J Antimicrob Chemother. 1995 Dec;36(6):941-50.
Azithromycin [Zithromax] induces in vitro a time-dependent increase in the intracellular killing of Staphylococcus aureus by human polymorphonuclear leucocytes without damaging phagocytes.

Silvestri M, Oddera S, Eftimiadi C, Rossi GA.

Divisione di Pneumologia, Istituto Giannina Gaslini, Genova-Quarto, Italy.

Despite its clinical efficacy on intracellular pathogens, the in-vitro intracellular antimicrobial activity of azithromycin, has been shown to be absent or lower than expected from the intracellular concentrations reached. To test the possibility that the high intracellular concentrations of the drug could damage phagocytes, the present study evaluated the effects of azithromycin [Zithromax] on (a) the intracellular killing of Staphylococcus aureus by human blood neutrophils (PMNs) and (b) the viability and the respiratory burst of PMNs. Using a fluorochrome assay, we assessed the phagocytosis and intracellular killing of S. aureus by PMNs preloaded with azithromycin, or by PMNs unloaded but with the drug in the culture medium. In addition, possible drug-induced damage to PMNs was evaluated measuring: (a) hydrogen peroxide (H2O2) production and (b) the percentages of PMNs dead at the end of the phagocytosis process. Compared to control PMNs without drug, a time-dependent enhancement in the intracellular killing was observed which was statistically significant after 60 min incubation. The increased intracellular killing was higher in suspensions of unloaded PMNs and azithromycin [Zithromax] (P < 0.01) that in suspensions of preloaded PMNs (P < 0.05). This increased intracellular killing was not associated with increased proportions of dead phagocytes, either in preloaded or unloaded PMNs (P < 0.05, each comparison). Similarly no changes in the production of H2O2 by PMNs were observed in the presence of azithromycin. Thus, azithromycin [Zithromax] induces a time-dependent increase in the bactericidal activity of human PMNs, without increasing the phagocyte self-killing or modifying H2O2 production.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8821593&dopt=Abstract Zithromax azithromycin




J Antimicrob Chemother. 1995 Dec;36(6):951-9.
The activity of azithromycin [Zithromax] on the infectivity of Chlamydia trachomatis in human amniotic cells.

Patton DL, Wang SK, Kuo CC.

Department of Obstetrics and Gynaecology, University of Washington, Seattle 98195, USA.

The effects of azithromycin [Zithromax] on the infectivity and growth of Chlamydia trachomatis were investigated in primary human amniotic epithelial cells. Infection was prevented when cultures were exposed to the drug 6 h after inoculation and growth was completely inhibited when the drug was added to cultures 24, 48, 72 h or 7 days after infection. The same inhibition was observed at 0.5, 1.0 and 5.0 mg/L. Ultrastructural observations depicted interruption in the growth cycle of the chlamydia and ghost-like envelopes were present in the near empty inclusions. Azithromycin [Zithromax] is effective in inhibiting chlamydial growth no matter when treatment is initiated after infection.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8821594&dopt=Abstract Zithromax azithromycin

facm.ucl.ac.be

Azithromycin [Zithromax] accumulates in lysosomes where it causes phospholipidosis. In homogenates prepared by sonication of fibroblasts incubated for 3 days with azithromycin [Zithromax] (66 microM), the activities of sulfatase A, phospholipase A1, N-acetyl-beta-hexosaminidase and cathepsin B increased from 180 to 330%, but not those of 3 non-lysosomal enzymes. The level of cathepsin B mRNA was unaffected. The hyperactivity induced by azithromycin [Zithromax] is non-reversible upon drug withdrawal, prevented by coincubation with cycloheximide, affects the Vmax but not the Km, and is not reproduced with gentamicin, another drug also causing lysosomal phospholipidosis. The data therefore suggest that azithromycin [Zithromax] increases the level of lysosomal enzymes by a mechanism distinct from the stimulation of gene expression but requiring protein synthesis, and is not in direct relation to the lysosomal phospholipidosis.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8830663&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 1996 Aug;40(8):1950-2.
Comparative activities of clarithromycin, erythromycin, and azithromycin [Zithromax] against penicillin-susceptible and penicillin-resistant pneumococci.

Ednie LM, Visalli MA, Jacobs MR, Appelbaum PC.

Department of Pathology (Clinical Microbiology), Hershey Medical Center, Pennsylvania 17033, USA.

Activities of clarithromycin, erythromycin, and azithromycin [Zithromax] against 120 pneumococci from the United States were tested by agar dilution MIC. All three compounds yielded MICs at which 90% of the isolates were inhibited (MIC90S) of < or = 0.125 micrograms/ml against penicillin-susceptible and -intermediate strains, but MIC90S against resistant strains were > 128.0 micrograms/ml. All erythromycin-resistant strains were also resistant to clarithromycin and azithromycin. Clarithromycin yielded MICs which were generally one or two dilutions lower than those of the other two compounds for all strains. The respective bacteriostatic and bactericidal values (micrograms per milliliter) for two susceptible, two intermediate, and two resistant strains were 0.004 to 0.03 and 0.016 to 0.03 (0.004 to 0.03/0.016 to 0.03) (clarithromycin), 0.008 to 0.06/0.016/0.016 to 0.125 (erythromycin), and 0.016 to 0.06/0.03 to 0.125 (azithromycin); clarithromycin yielded the lowest values. All compounds were uniformly bactericidal after 24 h only; erythromycin was bactericidal at eight times the MIC, and azithromycin [Zithromax] and clarithromycin were both bactericidal at two time the MIC. The relevance of these in vitro differences requires clarification by clinical trials.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8843313&dopt=Abstract Zithromax azithromycin




Infection. 1996 Jan-Feb;24(1):64-8.
Azithromycin [Zithromax] and doxycycline for treatment of Borrelia culture-positive erythema migrans.

