Long-term Risk of Serious Infections and Mortality Among Patients Surviving Drug Use-Associated Infective Endocarditis.

Among a statewide cohort of 1874 patients surviving hospitalization for drug use-associated endocarditis during 2017-2020, the 3-year risk of death or future hospitalization was 38% (16% for death before later infection, 14% for recurrent endocarditis, 14% for soft tissue, 9% for bacteremia, 5% for bone/joint, and 4% for spinal infections).

Quantifying the Time to Administer Outpatient Parenteral Antimicrobial Therapy: A Missed Opportunity to Compensate for the Value of Infectious Diseases.

Outpatient parenteral antimicrobial therapy (OPAT) relies on substantial uncompensated provider time. In this study of a large academic OPAT program, the median amount of unbilled OPAT management time was 27 minutes per week, per OPAT course. These data should inform benchmarks in pursuing novel payment approaches for OPAT.

Medications for Opioid Use Disorder and Mortality and Hospitalization Among People With Opioid Use-related Infections.

BACKGROUND: Severe skin and soft tissue infections related to injection drug use have increased in concordance with a shift to heroin and illicitly manufactured fentanyl. Opioid agonist therapy medications (methadone and buprenorphine) may improve long-term outcomes by reducing injection drug use. We aimed to examine the association of medication use with mortality among people with opioid use-related skin or soft tissue infections. METHODS: An observational cohort study of Medicaid enrollees aged 18 years or older following their first documented medical encounters for opioid use-related skin or soft tissue infections during 2007-2018 in North Carolina. The exposure was documented medication use (methadone or buprenorphine claim) in the first 30 days following initial infection compared with no medication claim. Using Kaplan-Meier estimators, we examined the difference in 3-year incidence of mortality by medication use, weighted for year, age, comorbidities, and length of hospital stay. RESULTS: In this sample, there were 13,286 people with opioid use-related skin or soft tissue infections. The median age was 37 years, 68% were women, and 78% were white. In Kaplan-Meier curves for the total study population, 12 of every 100 patients died during the first 3 years. In weighted models, for every 100 people who used medications, there were four fewer deaths over 3 years (95% confidence interval = 2, 6). CONCLUSION: In this study, people with opioid use-related skin and soft tissue infections had a high risk of mortality following their initial healthcare visit for infections. Methadone or buprenorphine use was associated with reductions in mortality.

Serratia endocarditis: antimicrobial management strategies and clinical outcomes.

OBJECTIVES: The incidence of Serratia endocarditis is increasing, yet optimal treatment has not been defined. Our objective was to investigate the outcomes of patients with Serratia endocarditis by treatment strategy. METHODS: We reviewed adult patients with definitive Serratia endocarditis at two independent health systems between July 2001 and April 2023. Combination therapy was defined as receipt of ≥2 in vitro active agents for ≥72 h. RESULTS: Seventy-five patients were included; 64% (48/75) were male and 85% (64/75) were people who inject drugs. Compared with monotherapy, receipt of combination therapy was associated with lower rates of microbiological failure (0% versus 15%, P = 0.026) and 90 day all-cause mortality (11% versus 31%, P = 0.049). Antimicrobial discontinuation due to an adverse event was more common among patients receiving combination therapy compared with monotherapy (36% versus 8%, P = 0.058). CONCLUSIONS: In the largest series of Serratia endocarditis to date, combination antibiotic treatment was associated with improved outcomes. However, larger, prospective studies are warranted.

The Impact of Discharge Against Medical Advice on Readmission After Opioid Use Disorder-Associated Infective Endocarditis: a National Cohort Study.

