Antimicrob Agents Chemother. 1994 Oct;38(10):2296-9.
In vitro and in vivo activities of azithromycin, a new azalide antibiotic, against chlamydia.

Niki Y, Kimura M, Miyashita N, Soejima R.

Department of Medicine, Kawasaki Medical School, Japan.

The in vitro and in vivo activities of azithromycin [Zithromax] against chlamydia were investigated. The MIC of azithromycin [Zithromax] for five standard strains of different species of chlamydia and six wild-type strains of Chlamydia pneumoniae was 0.125 microgram/ml, which was superior to that of erythromycin but inferior to those of clarithromycin and minocycline. However, the therapeutic effect of a 7-day course of azithromycin [Zithromax] at a dose of 10 mg/kg of body weight administered orally once daily to mice with experimental Chlamydia psittaci pneumonia was excellent, with a 100% survival rate at 14 days after infection, which was the same as that for treatment with minocycline administered at 10 mg/kg twice daily; all erythromycin treated animals died within 10 days. When treatment was discontinued 3 days after the infection, the survival rate for mice treated with azithromycin [Zithromax] was 90% and that for mice administered minocycline was 30%. These results suggest that azithromycin [Zithromax] may be useful in the treatment of respiratory infections caused by intracellular pathogens, including chlamydia because of its excellent accumulation within host cells.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7840560&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 1994 Oct;38(10):2449-51.
Intracellular and extracellular penetration of azithromycin [Zithromax] into inflammatory and noninflammatory blister fluid.

Freeman CD, Nightingale CH, Nicolau DP, Belliveau PP, Banevicius MA, Quintiliani R.

Department of Pharmacy, Hartford Hospital, Connecticut 06115.

The penetration of azithromycin [Zithromax] into the blister fluids of six volunteers was analyzed after a 5-day regimen (total of 1.5 g). Differences in drug concentrations in a paper disk and serum and in the mass of azithromycin [Zithromax] from inflammatory blister chamber leukocytes and noninflammatory blister chamber leukocytes were significant (P < 0.05).

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7840585&dopt=Abstract Zithromax azithromycin




Am J Trop Med Hyg. 1995 Feb;52(2):159-61.
Activity of azithromycin [Zithromax] as a blood schizonticide against rodent and human plasmodia in vivo.

Andersen SL, Ager A, McGreevy P, Schuster BG, Wesche D, Kuschner R, Ohrt C, Ellis W, Rossan R, Berman J.

Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, District of Columbia.

We compared the efficacy of azithromycin [Zithromax] to the clinical antimalarial doxycycline in Plasmodium berghei-infected mice and in P. falciparum-infected Aotus monkeys. When mice were administered drug orally twice a day for three days, the minimum total dose of azithromycin [Zithromax] that cured all mice was 768 mg/kg. Doxycycline at a dose of 1,536 mg/kg cured no mice. The efficacy of fast-acting blood schizonticides (quinine, halofantrine, artemisinin) against P. berghei was augmented by azithromycin. In monkey experiments in which there were two animals per experimental group, azithromycin [Zithromax] (100 mg/kg/day for seven days) eliminated parasitemia; azithromycin [Zithromax] (30 mg/kg/day) initially cleared 99.8-100% of the parasites with recrudescence in the one completely cleared case. Doxycycline (30 mg/kg/day) cleared 100% of the parasites with recrudescence in both cleared cases. Since azithromycin [Zithromax] can be clinically administered at a somewhat higher daily dosage than doxycycline, the data suggest that it may be possible to replace drugs of the tetracycline class with azithromycin [Zithromax] in combination with fast-acting blood schizonticides for the treatment of P. falciparum infection.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7872444&dopt=Abstract Zithromax azithromycin




Int J Clin Pharmacol Ther. 1994 Jul;32(7):356-60.
Distribution of orally administered azithromycin [Zithromax] in various blood compartments.

Wildfeuer A, Laufen H, Zimmermann T.

Forschung und Entwicklung, Pfizer/Mack, Illertissen, Germany.

The concentrations of azithromycin [Zithromax] in whole blood, plasma, erythrocytes and polymorphonuclear leucocytes (PMNLs) were measured in 6 healthy volunteers following the last administration of a three-day regimen of 500 mg once daily. Marked enrichment of azithromycin [Zithromax] was observed in PMNLs; the drug concentration amounted to 119 +/- 31 (SD) mg/l 6 hours after the administration. Twelve days thereafter 42 +/- 10 mg/l azithromycin [Zithromax] was still measured in the PMNLs, although the drug was no longer demonstrable in plasma (< 0.02 mg/l). The elimination of azithromycin [Zithromax] from the PMNLs (half-life 210 +/- 69 hours) was clearly slower than the elimination from plasma (half-life 93 +/- 70 hours). The maximal concentrations of azithromycin [Zithromax] in plasma (0.64 +/- 0.27 mg/l) and erythrocytes (0.17 +/- 0.06 mg/l) were much lower and occurred earlier (tmax = 3 hours) than those observed in the PMNLs. The enrichment factor for azithromycin [Zithromax] in PMNLs relative to plasma came to 177 +/- 92 at 3 hours or 1814 +/- 706 at 120 hours after the last administration. In a parallel in vitro study, the effect of accumulation of azithromycin [Zithromax] in PMNLs on the intracellular survival of ingested staphylococci was investigated. At subinhibitory extracellular concentrations of azithromycin [Zithromax] as low as 0.03 mg/l (MIC = 1 mg/l), a significant reduction in bacterial viability was observed, thus demonstrating antibacterial activity of the intracellularly enriched antibiotic.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7952797&dopt=Abstract Zithromax azithromycin




