Real-World Dalbavancin Use for Serious Gram-Positive Infections: Comparing Outcomes Between People Who Use and Do Not Use Drugs.

Background: Dalbavancin has been used off-label to treat invasive bacterial infections in vulnerable populations like people who use drugs (PWUD) because of its broad gram-positive coverage and unique pharmacological properties. This retrospective, multisite study examined clinical outcomes at 90 days in PWUD versus non-PWUD after secondary treatment with dalbavancin for bacteremia, endocarditis, osteomyelitis, septic arthritis, and epidural abscesses. Methods: Patients at 3 teaching hospitals who received dalbavancin for an invasive infection between March 2016 and May 2022 were included. Characteristics of PWUD and non-PWUD, infection highlights, hospital stay and treatment, and outcomes were compared using χ2 for categorical variables, t test for continuous variables, and nonparametric tests where appropriate. Results: There were a total of 176 patients; 78 were PWUD and 98 were non-PWUD. PWUD were more likely to have a patient-directed discharge (26.9% vs 3.1%; P < .001) and be lost to follow-up (20.5% vs 7.14%; P < .01). Assuming loss to follow-up did not achieve clinical cure, 73.1% of PWUD and 74.5% of non-PWUD achieved clinical cure at 90 days (P = .08). Conclusions: Dalbavancin was an effective treatment option for invasive gram-positive infections in our patient population. Despite higher rates of patient-directed discharge and loss to follow-up, PWUD had similar rates of clinical cure at 90 days compared to non-PWUD.

"I know my body better than anyone else": a qualitative study of perspectives of people with lived experience on antimicrobial treatment decisions for injection drug use-associated infections.

Background: People who inject drugs (PWID) are at risk for severe bacterial and fungal infections including skin and soft tissue infections, endocarditis, and osteomyelitis. PWID have high rates of self-directed discharge and are often not offered outpatient antimicrobial therapies, despite studies showing their efficacy and safety in PWID. This study fills a gap in knowledge of patient and community partner perspectives on treatment and discharge decision making for injection drug use (IDU)-associated infections. Methods: We conducted semi-structured interviews with patients (n = 10) hospitalized with IDU-associated infections and community partners (n = 6) in the Portland, Maine region. Community partners include peer support workers at syringe services programs (SSPs) and outreach specialists working with PWID. We transcribed and thematically analyzed interviews to explore perspectives on three domains: perspectives on long-term hospitalization, outpatient treatment options, and patient involvement in decision making. Results: Participants noted that stigma and inadequate pain management created poor hospitalization experiences that contributed to self-directed discharge. On the other hand, patients reported hospitalization provided opportunities to connect to substance use disorder (SUD) treatment and protect them from outside substance use triggers. Many patients expressed interest in outpatient antimicrobial treatment options conditional upon perceived efficacy of the treatment, perceived ability to complete treatment, and available resources and social support. Finally, both patients and community partners emphasized the importance of autonomy and inclusion in medical decision making. Although some participants acknowledged their SUD, withdrawal symptoms, or undertreated pain might interfere with decision making, they felt these medical conditions were not justification for health care professionals withholding treatment options. They recommended open communication to build trust and reduce harms. Conclusion: Patients with IDU-associated infections desire autonomy, respect, and patient-centered care from healthcare workers, and may self-discharge when needs or preferences are not met. Involving patients in treatment decisions and offering outpatient antimicrobial options may result in better outcomes. However, patient involvement in decision making may be complicated by many contextual factors unique to each patient, suggesting a need for shared decision making to meet the needs of hospitalized patients with IDU-associated infections.

Perspectives on the Use of Outpatient Parenteral Antibiotic Therapy for People who Inject Drugs: Results From an Online Survey of Infectious Diseases Clinicians.

Injection-related infections require prolonged antibiotic therapy. Outpatient parenteral antimicrobial therapy (OPAT) has been shown to be feasible for people who inject drugs (PWID) in some settings. We report a national survey on practice patterns and attitudes of infectious diseases clinicians in the United States regarding use of OPAT for PWID.

'I feel like they're actually listening to me': a pilot study of a hospital discharge decision-making conversation guide for patients with injection drug use-associated infections.

