An evaluation of antimicrobial prophylaxis for transrectal prostate biopsies: A potential stewardship target.

BACKGROUND: Transrectal prostate biopsy (TRPB) is a common procedure used to obtain a prostate biopsy. Although generally safe, complications may occur including infection. Preprocedural antimicrobial prophylaxis is recommended to minimize risk of subsequent infection. METHODS: This study is a retrospective chart review via the computerized patient record system from January 1, 2018 to February 28, 2022. The study included patients who underwent a TRPB at the Western New York, Syracuse, or Albany Stratton Veterans Affairs Healthcare Systems. RESULTS: This study included a total of 932 patients who underwent TRPB. Postoperative infection occurred in 3.2% (n = 30) of patients within 14days of the TRPB. Of the 30 patients who developed an infection, 30% (n = 9) resulted in bacteremia. For the 932 patients evaluated, 24 different antibiotic regimens were used, none of which followed guideline recommendations. None of the regimens were found to have an impact on rates of subsequent infection. CONCLUSIONS: The results of this study suggest a need for guideline adherence. There was no benefit to using the guideline-discordant regimens as they were not associated with a decreased risk of infection, and in many cases exposed patients to unnecessarily broad and prolonged antibiotic regimens.

Identifying racial disparities in the management of heart failure with reduced ejection fraction.

OBJECTIVE(S): Heart failure (HF) is chronic and progressive. Individuals with a left ventricular ejection fraction (LVEF or EF) < 40% are classified as having heart failure with reduced ejection fraction (HFrEF). Black patients have the highest incidence of HF and are more likely to suffer serious consequences from the disease. Identifying and addressing racial disparities in care is vital to ensuring health equity. The primary objective was to determine the association of race with 1-year heart HF admission rates for white and black patients, when adjusted for EF and age. The secondary objective was to determine the proportion of patients not on guideline-directed medication therapy (GDMT). DESIGN: This study was a retrospective chart review conducted between 10/22/2021 and 11/22/2022 of Veteran patients with HFrEF who were identified via the VA Heart Failure Dashboard. Only White and Black patients were included. A multivariable logistic regression was used to determine odds of admission due to HF. Pharmacotherapy was analyzed to identify gaps in GDMT and if racial disparities existed. SETTING AND PARTICIPANTS: Veterans within the Veterans Affairs Western New York Healthcare System. OUTCOME MEASURES: One-year HF admission rates for white and black patients, when adjusted for EF and age. Proportion of patients not on GDMT. RESULTS: Of the 345 patients with HF originally identified, 172 were included; 22% were admitted within one year. Black patients were 2.9 times more likely to be admitted. (P = 0.031). A median of two drugs (interquartile range [IQR] 1-3) could be added and one dose could be optimized (IQR 1-4) to reach GDMT goals. No differences were found in the prescribing of GDMT or in proportion of patients not on GDMT at recommended doses between white and black patients. CONCLUSION: Black patients were more likely to be admitted for HF than white patients. Pharmacists can play an important role in identifying the need for optimizing GDMT. Future studies could focus on pharmacist-led prospective interventions with an aim to close the gap in racial disparities.

Impact of doxycycline on Clostridioides difficile infection in patients hospitalized with community-acquired pneumonia.

BACKGROUND: Antibiotic use is a significant risk factor associated with Clostridioides difficile (C difficile) infection (CDI). Community-acquired pneumonia (CAP) is a common infection leading to hospital admission and the use of antibiotics that are highly associated with CDI. It has been proposed that doxycycline, a tetracycline antibiotic, may be protective against CDI. METHODS: A retrospective analysis was conducted in hospitalized patients in Veterans Affairs Hospitals across the United States to determine if doxycycline was associated with a decreased risk of CDI. The primary outcome was the development of CDI within 30 days of initiation of doxycycline or azithromycin, as part of a standard pneumonia regimen. RESULTS: Approximately 156,107 hospitalized patients who received care at a Veterans Affairs Hospital and were diagnosed with CAP during the study timeframe were included. A 17% decreased risk of CDI was identified with doxycycline compared to azithromycin when used with ceftriaxone for the treatment of pneumonia (P = .03). In patients who had a prior history of CDI, doxycycline decreased the incidence of CDI by 45% (odds ratio 0.55; P = .02). CONCLUSIONS: Doxycycline is associated with a lower risk of CDI compared to azithromycin when used for atypical coverage in CAP. Thus, patients who are at such risk may benefit from doxycycline as a first-line agent for atypical coverage, rather than the use of a macrolide antibiotic, if Legionella is not of concern.

