TB that developed resistance to every drug kills two in Italy

Michael Carter
Published: 21 May 2007

Tuberculosis with resistance to every drug has been reported in Italy. In 2003, two middle-class, HIV-negative, Italian women died of tuberculosis that had resistance to every anti-tuberculosis drug. A report of the cases is published in the May 17th edition of Eurosurveillance Weekly Release. The authors of the report emphasise that medical mismanagement and inappropriate use of anti-tuberculosis therapy was instrumental in the development of ultimately fatal, extremely drug-resistant tuberculosis (XXDR-TB).

Extensively drug-resistant tuberculosis (XDR-TB) was first formally defined in early 2006 and described a form of tuberculosis with resistance to the first-line anti-tuberculosis drugs, isoniazid and rifampicin, and three of the six classes of drugs that constitute second-line tuberculosis therapy. This definition was revised in late 2006 to describe cases that involve resistance to isoniazid and rifampicin, as well as any drug from the flouroquinolone class, and any of the three injectable drugs used to treat tuberculosis; capreomycin, kanamycin and amikacin.

An analysis conducted in March 2007 revealed that ten of the 21 countries that have reported cases of XDR-TB so far are either in, or border, Europe. In many cases, XDR-TB has affected HIV-positive individuals and has been associated with a very poor prognosis.

Doctors have developed a further diagnostic term to describe tuberculosis with an even greater degree of drug resistance. Extensively drug-resistant tuberculosis, or XXDR-TB, defines any case of tuberculosis with resistance to all first- and second-drugs with anti-tuberculosis activity.

Two cases of XXDR-TB have occurred in Italy. The cases had some similarities, both involving young, Italian-born, HIV-negative, middle-class women. Both cases also involved medical mismanagement which appears to have been instrumental in the development of XXDR-TB. This mismanagement occurred at a succession of non-specialist healthcare facilities before final referral to a hospital with a specialist tuberculosis facility. By this time, however, both women had extensive drug resistance and died in 2003 after receiving unsuccessful therapy with every anti-tuberculosis drug.

The first case involved a woman who acquired multidrug resistant tuberculosis (MDR-TB – the form of the infection with resistance to isoniazid and rifampicin) from her mother. Over the course of 18 months, the woman was admitted to three different hospitals and received recognised first- and second-line anti-tuberculosis therapy. She was then referred to a specialist tuberculosis clinic and was treated with a third-line regimen of rifabutin, clofazimine, dapsone, thiacetazon and clarithromycin for 94 months until her death. The investigators note that although the patient was not tested for resistance to dapsone, clarithromycin and thiacetazon, she was found to be resistant to all other drugs used to treat her.

Case two was admitted to three different hospitals over approximately two years. She also received first, second, and third-line treatment regimens. As in the first case, unsuccessful third-line therapy was provided by the specialist tuberculosis facility, this time for 60 months. Drug sensitivity testing indicated that the patient had developed resistance to every drug she received.

The authors of the case reports emphasise the role that inappropriate treatment and mismanagement played in the emergence of XXDR-TB in these women and their ultimate deaths. They conclude that effective tuberculosis control in Europe is dependent upon “improvement of policies and practices.”


Migliori GB et al. First tuberculosis cases in Italy resistant to all tested drugs. Eurosurveillance Weekly Release 12: 5, 2007.

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