Pharmacol Res. 2002 Jul;46(1):95-100.
Improved tonsillar disposition of azithromycin [Zithromax] following a 3-day oral treatment with 20 mg kg(-1) in paediatric patients.

Baschiera F, Fornai M, Lazzeri G, Blandizzi C, Bruschini P, del Tacca M.

Division of Pharmacology and Chemotherapy, Department of Oncology, Transplants and Advanced Technologies in Medicine, University of Pisa, Italy.

The present study was performed in order to compare azithromycin [Zithromax] concentrations in tonsils of paediatric patients treated with different dose regimens of this antibiotic. Sixty-four children, scheduled to undergo surgical removal of tonsils, were treated with azithromycin [Zithromax] 10 or 20 mgkg(-1) daily as oral suspension for 3 days. Samples of blood and tonsil were collected during surgery at days 0.5, 2.5, 4.5, 6.5 or 8.5 after the last dose. Azithromycin [Zithromax] concentrations were measured by reversed phase high-performance liquid chromatography. In patients treated with 10 mgkg(-1), the highest concentrations of azithromycin [Zithromax] were detected in plasma and tonsils at day 0.5 and 2.5, respectively. Consistent drug levels could be measured in tonsils up to 8.5 days. After administration of 20 mgkg(-1), azithromycin [Zithromax] tonsillar concentrations were higher than those obtained with 10 mgkg(-1) up to day 6.5, whereas plasma levels did not differ significantly. The present results indicate that an improved tonsillar distribution of azithromycin [Zithromax] can be achieved when this antibiotic is administered for 3 days at doses higher than 10 mgkg(-1) daily. These findings give pharmacokinetic support to the suggestion that increments of azithromycin [Zithromax] dosing might ensure enhanced therapeutic levels at infective sites of the upper respiratory tract.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12208127&dopt=Abstract Zithromax azithromycin

medizin.uni-ulm.de

BACKGROUND: Due to its unique pharmacokinetic properties, azithromycin [Zithromax] may be an attractive combination partner for H. pylori eradication regimens. However, up to 15% of clinical isolates are primarily resistant to azithromycin [Zithromax] as well as to other macrolide antibiotics. Combination therapy with lansoprazole, a proton pump inhibitor known to have intrinsic antibacterial activity against H. pylori, may be useful to counteract such resistance. We therefore evaluated the combined effects of azithromycin [Zithromax] and lansoprazole in vitro. MATERIALS AND METHODS: Minimal inhibitory concentrations (MICs) of azithromycin [Zithromax] and lansoprazole alone and in combination were determined for 106 clinical H. pylori isolates by means of an agar dilution technique. Killing kinetics of seven isolates were also studied in fluid medium. RESULTS: MIC values for 50 and 90% of the isolates (MIC50, MIC90) were 0.19 and 0.5 mg/l for azithromycin, and 44.5 and 104 mg/l for lansoprazole. Nine strains (8.5%) had an MIC of azithromycin [Zithromax] > or = 16 mg/l and were regarded as resistant. An additive interaction between the two drugs was found in 72 (68%), and indifferent effects in 24 strains (23%). Three of 9 azithromycin-resistant strains regained sensitivity in the presence of lansoprazole. In fluid culture, synergism between the two drugs occurred in 6 out of 7 strains tested. CONCLUSION: In the majority of strains, lansoprazole and azithromycin [Zithromax] interacted in an additive or synergistic manner depending on the test method employed. Addition of lansoprazole restored in vitro sensitivity to azithromycin [Zithromax] in 3 out of 9 azithromycin-resistant strains. Such effects may enhance the elimination of H. pylori during clinical eradication therapy.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10382125&dopt=Abstract Zithromax azithromycin

