J Antimicrob Chemother. 1991 Nov;28(5):741-6.
The effect of a single oral dose of azithromycin [Zithromax] on chlamydial salpingitis in mice.

Tuffrey M, Woods C, Taylor-Robinson D.

Division of Sexually Transmitted Diseases, Clinical Research Centre, Harrow, Middlesex, UK.

Progesterone-treated C3H mice were inoculated under the ovarian bursa with a human Chlamydia trachomatis strain, serovar E, and treated variously from one week before inoculation to two weeks afterwards with a single oral dose of azithromycin. At autopsy, all 27 control mice, not given azithromycin, had histological evidence of salpingitis. Any tubal inflammation in the 139 mice which had received greater than or equal to 60 mg azithromycin/kg was always less severe than that in control mice killed on the same day. This was true also for three of the six mice given azithromycin [Zithromax] 25 mg/kg. Salpingitis was prevented in all 38 mice given greater than or equal to 60 mg of azithromycin [Zithromax] on the day chlamydiae were inoculated. Inflammation was found in only 35% of mice given 60-80 mg/kg of drug from two to ten days after inoculation and was less severe than in untreated control mice. This dose given later was not as effective in preventing disease. Doses of 200-240 and 100-180 mg/kg given up to a week before inoculation reduced the proportion of mice with salpingitis to 33% and 77%, respectively, while no reduction occurred with 60-80 mg/kg, although lesions were less severe than in control mice. Chlamydiae were not detected in any part of the genital tract when greater than or equal to 60 mg/kg of azithromycin [Zithromax] were given on the day of inoculation and were rarely detected when the drug was given a week before or up to 12 days after inoculation. Re-isolation of organisms was not always associated with histological evidence of disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1663931&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 1991 Dec;35(12):2625-9.
Stimulation with cytokines enhances penetration of azithromycin [Zithromax] into human macrophages.

Bermudez LE, Inderlied C, Young LS.

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

An effective intracellular concentration of an antimicrobial agent is essential for therapy of infections caused by organisms of the Mycobacterium avium complex. We previously reported on the effect of the combination of azithromycin [Zithromax] and tumor necrosis factor (TNF) against M. avium infection in macrophages. We now report that stimulation of macrophages either with recombinant human gamma interferon (IFN-gamma, 10(2) U/ml) or with recombinant human TNF-alpha (10(2) U/ml) resulted in an increase in the intracellular concentration of azithromycin [Zithromax] by approximately 200% within 3 h, compared with the concentration in unstimulated macrophages. Infection of macrophages with M. avium complex led to a decrease in the uptake of [14C]azithromycin [Zithromax] by infected cells, compared with that by uninfected controls. Stimulation of infected macrophages with recombinant IFN-gamma or TNF-alpha overcame the inhibitory effect associated with infection. These results suggest that the increased bactericidal activity of the TNF-alpha-azithromycin [Zithromax] or IFN-gamma-azithromycin [Zithromax] combination against M. avium is related to enhanced uptake of the antibiotic by the stimulated phagocyte.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1667256&dopt=Abstract Zithromax azithromycin




J Protozool. 1991 Nov-Dec;38(6):232S-233S.
Chemotherapeutic effect of azithromycin [Zithromax] and lasalocid on Cryptosporidium infection in mice.

Kimata I, Uni S, Iseki M.

Department of Medical Zoology, Osaka City University Medical School, Japan.

Prednisolone-immunosuppressed mice (ICR, 7-wk-old female) were each inoculated with 1 x 10(5) oocysts of Cryptosporidium parvum. Medication with azithromycin [Zithromax] (400 mg/kg/day) or lasalocid (64, or 128 mg/kg/day) was started 13 h after inoculation and continued for 3 days. The number of oocysts discharged by each mouse was calculated on days 4-12 post-inoculation. Compared with non-medicated controls, oocyst production by the medicated mice was markedly reduced; some mice did not discharge oocysts and the remaining mice discharged less than 1/100 the number of oocysts of the control mice. These results indicate that both azithromycin [Zithromax] and lasalocid have prophylactic or therapeutic activity against Cryptosporidium.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1667931&dopt=Abstract Zithromax azithromycin




Eur J Clin Microbiol Infect Dis. 1991 Oct;10(10):868-71.
Concentration of azithromycin [Zithromax] in human prostatic tissue.

Foulds G, Madsen P, Cox C, Shepard R, Johnson R.

Central Research Division, Pfizer Inc., Groton, Connecticut 06340.

Prostatic tissue was obtained from 36 patients at two study locations and assayed for azithromycin [Zithromax] by HPLC or bioassay. The mean concentration of azithromycin [Zithromax] in human prostatic tissue (2.54 micrograms/ml) 14 h after 500 mg oral dosing (two 250 mg doses 12 h apart) was much greater than plasma concentrations (less than or equal to 0.1 micrograms/ml). Azithromycin [Zithromax] was slowly eliminated from prostatic tissue (half-life 60 h) and a mean concentration of 0.62 micrograms/ml remained 137 h after dosing.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1722460&dopt=Abstract Zithromax azithromycin




Chemotherapy. 1990;36(6):407-15.
Chlamydia trachomatis: in vitro susceptibility of genital and ocular isolates to some quinolones, amoxicillin and azithromycin.

