatinine (SCr) were significant covariates associated with clearance (p < 0.001) and body WT was a significant covariate associated with V (p = 0.009). Our study's popPK model has similar or better accuracy and precision than other published models. MCS-derived vancomycin doses from the validated model achieved >90% target attainment for a steady state through target range of 10-15 mg/L in the majority of PMA and SCr categories (78%) to treat CoNS sepsis. A vancomycin dosing guideline derived from a validated popPK model in neonates with CoNS sepsis is recommended to improve target attainment.

Impact of Limiting Vancomycin Loading Doses in Patients With Methicillin-resistant Staphylococcus aureus Infections After Hospital Protocol Revision.

Background: Vancomycin loading doses are commonly used to quickly attain target serum concentrations; however, data supporting their effect on clinical patient outcomes is limited. In April 2020, our institution revised our pharmacist-driven vancomycin dosing protocol to reserve loading doses for hemodynamically unstable patients with suspected serious methicillin-resistant Staphylococcus aureus (MRSA) infections. Prior to the protocol update, all patients treated with vancomycin at our institution received a weight-based loading dose. The purpose of this study is to assess clinical efficacy and safety outcomes related to the use of vancomycin loading doses. Methods: A retrospective, quasi-experimental study was performed to compare clinical outcomes in adult patients treated with vancomycin for laboratory-confirmed MRSA infections. Patients who received vancomycin therapy prior to our institution's vancomycin dosing protocol revisions (pre-intervention) were compared to patients who received vancomycin after the revisions (post-intervention). The primary outcome was all-cause, inpatient mortality. Secondary outcomes included persistent signs and symptoms of infection ≥5 days after vancomycin initiation, switch to alternative anti-MRSA therapy, and nephrotoxicity. Results: A total of 122 patients (63 pre-intervention patients and 59 post-intervention patients) were included. Receipt of a vancomycin loading dose did not impact the rate of inpatient mortality (4.76%vs 6.78%; OR 1.46, 95% CI [0.31, 6.79]). All secondary outcomes were similar between the two groups, including persistent signs and symptoms of infection, switch to alternative anti-MRSA therapy, and nephrotoxicity. Conclusions: Routine use of vancomycin loading doses is not associated with improved outcomes in hemodynamically stable patients with MRSA infections.

Individualized Delivery of Vancomycin by Model-Informed Bayesian Dosing Approach to Maintain an AUC24 Target in Critically Ill Patients

Introduction: Monitoring of AUC24 was updated recommendation in the guideline for the therapeutic drug monitoring (TDM) of vancomycin in Chinese pharmacological society published in 2020. Vancomycin pharmacokinetic profiles are diverse and unique in critically ill patients because of the drastic variability of the patients’ physiological parameters, while the study for population pharmacokinetic (PPK) models in Chinese critically ill patients has been rarely reported. The objectives of this study were to construct a PPK model to describe the pharmacokinetic characteristics of vancomycin in critically ill patients and to individualize vancomycin dosing by model-informed Bayesian estimation for maintenance of AUC24 target at 400–650 mg h/L recommended by the 2020 guideline. Methods: Vancomycin with different dosing was administered intravenously over 1 h for critically ill patients, TDM was started at 48 h or 72 h since initiation of vancomycin therapy for patients. Blood samples were collected from patients for trough concentrations or Cmax. Vancomycin concentrations were determined by high-performance liquid chromatography method with ultraviolet detection. PPK model was performed using the nonlinear mixed-effect model (NONMEM®). Individual PK parameters for critically ill patients treated with vancomycin were estimated using a post hoc empirical Bayesian method based on the final PPK model. AUC24 was calculated as the total daily dose divided by the clearance (L/h). Results: The PPK of vancomycin was determined by a one-compartment model with creatinine clearance as fixed effects. The PK estimates in the final model generally agreed with the median estimates and were contained within the 95% CI generated from the bootstrap results, indicating good precision and stability in the final model. The visual predictive check plots showed the adequate predictive performance of the final PK model and supported a good model fit. The model-informed Bayesian estimation was used to predict the AUC24 of critically ill patient by the acquired TDM results, and the dosing adjustment by maintenance of AUC24 at 400–650 mg h/L had made a great therapeutic effect for the case. Conclusion: This study established a PPK model of vancomycin in Chinese critically ill patients, and individualized dosing of vancomycin by model-informed Bayesian estimation to maintain an AUC24 target at 400–650 mg h/L has been successfully applied in clinic. This result supports the continued use of model-informed Bayesian estimation to vancomycin treatment in critically ill patients.

