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Comparative efficacies of azithromycin ( Zithromax ) and ciprofloxacin against experimental Salmonella typhimurium infection in mice.

Azithromycin ( Zithromax ) was compared with ciprofloxacin for the treatment of established intracellular infection with Salmonella typhimurium LT-2 in CF-1 mice. For studies of mortality, mice received five times the LD50 of organisms intraperitoneally and were given drugs intragastrically once daily for seven days. For studies of in-vivo antibacterial activity, splenic viable counts were measured in mice that had received 0.5 times the intraperitoneal LD50 and had been given drugs for three days. The MICs of azithromycin ( Zithromax ) and ciprofloxacin, respectively, against LT-2 were 4.0 and 0.03 mg/L. The 50% protective doses of the drugs required to prevent mortality were azithromycin ( Zithromax ) 24.7 mg/kg/day, and ciprofloxacin 30.2 mg/kg/day. Treatment with azithromycin ( Zithromax ) and ciprofloxacin in doses of 25 and 100 mg/kg/day resulted in reduction of mean log10 cfu per spleen. Splenic concentrations of azithromycin ( Zithromax ) up to 8 h after treatment exceeded its MIC against the LT-2 strain, whereas serum levels were less than the MIC. These results indicated that azithromycin ( Zithromax ) given orally once daily was as effective as ciprofloxacin against established murine Salmonella infection and that the efficacy of azithromycin ( Zithromax ) correlated with adequate tissue concentrations of antibiotic.

Azithromycin ( Zithromax ) is the first of a class of antibiotics classified as azalides. Six ball pythons (Python regius) were given a single dose of azithromycin ( Zithromax ) at 10 mg/kg p.o. and i.v. in a crossover design. Serial blood samples were collected for unchanged azithromycin ( Zithromax ) and to determine, if possible, the structure and number of circulating azithromycin ( Zithromax ) metabolites. After a 4-month wash-out period, the snakes were given azithromycin ( Zithromax ) p.o. as a single dose of 10 mg/kg for the study of azithromycin ( Zithromax ) metabolism and metabolite tissue distribution. Bile, liver, lung, kidney, and skin samples were analyzed for the metabolites identified from the first experiment. Unchanged azithromycin ( Zithromax ) accounted for 80, 68, and 60% of the total material at 12, 24, and 48 h postadministration in plasma, independent of route of administration. At both 24 and 72 h postadministration, azithromycin ( Zithromax ) accounted for 70% of total azithromycin ( Zithromax )- associated material in bile. In liver and kidney, unchanged azithromycin ( Zithromax ) accounted for 40% of the total azithromycin ( Zithromax )-associated material; this doubled in lung and skin. Fifteen metabolites were positively or tentatively identified in plasma, bile, or tissues of all snakes. Four of these possible metabolites: 3'-desamine-3-ene-azithromycin ( Zithromax ), descladinose dehydroxy-2-ene-azithromycin ( Zithromax ), 3'-desamine-3-ene descladinose-azithromycin ( Zithromax ), and 3'-N-nitroso,9a-N-desmethyl-azithromycin ( Zithromax ) are unique to this species. Descladinose-azithromycin ( Zithromax ), 3'-N-desmethyl,9a-N-desmethyl-azithromycin ( Zithromax ), and 3'-N-desmethyl, 3'-O-desmethyl-azithromycin ( Zithromax ) were the only metabolites identified in skin. Kidney tissue contained a greater number of metabolites than liver tissue, with 3'-N-didesmethyl-azithromycin ( Zithromax ) being identified only in the kidney. Compared with the dog and cat, a greater number of metabolites were identified in ball python plasma. The percentage of unchanged azithromycin ( Zithromax ) in bile is not different between the three species.

Four children on chemotherapy for acute lymphoblastic leukemia presented with severe diarrhea and dehydration. Cryptosporidium was identified in the stools using modified Ziehl-Neelsen stain. Two of them received paromomycin and responded well. One was started on paromomycin for 10 days and although there was clinical improvement, his stools examination continued to be positive for Cryptosporidium. He then received azithromycin ( Zithromax ) for 10 days. He responded well and his stools became negative for Cryptosporidium. The fourth patient received azithromycin ( Zithromax ) from the start and responded well. Cryptosporidium should be considered in all immunocompromised children with severe or prolonged diarrhea, and since it is not seen in a routine ova and parasite examination, the laboratory should be notified for diagnostic confirmation using modified Ziehl-Neelsen stain. Immunocompromised children with Cryptosporidium diarrhea may benefit from paromomycin or azithromycin ( Zithromax ) therapy.

In vitro evaluation of the activities of azithromycin ( Zithromax ) alone and combined with pyrimethamine against Toxoplasma gondii.

By using an in vitro microassay to assess drug interaction, azithromycin ( Zithromax ) combined to pyrimethamine was found more active than pyrimethamine alone against Toxoplasma gondii, and additivity between those drugs was demonstrated. Our results show that the combination of azithromycin ( Zithromax ) and pyrimethamine may lead to a more rapid control of T. gondii.

 

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