Antimicrob Agents Chemother. 1994 Feb;38(2):217-22.
Azithromycin [Zithromax] pharmacokinetics and intracellular concentrations in Legionella pneumophila-infected and uninfected guinea pigs and their alveolar macrophages.

Stamler DA, Edelstein MA, Edelstein PH.

Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-4283.

Azithromycin [Zithromax] pharmacokinetics in Legionella pneumophila-infected and uninfected guinea pigs were assessed by measuring the drug concentration in whole lungs or the drug content in bronchoalveolar lavage (BAL) fluid in separate experiments. Azithromycin [Zithromax] concentrations were measured by using a bioassay. The mean azithromycin [Zithromax] content in the BAL fluid of infected guinea pigs was higher than that in controls at 10 h (0.87 versus 0.39 microgram; P = 0.05), 24 h (1.10 versus 0.37 microgram; P = 0.003), and 48 h (1.21 versus 0.28 microgram; P = 0.05) after a single intraperitoneal injection of drug (15 mg/kg). The mean peak lung azithromycin [Zithromax] concentration was higher in control animals than in infected animals (15.8 versus 13.4 micrograms/ml). The mean lung azithromycin [Zithromax] concentration in infected animals was significantly higher than that in controls 48 h after dosing (12.7 versus 10.4 micrograms/g; P = 0.04). There were no significant differences between infected and uninfected animals in serum azithromycin [Zithromax] levels. Complementary experiments assessed intracellular/extracellular concentration ratios of azithromycin [Zithromax] and erythromycin in L. pneumophila-infected and control guinea pig alveolar macrophages. Azithromycin [Zithromax] was highly concentrated in alveolar macrophages, and the intracellular/extracellular concentration ratios for infected cells were significantly higher (P < 0.0001) than those observed in controls after 4 h (127 versus 119), 24 h (481 versus 361), and 48 h (582 versus 520) of incubation. Erythromycin was also preferentially concentrated in infected cells (P < 0.0001). AZ intracellular concentrations were at least fivefold higher than those measured for erythromycin, and this differential increased with incubation time. Thus, azithromycin [Zithromax] recovery from BAL fluid, and from guinea pig lungs at the 48-h time point, was higher in the presence of experimental Legionnaires' disease. This likely results from recruitment of phagocytes, including macrophages, that have an enhanced capacity to highly concentrate the drug.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8192446&dopt=Abstract Zithromax azithromycin




Minerva Gastroenterol Dietol. 1994 Mar;40(1):47-9.
[Azithromycin-omeprazole. Treatment for the eradication of Helicobacter pylori]

[Article in Italian]

Marchi M, Vacondio R, Bagnulo A, Mengoli M.

Servizio di Endoscopia Digestiva, Ospedale S. Sebastiano, Correggio, Reggio Emilia.

AIM. To evaluate the benefit of 4-week regimen including azithromycin+omeprazole (vs omeprazole alone) for eradication of Helicobacter pylori. METHODS. Twenty HP positive patients with an ulcer dyspepsia (NUD) were included in this study. They were given either omeprazole 40 mg for 4 weeks alone or in combination with azithromycin [Zithromax] 1 g/die for 1 week. Endoscopy was performed before 4 weeks after and 4 months after treatment. The presence of HP was assessed in antral and corporeal biopsies by urease test and histology. RESULTS. HP eradication was observed in 9/10 (90%) patients in the omeprazole+azithromycin [Zithromax] group and 0/10 patients in the omeprazole alone group. CONCLUSION. Omeprazole 40 mg for 4 weeks in combination with azithromycin [Zithromax] 1 g die for 1 week eradicates HP in 90% of these patients. The good eradication percentage and absence of collateral effect make us extend patients' number to test.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8204705&dopt=Abstract Zithromax azithromycin




Chemotherapy. 1993 Nov-Dec;39(6):432-7.
Interference by subinhibitory concentrations of azithromycin [Zithromax] with the mechanism of bacterial adhesion to human epithelial cells.

Braga PC, Piatti G.

Dept. of Pharmacology, School of Medicine, University of Milan, Italy.

Azithromycin [Zithromax] is the first member of a novel 15-membered-ring 'azalide' group of macrolides that has entered into clinical practice, and its activity is not restricted to gram-positive bacteria, but extends also to gram-negative bacteria. The aim of this study was to investigate the ability of subinhibitory concentrations (sub-MICs) of azithromycin [Zithromax] to interfere with the mechanism of bacterial adhesion to human epithelial cells. Azithromycin [Zithromax] induced a significant inhibition of adhesion from 1/2 to 1/32 MIC for Staphylococcus aureus and from 1/2 to 1/16 MIC for Escherichia coli. 1/32 of the MIC for S. aureus means 0.048 microgram/ml, while 1/16 of the MIC for E. coli means 0.25 microgram/ml. At these concentrations no morphological changes in E. coli shape were seen, while sometimes S. aureus cells larger than the normal size appeared. Tissue concentrations of azithromycin [Zithromax] decline with an estimated half-life of 2.5-3 days. Since sub-MICs of 0.25 and 0.048 microgram/ml are still able to interfere with bacterial physiology, the effective activity of azithromycin, from a pharmacokinetic point of view, could be extended for 3 days beyond the expected period of antimicrobial activity.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8222872&dopt=Abstract Zithromax azithromycin




J Infect Dis. 1993 Nov;168(5):1289-92.
Efficacy of azithromycin [Zithromax] for treating Babesia microti infection in the hamster model.