BACKGROUND: Hospitalizations for infective endocarditis (IE) associated with opioid use disorder (O-IE) have increased in the USA and have been linked to high rates of discharge against medical advice (DAMA). DAMA represents a truncation of care for a severe infection, yet patient outcomes after DAMA are unknown. OBJECTIVE: This study aimed to assess readmissions following O-IE and quantify the impact of DAMA on outcomes. DESIGN: A retrospective study of a nationally representative dataset of persons' inpatient discharges in the USA in 2016 PARTICIPANTS: A total of 6018 weighted persons were discharged for O-IE, stratified by DAMA vs. other discharge statuses. Of these, 1331 (22%) were DAMA. MAIN MEASURES: The primary outcome of interest was 30-day readmission rates, stratified by discharge type. We also examined the total number of hospitalizations during the year and estimated the effect of DAMA on readmission. KEY RESULTS: Compared with non-DAMA, those experiencing DAMA were more commonly female, resided in metropolitan areas, lower income, and uninsured. Crude 30-day readmission following DAMA was 50%, compared with 21% for other discharge types. DAMA was strongly associated with readmission in an adjusted logistic regression model (OR 3.72, CI 3.02-4.60). Persons experiencing DAMA more commonly had ≥2 more hospitalizations during the period (31% vs. 18%, p<0.01), and were less frequently readmitted at the same hospital (49% vs 64%, p<0.01). CONCLUSIONS: DAMA occurs in nearly a quarter of patients hospitalized for O-IE and is strongly associated with short-term readmission. Interventions to address the root causes of premature discharges will enhance O-IE care, reduce hospitalizations and improve outcomes.

Inpatient Hepatitis C Treatment Coordination and Initiation for Patients Who Inject Drugs.

BACKGROUND: With hepatitis C (HCV) incidence rising due to injection drug use, people who inject drugs (PWID) are a priority population for direct-acting antivirals (DAA). However, significant barriers exist. At our institution, hospitalized PWID were screened for HCV but not effectively linked to care. AIM: To improve retention in HCV care among hospitalized PWID. SETTING: Quaternary academic center in the Southeast US from August 2021 through August 2022. PARTICIPANTS: Hospitalized PWID with HCV. PROGRAM DESCRIPTION: E-consultation-prompted care coordination and HCV treatment with outpatient telehealth. PROGRAM EVALUATION: Care cascades were constructed to assess retention and HCV treatment, with the primary outcome defined as DAA completion or sustained virologic response after week 4. Of 28 patients, 11 started DAAs inpatient, 8 initiated outpatient, and 9 were lost to follow-up or transferred care. Overall, 82% were linked to care and 52% completed treatment. For inpatient initiators, 73% achieved the outcome. Of non-inpatient initiators, 71% were linked to care, 53% started treatment, and 36% achieved the outcome. DISCUSSION: Inpatient HCV treatment coordination, including DAA initiation, and telehealth follow-up, was feasible and highly effective for hospitalized PWID. Future steps should address barriers to inpatient DAA treatment and expand this model to other similar patient populations.

Opioid misuse among persons with HIV engaged in care in the Southeastern US.

The prevalence of opioid misuse by people living with HIV (PLWH) during the current US opioid epidemic has not been fully described. Among a cohort of persons engaged in HIV care in North Carolina, we examined the prevalence of and risk factors for opioid misuse, defined as self-reported "street" opioid use (e.g., heroin) or nonmedical prescription opioid use on a patient reported outcomes survey. Recent (past three-month) opioid misuse among 1,440 PLWH in care 2012-2017 was 2% (95% CI 2-3%) and lifetime misuse 15% (13-16%). Persons reporting lifetime or recent misuse more commonly had hepatitis C and reported injecting drugs. In multivariable logistic regression models, male-to-male sexual contact was inversely associated with recent or lifetime misuse. White/non-Hispanic race/ethnicity was associated with lifetime misuse and CD4 count and viral load were not associated with opioid misuse. Among 32 persons reporting recent misuse, 81% had a contemporaneous viral load <50 copies/mL. In this cohort of PLWH engaged in care, recent opioid misuse prevalence was similar to general population estimates. Assessments of opioid misuse among PLWH not in care are urgently needed to fully characterize the impact of opioids on all PLWH.

STratification risk analysis in OPerative management (STOP score) for drug-induced endocarditis.

