Developing Parametric and Nonparametric Models for Model-Informed Precision Dosing: A Quality Improvement Effort in Vancomycin for Patients With Obesity.

BACKGROUND: Both parametric and nonparametric methods have been proposed to support model-informed precision dosing (MIPD). However, which approach leads to better models remains uncertain. Using open-source software, these 2 statistical approaches for model development were compared using the pharmacokinetics of vancomycin in a challenging subpopulation of class 3 obesity. METHODS: Patients on vancomycin at the University of Vermont Medical Center from November 1, 2021, to February 14, 2023, were entered into the MIPD software. The inclusion criteria were body mass index (BMI) of at least 40 kg/m2 and 1 or more vancomycin levels. A parametric model was created using nlmixr2/NONMEM, and a nonparametric model was created using metrics. Then, a priori and a posteriori predictions were evaluated using the normalized root mean squared error (nRMSE) for precision and the mean percentage error (MPE) for bias. The parametric model was evaluated in a simulated MIPD context using an external validation dataset. RESULTS: In total, 83 patients were included in the model development, with a median age of 56.6 years (range: 24-89 years), and a median BMI of 46.3 kg/m2 (range: 40-70.3 kg/m2). Both parametric and nonparametric models were 2-compartmental, with creatinine clearance and fat-free mass as covariates to c clearance and volume parameters, respectively. The a priori MPE and nRMSE for the parametric versus nonparametric models were -6.3% versus 2.69% and 27.2% versus 30.7%, respectively. The a posteriori MPE and RMSE were 0.16% and 0.84%, and 13.8% and 13.1%. The parametric model matched or outperformed previously published models on an external validation dataset (n = 576 patients). CONCLUSIONS: Minimal differences were found in the model structure and predictive error between the parametric and nonparametric approaches for modeling vancomycin class 3 obesity. However, the parametric model outperformed several other models, suggesting that institution-specific models may improve pharmacokinetics management.

Antibiograms Cannot Be Used Interchangeably Between Acute Care Medical Centers and Affiliated Nursing Homes.

OBJECTIVE: To determine whether antibiograms for Veterans Affairs (VA) nursing homes (NHs), termed Community Living Centers, are similar to those from their affiliated acute care medical centers. DESIGN: Descriptive study. SETTING AND PARTICIPANTS: We compared the 2017 antibiograms for VA NHs to their affiliated VA medical centers (VAMCs). Antibiograms included antibiotic susceptibility rates for commonly observed bacteria in this setting (Staphylococcus aureus, Enterococcus spp, Escherichia coli, Klebsiella spp, Proteus mirabilis, and Pseudomonas aeruginosa). METHODS: Antibiograms were considered to be in complete agreement when the overall susceptibility rate between the NH and affiliated VAMC was either at or above 80% or below 80% across all bacteria and antibiotics. Average percentage of bacteria-antibiotic comparisons in disagreement per facility pair, and number of facilities with agreement for specific bacteria-antibiotic comparisons were also assessed. The chi-square test was used to compare disagreement between NH-VAMC facilities based on geographic proximity of the NH to the VAMC, culture source, and bed size. RESULTS: A total of 119 NH-VAMC affiliate pairs were included in this analysis, with 71% (84/119) on the same campus and 29% (35/119) on geographically distinct campuses. None of the NH-VAMC pairs demonstrated complete agreement (all bacteria vs all antibiotics) between their antibiograms. On average, 20% of the bacteria-antibiotic comparisons from the antibiogram disagreed clinically per NH-VAMC pair, and almost twice as often the nursing home had lower susceptibility (higher resistance) than the acute care facility. Some bacteria-antibiotic comparisons agreed in all facilities (eg, E coli-imipenem; S aureus-linezolid; S aureus-vancomycin), while others showed greater disagreement (eg, Klebsiella spp-cefazolin; Klebsiella spp-ampicillin-sulbactam; P aeruginosa-ciprofloxacin). Rates of clinical disagreement were similar by geographic proximity of the NH to the VAMC, culture source, and bed size. CONCLUSIONS AND IMPLICATIONS: Overall, this study showed a moderate lack of agreement between VA NH antibiograms and their affiliate VAMC antibiograms. Our data suggest that antibiograms of acute care facilities are often not accurate approximations of the nursing home resistance patterns and therefore should be used with caution (if at all) in guiding empiric antibiotic therapy.

A Review of Nonantibiotic Agents to Prevent Urinary Tract Infections in Older Women.

