J Antimicrob Chemother. 1993 Jun;31 Suppl E:17-28.
Comparison of azithromycin, roxithromycin, and cephalexin penetration kinetics in early and mature abscesses.

Girard D, Bergeron JM, Milisen WB, Retsema JA.

Central Research Division, Pfizer Inc, Groton, CT 06340.

During the process of abscess formation, a myriad of changes are observed histologically that impede the penetration of antimicrobial agents into infection loci. A Staphylococcus aureus foreign body abscess, developed in rats, was employed to evaluate the penetration kinetics of azithromycin, roxithromycin and cephalexin at various stages of abscess development; the progressive patho-histological changes of abscess formation were also characterized in this model. In an early abscess (18 h post-challenge), azithromycin [Zithromax] penetration into inflammatory fluid was enhanced (AUC of 351 vs 130 mg.h/kg) and residence prolonged relative to an inflammation control (half-life of 88 vs 27 h). In contrast, roxithromycin and cephalexin penetration into, and residence in, inflammatory fluid were unaltered in the early abscess. However, penetration into, and egress from, a mature abscess (ten days post-challenge) were impeded for all three antimicrobials (P < or = 0.03). The penetration kinetics of azithromycin [Zithromax] into inflammatory fluid in an early abscess were independent of the dose regimen, but dependent on the total dose. The persistently high concentrations of azithromycin [Zithromax] in inflammatory fluid within abscess were associated with the infiltration of phagocytic cells and encapsulation by fibrous tissue. These data are consistent with a phagocytic delivery mechanism for azithromycin, whereby the presence of high concentrations of azithromycin [Zithromax] in inflammatory fluid are a consequence of augmented drug distribution via the release of accumulated intracellular drug from the infiltrating phagocytic cells and fibroblasts associated with abscess formation.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8396089&dopt=Abstract Zithromax azithromycin




J Antimicrob Chemother. 1993 Jun;31 Suppl E:171-6.
A comparison of the efficacy of azithromycin [Zithromax] and clarithromycin in oral therapy of experimental airborne Legionnaires' disease.

Fitzgeorge RB, Lever S, Baskerville A.

Public Health Laboratory Service Centre for Applied Microbiology and Research, Salisbury, Wiltshire, UK.

The activities of two new macrolides, azithromycin [Zithromax] and clarithromycin, were compared in an aerosol-infected guinea-pig model of legionnaires' disease. The results of this study indicate that a low oral dose of azithromycin [Zithromax] (3.6 mg/kg) administered once daily gives 100% survival in Legionella pneumophila-infected animals. An eight-fold higher dose of clarithromycin (28.8 mg/kg) given twice-daily was required to achieve the same effect. Similarly, azithromycin [Zithromax] was more effective than clarithromycin in preventing pyrexia and in reducing numbers of bacteria and lesions in the lung.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8396090&dopt=Abstract Zithromax azithromycin




J Antimicrob Chemother. 1993 Jun;31 Suppl E:193-8.
Open study of the safety and efficacy of a single oral dose of azithromycin [Zithromax] for the treatment of uncomplicated gonorrhoea in men and women.

Waugh MA.

Department of Genito-urinary Medicine, General Infirmary, Leeds, UK.

An open, non-comparative study was undertaken to assess the safety and efficacy of a single 1 g oral dose of azithromycin [Zithromax] in patients with uncomplicated gonorrhoea. One hundred and eighteen patients (105 male, 13 female) took part in the study. Only patients culture-positive for Neisseria gonorrhoeae were evaluated. The majority of male patients (84) had urethral gonorrhoea, but four had rectal and two pharyngeal infections. Four patients had positive cultures at more than one site (two urethral and rectal; two urethral and pharyngeal). All nine female patients had infection of the cervix only. Bacteriological eradication of N. gonorrhoeae was achieved in 76/82 (93%) patients with positive urethral cultures, 9/9 with positive cervical, 4/4 with positive rectal, and 2/2 with positive pharyngeal cultures. Twenty-two patients (18 males, four females) had concomitant chlamydial infection. Chlamydia trachomatis was eradicated in all patients who returned for follow-up assessment and in whom culture was done. Azithromycin [Zithromax] was very well tolerated, with only two patients reporting mild-to-moderate side-effects. This study shows that single-dose azithromycin [Zithromax] is effective in uncomplicated gonorrhoea and in mixed gonococcal and chlamydial infections.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8396093&dopt=Abstract Zithromax azithromycin




