J Med Microbiol. 1995 May;42(5):362-6.
Post-antibiotic effect of azithromycin [Zithromax] and erythromycin on streptococcal susceptibility to phagocytosis.

Ramadan MA, Tawfik AF, Shibl AM, Gemmell CG.

Division of Microbiology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

The effect of azithromycin [Zithromax] and erythromycin on growth, cell surface hydrophobicity and the susceptibility to the bactericidal activity of human polymorphonuclear leucocytes (PMNL) was examined in four Streptococcus species. Exposure to either 10 x MIC azithromycin [Zithromax] or erythromycin induced a post-antibiotic effect (PAE) of between 2.4 and 4.3 h. Erythromycin caused a longer PAE for S. sanguis than azithromycin [Zithromax] under the same conditions. The cell surface charge (hydrophobic or hydrophilic) of the streptococci was altered significantly during PAE; loss of hydrophobicity was induced by both macrolides, and this effect was variable amongst the species. The decrease in hydrophobicity was not related to inhibition of growth. The effect of each drug during PAE on the interaction of opsonised suspensions of the streptococci with human PMNL revealed that erythromycin, and to a lesser extent azithromycin, increased susceptibility to the bactericidal activity of human PMNL; this effect was abolished following PAE. The present study clearly showed that PAE should not only be considered as delayed bacterial growth, but also as modulation of bacterial susceptibility to phagocytosis which may influence the outcome of the host-parasite relationship.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7752216&dopt=Abstract Zithromax azithromycin




J Vet Pharmacol Ther. 1995 Feb;18(1):38-46.
Pharmacokinetics, oral bioavailability and tissue distribution of azithromycin [Zithromax] in cats.

Hunter RP, Lynch MJ, Ericson JF, Millas WJ, Fletcher AM, Ryan NI, Olson JA.

Department of Drug Metabolism, Pfizer Inc., Central Research Division, Groton, CT 06340, USA.

Azithromycin [Zithromax] is the first of a class of antibiotics classified as azalides. In an initial experiment four cats were given a single dose of azithromycin [Zithromax] 5 mg/kg orally (p.o.), followed 2 weeks later by a single intravenous bolus (i.v.) dose of 5 mg/kg. Subsequently, six cats were given [14C]azithromycin [Zithromax] p.o. in a single dose of 5.4 mg/kg for the study of tissue distribution and metabolism. In both experiments, serial blood samples were collected and the plasma assayed for unchanged azithromycin [Zithromax] to determine various pharmacokinetic parameters. After p.o. administration, bioavailability was 58% and absorption rapid with a tmax of 0.85 +/- 0.72 h and a Cmax of 0.97 +/- 0.65 microgram/mL. The harmonic mean terminal t1/2 after i.v. administration was 35 h. Tissue half-lives varied from 13 h in fat to 72 h in cardiac muscle. Three metabolites were identified in bile. Unchanged azithromycin [Zithromax] accounted for 100% of the total radioactivity in lung and skin tissues when assayed. In comparison with other species, the bioavailability in cats is higher than in humans but lower than in dogs. As in the dog, > 50% of the azithromycin-related material in feline bile was unchanged azithromycin.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7752305&dopt=Abstract Zithromax azithromycin




AIDS. 1995 Mar;9(3):261-6.
Impact of clarithromycin and azithromycin [Zithromax] on patterns of treatment and survival among AIDS patients with disseminated Mycobacterium avium complex.

Ives DV, Davis RB, Currier JS.

Division of Infectious Diseases, Beth Israel Hospital, Boston, MA 02215, USA.

OBJECTIVE: To determine the impact of the introduction of clarithromycin and azithromycin [Zithromax] on the treatment and survival of patients with AIDS and disseminated Mycobacterium avium complex (DMAC). DESIGN: Retrospective review over a 3.5-year interval. SETTING: Tertiary-care, university teaching hospital. PATIENTS: Charts of all patients with cultures of blood or bone-marrow positive for acid-fast bacilli (n = 103) were reviewed. Data on laboratory results at the time of DMAC diagnosis, antimycobacterial therapy, antiretroviral therapy, and survival was collected. RESULTS: Prior to the availability of clarithromycin and azithromycin [Zithromax] 61.5% of patients received antimycobacterial treatment compared with 92% afterwards (P = 0.0014). Median survival of treated patients was 255 versus 145 days for untreated patients (P < 0.001). Median survival of macrolide-treated patients was 284 versus 168 days for patients receiving treatment without a macrolide (P = 0.09). Univariate predictors of survival were antimycobacterial treatment, use of antiretrovirals, and year of diagnosis. In a multivariate model, no antimycobacterial treatment (hazard ratio, 3.83; P = 0.003) was associated with shorter survival, and treatment without a macrolide (hazard ratio, 2.29; P = 0.075) showed a trend towards shorter survival versus treatment with macrolide-containing regimens. CONCLUSIONS: The introduction of clarithromycin and azithromycin [Zithromax] has been associated with an increase in the proportion of patients with DMAC receiving treatment and with increased survival of these patients.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7755914&dopt=Abstract Zithromax azithromycin




J Antimicrob Chemother. 1995 Jan;35(1):85-93.
Factors affecting the intracellular accumulation and activity of azithromycin.

Pascual A, Conejo MC, Garcia I, Perea EJ.

Department of Microbiology, School of Medicine, Sevilla, Spain.

