Significant Publications on Infectious Diseases Pharmacotherapy in 2022.

Purpose: To provide summarization of the most significant infectious diseases (ID) pharmacotherapy articles published in peer-reviewed literature in 2022. Summary: Members of the Houston Infectious Diseases Network (HIDN) nominated notable articles providing significant contributions to ID pharmacotherapy in 2022. Article nominations included those pertaining to general ID, as well as those including coronavirus disease 2019 (COVID-19), and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) pharmacotherapy. A total of 71 articles were nominated by HIDN. Members: 68 articles pertaining to general ID pharmacotherapy and 3 articles focusing on HIV/AIDS. To aid selection of the most these most notable articles of 2022, a survey was created and distributed to members of the Society of Infectious Diseases Pharmacists (SIDP). Of the 153 SIDP members who participated in the survey, there were 128 recorded votes for the top 10 general ID pharmacotherapy articles and 30 votes recorded for the top HIV/AIDS article. The most notable publications are summarized. Conclusion: Post pandemic significant advances in antimicrobial stewardship and infectious disease states continues to occur in a world recently focused on the coronavirus disease 2019 (COVID-19) global pandemic. Continuous growth in publication of ID-related articles over the past year lends towards the aims of this review to aid clinicians in remaining current on key practice-changing ID pharmacotherapy publications from 2022.

Impact of a pharmacy resident on a transitions of care rotation for inpatients enrolled in an outpatient parenteral antimicrobial therapy (OPAT) program.

A novel pharmacy residency rotation was created to meet the needs of patients enrolled in an outpatient parenteral antimicrobial therapy (OPAT) program but not yet discharged from the inpatient setting. This service resulted in a high number of antimicrobial stewardship interventions identified and accepted by the primary team(s).

Value of a Pharmacy-Adjudicated Community Care Prior Authorization Drug Request Service.

Background: Many veterans are eligible to receive prescriptions from community-based pharmacies. Swift and accurate review of prior authorization drug requests by the US Department of Veterans Affairs (VA) pharmacy is necessary to mitigate treatment delays, medication misuse, adverse drug events, medication errors, and unnecessary cost to the health care system. Methods: We performed a retrospective review of community care prior authorization drug requests to assess the direct cost savings achieved through a centralized process and to characterize submitted requests. Results: The centralized community care pharmacy team demonstrated a cost savings of $515,872.31 over 6 months and increased patient safety. Community care prior authorization drug requests had a 46.2% approval rate. Coordination of care took an average of 8 days. Conclusions: Use of a centralized community care pharmacy team could result in significant annual cost savings for the VA. Considering the approval rate seen in this study, VA could allocate resources to educate community-based prescribers about its formulary to increase the approval rate and reduce administrative burden for VA pharmacies and prescribers.

Antibiotic Stewardship and Inpatient Clostridioides difficile Testing in Solid Organ Transplant Recipients: The Need for Multilevel Checks and Balances.

BACKGROUND: Diarrhea among recipients of solid organ transplants is a commonly encountered problem and is often multifactorial in etiology. Owing to the combination of perioperative antibiotic administration and the immunosuppressed status of transplant recipients, a high degree of suspicion for Clostridioides difficile (C. difficile) colitis is prudent. The purpose of this study is to demonstrate the association of an institutional integrated stewardship program with C. difficile testing practices after abdominal solid organ transplantation. METHODS: Starting in July 2017, a diagnostic stewardship was enacted in our institution requiring the ordering provider to answer a series of questions within the electronic medical record before ordering a C. difficile toxin test. The charts were reviewed for all solid organ transplant recipients on whom a test was ordered between January 2016 and September 2019. RESULTS: Orders for C. difficile toxin per quarter significantly decreased in the postintervention era (18 vs 8.5, P = .038). Median cost of inpatient treatment and days of therapy per thousand patient days was significantly lower in the postintervention era (median cost, $2,944.55 vs $416.92; P = .01) (days of therapy per thousand patient days, 521.9 vs 300.5; P < .01). Quarterly rates of negative tests were similar between the pre- and postintervention eras (65% vs 73%, P = .38). CONCLUSIONS: Although no orders were blocked based on the responses, this multilevel intervention was associated with a 47% decrease in C. difficile testing without effecting the rate of negative testing. These results suggest that we have achieved significant cost savings, in testing and isolation, without sacrificing critical aspects of clinical care.

