Acquired Multidrug-Resistant Tuberculosis -- Buenaventura, Colombia, 1998

In 1996, the incidence of tuberculosis (TB) in Colombia was 26.5 per 100,000 population, and mortality was 3.4 per 100,000; in comparison, the incidence in Buenaventura, a port town on the Pacific coast, was 90.5 per 100,000, and mortality was 9.4 per 100,000 (1). The prevalence of multidrug-resistant tuberculosis (MDR-TB) (i.e., Mycobacterium tuberculosis isolates resistant to at least isoniazid {INH} and rifampin {RIF}) was not known because susceptibility testing is not performed routinely, and data on drug resistance for the country have not been collected systematically. During October-November 1997, at the request of the Secretary of Health in Cali, Colombia, the International Center for Training and Medical Investigation in Cali performed sputum cultures for M. tuberculosis and drug-susceptibility testing on isolates from 18 (75%) of 24 TB patients in Buenaventura who were known to be clinically unresponsive to standard TB treatment. MDR-TB was identified in 12 (67%) of these patients, four of whom subsequently died. In March 1998, the International Center for Training and Medical Investigation and the Secretary of Health of Colombia invited CDC to participate in an investigation of these patients with MDR-TB. This report summarizes the findings of this investigation, which indicated that inconsistencies in treatment may have contributed to this outbreak, and provides recommendations for the prevention and control of MDR-TB in Buenaventura.

A case was defined as laboratory-confirmed MDR-TB in any of the 24 clinically unresponsive TB patients. The median age of the 12 MDR-TB case-patients was 30 years (range: 18-79 years); nine (75%) were men, and all were long-term residents of Buenaventura (median: 29 years; range: 17-80 years). Of the 12, 10 (83%) had no known epidemiologic link to another MDR-TB case. Of seven persons who were tested for human immunodeficiency virus infection, none were positive. Sputum specimens from five case-patients were smear-positive for acid-fast bacilli (AFB).

Clinical charts of all persons with MDR-TB were reviewed for possible factors associated with the development of MDR-TB. All case-patients had received a median of 3.5 years of TB treatment (range: 2-13 years); however, 11 (92%) had treatment interrupted and reinitiated several times. Of the 12 case-patients, 10 had a history of not taking the prescribed anti-TB medications for at least 1 month. One patient had been started on a suboptimal initial treatment regimen instead of the recommended regimen of 4 months of treatment with INH, RIF, pyrazinamide, and streptomycin, followed by 2 months of INH and RIF. Nine patients rema-ning AFB-smear-positive after 4 months had not received the recommended retreatment regimen. Eleven (92%) patients had TB medications improperly added and subtracted to their treatment regimen. Seven (58%) patients had a single drug added to a failing regimen. In addition, three of 10 case-patients with available data did not have sputum specimens obtained after failing to appear for treatment during at least 1 month, and six of nine case-patients with available data did not receive directly observed therapy (DOT). All 12 case-patients experienced at least two instances of incorrect treatment or management of their illness (median: 3.9; range: two-six) based on World Health Organization (WHO) and Colombian treatment protocols.

Reported by: LE Osorio, MV Villegas, AM Benitez, H Hernandez, JF Miranda, N Saravia, International Center for Training and Medical Investigation, Cali; MC Castano, N Henriquez, S Quinonez, Secretary of Health of the Valle del Cauca; LE Sanchez, Buenaventura Hospital, Cali, Colombia. TB/Mycobacteriology Br, Div of AIDS, STD, and TB Laboratory Research, National Center for Infectious Diseases; International Activity, Field Svcs Br, Div of Tuberculosis Elimination, National Center for HIV, STD, and TB Prevention; and an EIS Officer, CDC.

Editorial Note

Editorial Note: Each year, approximately 8 million new cases and 3 million deaths worldwide are attributable to TB (2). Most patients diagnosed with TB harbor drug-susceptible strains of M. tuberculosis that respond well to a short-course (6-8 months) multidrug chemotherapy regimen recommended by WHO (3). Although the cure rate is greater than 80% in most countries where the regimen has been successfully applied and its administration appropriately supervised (3), the worldwide emergence of MDR-TB threatens global TB-control efforts (4).

Treatment history is the most significant factor associated with the appearance of drug-resistant TB (5). This report identified specific aspects of treatment and patient management that contributed to acquired drug resistance in Buenaventura. The most common factors in this study were failure to start the WHO-recommended retreatment regimen in patients who were unresponsive to the initial regimen and inappropriate additions or subtractions of medications during treatment. M. tuberculosis organisms also may have acquired drug resistance as a result of patient factors (e.g., nonadherence with treatment) and programmatic factors (e.g., lack of DOT) (4). Many patients had treatment interrupted and reinitiated in part because, in 1996, the TB-control program was decentralized from a hospital-based system to a health-post-based system.

The findings in this report are subject to at least three limitations. First, details of the initial TB diagnosis and treatment episode were not available for all patients. Second, clinical records and specimens were not available to ascertain whether a patient was originally infected with a drug-resistant strain or the strain acquired the drug resistance during therapy. Third, MDR-TB case-patients described in this report may not be representative of all MDR-TB patients in Buenaventura.

The findings from this investigation have led to improvements in TB-control efforts in Buenaventura in the context of a decentralized health system. Structural changes in the overall TB program have been implemented, including the designation of personnel to direct the program and the installation of mechanisms to monitor and evaluate TB services. Training for physicians and health-care workers in the management of TB and MDR-TB has been initiated. To improve patient adherence to TB treatment, the use of WHO-recommended DOT was initiated for both MDR-TB patients and other TB patients. Finally, new treatment regimens have been designed for each patient, based on drug-susceptibility testing performed by the International Center for Training and Medical Investigation.

References

1. Ministry of Health, Republic of Colombia. Guide to integrated care: prevention and control of tuberculosis {Spanish}. Bogota, Colombia: Ministry of Health, 1997.

2. Dolin PJ, Raviglione MC, Kochi A. Global tuberculosis incidence and mortality during 1990-2000. Bull World Health Organ 1994;72:213-20.

3. World Health Organization. Treatment of tuberculosis: guidelines for national programmes. 2nd ed. Geneva, Switzerland: World Health Organization, 1997; report no. WHO/TB/97.220.

4. Pablo-Mendez A, Raviglione MC, Laszlo A, et al. Global surveillance for antituberculosis-drug resistance, 1994-1997. N Engl J Med 1998;338: 1641-9.

5. World Health Organization. Anti-tuberculosis drug resistance in the world: the WHO/IUTALD Global Project on Anti-tuberculosis Drug Resistance Surveillance, 1994-1997. Geneva, Switzerland: WHO Global Tuberculosis Programme, 1997; report no. WHO/TB/97.229.

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