Antibiot Khimioter. 2002;47(7):6-12.
[Mechanisms of azithromycin [Zithromax] accumulation and efflux in human polymorphonuclear leukocytes]

[Article in Russian]

Hand WI, Hand DL.

Department of Research Development and Internal Medicine, Texas Tech. University Health Sciences Center, Texas, USA.

Azithromycin [Zithromax] achieves prolonged, high tissue concentrations in spite of low serum levels and obviously must be effective at tissue sites of infection. These unique features prompted us to evaluate the interactions of azithromycin [Zithromax] and human polymorphonuclear leukocytes (PMN). Uptake of radiolabeled antibiotic by PMN was determined by a velocity-gradient centrifugation technique and expressed as the ratio of cellular to extracellular drug concentration (C/E). Azithromycin [Zithromax] was massively accumulated by human PMN (C/E = 387.2 at 2 h). Uptake was not influenced by inhibitors of cellular metabolism, but phagocytosis slightly inhibited the entry of azithromycin [Zithromax] into PMN. After removal of extracellular drug, the release (efflux) of azithromycin [Zithromax] from PMN was extremely slow. Agents which neutralize lysosomal pH, preventing protonation and trapping of azithromycin, markedly increased antibiotic efflux. Active concentration and prolonged retention of azithromycin [Zithromax] by phagocytic cells should allow delivery and subsequent release of accumulated drug at sites of infection.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12516190&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 2003 Feb;47(2):524-8.
Activities of azithromycin [Zithromax] and amphotericin B against Naegleria fowleri in vitro and in a mouse model of primary amebic meningoencephalitis.

Goswick SM, Brenner GM.

Department of Pharmacology, Oklahoma State University Center for Health Sciences, Tulsa, Oklahoma 74107-1898, USA.

Inhalation of fresh water containing the free-living ameba Naegleria fowleri may lead to a potentially fatal infection known as primary amebic meningoencephalitis. Amphotericin B is the only agent with established clinical efficacy in the treatment of primary amebic meningoencephalitis in humans, but therapy with this drug is often associated with adverse effects on the kidneys and other organs, and not all persons treated with amphotericin B have survived. We investigated the in vitro activity and in vivo efficacy of newer therapeutic agents in an attempt to identify other useful agents for treating primary amebic meningoencephalitis. Azithromycin [Zithromax] has shown in vitro activity against Acanthamoeba spp. and in vivo activity against experimental toxoplasmosis. In our study, the MIC of azithromycin [Zithromax] against N. fowleri was 13.4 micro M (10 micro g/ml), which was 123 times greater than the MIC of amphotericin B, which was 0.108 micro M (0.1 micro g/ml). Azithromycin [Zithromax] protected 100% of mice infected with N. fowleri at a dose of 75 mg/kg/day for 5 days, whereas amphotericin B protected only 50% of mice at a dose of 7.5 mg/kg/day for 5 days, and all control mice died during the 28-day observation period. We conclude that azithromycin [Zithromax] has both in vitro and in vivo activity versus N. fowleri and may be a useful addition to therapy for primary amebic meningoencephalitis.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12543653&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 2003 Feb;47(2):739-46.
Influence of macrolide susceptibility on efficacies of clarithromycin and azithromycin [Zithromax] against Streptococcus pneumoniae in a murine lung infection model.

Hoffman HL, Klepser ME, Ernst EJ, Petzold CR, Sa'adah LM, Doern GV.

Colleges of Pharmacy, University of Iowa, Iowa City, Iowa, USA.

We evaluated the activities of clarithromycin and azithromycin [Zithromax] against 19 isolates of Streptococcus pneumoniae using a neutropenic lung infection model. The isolates included five susceptible isolates (clarithromycin and azithromycin [Zithromax] MICs, </=0.12 micro g/ml), nine isolates exhibiting low-level, mefA-mediated resistance (clarithromycin and azithromycin [Zithromax] MICs, 0.5 to 32 micro g/ml), and five isolates expressing high-level, ermB-mediated macrolide resistance (clarithromycin and azithromycin [Zithromax] MICs, >/=64 micro g/ml). Infected mice were administered either saline (control), clarithromycin (4, 40, or 200 mg/kg of body weight twice daily or 200 mg/kg once daily), or azithromycin [Zithromax] (4, 40, or 200 mg/kg once daily or 40 mg/kg twice daily) by oral gavage for 72 h. Mortality was assessed at regular intervals for 10 days, and survival in each group was compared to that of untreated controls. Animals infected with susceptible isolates demonstrated significant improvement in survival compared to the controls following treatment with either agent at doses of >/=40 mg/kg. In contrast, none of the regimens improved the survival of animals infected with isolates exhibiting high-level macrolide resistance. Among mice infected with strains expressing low-level resistance, significant improvement in survival compared to the controls was noted among isolates treated with clarithromycin at 40 (seven of nine isolates) and 200 (nine of nine isolates) mg/kg twice a day and with azithromycin [Zithromax] at 40 (one of nine isolates) and 200 (three of nine isolates) mg/kg once a day. Animals infected with isolates of S. pneumoniae exhibiting low-level, mefA-mediated macrolide resistance responded to treatment with clarithromycin at rates similar to those observed among mice infected with fully susceptible isolates.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12543686&dopt=Abstract Zithromax azithromycin




J Antimicrob Chemother. 1999 Jun;43(6):825-7.
Comparative in-vitro activity of moxifloxacin, minocycline and azithromycin [Zithromax] against Chlamydia spp.

Donati M, Rodriguez Fermepin M, Olmo A, D'Apote L, Cevenini R.