Practices, Knowledge, and Attitudes of Nephrologists Towards Prescribing and Monitoring Vancomycin at Dialysis Centers

ABSTRACT Background Vancomycin dosing protocols are varied in the literature for hemodialysis patients. This study sought to determine nephrologists’ practices, knowledge, attitudes, and barriers toward prescribing and monitoring vancomycin at dialysis centers. Methods A cross-sectional and multi-center study was conducted in Kuwait using a validated self-administered questionnaire among 168 nephrologists. Descriptive and comparative analyses were performed using SPSS (version 28). Results The response rate was 75% (n = 126). Over half of nephrologists frequently prescribed a vancomycin loading dose of 1000 mg (53.2%) and a maintenance dose of 500 mg (51.6%) to all patients. Their overall median (IQR) percentage knowledge about the therapeutic monitoring of vancomycin was 66.7% (33.3) and was found to be higher in nephrologists aged ≤ 40 years and in registrars/senior registrars (p < 0.05). Their overall median (IQR) attitude score was 4.0 (1.0) [positive attitude]. Nephrologists with > 15 years of practice experience expressed higher attitudes (p < 0.05). The top two perceived barriers were a lack of clear local hospital/national guidelines (60.3%) for vancomycin dosing in dialysis and inconsistencies among different dosing references and guidelines (51.6%). Conclusion Findings showed that nephrologists have varying practices, moderate knowledge, and positive attitudes toward prescribing and monitoring vancomycin and highlight the need for interventions to overcome the perceived barriers.

Discrepancy between perceptions and acceptance of clinical decision support Systems: implementation of artificial intelligence for vancomycin dosing

BackgroundArtificial intelligence (AI) tools are more effective if accepted by clinicians. We developed an AI-based clinical decision support system (CDSS) to facilitate vancomycin dosing. This qualitative study assesses clinicians' perceptions regarding CDSS implementation.MethodsThirteen semi-structured interviews were conducted with critical care pharmacists, at Mayo Clinic (Rochester, MN), from March through April 2020. Eight clinical cases were discussed with each pharmacist (N = 104). Following initial responses, we revealed the CDSS recommendations to assess participants' reactions and feedback. Interviews were audio-recorded, transcribed, and summarized.ResultsThe participants reported considerable time and effort invested daily in individualizing vancomycin therapy for hospitalized patients. Most pharmacists agreed that such a CDSS could favorably affect (N = 8, 62%) or enhance (9, 69%) their ability to make vancomycin dosing decisions. In case-based evaluations, pharmacists' empiric doses differed from the CDSS recommendation in most cases (88/104, 85%). Following revealing the CDSS recommendations, we noted 78% (69/88) discrepant doses. In discrepant cases, pharmacists indicated they would not alter their recommendations. The reasons for declining the CDSS recommendation were general distrust of CDSS, lack of dynamic evaluation and in-depth analysis, inability to integrate all clinical data, and lack of a risk index.ConclusionWhile pharmacists acknowledged enthusiasm about the advantages of AI-based models to improve drug dosing, they were reluctant to integrate the tool into clinical practice. Additional research is necessary to determine the optimal approach to implementing CDSS at the point of care acceptable to clinicians and effective at improving patient outcomes.

