Qualitative Interviews Exploring Adverse Event Mitigation Strategies in Adults Receiving Amikacin Liposome Inhalation Suspension.

INTRODUCTION: This study aimed to gain insight from patients with refractory Mycobacterium avium complex lung disease (MAC-LD) into strategies used to manage adverse events (AEs) associated with amikacin liposome inhalation suspension (ALIS). METHODS: We conducted semi-structured interviews with US patients with refractory MAC-LD prescribed ALIS in a real-world setting. Interview transcripts were analyzed and coded to identify patterns in participants' descriptions of their ALIS treatment experiences, including AEs and their disruptiveness, and AE mitigation strategies, including participants' ratings of strategies' effectiveness. Concept saturation was also assessed. RESULTS: Twenty participants (mean age 48.7 years; 80% women; mean ALIS duration 5.45 months) were interviewed. At the time of the interview, 15 participants (75%) had received ALIS for > 1 month and 13 (65%) were currently receiving ALIS. Participants described 44 unique AE mitigation strategies, which can be categorized into three groups: prepare for treatment; prevent increased emergence of AEs; and persist on treatment by mitigating AEs. Common strategies (reported by ≥ 50% of participants) included use of educational materials from the patient support program, localized management of throat irritation, and symptom management to reduce fatigue. Evidence of concept saturation was observed: no new strategies were identified in the last five interviews, which suggests the sample was robust enough to identify all mitigation strategies likely to be used by the broader patient population. CONCLUSIONS: This real-world study identified a diverse set of potential AE mitigation strategies intended to help individual patients prepare for ALIS treatment, prevent the increased emergence of certain AEs, and mitigate the impact of AEs on treatment persistence. Developing a comprehensive accounting of the types of mitigation strategies in use among patients in real-world settings can inform future investigation of the effectiveness of such strategies, and support evidence-based recommendations for treatment management.

Five-Year Outcomes among U.S. Bronchiectasis and NTM Research Registry Patients.

Rationale: Nontuberculous mycobacteria (NTM) are prevalent among patients with bronchiectasis. However, the long-term natural history of patients with NTM and bronchiectasis is not well described. Objectives: To assess the impact of NTM on 5-year clinical outcomes and mortality in patients with bronchiectasis. Methods: Patients in the Bronchiectasis and NTM Research Registry with ⩾5 years of follow-up were eligible. Data were collected for all-cause mortality, lung function, exacerbations, hospitalizations, and disease severity. Outcomes were compared between patients with and without NTM at baseline. Mortality was assessed using Cox proportional hazards models and the log-rank test. Measurements and Main Results: In total, 2,634 patients were included: 1,549 (58.8%) with and 1,085 (41.2%) without NTM at baseline. All-cause mortality (95% confidence interval) at Year 5 was 12.1% (10.5%, 13.7%) overall, 12.6% (10.5%, 14.8%) in patients with NTM, and 11.5% (9.0%, 13.9%) in patients without NTM. Independent predictors of 5-year mortality were baseline FEV1 percent predicted, age, hospitalization within 2 years before baseline, body mass index, and sex (all P < 0.01). The probabilities of acquiring NTM or Pseudomonas aeruginosa were approximately 4% and 3% per year, respectively. Spirometry, exacerbations, and hospitalizations were similar, regardless of NTM status, except that annual exacerbations were lower in patients with NTM (P < 0.05). Conclusions: Outcomes, including exacerbations, hospitalizations, rate of loss of lung function, and mortality rate, were similar across 5 years in patients with bronchiectasis with or without NTM.

Latent TB treatment regimens in 2023: Wetmore TB clinic in New Orleans.

The USPSTF has updated Latent TB Infection (LTBI) screening and treatment recommendations in 2023; describing treatment courses, side effects and benefits associated with each regimen. Overall, rifampin-containing shortened regimens are the preferred modality for LTBI treatment. A recent study in 2023 evaluated adherence and tolerance of the isoniazid(INH) + rifapentine(RPT), or "3HP" regimen and identified patient groups that may be at higher risk for non-completion of this regimen. It emphasized the need for targeted education at the beginning of treatment, to avoid early discontinuation. Our experience in New Orleans demonstrated that the 3HP is well-tolerated, with higher completion rates than other LTBI regimens. Utilizing a retrospective chart review model, we reviewed 756 patients who were treated for LTBI over a two-year period from 1/2021--12/2022. The three possible treatment regimens included isoniazid (INH) alone, rifampin (RIF) alone, or INH + RPT (3HP). Of these regimens, the highest completion rate was in the 3HP group, despite literature suggesting this regimen is difficult to tolerate. Our experience suggests that this may still be an efficacious regimen that is well-tolerated if there is good access to clinicians to discuss mitigating side effects. More data is needed to determine factors that led to the success or failure for each regimen. Our clinic does have increased availability of nursing and medical staff to discuss side effects and answer questions, which may have contributed to our relatively higher success rate. In addition, we applied the review recommendations to our patient population, and would recommend the consideration of diabetes, heavy alcohol use, and tobacco use as risk factors for patients that would benefit from LTBI screening and treatment.