OBJECTIVE: This article provides a comprehensive literature review on nonantibiotic agents used for the prevention of urinary tract infections (UTIs) in women ≥45 years of age. DESIGN: A structured review was performed by conducting a literature search to identify relevant studies pertaining to the use of nonantibiotic agents to prevent UTIs in women who were perimenopausal through postmenopausal. Recommendations were made for or against the use of each nonantibiotic agent, unless data were unavailable. Levels of evidence were assigned to each recommendation made. SETTING AND PARTICIPANTS: Studies on the prevention of UTIs with women subjects ≥45 years of age in the community, inpatient, and long-term care settings were considered for inclusion. MEASURE: The efficacy and safety of using ascorbic acid, cranberry products, d-mannose, estrogens, lactobacilli, and methenamine hippurate for prevention of UTIs was assessed. RESULTS: There is evidence to support use of estrogens (A-I) in postmenopausal women, and cranberry capsules (C-I) in women ≥45 years of age for the prevention of UTIs. There was a lack of evidence to make recommendations for or against the use of ascorbic acid, cranberry juice, cranberry capsules with high proanthocyanidin (PAC) content, d-mannose, lactobacillus, and methenamine hippurate in this population. CONCLUSIONS/IMPLICATIONS: Current studies support that estrogens and cranberry capsules may have a role in preventing UTIs in women ≥45 years of age. Further research is needed to elucidate the role of these nonantibiotic agents and how they may be used to decrease antibiotic use.

Trends in Collection of Microbiological Cultures Across Veterans Affairs Community Living Centers in the United States Over 8 Years.

OBJECTIVES: To describe and evaluate changes in the collection of microbiological cultures across Veterans Affairs (VA) Community Living Centers (CLCs) nationally. DESIGN: Descriptive study. SETTING: 146 VA CLCs. PARTICIPANTS: We identified both positive and negative microbiological cultures collected during VA CLC admissions from January 2010 through December 2017. MEASURES: We measured the average annual percentage change (AAPC) in the rate of cultures collected per 1000 bed days and per admission, overall and stratified by culture type (ie, urine, blood, skin and soft tissue, and respiratory tract). AAPCs were also calculated for the proportion and rate of positive cultures collected, overall and stratified by culture type and organism (ie, Escherichia coli, Proteus mirabilis, Staphylococcus aureus, Enterococcus spp, Pseudomonas aeruginosa, Klebsiella spp, Enterobacter spp, Morganella morganii, Citrobacter spp, Serratia marcescens, and Streptococcus pneumoniae). Joinpoint regression software was used to assess trends and estimate AAPCs and 95% confidence intervals (CIs). RESULTS: Over 8 years, 355,329 cultures were collected. The rate of cultures collected per 1000 bed days of care decreased significantly by 6.0% per year (95% CI -8.7%, -3.2%). The proportion of positive cultures decreased by 0.9% (95% CI -1.4%, -0.4%). The most common culture types were urine (48.4%), followed by blood (27.7%). The rate of cultures collected per 1000 bed days of care decreased per year by 6.3% for urine, 5.0% for blood, 4.4% for skin and soft tissue, and 4.9% for respiratory tract. In 2010, S aureus was the most common organism identified, and in all subsequent years E coli was the most common. CONCLUSION AND IMPLICATIONS: We identified a significant reduction in the number of cultures collected over time among VA CLCs. Our findings may be explained by decreases in the collection of unnecessary cultures in VA CLCs nationally due to increased antibiotic stewardship efforts targeting unnecessary culturing and antibiotic treatment.

Bayesian clinical decision support-guided versus clinician-guided vancomycin dosing in attainment of targeted pharmacokinetic parameters in a paediatric population.

OBJECTIVES: To compare a Bayesian clinical decision support (CDS) dose-optimizing software program with clinician judgement in individualizing vancomycin dosing regimens to achieve vancomycin pharmacokinetic (PK)/pharmacodynamic (PD) targets in a paediatric population. METHODS: A retrospective review combined with a model-based simulation of vancomycin dosing was performed on children aged 1 year to 18 years at the University of California, San Francisco Benioff Children's Hospital Mission Bay. Dosing regimens recommended by the clinical pharmacists, 'clinician-guided', were compared with alternative 'CDS-guided' dosing regimens. The primary outcome was the percentage of occasions predicted to achieve steady-state trough levels within the target range of 10-15 mg/L, with a secondary outcome of predicted attainment of AUC24 ≥400 mg·h/L. Statistical comparison between approaches was performed using a standard t-test. RESULTS: A total of n=144 patient occasions were included. CDS-guided regimens were predicted to achieve vancomycin steady-state troughs in the target range on 70.8% (102/144) of occasions, as compared with 37.5% (54/144) in the clinician-guided arm (P<0.0001). An AUC24 of ≥400 mg·h/L was achieved on 93% (112/121) of occasions in the CDS-guided arm versus 72% (87/121) of occasions in the clinician-guided arm (P<0.0001). CONCLUSIONS: In a simulated analysis, the use of a Bayesian CDS tool was better than clinician judgement in recommending vancomycin dosing regimens in which PK/PD targets would be attained in children.