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PROCAARE: RELATED EPIDEMICS--TUBERCULOSIS--RIFAMPIN RESISTANCE
- From: Albert Shaw <firstname.lastname@example.org>
- Date: Wed, 12 Jun 1996 02:01:37 -0400 (EDT)
KEYWORDS: TUBERCULOSIS/ RESISTANCE/ RIFAMPIN/ RIFABUTIN/ PROPHYLAXIS
Reference: Bishai, W.R., Graham, N.M.H., Harrington, S., Page, C.,
Moore-Rice, K., Hooper, N., Chaisson, R.E. (1996). Brief report:
rifampin-resistant tuberculosis in a patient receiving rifabutin
prophylaxis. New Engl. J. Med. 334: 1573-6.
This report describes the case of a 35 year old man with AIDS and a CD4
count of 7/mm3. The patient presented with a two-month history of fever,
sweats, cough, dyspnea and weight loss; chest x-ray revealed hilar
adenopathy without infiltrates, and sputum smears demonstrated numerous
acid-fast bacilli. M. tuberculosis was subsequently cultured, and this
isolate was sensitive to INH, rifampin, pyrazinamide, ethambutol, and
The patient received six months of directly observed therapy, beginning
with INH/ rifampin/ pyrazinamide/ ethambutol daily for 16 days, then
twice a week for 6 weeks, followed by INH/ rifampin twice a week for 33
doses. Cultures were negative for M. tuberculosis after 2 months of
Nine months after the beginning of antituberculous therapy, a follow-up
chest radiograph was normal, and sputum smears and cultures were negative
at 10 months. The patient subsequenly saw a new physician who prescribed
rifabutin (300 mg qD) for Mycobacterium avium complex prophylaxis. Two
months later, fever, cough and dyspnea along with diffuse interstitial
infiltrates on chest x-ray were reported, and the patient died of
respiratory failure. M. tuberculosis resistant to rifampin and
rifabutin, but sensitive to INH, pyrazinamide, ethambutol, and
streptomycin was isolated from sputum.
DNA restriction fragment length polymorphism (RFLP) analyses revealed
that the M. tuberculosis strains from the first and second episodes of
tuberculosis were virtually identical, implying a clonal genetic
relationship between the strains. Sequence determination of the M.
tuberculosis rpoB gene demonstrated a point mutation in the resistant
strain commonly found in other rifampin-resistant isolates. This
mutation and RFLP pattern was rare in the community (only 2 of 101
isolates) and no epidemiologic link between the patient and subjects with
an apparently similar strain could be established. Thus, it seems
unlikely that the patient was reinfected with the resistant M.
tuberculosis, and a reasonable hypothesis would implicate relapsed
disease with rifabutin use potentially selecting for acquired rifampin
resistance (if rifabutin use were sporadic, acquired resistance might be
even more likely).
This report emphasizes the difficulties of tuberculosis treatment in the
setting of AIDS. In addition, the importance of screening patients for
active mycobacterial infection prior to the institution of rifabutin
prophylaxis appears clear, as it seems most likely that selection
pressures imposed by rifabutin contributed to the acquisition of resistance.