A tale of two images: From mycobacterium avium complex-lung disease (MAC-LD) to mycobacterium avium complex-pleural disease.

The typical radiographic presentation for Mycobacterium avium complex lung disease (MAC-LD) is either nodular bronchiectasis or cavitary lung disease. The former is seen most commonly in middle-aged or elderly Caucasian females with the characteristic asthenic phenotype, and the latter in middle-aged male smokers with COPD. We present the case of a young, otherwise healthy woman, with no significant risk factors, who was incidentally found to have MAC-LD with associated bronchiectasis. The patient's treatment and clinical course over a period of 5 years was marred by erratic follow up, intermittent treatment and poor adherence to guideline-based antibiotic therapy. Over this period of time, the patient developed significant worsening of her MAC-LD, macrolide resistance and failure to thrive. Upon presentation 5 years after her initial diagnosis, she had developed MAC-Pleural Disease with an empyema and broncho-pleural fistula. This case illustrates the progression of MAC-LD from nodular bronchiectasis to cavitary disease and pleural involvement leading to clinical deterioration. It highlights challenges related to short and long term management of macrolide resistant MAC-LD and the importance and need for surgical intervention and drainage procedures in patient with MAC-Pleural Disease.

A multidisciplinary approach to the management of nontuberculous mycobacterial lung disease: a clinical perspective.

INTRODUCTION: Management of nontuberculous mycobacterial lung disease (NTM-LD) can be encumbered by difficult diagnostic criteria and complex treatment decisions. As prevalence of this debilitating, often refractory, progressive lung disease increases globally, management must evolve beyond antimicrobials to encompass holistic and customized treatments coordinated by practitioners across various specialties. AREAS COVERED: This review aims to complement the recently updated NTM-LD treatment guidelines and expand current approaches to diagnosis, treatment, and disease management in a multidisciplinary dimension. The foundation of effective long-term management of NTM-LD is awareness of diagnostic criteria, individual patient risk factors, and the importance of managing underlying pulmonary and nonpulmonary comorbidities. The value of adopting all available pharmacological and nonpharmacological treatment modalities with a patient-centered approach to address the needs of long-term patient care cannot be minimized. EXPERT OPINION: This section, while acknowledging the limited advances in understanding of NTM-LD and the availability of newer diagnostic and therapeutic tools over the last decade, underscores the need for a programmatic approach to this chronic, debilitating pulmonary infection. This will not only lead to more comprehensive patient care with better outcomes, but will also inspire and activate robust networks of research and public health initiatives in this field.

The chicken and the egg dilemma: A case of disseminated MAC with Hodgkin's lymphoma.

INTRODUCTION: Mycobacterium avium complex (MAC) as a cause of disseminated disease has been well described in immunocompromised hosts. We report a case of disseminated MAC diagnosed in an otherwise healthy patient, one year before further testing and follow-up revealed a diagnosis of Hodgkin's lymphoma. CASE PRESENTATION: A 48-year-old woman with no significant medical history presented with new-onset fever, chills and night sweats. Chest imaging revealed large conglomerate mediastinal lymph nodes (LN). Endobronchial ultrasound-guided biopsy demonstrated caseating granulomatous inflammation and MAC on broth culture. She was started on guideline-based antibiotic therapy for disseminated MAC but showed no improvement after 6 months. An open mediastinal biopsy confirmed the findings of non-caseating granuloma. However, due to continued symptoms and widespread lymphadenopathy on additional full body imaging, an iliac lymph node core biopsy was performed which revealed abnormal CD30+ lymphoid infiltrate consistent with Hodgkin's lymphoma (HL). She was started on steroids and chemotherapy, whilst maintained on MAC treatment. DISCUSSION: Disseminated MAC is largely limited to immunocompromised hosts, signs and symptoms of which may overlap with lymphoma. Our case demonstrated that multiple initial LN biopsies were unrevealing except for MAC. As no clinical improvement was observed with guideline based MAC treatment, further diagnostic measures were aggressively pursued ultimately leading to a diagnosis of HL. It is unclear whether disseminated MAC preceded lymphoma, an early undiagnosed lymphoma led to MAC infection or an undefined systemic immune disorder was causative for both these processes.