Sezione di Microbiologia, Policlinico S. Orsola, University of Bologna, Italy.

The in-vitro activity of moxifloxacin, a new 8-methoxyquinolone, was compared with minocycline and azithromycin [Zithromax] against 40 strains of Chlamydia trachomatis, Chlamydia pneumoniae and Chlamydia psittaci. Both the MIC and the MBC of moxifloxacin ranged from 0.03 to 0.125 mg/L. MICs of minocycline ranged from 0.015 to 0.06 mg/L and MBCs between 0.03 and 0.25 mg/L. MICs of azithromycin [Zithromax] ranged from 0.03 to 0.125 mg/L and the MBCs between 0.06 and 0.5 mg/L. MBC values of moxifloxacin were the same as MICs in 32 (80%) of 40 strains tested, whereas those of minocycline and azithromycin [Zithromax] were two to four times higher than their MICs. These data confirm those previously obtained indicating that quinolones kill chlamydial strains at concentrations equivalent to their MICs.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10404322&dopt=Abstract Zithromax azithromycin




Rapid Commun Mass Spectrom. 2003;17(4):342-50.
Analysis of unknown compounds in azithromycin [Zithromax] bulk samples with liquid chromatography coupled to ion trap mass spectrometry.

Debremaeker D, Visky D, Chepkwony HK, Van Schepdael A, Roets E, Hoogmartens J.

Katholieke Universiteit Leuven, Faculteit Farmaceutische Wetenschappen, Laboratorium voor Farmaceutische Chemie en Analyse van Geneesmiddelen, E. Van Evenstraat 4, B-3000 Leuven, Belgium.

A selective reversed-phase liquid chromatography/mass spectrometry (LC/MS(n)) method is described for the identification of azithromycin [Zithromax] impurities and related substances in commercial azithromycin [Zithromax] samples. Mass spectral data are acquired on an LCQ ion trap mass spectrometer equipped with an atmospheric pressure chemical ionization interface operated in positive ion mode. The LCQ provides on-line LC/MS(n) capability, making it ideally suited for identification purposes. In comparison with UV detection, this hyphenated technique provides as its main advantage efficient identification of novel substances without time-consuming isolation and purification procedures. Using this technique, six novel related substances detected in commercial azithromycin [Zithromax] samples have been studied. Copyright 2003 John Wiley & Sons, Ltd.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12569445&dopt=Abstract Zithromax azithromycin




Jpn J Antibiot. 2000 Jun;53 Suppl B:22-42.
[In vitro and in vivo antibacterial activities of azithromycin]

[Article in Japanese]

Miyazaki S, Yamaguchi K.

Department of Microbiology, Toho University School of Medicine.

In Vitro and in vivo antibacterial activities of azithromycin [Zithromax] were compared with those of macrolides and other antimicrobial agents. In the in vitro activity azithromycin [Zithromax] has a potent activity against both gram-positive and gram-negative bacteria, but against the latter organisms the other macrolides have little potent activity. The in vitro results demonstrate that azithromycin [Zithromax] has a high potent activity against respiratory pathogens such as erythromycin-susceptible staphylococci, streptococci (except for organisms possessing erm gene), H, influenzae, B. prtussis, Legionella spp., M. pneumoniae, C. trachomatis. In the pharmacokinetic of azithromycin [Zithromax] in mice, it is found that its half life is longer than the other macrolides and the concentration of it in polymorphonuclear leukocytes and lung tissues is higher than the other macrolides. These specific properties in the pharmacodynamic and the in vitro antibacterial activities reflect the therapeutic efficacies in experimental infection models. Finally, the therapeutic efficacies of azithromycin [Zithromax] in various infection models better than those of the other macrolides.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12572087&dopt=Abstract Zithromax azithromycin




Jpn J Antibiot. 2000 Jun;53 Suppl B:91-102.
[Summary of the clinical studies with azithromycin [Zithromax] in the pediatric fields]

[Article in Japanese]

Sunakawa K.

KITASATO University School of Medicine.

The clinical studies with azithromycin [Zithromax] fine granules and capsules were conducted during the period from March 1993 to October 1994. Cmax's in 16 patients who received 10 mg/kg fine granules, were 0.29 +/- 0.24 microgram/ml, T1/2's were 42.0 +/- 11.8 hours, and AUC 0 approximately infinity's were 10.72 +/- 5.00 micrograms.hr/ml. The clinical results for azithromycin [Zithromax] fine granule and capsules 10 mg/kg once daily for 3 days are as follows. The efficacy rate of fine granules, combining both "Excellent" and "Good", for pneumoniae where causative pathogenes were identified, was 95.3%, and for those which had failed to respond to previous chemotherapies, was 94.6%, respectively. The efficacy rate of capsules for 3 to 5 days was 100% in 40 cases where causative pathogenes were identified. Adverse reactions were found in 2.5%(fine granules) and in 5.4%(capsules) in cases eligible for evaluation. Abnormal changes in laboratory test were as follows: decrease of WBC by 5.6%(fine granules) and 9.3%(capsules) and increase in eosinophils by 7.1%(fine granules) and 11.4% (capsules). 59.8% of the patients claimed that the azithromycin [Zithromax] 10% fine granules product was "easy to take". The result of a questionnaire on parents' demand on the improvement of antibiotics, showed that most concern was on the drug frequency(preferably once or twice daily) and the drug administering period(preferably short: 3 days). With regard to the efficacy, safety and compliance, it can be concluded that Azithromycin [Zithromax] is one of the useful therapeutic regimens in the treatment of pediatric infections.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12572092&dopt=Abstract Zithromax azithromycin