Background: The prevalence of injection drug use (IDU)-associated infections and associated hospitalizations has been increasing for nearly two decades. Due to issues ranging from ongoing substance use to peripherally inserted central catheter safety, many clinicians find discharge decision-making challenging. Typically, clinicians advise patients to remain hospitalized for several weeks for intravenous antimicrobial treatment; however, some patients may desire other antimicrobial treatment options. A structured conversation guide, delivered by infectious disease physicians, intended to inform hospital discharge decisions has the potential to enhance patient participation in decisions. We developed a conversation guide in order to: (1) investigate its feasibility and acceptability and (2) examine experiences, outcomes, and lessons learned from use of the guide. Methods: We interviewed physicians after they each piloted the conversation guide with two patients. We interviewed patients immediately after the conversation and again 4-6 weeks later. Two analysts indexed transcriptions and used the framework method to identify and organize relevant information. We conducted retrospective chart review to corroborate and contextualize qualitative data. Results: Eight patients and four infectious disease physicians piloted the conversation guide. All patients (N = 8) completed antimicrobial treatment. Nearly all participants believed the conversation guide was important for incorporating patient values and preferences. Patients reported an increased sense of autonomy, but felt post-discharge needs could be better addressed. Physician participants identified the guide's long length and inclusion of pain management as areas for improvement. Conclusions: A novel conversation guide to inform hospital discharge decision-making for patients with IDU-associated infections was feasible, acceptable, and fostered the incorporation of patient preferences and values into decisions. While we identified areas for improvement, overall participants believed that this novel conversation guide helped to improve patient care and autonomy.

Phage Therapy of Mycobacterium Infections: Compassionate Use of Phages in 20 Patients With Drug-Resistant Mycobacterial Disease.

BACKGROUND: Nontuberculous Mycobacterium infections, particularly Mycobacterium abscessus, are increasingly common among patients with cystic fibrosis and chronic bronchiectatic lung diseases. Treatment is challenging due to intrinsic antibiotic resistance. Bacteriophage therapy represents a potentially novel approach. Relatively few active lytic phages are available and there is great variation in phage susceptibilities among M. abscessus isolates, requiring personalized phage identification. METHODS: Mycobacterium isolates from 200 culture-positive patients with symptomatic disease were screened for phage susceptibilities. One or more lytic phages were identified for 55 isolates. Phages were administered intravenously, by aerosolization, or both to 20 patients on a compassionate use basis and patients were monitored for adverse reactions, clinical and microbiologic responses, the emergence of phage resistance, and phage neutralization in serum, sputum, or bronchoalveolar lavage fluid. RESULTS: No adverse reactions attributed to therapy were seen in any patient regardless of the pathogen, phages administered, or the route of delivery. Favorable clinical or microbiological responses were observed in 11 patients. Neutralizing antibodies were identified in serum after initiation of phage delivery intravenously in 8 patients, potentially contributing to lack of treatment response in 4 cases, but were not consistently associated with unfavorable responses in others. Eleven patients were treated with only a single phage, and no phage resistance was observed in any of these. CONCLUSIONS: Phage treatment of Mycobacterium infections is challenging due to the limited repertoire of therapeutically useful phages, but favorable clinical outcomes in patients lacking any other treatment options support continued development of adjunctive phage therapy for some mycobacterial infections.

Medical Complications of Injection Drug Use - Part II.

Medical Complications of Injection Drug Use - Part IIDuring the past 2 decades, the risk of death, as well as the prevalence of hospitalizations in the United States, has increased substantially among people who inject drugs, mainly because of the opioid epidemic. In Part Two of this two-part review, the authors review complications observed in people who inject drugs and strategies to reduce harm.

Medical Complications of Injection Drug Use - Part I.

Medical Complications of Injection Drug Use - Part IDuring the past 2 decades, the risk of death and the prevalence of hospitalizations in the United States have increased substantially among people who inject drugs, in large part because of the opioid epidemic. This article reviews the complications observed in people who inject drugs as well as strategies to reduce harm.

A student-led interprofessional virtual outreach program for people with HIV during the Covid-19 pandemic: a pilot program at an academic medical center in Boston.

BACKGROUND: The Coronavirus disease 2019 (Covid-19) pandemic caused an abrupt disruption in clinical care and medical education, putting patients at increased risk for social stressors and displacing medical students from traditional clerkships. The pandemic also exposed the need for virtual tools to supplement clinical care and an opportunity to create meaningful roles for learners. METHODS: An interdisciplinary group designed a student-led virtual outreach program for patients with HIV whose care was limited by the pandemic. Patients were identified by clinicians and social workers using a clinic-based registry. Students called patients to conduct needs assessments, provide Covid-19 education, and to facilitate connection to services. Students participated in case-based didactics and workshops on motivational interviewing and patient engagement using virtual tools. Facilitated team meetings were held weekly during which themes of calls were identified. RESULTS: During a three-month period, five students participated in the outreach program. Two hundred sixteen patients were identified for outreach calls, of which 174 (75.9%) were successfully reached by telephone. Rate of completed phone call did not differ by age or gender. Sixty patients had a preferred language other than English of which 95.6% were reached in their preferred language. CONCLUSIONS: Virtual proactive outreach can be used as a tool to support patients and engage students in clinical care when access to in-person care is limited. This model of care could be adapted to other ambulatory practices and integrated into pre-clerkship curriculum as an introduction to the social history and structural drivers of health (SDOH) (245/350).