Increased Myocardial Infarction Risk Following Herpes Zoster Infection.

Background: Myocardial infarction (MI) has been reported as a postinfection sequela of herpes zoster, but with limited data on incidence after zoster and protective effect of the zoster vaccine. This study investigates the risk of developing an MI 30 days postzoster, determines patient-specific risk factors, and investigates the impact of herpes zoster vaccination. Methods: This retrospective cohort study included patients who received care at a Veterans Affairs facility between 2015 and 2020. Time to MI was determined from either 30 days post-zoster infection (zoster cohort) or a primary care appointment (control cohort). Results: This study assessed a total of 2 165 584 patients. MI within 30 days occurred in 0.34% (n = 244) of the zoster cohort and 0.28% (n = 5782) of the control cohort (P = .0016). Patients with a documented herpes zoster infection during the study period were 1.35 times more likely to develop an MI within the first 30 days postinfection compared to the control cohort. Patients who received the recombinant zoster vaccine were less likely to have an MI postinfection (odds ratio, 0.82 [95% confidence interval, .74-.92]; P = .0003). Conclusions: Herpes zoster infection was associated with an increased risk of MI within the first 30 days postinfection. History of prior MI, male sex, age ≥50 years, history of heart failure, peripheral vascular disease, human immunodeficiency virus, prior cerebrovascular accident, and renal disease increased odds of MI 30 days postinfection with herpes zoster. Herpes zoster vaccination decreased the odds of developing an MI in patients aged ≥50 years.

Increased Stroke Risk Following Herpes Zoster Infection and Protection With Zoster Vaccine.

BACKGROUND: Studies evaluating stroke following varicella zoster virus (VZV) infection are limited, and the utility of zoster vaccination against this phenomenon is unclear. This study aimed to determine the risk of stroke 30 days following zoster infection and to evaluate the impact of zoster vaccinations on the risk of stroke in VZV-infected patients. METHODS: This retrospective case-control study was conducted from January 2010 to January 2020 utilizing nationwide patient data retrieved from the Veterans Affairs' Corporate Data Warehouse. RESULTS: A total of 2 165 505 patients ≥18 years of age who received care at a Veterans Affairs facility were included in the study, of whom 71 911 had a history of zoster infection. Zoster patients were found to have 1.9 times increased likelihood of developing a stroke within 30 days following infection (odds ratio [OR], 1.93 [95% confidence interval {CI}, 1.57-2.4]; P < .0001). A decreased risk of stroke was seen in patients who received the recombinant zoster vaccine (OR, 0.57 [95% CI, .46-.72]; P < .0001) or the live zoster vaccine (OR, 0.77 [95% CI, .65-.91]; P = .002). CONCLUSIONS: Patients had a significantly higher risk of stroke within the first month following recent herpes zoster infection. Receipt of at least 1 zoster vaccination was found to mitigate this increased risk. Vaccination may therefore be viewed as a protective tool against the risk of neurologic postinfection sequelae.

Risk factors associated with mortality in hospitalized patients with laboratory confirmed SARS-CoV-2 infection during the period of omicron (B.1.1.529) variant predominance.

BACKGROUND: SARS-CoV-2 Omicron variant has a high transmission rate. In December 2021, Omicron became the dominant variant and quickly accounted for majority of infections in the United States. Drug shortages have led to prioritization of patients for COVID-19 treatment based on risk factors for severe disease. METHODS: A retrospective analysis of hospitalized patients with COVID-19 infection at Veteran Affairs Healthcare System across the United States. The primary outcome was 14-day all-cause mortality after the first documented positive SARS-CoV-2 laboratory test. Odds ratios were generated from a multivariate logistic regression of significant factors. RESULTS: This study included 12,936 COVID-19 inpatients during a period of Omicron predominance. Age ≥ 65 years is a predictor of 14-day mortality among the vaccinated and unvaccinated population (OR 4.05, CI 3.06-5.45, P ≤ .0001). Triple vaccinated patients demonstrated a 52% decreased risk of death with COVID-19 infection (OR 0.48, CI 0.37-0.61, P ≤ .0001). Patients who were double vaccinated had a 39% decreased risk of death with COVID-19 infection (OR 0.61, CI 0.46-0.80, P = .003). CONCLUSION: Advanced age ≥ 65 is the greatest risk factor for mortality in hospitalized COVID-19 patients. COVID-19 vaccination, especially booster doses, was associated with a decreased risk of 14-day mortality compared to double vaccinated or non-vaccinated patients. Results of this study suggest that advanced age should be considered first for prioritization of COVID-19 treatments for Omicron.