Development of a specialty medication clinical dashboard to improve tumor necrosis factor-α inhibitor safety and adherence monitoring.

PURPOSE: To describe the development of a pilot specialty medication clinical dashboard targeting tumor necrosis factor (TNF)-α inhibitor therapy. SUMMARY: This was a quality improvement project conducted between August 2019 and April 2020. The dashboard was designed with collaboration between clinical pharmacists and specialty providers in rheumatology, gastroenterology, and dermatology. Data was queried from the Veterans Affairs Corporate Data Warehouse. Patients with an active prescription or intravenous order for a TNF-α inhibitor were included. Dashboard flag criteria focused on TNF-α inhibitor safety and adherence monitoring. Flag results from the dashboard were characterized from data captured at a single time point. For 431 patients on TNF-α inhibitor treatment at the institution, 304 flags corresponding to 223 unique patients (51.7%) were identified on the dashboard: 3% of patients had a new infection, 9% had overdue monitoring laboratory tests, 5% had a critical laboratory result, 2% were on 2 biologic agents, 27% were overdue for a refill, 6% had an emergency department visit, and 2% had an inpatient admission. No patients were flagged for heart failure exacerbation or new malignancy. Seventeen percent of patients were prescribed high-dose etanercept or adalimumab, representing a potential annual cost savings of $302,497 if 50% of these patients had their dose successfully reduced to labeled dosing. Opportunities for pharmacist intervention utilizing the dashboard were identified and characterized through chart review of flagged patients. CONCLUSION: Pharmacists have the opportunity to improve safety and adherence for TNF-α inhibitor therapy through use of a specialty medication clinical dashboard. The dashboard should be used in conjunction with collaborative practice protocols.

Methylphenidate use in geriatric depression: A systematic review.

OBJECTIVES: Geriatric depression is common and is often associated with coexisting medical illnesses, cognitive dysfunction, or both. Treatment with pharmacotherapy is usually required, and many patients may not respond to initial therapy. Thus, there is a need for adjunctive treatment options. The objective of this systematic review is to assess the efficacy and safety of methylphenidate (MPH) in the treatment of geriatric depression. METHODS: PubMed (1946-December 2020) and Embase (1947-December 2020) were queried using the following search terms: geriatrics, aged, geriatric patient, or elderly and depressive disorder, depression, major depression or late-life depression, and MPH. Studies were included if they were a randomized-controlled trial or open-label trial that investigated use of MPH for treatment of depression in adults aged 60 years and older. RESULTS: After screening per the inclusion criteria, five prospective trials were included. All studies found improvement in depressive symptoms with use of MPH or MPH combined with citalopram. Study durations ranged from 8 to 16 weeks and MPH dosing ranged from 5 to 90 mg per day. CONCLUSIONS: Based on the reviewed literature, MPH appears to be most effective when combined with citalopram and used short-term. MPH should be initiated at a low dose and titrated up to 10 or 20 mg per day based on response. Larger, long-term trials are needed to further define the role of MPH in this population.

Proton pump inhibitor usage reduces sustained viral response rates for veterans with HIV/HCV coinfection on ledipasvir/sofosbuvir: a real-world study from a multicentre VA cohort.

