Changes in leprosy clinical pattern after multidrug therapy implementation.
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Biomedical subjects
Publications and source records attributed to M A Grossi.
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The activity of KRM-1648 was evaluated in a murine model of tuberculosis. Approximately 10(7) viable Mycobacterium tuberculosis ATCC 35801 organisms were given intravenously to 4-week-old female outbred mice. Treatment was started 1 week postinfection and given by gavage for 4 weeks. Viable-cell counts were determined from homogenates of spleen and lung tissues. The activity of KRM-1648 was compared with those of rifampin and rifabutin at 20 mg/kg of body weight. KRM-1648 was more active than either rifampin or rifabutin against organisms in spleens and lungs. KRM-1648 alone and in combination with either isoniazid, ethambutol, pyrazinamide, or levofloxacin was evaluated. Other treatment groups received isoniazid, ethambutol, pyrazinamide, or levofloxacin as single agents. KRM-1648 was the most active single agent evaluated. KRM-1648-pyrazinamide and KRM-1648-isoniazid were the most active combinations. These combinations were more active than KRM-1648 alone. The promising activity of KRM-1648 in M. tuberculosis-infected mice suggests that it is a good candidate for clinical development as a new antituberculosis agent.
The dose-response activity of rifabutin and the comparative activities of rifabutin and rifapentine were evaluated in the beige mouse model of disseminated Mycobacterium avium complex (MAC) infection. In the dose-response study, mice were infected intravenously with approximately 10(7) viable M. avium ATCC 49601. Treatment with rifabutin at 10, 20, or 40 mg/kg of body weight was started 7 days postinfection and was administered daily for 10 days. The mice were sacrificed 3 to 5 days after the last dose. Spleens, livers, and lungs were homogenized, and viable cell counts were determined by serial dilution and plating onto Middlebrook 7H10 agar. A dose-related reduction in MAC cell counts in the organs was noted for this MAC isolate. The comparative activities of rifabutin and rifapentine were determined against a total of five MAC isolates in the beige mouse model. Rifabutin or rifapentine (20 mg/kg each) was administered to infected mice for 10 days. Groups of treated mice were compared with untreated control animals. Despite favorable in vitro susceptibility results, rifabutin and rifapentine had activities in the spleens against only two of the five MAC isolates. For these two MAC isolates, rifabutin was more active than rifapentine. These agents had activities in the lungs against three of five isolates. Further study of rifabutin or rifapentine against a broader range of clinical isolates in a murine infection model may be useful as part of the continuing development of newer rifamycins as anti-MAC agents.
The comparative activities of azithromycin (AZI) and clarithromycin (CLA) against eight Mycobacterium avium complex (MAC) isolates were evaluated in the beige mouse model of disseminated infection. Mice were infected intravenously with approximately 10(7) viable MAC isolate. AZI at 100 or 200 mg/kg of body weight or CLA at 200 mg/kg of body weight was given by gavage daily for 10 days starting at 7 days postinfection. In each study, groups of treated mice were compared with untreated control animals. A dose-related reduction in organism cell counts in the spleens between the groups receiving AZI at 100 and 200 mg/kg was observed. AZI at 200 mg/kg was more active than CLA at 200 mg/kg against six of eight MAC isolates in the spleens. CLA at 200 mg/kg was more active than AZI at 200 mg/kg against three of eight MAC isolates in the lungs. The difference between AZI at 200 mg/kg and CLA at 200 mg/kg against organisms in the lungs was not significant for the remaining five isolates. Clinical trials comparing the activities of AZI and CLA in combination with other agents in patients with disseminated MAC infection are necessary to ascertain any clinically significant differences in the efficacies of these agents.
In this study, 997 leprosy patients were examined, 528 of them with lepromatous leprosy (53%), 199 with borderline leprosy (20%), 167 with tuberculoid leprosy (16%) and 103 (10.3%) with indeterminate leprosy. Changes in the ocular bulb were noted in 314 patients (31.5%) specially in those with lepromatous leprosy. These alterations were greater with increasing age of the patient and length of disease. Severe ocular lesions were rare, probably due to previous systemic treatment. The "pearls" in the fundus of the eye resulting from leprosy were also studied.