RESUMEN
Numerous studies have linked mutations in the pncA gene with resistance to pyrazinamide (Z) in Mycobacterium tuberculosis. However, variations in these mutations are specific to the country of origin of the isolate. The aim of this study was to characterize changes in pncA gene sequence in isolates of M. tuberculosis with resistance to Z, from patients in Mexico. M. tuberculosis isolates were recovered from individuals suspected of carrying drug resistant tuberculosis and respective susceptibility tests were developed. In isolates with resistance to pyrazinamide the pncA gene and its promoter were analyzed by capillary sequencing. From 127 drug-resistant isolates collected, 42 (33%) were resistant to pyrazinamide. The pncA sequences showed 26 changes in 34 (81%) isolates: 18 SNPs (n=26, 62%), four insertions (n=4, 9.5%) and four deletions (n=4, 9.5%). Absence of modifications was observed in eight (19%) sequences/isolates. The most frequent changes were the mutations L120P (n=7) and K96R (n=4). Twelve changes found are reported for the first time. This is the first description of pncA gene modifications in pyrazinamide resistant isolates originating in Mexico. We conclude that the diversity of changes in pncA indicates the presence of a noteworthy variety of pyrazinamide resistant strains occurring in the area.
Asunto(s)
Amidohidrolasas/genética , Antituberculosos/farmacología , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Pirazinamida/farmacología , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Adulto , Femenino , Humanos , Masculino , México/epidemiología , Persona de Mediana Edad , Mutación , Polimorfismo de Nucleótido Simple , Tuberculosis Resistente a Múltiples Medicamentos/epidemiologíaRESUMEN
OBJECTIVE: To describe the respiratory pathogens found in the bronchoalveolar lavage of a Puerto Rican population infected with the human immunodeficiency virus (HIV). BACKGROUND: Empirical treatment is an accepted strategy for management of HIV-related pneumonia, but it is usually recommended for countries that have knowledge of the prevalent organisms in their population. In Puerto Rico, we have relied on data from the United States, but ethnic and geographical differences have been reported. DESIGN: Case series of a HIV-infected population admitted to an academic hospital in Puerto Rico because of respiratory symptoms and who underwent diagnostic standard bronchoalveolar lavage. RESULTS: From August 1998 to March 2000, 32 bronchoalveolar lavages (BAL) were performed in 31 Puerto Rican HIV patients. Nine (31%) were female. Mean age was 37 years old. Predominant mode of infection of the virus was intravenous drug use in men and heterosexual contact in women. BAL was diagnostic in 17/32 (53%) of the cases. Identified respiratory pathogens were Pneumocystis carinii (5), Mycobacterium tuberculosis (4), Staphylococcus aureus (2), Pseudomonas aeuruginosa (1), Bordetella bronchiseptica (1), viridans streptococcus (1), Histoplasma capsulatum (1), Cytomegalovirus (1), and, Mycobacterium kansassi (1). Retrospective review of medical records of non bronchoscoped patients for the period added six culture confirmed tuberculosis cases increasing tuberculosis rate to 18% (10/56). CONCLUSIONS: Tuberculosis appears to be a more frequent pathogen in Puerto Rico than is reported in the United States. A larger study is needed to confirm this finding and thus to clarify whether an initial presumption of tuberculosis should be assumed in the Puerto Rican HIV population.