BACKGROUND: The opioid epidemic has seen a drastic increase in the incidence of drug-associated infective endocarditis (IE). No clinical tool exists to predict operative morbidity and mortality in patients undergoing surgery. METHODS: A multi-institutional database was reviewed between 2011 and 2018. Multivariate logistic regression was fitted in an automated stepwise fashion. The STratification risk analysis in OPerative management of drug-associated IE (STOP) score was constructed. Morbidity was defined as reintubation, prolonged ventilation, pneumonia, renal failure, dialysis, stroke, reoperation for bleeding, and a permanent pacemaker. Cross-validation provided an unbiased estimate of out-of-sample performance. RESULTS: A total of 1181 patients underwent surgery for drug-associated IE (median age, 39; interquartile range [IQR], 30-54, 386 women [32.7%], 341 reoperations for prosthetic valve endocarditis [28.9%], 316 patients with multivalve disease [26.8%]). Operative morbidity and mortality were 41.1% and 5.9%, respectively. Predictors of morbidity were dialysis (95% confidence interval [CI], 1.16-2.82), emergent intervention (1.83-4.73), multivalve procedure (1.01-1.98), causative organisms other than Streptococcus (1.09-2.02), and type of valve procedure performed [aortic valve procedure (1.07-2.15), mitral valve replacement (1.03-2.05), tricuspid valve replacement (1.21-2.60)]. Predictors of mortality were dialysis (1.29-5.74), active endocarditis (1.32-83), lung disease (1.25-5.43), emergent intervention (1.69-6.60), prosthetic valve endocarditis (1.24-3.69), aortic valve procedure (1.49-5.92) and multivalve disease (1.00-2.95). Variables maximizing explanatory power were translated into a scoring system. Each point increased odds of morbidity and mortality by 22.0% and 22.4% with an accuracy of 94.0% and 94.1%, respectively. CONCLUSION: Drug-related IE is associated with significant morbidity and mortality. An easily-applied risk stratification score may aid in clinical decision-making.

Not Just Endocarditis: Hospitalizations for Selected Invasive Infections Among Persons With Opioid and Stimulant Use Diagnoses-North Carolina, 2010-2018.

BACKGROUND: While increases in overdoses, viral hepatitis, and endocarditis associated with drug use have been well-documented in North Carolina, the full scope of invasive drug-related infections (IDRIs) has not. We characterized trends in IDRIs among hospitalized patients in North Carolina. METHODS: We compared invasive infections that were related or not related to drug use among hospitalized patients aged 18-55 years based on retrospective review of administrative records from 2010-2018. Hospitalizations for endocarditis, central nervous system/spine infections, osteomyelitis, and septic arthritis were labeled as IDRIs if discharge codes included opioid and/or amphetamine misuse. Trends, rates, and distributions were calculated. RESULTS: Among 44 851 hospitalizations for the specified infections, 2830 (6.3%) were IDRIs. The proportion of infections attributable to drug use increased from 1.5% (2010) to 13.1% (2018), and the rate grew from 1.2 to 15.1 per 100 000. Compared with those who had non-drug-related infections, patients with IDRIs were younger (median age, 35 vs 46 years), more likely to be non-Hispanic white (81% vs 56%), and had longer hospitalizations (median, 8 vs 6 days). 43% of hospitalizations for IDRIs involved infective endocarditis. CONCLUSIONS: The rate of IDRIs in North Carolina increased substantially during 2010-2018, indicating an urgent need for enhanced infection prevention, harm reduction, and addiction services aimed at community and inpatient settings.

Trends in Drug Use-Associated Infective Endocarditis and Heart Valve Surgery, 2007 to 2017: A Study of Statewide Discharge Data.

Background: Drug use-associated infective endocarditis (DUA-IE) is increasing as a result of the opioid epidemic. Infective endocarditis may require valve surgery, but surgical treatment of DUA-IE has invoked controversy, and the extent of its use is unknown. Objective: To examine hospitalization trends for DUA-IE, the proportion of hospitalizations with surgery, patient characteristics, length of stay, and charges. Design: 10-year analysis of a statewide hospital discharge database. Setting: North Carolina hospitals, 2007 to 2017. Patients: All patients aged 18 years or older hospitalized for IE. Measurements: Annual trends in all IE admissions and in IE hospitalizations with valve surgery, stratified by patients' drug use status. Characteristics of DUA-IE surgical hospitalizations, including patient demographic characteristics, length of stay, disposition, and charges. Results: Of 22 825 IE hospitalizations, 2602 (11%) were for DUA-IE. Valve surgery was performed in 1655 IE hospitalizations (7%), including 285 (17%) for DUA-IE. Annual DUA-IE hospitalizations increased from 0.92 to 10.95 and DUA-IE hospitalizations with surgery from 0.10 to 1.38 per 100 000 persons. In the final year, 42% of IE valve surgeries were performed in patients with DUA-IE. Compared with other surgical patients with IE, those with DUA-IE were younger (median age, 33 vs. 56 years), were more commonly female (47% vs. 33%) and white (89% vs. 63%), and were primarily insured by Medicaid (38%) or uninsured (35%). Hospital stays for DUA-IE were longer (median, 27 vs. 17 days), with higher median charges ($250 994 vs. $198 764). Charges for 282 DUA-IE hospitalizations exceeded $78 million. Limitation: Reliance on administrative data and billing codes. Conclusion: DUA-IE hospitalizations and valve surgeries increased more than 12-fold, and nearly half of all IE valve surgeries were performed in patients with DUA-IE. The swell of patients with DUA-IE is reshaping the scope, type, and financing of health care resources needed to effectively treat IE. Primary Funding Source: National Institutes of Health.

