Epidemiology and treatment of invasive Bartonella spp. infections in the United States.

OBJECTIVES: Bartonella spp., renowned for cat-scratch disease, has limited reports of dissemination. Tissue and blood cultures have limitations in detecting this fastidious pathogen. Molecular testing (polymerase chain reaction, PCR) and cell-free DNA have provided an avenue for diagnoses. This retrospective observational multicenter study describes the incidence of disseminated Bartonella spp. and treatment-related outcomes. METHODS: Inclusion criteria were diagnosis of bartonellosis via diagnosis code, serology testing of blood, polymerase chain reaction (PCR) of blood, 16/18S tests of blood or tissue, cultures of blood or tissue, or cell-free DNA of blood or tissue from January 1, 2014, through September 1, 2021. Exclusions were patients who did not receive treatment, insufficient data on treatment course, absence of dissemination, or retinitis as dissemination. RESULTS: Patients were primarily male (n = 25, 61.0%), white (n = 28, 68.3%), with mean age of 50 years (SD 14.4), and mean Charlson comorbidity index of 3.5 (SD 2.1). Diagnosis was primarily by serology (n = 34, 82.9%), with Bartonella henselae (n = 40, 97.6%) as the causative pathogen. Treatment was principally doxycycline with rifampin (n = 17, 41.5%). Treatment failure occurred in 16 (39.0%) patients, due to escalation of therapy during treatment (n = 5, 31.3%) or discontinuation of therapy due to an adverse event or tolerability (n = 5, 31.3%). CONCLUSIONS: In conclusion, this is the largest United States-based cohort of disseminated Bartonella spp. infections to date with a reported 39% treatment failure. This adds to literature supporting obtaining multiple diagnostic tests when Bartonella is suspected and describes treatment options.

The Future of Telehealth in Human Immunodeficiency Virus Care: A Qualitative Study of Patient and Provider Perspectives in South Carolina.

To ensure care continuity during the COVID-19 pandemic, telehealth has been widely implemented in human immunodeficiency virus (HIV) care. However, participation in and benefits from telehealth were unequal. This study aims to assess the willingness of people living with HIV (PWH) and HIV care providers to use telehealth and perceptions of the future role of telehealth. In-depth interviews with 18 PWH and 10 HIV care providers from South Carolina assessed their willingness to use telehealth, their perspectives on the future of telehealth in HIV care, and recommendations to improve telehealth. Interviews were analyzed using thematic analysis. Most PWH were female (61%), Black/African American (67%), and non-Hispanic (78%). Most PWH (61%) and all providers had used telehealth for HIV care. Most PWH and all providers reported being willing to use or (re-)consider telehealth HIV care services in the future. Providers suggested that telehealth is most suitable for routine HIV care encounters and for established, clinically stable, generally healthy PWH. Attitudes toward telehealth were heterogeneous, with most interviewees valuing telehealth similarly or superior to in-person care, yet >20% perceiving it less valuable. Recommendations to improve telehealth included multilevel strategies to address challenges across four domains: technology, the virtual nature of telehealth, administrative processes, and the sociodemographic profile of PWH. Telehealth in HIV care is here to stay; however, it may not yet be suitable for all PWH and all care encounters. Decision processes related to telehealth versus in-person care need to involve providers and PWH. Existing telehealth options require multilevel adjustments addressing persistent challenges.

A survey of South Carolina pharmacists' readiness to prescribe human immunodeficiency virus pre-exposure prophylaxis.