Outcomes of multiple sclerosis patients admitted with COVID-19 in a large veteran cohort.

BACKGROUND: Given concerns over immune function, the decision whether to continue disease modifying therapy (DMT) in multiple sclerosis (MS) patients during the COVID-19 pandemic has been challenging, complicated by the risk of MS disease progression in the absence of treatment. METHODS: This retrospective analysis of patients treated for COVID-19 infection at veteran affairs healthcare systems across the United States, investigated 30-day all-cause mortality after first positive COVID-19 in patients with and without MS. We examined mortality risk impact of disease modifying therapy for MS, accounting for other relevant factors known to be associated with COVID-19 mortality. Patients were propensity score matched in a 1:20 fashion based on MS diagnosis. RESULTS: 49,737 COVID-19 inpatient cases were identified, of which 258 were diagnosed with MS. In the propensity score matched cohort, MS patients taking DMT (excluding those receiving anti-CD20 antibodies) had a lower odds of 30 day mortality (OR: 0.18 [95%CI: 0.00988-0.94] p=0.041). Similarly, in the unmatched cohort, patients on DMT had a lower risk of death (OR: 0.16 [95%CI: 0.01-0.82] p=0.023). There was no statistically significant difference in mortality between those with and without MS. In the propensity matched cohort, age over 65, heart failure, chronic kidney disease (CKD), and diabetes increased the risk of mortality while vaccination reduced the risk of mortality. CONCLUSION: Veteran patients with MS hospitalized for COVID-19 were less likely to die when taking DMTs (excluding those receiving anti-CD20 antibodies), accounting for other relevant factors. Results suggest that, in relation to the COVID-19 pandemic, not only is it safe to continue most DMTs in people with MS, but it may be beneficial given the decreased risk of COVID-19 mortality and decreased risk of MS disease progression.

Admissions and Mortality Related to Urinary Tract Infections in Male Veterans with Dementia.

Objective To examine mortality and hospital readmission rates in male veterans with dementia diagnosed with urinary tract infection (UTI) compared with patients without dementia. Design Retrospective cohort study. Setting Veterans Healthcare Systems (VA). Participants Male inpatients with a diagnosis of UTI who were treated at any VA Healthcare Center from January 1, 2009, to December 31, 2018. Interventions None. Main Outcome Measures Mortality and hospital readmission for patients with and without dementia at 30, 60, and 90 days from UTI diagnosis. Results 262,515 veterans admitted with UTI were analyzed, and 58,940 (22.5%) had dementia. The mean age for veterans with dementia was 80.0 +/- 9.7 years. Veterans with dementia experienced less mortality than patients without dementia at 30 days (8.3% vs 8.5%; P < 0.001), but more mortality at 60-day (4.9% vs 4.7%; P < 0.001) and 90-day (3.6% vs 3.3%; P < 0.001) intervals. Death was 20% less likely at 30 days in patients with dementia. Veterans with dementia were readmitted more than those without dementia at 30-day (18.4% vs 16.0%), 60-day (4.5% vs 2.8%), and 90-day (3.4% vs 2.5%) intervals; P < 0.0001. Conclusion Though patients with dementia are at an increased risk for death long-term, risk of death is less than those without dementia shortly following UTI diagnosis. This highlights the possibility that veterans with dementia may be hospitalized and diagnosed with UTIs when in actuality they have asymptomatic bacteriuria. Patients with dementia and UTI therefore represent an important group of geriatric patients that could benefit from the oversight of a senior care pharmacist to help prevent unnecessary treatment of asymptomatic bacteriuria.

Smoking status related to Covid-19 mortality and disease severity in a veteran population.