Previous studies have reported an association of proton pump inhibitor (PPI) use and decreased sustained viral response rate (SVR) in patients taking ledipasvir/sofosbuvir (LDV/SOF). The relationship between PPI usage and SVR is less clear in patients with HIV/HCV coinfection, where concomitant antiretrovirals may result in more complex drug interactions. This retrospective study evaluates the effects of acid suppression medications (PPI or H2 -receptor antagonist [H2 B]) use and SVR rates in patients with HIV/HCV or HCV and taking LDV/SOF in a large multicentre veteran cohort. Patients in the Veterans Affairs Health Care System who received LDV/SOF ± ribavirin from 10/10/2014 to 12/31/2015 were included. The odds ratios (OR) of PPI or H2 B use for SVR were adjusted for clinical factors and with inverse probability of treatment weighting for non-random treatment selection for acid suppression medication use. There were 9703 veterans included in our final analysis. After adjustment of other clinical factors, PPI use is associated with a lower SVR in the overall cohort (95.0% vs. 96.1%, OR: 0.86, 95% CI: 0.74-0.99, p = .03, number needed to harm 90.9) and HIV/HCV coinfection subgroup (93.4% vs. 96.9%, OR: 0.47, 95% CI: 0.26-0.85, p = .01, number needed to harm 28.6). This present study reveals PPI use is associated with reduced SVR after LDV/SOF treatment, with a more significant impact in the subgroup of patients with HIV/HCV coinfection. Precautions need to be taken when using PPI and LDV/SOF in this group of patients.

Significant Publications on Infectious Diseases Pharmacotherapy in 2019.

PURPOSE: To provide a summary of the most prominent peer-reviewed infectious diseases (ID) pharmacotherapy and Human Immunodeficiency Virus (HIV)-related articles published in 2019. SUMMARY: Houston Infectious Diseases Network (HIDN) members were asked to nominate articles that they believed were most influential within the ID and HIV pharmacotherapy science communities. A total of 48 general ID and 6 HIV-related articles were nominated. Following nominations, an online survey was distributed via e-mail to Society of Infectious Diseases Pharmacists (SIDP) members, with a total of 156 and 54 members voting for general ID and HIV-related articles, respectively. The results of this survey were ranked to determine the top 10 general ID and top HIV articles. The top articles were then summarized by HIDN members, including residents, fellows, and clinical pharmacists. CONCLUSION: This review covers many of the most influential ID articles published in 2019, including 3 practice guideline updates. Due to the high rate of ID literature published each year, this review continues to help summarize these articles for the ID community, allowing clinicians to remain up-to-date on practice-changing publications in ID and HIV pharmacotherapy.

Standard Versus Extended Duration Direct-Acting Antiviral Therapy in Hepatitis C Patients With Slow Response to Treatment.

BACKGROUND: Response-guided hepatitis C therapy was standard with interferon-based regimens but is not used for direct-acting antivirals (DAAs). Week 4 viral kinetics may predict sustained virological response (SVR) with DAAs, but it is unclear whether extending therapy in slow responders affects outcomes. OBJECTIVES: The primary objective was to compare SVR rates between traditional and extended duration groups. Secondary objectives were to compare SVR rates among subgroups and to determine factors associated with SVR. METHODS: This institutional review board-approved, retrospective, single-center study identified patients with chronic hepatitis C virus (HCV) infection with detectable week 4 HCV RNA who were treated with DAAs. Patients were excluded for early discontinuation, treatment regimen not recommended first-line, or missing HCV RNA labs. Patients were stratified into traditional and extended duration groups. The primary end point was SVR. Secondary end points included factors associated with SVR and rationale for extension of therapy duration. RESULTS: A total of 363 patients were included; 58 (16%) received extended therapy. Patients were primarily genotype 1a (70%) and treatment naïve (80%). More than half had advanced fibrosis or cirrhosis. SVR12 rates were 100% in the extended duration group and 96.7% in the traditional duration group (P = 0.37). There were no associations with SVR and prespecified patient-specific factors. Sample size was limited. CONCLUSION AND RELEVANCE: Based on these findings, a recommendation for extension of therapy cannot be made for patients with detectable HCV RNA at week 4 of treatment at this time. Cost analyses may help guide recommendations to re-treat rare failures versus extend therapy in all slow responders.

Comparative-effectiveness of ceftaroline and daptomycin as first-line MRSA therapy for patients with sepsis admitted to hospitals in the United States Veterans Health Care System.