Analytical Study of a Case Series Of Vancomycin Associated Adverse Drug Reactions In Paediatric Population at a Tertiary Care Hospital: A Brief Report

Background: Red man syndrome (RMS) is frequently reported from pediatric ward in patients receiving vancomycin, at the medical store of SGH, Pune. Though common in pediatric patients, not all patients receiving vancomycin developed Red man syndrome. Hence, this study was done to analyse the demographic, pathophysiological, and pharmacological aspects of the subject who experience adverse drug reactions with vancomycin and to determine if this predisposition is associated with any of these factors.&#x0D; Methods: All adverse drug reactions (ADR) to injection vancomycin in the pediatric ward that were reported from April 2018 - January 2022 were included. Controls were a similar number of randomly selected pediatric cases from the same ward who had received Intravenous vancomycin during the same period but did not experience the adverse drug reactions&#x0D; Results: The mean age was 29.91 ± 34.87 months in subjects who experienced ADR and 57.37 ± 41.58 months, in non-ADR group (p=0.0286). 37.4% were infants, 29.69% toddlers in ADR Group. Seventy four percent of patients who manifested with ADR were below age of 3 compared to barely 38% in controls (p=0.03). 66.6% were malnourished in the ADR group compared to 27.6% in controls (p=0.007). There was no association between the ADR and ethnicity, religion, gender, diagnosis, co-morbidities, co-administered drugs, or administered dose of vancomycin among the children. There was no apparent seasonal variation in occurrence of the ADR.&#x0D; Conclusion: RMS is more common in paediatric population than adults and is usually uneventful. Around 75% of the reactions occur within first 4 days of start of Vancomycin and usually occurs within 30 min of the preceding dose. Younger age groups (infants) and malnourishment were the two factors significantly associated with occurrence of RMS. We may also consider using lower than conventional doses and much slower infusions in such at-risk population.

Dialysis Central Venous Catheter–Associated Sepsis: Complimentary Role of Local Susceptibility Pattern

Introduction: Effective treatment of central venous catheters infections could be very challenging, and may require catheter removal. Reinsertion could worsen the economic burden on patient, particularly those paying out of pocket.&#x0D; Methods: Management was anchored on dialysis-based nitrogenous waste, antigen and cytokines clearance, in addition to antibiotic treatment that was based on sensitivity results and, local microbial susceptibility pattern, to minimize cost.&#x0D; Results: He was febrile (38.40C), had a non-tunnelled jugular vein catheter with a dirty, wet dressing with a greenish tinge. He had tachycardia (110/min), fine crepitaions in the lung bases and ascites. Blood and central line samples grew Pseudomonas aeuriginosa sensitive to Imipenem ++ (both), Vancomycin + (blood) and Ciprofloxacin + (central line). He had 4 haemodialysis sessions through the infected catheter, a dose of Vancomycin but none of Imipenem (on account of cost). He had a full course of intravenous Ciprofloxacin and Ceftazidime which was introduced on the basis of local microbial susceptibility pattern as it had been very effective in managing infective conditions in our CKD patients (either in mono or in combination therapy), particularly in patients unable to afford culture and sensitivity test . He had a good clinical and, microbiological recovery as a repeat culture after seven days of antibiotics treatment showed no growth. The catheter was retained for use in further dialysis sessions.&#x0D; Conclusion: Treatment of infected non-tunnelled dialysis catheters could be very challenging particularly in resource poor settings. The use of low cost antibiotics with positive local microbial susceptibility pattern could be very beneficial, additive and effective in treatment and in minimizing complications.

Feasibility of individualised patient modelling for continuous vancomycin infusions in outpatient antimicrobial therapy, a retrospective study.