INTRODUCTION: Cigarette smoking is associated with development of significant comorbidities. Patients with underlying comorbidities have been found to have worse outcomes associated with Coronavirus Disease 2019 (Covid-19). This study evaluated 30-day mortality in Covid-19 positive patients based on smoking status. METHODS: This retrospective study of veterans nationwide examined Covid-19 positive inpatients between March 2020 and January 2021. Bivariate analysis compared patients based on smoking history. Propensity score matching adjusted for age, gender, race, ethnicity, Charlson comorbidity index (0-5 and 6-19) and dexamethasone use was performed. A multivariable logistic regression with backwards elimination and Cox Proportional Hazards Ratio was utilized to determine odds of 30-day mortality. RESULTS: The study cohort consisted of 25,958 unique Covid-19 positive inpatients. There was a total of 2,995 current smokers, 12,169 former smokers, and 8,392 non-smokers. Death was experienced by 13.5% (n = 3503) of the cohort within 30 days. Former smokers (OR 1.15; 95% CI, 1.05-1.27) (HR 1.13; 95% CI, 1.03-1.23) had higher risk of 30-day mortality compared with non-smokers. Former smokers had a higher risk of death compared to current smokers (HR 1.16 95% CI 1.02-1.33). The odds of death for current vs. non-smokers did not significantly differ. CONCLUSION: Compared to veteran non-smokers with Covid-19, former, but not current smokers with Covid-19 had a significantly higher risk of 30-day mortality.

Open-source maximum a posteriori-bayesian dosing AdDS to current therapeutic drug monitoring: Adapting to the era of individualized therapy.

Recent updates in the therapeutic drug monitoring (TDM) guidelines for vancomycin have rekindled interest in maximum a posteriori-Bayesian (MAP-Bayesian) estimation of patient-specific pharmacokinetic parameters. To create a versatile infrastructure for MAP-Bayesian dosing of vancomycin or other drugs, a freely available, R-based software package, Advanced Dosing Solutions (AdDS), was created to facilitate clinical implementation of these improved TDM methods. The objective of this study was to utilize AdDS for pre- and post-processing of data in order to streamline the therapeutic management of vancomycin in healthy and obese veterans. Patients from a local Veteran Affairs hospital were utilized to compare the process of full re-estimation versus Bayesian updating of priors on healthy adult and obese patient populations for use with AdDS. Twenty-four healthy veterans were utilized to train (14/24) and test (10/24) the base pharmacokinetic model of vancomycin while comparing the effects of updated and fully re-estimated priors. This process was repeated with a total of 18 obese veterans for both training (11/18) and testing (7/18). Comparison of MAP objective function between the original and re-estimated models for healthy adults indicated that 78.6% of the subjects in the training and 70.0% of the subjects in the testing datasets had similar or improved predictions by the re-estimated model. For obese veterans, 81.8% of subjects in the training dataset and 85.7% of subjects in the testing dataset had similar or improved predictions. Re-estimation of model parameters provided more significant improvements in objective function compared with Bayesian updating, which may be a useful strategy in cases where sufficient samples and subjects are available. The generation of bespoke regimens based on patient-specific clearance and minimal sampling may improve patient care by addressing fundamental pharmacokinetic differences in healthy and obese veteran populations.

Trends in beta-hemolytic Streptococcus infections within Veterans' Affairs medical centers from 2009 to 2018.

OBJECTIVE: The purpose of this study was to describe the recent trends of invasive and noninvasive ß-hemolytic Streptococcus cultures in the Veterans' Affairs (VA) cohort from 2009 to 2018. DESIGN: Retrospective cohort study from January 1, 2009, to January 1, 2019. SETTING: Veterans' Affairs medical centers. PATIENTS OR PARTICIPANTS: All patients aged 18 years and older with cultures positive for ß-hemolytic Streptococcus at a VA facility were included in the study. INTERVENTION(S): Data were retrieved from the VA Corporate Data Warehouse using structure query language through the SQL Server Management Studio software. RESULTS: Between 2009 and 2018, there were 40,625 patients with cultures with ß-hemolytic Streptococcus. The median age was 64 years (interquartile range [IQR], 55-71) and the median Charlson comorbidity index was 4 (IQR, 2-7). Distributions for each type of ß-hemolytic Streptococcus based on site of culture are provided. The 30-day all-cause mortality rate from all invasive ß-hemolytic Streptococcus cases was 2.3%, and the 90-day all-cause mortality rate was 4.4%. The 30- and 90-day all-cause mortality rates for Streptococcus cases were higher for group A (3.9% and 6.1% respectively) and for groups C and G combined (3.2% and 6.1%, respectively) than for group B (2.0% and 4.0%, respectively). CONCLUSIONS: Trends of cultures for invasive and noninvasive ß-hemolytic Streptococcus suggest an association with disease and mortality. The burden associated with ß-hemolytic Streptococcus infections should not be underestimated.