Objectives: This study compared hospital readmission and mortality for patients with sepsis who received ceftaroline or daptomycin as first-line MRSA therapy.Methods: This retrospective comparative-effectiveness study included adults ≥18 years old hospitalized in the United States Veterans Health Care System with sepsis between 10/1/2010-9/30/2014, who received ceftaroline or daptomycin within 14 days of hospital admission as the first antibiotic effective against methicillin resistant Staphylococcus aureus (MRSA). Patients with pneumonia, and those who received both study drugs, were excluded. Baseline characteristics were compared using Chi-square, Fischer's exact, Student's t, and Wilcoxon Rank Sum tests. Patient outcomes were compared with multivariable logistic regression models.Results: 409 patients were included (ceftaroline = 67, daptomycin = 342). Ceftaroline patients were older, less likely to be Black, more likely to have diabetes with complications, and had higher Charlson comorbidity scores. Median (interquartile range) time from admission to drug initiation was 1 (0-1) day for ceftaroline and 1 (1-3) day for daptomycin (p = 0.01). Unadjusted hospital readmission rates for ceftaroline and daptomycin, respectively, were: 30-day (25%/37%, p = 0.06), 60-day (27%/44%, p = 0.008), and 90-day (28%/46%, p = 0.01). Unadjusted mortality rates were: in-hospital (7%/12%, p = 0.4), 30-day (3%/9%, p = 0.1), 60-day (6%/12%, p = 0.2), and 90-day (7%/15%, p = 0.1). In multivariable models with all divergent baseline characteristics included as covariates, patients treated with ceftaroline were less likely to experience (OR, 95% CI): 30/60/90-day hospital readmission (0.54, 0.29-0.98; 0.42, 0.23-0.76; 0.42, 0.23-0.75) and 30/60/90-day mortality (0.23, 0.04-0.82; 0.34, 0.10-0.93; 0.34, 0.11-0.86).Conclusion: In patients with sepsis, ceftaroline was associated with fewer hospital readmissions and lower mortality as compared to daptomycin. Prospective investigations in larger, more generalized cohorts are needed to examine outcomes with specific MRSA therapies.

Economic Outcomes Associated with Safety Interventions by a Pharmacist-Adjudicated Prior Authorization Consult Service.

BACKGROUND: The establishment of a formulary management system ensures that health care professionals work together in an integrated patient care process to promote clinically sound, safe, and cost-effective medication therapy. Pharmacists have a foundational role within this system. A pharmacist-adjudicated prior authorization drug request (PADR) consult service has the potential to optimize drug therapy by decreasing medication misuse, minimizing adverse drug events (ADEs), and preventing medication errors. OBJECTIVES: To (a) determine cost avoidance associated with pharmacist-adjudicated PADR safety interventions within the Durham Veterans Affairs Health Care System and (b) evaluate cost savings associated with pharmacist-adjudicated PADRs not approved due to a safety intervention, evaluate cost avoidance and direct cost savings based on clinical specialty of pharmacist adjudicating PADR, and characterize severity of avoided ADEs. METHODS: Pharmacist-adjudicated PADRs not approved between July 1, 2016, and June 30, 2017, because of safety interventions were retrospectively reviewed. Cost avoidance was determined by multiplying the probability of ADE occurrence in the absence of PADR safety intervention by the estimated cost avoided based on the type of intervention. Direct cost savings was calculated by totaling the cost of requested medications not approved for each PADR and subtracting the cost of recommended alternative therapies and cost of pharmacist PADR review. All potential ADEs avoided were reviewed by a panel of 3 clinical pharmacists to validate ADE classification and ADE probability and severity scores. Descriptive statistics were used for all analyses. RESULTS: Of the 910 PADRs that were not approved during the study period, 96 met inclusion criteria. Pharmacist-adjudicated PADR safety interventions resulted in a total cost avoidance of $24,485.34 (mean = $255.06) and a direct cost savings of $288,695.63 (mean = $3,007.25). The practice settings of anticoagulation and infectious diseases PADRs resulted in the largest contribution to cost avoidance and direct cost savings, respectively. Prevented ADEs were classified as major for 64.6% of the PADRs. CONCLUSIONS: Pharmacist-adjudicated PADR safety reviews resulted in substantial economic benefit and prevention of major ADEs. This analysis supports the pharmacist's role in a formulary management system to optimize medication therapy. DISCLOSURES: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for profit sectors. The authors have nothing to disclose.

Identifying and Treating Nonalcoholic Fatty Liver Disease.

NAFLD improves with 7% or greater weight loss.