The area under the curve (AUC) to minimum inhibitory concentration (MIC) ratio is proposed as a therapeutic drug-monitoring parameter for dosing vancomycin continuous infusion in methicillin-resistant Staphylococcus aureus (MRSA) infection. Individualised pharmacokinetic-pharmacodynamic (PK/PD) calculation of AUC24 may better represent therapeutic dosing than current Therapeutic Drug Monitoring (TDM) practices, targeting a Steady State Concentration of 15-25mg/L. To compare real world TDM practice to theoretical, individualised, PK/PD target parameters utilising Bayesian predictions to steady state concentrations (Css) for outpatients on continuous vancomycin infusions. A retrospective single centre study was conducted at a tertiary hospital on adult patients, enrolled in an outpatient parenteral antimicrobial therapy (OPAT) program, receiving vancomycin infusions for MRSA infection. Retrospective Bayesian dosing was modelled to target PK/PD parameters and compared to real world data. Fifteen patients were evaluated with 53% (8/15) achieved target CSS during hospitalisation, and 83% (13/15) as outpatient. Median Bayesian AUC/MIC was 613mg.h/L with CSS 25mg/L. Patients suffering an Acute Kidney Injury (33%) had higher AUC0-24/MIC values. Retrospective Bayesian modelling demonstrated on median 250mg/24h lower doses than that administered was required (R2 = 0.81) which achieved AUC24/MIC median 444.8 (range 405-460) mg.h/L and CSS 18.8 (range 16.8-20.4) mg/L. Bayesian modelling could assist in obtaining more timely target parameters at lower doses for patients receiving continuous vancomycin infusion as part of an OPAT program, which may beget fewer adverse effects. Utilisation of personalised predictive modelling may optimise vancomycin prescribing, achieving earlier target concentrations as compared to empiric dosing regimens.

Evaluation of an Empiric Vancomycin Dosing Protocol on Goal Troughs and Acute Kidney Injury in a Neonatal Intensive Care Unit.

Review the efficacy and safety of an updated empiric vancomycin dosing protocol in a neonatal intensive care unit (NICU). Retrospective chart review including neonates with postmenstrual age (PMA) less than 40 weeks without renal dysfunction who received vancomycin per protocol at a single institution's NICU before and after implementation of an updated dosing protocol. The primary outcome is the proportion of initial therapeutic troughs. Secondary outcomes include average trough, achievement of a therapeutic trough, number of days before attainment of a therapeutic trough, and proportion of acute kidney injury (AKI) during therapy. The 2 groups were similar in gestational age, race, birth weight, PMA, and weight at time of vancomycin initiation. The post-implementation group had a higher proportion of initial therapeutic troughs (33.0% vs 55.1%) and a lower proportion of a subtherapeutic (58.7% vs 43.8%) and supratherapeutic (8.3% vs 1.1%) initial troughs (p = 0.002). The median trough was not different (9.20 vs 10.50 mg/L; p = 0.092). There was no difference in the proportions of achieving a therapeutic trough throughout therapy (69% vs 76%; p = 0.235); however, the post-implementation group achieved a therapeutic trough 1 day earlier (3 vs 2 days; p < 0.001). There was no difference in proportions of AKI developing between the pre-implementation vs post-implementation groups (10.1% vs 5.6%; p = 0.251). Implementation of an updated vancomycin dosing protocol yielded a higher percentage of initial therapeutic vancomycin troughs and patients reached the therapeutic range 1 day earlier without increasing the proportion of AKI.

AUC-based monitoring and model-informed precision dosing of vancomycin in critically ill patients: why and how?

AUC-based monitoring and model-informed precision dosing of vancomycin in critically ill patients: why and how?

Vancomycin dosing in high-intensity continuous renal replacement therapy: A retrospective cohort study.