Clin Ter. 1994 Jul;145(7):35-9.
[Evaluation of the clinical efficacy of azithromycin [Zithromax] in acute respiratory infections in children]

[Article in Italian]

Bottaro G, Rotolo N, Bonforte S, Bucchieri R, De Luca P, Ficarra G, Gulino A, Melillo P, Nicosia A, Prestifilippo F, et al.

I Clinica Pediatrica, Universita degli Studi di Catania.

Azithromycin [Zithromax] activity in vivo has been studied in a group of children with acute respiratory tract infections in order to test the efficacy and tolerability of this antibiotic. The study involved 135 children treated with a single daily 10 mg/kg dose of azithromycin [Zithromax] for three consecutive days. Ten days after this treatment 100% of children with otitis media, tracheobronchitis, or rhinosinusitis and 95.9% of children with pharyngo-tonsillitis were cured. Recurrences were never observed. Azithromycin [Zithromax] proved remarkably effective for treatment of acute respiratory infections and otitis media in children. Tolerability and therapeutic compliance were excellent.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7955949&dopt=Abstract Zithromax azithromycin




J Antimicrob Chemother. 1994 Jul;34(1):111-8.
Evaluation of the efficacy of prolonged administration of azithromycin [Zithromax] in a murine model of chronic toxoplasmosis.

Dumas JL, Chang R, Mermillod B, Piguet PF, Comte R, Pechere JC.

Department of Genetics and Microbiology, Centre Medical Universitaire, Geneva, Switzerland.

The efficacy of prolonged administration of azithromycin [Zithromax] was evaluated in a murine model of lethal chronic toxoplasmosis. Mice were challenged intraperitoneally with cysts of a moderately virulent strain of Toxoplasma gondii, observed for 4 weeks and then allocated to the treatment or control group. All 26 animals given azithromycin [Zithromax] 100 mg/kg/day for 100 days were protected compared with 19 of 25 control animals which died (P < 0.001). Nineteen of the 20 mice in the treatment group survived for an additional month while receiving the same azithromycin [Zithromax] regimen but viable cysts were identified in the brain tissue of these animals when they were killed. Although there was no significant difference between the groups in terms of the number of cysts in the brain, the administration of azithromycin [Zithromax] was associated with a reduction in brain inflammation. The concentrations of azithromycin [Zithromax] in the brains of five animals ranged from 0.7 to 2.3 micrograms/g; there was no evidence of accumulation even after 100 doses. Azithromycin [Zithromax] merits further evaluation as primary or secondary prophylaxis against toxoplasma encephalitis in individuals at risk of developing this complication.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7961197&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 1994 Jul;38(7):1620-7.
Localization of azithromycin [Zithromax] in Toxoplasma gondii-infected cells.

Schwab JC, Cao Y, Slowik MR, Joiner KA.

Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8022.

Agents effective against intracellular pathogens must enter infected cells, crossing vacuolar membranes surrounding the organisms and then penetrating into the microbe and localizing to the microbial target site. We have characterized these parameters for azithromycin [Zithromax] entry into Toxoplasma gondii-infected Chinese hamster ovary cells and murine macrophage-like J774 cells. Azithromycin [Zithromax] uptake into infected host cells was concentrative and was dependent upon proton gradients. Subcellular fractionation of azithromycin-loaded infected CHO cells demonstrated > 95% intracellular drug in host cell lysosomes and cytosol, with < 5% associated with the parasite. Uptake of azithromycin [Zithromax] into the T. gondii vacuole increased if parasites were coated with antibody prior to internalization by murine J774 cells, conditions which result in the formation of acidified phagolysosomes. No redistribution or retention of azithromycin [Zithromax] in the parasite was observed when drug efflux from antibiotic-loaded infected CHO cells was monitored. Azithromycin [Zithromax] entry into extracellular T. gondii was concentrative, was temperature and pH dependent, and was not different when azithromycin-sensitive and -resistant parasites were compared. These results demonstrate that azithromycin [Zithromax] concentrates primarily in acidified compartments in parasites and host cells. The high concentration of azithromycin [Zithromax] within these compartments may not be biologically relevant to inhibition of intracellular parasite growth by this agent.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7979295&dopt=Abstract Zithromax azithromycin