Clofazimine Inhalation Suspension Demonstrates Promising Toxicokinetics in Canines for Treating Pulmonary Nontuberculous Mycobacteria Infection.

Pulmonary nontuberculous mycobacteria (NTM) infection is recognized as a major global health concern due to its rising prevalence worldwide. As an opportunistic pathogen with increasing antibiotics resistance, prolonged systemic dosing with multiple antibiotics remains the primary treatment paradigm. These prolonged treatments, administered predominantly by oral or parenteral routes, often lead to systemic toxicity. A novel inhaled formulation of clofazimine may finally resolve issues of toxicity, thereby providing for improved NTM therapy. Clofazimine inhalation suspension was evaluated in canines to determine toxicity over 28 days of once-a-day dosing. The good laboratory practice (GLP) repeat dosing study evaluated low, mid, and high dosing (2.72 mg/kg and 2.95 mg/kg; 5.45 mg/kg and 5.91 mg/kg; and 10.87 mg/kg and 10.07 mg/kg, average male versus female dosing) of nebulized clofazimine over 30, 60, and 120 min using a jet nebulizer. Toxicokinetic analyses were performed on study days 29, 56, and 84. All three dose levels showed significant residual drug in lung tissue, demonstrating impressive lung loading and long lung residence. Drug concentrations in the lung remained well above the average NTM MIC at all time points, with measurable clofazimine levels at 28 and 56 days postdosing. In contrast, plasma levels of clofazimine were consistently measurable only through 14 days postdosing, with measurements below the limit of quantitation at 56 days postdosing. Clofazimine inhalation suspension may provide an effective therapy for the treatment of NTM infections through direct delivery of antibiotic to the lungs, overcoming the systemic toxicity seen in oral clofazimine treatment for NTM.

Nontuberculous mycobacterial infection presenting as empyema and life threatening pneumothorax: A challenging situation in the emergency department.

Nontuberculous mycobacterial infection in an immunocompetent young patient complicated with empyema and pneumothorax is rarely reported. A 36-year-old man presented to the emergency department with a history of worsening dyspnea and pleuritic chest pain. The patient had unstable vital signs on presentation, and was referred to the resuscitation area on a monitored bed. The patient had a chest x-ray (CXR) performed on a prior occasion at a primary health clinic, revealing pneumothorax and some fluid at the left costophrenic angle. On arrival at the hospital, bedside ultrasound was performed which confirmed the diagnosis of pneumothorax. His vital signs were pulse 153, BP 88/62, RR 50 breaths per minute and his oxygen saturation on air was 92%. Tension pneumothorax was diagnosed based on clinical presentation and given vital signs. It was managed immediately with needle decompression followed by chest tube insertion. The patient improved dramatically after needle decompression with stabilization of vital signs. A CXR was repeated post-needle decompression which showed an incompletely resolved pneumothorax with an increase in the size of the effusion. Iatrogenic haemothorax was a possible explanation for this increase in effusion size. Chest tube was successfully inserted in the fourth intercostal space just anterior to the midaxillary line under full aseptic precautions. The chest tube drained 1.4 liters of blood, which on analysis showed a low pH and elevated adenosine deaminase level. Two out of three sputum samples sent from the medical ward were positive for mycobacteria other than tuberculosis as confirmed on culture. The patient's symptoms improved with percutaneous tube drainage of hemopneumothorax and antituberculous medications.