Use of Delamanid for Extensively Drug-Resistant Tuberculosis
In August 2017, the FDA granted an NDA for a single-use of delamanid for a case of extensively drug-resistant tuberculosis.
Extensively drug-resistant tuberculosis (XDR TB) is a defined by the Centers for Disease Control and Prevention (CDC) as a TB infection that is resistant to isoniazid and rifampin, any fluoroquinolone, and at least 1 of the 3 second-line injectable drugs. There are substantially limited treatment options for these infections, and the ones that are available are expensive, less effective, and cause more side effects.
In April 2017, an Eastern-European male patient presented with cough, chest pain, weakness, and weight loss. A sputum sample was found to be smear positive for acid-fast bacilli (AFB) and a chest radiograph and chest computerized tomography scan showed bilateral pulmonary, cavity disease with vertebral involvement.
As part of the investigation, 3 members of his family were evaluated for TB and his wife tested positive and was treated for latent TB with 4 months of rifampin.
The patient was given standard first-line therapy of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE). After 2 weeks of receiving treatment, the patient developed a rash and further TB consultation was required. As a result, HRZE was discontinued and the patient was put on levofloxacin and linezolid prior to being discharged from the hospital.
The sputum samples were sent to the CDC for drug resistance testing which identified resistance to HRZE, fluoroquinolones, and injectable aminoglycosides amikacin, kanamycin, and capreomycin, indicating an XDR TB infection.
Susceptibility testing by 7H11 agar proportion at the National Jewish Health Mycobacteriology Laboratory confirmed resistance to HRZE, streptomycin, kanamycin, amikacin, capreomycin, ethionamide, and ciprofloxacin/ofloxacin, and reported susceptibility to cycloserine, para-aminosalicyclic acid (PAS), linezolid, clofazimine, and bedaquiline, according to the report published in the CDC’s Morbidity and Mortality Weekly Report.
With limited options, the patient was designated to receive a regimen of bedaquiline, clofazimine, linezolid, PAS, and cycloserine. Due to the severity of the infection, the use of delamanid, which has not yet been approved by the US Food and Drug Administration, was granted by the CDC-funded TB Center of Excellence as well as the CDC’s Division of TB Elimination.
Delamanid is a nitro-imidazole that has been developed to address some of the adverse reactions as well as adherence difficulties associated with current treatment options for drug-resistant TB.
The drug has been evaluated in trials assessing safety, tolerability, and early bactericidal activity, according to the report. Additionally, delamanid has been shown to improve treatment outcomes and effectiveness in XDR TB infections when used in combination with World Health Organization recommended drugs.
As part of the protocols, the physician requested an emergency investigational new drug application (DNA) for a single-patient treatment with the FDA. The NDA was approved, and the physician participated in pharmacovigilance training after reviewing the protocol with the European Respiratory Society/WHO Consilium.
The patient began the new regimen in late August and his initial symptoms improved within the first month of treatment. His sputum smear converted to negative on August 22 and his culture converted to negative on October 31.
The patient continues to adhere to a 24-month treatment regimen with continued clinical improvement and no reported adverse events, thus far.
“Prompt access to this new anti-TB drug increased therapeutic options for this patient with XDR disease,” authors of the report write.
Providers considering delamanid as an option for patients with XDR TB infections can seek advisement from the CDC’s Division of Tuberculosis Elimination or the regional TB Center of Excellence.