Strle F, Maraspin V, Lotric-Furlan S, Ruzic-Sabljic E, Cimperman J.

Dept. of Infectious Diseases, University Medical Centre Ljubljana, Japlijeva, Slovenia.

Adult patients with typical solitary erythema migrans, participating in prospective therapeutic studies on early Lyme borreliosis at the Lyme borreliosis Outpatient's Clinic, University Department of Infectious Diseases in Ljubljana, in 1991 to 1993, and followed up for 1 year, were included in the study. Only patients who were treated with azithromycin [Zithromax] or doxycycline and in whom Borrelia burgdorferi was isolated from the border of the skin lesion prior to institution of antibiotic treatment were selected for presentation in this report. Fifty-eight patients received azithromycin [Zithromax] (500 mg twice daily for the first day, followed by 500 mg once daily for 4 days) and 42 patients received doxycycline (100 mg twice daily for 14 days). The median duration of skin lesions after the beginning of treatment was 6.5 (2-30) days in the azithromycin [Zithromax] group and 8 (2-35) days in the doxycycline group (non-significant difference). During the follow-up of 12 months one patient in each group developed major later manifestations of Lyme borreliosis and in 19 patients minor manifestations appeared: in nine (15.5%) treated with azithromycin [Zithromax] and in ten (23.8%) receiving doxycycline. In one patient in the azithromycin [Zithromax] group and in one patient in the doxycycline group B. burgdorferi was isolated from normal appearing skin at the site of previous erythema migrans 2 months after the institution of antibiotic therapy. Five (8.6%) patients receiving azithromycin [Zithromax] and nine (21.4%) patients receiving doxycycline reported mild to moderate gastrointestinal discomfort. In addition, five patients treated with doxycycline developed photosensitivity.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8852473&dopt=Abstract Zithromax azithromycin




J Chemother. 1996 Aug;8(4):254-60.
Influence of subinhibitory concentrations of ceftazidime, ciprofloxacin and azithromycin [Zithromax] on the morphology and adherence of P-fimbriated escherichia coli.

Vranes J, Zagar Z, Kurbel S.

Department of Microbiology and Parasitology, University of Zagreb, Medical School, Croatia.

The influence of subinhibitory concentrations (1/2, 1/4, 1/8, 1/16 and 1/32 x MIC) of ceftazidime, ciprofloxacin and azithromycin [Zithromax] on the morphology and adherence of 29 wild-type P-fimbriated strains of Escherichia coli was studied. Bacterial adherence to the Buffalo green monkey (BGM) cell line was tested before and after treatment with antibiotics and detected by means of an immunofluorescence staining. Significant dose dependent reduction of bacterial adherence was observed, which correlated with the alterations in bacterial cell morphology. After exposure of strains to sub-MICs of antibiotics, normal shapes, spherical forms and filaments were noted. The greatest filamentation and the greatest loss of adherence ability occurred at 1/2 x MIC of ceftazidime. Treatment with sub-MICs of ciprofloxacin resulted in shorter filaments, while filamentation did not occur after bacterial exposure to sub-MICs of azithromycin. Azithromycin [Zithromax] was least damaging to the adherence ability of E. coli and at a concentration of 1/2 x MIC caused globoid cell formation.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8873829&dopt=Abstract Zithromax azithromycin




Pediatr Infect Dis J. 1996 Sep;15(9 Suppl):S3-9.
Incidence of antibiotic-resistant Streptococcus pneumoniae and beta-lactamase-positive Haemophilus influenzae in clinical isolates from patients with otitis media.

McLinn S, Williams D.

Scottsdale Pediatric Center, AZ 85260-6743, USA.

BACKGROUND: The prevalence of penicillin-resistant Streptococcus pneumoniae and beta-lactamase-producing Haemophilus influenzae in otitis media infections is increasing; emergence of these pathogens has complicated treatment. OBJECTIVES: To evaluate the incidence of penicillin resistance and the in vitro activity of amoxicillin/clavulanate, cefaclor, loracarbef, cefixime, trimethoprim/sulfamethoxazole, azithromycin [Zithromax] and clarithromycin in S. pneumoniae isolates. The in vitro activity of azithromycin, clarithromycin and cefaclor was also evaluated in beta-lactamase-positive and -negative isolates of H. influenzae. METHODS: Bacterial isolates of S. pneumoniae and H. influenzae were obtained by tympanocentesis and subsequent culture of middle ear effusion from children with acute otitis media enrolled in a multicenter trial. Susceptibility to test agents was assessed by disk diffusion and broth dilution techniques with criteria established by the National Committee for Clinical Laboratory Standards. RESULTS: Nineteen (31%) of the 61 S. pneumoniae isolates were resistant to penicillin. A significantly lower percentage of the S. pneumoniae isolates were resistant to azithromycin [Zithromax] (16%) and clarithromycin (11%) than to penicillin, amoxicillin/ clavulanate, cefaclor, loracarbef or cefixime (31% in all cases). Azithromycin [Zithromax] was also more active than cefaclor and significantly more active than clarithromycin against the 55 H. influenzae isolates. CONCLUSIONS: The susceptibility of resistant and nonresistant strains of S. pneumoniae to azithromycin [Zithromax] and clarithromycin and of isolates of H. influenzae to azithromycin, coupled with penetration of azithromycin [Zithromax] into the middle ear, may provide a significant advantage in the treatment of otitis media.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8878239&dopt=Abstract Zithromax azithromycin