Pediatr Infect Dis J. 1996 Sep;15(9 Suppl):S30-7.
Properties of azithromycin [Zithromax] that enhance the potential for compliance in children with upper respiratory tract infections.

Powers JL.

Hill Top Research, Inc., Scottsdale, AZ, USA.

BACKGROUND: Azithromycin, the prototypical azalide antibiotic, has a wide spectrum of activity that is characterized by resistance to beta-lactamase-producing microbes and efficacy against Gram-positive and Gram-negative pathogens, including Haemophilus influenzae. Tissue-directed pharmacokinetics include tissue concentrations up to 100-fold higher than those in plasma and a tissue half-life of up to 4 days. Pharmacokinetics of azithromycin [Zithromax] permits a reduction in dosage frequency and duration while maintaining efficacy comparable to that of conventional 7- to 10-day three or four times daily regimens. Dosage interval, duration of treatment, side effects and palatability can affect compliance and thus clinical outcome. Compliance among children is important in light of the high incidence of community-acquired infections such as otitis media and streptococcal pharyngitis. OBJECTIVE: To compare the flavor, taste acceptability and color preference of oral antibiotic suspensions given to children. METHODS: The taste and acceptability of the oral suspension form of azithromycin [Zithromax] vs. cefixime, cefpodoxime proxetil, cefprozil, clarithromycin or loracarbef were rated by children during blinded taste tests and with acceptability/ preference questionnaires. RESULTS: Analysis of the mean acceptability/ preference rating from 769 children demonstrated that the flavor of azithromycin [Zithromax] was rated significantly higher than that of cefpodoxime (4.3 vs. 2.8), cefprozil (4.0 vs. 3.4) and clarithromycin (4.3 vs. 2.7) and was comparable to that of cefixime (4.0 vs. 4.2) and loracarbef (4.4 vs. 4.5). A greater percentage of children preferred the taste of azithromycin [Zithromax] to that of cefpodoxime (90.0% vs. 5.2%), cefprozil (63.0% vs. 33.1%) and clarithromycin (89.0% vs. 11.0%). The taste of azithromycin [Zithromax] was not preferred to that of cefixime (39.0% vs. 53.9%) or loracarbef (36% vs. 58.5%). CONCLUSIONS: The efficacy and safety of azithromycin [Zithromax] in otitis media and streptococcal pharyngitis, the simple dosing regimen and a highly palatable oral suspension formulation should increase compliance among pediatric patients and thereby improve clinical outcomes.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8878244&dopt=Abstract Zithromax azithromycin

sirius.med.toho-u.ac.jp

Several previous investigators have reported that long-term administration of certain macrolides is efficacious in patients with persistent pulmonary Pseudomonas aeruginosa infections, even though the clinically achievable concentrations of these medications are far below their MICs. In the present study, we examined how sub-MICs of macrolide antibiotics affect the viability of and protein synthesis in several strains of P. aeruginosa. We report that 48 h, but not 12 or 24 h, of growth on agar containing a clinically achievable concentration of azithromycin [Zithromax] (0.5 microgram/ml, 1/128 the MIC) significantly reduces the viability of strain PAO-1. Similar effects were seen with erythromycin and clarithromycin at 2 micrograms/ml (1/128 and 1/64 the respective MICs), whereas josamycin, oleandomycin, ceftazidime, tobramycin, minocycline, and ofloxacin had no effect on viability, even following 48 h of incubation with concentrations representing relatively high fractions of their MICs. The bactericidal activity of azithromycin [Zithromax] seen following 48 h of incubation was not limited to strain PAO-1 but was also seen against 13 of 14 clinical isolates, including both mucoid and nonmucoid strains. Although viability was not decreased prior to 48 h, we found that 4 micrograms of azithromycin [Zithromax] per ml inhibits protein synthesis after as little as 12 h and that protein synthesis continues to decrease in a time-dependent manner. We likewise found that P. aeruginosa accumulates azithromycin [Zithromax] intracellulary over the period from 12 to 36 h. These results suggested that sub-MICs of certain macrolides are bactericidal to P. aeruginosa when the bacteria are exposed to these antibiotics for longer periods. Exposure-dependent intracellular accumulation of the antibiotic and inhibition of protein synthesis may partially account for the antipseudomonal activity of macrolides over relatively prolonged incubation periods.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8891128&dopt=Abstract Zithromax azithromycin




Clin Infect Dis. 1996 Nov;23(5):983-9.
Azithromycin [Zithromax] activity against Mycobacterium avium complex lung disease in patients who were not infected with human immunodeficiency virus.

