In vivo efficacy of zidovudine (3'-azido-3'-deoxythymidine) in experimental gram-negative-bacterial infections.
The therapeutic efficacy of orally administered zidovuldine (3'-azido-3'-deoxythymidine) was determined in animals infected with Escherichia coli and Salmonella dublin. The 50% effective dose (ED50) of zidovudine (9.6 to 11.8 mg/kg of body weight) compared favorably with that of trimethoprim (19.4 to 22.2 mg/kg) in mice with systemic E. coli infection. At 50 mg/kg, both zidovudine and ampicillin reduced the number of bacteria in the kidneys of mice and prevented lethal infection in mice with ascending pyelonephritis caused by E. coli. Zidovudine prevented a lethal S. dublin infection in calves over a wide dose range (8.0 to 31.0 mg/kg per day). Zidovudine levels in plasma of uninfected mice were 28.2 +/- 4.5 and 7.9 +/- 2.2 micrograms/ml at 30 and 60 min, respectively, exceeding the MICs for the bacteria used in the infections. Few zidovudine-resistant strains were observed. The in vivo data raise the possibility that zidovudine may have an antibacterial effect in patients receiving this therapy.
Keith
B R
BR
Division of Molecular Genetics and Microbiology, Wellcome Research Laboratories, Research Triangle Park, North Carolina 27709.
White
G
G
Wilson
H R
HR
D000667:Ampicillin / Q000627:therapeutic use; D000818:Animals; D001424:Bacterial Infections / Q000188:drug therapy*; D002417:Cattle; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000382:microbiology; D005260:Female; D006090:Gram-Negative Bacteria; D051379:Mice; D008807:Mice, Inbred BALB C; D011704:Pyelonephritis / Q000188:drug therapy; D012480:Salmonella Infections / Q000188:drug therapy / Q000382:microbiology; D014295:Trimethoprim / Q000627:therapeutic use; D015215:Zidovudine / Q000493:pharmacokinetics / Q000627:therapeutic use*
D015215:Zidovudine; D000667:Ampicillin; D014295:Trimethoprim