An inverse relationship exists between vancomycin serum concentrations and the intensity of continuous renal replacement therapy (CRRT), reflected through the dialysate flow rate (DFR). There remains a lack of evidence to guide initial vancomycin dosing in the setting of high-intensity CRRT (i.e., DFR >30 mL/kg/h). Additionally, recommendations for pharmacokinetic monitoring of vancomycin have transitioned from a trough-based to area under the curve (AUC)-based dosing strategy to optimize efficacy and safety. Therefore, an improved understanding of the impact of CRRT intensity on AUC/MIC (minimum inhibitory concentration) has the potential to enhance vancomycin dosing in this patient population. The goal of this study is to evaluate current vancomycin dosing strategies and achievement of pharmacokinetic targets in patients on high-intensity CRRT. This was a single-center, retrospective cohort study of adult critically ill patients admitted to Houston Methodist Hospital between May 2019 and October 2021 and received vancomycin therapy while on high-intensity CRRT. High-intensity CRRT was defined by a DFR that was both ≥3 L/h and >30 mL/kg/h. Depending on the initial vancomycin dosing strategy, patients were stratified into either the traditional (15 mg/kg/day) or enhanced (≥15 mg/kg/day) dosing group. The primary outcome was the percent of patients who attained steady-state AUC24 /MIC ≥400 mg*h/L at the first obtained vancomycin level in the enhanced group compared with the traditional group. A total of 125 patients were included in the final analysis, 56 in the traditional and 69 in the enhanced dosing group. The primary end point occurred in 74% and 54% of patients in the enhanced and traditional dosing groups, respectively (p = 0.029). Therapeutic vancomycin trough levels (10-20 μg/mL) were more commonly achieved in the enhanced dosing group compared with the traditional dosing group (66.7% vs. 45%, p = 0.013). As DFR rose, increasingly higher doses of vancomycin, up to 27 mg/kg/day, were required to achieve the therapeutic targets. This is the first study to evaluate the influence of variable CRRT intensities on vancomycin AUC/MIC. Our findings suggest that vancomycin doses of ≥15 mg/kg/day are needed to achieve early therapeutic targets in patients on high-intensity CRRT.

Impact of antimicrobial stewardship program-driven educational intervention for vancomycin loading dose on mortality

BackgroundAlthough the loading dose (LD) of vancomycin (VCM) contributes to its efficacy, it may not be conducted adequately. Herein, the objective was to evaluate the effect of LD on patient prognosis using therapeutic drug monitoring by pharmacists and elucidate the impact of an antimicrobial stewardship program (ASP)-driven educational intervention on the LD implementation rate and patient prognosis. Materials and methodsFirst, a retrospective cohort study was conducted involving 121 adult patients administered with VCM and compared with 28-day mortality in LD and non-LD groups. To avoid confounding, the propensity score method was employed. Second, post-training with ASP-driven lectures, a questionnaire survey was conducted for healthcare workers, including physicians, nurses, and pharmacists. The rates of VCM LD implementation and 28-day mortality were compared during a period of one year and 9 months between the pre-ASP (n = 38) and post-ASP (n = 33) groups. ResultsAfter propensity score matching, the 28-day mortality in the LD group was significantly improved, suggesting that the early increase in blood levels of VCM due to an LD is an important factor influencing patient prognosis. After the lecture, a questionnaire survey revealed that the understanding rates of "well" and "slightly well" for educational lectures exceeded 80% of all healthcare workers. The rate of LD implementation significantly increased to 63.6% (21/33) in the post-ASP group compared with 31.6% (12/38) in the pre-ASP group (p = 0.007), and the 28-day mortality declined from 23.7% (9/38) to 6.1% (2/33) (p = 0.041). ConclusionThis method of ASP-driven educational intervention would facilitate LD implementation, improving patient prognosis.

Model-informed precision dosing of antimicrobial drugs in pediatrics: experiences from a pilot scale program.

