Multidrug resistant tuberculosis: practical lessons for HIV units.

The emergence of drug resistant and multidrug resistant (MDR) tuberculosis has been well documented in the United States and other parts of the world. Since 1990, at least ten nosocomial outbreaks ofMDR tuberculosis have been reported in the United States and Europe,'-' including two recent outbreaks in London.67 Most of those who developed tuberculosis in these outbreaks were HIVinfected patients, although transmission and active disease have also been documented in immunocompetent health care workers.' Two recent studies based on restrictionfragment length polymorphisms have suggested that recent transmission accounts for as much as 40% of drug resistant adult cases, particularly among HIV infected persons.89 Factors identified as contributing to these outbreaks included a failure or delay in the recognition and diagnosis of tuberculosis, delayed laboratory identification of drug-resistance and thus initiation of appropriate treatment, failure to achieve and maintain effective isolation of known or suspected tuberculosis cases, and inadequate ventilation in the ward or areas where procedures leading to aerosolisation of sputum are performed.'0 Initial follow-up studies of patients with MDR tuberculosis and HIV infection reported extremely high mortality rates, particularly among patients with AIDS. Survival data showed a median survival of 4 to 16 weeks for patients with MDR-tuberculosis and AIDS," and 14 months for HIV infected patients without a diagnosis of AIDS.'2 More recent studies have observed improved outcomes when HIV infected patients received prompt diagnosis and treatment with two or more drugs that had in vitro activity against the drug-resistant isolates. However, only a small percentage of patients with MDR-tuberculosis achieve a sustained sputum culture conversion to negative, and many remain intermittently smear and culture positive for some time, despite clinical signs of response." An important source of the delay in diagnosis is the difficulty in recognizing tuberculosis in patients with HIV infection. Such patients are more likely to present atypically, with, for example, meningitis, skin lesions, bacteraemia, or features of primary disease.'2 The presenting signs and symptoms also tend to be non-specific, and may be confused with Mycobacterum avium intracellulare infection, lymphoma, AIDS wasting syndrome, cytomegalovirus infection, or other opportunistic diseases. The clinical presentation of patients with drug-susceptible and MDR tuberculosis tend to be similar, although one report found that those with MDR tuberculosis were more likely to have both pulmonary and extrapulmonary disease." There is no evidence that MDR strains are more infectious than drug-susceptible ones. In contrast to the well-established treatment protocols for drug-susceptible tuberculosis, the optimal therapy for drug-resistant and MDR tuberculosis is neither well studied nor standardised. It is generally recommended that patients should receive at least three, and usually four drugs to which the current isolate is susceptible, and which the patient has not received in the past. The list of candidate drugs used to treat MDR tuberculosis and the most common side effects are shown in the table. The selection of specific empirical regimens will depend on the local pattern of drug susceptibility, since resistance patterns may vary from country to country and from hospital