J Antimicrob Chemother. 1993 Jun;31 Suppl E:29-37.
The comparative activity of azithromycin, macrolides and amoxycillin against streptococci in experimental infections.

Girard AE, Cimochowski CR, Faiella JA.

Central Research Division, Pfizer Inc., Groton, CT 06340.

Since serious sequelae may follow streptococcal infections, eradication is viewed as necessary for successful therapy. Studies were therefore conducted to compare the effectiveness of azithromycin [Zithromax] with other macrolide antibiotics and amoxycillin to eliminate these organisms in experimental localized infections. In a Streptococcus pneumoniae lung infection induced by transtracheal challenge, the pathogen was not recovered after therapy with azithromycin [Zithromax] (ED50 7.9 mg/kg), while clarithromycin was not effective (ED50 > 100 mg/kg). However, in a S. pneumoniae middle ear infection, azithromycin [Zithromax] and clarithromycin were effective (ED50 2.9 and 6.3 mg/kg, respectively) in eradicating the pathogen from this closed space infection. Against a localized Streptococcus pyogenes infection (implanted inoculated disc), azithromycin [Zithromax] effectively eradicated the pathogen, while clarithromycin, roxithromycin and erythromycin did not. Eradication of a viridans streptococcus or Streptococcus gordonii (formerly Streptococcus sanguis) from heart tissue in experimental bacterial endocarditis was also evaluated. Azithromycin [Zithromax] given prophylactically or therapeutically was efficacious in eliminating the viridans streptococcus and S. gordonii in the bacterial endocarditis model of infection; erythromycin was only marginally effective in the same studies. All studies provided evidence of the bactericidal action of azithromycin [Zithromax] in vivo and demonstrated the ability of the compound to eradicate streptococcal pathogens in localized infections.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8396094&dopt=Abstract Zithromax azithromycin




J Antimicrob Chemother. 1993 Jun;31 Suppl E:39-50.
Selection of dose regimens of azithromycin [Zithromax] .

Foulds G, Johnson RB.

Drug Metabolism Department, Pfizer Inc, Groton, CT 06340.

The unique pharmacokinetics of azithromycin [Zithromax] are characterized by high, sustained tissue concentrations. The concentrations of azithromycin [Zithromax] were predicted, following various multiple dose regimens, from concentrations in tonsillar, prostatic, and uterine tissues following single oral doses. Following a five-day treatment regimen (500 mg on day 1, followed by 250 mg on days 2-5), or a three-day regimen (500 mg daily for three days), concentrations of azithromycin [Zithromax] in tonsillar tissue, representative of respiratory tract tissues, will continuously be greater than the MICs for key target pathogens (Streptococcus pyogenes, Haemophilus influenzae, Staphylococcus aureus) in infections of the respiratory tract for up to 10 days. Since tissue concentrations above the MICs for infecting organisms were correlated with efficacy in animal models of infection, short treatment regimens consisting of once-daily oral administration of azithromycin [Zithromax] should be effective in the treatment of a variety of infections. A single 1 g oral dose will provide concentrations in the uterus and prostate, representing urogenital tissues, above the MIC for Chlamydia trachomatis for approximately 10 days. Thus, this regimen should be effective in the treatment of chlamydial infections of the genital tract.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8396095&dopt=Abstract Zithromax azithromycin




J Antimicrob Chemother. 1993 Jun;31 Suppl E:5-16.
Preferential concentration of azithromycin [Zithromax] in an infected mouse thigh model.