Antibiotics are among the most utilized drugs in pediatrics. Nonetheless, there is a lack in pharmacokinetics information for this population, and dosing criteria may vary between healthcare centers. Physiological variability associated with maturation in pediatrics makes it challenging to reach a consensus on adequate dosing, which is further accentuated in more vulnerable groups, such as critically ill or oncology patients. Model-informed precision dosing is a useful practice that allows dose optimization and attainment of antibiotic-specific pharmacokinetic/pharmacodynamic targets. The aim of this study was to evaluate the needs of model-informed precision dosing of antibiotics in a pediatrics unit, at a pilot scale. Pediatric patients under antibiotic treatment were monitored with either a pharmacokinetic/pharmacodynamic optimized sampling scheme or through opportunistic sampling. Clindamycin, fluconazole, linezolid, meropenem, metronidazole, piperacillin, and vancomycin plasma concentrations were quantified through a liquid chromatography coupled to mass spectrometry method. Pharmacokinetic parameters were estimated using a Bayesian approach to verify pharmacokinetic/pharmacodynamic target attainment. A total of 23 pediatric patients aged 2 to 16years were included, and 43 dosing regimens were evaluated; 27 (63%) of them required adjustments as follows: 14 patients were underdosed, 4 were overdosed, and 9 patients needed infusion rate adjustments. Infusion rate adjustments were mostly recommended for piperacillin and meropenem; daily doses were augmented for vancomycin and metronidazole, meanwhile linezolid was adjusted for under- and overdosing. Clindamycin and fluconazole regimens were not adjusted at all. Conclusion: Results showcase a lack of antibiotic pharmacokinetic/pharmacodynamic target attainment (particularly for linezolid, vancomycin, meropenem, and piperacillin), and the need for model-informed precision dosing in pediatrics. This study provides pharmacokinetic evidence which can further improve antibiotic dosing practices. What is Known: • Model-informed precision dosing is performed in pediatrics to optimize the treatment of antimicrobial drugs such as vancomycin and aminoglycosides, while its usefulness is debated for other groups (beta-lactams, macrolides, etc.). What is New: • Vulnerable pediatric subpopulations, such as critically ill or oncology patients, can benefit the most from model-informed precision dosing of antibiotics. • Model-informed precision dosing of linezolid, meropenem, piperacillin, and vancomycin is particularly useful in pediatrics, and further research mayimprove dosing practices altogether.

Optimizing the dosing of vancomycin in patients receiving intermittent haemodialysis with low-flux filters, and the potential impact of dosing software.

Iterative approaches to vancomycin dosing (e.g., dosing when trough concentrations <15-20 mg/L) can be inadequate. Computer-guided dosing may be superior but has not been evaluated in patients with kidney failure receiving replacement therapy. We evaluated vancomycin concentrations using a hospital protocol and a pharmacokinetic software. We measured vancomycin clearance by the FX8 low-flux filter because data are absent. We retrospectively reviewed records of adults with kidney failure requiring replacement therapy receiving vancomycin and dialysed with the FX8 low-flux filter, and calculated the proportion of pre-dialysis concentrations that were within, above or below a specified range. One and two-compartment models in the pharmacokinetic software were assessed by computing mean prediction error (MPE) and root mean square error (RMSE) of observed versus predicted concentrations. Vancomycin extracorporeal clearance was prospectively determined using the extraction method. In 24 patients (34 courses; 139 paired observed and predicted concentrations), 62/139 (45%) pre-dialysis concentrations were 15-25 mg/L, 29/139 (21%) were above, and 48/139 (35%) were below. MPE for the one-compartment model was -0.2 mg/L, RMSE 5.3 mg/L. MPE for the two-compartment model was 2.0 mg/L, RMSE 5.6 mg/L. Excluding the first paired concentrations, the subsequent MPE (n = 105) using one-compartment model was -0.5 mg/L, RMSE 5.6 mg/L. The MPE for the two-compartment model was 2.1 mg/L, RMSE 5.8 mg/L. The median extracorporeal clearance was 70.7 mL/min (range: 10.3-130.3; n = 22). Vancomycin dosing was suboptimal and the pharmacokinetic software was not sufficiently predictive. These may improve with a loading dose. The substantial removal of vancomycin by low-flux filters is not accounted for by the models tested.