Weiss LM, Wittner M, Wasserman S, Oz HS, Retsema J, Tanowitz HB.

Dept. of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461.

Because of its prevalence and severity, Babesia microti infection is an important public health problem. The current treatment of choice is clindamycin plus quinine. However, in some cases other treatments are needed because of drug intolerance or relapse. The activity of azithromycin [Zithromax] was investigated for treatment of babesiosis in the hamster model. All animals received vancomycin to prevent antibiotic-associated colitis. Quinine (250 mg/kg/day), azithromycin [Zithromax] (150 mg/kg/day), and the combination of azithromycin [Zithromax] and quinine were compared. A significant suppression of parasitemia was found in all treatment groups (combination had the greatest effect, followed by azithromycin, then quinine; P < .05). The mean survival was significantly prolonged in the combination group (P < .05). Azithromycin [Zithromax] as monotherapy in a higher dose (300 mg/kg/day) also resulted in a significant prolongation of survival (P < .05). Spirogermanium and ciprofloxacin, which have been reported to have antimalarial activity, had no effect on parasitemia or survival in this experimental babesiosis model.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8228366&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 1993 Sep;37(9):1746-8.
In vitro activity of azithromycin [Zithromax] (CP-62,993) against Chlamydia trachomatis and Chlamydia pneumoniae.

Agacfidan A, Moncada J, Schachter J.

Department of Microbiology, Istanbul Faculty of Medicine, Turkey.

The in vitro susceptibilities of 49 strains of Chlamydia trachomatis and 3 strains of Chlamydia pneumoniae to azithromycin [Zithromax] and tetracycline or doxycycline were determined. The MIC of azithromycin [Zithromax] ranged from < or = 0.06 to 1.0 micrograms/ml, the MIC of tetracycline ranged from 0.03 to 0.12 micrograms/ml, and the MIC of doxycycline ranged from 0.015 to 0.06 micrograms/ml against C. trachomatis. The MIC ranges for C. pneumoniae were 0.12 to 0.25 micrograms/ml for azithromycin [Zithromax] and 0.06 to 0.12 micrograms/ml for tetracycline. All minimal chlamydicidal concentrations were either equal to the MIC or one or two dilutions higher. No strains resistant to these antibiotics were detected. In vitro activity shows that azithromycin [Zithromax] is highly active against C. trachomatis and C. pneumoniae.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8239579&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 1993 Sep;37(9):1993-6.
In vitro evaluation of the activities of azithromycin [Zithromax] alone and combined with pyrimethamine against Toxoplasma gondii.

Cantin L, Chamberland S.

Laboratoire et Service d'Infectiologie, Centre de Recherche du Centre Hospitalier, Universite Laval, Quebec, Canada.

By using an in vitro microassay to assess drug interaction, azithromycin [Zithromax] combined to pyrimethamine was found more active than pyrimethamine alone against Toxoplasma gondii, and additivity between those drugs was demonstrated. Our results show that the combination of azithromycin [Zithromax] and pyrimethamine may lead to a more rapid control of T. gondii.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8239619&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 1993 Oct;37(10):2080-6.
Erythromycin, clarithromycin, and azithromycin: use of frequency distribution curves, scattergrams, and regression analyses to compare in vitro activities and describe cross-resistance.

Fass RJ.

Department of Internal Medicine, Ohio State University College of Medicine, Columbus 43210.

MICs of erythromycin, clarithromycin, and azithromycin [Zithromax] for 852 recent clinical isolates were determined by broth microdilution methods. Frequency distribution curves, scattergrams, and regression analyses were used to compare in vitro activities and describe cross-resistance. Clarithromycin was the most active drug against Bacteroides spp. but the least active against Haemophilus influenzae. Azithromycin [Zithromax] was most active against H. influenzae, Moraxella catarrhalis, Pasteurella multocida, and Fusobacterium spp. but the least active against Streptococcus spp. and Enterococcus spp. All three drugs had equivalent activities against Staphylococcus spp. and gram-positive anaerobes. None of the three drugs was particularly active against members of the family Enterobacteriaceae or nonfermentative gram-negative bacilli, although concentrations of 4 micrograms of azithromycin [Zithromax] per ml inhibited some strains of the family Enterobacteriaceae (particularly Escherichia coli and Citrobacter diversus) and Acinetobacter baumannii. Although relative drug activities varied by organism, organisms relatively susceptible to one were relatively susceptible to all and organisms relatively resistant to one were relatively resistant to all; an exception was fusobacteria, which were usually susceptible only to azithromycin. Cross-susceptibility and cross-resistance were, therefore, the rule (except for Fusobacterium spp.), although the percentage of susceptible organisms could be varied considerably on the basis of the selection of breakpoints.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8257127&dopt=Abstract Zithromax azithromycin