Challenges Facing a Rural Opioid Epidemic: Treatment and Prevention of HIV and Hepatitis C.

PURPOSE OF REVIEW: This article reviews recent epidemiologic trends in HIV and hepatitis C virus (HCV) and strategies for treatment and prevention of these infections as they relate to the opioid epidemic. RECENT FINDINGS: Among people who inject drugs (PWID) in the United States (US), HIV diagnoses are decreasing, while HCV is increasing. Care for HIV and HCV relies heavily on specialist infrastructure, which is lacking in rural areas. Antiretrovirals for HIV and direct-acting antivirals for HCV are effective among PWID, yet multiple barriers make it difficult for rural injectors to access these treatments. Similarly, access to syringe service programs, medication-assisted therapy for opioid addiction, and pre-exposure prophylaxis for HIV are all limited in rural areas. Previous research on HIV and HCV among PWID has focused on urban or international populations, yet the US opioid epidemic is moving away from metropolitan centers. Increasing rurality of opioid injection brings unique challenges in treatment and prevention. Research into the care of HIV, HCV, and opioid use disorder among rural populations is urgently needed.

Outcomes of HIV-infected patients receiving care at multiple clinics.

Receiving care at multiple clinics may compromise the therapeutic patient-provider alliance and adversely affect the treatment of people living with HIV. We evaluated 12,759 HIV-infected adults in Philadelphia, PA between 2008 and 2010 to determine the effects of using multiple clinics for primary HIV care. Using generalized estimating equations with logistic regression, we examined the relationship between receiving care at multiple clinics (≥ 1 visit to two or more clinics during a calendar year) and two outcomes: (1) use of ART and (2) HIV viral load ≤ 200 copies/mL for patients on ART. Overall, 986 patients (8 %) received care at multiple clinics. The likelihood of attending multiple clinics was greater for younger patients, women, blacks, persons with public insurance, and for individuals in their first year of care. Adjusting for sociodemographic factors, patients receiving care at multiple clinics were less likely to use ART (AOR = 0.62, 95 % CI 0.55-0.71) and achieve HIV viral suppression (AOR = 0.78, 95 % CI 0.66-0.94) than individuals using one clinic. Qualitative data are needed to understand the reasons for visiting multiple clinics.

Strategies to Improve Patient-Centered Care for Drug Use-Associated Infective Endocarditis: JACC Focus Seminar 2/4.

Drug use-associated infective endocarditis (DUA-IE) is a major cause of illness and death for people with substance use disorder (SUD). Investigations to date have largely focused on advancing the care of patients with DUA-IE and included drug use disorder treatment, decisions about surgery, and choice of antibiotics during the period of hospitalization. Transitions from hospital to outpatient care are relatively unstudied and frequently a key factor of uncontrolled infection, continued substance use, and death. In this paper, we review the evidence supporting cross-disciplinary care for people with DUA-IE and highlight domains that need further clinician, institutional, and research investment in clinicians and institutions. We highlight best practices for treating people with DUA-IE, with a focus on addressing health disparities, meeting health-related social needs, and policy changes that can support care for people with DUA-IE in the hospital and when transitioning to the community.

Endocarditis, drug use and biological sex: A statewide analysis comparing sex differences in drug use-associated infective endocarditis with other drug-related harms.

