The increasing number of infections produced by beta-lactam-resistant Gram-positive bacteria and the morbidity secondary to these infections make it necessary to optimize the use of vancomycin. In 2009, the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Disease Pharmacists published specific guidelines about vancomycin dosage and monitoring. However, these guidelines have not been updated in the past 6 years. This review analyzes the new available information about vancomycin published in recent years regarding pharmacokinetics and pharmacodynamics, serum concentration monitoring, and optimal vancomycin dosing in special situations (obese people, burn patients, renal replacement therapy, among others). Vancomycin efficacy is linked to a correct dosage which should aim to reach an area under the curve (AUC)/MIC ratio of ≥400; serum trough levels of 15 to 20 mg/liter are considered a surrogate marker of an AUC/MIC ratio of ≥400 for a MIC of ≤1 mg/liter. For Staphylococcus aureus strains presenting with a MIC >1 mg/liter, an alternative agent should be considered. Vancomycin doses must be adjusted according to body weight and the plasma trough levels of the drug. Nephrotoxicity has been associated with target vancomycin trough levels above 15 mg/liter. Continuous infusion is an option, especially for patients at high risk of renal impairment or unstable vancomycin clearance. In such cases, vancomycin plasma steady-state level and creatinine monitoring are strongly indicated.

Optimizing the Clinical Use of Vancomycin

Purpose of reviewObesity is becoming a major burden on healthcare systems worldwide. The management of infections is problematic due to both an increased risk of morbidity and mortality, as well as a lack of information about dosing of antibiotics in the obese population. Recommendations in this pat

Dosing of antibiotics in obesity.

Physiologic alterations seen in obesity commonly impact the pharmacokinetics (PK) and pharmacodynamics (PD) of antibiotics and may result in suboptimal dosing in this expanding but understudied population. Much of the published clinical and PK evidence to date consists of small patient populations and are retrospective with, not infrequently, heterogeneous results that in some cases are contradictory. In the last 10 years, additional antimicrobial PK/PD and clinical data encompassing prolonged infusion strategies and examination of critically ill populations have emerged to inform antimicrobial dosing in obesity. In this narrative review, we critically review literature on dosing, PK, and possible dosing strategies in obese adults. We searched PubMed, Scopus, and the Cochrane Library using Medical Subject Headings including anti-infectives, specific antimicrobial names, obese, pharmacokinetics, and others. We reviewed articles, cross-referenced select cited references, and when applicable, referenced drug databases and package inserts to develop dosing recommendations. We provide an overall critical review of the available data regarding PK and dosing issues including dosing recommendations in both critically ill and noncritically ill patients with significant obesity. We developed dosing recommendations for 34 antimicrobials based on 121 articles of the 2336 identified by the search strategy. Although 11 of these do not appear to require dose adjustment, obesity-specific dosing guidance is provided for the remaining 23 antimicrobials. Additional studies are needed to better understand and resolve discrepant published results regarding the PK of antibiotics to establish optimal dosing strategies in obese adults. Alternative dosing strategies, such as extended infusions, should be considered for time-dependent antibiotics (e.g., β-lactams) in obese patients to achieve PD targets reliably. Therapeutic drug monitoring across the spectrum of antimicrobials is of increasing importance in this and other populations to ensure optimized dosing.

https://accpjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/phar.2023

Comprehensive Guidance for Antibiotic Dosing in Obese Adults

Study objective To estimate vancomycin pharmacokinetic parameters and dosing requirements in a cohort of extremely obese patients. Design Prospective pharmacokinetic study. Setting Acute care community teaching hospital. Patients Thirty-one extremely obese (body mass index [BMI] ≥ 40 kg/m(2) ) men and women who were receiving vancomycin for at least 3 days for suspected or confirmed Staphylococcus aureus infections. Measurements and main results Population pharmacokinetic parameters were used to determine vancomycin doses that target trough concentrations of 10-20 μg/ml. Three serum vancomycin concentrations (peak, trough, and midpoint) were measured at steady state for each patient. A 24-hour urine collection was performed to determine creatinine clearance (Clcr ). A one-compartment intravenous infusion model was fit to the serum vancomycin concentrations by using nonlinear mixed-effects modeling. Covariates that affect the volume of distribution and clearance of vancomycin were explored. Patients had a median weight of 147.9 kg, BMI of 49.5 kg/m(2) , and a Cockcroft-Gault Clcr of 124.8 ml/minute/1.73 m(2) . Patients received a median vancomycin dose of 4000 mg/day that provided a median 24-hour area under the concentration-time curve (AUC) of 582.9 (interquartile range 513.8-726.2) mg·hour/L. The population mean volume of distribution was 0.51 L/kg, and clearance was 6.54 L/hour. Simulations indicated that 4000-5000 mg/day of vancomycin provided ≥ 93% probability 24-hour AUC/minimum inhibitory concentration (MIC) ratio of ≥ 400 for an MIC of 1 μg/ml. Conclusion Total body weight and Clcr influenced volume of distribution and vancomycin clearance, respectively. Vancomycin can be initiated in extremely obese patients at dosages determined based on renal function and pharmacokinetic parameter estimates from this study. Vancomycin serum concentrations should be monitored to ascertain attainment within the therapeutic range.