Griffith DE, Brown BA, Girard WM, Murphy DT, Wallace RJ Jr.

Department of Medicine, University of Texas Health Center, Tyler 75710, USA.

We initiated a prospective trial of an azithromycin-containing regimen for the treatment of human immunodeficiency virus-negative patients with Mycobacterium avium complex (MAC) lung disease; the initial 4 months of therapy were with azithromycin [Zithromax] (600 mg/d) alone. The primary study endpoint was microbiological response measured at 4 and 6 months of therapy. Of 29 patients enrolled in the study, 23 completed therapy. Fifty-two percent of these 23 patients were male, and 65% were smokers. All 23 patients were older than 45 years of age; 83% had bilateral disease, and 48% had fibrocavitary disease. Macrolide (clarithromycin)-susceptible MAC isolates were recovered from these 23 patients before treatment. Cultures of sputum from 38% of these patients became negative, and the positivity of cultures of sputum from 76% of these patients was significantly reduced. Sixty-eight percent of sputum cultures were strongly positive (> 200 colonies) before therapy, while only 27% were strongly positive after therapy. Although most patients continued to receive 600 mg of azithromycin/d, the high incidence of gastrointestinal side effects (76%) and altered hearing (41%) suggests the need for lower or less frequent dosing. Macrolide (clarithromycin) resistance did not develop in any MAC isolates during monotherapy. These results, which demonstrate that azithromycin [Zithromax] is active against MAC pulmonary disease, provide a rationale to include this drug in the initial multidrug regimens recommended for the treatment of this disease.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8922790&dopt=Abstract Zithromax azithromycin




Antibiot Khimioter. 1996 Feb;41(2):9-13.
[Clinico-laboratory evaluation of the effectiveness of azithromycin [Zithromax] in the treatment of patients with Chlamydia and mixed Chlamydia-gonorrhea infections]

[Article in Russian]

Vasil'ev MM, Gazarian IIu.

One hundred and fifteen females with nonsevere inflammatory diseases of the urogenital tracts were examined. Mixed chlamydial and gonorrheal infection was stated in 35 patients. In 38 patients chlamydial infection was diagnosed. To develop an optimal procedure for the treatment, the pharmacokinetics of azithromycin [Zithromax] was studied. The results showed that the optimal primary dose of the drug was 1000 mg. Two regimens were recommended for the treatment of the patients. According to the first regimen azithromycin [Zithromax] was administered in a single dose of 1000 mg. The efficacy amounted to 82.4 per cent in the cases with the mixed infection and to 89.9 per cent in the cases with chlamydiosis. According to the second regimen azithromycin [Zithromax] was administered in a course dose of 3000 mg, the duration of the course being 9 days. The efficacy of the therapy amounted to 89.9 and 95 per cent respectively.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8929122&dopt=Abstract Zithromax azithromycin




J Antimicrob Chemother. 2000 Mar;45(3):375-7.
Anticryptosporidial activity of ranalexin, lasalocid and azithromycin [Zithromax] alone and in combination in cell lines.

Giacometti A, Cirioni O, Barchiesi F, Scalise G.

Institute of Infectious Diseases and Public Health, University of Ancona, Italy.

The in vitro anticryptosporidial activities of ranalexin, lasalocid and azithromycin [Zithromax] alone and in combination were investigated against four clinical isolates of Cryptosporidium parvum. Susceptibility was tested by inoculating the isolates on to cell monolayers and determining the parasite count after 48 h incubation at 37 degrees C. The culture medium was supplemented with Dulbecco's modified Eagle's medium containing serial dilutions of the above-mentioned compounds. Ranalexin showed moderate anticryptosporidial activity: at a concentration of 64 mg/L it reduced parasite counts by 33.8%. Azithromycin [Zithromax] at a concentration of 8 mg/L gave inhibition comparable to that observed with the highest concentration of ranalexin. Lasalocid showed the highest activity, with a 70.3% reduction in parasite counts at 2 mg/L. The combination of ranalexin 64 mg/L and lasalocid 2 mg/L completely suppressed parasite growth without harming the monolayer.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10702561&dopt=Abstract Zithromax azithromycin




Eur J Pharmacol. 1996 Oct 24;314(1-2):215-27.
Interaction of the macrolide azithromycin [Zithromax] with phospholipids. II. Biophysical and computer-aided conformational studies.