uni-muenster.de

Macrolide antibiotics are known to have a different proarrhythmic potential in the presence of comparable QT prolongation in the surface ECG. Because the extent of QT prolongation has been used as a surrogate marker for cardiotoxicity, we aimed to study the different electrophysiological effects of the macrolide antibiotics erythromycin, clarithromycin, and azithromycin [Zithromax] in a previously developed experimental model of proarrhythmia. In 37 Langendorff-perfused rabbit hearts, erythromycin (150-300 microM, n = 13) clarithromycin (150-300 microM, n = 13), and azithromycin [Zithromax] (150-300 microM, n = 11) led to similar increases in QT interval and monophasic action potential (MAP) duration. In bradycardic (atrioventricular-blocked) hearts, eight simultaneously recorded epi- and endocardial MAPs demonstrated increased dispersion of repolarization in the presence of all three antibiotics. Erythromycin and clarithromycin led to early afterdepolarizations (EADs) and torsade de pointes (TdP) after lowering of potassium concentration. In the presence of azithromycin, no EAD or TdP occurred. Erythromycin and clarithromycin changed the MAP configuration to a triangular pattern, whereas azithromycin [Zithromax] caused a rectangular pattern of MAP prolongation. In 13 additional hearts, 150 microM azithromycin [Zithromax] was administered after previous treatment with 300 microM erythromycin and suppressed TdP provoked by erythromycin. In conclusion, macrolide antibiotics lead to similar prolongation of repolarization but show a different proarrhythmic potential (erythromycin > clarithromycin > azithromycin). In the presence of azithromycin, neither EAD nor TdP occur. This effect may be related to a rectangular pattern of action potential prolongation, whereas erythromycin and clarithromycin cause triangular action potential prolongation and induce TdP.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12235254&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 2002 Nov;46(11):3478-83.
Effects of azithromycin [Zithromax] on shiga toxin production by Escherichia coli and subsequent host inflammatory response.

Ohara T, Kojio S, Taneike I, Nakagawa S, Gondaira F, Tamura Y, Gejyo F, Zhang HM, Yamamoto T.

Division of Bacteriology, Department of Infectious Disease Control and International Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Shiga toxin (Stx)-producing Escherichia coli (STEC) colonizes the human intestinal mucosa, produces Stx from phage, and causes the development of hemolytic-uremic syndrome via Stx-induced inflammatory cytokine production. Azithromycin [Zithromax] exhibited strong in vitro activity against STEC without inducing Stx-converting phage, in marked contrast to norfloxacin. Azithromycin [Zithromax] decreased the tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6 production from Stx-treated human peripheral mononuclear cells or monocytes to a greater extent than did clarithromycin. In Stx-injected mice, azithromycin [Zithromax] significantly suppressed Stx-induced TNF-alpha, IL-1beta, and IL-6 levels in serum and improved the outcome as assessed by survival rate. In the STEC oral infection experiment using immature mice immediately after weaning (weaned immature-mouse model), all mice died within 7 days postinfection. Azithromycin [Zithromax] administration gave the mice 100% protection from killing, while ciprofloxacin administration gave them 67% protection. The data suggest that azithromycin [Zithromax] (at least at higher concentrations) has a strong effect on Stx production by STEC and on the Stx-induced inflammatory host response and prevents death in mice. Azithromycin [Zithromax] may have a beneficial effect on STEC-associated disease.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12384353&dopt=Abstract Zithromax azithromycin




Am J Trop Med Hyg. 2002 Sep;67(3):273-7.
Activity of azithromycin [Zithromax] against Leishmania major in vitro and in vivo.

Krolewiecki A, Leon S, Scott P, Abraham D.

Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.