Impact of Substance Use Disorder on the Rate of Sustained Virological Response in Veterans With Chronic Hepatitis C Treated With Direct-Acting Antivirals.

BACKGROUND: Substance use disorders (SUDs) are commonly encountered in patients with chronic hepatitis C virus (HCV) infection. It is important to consider the impact of SUDs on HCV treatment. OBJECTIVE: To compare the rate of clinical cure (sustained virological response at least 12 weeks after end of therapy [SVR12]) in veterans with chronic HCV infection treated with direct-acting antivirals (DAAs) with and without ongoing or recent substance use. METHODS: This single-center, retrospective cohort study evaluated 220 HCV patients treated with DAAs based on 2 groups: SUD (ongoing or recent substance use) or non-SUD (without ongoing or recent substance use). The primary end point was SVR12 achievement. Secondary end points included safety, adherence, early discontinuation, SVR12 achievement among SUD subgroups, and enrollment in a SUD treatment program. RESULTS: Most patients were African American men with an average age of 60 years and infected with HCV genotype 1. Almost half of the patients had advanced fibrosis or cirrhosis. There was no difference in SVR12 between groups (SUD: 96.2%; non-SUD: 94.3%; P = 0.54). Overall, 35.5% of patients missed at least 1 dose of DAA therapy, with a significant difference noted between groups (SUD: 44.5%; non-SUD: 26.4%; P = 0.005). Early discontinuation of DAA therapy was similar between groups. SVR12 among SUD subgroups ranged from 92.9% to 100%. In the SUD group, 27.3% of patients were enrolled in a SUD treatment program. Conclusion and Relevance: This study suggests that recent/ongoing substance use does not affect achievement of clinical cure of chronic HCV and reinforces treatment in this patient population.

Evaluation of Inpatient Antimicrobial Regimens for Readmitted Outpatient Parenteral Antimicrobial Therapy Patients Receiving Daptomycin or Ertapenem for Ease of Administration.

BACKGROUND: Outpatient parenteral antimicrobial therapy (OPAT) allows for long-course intravenous treatment of infections without lengthy hospital stays. Upon discharge, antimicrobial therapy may be broadened for "ease" of once-daily administration (EOA). Patients requiring subsequent readmission can be tailored to pre-OPAT regimens to minimize adverse effects. This study assessed continuation of EOA regimens upon hospital readmission during or immediately after OPAT. METHODS: This was a retrospective review of adults enrolled in OPAT and discharged on ertapenem or daptomycin for EOA, defined by the terms "convenience" or "EOA" in OPAT notes or by switching to ertapenem or daptomycin upon OPAT enrollment despite adequate therapy with narrower-spectrum agents. The primary outcome was the percentage of patients readmitted during or after their OPAT course and maintained on an EOA regimen. Secondary outcomes included inpatient therapy cost, rates of Clostridioides difficile infection, and adverse events. RESULTS: Of 188 patients receiving an OPAT EOA regimen, 71 were readmitted, representing 113 unique readmissions. Patients were mostly males (81%) aged 57 years. The EOA regimens were continued in 27% of hospital readmissions. The Infectious Diseases (ID) team was consulted in 48% of readmissions, and the Antimicrobial Stewardship Program (ASP) intervened in 26%. Combined, this resulted in de-escalation in 28% of cases. Clostridioides difficile infections and adverse events occurred in 7% and 12% of readmissions, respectively. The median acquisition cost of inpatient EOA regimens was $150 per readmission. CONCLUSIONS: The OPAT EOA regimens were continued in 27% of hospital readmissions indicating a role for improved indication documentation and collaboration between ID services, ASPs, and OPAT teams.

Pharmacy resident involvement in prior-authorization drug request adjudication.