English

The 24-h area under the curve concentration (AUC24 h) is associated with better clinical and bacteriological response to vancomycin in patients with methicillin-resistant Staphylococcus aureus who achieve the target AUC24 h between 400 and 700 mg&times;h/L. Recent consensus recommends maintaining trough concentrations between 15 and 20 mg/mL as a convenient target&nbsp; to reach an AUC/minimum inhibitory concentration (MIC) &ge; 400. The aim of this study was to determine the correlation between a calculated AUC24 h and a measured trough vancomycin concentration (C0). We conducted a retrospective observational study. Hospitalized patients prescribed vancomycin for a presumed or documented invasive staphylococcal infections were evaluated. A formula based on the relationship between dose, vancomycin clearance and creatinine clearance was used to determine each patient&#39;s AUC24 h. 161 patients were included in the study. Median age was 34 years. The mean daily dose of vancomycin was 28 mg/kg/day. The median vancomycin C0 was 12.2 mg/mL, 17.3% were in the therapeutic range. The median AUC was 246.84 mg&times;h/L, only 8% achieved the target AUC24 h between 400 and 700 mg&times;h/L. Of these, 3 patients had C0 between 15 and 20 mg/mL and 9 patients had C0&gt; 20 mg/mL. A poor correlation was found between C0 and AUC24 h = 0.37; r2 = 0.14; p&lt;0.0001. In conclusion, vancomycin C0 correlated poorly with AUC24/MIC targets. C0 seems to underestimate AUC24 h. So, a patient specific AUC24/MIC may serve to predict efficacy while C0 can be used as indicators of possible nephrotoxicity and development of resistance. Key words: Vancomycin, area under the curve (AUC), trough concentration, minimum inhibitory concentration, therapeutic drug monitoring.

International survey of antibiotic dosing and monitoring in adult intensive care units

BackgroundIn recent years, numerous dosing studies have been conducted to optimize therapeutic antibiotic exposures in patients with serious infections. These studies have led to the inclusion of dose optimization recommendations in international clinical practice guidelines. The last international survey describing dosing, administration and monitoring of commonly prescribed antibiotics for critically ill patients was published in 2015 (ADMIN-ICU 2015). This study aimed to describe the evolution of practice since this time.MethodsA cross-sectional international survey distributed through professional societies and networks was used to obtain information on practices used in the dosing, administration and monitoring of vancomycin, piperacillin/tazobactam, meropenem and aminoglycosides.ResultsA total of 538 respondents (71% physicians and 29% pharmacists) from 409 hospitals in 45 countries completed the survey. Vancomycin was mostly administered as an intermittent infusion, and loading doses were used by 74% of respondents with 25 mg/kg and 20 mg/kg the most favoured doses for intermittent and continuous infusions, respectively. Piperacillin/tazobactam and meropenem were most frequently administered as an extended infusion (42% and 51%, respectively). Therapeutic drug monitoring was undertaken by 90%, 82%, 43%, and 39% of respondents for vancomycin, aminoglycosides, piperacillin/tazobactam, and meropenem, respectively, and was more frequently performed in high-income countries. Respondents rarely used dosing software to guide therapy in clinical practice and was most frequently used with vancomycin (11%).ConclusionsWe observed numerous changes in practice since the ADMIN-ICU 2015 survey was conducted. Beta-lactams are more commonly administered as extended infusions, and therapeutic drug monitoring use has increased, which align with emerging evidence.

Pursuing the Real Vancomycin Clearance during Continuous Renal Replacement Therapy in Intensive Care Unit Patients: Is There Adequate Target Attainment?

Introduction: Vancomycin is used in intensive care unit (ICU) patients for the treatment of infections caused by gram-positive bacteria. The vancomycin pharmacokinetic/pharmacodynamic index is a ratio of the area under the concentration to the minimum inhibitory concentration ≥400–600 h*mg/L. This target can generally be achieved by a plasma concentration of 20–25 mg/L. Together with the pathophysiological alterations and pharmacokinetic variability associated with critical illness, the use of continuous renal replacement therapy (CRRT) may complicate the attainment of adequate vancomycin concentrations. The primary objective was the prevalence of attainment of vancomycin concentrations 20–25 mg/L after 24 h in adult ICU patients receiving CRRT. Secondary outcomes were to evaluate target attainment at days 2 and 3 and to calculate vancomycin clearance (CL) by CRRT and residual diuresis. Methods: We performed a prospective observational study in adult ICU patients on CRRT, which received at least 24 h continuous infusion of vancomycin. Between May 2020 and February 2021, daily vancomycin residual blood gas and dialysate samples were collected from 20 patients, every 6 h and if possible vancomycin urine samples. Vancomycin was analysed with an immunoassay method. The CL by CRRT was calculated by a different approach correcting for the downtime and providing insight into the degree of filter patency. Results: The proportion of patients with vancomycin concentrations <20 mg/L was 50% 24 h after starting vancomycin (n = 10). No differences were observed in patient characteristics. The target vancomycin concentration 20–25 mg/L was only achieved in 30% of the patients. On days 2 and 3, despite the use of TDM and albeit in lower percentages, sub- and supratherapeutic levels were still observed. Taking downtime and filter patency into account resulted in lower vancomycin CL. Conclusions: 50% of the studied ICU patients on CRRT showed subtherapeutic vancomycin concentrations 24 h after starting therapy. The results reveal that optimization of vancomycin dosage during CRRT therapy is needed.