Clinical Management of Respiratory Adverse Events Associated With Amikacin Liposome Inhalation Suspension: Results From a Patient Survey.

Patients with Mycobacterium avium complex lung disease treated with amikacin liposome inhalation suspension (ALIS) at 2 clinics in the United States were surveyed to assess the frequency and management of ALIS-associated respiratory adverse events. Most respondents experienced these events, but management through physician-guided measures (eg, bronchodilator use, oral rinses, and/or temporary dosing adjustments) resulted in symptomatic improvement.

Louisiana physician population trends: will increase in supply meet demand?

Physician shortages in the United States are now recognized broadly and widespread by specialty and geography. While supply is increasing, demand inexorably rises. This situation will probably be further stressed post implementation of healthcare reform. The variations by region and by state are many and significant; this complexity is not fully understood nor yet characterized. Trends similar to the averages of the US have been identified in Louisiana, including the aging of physicians. Lack of physicians, both specialists and generalists, has been reported to compromise quality and effectiveness of healthcare. Thus, the importance of matching up supply and demand is evident. The supply of physicians is increasing in absolute number and in the physicians-to-population ratio. Variations in population, aging, geography, and specialties indicate, in some areas, that this may not be enough to deal with the increasing demand. This paper aims to assess historically how physician shortages may affect the balance of supply and demand in future healthcare delivery, particularly in Louisiana.

Mycobacterium avium complex pulmonary disease: management options in HIV-negative patients.

OBJECTIVE: We present a case series and review of the literature of the management options in non-HIV-infected patients with Mycobacterium avium complex pulmonary disease (MAC-PD) with a focus on treatment failure and drug resistant disease. CASE SERIES: Five case histories are presented, depicting various clinical scenarios necessitating different approaches to therapy and highlighting the limitations and complications of these options. DISCUSSION: Mycobacterium avium complex (MAC) is well recognized as a significant cause of pulmonary disease in non-HIV infected patients and in those with intact immunity. Isolation of non-tuberculous mycobacteria (NTM) in culture is essential for the diagnosis of NTM lung disease. The typical presentation of MAC lung disease is apical fibrocavitary lung disease in men in their late 40s and early 50s who have a history of cigarette smoking and, frequently, excessive alcohol use. Other presentations of NTM lung disease include nodular bronchiectasis, solitary or multiple pulmonary nodules, and hypersensitivity pneumonitis. When indicated, the standard recommended treatment for most patients is a three-times-weekly regimen of clarithromycin or azithromycin, rifampin, and ethambutol with or without amikacin. Daily therapy is recommended for fibrocavitary disease. Based on published studies, macrolides are the only agents used for treatment of MAC disease for which there is a correlation between in vitro susceptibility and in vivo (clinical) response. Data regarding treatment of macrolide-resistant MAC (MRMAC) and multi-drug resistant MAC (MDRMAC) is sparse. Several drugs have been evaluated in drug-resistant MAC and have potential as effective therapy. Use of multiple drugs to which the isolate is susceptible is preferred to avoid development of future resistance. Surgery in mycobacterial disease is technically difficult, but selected patients with focal disease do benefit from resection of the involved lung. CONCLUSIONS: MAC has protean pulmonary manifestations, especially in those with no recognizable impairments in their immune system. Drug treatment, however, remains difficult with high failure rates and poor long-term sputum conversion. This case series is based on our clinical experience highlighting treatment options and the often unrecognized morbidity and mortality of severe, progressive MAC-PD. It underscores the need for increased awareness of MAC-PD and MDRMAC and the difficulties encountered in their management.

Use of mefloquine in multidrug-resistant Mycobacterium avium complex pulmonary disease in an HIV-negative patient.