PURPOSE: Results of a study to determine economic outcomes of pharmacy residents' involvement in prior-authorization drug request (PADR) adjudication within a Veterans Affairs (VA) healthcare system are reported. METHODS: A retrospective review was conducted to identify PADRs adjudicated by pharmacy residents under a preceptor's supervision during the 2015-16 residency year. Only PADRs that were not approved as submitted (i.e., only those requiring formulary intervention) and that met other inclusion criteria were included in the analysis. Prior-authorization requests and adjudication decisions were characterized, and cost savings resulting from those decisions were calculated. RESULTS: Of the total of 752 PADRs adjudicated by 6 pharmacy residents during the study period, 42 met the inclusion criteria. About 90% of included PADRs were categorized as general medicine requests, and 9.5% were for oncology medications. The most common rationale for PADR nonapproval (cited in 60% of requests) was the availability of a preferred formulary alternative; the remainder of nonapprovals were due to medication safety concerns (e.g., contraindication to therapy, drug interaction potential, likelihood of adverse drug event resulting in patient harm, history of allergy to requested medication). Resident adjudication of PADRs resulted in total direct cost savings of $169,877.53 over the 12-month period, a mean of $4,044.70 per request. CONCLUSION: Pharmacy residents' involvement in adjudicating PADRs at a VA healthcare system resulted in substantial cost savings over the course of the residency year.

Incidence of Drug Interactions Identified by Clinical Pharmacists in Veterans Initiating Treatment for Chronic Hepatitis C Infection.

BACKGROUND: Many direct-acting antivirals (DAAs) have drug-drug interactions (DDIs) with the potential to affect efficacy and safety. OBJECTIVE: To describe the incidence and severity of DDIs with DAAs identified by the hepatitis C virus (HCV) clinical pharmacist within a Veterans Affairs health care system. METHODS: This single-center, retrospective cohort study evaluated patients with HCV treated with DAA therapy. Primary end points included the total number of identified DDIs, percentage of patients with at least 1 DDI, mean number of DDIs per patient, and the number of DDIs by severity category. Additional end points included characterization of interacting drugs, clinical consequence of interaction, intervention recommended, acceptance rate of actionable recommendations, and achievement of sustained virological response 12 weeks after treatment (SVR12). RESULTS: A total of 300 patients were included. There were 554 identified DDIs, and 80.3% of patients had at least 1 DDI, with an average of 1.85 DDIs per patient; 76% of the DDIs identified were categorized as either a potentially clinically significant or critical interaction. The most common DDIs involved acid suppression agents (20%). Patient monitoring was the most commonly recommended intervention (59%), followed by dose modification of the interacting medication (30%). There was no difference in SVR12 between patients with at least 1 DDI compared with those with no DDIs (94.8% vs 95.8%; P = 0.73). There were a total of 227 actionable recommendations, with an acceptance rate of 84.1%. CONCLUSIONS: This study suggests that DDIs are prevalent among patients treated with DAAs for HCV. A HCV clinical pharmacist can help optimize patient care by identifying DDIs and recommending interventions to providers.

Characterizing the Severe Reactions of Parenteral Vitamin K1.

Parenteral vitamin K1 (phytonadione) is used for anticoagulant reversal, and a boxed warning exists with intravenous and intramuscular administration due to the possibility of severe reactions, including fatalities. These reactions resemble hypersensitivity or anaphylaxis, including anaphylactoid reaction, and have led to shock and cardiac and/or respiratory arrest. The objective of this review is to summarize the available literature detailing the anaphylactic/anaphylactoid reactions with parenteral vitamin K1 in order to better characterize the reaction and provide a more in-depth understanding of its importance. A comprehensive literature search of MEDLINE (1946 to June 2016) and EMBASE (1947 to June 2016) was conducted using the terms vitamin K1, phytonadione, phytomenadione, vitamin K group, anaphylaxis, polyoxyethylated castor oil, and cremophor. A total of 2 retrospective surveillance studies, 2 retrospective cohort studies, and 17 case reports were identified for inclusion and assessment. Based on a review of the literature, use of parenteral vitamin K1 may result in severe hypotension, bradycardia or tachycardia, dyspnea, bronchospasm, cardiac arrest, and death. These reactions are most consistent with a nonimmune-mediated anaphylactoid mechanism. It appears that intravenous administration is more frequently associated with these reactions and occurs at an incidence of 3 per 10 000 doses of intravenous vitamin K1. The solubilizer may also increase the risk of adverse reactions, which occurred in patients with and without previous exposure to vitamin K1. Although there are known factors that increase the risk of an adverse drug event occurring, reactions have been reported despite all precautions being properly followed.