Cell Biochem Funct. 2003 Mar;21(1):93-6.
Determination of intracellular efficacies of azithromycin [Zithromax] against Leishmania major infection in human neutrophils in vitro.

Tanyuksel M, Bas AL, Araz E, Aybay C.

Division of Medical Parasitology, Department of Microbiology and Clinical Microbiology, Gulhane Military Medical Academy, Ankara, Turkey.

Azithromycin [Zithromax] is one of a new class of antibiotics known as azalides. Azithromycin [Zithromax] has high tissue affinity and this feature is thought to be due to the presence of two basic tertiary amine groups. Leishmania major, one of the causative agents of cutaneous leishmaniosis, is an obligate intracellular parasite. In this in vitro study, the potential anti-leishmanial effect of azithromycin [Zithromax] upon intracellular forms namely the amastigote of L. major in mice peritoneal macrophages was investigated. L. major promastigotes were propagated in RPMI-1640 supplemented with 20% fetal calf serum in the log phase. The percentage of phagocytosis and microbiacidal activity of azithromycin [Zithromax] on macrophages was assessed in the control and study groups by fluorescence microscopy, using acridine orange. Our results showed that at all the concentrations used (0.05, 0.1, 0.3, 0.6 microg ml(-1)) azithromycin [Zithromax] had no inhibitory effect on the phagocytic capacity of mouse peritoneal macrophages. Although no significant difference was observed for leishmaniacidal activity between the study and the control groups at a concentration of 0.05 microg ml(-1) (p>0.05), a significant (p<0.05) increase in leishmaniacidal activity was detected at 0.1, 0.3 and 0.6 microg ml(-1). As a result, azithromycin [Zithromax] does not provide any contribution to the phagocytosis of L. major promastigotes in macrophages in vitro, but it increases the intracellular killing rates of amastigotes. These results suggest that it has a potential anti-leishmanial effect, and may provide a significant advantage in the treatment of the disease. Copyright 2002 John Wiley & Sons, Ltd.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12579528&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 2003 Mar;47(3):1017-22.
Effects of an efflux mechanism and ribosomal mutations on macrolide susceptibility of Haemophilus influenzae clinical isolates.

Peric M, Bozdogan B, Jacobs MR, Appelbaum PC.

Department of Pathology, Hershey Medical Center, Pennsylvania 17033, USA.

This study investigated macrolide resistance mechanisms in clinical Haemophilus influenzae strains with different levels of susceptibility to macrolides. A total of 6,382 isolates were collected during the Alexander Project from 1997 to 2000. For 96.9% of these isolates, the azithromycin [Zithromax] MICs were 0.25 to 4 micro g/ml, and these were defined as baseline strains. For 1.8% of the isolates, the azithromycin [Zithromax] MICs were lower (<0.25 micro g/ml), and for 1.3% of the isolates, the MICs were higher (>4 micro g/ml). These isolates were defined as hypersusceptible and high-level macrolide-resistant strains, respectively. To identify the mechanisms associated with these three susceptibility patterns, representative strains were studied for the presence of macrolide efflux pumps and for ribosomal alterations. Macrolide efflux was studied by measuring the accumulation of radioactive azithromycin [Zithromax] and clarithromycin in the presence or absence of carbonyl cyanide m-chlorophenylhydrazone (CCCP), a protonophore. Treatment with CCCP increased the accumulation of macrolides in baseline as well as high-level resistant strains, demonstrating the presence of an efflux mechanism, but not in the 20 hypersusceptible strains tested. Among the 31 strains studied that showed high-level resistance to both azithromycin [Zithromax] and clarithromycin, 28 had ribosomal alterations, 7 had mutations in ribosomal protein L4, 11 had mutations in L22, 2 had mutations in 23S rRNA, 8 had multiple mutations, and 3 had no mutations. From these results, we conclude that the vast majority (>98%) of H. influenzae strains have a macrolide efflux mechanism, with a few of these being hyperresistant (1.3%) due to one or several ribosomal mutations. Occasional hypersusceptible strains (1.8%) were found and had no macrolide resistance mechanisms and appeared to be the only truly macrolide-susceptible variants of H. influenzae.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12604536&dopt=Abstract Zithromax azithromycin




Structure (Camb). 2003 Mar;11(3):329-38.
Structural basis for the antibiotic activity of ketolides and azalides.