Bacteriophage treatment of disseminated cutaneous Mycobacterium chelonae infection.

Mycobacterium chelonae is a rare cause of chronic disseminated cutaneous infections in immunocompromised patients. Multidrug-resistant M. chelonae infections present a challenge for treatment, and prolonged antimicrobial courses lead to significant toxicities and further antimicrobial resistance. We report a case of refractory cutaneous disseminated M. chelonae infection in a patient with seronegative arthritis on immunotherapy with tofacitinib that was treated with combination antimicrobial, surgical, and single bacteriophage therapy with excellent clinical response. The patient developed neutralizing antibodies against the bacteriophage but continues to have stable improvement of disease with negative biopsies and no evidence of bacterial resistance to the phage.

Altered Phase Separation and Cellular Impact in C9orf72-Linked ALS/FTD.

Since the discovery of the C9orf72 repeat expansion mutation as causative for chromosome 9-linked amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) in 2011, a multitude of cellular pathways have been implicated. However, evidence has also been accumulating for a key mechanism of cellular compartmentalization-phase separation. Liquid-liquid phase separation (LLPS) is fundamental for the formation of membraneless organelles including stress granules, the nucleolus, Cajal bodies, nuclear speckles and the central channel of the nuclear pore. Evidence has now accumulated showing that the formation and function of these membraneless organelles is impaired by both the toxic arginine rich dipeptide repeat proteins (DPRs), translated from the C9orf72 repeat RNA transcript, and the repeat RNA itself. Both the arginine rich DPRs and repeat RNA themselves undergo phase separation and disrupt the physiological phase separation of proteins involved in the formation of these liquid-like organelles. Hence abnormal phase separation may explain a number of pathological cellular phenomena associated with C9orf72-ALS/FTD. In this review article, we will discuss the principles of phase separation, phase separation of the DPRs and repeat RNA themselves and how they perturb LLPS associated with membraneless organelles and the functional consequences of this. We will then discuss how phase separation may impact the major pathological feature of C9orf72-ALS/FTD, TDP-43 proteinopathy, and how LLPS may be targeted therapeutically in disease.

Feasibility and Safety of Outpatient Parenteral Antimicrobial Therapy in Conjunction With Addiction Treatment for People Who Inject Drugs.

BACKGROUND: Research is limited on combining outpatient parenteral antimicrobial therapy (OPAT) with addiction treatment for people who inject drugs (PWID) with serious infections. METHODS: This is a retrospective study of PWID (n = 68) requiring intravenous antibiotics evaluated for suitability for our OPAT program with concurrent addiction treatment. RESULTS: Most common infections were bacteremia and/or endocarditis (73.5%), bone and/or joint infections (32.4%), and epidural abscess (22.1%). Of the 20 patients (29.4%) who qualified, 100.0% completed the course of antibiotics, 30.0% experienced a 30-day readmission, and 15.0% relapsed. No overdoses, deaths, or peripherally inserted central catheter-line complications were reported. CONCLUSIONS: Outpatient parenteral antimicrobial therapy with addiction treatment may be feasible and safe for PWID with serious infections.

Impact of Medications for Opioid Use Disorder on Discharge Against Medical Advice Among People Who Inject Drugs Hospitalized for Infective Endocarditis.

BACKGROUND AND OBJECTIVES: The impact of medications for opioid use disorder (MOUD) on against medical advice (AMA) discharges among people who inject drugs (PWID) hospitalized for endocarditis is unknown. METHODS: A retrospective review of all PWID hospitalized for endocarditis at our institution between 2016 and 2018 (n = 84). RESULTS: PWID engaged with MOUD at admission, compared with those who were not, were less likely to be discharged AMA but this did not reach statistical significance in adjusted analysis (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.033-1.41; P = .11). Among out-of-treatment individuals, newly initiating MOUD did not lead to significantly fewer AMA discharges (OR, 0.98; 95% CI, 0.26-3.7; P = .98). CONCLUSION AND SCIENTIFIC SIGNIFICANCE: PWID hospitalized for endocarditis are at high risk for discharge AMA but more research is needed to understand the impact of MOUD. (Am J Addict 2020;29:155-159).