Societal factors contributing to infections caused by Chlamydia trachomatis and Neisseria gonorrhoeae in a veteran population.

BACKGROUND: Veterans have a higher incidence of sexually transmitted infections (STIs) compared to the general population. The objective of this study is to evaluate the association of societal factors on the risk of chlamydia or gonorrhea. METHODS: This retrospective cohort study evaluated data from Veteran Health Administration. Patients tested for chlamydia or gonorrhea between January 2009 and January 2019 were included. Descriptive statistics and regression were used to evaluate societal factors. RESULTS: A total of 1,232,173 tests for chlamydia or gonorrhea were performed. There were 51,987 (4.2%) positive cases with 74.18% for chlamydia and 24.96% for gonorrhea. In 13.6% of veterans with reported military sexual trauma, there was no difference in risk of positivity (p = 0.39). Veterans with a history of combat had lower odds of testing positive (OR, 0.94; 95% CI, 0.91-0.97). Tests in veterans who were married had a 24% less chance of positivity (OR, 0.76; 95% CI, 0.74-0.79) compared to tests in divorced veterans. Positive number of cases increased each year. CONCLUSION: Sexually transmitted infections are a growing concern. Gender, age, ethnicity, marital status, and race are societal identifiers which influence likelihood of STI acquisition.

Risk Factors for Mortality in an Older Veteran Population With infective Endocarditis.

OBJECTIVE: To determine 30-day and 1-year mortality in patients treated for infective endocarditis (IE) in a VA population. The secondary objective was to identify risk factors for increased risk of mortality in veterans diagnosed with IE. DESIGN: A retrospective cohort study. SETTING: Veterans Affairs Western New York Healthcare System PARTICIPANTS: Patients who had a diagnosis of IE between the years 2005 and 2016. Patients were identified via International Classification of Diseases (ICD) codes. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Factors for death and survival were compared using a bivariate analysis. Significant factors were built into a multivariate logistic regression analysis to determine risk factors for death at 30 days and 1 year. RESULTS: Between 2005 and 2016, there were 153 patients with IE. All-cause mortality at 30 days was 14% versus 39% at 1 year. Patients were more likely to die at 1 year with higher Pitt Bacteremia Scores, older age, and lower number of minor criteria according to Duke Criteria. Comorbidities were similar between groups. CONCLUSIONS: Older patients with higher Pitt Bacteremia Scores and lower numbers of minor criteria are more likely to experience mortality at one year. Given the high rates of death at one year, close monitoring, even after completion of therapy may be necessary in older patients. Senior care pharmacists are in a unique position to monitor these patients.

Clinical Course and Outcome of COVID-19 Acute Respiratory Distress Syndrome: Data From a National Repository.

BACKGROUND: Mortality attributable to coronavirus disease-19 (COVID-19) 2 infection occurs mainly through the development of viral pneumonia-induced acute respiratory distress syndrome (ARDS). RESEARCH QUESTION: The objective of the study is to delineate the clinical profile, predictors of disease progression, and 30-day mortality from ARDS using the Veterans Affairs Corporate Data Warehouse. STUDY DESIGN AND METHODS: Analysis of a historical cohort of 7,816 hospitalized patients with confirmed COVID-19 infection between January 1, 2020, and August 1, 2020. Main outcomes were progression to ARDS and 30-day mortality from ARDS, respectively. RESULTS: The cohort was comprised predominantly of men (94.5%) with a median age of 69 years (interquartile range [IQR] 60-74 years). 2,184 (28%) were admitted to the intensive care unit and 643 (29.4%) were diagnosed with ARDS. The median Charlson Index was 3 (IQR 1-5). Independent predictors of progression to ARDS were body mass index (BMI) ≥40 kg/m2, diabetes, lymphocyte counts <700 × 109/L, LDH >450 U/L, ferritin >862 ng/ml, C-reactive protein >11 mg/dL, and D-dimer >1.5 ug/ml. In contrast, the use of an anticoagulant lowered the risk of developing ARDS (OR 0.66 [95% CI 0.49-0.89]. Crude 30-day mortality rate from ARDS was 41% (95% CI 38%-45%). Risk of death from ARDS was significantly higher in those who developed acute renal failure and septic shock. Use of an anticoagulant was associated with 2-fold reduction in mortality. Survival benefit was observed in patients who received corticosteroids and/or remdesivir but there was no advantage of combination therapy over either agent alone. CONCLUSIONS: Among those hospitalized for COVID-19, nearly 1 in 10 progressed to ARDS. Septic shock, and acute renal failure are the leading causes of death in these patients. Treatment with either remdesivir and corticosteroids reduced the risk of mortality from ARDS. All hospitalized patients with COVID-19 should be placed at a minimum on prophylactic doses of anticoagulation.