Borsum T, Dannevig L, Storvold G, Melby K.

Department of Microbiology, Ulleval University Hospital, Oslo, Norway.

The minimum inhibitory concentration (MIC) of ofloxacin, ciprofloxacin, norfloxacin, amoxicillin and a new erythromycin analogue (azithromycin [Zithromax] or CP 62993) against Chlamydia trachomatis was determined. There was a large difference between the MICs (microgram/ml) of different quinolones (median of 3 independent measurements; range): ofloxacin (0.5; 0.5-1) less than ciprofloxacin (1; 1-2) less than norfloxacin (16; 16-32). The MIC of amoxicillin varied from 0.25 to 1 (median 0.5) in different experiments. The MIC of azithromycin [Zithromax] (0.125; 0.063-0.25) was lower than that of erythromycin (0.25; 0.125-0.5). The minimum lethal concentration (MLC) of ofloxacin and azithromycin [Zithromax] was determined with and without passage of the McCoy cells. Both methods gave the same results. Ofloxacin seemed to have a lethal effect on C. trachomatis, as the MIC and MLC were equal. In contrast, the effect of the MIC of azithromycin [Zithromax] on C. trachomatis was bacteriostatic. The MLC of azithromycin [Zithromax] was 2-4 times higher than the MIC (p less than 0.001).

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1963393&dopt=Abstract Zithromax azithromycin




Eur Respir J. 1990 Sep;3(8):886-90.
Azithromycin [Zithromax] concentrations at the sites of pulmonary infection.

Baldwin DR, Wise R, Andrews JM, Ashby JP, Honeybourne D.

Dept of Thoracic Medicine, Dudley Road Hospital, Birmingham, UK.

Azithromycin [Zithromax] is a new macrolide antimicrobial. The distribution to the potential sites of pulmonary infection was assessed after the administration of a single 500 mg oral dose to 22 patients undergoing fibreoptic bronchoscopy. Concentrations of azithromycin [Zithromax] in sputum, bronchial mucosa, eptihelial lining fluid (ELF) and alveolar macrophages (AM) were determined at intervals up to 96 h after dosing. The mean serum concentration was low at 12 h (0.13 micrograms.ml-1, SEM 0.05) but was still detectable at 96 h (0.01 micrograms.ml-1). In contrast, peak sputum ELF, bronchial mucosal and AM levels were found at 48 h. Bronchial mucosal concentrations were significantly greater than ELF concentrations, which were in turn greater than sputum concentrations. Mean peak AM concentrations were sixfold greater than bronchial mucosal concentrations (23 micrograms.ml-1, SEM 5.1 and 3.89 micrograms.ml-1, SEM 1.2, respectively). The high intracellular concentrations indicate that azithromycin [Zithromax] is likely to be effective for sensitive intracellular pathogens and the favourable penetration into sputum, ELF and bronchial mucosa suggest that it should be useful in pneumonia and bronchial infections.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1963411&dopt=Abstract Zithromax azithromycin




Drugs Exp Clin Res. 1990;16(12):615-9.
Post-antibiotic effect of azithromycin [Zithromax] on respiratory tract pathogens.

Debbia EA, Molinari G, Paglia P, Schito GC.

Institute of Microbiology, University of Genoa, Italy.

Azithromycin [Zithromax] is a new azalide antibiotic with structural modifications that confer to the molecule acid stability, extension of antibacterial spectrum that includes important Gram-negative pathogens, long elimination half-life, and tendency to concentrate into various tissues where it persists for extended periods of time. The existence and length of a post-antibiotic effect (PAE), an important parameter for the characterization of new antibiotic molecules, has not yet been evaluated for this agent. In this study the PAE of azithromycin [Zithromax] was assessed against representative respiratory pathogens included in the in vitro antimicrobial activity of the drug. The results obtained indicate that azithromycin [Zithromax] produce a significant PAE on all Gram-positive and Gram-negative bacteria tested, resulting in an average value of 3.5 h for both S. pyogenes and S. pneumoniae, 3 h for B. catarrhalis and H. influenzae, and 2 h for Klebsiella spp. These findings support previous reports underlining the remarkable in vitro activity of azithromycin [Zithromax] against H. influenzae, a pathogen poorly susceptible to the classical macrolides. Furthermore, the present demonstration of the existence of a long PAE of azithromycin [Zithromax] against other Gram-positive and Gram-negative bacteria extends the pharmacokinetic advantages of the drug and strongly supports the application of this azalide in the therapy of respiratory infections.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1966617&dopt=Abstract Zithromax azithromycin