Montenez JP, Van Bambeke F, Piret J, Schanck A, Brasseur R, Tulkens PM, Mingeot-Leclercq MP.

Unite de Pharmacologie Cellulaire et Moleculaire, Universite Catholique de Louvain, UCL 73.70, Bruxelles, Belgium.

In a comparison paper, we show the azithromycin [Zithromax] causes a lysosomal phospholipidosis in cultured cells, binds in vitro to negatively charged bilayers without causing aggregation or fusion, and inhibits lysosomal phospholipase A1. In this paper, we show that azithromycin [Zithromax] decreases the mobility of the phospholipids in negatively charged liposomes (using 31P nuclear magnetic resonance) and that it increases the fluidity of the acyl chains close to the hydrophilic/hydrophobic interface, but not deeper into the hydrophobic domain (assessed by measuring the fluorescence polarization of trimethylammonium-diphenylhexatriene and diphenyhexatriene, respectively). Computer-aided conformational analysis of mixed monolayers of azithromycin [Zithromax] and phosphatidylinositol shows that the drug can be positioned largely in the hydrophobic domain, but close to the interface, with the macrocycle facing the C1 of the fatty acids (allowing the N9a endocyclic tertiary amine to interact with the phospho-groups), the cladinose located on the hydrophobic side of the lipid/water interface and the desosamine projected into the hydrophobic domain. This position is consistent with the experimental data. Analysis of virtual molecules shows that this unanticipated behavior to the shielding of the ionizable N3' amino-group in the desosamine by methyl-groups, and to the wide dispersion of hydrophobic domains all over the molecule. The interaction of azithromycin [Zithromax] with phospholipids may account for some of its unusual pharmacokinetic properties and for its potential to cause lysosomal phospholipidosis.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8957239&dopt=Abstract Zithromax azithromycin




Chemotherapy. 1996 May-Jun;42(3):177-85.
Effect of subinhibitory concentrations of ceftazidime, ciprofloxacin, and azithromycin [Zithromax] on the hemagglutination and adherence of uropathogenic Escherichia coli strains.

Vranes J.

Medical School, University of Zagreb, Croatia.

The effect of subinhibitory concentrations (sub-MICs) of ceftazidime, ciprofloxacin, and azithromycin [Zithromax] on the hemagglutination (HA) and adherence ability of 29 P-fimbriated Escherichia coli strains to the buffalo green monkey kidney (BGMK) cell line was investigated. Comparisons were made between the values of HA titer before and those after exposure of strains to 1/2, 1/4, 1/8, 1/16 and 1/32 MIC of antibiotics, as well as between the number of bacteria attached to the BGMK cells before and the number after their exposure to the same concentrations of antibiotics. Azithromycin [Zithromax] at concentrations of 1/2 and 1/4 MIC damaged the HA capacity of the studied strains, while ceftazidime at concentrations of 1/2, 1/4, 1/8 and 1/16 MIC and ciprofloxacin at concentrations of 1/2 and 1/4 MIC increased the HA capacity of P-fimbriated E. coli. All three antibiotics decreased the adhesive capacity of E. coli to the BGMK cells. Comparing the number of adhered bacteria before and after exposure to sub-MICs of antibiotics, statistically significant differences were determined (p < 0.01) after exposure of the strains to all the concentrations of ceftazidime used after exposure to 1/2, 1/4, 1/8 and 1/16 MIC of ciprofloxacin, and after exposure to 1/2, 1/4 and 1/8 MIC of azithromycin. Filaments formed by sub-MICs of ceftazidime and ciprofloxacin in a static experimental system caused HA, but in an experimental system imitating in vivo conditions, the strains adhered poorly to the cells.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8983884&dopt=Abstract Zithromax azithromycin