Surveillance of adverse events in the treatment of drug-resistant tuberculosis: first global report.

The World Health Organization (WHO) recommends that countries implement pharmacovigilance and collect information on active drug safety monitoring (aDSM) and management of adverse events.The aim of this prospective study was to evaluate the frequency and severity of adverse events to anti-tuberculosis (TB) drugs in a cohort of consecutive TB patients treated with new (i.e. bedaquiline, delamanid) and repurposed (i.e. clofazimine, linezolid) drugs, based on the WHO aDSM project. Adverse events were collected prospectively after attribution to a specific drug together with demographic, bacteriological, radiological and clinical information at diagnosis and during therapy. This interim analysis included patients who completed or were still on treatment at time of data collection.Globally, 45 centres from 26 countries/regions reported 658 patients (68.7% male, 4.4% HIV co-infected) treated as follows: 87.7% with bedaquiline, 18.4% with delamanid (6.1% with both), 81.5% with linezolid and 32.4% with clofazimine. Overall, 504 adverse event episodes were reported: 447 (88.7%) were classified as minor (grade 1-2) and 57 (11.3%) as serious (grade 3-5). The majority of the 57 serious adverse events reported by 55 patients (51 out of 57, 89.5%) ultimately resolved. Among patients reporting serious adverse events, some drugs held responsible were discontinued: bedaquiline in 0.35% (two out of 577), delamanid in 0.8% (one out of 121), linezolid in 1.9% (10 out of 536) and clofazimine in 1.4% (three out of 213) of patients. Serious adverse events were reported in 6.9% (nine out of 131) of patients treated with amikacin, 0.4% (one out of 221) with ethionamide/prothionamide, 2.8% (15 out of 536) with linezolid and 1.8% (eight out of 498) with cycloserine/terizidone.The aDSM study provided valuable information, but implementation needs scaling-up to support patient-centred care.

Bedaquiline and Delamanid Combination Treatment of 5 Patients with Pulmonary Extensively Drug-Resistant Tuberculosis.

We report the experiences of 5 patients taking bedaquiline with delamanid in combination: 1 patient was cured; 3 culture converted, with 2 continuing and 1 changing therapy; and 1 died from respiratory insufficiency. For 2 patients, QT-interval prolongation but no arrhythmias occurred. Use of this therapy is justified for patients with limited options.

Fibrotic interstitial lung disease occurring as sequelae of COVID-19 pneumonia despite concomitant steroids.

A 75-year-old female with no history of lung disease developed severe pulmonary fibrosis within 1 month of acute severe COVID-19 pneumonia. She developed dry basal crackles, hypoxia needing home oxygen, and computed tomography changes which dramatically evolved from acute ground-glass opacities to honeycombing and traction bronchiectasis. Interestingly, these changes occurred despite her being on steroids through most of her hospital stay. She is being commenced on pirfenidone and her responses are carefully monitored, but the role of antifibrotic drugs are unclear and will only be established from large clinical trials.

A 12-year-old girl with Hodgkin's disease presenting as a non-resolving pneumonia and an endobronchial nodule.

The presence of a non-resolving pneumonia warrants the suspicion of a possible malignancy. While pulmonary involvement in Hodgkin's disease can present as a non-resolving pneumonia, the clinical clues of dyspnoea, stridor and wheeze point to a possible endobronchial involvement. A bronchoscopy in such a situation can be valuable for diagnosis, and can aid in staging of the disease. The true incidence of endobronchial involvement in Hodgkin's disease is not known, but when diagnosed early and treated appropriately, the prognosis is usually good, and a complete cure is possible.

Outcomes of patients with drug-resistant-tuberculosis treated with bedaquiline-containing regimens and undergoing adjunctive surgery.

OBJECTIVES: No study evaluated the contribution of adjunctive surgery in bedaquiline-treated patients. This study describes treatment outcomes and complications in a cohort of drug-resistant pulmonary tuberculosis (TB) cases treated with bedaquiline-containing regimens undergoing surgery. METHODS: This retrospective observational study recruited patients treated for TB in 12 centres in 9 countries between January 2007 and March 2015. Patients who had surgical indications in a bedaquiline-treated programme-based cohort were selected and surgery-related information was collected. Patient characteristics and surgical indications were described together with type of operation, surgical complications, bacteriological conversion rates, and treatment outcomes. Treatment outcomes were evaluated according to the time of surgery. RESULTS: 57 bedaquiline-exposed cases resistant to a median of 7 drugs had indication for surgery (52 retreatments; 50 extensively drug-resistant (XDR) or pre XDR-TB). Sixty percent of cases initiated bedaquiline treatment following surgery, while 36.4% underwent the bedaquiline regimen before surgery and completed it after the operation. At treatment completion 90% culture-converted with 69.1% achieving treatment success; 21.8% had unfavourable outcomes (20.0% treatment failure, 1.8% lost to follow-up), and 9.1% were still undergoing treatment. CONCLUSIONS: The study results suggest that bedaquiline and surgery can be safely and effectively combined in selected cases with a specific indication.

Who will teach the teachers: An analysis of the inhaler technique of Indian patients and health care providers in a tertiary health care centre.

INTRODUCTION: The proper use of inhalers is essential for ensuring proper control of the disease. Various studies have shown high levels of improper use and lack of knowledge of the correct technique among patients with asthma. However, less data are available on how health care workers (HCW's) use inhalers. MATERIALS AND METHODS: The study was conducted at a Tertiary Care Hospital in Mumbai. We evaluated the pMDI technique in 141 consecutive adult asthmatics and 100 HCW's. All patients and HCW's were graded out of 10 points for following 10 steps. These were derived from Melani et al.'s study on inhaler mishandling. RESULTS: Techniques of 141 patients and 100 HCW's (55 nurses and 45 doctors) were analyzed. The average technique score among patients ranged from 0 to 10 with a mean of 4.65 ± 2.00. The combined score for health workers ranged from 3 to 9 with a mean of 5.45 ± 1.47. Doctors had a higher score of 6.35 ± 1.33 as opposed to the nurses' score of 4.70 ± 1.13 (P < 0.05). There was no significant difference between scores of nurses and patients (P > 0.05). CONCLUSIONS: Our study highlights the need for better education of not only patients but also health care providers regarding the appropriate use of inhaler devices in order to achieve optimal control of obstructive airway diseases.