Introduction: HIV pre-exposure prophylaxis (PrEP) is largely underutilized in the Southern United States. Given their community presence, pharmacists are well positioned to provide PrEP within rural, Southern regions. However, pharmacists' readiness to prescribe PrEP in these communities remains unknown. Objective: To determine the perceived feasibility and acceptability of prescribing PrEP by pharmacists in South Carolina (SC). Methods: We distributed a 43-question online descriptive survey through the University of SC Kennedy Pharmacy Innovation Center's listerv of licensed SC pharmacists. We assessed pharmacists' comfort, knowledge, and readiness to provide PrEP. Results: A total of 150 pharmacists responded to the survey. The majority were White (73%, n=110), female (62%, n=93), and non-Hispanic (83%, n=125). Pharmacists practiced in retail (25%, n=37), hospital (22%, n=33), independent (17%, n=25), community (13%, n=19), specialty (6%, n=9), and academic settings (3%, n=4); 11% (n=17) practiced in rural locales. Pharmacists viewed PrEP as both effective (97%, n=122/125) and beneficial (74% n=97/131) for their clients. Many pharmacists reported being ready (60% n=79/130) and willing (86% n=111/129) to prescribe PrEP, although over half (62% n=73/118) cited lack of PrEP knowledge as a barrier. Pharmacists described pharmacies as an appropriate location to prescribe PrEP (72% n=97/134). Conclusions: Most SC pharmacists surveyed considered PrEP to be effective and beneficial for individuals who frequent their pharmacy and are willing to prescribe this therapy if statewide statutes allow. Many felt that pharmacies are an appropriate location to prescribe PrEP but lack a complete understanding of required protocols to manage these patients. Further investigation into facilitators and barriers of pharmacy-driven PrEP are needed to enhance utilization within communities.

Epidemiology, Outcomes and Tolerability of Protracted Treatment of Nontuberculous Mycobacterial Infections at a Community Teaching Hospital in the Southeastern United States.

Nontuberculous mycobacterial (NTM) infections present a treatment challenge for clinicians and patients. There are limited data about current susceptibility patterns and treatment outcomes in U.S. adults. This was a 10-year, single-center, retrospective, observational cohort study of adults with a positive NTM culture and clinical suspicion of infection between 1 January 2010 and 30 June 2020. The primary objective was to identify predictors for favorable treatment outcomes. Key secondary objectives were characterization of NTM epidemiology, susceptibility profiles, and safety and tolerability of treatment, including the proportion of subjects with an antimicrobial change and the reasons for the change. Of 250 subjects diagnosed with NTM infection, the most prevalent NTM isolates were Mycobacterium avium intracellulare complex (66.8%) followed by Mycobacterium abscessus (17.6%). Antimicrobial susceptibility data were available for 52.4% of the cohort (45.8% slow growers; 54.2% rapid growers). Only 88 (35%) subjects received treatment with evaluable clinical outcomes. The proportion of subjects with a favorable outcome was 61.4%. More subjects in the unfavorable outcome group experienced a change in antimicrobial therapy (73.5% vs. 51.9%, p = 0.043). The most common reason for antimicrobial change was adverse drug events (n = 36, 67.9%). In the regression model, private insurance was associated with a favorable outcome, whereas having multiple antimicrobial changes was associated with an unfavorable outcome. The complexity of NTM treatment and high incidence of medication-related issues suggest the necessity of interdisciplinary collaboration to improve overall treatment outcomes in NTM infections.

Increased viral load in a hospitalized patient on treatment with crushed bictegravir/emtricitabine/tenofovir alafenamide: A case report and review of the literature.

PURPOSE: To describe a case of increased viral load in a patient with HIV-1 infection receiving treatment with crushed bictegravir/emtricitabine/tenofovir alafenamide (B/FTC/TAF). SUMMARY: A 43-year-old man, newly diagnosed with HIV, was hospitalized due to failure to thrive, neurological changes, and hypotension. Before treatment, the HIV viral load (VL) was 769,704 copies/mL and the CD4+ T-cell count was 36 cells/µL. On hospital day (HD) 8, B/FTC/TAF by mouth daily was initiated. During the hospitalization, the patient's course was complicated by opportunistic infections, bilateral pneumothorax, seizure activity, and acute respiratory distress, requiring multiple intubations and extended time in the intensive care unit. A repeat VL measurement on HD 28 was 5,887 copies/mL after the patient had received 14 of 20 scheduled B/FTC/TAF doses. Because of a failed swallow study and continued nutritional deficits, a percutaneous endoscopic gastrostomy (PEG) tube was placed on HD 38 and continuous tube feeds via the PEG tube were initiated. Subsequently, the B/FTC/TAF order was modified to be crushed, mixed in 30 mL water, and administered daily via the PEG tube. A repeat VL measurement on HD 65 showed an increase to 8,047 copies/mL, despite receipt of 37 consecutive doses of B/FTC/TAF. B/FTC/TAF was discontinued and dolutegravir 50 mg twice daily, darunavir 800 mg plus ritonavir 100 mg (DRV/r), and tenofovir disoproxil fumarate/FTC 300 mg/200 mg were started due to virological increase, need for a viable option compatible with PEG tube delivery, and potential for integrase inhibitor resistance. At the time of regimen change (HD 67), a resistance panel showed minor mutations, E157Q and V118I. The regimen was streamlined with discontinuation of DRV/r on HD 92. The patient was discharged on HD 161. The PEG tube was removed 2 months after discharge, oral B/FTC/TAF was reinitiated, and the patient was virologically suppressed at 1 year after discharge. CONCLUSION: Controlled studies are needed to verify acceptable pharmacokinetic and pharmacodynamic metrics for crushed B/FTC/TAF given via tube, with and without tube feeds, before use in this manner.

