Isoniazid resistant TB and non-compliance.

We read with interest the report by Ruddy et al on the outbreak of isoniazid resistant tuberculosis in North London. We share their concern about the development of multidrug resistant tuberculosis (MDR-TB) in patients infected with a Mycobacterium tuberculosis strain with primary isoniazid resistance which may occur especially in cases of noncompliance. In the Netherlands the incidence of TB is approximately 9 per 100 000, and it occurs more frequently in the high risk groups comprising people with a high risk for noncompliance. We therefore consider directly observed therapy (DOT) absolutely mandatory in all patients in the high risk groups, especially those infected with a primary isoniazid resistant strain. Over the last 10 years 620 patients with TB have been treated in our hospital, of whom 33 (5%) had a primary isoniazid resistant strain, a percentage close to the 6% reported in England and Wales. To date, all but one of these 33 patients successfully finished the standard treatment (isoniazid, rifampicin, pyrazinamide and ethambutol). The one patient who was non-compliant developed MDR-TB. Restriction fragment length polymorphism (RFLP) typing confirmed that the MDR-TB was caused by the same strain. However, besides non-compliance, two other factors are also important in the development of MDR-TB. Firstly, it may develop in patients with proven compliance but in whom perfusion is inadequate; and, secondly, it may be the result of poor penetration by the medication such as in cases with abscesses and empyemas. 3 This occurred in two of our patients with gross thickening and extensive calcifications of the pleura who were infected with a susceptible M tuberculosis strain at the beginning of their treatment. We do not agree that prolonged treatment should be applied in non-compliant patients with isoniazid resistance 4 as recommended by the BTS. Simply extending the duration of unsupervised treatment might even increase the problem of resistance. In the Netherlands it is easier to detain patients who are infectious, and also those who are nonadherent if there is a reasonable risk that the patient may become infectious.