Pharmacokinetics of Vancomycin in Extremely Obese Patients with Suspected or Confirmed Staphylococcus aureus Infections

SummaryWhat is known and objective
Obesity is a significant burden on the healthcare system in the United States, and determining the appropriate antimicrobial dosing regimen in morbidly obese patients is challenging Morbidly obese patients have documented differences in pharmacokinetic and pharmacodynamic properties compared to normal-weight patients, which impact antibiotic efficacy and toxicity The Food and Drug Administration does not recognize obesity as a special population and does not require pharmaceutical companies to perform studies specific to obese patients However, there are an increasing number of post-approval studies in obese patients, and this manuscript reviews available clinical and pharmacokinetic literature regarding weight-based antimicrobial agents Additionally, we describe a single-centre approach to optimize dosing in morbidly obese patients

Methods
A comprehensive literature search was performed on 15 weight-based antimicrobials in the setting of obesity: acyclovir, aminoglycosides, amphotericin B, cidofovir, colistimethate, daptomycin, flucytosine, foscarnet, ganciclovir, quinupristin/dalfopristin, trimethoprim/sulfamethoxazole, vancomycin and voriconazole A weight-based antimicrobial dosing guideline for morbidly obese patients was developed An analysis of guideline compliance and cost analysis were performed following guideline implementation

Results and discussion
This review describes the pharmacokinetic changes that occur in obese patients, including increased volume of distribution, altered hepatic metabolism, renal excretion and changes in protein binding The majority of weight-based antimicrobials result in increased serum concentrations in morbidly obese patients compared to normal-weight patients when the calculated dose is based on actual body weight

What is new and conclusion
This review demonstrates different antibiotic pharmacokinetic properties are altered in obese patients that could impact efficacy and toxicity A single-centre guideline for weight-based antimicrobial dosing in obesity was developed and provides recommendations for using ideal body weight, adjusted body weight or actual body weight when calculating antimicrobial doses However, more research is needed to better elucidate optimal dosing of weight-based antimicrobials in obesity, with particular focus on efficacy and toxicity

https://onlinelibrary.wiley.com/doi/pdf/10.1111/jcpt.12200

Impact of hospital guideline for weight-based antimicrobial dosing in morbidly obese adults and comprehensive literature review.

Purpose An original and a revised vancomycin dosing protocol for obese patients were compared with respect to attainment of target serum trough vancomycin concentrations and the occurrence of nephrotoxicity.

Methods The attainment of target vancomycin trough values (10–20 μg/mL) and nephrotoxicity were compared retrospectively between an original protocol (vancomycin 15 mg/kg i.v. every 8–12 hours), which had been associated with high troughs, and a revised protocol (10 mg/kg i.v. every 12 hours or 15 mg/kg every 24 hours). Patients were included if they were obese (weight ≥ 100 kg and total body weight ≥ 140% of ideal body weight), had normal renal function (creatinine clearance ≥ 60 mL/min), had received i.v. vancomycin for at least 48 hours, and had one evaluable vancomycin trough value. Nephrotoxicity was defined as an increase in serum creatinine concentration of 0.5 mg/dL or of 50% over baseline, whichever was greater.

Results Seventy-four and 64 patients were stratified into groups that had been treated with the revised and original protocols, respectively. The mean ± S.D. maintenance dose was 19 ± 2 mg/kg/day with the revised protocol and 34 ± 7 mg/kg/day with the original protocol ( p < 0.001). Compared with the original protocol, the revised protocol resulted in a higher frequency of target troughs (59% versus 36%, p = 0.006) and below-target troughs (23% versus 9%, p = 0.033) and a lower frequency of above-target troughs (18% versus 55%, p < 0.001). Nephrotoxicity occurred in two patients in each group.

Conclusion Compared with the original vancomycin protocol for obese patients, a revised vancomycin protocol using lower total daily doses improved the attainment of target trough concentrations, with minimal nephrotoxicity.

Performance of a vancomycin dosage regimen developed for obese patients

Primary care plays an integral role in the management of complex, chronic disease states such as heart failure. However, there is a disconnect between the characteristics of those recruited into clinical trials and those managed in the real world, which means the contribution and consideration of primary care in current guidelines is suboptimal. In this article, the authors explore key issues in the diagnosis and management of heart failure that need to be addressed from a primary care perspective. This article focuses on the issue of heart failure with preserved ejection fraction and the integration of new clinical epidemiology and trial evidence into clinical practice. In response, the authors advocate for dedicated guidelines for the primary care management of heart failure, the development of strategies to facilitate communications between health professionals in acute and community care and a renewed focus on researching optimal models of heart failure care in the community.

Out with the Old and In with the New: Primary Care Management of Heart Failure with Preserved Ejection Fraction

The role of a pharmacist as a member of the inpatient health care team has continued to evolve as the profession advances. Recent changes in recommended inpatient pharmacy practice models require increasing clinical involvement and interaction with patients and other health care practitioners.[1][1

Laura H. Waite

Papers

Performance of a vancomycin dosage regimen developed for obese patients

Out with the Old and In with the New: Primary Care Management of Heart Failure with Preserved Ejection Fraction

Advanced clinical pharmacy services in a nonacademic community hospital.