pcs.mb.ca

BACKGROUND: The association between macrolide resistance mechanisms and bacteriological eradication of Streptococcus pneumoniae remains poorly studied. The present study, using an in vitro pharmacodynamic model, assessed azithromycin [Zithromax] activity against macrolide-susceptible and -resistant S. pneumoniae simulating clinically achievable free serum (S), epithelial lining fluid (ELF) and middle ear fluid (MEF) concentrations. MATERIALS AND METHODS: Two macrolide-susceptible [PCR-negative for both mef(A) and erm(B)] and six macrolide-resistant [five mef(A)-positive/erm(B)-negative displaying various degrees of macrolide resistance and one mef(A)-negative/erm(B)-positive] S. pneumoniae were tested. Azithromycin [Zithromax] was modelled simulating a dosage of 500 mg/250 mg by mouth, once a day [free S: maximum concentration (Cmax) 0.2 mg/L, t1/2 68 h; free ELF Cmax 1.0 mg/L, t1/2 68 h] and 10 mg/kg by mouth, once a day (free MEF: Cmax 1.0 mg/L, t1/2 68 h) using a one compartment model. Starting inocula were 1 x 10(6) cfu/mL in Mueller-Hinton broth with 2% lysed horse blood. Sampling at 0, 2, 4, 6, 12, 24 and 48 h assessed the extent of bacterial killing (decrease in log10 cfu/mL versus initial inoculum). RESULTS: Free azithromycin [Zithromax] concentrations in serum, ELF and MEF simulating time above the MIC (T > MIC) of 100% [area under the curve to MIC (AUC0-24/MIC] > or = 36.7] were bactericidal (> or = 3 log10 killing) at 24 and 48 h versus macrolide-susceptible S. pneumoniae. Against macrolide-resistant S. pneumoniae, free serum concentrations providing T > MIC of 0% or AUC0-24/MIC < or = 1.1 demonstrated no bacterial inhibition followed by regrowth at 24 and 48 h, whereas free ELF and MEF providing T > MIC of 0% or AUC0-24/MIC of 4.6 produced a bacteriostatic (0.2-0.5 log10 killing at 24 h) effect with a mef(A) strain with an azithromycin [Zithromax] MIC of 2 mg/L. Against mef(A)-positive S. pneumoniae strains with azithromycin [Zithromax] MICs > or = 4 mg/L, no bacterial killing occurred at any time point and rapid regrowth was observed simulating ELF or MEF T > MIC of 0% or AUC0-24/MIC < or = 2.3. CONCLUSION: Azithromycin [Zithromax] serum, ELF and MEF concentrations rapidly eradicated macrolide-susceptible S. pneumoniae but did not eradicate macrolide-resistant S. pneumoniae regardless of resistance phenotype.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12775677&dopt=Abstract Zithromax azithromycin

cdc.gov

BACKGROUND: Treatment of incubating syphilis with intramuscular benzathine penicillin in exposed sex partners is not always practical in the field, and exposed partners may not adhere to referrals for treatment at clinical facilities. The availability of a single-dose oral therapy could increase the number of partners treated and reduce future infections. GOAL: The goal of the study was to evaluate the cost-effectiveness of directly observed oral administration of azithromycin [Zithromax] as an alternative to referral for treatment with benzathine penicillin. STUDY DESIGN: Using published probability and cost estimates, we constructed a decision-analysis model to compare the direct costs and effectiveness of field treatment with azithromycin [Zithromax] (1-g single dose) versus referral for standard benzathine penicillin therapy. RESULTS: At public-sector pricing ($11.50 U.S. dollars), directly observed field treatment with azithromycin [Zithromax] is cost-saving from both the program and healthcare system perspectives at efficacy levels as low as 75%. Azithromycin [Zithromax] therapy is cost-saving at the wholesale price of $17.32 U.S. dollars (sachet formulation) when efficacy is at least 90%. The more expensive tablet formulation (average wholesale price of $27.89 U.S. dollars) is not cost-saving from a program perspective, but it remains cost-saving from a healthcare system perspective if efficacy rates are at least 90%. Azithromycin [Zithromax] therapy (1-g single dose) will result in fewer cases of early syphilis among exposed partners, provided that the drug's efficacy is at least 87%. CONCLUSIONS: Azithromycin [Zithromax] is a cost-effective alternative treatment for incubating syphilis in settings where standard intramuscular therapy is not practical.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12782951&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 1992 Oct;36(10):2304-9.
Azithromycin-induced block of elementary body formation in Chlamydia trachomatis.