Crushing and Splitting Direct-Acting Antivirals for Hepatitis C Virus Treatment: A Case Series and Literature Review.

Limited data exist regarding the use of direct-acting antivirals (DAAs) for hepatitis C virus (HCV) in patients who are unable to swallow tablets. This case series describes HCV treatment in patients requiring tablet manipulation, providing evidence for safety and effectiveness of HCV DAA tablet manipulation.

Short-term Adverse Events With BIC/FTC/TAF: Postmarketing Study.

Bictegravir (BIC)/emtricitabine (FTC)/tenofovir alafenamide (TAF) was Food and Drug Administration approved in February 2018. The paucity of real-world data prompted this retrospective, observational evaluation of discontinuation rates, adverse effects, and virologic control. In a Southern US, predominantly African American overweight population, we found optimal virologic control and low discontinuation rates, with 4% discontinuing BIC/FTC/TAF due to rash, low platelets, loss of appetite, and insomnia.

Heterogeneous Patient Preferences for Modern Antiretroviral Therapy: Results of a Discrete Choice Experiment.

OBJECTIVE: Limited data describe patient preferences for the growing number of antiretroviral therapies (ARTs). We quantified preferences for key characteristics of modern ART deemed relevant to shared decision making. METHODS: A discrete choice experiment survey elicited preferences for ART characteristics, including dosing (frequency and number of pills), administration characteristics (pill size and meal requirement), most bothersome side effect (from diarrhea, sleep disturbance, headaches, dizziness/difficulty thinking, depression, or jaundice), and most bothersome long-term effect (from increased risk of heart attacks, bone fractures, renal dysfunction, hypercholesterolemia, or hyperglycemia). Between March and August 2017, the discrete choice experiment was fielded to 403 treatment-experienced persons living with human immunodeficiency virus (HIV), enrolled from 2 infectious diseases clinics in the southern United States and a national online panel. Participants completed 16 choice tasks, each comparing 3 treatment options. Preferences were analyzed using mixed and latent class logit models. RESULTS: Most participants were male (68%) and older (interquartile range: 42-58 years), and had substantial treatment experience (interquartile range: 7-21 years). In mixed logit analyses, all attributes were associated with preferences. Side and long-term effects were most important, with evidence of substantial preference heterogeneity. Latent class analysis identified 5 preference classes. For classes 1 (40%), 2 (24%), and 3 (21%), side effects were most important, followed by long-term effects. For class 4 (10%), dosing was most important. Class 5 (4%) was largely indifferent to ART characteristics. CONCLUSION: Overall, treatment-experienced persons living with HIV valued minimizing side effects and long-term toxicities over dosing and administration characteristics. Preferences varied widely, highlighting the need to elicit individual patient preferences in models of shared antiretroviral decision making.

Multicenter, Observational Cohort Study Evaluating Third-Generation Cephalosporin Therapy for Bloodstream Infections Secondary to Enterobacter, Serratia, and Citrobacter Species.