Azithromycin [Zithromax] is a new macrolide which accumulates in high concentrations in human phagocytes. The cellular to extracellular ratio (C/E) of azithromycin [Zithromax] concentrations (fixed extracellular concentration 1 mg/L) in human polymorphonuclear leucocytes (PMN) were significantly affected by small increases in the environmental temperature (C/E 20.3 +/- 2 and 59.4 +/- 6 at 37 degrees C and 40 degrees C, respectively). PMN-associated azithromycin [Zithromax] was not affected by the presence of different concentrations of human serum. The intracellular accumulation of azithromycin [Zithromax] decreased slightly (C/E approximately 5) when cells were activated with PMA or opsonized with zymosan. The phagocytosis of opsonized Staphylococcus aureus or Haemophilus influenzae, however, slightly increased the intracellular concentrations of azithromycin. At different extracellular concentrations, azithromycin [Zithromax] did not affect the production of hydrogen peroxide and superoxide radicals by PMN. The intracellular survival of H. influenzae in human PMN was abolished in the presence of concentrations higher than 0.125 mg/L of azithromycin. Under the same experimental conditions, however, azithromycin [Zithromax] did not show any intracellular activity against S. aureus.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7768786&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 1994 Sep;38(9):1915-21.
Intracellular activity of azithromycin [Zithromax] against bacterial enteric pathogens.

Rakita RM, Jacques-Palaz K, Murray BE.

Department of Internal Medicine, University of Texas Medical School at Houston 77030.

Azithromycin, a new azalide antibiotic, is active in vitro against a variety of enteric bacterial pathogens. Since it is concentrated inside human neutrophils and other cells, it might be particularly useful in the treatment of infections caused by enteropathogens that invade host tissues. The intracellular activity of azithromycin [Zithromax] against several enteric pathogens that had been phagocytosed by neutrophils was determined. Azithromycin [Zithromax] was effective in reducing the intracellular viabilities of almost all strains tested, including representative strains of Salmonella, Shigella, and enteroinvasive, enteropathogenic, enterotoxigenic, and enterohemorrhagic Escherichia coli. Erythromycin was also effective in this model system, although azithromycin [Zithromax] was generally more effective than erythromycin against strains of invasive enteric pathogens. Cefotaxime reduced intracellular bacterial viability to a lesser extent than either azithromycin [Zithromax] or erythromycin. The presence of neutrophils did not significantly affect the activity of azithromycin [Zithromax] in this system. Azithromycin [Zithromax] may be a useful agent for the treatment of bacterial diarrhea, and clinical trials should be considered.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7810998&dopt=Abstract Zithromax azithromycin




Pediatr Infect Dis J. 1999 Nov;18(11):955-8.
Impact of community-based mass treatment for trachoma with oral azithromycin [Zithromax] on general morbidity in Gambian children.

Whitty CJ, Glasgow KW, Sadiq ST, Mabey DC, Bailey R.

Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, UK.

BACKGROUND: The World Health Organization has recently targeted the elimination of trachoma as a public health problem by the year 2020. Community-based treatment with antibiotics, including oral azithromycin, is recommended for severely affected communities. The incidence of adverse effects after azithromycin [Zithromax] treatment is not known in trachoma endemic communities. METHODS: We compared the effects of azithromycin [Zithromax] with those of topical tetracycline given as mass treatment for trachoma on childhood morbidity in eight rural Gambian villages. The entire population of four villages received oral azithromycin [Zithromax] suspension (Zithromax, Pfizer) in doses of 20 mg/kg on Days 1, 8 and 15; the other four villages received topical tetracycline eye ointment for 42 days. Morbidity surveys of subjects 3 months to 14 years old were conducted on Days 0, 7, 14, 21 and 28. RESULTS: Of the 804 subjects recruited complete follow-up data were available on 791 (412 azithromycin, 379 tetracycline). Fever and headache were the most common complaints. Apart from cough other symptoms were equally prevalent in both groups at baseline. The azithromycin [Zithromax] group had 20% fewer illness, fever and headache episodes and 40% fewer diarrhea and vomiting episodes at follow-up than did the tetracycline group. CONCLUSIONS: Azithromycin [Zithromax] treatment for trachoma had favorable short term effects on childhood morbidity in rural Gambian villages, particularly in the high malaria transmission season, and adverse effects were not a problem.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10571428&dopt=Abstract Zithromax azithromycin




J Antimicrob Chemother. 1994 Sep;34(3):371-82.
Azithromycin [Zithromax] uptake and intracellular accumulation by Toxoplasma gondii-infected macrophages.

Blais J, Beauchamp D, Chamberland S.

Laboratoire et Service d'Infectiologie, Centre de Recherche du Centre Hospitalier de l'Universite Laval, Quebec, Canada.

The uptake of azithromycin [Zithromax] and erythromycin was measured in RAW 264.7 mouse macrophages infected with Toxoplasma gondii to determine whether the activity of macrolides could be correlated with their degree of host cell penetration. Uptake was expressed as the ratio of the intracellular (I) to the extracellular (E) concentrations. After infection, the intracellular accumulation of macrolides was equivalent to that measured in uninfected cells and azithromycin [Zithromax] reached an I/E ratio of 105.8 +/- 8.0 in infected macrophages incubated with 20 mg/L of drug. The release of azithromycin [Zithromax] from macrophages previously exposed to the drug was enhanced by exposure to Micrococcus luteus and phorbol myristate acetate but not after infection with T. gondii. Azithromycin [Zithromax] accumulates readily and remains inside T. gondii-infected macrophages thereby interfering with the growth of the parasite which was confirmed by growth-inhibition experiments and by electron microscopy.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7829411&dopt=Abstract Zithromax azithromycin