J Antibiot (Tokyo). 1995 Oct;48(10):1141-7.
In vivo evaluation of three acid-stable azalide compounds, L-701,677, L-708,299 and L-708,365 compared to erythromycin, azithromycin [Zithromax] and clarithromycin.

Gill CJ, Abruzzo GK, Flattery AM, Smith JG, Jackson J, Kong L, Wilkening R, Shankaran K, Kropp H, Bartizal K.

Merck Research Laboratories, Merck & Company, Inc., Rahway, NJ 07065-0900, USA.

L-701,677, L-708,299 and L-708,365 are novel azalide derivatives of erythromycin that exhibit improved acid stability over erythromycin, azithromycin [Zithromax] and clarithromycin. The half-life in aqueous solution at pH = 2.1 of these compounds ranged from 0.3 hour for erythromycin to 16.2 hours for L-708,299. The rank order of half-life in acid solution from most to least stable was L-708,299 > L-701,677 > L-708,365 > azithromycin [Zithromax] = clarithromycin > erythromycin. In a disseminated Streptococcus pyogenes mouse infection model, azithromycin [Zithromax] and L-708,365 were slightly more efficacious than clarithromycin, L-701,677 and L-708,299; all 5 compounds being more active than erythromycin. In a Klebsiella pneumoniae pulmonary challenge mouse model, azithromycin, L-701,677, L-708,299 and L-708,365 were all equal in efficacy and at least four-fold more active than clarithromycin and erythromycin. Clarithromycin, L-708,365 and interestingly erythromycin, showed greater bacterial clearance than azithromycin, L-701,677 and L-708,299 in a localized infection model that measured clearance of Staphylococcus aureus from mouse thigh tissues. Our results indicate that L-701,677, L-708,299 and L-708,365 exhibit improved acid stability and were at least equally efficacious as presently marketed macrolide/azalide antibiotics.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7490222&dopt=Abstract Zithromax azithromycin




Sex Transm Dis. 1995 Sep-Oct;22(5):274-80.
The cost effectiveness of azithromycin [Zithromax] for Chlamydia trachomatis infections in women.

Haddix AC, Hillis SD, Kassler WJ.

Epidemiology Program Office, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.

BACKGROUND AND OBJECTIVES: Azithromycin, an approved single-dose therapy for cervical chlamydia infections, costs four times as much as doxycycline, the standard multidose theapy. GOAL OF THIS STUDY: This study examined whether azithromycin [Zithromax] is cost effective for treating cervical chlamydia infections. STUDY DESIGN: Two diagnostic strategies were compared: 1) laboratory confirmation of chlamydia, and 2) presumptive diagnosis from the perspective of the healthcare system and the publicly funded clinic. RESULTS: From the healthcare perspective, the cost per case of pelvic inflammatory disease prevented with azithromycin [Zithromax] ranges from a savings of $3,502 for laboratory confirmation to a cost of $792 for presumptive diagnosis. From the publicly funded clinic perspective, the cost per case of pelvic inflammatory disease prevented ranges from $709 for lab-confirmed diagnosis to $3,969 for presumptive treatment. CONCLUSION: For the healthcare system, azithromycin [Zithromax] is a cost-effective alternative to doxycycline. However, the cost of azithromycin [Zithromax] must decrease markedly for it to be less costly to the publicly funded clinic.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7502180&dopt=Abstract Zithromax azithromycin




Ann Intern Med. 1996 Jan 1;124(1 Pt 1):1-7.
A cost-effectiveness analysis of screening and treatment for Chlamydia trachomatis infection in asymptomatic women.

Genc M, Mardh A.

Uppsala University Centre for STD Research, Sweden.

OBJECTIVE: To assess the cost-effectiveness of identifying and treating asymptomatic female carriers of Chlamydia trachomatis. DESIGN: Cost-effectiveness analysis based on previously reported cohort analytic studies and average salaries and costs of medical care in Sweden. SETTING: Women attending youth, family planning, and gynecology clinics. PARTICIPANTS: 1000 women and their male sex partners. INTERVENTION: Screening with tissue cell culture, confirmed enzyme immunoassay, and DNA amplification assays based on either polymerase chain reaction or ligase chain reaction was compared with no screening (no treatment and no tracing of sexual contacts). The effect of antibiotic regimens on the outcome of the screening strategies was also evaluated. RESULTS: When the prevalence of chlamydial infection exceeded 6%, screening of women with DNA amplification assay and treatment of positive patients with a single oral dose of azithromycin [Zithromax] given under supervision in the clinic was the most cost-effective intervention strategy. At greater prevalences, screening with enzyme immunoassay also generated savings and improved the cure rates compared with no screening, but such screening was less cost-effective than screening with a DNA amplification assay. Compared with no intervention, tissue cell culture is cost-effective only when the prevalence of infection is greater than 14%. Compared with the azithromycin [Zithromax] regimen, the standard 7-day, twice-daily doxycycline regimen resulted in significantly lower cure rates because of patients' poor compliance with this regimen. CONCLUSION: For asymptomatic female carriers of C. trachomatis, screening with a DNA amplification assay combined with the single-dose azithromycin [Zithromax] treatment of positive patients is the most cost-effective strategy when the prevalence is 6%. When the prevalence is lower than 6%, the decision to choose a competing strategy depends on the physician's view of the value of preventing an illness caused by untreated chlamydial infection.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7503471&dopt=Abstract Zithromax azithromycin




Int J Tissue React. 1994;16(5-6):211-20.
Accumulation, release and subcellular localization of azithromycin [Zithromax] in phagocytic and non-phagocytic cells in culture.