Retsema JA, Bergeron JM, Girard D, Milisen WB, Girard AE.

Central Research Division, Pfizer Inc, Groton, CT 06340.

The possibility of augmentation of azithromycin [Zithromax] delivery to infection loci was evaluated by the use of Staphylococcus aureus thigh infection models with CD-1 mice. The intramuscular infections that developed were characterized by rapid growth of bacteria and induction of a localized oedema that was assessed gravimetrically. Microscopic examination of infected thighs showed massive infiltration of polymorphonuclear leucocytes (viable and degranulated), when compared to saline-injected thighs, from 24 to > or = 72 h after infection. Azithromycin [Zithromax] concentrations were enhanced significantly (P < or = 0.02) in infected thigh tissues compared with contralateral non-infected tissues, and correlated with oedema from 24-72 h after challenge and dosing. The azithromycin [Zithromax] levels in infected tissue after a 5 mg/kg dose were sufficient to cause a significant reduction in the number of cfu. If azithromycin [Zithromax] administration was delayed until inflammation was more severe, the result was an even greater preferential concentration of azithromycin [Zithromax] into the infected thigh. Preferential concentration of azithromycin [Zithromax] was not observed when extensive oedema was produced by injection of histamine. However, this oedema was not associated with a significant influx of polymorphonuclear leucocytes. In comparative studies, macrolide antibiotics known to be concentrated in phagocytes, such as erythromycin, roxithromycin, and clarithromycin, were not concentrated preferentially in infected tissues under the experimental conditions used; tissue levels were above or at the in-vitro MIC level for < or = 24 h. The data indicate that delivery of biologically available azithromycin [Zithromax] to infected tissues is enhanced by cellular inflammatory processes.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8396096&dopt=Abstract Zithromax azithromycin




J Antimicrob Chemother. 1993 Jun;31 Suppl E:51-6.
Comparison of the pharmacokinetics of three-day and five-day regimens of azithromycin [Zithromax] in plasma and urine.

Wildfeuer A, Laufen H, Leitold M, Zimmermann T.

Pfizer/Mack, R & D Laboratories, Illertissen, Germany.

In an open crossover study, the pharmacokinetics of three-day and five-day regimens of azithromycin [Zithromax] were compared. Fourteen healthy volunteers received oral doses of azithromycin [Zithromax] once-daily, over three days (500 mg/day) and over five days (500 mg on day 1, followed by 250 mg/day on days 2-5). Plasma and urine concentrations were determined by HPLC. Azithromycin [Zithromax] was found to be absorbed rapidly on the first and the last days of both regimens, with mean Tmax ranging between 2.5-3 h. On day 1, peak plasma concentrations were 0.37 mg/L and 0.31 mg/L, respectively, with three- and five-day regimens, and increased to 0.42 mg/L on the last day of the three-day regimen, but decreased to 0.18 mg/L at the end of the five-day regimen. Similarly, the AUC0-24 increased from 1.30 to 1.88 h.mg/L during the three-day regimen, and decreased from 1.24 to 0.80 h.mg/L on the five-day regimen. After absorption, azithromycin [Zithromax] was distributed rapidly; the respective half-lives were 2.4 h and 2.2 h with the three-day and five-day regimens. Thereafter, a polyphasic decline of plasma concentrations was observed; the average half-lives between 8-48 h after administration were 27.9 h (three-day regimen) and 35.8 h (five-day regimen). In urine, 5.5% (three-day regimen) and 4.6% (five-day regimen) of the total dose was found as unchanged azithromycin [Zithromax] over a 12-day period. The observed pharmacokinetics of azithromycin [Zithromax] with both regimens conformed with the known pharmacokinetic behaviour of the drug. The treatment-related differences seen in the plasma concentrations were as expected from the different dosage schedules.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8396097&dopt=Abstract Zithromax azithromycin