Evaluation of Real-World Vancomycin Dosing and Attainment of Therapeutic Drug Monitoring Targets.

In 2020, the Infectious Diseases Society of America (IDSA) recommended a change in vancomycin therapeutic drug monitoring from trough-based to AUC/MIC-based to optimize vancomycin's efficacy and reduce nephrotoxicity. Many hospitals have not implemented this change due to barriers such as the cost of AUC/MIC software and lack of provider familiarity. The purpose of this study was to determine the rate of AUC/MIC ratio target attainment using current trough-based vancomycin dosing practices at a city hospital. The rates of acute kidney injury (AKI) were also evaluated. Vancomycin orders were reviewed retrospectively to determine the expected AUC/MIC ratios using first-order pharmacokinetic equations over a 7-month period. Orders were excluded if they were written for a one-time dose, for individuals less than 18 years of age, or for those on hemodialysis. A total of 305 vancomycin orders were included in this review. Overall, 27.9% (85/305) of vancomycin orders attained the AUC/MIC ratio target of 400-600 mg·h/L as recommended by the guidelines. Nearly 35% (106/305) achieved AUC/MIC ratios below 400 mg·h/L and 37.4% (114/305) achieved AUC/MIC ratios above 600 mg·h/L. Orders for obese patients were significantly more likely to have below the target AUC/MIC ratios (68% vs. 23.9%, X2 48.48, p < 0.00001) and non-obese patients were significantly more likely to have above the target AUC/MIC ratios (45.7% vs. 12%, X2 27.36, p < 0.00001). The overall rate of acute kidney injury observed was 2.6%. Most vancomycin orders did not attain therapeutic drug monitoring targets, reflecting the ongoing clinical challenge of optimizing vancomycin doses and implementing new guideline recommendations.

Clinical Evaluation of a Vancomycin Dosage Strategy Based on a Serum Trough Concentration Model in Elderly Patients with Severe Pneumonia

ObjectiveThis study aimed to evaluate the clinical benefits of a vancomycin dosage strategy based on a serum trough concentration model in elderly patients. MethodsThis prospective single-center, open-label, randomized controlled trial categorized 66 elderly patients with severe pneumonia into study and control groups. The control group received vancomycin using a regimen decided by the attending physician. Meanwhile, the study group received individualized vancomycin therapy with a dosing strategy based on a serum trough concentration model. The primary endpoint was the proportion of patients with serum trough concentrations reaching the target values. The secondary endpoints were clinical response, vancomycin treatment duration, and vancomycin-associated acute kidney injury (VA-AKI) occurrence. ResultsAll patients were at least 60 years old (median age = 81 years). The proportion of patients with target trough concentration achievement (≥ 15 mg/L) with the initial vancomycin regimen was significantly higher in the study group compared to the control group (75.8% vs. 42.4%, P = 0.006). Forty-five patients (68.2%) achieved clinical success, the median duration of vancomycin therapy was 10.0 days, and VA-AKI occurred in eight patients (12.1%). However, there were no significant differences in these parameters between the two groups. The model for predicting vancomycin trough concentrations was upgraded to: serum trough concentration (mg/L) = 17.194 − 0.104 × creatinine clearance rate (mL/min) + 0.313 × vancomycin daily dose [(mg/(kg·d)]. ConclusionA vancomycin dosage strategy based on a serum trough concentration model can improve the proportion of patients achieving target trough concentrations in elderly patients with severe pneumonia.