RESUMEN
We identified 36 rifampin-resistant Mycobacterium kansasii isolates, including 17 (4%) of 464 isolates recovered in Texas between 1989 and 1992. Of 29 patients infected with rifampin-resistant M. kansasii whose history of medication was known, 90% had previously received rifampin, and 58% of these patients had been treated with one or two effective drugs. Thirty-two percent of rifampin-resistant isolates recovered since 1989 were from patients who were seropositive for human immunodeficiency virus (HIV) infection. Twenty courses of therapy with a four-drug regimen determined on the basis of in vitro susceptibilities were administered to 16 patients from whom rifampin-resistant isolates were recovered; the therapy did not include surgery. Sputum cultures converted to negative as the result of 90% of treatments (time to conversion: mean, 11 weeks; range, 4-20 weeks). Bacteriologic relapses occurred in four of five patients who withdrew from therapy after being culture negative for < or = 6 months of therapy and in one of 12 patients who were culture negative for at least 12 months of therapy (mean, 16.3 months). This study suggests that the prognosis for cure of infection due to rifampin-resistant M. kansasii with chemotherapy alone is excellent, although the number of cases appears to be increasing, in part because of the HIV disease epidemic.
Asunto(s)
Antituberculosos/uso terapéutico , Quimioterapia Combinada/uso terapéutico , Infecciones por Mycobacterium no Tuberculosas/epidemiología , Micobacterias no Tuberculosas/efectos de los fármacos , Rifampin/farmacología , Tuberculosis/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Amicacina/administración & dosificación , Antituberculosos/farmacología , Ciprofloxacina/administración & dosificación , Protocolos Clínicos , Farmacorresistencia Microbiana , Etambutol/administración & dosificación , Femenino , Humanos , Isoniazida/administración & dosificación , Masculino , Persona de Mediana Edad , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/microbiología , Pirazinamida/administración & dosificación , Piridoxina/administración & dosificación , Rifampin/administración & dosificación , Estreptomicina/administración & dosificación , Texas/epidemiología , Resultado del Tratamiento , Tuberculosis/tratamiento farmacológico , Tuberculosis/microbiologíaRESUMEN
Sputum conversion rates in Mycobacterium avium-intracellulare (MAI) complex lung disease have ranged from only 50 to 80% despite the use of three to five antituberculosis agents. We initiated a prospective, open, noncomparative trial of initial clarithromycin monotherapy at 500 mg twice a day for 4 months in HIV-negative patients with MAI lung disease. The primary study end point was microbiologic improvement. Of 30 patients enrolled, 20 completed therapy. This latter group was predominantly male (60%), smokers (70%), older than 45 yr of age (90%), infected with Mycobacterium intracellulare (70%) and with bilateral disease (85%). Of 19 patients with pretreatment minimum inhibitory concentrations (MIC) for clarithromycin < 16 micrograms/ml, 58% became sputum-negative, and 21% showed significant reductions in sputum positivity. Heavily positive sputum cultures (> 200 colonies) were reduced from 30 to 47 samples pretherapy (64%) to three of 54 (6%) post-therapy (p < 0.0001); 18 of 19 patients (95%) showed an improvement in sputum cultures, chest radiographs, or both. Only two patients (7%) discontinued the drug because of adverse events. Only three (16%) of 19 isolates developed clarithromycin resistance (MIC > 32 micrograms/ml). Clarithromycin-susceptible and -resistant MAI isolates from the same patient had identical DNA large-restriction fragment patterns. Clarithromycin is the first single agent to be shown efficacious in the treatment of MAI lung disease.
Asunto(s)
Claritromicina/uso terapéutico , Infección por Mycobacterium avium-intracellulare/tratamiento farmacológico , Tuberculosis Pulmonar/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Claritromicina/efectos adversos , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Complejo Mycobacterium avium/efectos de los fármacos , Complejo Mycobacterium avium/aislamiento & purificación , Infección por Mycobacterium avium-intracellulare/microbiología , Estudios Prospectivos , Esputo/microbiología , Tuberculosis Pulmonar/microbiologíaRESUMEN
Fourteen wild strains and 14 relapse or treatment failure isolates of Mycobacterium kansasii were tested and found to be highly susceptible to sulfamethoxazole (SMX), with 26 of 28 isolates having minimal inhibitory concentrations (MIC) of less than or equal to 4 micrograms/ml), using a broth microdilution method. Treatment failure isolates frequently exhibited resistance to rifampin (RMP) (greater than 2 micrograms/ml), isoniazid (INH) (greater than 4 micrograms/ml), and ethambutol (EMB) (greater than 4 micrograms/ml) not seen among the wild strain isolates. Eight patients with cavitary disease caused by RMP-resistant M. kansasii were treated with SMX-containing regimens that also included high dose INH (900 mg), EMB (25 mg/kg), and an aminoglycoside (either streptomycin or amikacin). Patients were treated initially in the hospital for 4 to 10 wk. In 7 of the 8 patients, sputum cultures became negative in a mean of 10 wk (range, 7 to 14 wk). Acquired drug resistance to INH, RMP, and EMB can be demonstrated in M. kansasii, and SMX in combination with other agents chosen on the basis of MIC determinations are effective in the treatment of disease caused by RMP-resistant M. kansasii.