OBJECTIVES: Hospitalizations for drug use-associated infective endocarditis (DUA-IE) have risen sharply across the United States over the past decade. The sex composition of DUA-IE remains less clear, and studies have indicated a possible shift to more females. We aimed to compare more recent statewide hospitalization rates for DUA-IE in females versus males and contextualize them among other drug-related harms in North Carolina (NC). METHODS: This study was a retrospective analysis using public health datasets of all NC hospital discharges for infective endocarditis from 2016 to 2020. Drug use-related hospitalizations were identified using ICD-10-CM codes. Discharge rates by year and sex for DUA-IE and non-DUA-IE were calculated and compared to fatal overdoses and acute hepatitis C (HCV). Temporal, demographic, and pregnancy trends were also assessed. RESULTS: Hospitalizations rates for DUA-IE were 9.7 per 100,000 over the five-year period, and 1.2 times higher among females than males. Females composed 57% of DUA-IE hospitalizations over the period. Conversely, fatal overdose, acute HCV, and non-DUA-IE hospitalization rates were higher among males. Age, county of residence, and pregnancy status did not explain the higher DUA-IE among females. CONCLUSION: Females now comprise the majority of DUA-IE hospitalizations in NC, unlike other drug-related harms. No clear demographic or geographic associations were found, and further research is needed to explain this phenomenon. Preventing invasive infections among females who inject drugs should be prioritized.

Mortality associated with bacterial and fungal infections and overdose among people with drug use diagnoses.

PURPOSE: Hospital visits for drug use-related bacterial and fungal infections have increased alongside overdose deaths. The incidence of mortality from these infections and the comparison to overdose mortality is not established. METHODS: This cohort study examined mortality outcomes among adults with drug use diagnoses who were insured by public and private plans during 2007 through 2018 in North Carolina. We examined bacterial- and fungal infection-related mortality and overdose mortality using cumulative incidence functions. RESULTS: Among 131,522 people with drug use diagnoses, the median age was 45 years (interquartile range: 31-57), 58% were women and 65% had an opioid use disorder diagnosis. The 1-year incidence of bacterial and fungal infection-associated mortality was progressively higher as age increased (35-49 years: 9 per 10,000 people, 50-64 years: 23 per 10,000, 65+ years: 50 per 10,000 people). Conversely, the 1-year incidence of overdose mortality was markedly lower among older adults compared to those under the age of 65 (18-34 years: 34 deaths per 10,000 people; 35-49 years: 47 per 10,000; 50-64 years: 41 per 10,000; 65+ years: 9 per 10,000). CONCLUSIONS: Bacterial and fungal infections and overdose were notable causes of death among adults with drug use diagnoses, and varied by age group.

Surgeons' Perspectives on Valve Surgery in People With Drug Use-Associated Infective Endocarditis.

BACKGROUND: Hospitalizations for drug-use associated infective endocarditis (DUA-IE) have led to increasing surgical consultation for valve replacement. Cardiothoracic surgeons' perspectives about the process of decision making around operation for people with DUA-IE are largely unknown. METHODS: This multisite semiqualitative study sought to gather the perspectives of cardiothoracic surgeons on initial and repeat valve surgery for people with DUA-IE through purposeful sampling of surgeons at 7 hospitals: University of Alabama, Tufts Medical Center, Boston Medical Center, Massachusetts General Hospital, University of North Carolina-Chapel Hill, Vanderbilt University Medical Center, and Rhode Island Hospital-Brown University. RESULTS: Nineteen cardiothoracic surgeons (53% acceptance) were interviewed. Perceptions of the drivers of addiction varied as well as approaches to repeat valve operations. There were mixed views on multidisciplinary meetings, although many surgeons expressed an interest in more efficient meetings and more intensive postoperative and posthospitalization multidisciplinary care. CONCLUSIONS: Cardiothoracic surgeons are emotionally and professionally impacted by making decisions about whether to perform valve operation for people with DUA-IE. The use of efficient, agenda-based multidisciplinary care teams is an actionable solution to improve cross-disciplinary partnerships and outcomes for people with DUA-IE.

Access to Medications for Opioid Use Disorder for Persons With Human Immunodeficiency Virus in the United States: Gaps in Coverage by State AIDS Drug Assistance Programs.

Life-saving medications for opioid use disorder are inaccessible for people with human immunodeficiency virus relying on the AIDS Drug Assistance Programs (ADAP) in 40% of jurisdictions. Funding/policies should address this through increasing access through ADAP and the Ryan White HIV/AIDS Program (RWHAP), partnerships between RWHAP and substance use programs, and other state/federal initiatives.