OBJECTIVES: There is debate on whether the use of third-generation cephalosporins (3GC) increases the risk of clinical failure in bloodstream infections (BSIs) caused by chromosomally-mediated AmpC-producing Enterobacterales (CAE). This study evaluates the impact of definitive 3GC therapy versus other antibiotics on clinical outcomes in BSIs due to Enterobacter, Serratia, or Citrobacter species. METHODS: This multicenter, retrospective cohort study evaluated adult hospitalized patients with BSIs secondary to Enterobacter, Serratia, or Citrobacter species from 1 January 2006 to 1 September 2014. Definitive 3GC therapy was compared to definitive therapy with other non-3GC antibiotics. Multivariable Cox proportional hazards regression evaluated the impact of definitive 3GC on overall treatment failure (OTF) as a composite of in-hospital mortality, 30-day hospital readmission, or 90-day reinfection. RESULTS: A total of 381 patients from 18 institutions in the southeastern United States were enrolled. Common sources of BSIs were the urinary tract and central venous catheters (78 (20.5%) patients each). Definitive 3GC therapy was utilized in 65 (17.1%) patients. OTF occurred in 22/65 patients (33.9%) in the definitive 3GC group vs. 94/316 (29.8%) in the non-3GC group (p = 0.51). Individual components of OTF were comparable between groups. Risk of OTF was comparable with definitive 3GC therapy vs. definitive non-3GC therapy (aHR 0.93, 95% CI 0.51-1.72) in multivariable Cox proportional hazards regression analysis. CONCLUSIONS: These outcomes suggest definitive 3GC therapy does not significantly alter the risk of poor clinical outcomes in the treatment of BSIs secondary to Enterobacter, Serratia, or Citrobacter species compared to other antimicrobial agents.

Pharmacist-Driven Culture and Sexually Transmitted Infection Testing Follow-Up Program in the Emergency Department.

Expanding pharmacist-driven antimicrobial stewardship efforts in the emergency department (ED) can improve antibiotic management for both admitted and discharged patients. We piloted a pharmacist-driven culture and rapid diagnostic technology (RDT) follow-up program in patients discharged from the ED. This was a single-center, pre- and post-implementation, cohort study examining the impact of a pharmacist-driven culture/RDT follow-up program in the ED. Adult patients discharged from the ED with subsequent positive cultures and/or RDT during the pre- (21 August 2018-18 November 2018) and post-implementation (19 November 2018-15 February 2019) periods were screened for inclusion. The primary endpoints were time from ED discharge to culture/RDT review and completion of follow-up. Secondary endpoints included antimicrobial agent prescribed during outpatient follow-up, repeat ED encounters within 30 days, and hospital admissions within 30 days. Baseline characteristics were analyzed using descriptive statistics. Time-to-event data were analyzed using the Wilcoxon signed-rank test. One-hundred-and-twenty-seven patients were included, 64 in the pre-implementation group and 63 in the post-implementation group. There was a 36.3% reduction in the meantime to culture/RDT data review in the post-implementation group (75.2 h vs. 47.9 h, p < 0.001). There was a significant reduction in fluoroquinolone prescribing in the post-implementation group (18.1% vs. 5.4%, p = 0.036). The proportion of patients who had a repeat ED encounter or hospital admission within 30 days was not significantly different between the pre- and post-implementation groups (15.6 vs. 19.1%, p = 0.78 and 9.4% vs. 7.9%, p = 1.0, respectively). Introduction of a pharmacist culture and RDT follow-up program in the ED reduced time to data review, time to outpatient intervention and outpatient follow-up of fluoroquinolone prescribing.

Management of Hepatitis C in the Older Adult.

OBJECTIVE: To provide a review of the epidemiology, clinical presentation, screening, diagnosis, treatment, and prevention of hepatitis C with an emphasis on older adults. DATA SOURCES: PubMed and Google Scholar were searched for relevant literature using a combination of the following terms: hepatitis C, epidemiology, hepatitis C virus (HCV), diagnosis, treatment, direct-acting antivirals (DAAs), and older adults. In addition, websites of the hepatitis C guidelines, Centers for Disease Control and Prevention (CDC), and manufacturers of DAAs were also reviewed for relevant information. (The authors reviewed the literature through May 2019. STUDY SELECTION/DATA EXTRACTION: The key resources reviewed were the CDC website, American Association for the Study of Liver Diseases/Infectious Diseases Society of America hepatitis C guidelines, prescribing information of DAAs, and pivotal clinical trials of DAAs. DATA SYNTHESIS: Hepatitis C disproportionately affects baby boomers and people who inject drugs (PWID). CDC recommends screening adults born from 1945 to 1965 and high-risk patients for the presence of hepatitis C antibody. The goal of therapy is to achieve sustained virologic response, defined as undetectable HCV ribonucleic acid 12 weeks after treatment completion. Treatment for those who are treatment-naive with or without compensated cirrhosis consists of administration of DAAs orally for 8 to 12 weeks. Regimen selection depends on HCV genotype, presence or absence of cirrhosis, comorbid conditions, and concurrent medications. Currently recommended DAAs are highly effective, well tolerated, and can be associated with significant drug interactions particularly in older adults. Access to DAAs remains an obstacle for many patients. CONCLUSION: Hepatitis C is common among baby boomers and PWID. Screening is recommended in these patient populations. Treatment with DAAs is curative and well tolerated.