INTRODUCTION: Mycobacterium avium complex (MAC) is a leading cause of pulmonary disease (PD), even in those with intact immunity, representing about 30% of the cases of pleuropulmonary mycobacterial infection. Based on previous studies, macrolides are the only agents used in the treatment of MAC disease for which there is a correlation between in vitro susceptibility and in vivo (clinical) response. However, resistance develops rapidly if single-agent treatment is used. Data regarding treatment of macrolide-resistant MAC (MRMAC) and multidrug-resistant MAC (MDRMAC) are sparse. CASE SUMMARY: A 50-year-old, HIV-negative white man, weighing 53.6 kg, with severe chronic obstructive pulmonary disease and bronchiectasis was initially on treatment for MAC-PD and MRMAC. The patient was followed between 1999 and 2006. His treatment history revealed that in addition to the multiple drugs administered during the course of his illness, thalidomide, interferon-γ, and mefloquine were also administered. The patient died ~7 years later due to respiratory failure and overwhelming infection CONCLUSIONS: This case report describes the use of mefloquine as adjunct treatment in an HIV-negative patient with MDRMAC-PD and discusses the associated outcomes of drug resistance.

Decreased expression of CD3zeta and nuclear transcription factor kappa B in patients with pulmonary tuberculosis: potential mechanisms and reversibility with treatment.

BACKGROUND: The protective immune response against Mycobacterium tuberculosis relies both on antigen-presenting cells and on T lymphocytes. In patients with different forms of tuberculosis, varying degrees of T cell function--ranging from positive delayed-type hypersensitivity, in asymptomatic infected healthy individuals, to the absence of the response, in patients with miliary or pulmonary tuberculosis (PTB)--have been reported. The decreased expression of CD3zeta reported in T cells from patients with either cancer or leprosy has provided possible explanations for the altered immune response observed in these diseases. METHODS: The present study aimed to compare the expression of CD3zeta , nuclear transcription factor- kappa B (NF- kappa B), arginase activity, and cytokine production in 20 patients with PTB, in 20 tuberculin-positive asymptomatic subjects, and in 14 tuberculin-negative control subjects. RESULTS: Compared with those in tuberculin (purified protein derivative)-negative control subjects, peripheral-blood T lymphocytes from patients with active PTB had significantly (P < .001) decreased expression of CD3zeta and absence of the p65/p50 heterodimer of NF- kappa B. These alterations were reversed only in patients who responded to treatment. Also reported here for the first time is that the presence of arginase activity in peripheral-blood mononuclear-cell lysates of patients with PTB parallels high production of interleukin-10. CONCLUSIONS: The presence of arginase could, in part, explain the decreased expression of CD3zeta . These findings provide a novel mechanism that may explain the T cell dysfunction observed in patients with PTB.

Mycobacterium avium complex pulmonary disease in immunocompetent patients.

Mycobacterium avium complex is becoming increasingly recognized as one of the most common mycobacterial pathogens in humans. It is rapidly becoming a significant cause of pulmonary disease even in those with an intact immunity. In 1997, the American Thoracic Society published recommendations for the diagnosis and treatment of nontuberculous mycobacteria. On the basis of the authors' clinical experience of the myriad presentations of pulmonary Mycobacterium avium complex disease in an immunocompetent host, a clinical classification is proposed. The current data are summarized, and a practical approach to management of the various pulmonary forms of the disease is provided.

Immunity against mycobacteria.

Mycobacterium tuberculosis is the most prevalent infectious pathogen in the world, largely due to its unique interactions with the human immune system. Even in a normal host, a frequent outcome of infection with M. tuberculosis is failure to completely eradicate the organisms, despite the development of cell-mediated immunity. Viable organisms persist in a state in which they do not progressively replicate, leading to latent infection, which carries a risk of breakdown into active (reactivation) tuberculosis at some point later in life. Key features of the immune response against mycobacteria are reviewed here, and potential mechanisms by which the organisms may subvert these host defenses are discussed. Despite the multicellular nature of the host response to infecting mycobacteria, the organisms cannot be eradicated and contribute to the ongoing worldwide epidemic with tuberculosis.

Hepatotoxic effects of tuberculosis therapy.

Preview The recent resurgence of tuberculosis in the United States- fueled in part by its increased incidence among those infected with HIV, substance abusers, and recent immigrants- necessitates a fresh look at tuberculosis therapy. Management is tricky because the first-line antituberculosis drugs can be hepatotoxic, particularly in the presence of underlying liver disease. Patient compliance and close follow-up are essential to achieving a cure while avoiding the pitfalls. Dr Ali describes some of the most commonly used antituberculosis drugs, discusses ways to avoid or minimize hepatotoxicity, and presents a useful algorithm.