Oral Microbiol Immunol. 1993 Oct;8(5):325-6.
In vitro antimicrobial susceptibility of Porphyromonas gingivalis to azithromycin, a novel macrolide.

Pajukanta R.

Department of Periodontology, University of Helsinki, Finland.

The in vitro antimicrobial susceptibility of Porphyromonas gingivalis to azithromycin, a new macrolide antibiotic of a new class known as azalides, was investigated by the agar dilution method on Brucella agar. Eighty-two P. gingivalis strains, 79 recent oral isolates, 1 nonoral isolate and 2 reference strains were included in the study. Azithromycin [Zithromax] was highly effective against P. gingivalis. All strains were inhibited at 1.0 microgram/ml of azithromycin [Zithromax] or less. The minimal inhibitory concentrations were 0.25 microgram/ml for 50% and 0.5 microgram/ml for 90%. These in vitro data as well as the favorable pharmacokinetics of azithromycin [Zithromax] indicate that this new oral macrolide might be a good candidate for future clinical trials aiming to eradicate P. gingivalis from refractory periodontitis.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8265209&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 1993 Nov;37(11):2261-4.
Azithromycin [Zithromax] inhibition of intracellular Legionella micdadei.

Donowitz GR, Earnhardt KI.

Department of Medicine, University of Virginia, Charlottesville 22908.

Legionella micdadei is an intracellular parasite that is ingested, but not killed, by leukocytes. Within monocytes, the organism has been shown to grow 1.0 to 2.0 log10 units over 48 h (D. L. Weinbaum, R. R. Benner, J. N. Dowling, A. Alpern, A. W. Pasculle, and G. R. Donowitz, Infect. Immun. 46:68-73, 1984). Intracellular L. micdadei would appear to be a useful model in which to study the effect of antibiotics which accumulate intracellularly. Azithromycin, a newly introduced azalide, is highly concentrated within leukocytes and was therefore studied to determine its effect on a single strain of L. micdadei that had been ingested by human monocytes. Peripheral blood monocytes were allowed to ingest L. micdadei and extracellular, nonadherent organisms were subsequently removed by washing. Cells and cell-associated bacteria were then incubated at 0, 24, and 48 h in media with serial concentrations of azithromycin [Zithromax] at sub-MIC levels (less than 1.0 microgram/ml). L. micdadei in cells not exposed to azithromycin [Zithromax] grew 0.8 +/- 0.1 log10 units (mean +/- standard deviation) at 24 h and 1.7 +/- 0.4 log10 units at 48 h. At both 24 and 48 h, the lowest concentrations of azithromycin [Zithromax] tested (0.02 microgram/ml) significantly inhibited bacterial growth in monocytes (P = 0.02). A stepwise inhibition of L. micdadei CFUs was noted with increasing azithromycin [Zithromax] concentrations. In contrast, when cells were exposed to antibiotic before ingesting L. micdadei, a less effective antibacterial effect was noted. Under certain in vitro conditions, azithromycin [Zithromax] is a potent agent against intracellular L. micdadei.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8285604&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 1993 Nov;37(11):2318-22.
Uptake of azithromycin [Zithromax] by human monocytes and enhanced intracellular antibacterial activity against Staphylococcus aureus.

Meyer AP, Bril-Bazuin C, Mattie H, van den Broek PJ.

Department of Infectious Diseases, University Hospital Leiden, The Netherlands.

The uptake of azithromycin [Zithromax] by human monocytes and the intracellular antibacterial activity of azithromycin [Zithromax] against Staphylococcus aureus were investigated. With an extracellular pH of 6.9, the maximum intracellular concentration of azithromycin [Zithromax] in monocytes was about six times the extracellular concentration. The half-life for diffusion was 44 min. The results support the view that no active transport is involved in the intracellular accumulation of azithromycin. In cell-free medium, the maximum effect of azithromycin [Zithromax] on S. aureus was bacteriostasis, which was achieved at a concentration of 5 mg/liter. In contrast, concentrations greater than 1.5 mg of azithromycin [Zithromax] per liter were bactericidal for S. aureus ingested by monocytes. The difference in maximum growth inhibition on S. aureus for the two conditions was 0.1.68 h-1 (95% confidence interval, 0.128 to 0.208). The concentration of the drug that achieved 50% of the maximum effect was 0.434 mg/liter for both conditions. The enhancement of the effect on S. aureus ingested by monocytes suggests that the intracellular environment in human monocytes favors the antibacterial action of azithromycin. Enhancement of the antibacterial activity of azithromycin [Zithromax] was not observed with granulocytes.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8285612&dopt=Abstract Zithromax azithromycin




J Antimicrob Chemother. 1993 Jan;31(1):139-50.
In-vitro activity of azithromycin [Zithromax] on Chlamydia trachomatis infected, polarized human endometrial epithelial cells.

Wyrick PB, Davis CH, Knight ST, Choong J.

Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill 27599-7290.

The in-vitro activity of azithromycin [Zithromax] on Chlamydia trachomatis infected human endometrial epithelial cells, both primary and transformed cells growing in a polarized and non-polarized orientation, was analyzed. Addition of azithromycin [Zithromax] two hours after adsorption inoculation with continued exposure until 72 h gave an MIC90 and MBC90 of 0.063 and 0.5 mg/L, respectively. In addition, the MBC results were more pronounced in infected cells growing in a polarized orientation. Numerous small fluorescent 'spots' (presumed small abnormal inclusions) were visible in the infected cells exposed to MIC concentrations of azithromycin. Immuno-transmission electron microscopy examination revealed intracellular inclusions filled with chlamydial envelope ghosts. Since standard diagnostic antigen detection methods use anti-envelope antibodies, the aberrant envelope-filled inclusions might be interpreted as viable inclusions by fluorescent microscopy and result in high false positive readings. To simulate treatment of an infected patient, azithromycin [Zithromax] was added at 18 h to infected cells containing many reticulate bodies and exposure continued for 54 h after which killing of chlamydiae was seen. The use of polarized human cells may offer a more relevant in-vitro model system for examining the efficacy of antimicrobial action.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8383102&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 1993 Feb;37(2):314-6.
Pharmacokinetics of azithromycin [Zithromax] in pediatric patients after oral administration of multiple doses of suspension.