Who Wants to Switch? Gauging Patient Interest in Novel Antiretroviral Therapies.

Study participants were asked about their interest in switching to novel drug delivery systems that reduce the dosing frequency of antiretroviral regimens. Across a diverse, treatment-experienced cohort, we describe greatest interest in switching to an oral regimen taken once weekly, followed by injections taken every other month and twice-annual implants.

Association between chronic hemodialysis and bloodstream infections caused by chromosomally mediated AmpC-producing Enterobacteriaceae.

BACKGROUND: The combination of inherent antimicrobial resistance and high mortality after bloodstream infections (BSIs) caused by chromosomally mediated AmpC-producing Enterobacteriaceae (CAE) emphasizes the importance of identifying patients at risk of BSI because of these bacteria. This retrospective case-control study examines chronic hemodialysis among other risk factors for BSI caused by CAE. METHODS: Hospitalized adults with Enterobacteriaceae BSI from January 1, 2010-June 30, 2014, at 2 large community hospitals in the Southeastern United States were identified. Multivariate logistic regression was used to examine risk factors for CAE BSI. RESULTS: Among 831 Enterobacteriaceae bloodstream isolates, 106 (13%) met the phenotypic definition of CAE. Enterobacter spp accounted for 47% (50/106) of CAE BSIs. Chronic hemodialysis was an independent risk factor for CAE BSI (adjusted odds ratio [aOR], 2.34; 95% confidence interval [CI], 1.21-4.44). Other predictors of CAE BSI included nosocomial acquisition (aOR, 1.72; 95% CI, 1.02-2.87) and exposure to ß-lactam antibiotics within the last 30 days (aOR, 2.39; 95% CI, 1.37-4.14). CONCLUSIONS: To our knowledge, this is the first study to demonstrate an increased risk of CAE BSI in patients with end-stage renal disease undergoing chronic hemodialysis. This highlights the importance of effective infection prevention and antimicrobial stewardship interventions in hemodialysis clinics. Further studies to examine the impact of antibiotics on intestinal microbiota and rates of CAE colonization in this patient population are warranted.

Safety and Tolerability of Stribild in the Southeast United States.

PURPOSE: The purpose of this study is to assess postmarketing safety and tolerability of Stribild (elvitegravir [EVG]/cobicistat [COBI]/tenofovir disoproxil fumarate [TDF]/emtricitabine [FTC]). METHODS: A retrospective, pharmacoepidemiologic study in 2 outpatient HIV clinics in the Southeast United States was conducted among adults receiving EVG/COBI/TDF/FTC. We evaluated incidence and treatment-related adverse events, including change in serum creatinine (SCr). RESULTS: Patients were primarily treatment experienced (n = 173, 60%), African American (n = 210, 73%), and males (n = 187, 65%). One hundred ninety-five (68%) patients had any increase in SCr, and 65 (23%) had an increase of ≥0.3 mg/dL. Mean SCr change from baseline to peak was 0.2 mg/dL. Being treatment experienced (odds ratio [OR] = 2.21, 95% confidence interval [CI]: 1.12-4.38) was associated with SCr ≥0.3 mg/dL, while body mass index ≥30 kg/m(2) (OR = 0.41, 95% CI: 0.18-0.93) was protective. Twenty (7%) patients discontinued therapy, 3 due to acute kidney injury. CONCLUSION: Our results demonstrate limited adverse events and low discontinuation rates associated with EVG/COBI/TDF/FTC.