Antimicrob Agents Chemother. 1994 Aug;38(8):1862-3.
Efficacy of azithromycin [Zithromax] as a causal prophylactic agent against murine malaria.

Andersen SL, Ager AL, McGreevy P, Schuster BG, Ellis W, Berman J.

Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, DC 20307-5100.

The efficacy of the newly marketed azalide azithromycin [Zithromax] was compared with that of the clinical agent doxycycline in a murine model of sporozoite-induced malaria. Drug was administered once; Plasmodium yoelii sporozoites were administered 2 h later; survival at day 60 was determined. For parenterally administered drug, 160 mg of azithromycin [Zithromax] or doxycycline per kg of body weight was 100% effective; 40 mg of azithromycin [Zithromax] per kg was 80% effective, but 40 mg of doxycycline per kg was 40% effective. Orally administered azithromycin [Zithromax] was somewhat less effective than parenterally administered drug, consistent with the 37% clinical oral bioavailability of this agent. For orally administered azithromycin, 160 mg/kg was 100% effective and 40 mg/kg was 40% effective. The efficacy of azithromycin [Zithromax] in comparison with that of doxycycline and the known prolonged levels of azithromycin [Zithromax] in the livers of humans suggest that azithromycin [Zithromax] has potential as a clinical causal prophylactic agent for malaria.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7986022&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 1994 Apr;38(4):790-8.
In vitro and in vivo activities of macrolides against Mycoplasma pneumoniae.

Ishida K, Kaku M, Irifune K, Mizukane R, Takemura H, Yoshida R, Tanaka H, Usui T, Suyama N, Tomono K, et al.

Department of Laboratory Medicine, Nagasaki University School of Medicine, Japan.

We investigated the in vitro and in vivo activities of macrolides against Mycoplasma pneumoniae. In vitro MICs of azithromycin, erythromycin, clarithromycin, and roxithromycin were determined. Azithromycin [Zithromax] was the most potent antimicrobial agent tested in vitro. Its MIC for 90% of the strains was 0.00024 micrograms/ml. MICs for 90% of the strains of erythromycin, clarithromycin, and roxithromycin were 0.0156, 0.0078, and 0.03125 micrograms/ml, respectively. In vivo activities were assessed in a pulmonary infection model with Syrian golden hamsters. We evaluated the in vivo effects on reduction of viable M. pneumoniae cell counts and on reduction of microscopic and macroscopic histopathologies for azithromycin, erythromycin, and clarithromycin given at 10 mg/kg once daily for 1 and 3 days and given at 15 mg/kg twice daily for 2.5 and 5 days. Azithromycin [Zithromax] was significantly more effective than erythromycin or clarithromycin in the same regimens. Especially at 10 mg/kg once daily for 1 day, only azithromycin [Zithromax] was significantly effective in the reduction of viable M. pneumoniae cells and histopathologies. These results show that azithromycin [Zithromax] is more efficacious than the other drugs tested against M. pneumoniae pneumonia in hamsters. These data suggest that clinical studies of macrolides in human patients are warranted.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8031048&dopt=Abstract Zithromax azithromycin




Aliment Pharmacol Ther. 1994 Apr;8(2):187-92.
Activity of metronidazole, azithromycin [Zithromax] and three benzimidazoles on Giardia lamblia growth and attachment to a human intestinal cell line.

Katelaris PH, Naeem A, Farthing MJ.

Department of Gastroenterology, St Bartholomew's Hospital, London, UK.

BACKGROUND: Attachment of Giardia lamblia trophozoites to enterocytes is essential for colonization of the small intestine and is considered a prerequisite for Giardia-induced enterocyte damage. Inhibition of attachment may therefore have therapeutic potential. METHODS: Enterocyte-like differentiated Caco-2 cells were used as a biologically appropriate attachment surface to determine the effect of three benzimidazole compounds (albendazole, mebendazole and thiabendazole), azithromycin [Zithromax] and metronidazole on Giardia attachment. The results were compared with the ability for each drug to inhibit Giardia growth, measured using [3H]-thymidine uptake. RESULTS: The benzimidazoles inhibited Giardia attachment at much lower concentrations than did metronidazole. However, metronidazole was a much more potent inhibitor of growth than any of the benzimidazoles. Azithromycin [Zithromax] did not significantly impair Giardia attachment or growth. The benzimidazoles decrease attachment but are less giardiacidal than metronidazole. CONCLUSION: This model appears useful for testing potential antigiardial compounds and investigating mechanisms of drug action.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8038350&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 1994 May;38(5):1200-2.
Rifabutin and sparfloxacin but not azithromycin [Zithromax] inhibit binding of Mycobacterium avium complex to HT-29 intestinal mucosal cells.

Bermudez LE, Young LS, Inderlied CB.

Kuzell Institute for Arthritis and Infectious Diseases, California Pacific Medical Center Research Institute, San Francisco 94115.