Carlier MB, Garcia-Luque I, Montenez JP, Tulkens PM, Piret J.

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

The authors have examined the pharmacokinetic parameters of azithromycin [Zithromax] in phagocytic (J774 macrophages) and non-phagocytic (rat embryo fibroblasts and NRK-cells) cultured cells. Azithromycin [Zithromax] demonstrates an exceptionally large accumulation in all the cell types tested (perhaps in two functionally and structurally distinct compartments) and a slow release of the cell-associated drug. Azithromycin [Zithromax] probably accumulates in cells by a non-specific transport process following the model of diffusion/segregation. The cell-associated drug distributes mostly in the lysosomal compartment (50-70%) and the remaining part is freely soluble in the cytosol. In fibroblasts, and to a lesser extent in NRK-cells, azithromycin [Zithromax] (10mg/l) induces a decrease of the buoyant density of the lysosomes which may be brought about by the drug itself together with osmotically-bound water and/or by the accumulation of low-density materials within these organelles. These observations open important questions with respect to the potential toxicity of azithromycin. The significance of such alterations and of their biological consequences are at present under investigation.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7558665&dopt=Abstract Zithromax azithromycin




Pathol Biol (Paris). 1995 Apr;43(4):281-3.
[Comparative activity of azithromycin [Zithromax] against 100 strains of Neisseria gonorrhoeae]

[Article in French]

Chevalier B, Crenn Y, Cavallo JD, Plotton N, Meyran M.

Laboratoire de Biologie, HIA Val-de-Grace, Paris, France.

Azithromycin [Zithromax] is a new semisynthetic, acid stable C15 macrolid. In our study, we compared in vitro activity of azithromycin [Zithromax] with 6 other antibiotics usually recommended for treatment of N. gonorrhoeae infections: erythromycin, ampicillin, amoxicillin, ceftriaxone, spectinomycin, ciprofloxacin. 100 strains have been selected: 95 clinical strains with different resistance patterns: 60 susceptible to beta-lactams, 25 PPNG, 10 chromosomal decreased susceptibility to beta-lactams. Among these strains, 13 had a decreased susceptibility to erythromycin (MIC: 2 and 4 mg/l) and 5 WHO reference strains: A: spectinomycin resistance, B: wild phenotype, C: chromosomal decreased susceptibility to penicillin and tetracycline, D: chromosomal resistance to penicillin and erythromycin+chromosomal decreased susceptibility to chloramphenicol, E: beta-lactamase producing strain (PPNG) and decreased susceptibility to tetracycline. MICs have been determined by GC agar dilution method. Azithromycin [Zithromax] is more active than erythromycin on all N. gonorrhoeae patterns with a two log 10 difference for MIC50 and MIC90 (p < 0.0001). Because of pharmacokinetic properties and activity against Chlamydia trachomatis and urogenital mycoplasms often associated with N. gonorrhoeae, azithromycin [Zithromax] is a good alternative for the treatment of genital infections.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7567115&dopt=Abstract Zithromax azithromycin




Genitourin Med. 1995 Aug;71(4):244-6.
Azithromycin [Zithromax] levels in cervical mucus and plasma after a single 1.0g oral dose for chlamydial cervicitis.

Worm AM, Osterlind A.

Department of Dermato-Venereology, Bispebjerg Hospital, Copenhagen NV, Denmark.

OBJECTIVE--To determine the kinetics of azithromycin [Zithromax] in cervical mucus and plasma. SUBJECTS AND METHODS--Azithromycin [Zithromax] concentrations were determined in plasma and mucus samples from 20 women with cervical chlamydial infection one, seven and fourteen days after a single oral 1.0 g dose. RESULTS--In mucus, all measurable azithromycin [Zithromax] concentrations were above the minimal inhibitory concentration against Chlamydia trachomatis on day 7 as well as on day 14. CONCLUSION--The high cervical mucus concentrations of azithromycin [Zithromax] can explain the high clinical and microbiological efficacy.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7590717&dopt=Abstract Zithromax azithromycin




J Antimicrob Chemother. 1995 May;35(5):623-9.
Azithromycin [Zithromax] in an experimental Staphylococcus aureus abscess model.

Bamberger DM, Herndon BL, Suvarna PR.

Section of Infectious Diseases, University of Missouri-Kansas City School of Medicine 64108-2792, USA.

We studied the efficacy and pharmacokinetics of azithromycin [Zithromax] in a rabbit tissue-cage Staphylococcus aureus abscess model. A dosage of 15 mg/kg/day azithromycin [Zithromax] was administered to rabbits with 24 h or 2 week old infected tissue cages and to uninfected controls. Concentrations of azithromycin [Zithromax] were higher in the infected compared with the uninfected tissue cages. Azithromycin [Zithromax] was effective in reducing the bacterial concentrations in both groups of infected tissue cages by approximately 3 log10 cfu/mL compared with untreated controls after 8 days of therapy. Fifty percent of the 24 h and 29% of the 2 week infected tissue cages became culture-negative.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7592175&dopt=Abstract Zithromax azithromycin