Long-term Outcomes of Injection Drug-related Infective Endocarditis Among People Who Inject Drugs.

OBJECTIVES: Infective endocarditis (IE) among people who inject drugs is associated with high rates of mortality and repeat episodes of endocarditis. We sought to report on longer-term clinical outcomes of patients with IE who were offered buprenorphine or methadone treatment for opioid use disorder (OUD) at their initial hospital admission. METHODS: Individuals with OUD hospitalized between 2013 and 2015 with IE were included for the retrospective study. The following data were extracted from the medical record: sociodemographic data, mortality, repeat episodes of endocarditis, and evidence of ongoing buprenorphine and methadone treatment. The impact of medication use on mortality and repeat episode of endocarditis was examined using survival analysis. RESULTS: Overall, 26 individuals were included in the study. The mean duration of follow-up was 45.0 months (SD 7.2, range 34.0-56.0). During the index admission, 8 received buprenorphine, 8 received methadone, and 10 declined medications. During the follow-up period, 4 (15.4%) individuals died and 10 (38.5%) individuals experienced a repeat episode of endocarditis. Survival analysis of mortality (log-rank P = 0.066) and repeat episode of endocarditis (log-rank P = 0.86) comparing those who received buprenorphine, received methadone, and declined medication did not differ significantly. CONCLUSIONS: Initiation of medication treatment alone may not be sufficient to impact long-term mortality and rates of repeat episode of endocarditis. More research is needed to identify optimal treatment strategies for people who inject drugs with IE.

Home Intravenous Antibiotic Treatment for a Patient with Opioid Use Disorder.

Intravenous drug abusers may incur bloodstream infections, in particular those involving the heart valves, that often require extended courses of antibiotics, commonly on the order of six weeks. Conventional wisdom has dictated that even when patients are sufficiently well to not need ongoing hospitalization, it is unsafe to complete their antibiotic course in any setting other than in a closely supervised facility, even if this is contrary to their wishes. The assumption has been that such patients would be at risk of using their indwelling intravenous catheter for illicit purposes. Recent advances in the care of patients who suffer from addiction disorders suggest that when patients receive state-of-the-art addiction treatment, many may be able to continue their intravenous antibiotic course unsupervised, at home. This represents a departure from the parentalistic model of care of impaired patients who are prone to self-harm, moving towards a model that respects autonomy and trusts patients who are in recovery to continue their care in a manner that is self-beneficial.

HIV Initial Assessment and Routine Follow-up: What Tests to Order and Why.

Laboratory tests are an important tool in the care of patients with human immunodeficiency virus. An organized approach to laboratory ordering helps clinicians to understand the utility of each test, ensure a comprehensive evaluation, and decrease use of unnecessary tests. Tests are organized around the following goals of care: confirm the diagnosis, assess for immune suppression, guide antiretroviral therapy, screen for coinfections and latent infections, monitor response to therapy, and provide preventative care. This article reviews appropriate testing for patients with human immunodeficiency virus to accomplish these goals with a focus on how each test is useful in clinical practice.

Health Considerations for HIV-Infected International Travelers.

PURPOSE OF THE REVIEW: International travel continues to steadily increase, including leisure travel, travel to one's country of origin to visit friends and relatives, travel for service work, and business travel. Travelers with HIV may have an increased risk for travel-associated infections. The pre-travel medical consultation is an important means of assessing one's risk for travel-related health issues. The aim of this review is to provide an update on key health considerations for the HIV-infected traveler. RECENT FINDINGS: Like all travelers, the HIV-infected traveler should adhere to behavioral precautions, including safety measures with food and water consumption, safe sexual practices, and arthropod bite avoidance. HIV is a risk factor for venous thromboembolism and patients should be educated regarding this risk. Most pre-travel vaccines are safe and immunogenic in HIV-infected individuals, though live vaccines should be avoided in patients with low CD4 counts. Malaria chemoprophylaxis is strongly recommended in patients with HIV traveling to endemic areas and no significant interactions exist between the commonly used prophylactic anti-malarial agents and anti-retroviral therapy (ART). Travelers with HIV, particularly those who are not on ART or who have low CD4 cell counts, may have increased risk for tuberculosis, malaria, enteric infections, visceral leishmaniasis, American trypanosomiasis, and endemic mycoses such as histoplasmosis, talaromycosis, and coccidioidomycosis. The immune status of the HIV-infected traveler should be assessed prior to travel along with the duration, itinerary, and activities planned during travel in order to carefully consider individual risk for travel-related health issues.