Three per cent of TB cases diagnosed at one of Lisbon’s major hospitals between 2003 and 2007 were extensively drug-resistant, and there was a strong correlation between HIV infection or hepatitis C infection and extensively drug-resistant TB, Portuguese researchers reported last week at the XVII International AIDS Conference in Mexico City.
Extensively drug-resistant tuberculosis (XDR-TB), first described in 2006, is defined as TB which is resistant to at least the two first-line drugs rifampicin and isoniazid, as well as any of the second-line anti-TB injectable drugs (amikacin, kanamycin or capreomycin), and to a fluoroquinolone.
XDR-TB has emerged on a large scale in South Africa, largely as a result of transmission within healthcare settings where large numbers of vulnerable HIV-positive patients congregate.
A poster presentation at the International AIDS Conference described the extent of XDR-TB seen in the infectious diseases ward of the Curry Cabral Hospital, Lisbon, Portugal between 2003 and 2007. For this retrospective study, all TB culture-positive strains gathered during that time period were analysed, with additional drug resistance assays and validation performed in reference laboratories.
The study found 595 patients with culture-confirmed TB during the five-year period, 68 (11.4%) of which had multi-drug-resistant TB (MDR-TB) and 17 (2.9%) had XDR-TB. Of the 17 XDR-TB cases, 82% were male, with a mean age of 41.7 years, 65% caucasian and 35% black. The mean duration of hospitalisation was 61 days. Sixty-five percent were HIV-positive, with a median CD4 cell count of 116 cells/mm3. Forty per cent of the XDR-TB cases were receiving antiretroviral therapy. Fifty-two percent were hepatitis C virus seropositive. There was a prior history of TB in 64% of cases, 63% of which had already been diagnosed as MDR-TB.
Mycobacterium tuberculosis was isolated in the sputum of 88% of the patients, 6% in gastric juice and 6% in broncho-alveolar lavage. All patients had pulmonary manifestations (76% with cavitations) and two had extra-pulmonary (nodal) manifestations. The mean time to persistent negative cultures was 49.4 days.
As for first-line drug resistance, 82% were resistant to all four drugs (isoniazid, rifampicin, ethambutol, pyrazinamide), 12% to three of these drugs and 6% to two. More than half were resistant to all second-line injectable drugs and fluoroquinolones. There were two deaths. Encouragingly, just over half (53%) of the patients were discharged after persistent (at least three) culture-negative samples.
The researchers concluded that "XDR-TB was in our study a prevalent infection closely related to HIV infection but also to HCV, intravenous drug abuse and worse socioeconomic conditions." (Detailed analyses of IDU and socioeconomic factors were not available.) They also stated that, although fatalities due to XDR-TB were "not very high … our data emphasize the need for better surveillance and effective treatment in all patients."