Organisms of the Mycobacterium avium complex (MAC) cause disseminated disease in patients with AIDS, and evidence points to the gastrointestinal tract as the major route of infection. Since MAC can bind to and invade intestinal mucosal cells, we examined whether subinhibitory concentrations of antibiotics which have anti-MAC activity in vitro affect the interaction between MAC and HT-29 intestinal mucosal cells. MAC isolates were exposed to subinhibitory concentrations of rifabutin (MIC, 2.6 micrograms/ml), sparfloxacin (MIC, 8.4 micrograms/ml), or azithromycin [Zithromax] (MIC, 32 micrograms/ml) for 30 to 120 min, washed, and incubated with HT-29 cell monolayers for 2 h at 4 degrees C. HT-29 cell monolayers were then washed to remove unbound bacteria and were subsequently lysed. The number of MAC isolates that bound to the HT-29 cells was determined by plating the cell lysate onto 7H10 agar. Preincubation of the MAC isolates with rifabutin at concentrations of 1 and 2 micrograms/ml reduced MAC binding to HT-29 cells by 80 to 90%, while MAC exposed to sparfloxacin at 1 and 7 micrograms/ml inhibited binding by 77 to 93%. Azithromycin [Zithromax] at concentrations of 2, 10, and 30 micrograms/ml had no effect on MAC binding to HT-29 cells. Inhibition of MAC binding to the gastrointestinal mucosa may be one underlying mechanism for the prophylactic effects of rifabutin and quinolones.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8067766&dopt=Abstract Zithromax azithromycin




Chemotherapy. 1994 Jul-Aug;40(4):252-5.
Therapeutic effects of roxithromycin and azithromycin [Zithromax] in experimental murine brucellosis.

Lang R, Shasha B, Ifrach N, Tinman S, Rubinstein E.

Infectious Diseases Unit, Meir Hospital, Sackler School of Medicine, Tel Aviv University, Israel.

Mice infected with Brucella melitensis were treated with azithromycin [Zithromax] or roxithromycin at a dose of 50 mg/kg/day i.p. alone and in combination with streptomycin 75 mg/kg/day for 14 days. Streptomycin at this dose was previously documented to be ineffective against murine brucellosis. Azithromycin- and azithromycin/streptomycin-treated animals demonstrated a significantly better cure rate than controls. Therapy failure was observed in all mice treated with roxithromycin 50 mg/kg/day i.p. alone or in combination with streptomycin 75 mg/kg/day. Our findings demonstrate that azithromycin [Zithromax] cures experimental murine brucellosis and may be an effective alternative in the therapy of human brucellosis.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8082413&dopt=Abstract Zithromax azithromycin




Eur J Clin Microbiol Infect Dis. 1993 Nov;12(11):864-5.
Azithromycin [Zithromax] resistance in Campylobacter jejuni and Campylobacter coli.

Rautelin H, Renkonen OV, Kosunen TU.

Department of Bacteriology and Immunology, University of Helsinki, Finland.

The MICs of erythromycin, azithromycin [Zithromax] and ciprofloxacin were determined for 60 human fecal isolates of Campylobacter. Of these, 30 strains selected on the basis of their resistance to erythromycin by disk diffusion were highly resistant to both erythromycin and azithromycin. Nine of these selected isolates were resistant to ciprofloxacin. The remaining 30 strains were non-selected, consecutive isolates of Campylobacter susceptible to erythromycin by disk diffusion and were shown to be two- to five-fold more susceptible to azithromycin [Zithromax] than to erythromycin as determined by MIC testing.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8112360&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 1994 Jan;38(1):31-7.
Comparison of mutants of Toxoplasma gondii selected for resistance to azithromycin, spiramycin, or clindamycin.

Pfefferkorn ER, Borotz SE.

Department of Microbiology, Dartmouth Medical School, Hanover, New Hampshire 03755-3842.

Azithromycin [Zithromax] and spiramycin markedly inhibited the growth of Toxoplasma gondii in cultured human fibroblasts. However, 3 days of treatment were required to reveal their full antitoxoplasma activity. This delayed onset of inhibition was similar to that previously reported for clindamycin. Mutants of T. gondii resistant to azithromycin [Zithromax] (AziR-1) and spiramycin (SprR-1) were isolated and compared with a previously described mutant resistant to clindamycin (ClnR-2). Mutant ClnR-2 was cross-resistant to all three antibiotics, while AziR-1 was cross-resistant only to spiramycin and SprR-1 was cross-resistant only to azithromycin. In short-term studies of protein synthesis by freshly prepared extracellular parasites, clindamycin and azithromycin [Zithromax] were effective only at concentrations much greater than their 50% inhibitory concentrations in infected cultures and the resistant mutants did not differ from the wild type in antibiotic sensitivity. Thus, protein synthesis on cytoplasmic ribosomes of the parasite did not seem to be the target of these antibiotics. To determine whether mitochondrial protein synthesis in T. gondii was inhibited by clindamycin or azithromycin, wild-type parasites were grown in cultured cells in the presence of antibiotic concentrations well above the 50% inhibitory concentrations. Mitochondrial function, measured by oxygen uptake per purified extracellular parasite, did not decrease substantially, after the parasites had multiplied 11-fold in the presence of antibiotic. Thus, mitochondrial protein synthesis did not seem to be the target of clindamycin or azithromycin. An alternative target is protein synthesis in the putative apicomplexan organelle that has a 35-kb genome.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8141576&dopt=Abstract Zithromax azithromycin