Four patients with tuberculosis (TB) resistant to five front-line drugs and seven second-line medications have been identified in India, making them virtually untreatable with available medications.

Researchers at PD Hinduja National Hospital and Medical Research Center (Mumbai, India) reported on the four patients, who were resistant to isoniazid, rifampicin, ethambutol, pyrazinamide, and streptomycin--the standard first-line drugs--as well as ofloxacin moxifloxacin, kanamycin, amikacin, capreomycin, para-aminosalicylic acid, and ethionamide. In three of the cases, the researchers conducted a careful analysis of their prescriptions and found that in an effort to cure their multidrug-resistant TB (MDR-TB), each had been given erratic, unsupervised second-line drugs, added individually and often in incorrect doses, from multiple private practitioners over an 18-month period.

As a result, the patients are now classified as more than extensively drug-resistant TB (XDR-TB), and have become totally drug-resistant TB (TDR-TB). These patients are the first in a series of 12 cases that have emerged since doctors at the institution began grappling with increasingly resistant strains of TB. The researchers blamed the rise of such resistance on India's healthcare system, which has had some success against normal TB, but which they said does not pay enough attention to resistant strains. As a result, many patients with resistant TB go to unqualified private physicians, resulting in inadequate care that leads to increasing resistance, rather than cure. The cases were reported in a letter published online on December 21, 2011, in Clinical Infectious Diseases.

“We must ensure treatment adherence to minimize interruption. We must also ensure the selection and use of appropriate drug regimens and rapid diagnostics so that people with drug resistant TB are started on the correct regimens at the right time,” said lead author Zarir Udwadia, MD.

The TB bacterium in most cases succumbs to a regimen consisting of isoniazid, rifampin, ethambutol, and pyrazinamide for eight weeks, followed by isoniazid and rifampin for another 18 weeks. But inadequate or interrupted treatment can lead to resistance; MDR-TB is resistant to isoniazid and rifampin, although other first-line drugs and several second-line drugs remain available. XDR-TB is resistant to isoniazid and rifampin, as well as any fluoroquinolone and at least one of three injectable second-line drugs, such as amikacin, kanamycin, or capreomycin.

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