Sputum susceptibilities in a nationwide veteran cohort.

BACKGROUND: Respiratory infections are one of the most common causes of morbidity and mortality. This study examined antimicrobial susceptibility of common respiratory isolates from veterans. METHODS: Sputum culture data from the Veteran Health Administration were obtained retrospectively between January 2009 and 2019. Cumulative antibiograms were constructed for bacterial isolate susceptibility. RESULTS: Sputum and bronchial cultures from approximately 10,345 veterans were included each year. Haemophilus influenzae has maintained high levels of susceptibility to third generation cephalosporins from 2009 (99.7%) to 2018 (97.2%). Third generation cephalosporin susceptibilities amongst Klebsiella pneumoniae have trended upward from 2009 to 2018 as well (79.1% vs 86.4%). In Pseudomonas aeruginosa isolates, there has been an increase in susceptibility rates to cefepime from 2009 to 2018 (79.6%, to 86.6%), gentamicin (81.5% to 89.1%), and piperacillin/tazobactam (86.5% to 90%). Fluoroquinolone susceptibilities amongst Escherichia coli have remained low but stable between 2009 and 2018. Third generation cephalosporin susceptibilities for S. pneumoniae improved slightly from 92.2% to 95% between 2009 and 2018 while susceptibility to azithromycin trended down slightly from 56.8% in 2009 to 51.7% in 2018 for S. pneumoniae. DISCUSSION: The antibiogram of sputum isolates from the VA Healthcare System were examined to determine changes in patterns of resistance over a decade of use. CONCLUSIONS: This large-scale study investigated nationwide sputum culture susceptibility trends. Avoidance of macrolides for empiric treatment of community acquired pneumonia and avoidance of fluoroquinolones for empiric treatment of hospital acquired or ventilator associated pneumonia may be warranted based on susceptibility trends.

Combatting the Rising Tide of Antimicrobial Resistance: Pharmacokinetic/Pharmacodynamic Dosing Strategies for Maximal Precision.

OBJECTIVE: Antimicrobial pharmacokinetics/pharmacodynamics (PK/PD) principles and PK/PD models have been essential in characterizing the mechanism of antibiotic bacterial killing and determining the most optimal dosing regimen that maximizes clinical outcomes. This review summarized the fundamentals of antimicrobial PK/PD and the various types of PK/PD experiments that shaped the utilization and dosing strategies of antibiotics today. METHODS: Multiple databases - including PubMed, Scopus, and EMBASE - were searched for published articles that involved PK/PD modelling and precision dosing. Data from in vitro, in vivo and mechanistic PK/PD models were reviewed as a basis for compiling studies that guide dosing regimens used in clinical trials. RESULTS: Literature regarding the utilization of exposure-response analyses, mathematical modelling and simulations that were summarized are able to provide a better understanding of antibiotic pharmacodynamics that influence translational drug development. Optimal pharmacokinetic sampling of antibiotics from patients can lead to personalized dosing regimens that attain target concentrations while minimizing toxicity. Thus the development of a fully integrated mechanistic model based on systems pharmacology can continually adapt to data generated from clinical responses, which can provide the framework for individualized dosing regimens. CONCLUSIONS: The promise of what PK/PD can provide through precision dosing for antibiotics has not been fully realized in the clinical setting. Antimicrobial resistance, which has emerged as a significant public health threat, has forced clinicians to empirically utilize therapies. Future research focused on implementation and translation of PK/PD-based approaches integrating novel approaches that combine knowledge of combination therapies, systems pharmacology and resistance mechanisms are necessary. To fully realize maximally precise therapeutics, optimal PK/PD strategies are critical to maximize antimicrobial efficacy against extremely-drug-resistant organisms, while minimizing toxicity.