Engel JN.

Department of Medicine, University of California, San Francisco 94143.

The mechanism of action of azithromycin [Zithromax] on the murine strain of Chlamydia trachomatis grown in tissue culture epithelial cells is addressed. Azithromycin [Zithromax] at a concentration of 100 ng/ml inhibits chlamydial growth in tissue culture, a value that agrees well with prior in vitro data from human strains of C. trachomatis grown in tissue culture. By morphological criteria, the block to chlamydial growth appears to occur early in its life cycle. Azithromycin [Zithromax] is not directly toxic to chlamydial elementary bodies but does inhibit chlamydial protein synthesis in chlamydia-infected cells. This inhibition appears quite general in nature and is rapid. It is further shown that azithromycin [Zithromax] does not directly inhibit mRNA synthesis. Azithromycin [Zithromax] blocks chlamydial protein synthesis in host cell-free chlamydial reticulate bodies in a manner similar to its inhibition in infected cells, albeit at slightly higher concentrations. The inhibition of chlamydial protein synthesis following a brief exposure to azithromycin [Zithromax] is more long lasting than that following a brief exposure to erythromycin.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1280057&dopt=Abstract Zithromax azithromycin




J Membr Biol. 2003 Apr 1;192(3):203-15.
The macrolide antibiotic azithromycin [Zithromax] interacts with lipids and affects membrane organization and fluidity: studies on Langmuir-Blodgett monolayers, liposomes and J774 macrophages.

Tyteca D, Schanck A, Dufrene YF, Deleu M, Courtoy PJ, Tulkens PM, Mingeot-Leclercq MP.

Unite de Pharmacologie Cellulaire et Moleculaire, Universite Catholique de Louvain, Brussels, Belgium.

The macrolide antibiotic azithromycin [Zithromax] was shown to markedly inhibit endocytosis. Here we investigate the interaction of azithromycin [Zithromax] with biomembranes and its effects on membrane biophysics in relation to endocytosis. Equilibrium dialysis and 31P NMR revealed that azithromycin [Zithromax] binds to lipidic model membranes and decreases the mobility of phospholipid phosphate heads. In contrast, azithromycin [Zithromax] had no effect deeper in the bilayer, based on fluorescence polarization of TMA-DPH and DPH, compounds that, respectively, explore the interfacial and hydrophobic domains of bilayers, and it did not induce membrane fusion, a key event of vesicular trafficking. Atomic force microscopy showed that azithromycin [Zithromax] perturbed lateral phase separation in Langmuir-Blodgett monolayers, indicating a perturbation of membrane organization in lateral domains. The consequence of azithromycin/ phospholipid interaction on membrane endocytosis was next evaluated in J774 macrophages by using three tracers with different insertion preferences inside the biological membranes and intracellular trafficking: C6-NBD-SM, TMA-DPH and N-Rh-PE. Azithromycin [Zithromax] differentially altered their insertion into the plasma membrane, slowed down membrane trafficking towards lysosomes, as evaluated by the rate of N-Rh-PE self-quenching relief, but did not affect bulk membrane internalization of C6-NBD-SM and TMA-DPH. Azithromycin [Zithromax] also decreased plasma membrane fluidity, as shown by TMA-DPH fluorescence polarization and confocal microscopy after labeling by fluorescent concanavalin A. We conclude that azithromycin [Zithromax] directly interacts with phospholipids, modifies biophysical properties of membrane and affects membrane dynamics in living cells. This antibiotic may therefore help to elucidate the physico-chemical properties underlying endocytosis.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12820665&dopt=Abstract Zithromax azithromycin