Azithromycin, an azalide antibiotic of the macrolide family, concentrates in the tissues and especially in macrophages. Because Leishmania parasites reside in these cells, we tested this antibiotic for a possible antileishmanial activity in vitro and in vivo. Azithromycin [Zithromax] decreased the Leishmania major promastigote count in cell-free cultures at log phase approximately 50-fold. In macrophage cultures infected with L. major amastigotes, azithromycin [Zithromax] caused a significant decrease in parasite levels with an ED50 of 12 microg/ml. The activity in vivo was evaluated after infection of the footpads of susceptible BALB/cByJ mice and resistant C57BL/6J mice with L. major. Treatment of BALB/cByJ mice with azithromycin, 100 to 200 mg/kg/d, resulted in a significant decrease in lesion size and in the number of parasites per lesion, whereas no effect was seen in the treated C57BL/6J mice. Azithromycin [Zithromax] has activity against L. major in vitro and in vivo. Given the severity of the disease and the limitations of the available therapeutic agents, azithromycin [Zithromax] may have a significant role in the treatment of this group of diseases.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12408666&dopt=Abstract Zithromax azithromycin




J Vasc Surg. 2002 Nov;36(5):1011-7.
Chlamydia pneumoniae antigens facilitate experimental aortic dilatation: prevention with azithromycin.

Tambiah J, Powell JT.

Imperial College at Charing Cross, London, United Kingdom.

OBJECTIVE: The purpose of this study was to investigate whether Chlamydia pneumoniae (live, antigens, or polysaccharide) cause abdominal aortic aneurysm in a susceptible animal host with appropriate drug reversal. METHODS: At laparotomy, preparations of C pneumoniae (live, formalin-inactivated, and heat-inactivated) in calcium chloride were applied to the adventitial surface of the abdominal aorta of rabbits fed a cholesterol-enriched diet. Aortic diameter was measured with ultrasonography. After 3 weeks, immunohistochemistry was used to detect aortic C pneumoniae and macrophages. Presence of C pneumoniae DNA also was assessed. RESULTS: At high doses (5 x 10(7) organisms) periaortic application of both live and formalin-inactivated preparations resulted in doubling of aortic diameter after 3 weeks, from 2.0 +/- 0.5 mm to 4.3 +/- 1.3 mm (P <.02). C pneumoniae DNA and antigens, together with a heavy macrophage infiltrate, were detected in the dilated aorta. In contrast, periaortic application of heat-inactivated preparations resulted in minimal macrophage influx and aortic dilatation. Treatment of rabbits with azithromycin [Zithromax] or carprofen for 10 days after laparotomy abolished the effects of formalin-inactivated C pneumoniae on aortic dilatation. Azithromycin [Zithromax] reduced the number of macrophages in the aortic wall more effectively than carprofen. CONCLUSION: Because membrane antigenicity is retained in formalin-inactivated but not heat-inactivated organisms, in this experimental model, chlamydial membrane antigens (rather than live organisms) appear to cause the aneurysmal dilatation and associated macrophage recruitment. Azithromycin [Zithromax] is likely to reverse these effects with an antiinflammatory mechanism.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12422113&dopt=Abstract Zithromax azithromycin




J Egypt Soc Parasitol. 2002 Dec;32(3):969-78.
Efficacy of azithromycin, praziquantel and mirazid in treatment of cryptosporidiosis in school children.

Allam AF, Shehab AY.

Department of Parasitology, Medical Research Institute, Alexandria University, Alexandria, Egypt.

The study was conducted at a primary school in Abis 8 village. 88 children aged eleven years consented to participate in the present study. After fecal examination, 43 (48.8%) cases were found infected with Cryptosporidium. The mean oocysts number per high power field (HPF) ranged from (1.6-48 oocysts/HPF). Azitbromycin, praziquantel (PZQ) and mirazid were given to 13, 16 and 14 infected children respectively. Three weeks after treatment, azithromycin [Zithromax] and praziquantel gave cure rates of 91% and 56.2% respectively with a percent reduction of oocysts in stools of 99% for azithromycin [Zithromax] and 71.5% for PZQ. Mirazid was not effective. All the three drugs were well tolerated. It was concluded that azithromycin [Zithromax] is highly effective in the treatment of children with cryptosporidiosis: PZQ decreases the infection rate and intensity.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12512828&dopt=Abstract Zithromax azithromycin