Antimicrobial susceptibility trends for urinary isolates in the veteran population.

BACKGROUND: Guidance on empiric treatment for urinary tract infections (UTIs) is lacking for the male population which comprises much of the Veteran population in the United States. This study evaluated susceptibility trends in antimicrobials used for treatment of UTIs in the inpatient and outpatient Veteran population nationwide. METHODS: Urine culture data was retrospectively obtained from Corporate Data Warehouse. All urine cultures from Veteran Health Administration patients 18 years of age or older who were treated at any VA health care center in the years 2009 and 2018 were eligible. Antibiograms were constructed for bacterial isolate susceptibility. RESULTS: In 2009 and 2018 isolates from 54,788 and 58,983 Veterans were analyzed, respectively. Escherichia coli was the most common bacteria isolated. For ceftriaxone, E coli susceptibilities were relatively high but trended downward from 2009 to 2018. Common urinary pathogen susceptibilities remained low for fluoroquinolones and trimethoprim-sulfamethoxazole. DISCUSSION: Empiric therapy for Veterans with UTIs should be based on local susceptibility patterns as previously recommended first-line agents have fallen out of favor due to increasing resistance rates. CONCLUSIONS: Both inpatient and outpatient stewardship is needed to ensure appropriate treatment, as viable treatment options for UTIs are becoming increasingly limited.

Comparison of in-hospital mortality risk prediction models from COVID-19.

OBJECTIVE: Our objective is to compare the predictive accuracy of four recently established outcome models of patients hospitalized with coronavirus disease 2019 (COVID-19) published between January 1st and May 1st 2020. METHODS: We used data obtained from the Veterans Affairs Corporate Data Warehouse (CDW) between January 1st, 2020, and May 1st 2020 as an external validation cohort. The outcome measure was hospital mortality. Areas under the ROC (AUC) curves were used to evaluate discrimination of the four predictive models. The Hosmer-Lemeshow (HL) goodness-of-fit test and calibration curves assessed applicability of the models to individual cases. RESULTS: During the study period, 1634 unique patients were identified. The mean age of the study cohort was 68.8±13.4 years. Hypertension, hyperlipidemia, and heart disease were the most common comorbidities. The crude hospital mortality was 29% (95% confidence interval [CI] 0.27-0.31). Evaluation of the predictive models showed an AUC range from 0.63 (95% CI 0.60-0.66) to 0.72 (95% CI 0.69-0.74) indicating fair to poor discrimination across all models. There were no significant differences among the AUC values of the four prognostic systems. All models calibrated poorly by either overestimated or underestimated hospital mortality. CONCLUSIONS: All the four prognostic models examined in this study portend high-risk bias. The performance of these scores needs to be interpreted with caution in hospitalized patients with COVID-19.

An Evaluation of Antimicrobial Prophylaxis for Dental Procedures at a Veterans Healthcare System; A Role for Senior Care Pharmacists?

OBJECTIVE: The primary objective of this study was to determine the prevalence of appropriate use of antibiotics before a dental procedure.
DESIGN: Retrospective cohort study.
SETTING: Veterans Healthcare Systems.
PARTICIPANTS: Veterans who filled outpatient prescriptions for antimicrobial dental prophylaxis at the Veterans Administration Western New York Healthcare System from December 1, 2017, through October 1, 2019.
INTERVENTIONS: None.
MAIN OUTCOME MEASURES: Use of antibiotic dental prophylaxis was deemed appropriate if in accordance with guideline recommendations. Descriptive statistics were used to summarize data.
RESULTS: A total of 130 veterans receiving antibiotics for dental prophylaxis were included in this evaluation. Of those who were included, only 16.9% received appropriate antibiotic dental prophylaxis. Patients with a prosthetic joint were significantly more likely to be inappropriately prescribed antibiotics for dental prophylaxis. Approximately 87% of patients who were inappropriately prescribed antibiotic prophylaxis had prosthetic joints (P < .0001).
CONCLUSION: Most antibiotics for dental prophylaxis are prescribed inappropriately. The large amount of inappropriately used antibiotics in this study highlights the need for dental stewardship in our veteran population. Antibiotics for dental prophylaxis therefore represent an important stewardship target in the outpatient setting. This may be an ideal opportunity for senior care pharmacists to intervene upon.