pharma.hr

The oxidative behaviour of azithromycin [Zithromax] was studied at s glassy carbon electrode in different buffer system using cyclic, linear sweep and differential pulse voltammetry. The oxidation process was shown to be irreversible over the entire pH range studied (5-11) and was diffusion-adsorption controlled. Analytical method with adequate precision and accuracy was developed for the determination of azithromycin [Zithromax] in phosphate buffer at pH 7 as supporting electrolyte containing 10% methanol and 0.05 M ammonium acetate. The peak current varied linearly with azithromycin [Zithromax] concentration in the range 1-15 microg/ml. The procedure was successfully applied for assay of the drug in the pharmaceutical dosage forms. The relative standard deviation (n = 5) of 2.18% was obtained.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12852463&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 2003 Sep;47(9):2765-9.
Impact of azithromycin [Zithromax] administration for trachoma control on the carriage of antibiotic-resistant Streptococcus pneumoniae.

Batt SL, Charalambous BM, Solomon AW, Knirsch C, Massae PA, Safari S, Sam NE, Everett D, Mabey DC, Gillespie SH.

Department of Medical Microbiology, University College London, Royal Free Campus, London NW3 2PF.

Community distribution of azithromycin [Zithromax] has an important role to play in trachoma control. Previous studies have suggested that this may increase the prevalence of macrolide-resistant Streptococcus pneumoniae. S. pneumoniae was isolated from children under 7 years of age in Rombo District, northern Tanzania, before and 2 and 6 months after community-wide administration of azithromycin. Overall carriage rates were 11, 12, and 7%, respectively. Only one macrolide-resistant isolate carrying the mef gene was obtained 6 months after azithromycin [Zithromax] administration. This contrasted with cotrimoxazole and penicillin resistance, both of which were common (cotrimoxazole resistance, 42, 43, and 47%, and penicillin resistance, 21, 17, and 16% at baseline, 2 months, and 6 months, respectively). There was a significant association between cotrimoxazole and penicillin resistance (P < 0.0001, Fisher's exact). These data suggest that in communities where macrolide resistance is rare, azithromycin [Zithromax] distribution for trachoma control is unlikely to increase the prevalence of resistant organisms.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12936971&dopt=Abstract Zithromax azithromycin




Acta Trop. 2003 Sep;88(1):45-50.
Efficacy of azithromycin [Zithromax] in a murine toxoplasmosis model, employing a Toxoplasma gondii strain from Turkey.

Degerli K, Kilimcioglu AA, Kurt O, Tamay AT, Ozbilgin A.

Department of Microbiology and Clinical Microbiology, School of Medicine, Celal Bayar University, Manisa 45010, Turkey.

A murine toxoplasmosis model with Balb/C mice was used to investigate the therapeutic and prophylactic efficacy of azithromycin [Zithromax] in a native strain of Toxoplasma gondii. Initially, seven groups--four studies and three controls--were established and 10(3) tachyzoites of this native strain of T. gondii were injected intraperitoneally to the mice in groups 1, 2, 3, 4 and 7. Azithromycin [Zithromax] was given to groups 1-4 at different times of infection orally between 100 and 300 mg/kg/day for 10 days. Azithromycin [Zithromax] was found to be effective at 200 mg/kg/day and above in the prophylaxis, at 250 mg/kg/day and above in the treatment of toxoplasmosis. These results suggest that azithromycin [Zithromax] is effective in the prophylaxis and early infection of a highly virulent strain of T. gondii, and it doubled the survival time in the late infection. Azithromycin [Zithromax] could be an alternative treatment regimen for human toxoplasmosis, if supported by further clinical investigations.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12943976&dopt=Abstract Zithromax azithromycin