Nahata MC, Koranyi KI, Gadgil SD, Hilligoss DM, Fouda HG, Gardner MJ.

College of Pharmacy, Ohio State University, Columbus 43210.

Azithromycin [Zithromax] is an azalide antibiotic. On the basis of data in adults, azithromycin [Zithromax] appears to have a greater distribution into tissues, a longer elimination half-life, and a lower incidence of adverse effects than the macrolide antibiotic erythromycin. However, little about the pharmacokinetics of azithromycin [Zithromax] in children is known. The objective of our study was to characterize the pharmacokinetics of azithromycin [Zithromax] after oral administration of multiple doses of suspension to children with streptococcal pharyngitis. Fourteen children (6 to 15 years of age) received a single oral dose of 10 mg of azithromycin [Zithromax] per kg of body weight on day 1 followed by single daily doses of 5 mg/kg on days 2 to 5. Each child fasted overnight before receiving the final dose on day 5. Blood samples were collected at 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, and 72 h after this last dose. Concentrations of azithromycin [Zithromax] in serum were measured by a specific high-performance liquid chromatography-mass spectrometry method. The mean +/- standard deviation for maximum concentration of drug in serum, time to maximum concentration of drug in serum, and area under the curve (0 to 24 h) were 383 +/- 142 ng/ml, 2.4 +/- 1.1 h, and 3,109 +/- 1,033 ng.h/ml, respectively. Concentrations in serum at 0 h (predose) and at 24, 48, and 72 h after the final dose were 67 +/- 31, 64 +/- 24, 41 +/- 17, and 29 +/- 14 ng/ml, respectively. Thus, once-daily administration of azithromycin [Zithromax] resulted in sustained systemic exposure to the drug.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8383944&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 1993 Feb;37(2):354-6.
Outer membrane permeability barrier to azithromycin, clarithromycin, and roxithromycin in gram-negative enteric bacteria.

Vaara M.

Department of Bacteriology and Immunology, University of Helsinki, Finland.

Mutations which severely affect the function of the outer membrane of Escherichia coli and Salmonella typhimurium (lpxA and firA mutations of lipid A synthesis and rfaE mutation of the lipopolysaccharide inner-core synthesis) were found to decrease the MICs of erythromycin, roxithromycin, clarithromycin, and azithromycin [Zithromax] by factors of 32 to 512, 32 to 1,024, 64 to 512, and 16 to 64, respectively. The sensitization factors for three other hydrophobic antibiotics (rifampin, fusidic acid, and mupirocin) ranged from 16 to 300. The outer membrane permeability-increasing agents polymyxin B nonapeptide (3 micrograms/ml) and deacylpolymyxin B (1 microgram/ml) sensitized wild-type E. coli to azithromycin [Zithromax] by factors of 10 and 30, respectively. Quantitatively very similar sensitization to the other macrolides took place. Polymyxin-resistant pmrA mutants of S. typhimurium displayed no cross-resistance to azithromycin. Proteus mirabilis mutants which were sensitized to polymyxin by a factor of > or = 300 to > or = 1,000 had a maximal two- to fourfold increase in sensitivity to azithromycin. These results indicate that azithromycin [Zithromax] and the other new macrolides use the hydrophobic pathway across the outer membrane and that the intact outer membrane is an effective barrier against them. Furthermore, the results indicate that azithromycin, in contrast to polymyxin, does not effectively diffuse through the outer membrane by interacting electrostatically with the lipopolysaccharide.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8383945&dopt=Abstract Zithromax azithromycin




J Antimicrob Chemother. 1993 Feb;31(2):313-9.
Comparative efficacies of azithromycin [Zithromax] and ciprofloxacin against experimental Salmonella typhimurium infection in mice.

Butler T, Girard AE.

Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock 79430.

Azithromycin [Zithromax] was compared with ciprofloxacin for the treatment of established intracellular infection with Salmonella typhimurium LT-2 in CF-1 mice. For studies of mortality, mice received five times the LD50 of organisms intraperitoneally and were given drugs intragastrically once daily for seven days. For studies of in-vivo antibacterial activity, splenic viable counts were measured in mice that had received 0.5 times the intraperitoneal LD50 and had been given drugs for three days. The MICs of azithromycin [Zithromax] and ciprofloxacin, respectively, against LT-2 were 4.0 and 0.03 mg/L. The 50% protective doses of the drugs required to prevent mortality were azithromycin [Zithromax] 24.7 mg/kg/day, and ciprofloxacin 30.2 mg/kg/day. Treatment with azithromycin [Zithromax] and ciprofloxacin in doses of 25 and 100 mg/kg/day resulted in reduction of mean log10 cfu per spleen. Splenic concentrations of azithromycin [Zithromax] up to 8 h after treatment exceeded its MIC against the LT-2 strain, whereas serum levels were less than the MIC. These results indicated that azithromycin [Zithromax] given orally once daily was as effective as ciprofloxacin against established murine Salmonella infection and that the efficacy of azithromycin [Zithromax] correlated with adequate tissue concentrations of antibiotic.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8385094&dopt=Abstract Zithromax azithromycin