Schlunzen F, Harms JM, Franceschi F, Hansen HA, Bartels H, Zarivach R, Yonath A.

Max-Planck-Research Unit for Ribosomal Structure, 22603, Hamburg, Germany.

The azalide azithromycin [Zithromax] and the ketolide ABT-773, which were derived by chemical modifications of erythromycin, exhibit elevated activity against a number of penicillin- and macrolide-resistant pathogenic bacteria. Analysis of the crystal structures of the large ribosomal subunit from Deinococcus radiodurans complexed with azithromycin [Zithromax] or ABT-773 indicates that, despite differences in the number and nature of their contacts with the ribosome, both compounds exert their antimicrobial activity by blocking the protein exit tunnel. In contrast to all macrolides studied so far, two molecules of azithromycin [Zithromax] bind simultaneously to the tunnel. The additional molecule also interacts with two proteins, L4 and L22, implicated in macrolide resistance. These studies illuminated and rationalized the enhanced activity of the drugs against specific macrolide-resistant bacteria.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12623020&dopt=Abstract Zithromax azithromycin

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OBJECTIVE: The purpose of this study was to characterize the pharmacokinetics of orally administered azithromycin [Zithromax] in the term gravid woman. STUDY DESIGN: Twenty women who were scheduled for elective cesarean delivery were enrolled prospectively and received 1 g of oral azithromycin [Zithromax] at either 6, 12, 24, 72, or 168 hours before the operation. All women received spinal anesthesia, at which time a sample of cerebrospinal fluid was obtained for analysis. Maternal serum and urine were obtained immediately before the operation. Intraoperatively, samples of myometrium, maternal adipose tissue, placenta, amniotic fluid, and umbilical arterial and venous cord blood were obtained. Azithromycin [Zithromax] levels were determined quantitatively with high-pressure liquid chromatography with electrochemical detection. RESULTS: All participants tolerated the preoperative azithromycin [Zithromax] without significant adverse reactions. Peak maternal serum azithromycin [Zithromax] levels occurred within 6 hours of drug administration. Although high serum levels of azithromycin [Zithromax] were reached early, a rapid decline in drug concentration was noted over the initial 24 hours after the drug administration (6-hour: 311 ng/mL; 24-hour: 63 ng/mL). In contrast, azithromycin [Zithromax] levels in myometrial, adipose, and placental tissue were higher (>500 ng/mL) and sustained for up to 72 hours after administration. High urine levels of azithromycin [Zithromax] (>5000 ng/mL) were noted similarly during the initial 72 hours after drug administration. Umbilical arterial and venous serum azithromycin [Zithromax] levels were low (19-38 ng/mL) during the first 72 hours. Amniotic fluid levels were highest at 6 hours (151 ng/mL) and declined rapidly. Maternal cerebrospinal azithromycin [Zithromax] concentrations were undetectable for all time points. CONCLUSION: Azithromycin [Zithromax] has a rapid serum half-life in the term gravid woman with a prolonged half-life and high-sustained antibiotic levels noted within myometrium, adipose, and placental tissue. Given the broad antimicrobial spectrum and placental penetration, azithromycin [Zithromax] may have potential use for the treatment of perinatal infections.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12634646&dopt=Abstract Zithromax azithromycin




Invest Ophthalmol Vis Sci. 2003 Apr;44(4):1464-9.
Antibiotic dosage in trachoma control programs: height as a surrogate for weight in children.

Munoz B, Solomon AW, Zingeser J, Barwick R, Burton M, Bailey R, Mabey D, Foster A, West SK.

Dana Center for Preventive Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.

PURPOSE: National programs for trachoma control are implementing mass treatment programs in which azithromycin [Zithromax] is used as part of the control strategy. Dose is determined by weight, which can be difficult to determine in field conditions. The purposes of this study were to determine whether an accurate dose could be determined by using height as a surrogate for weight and whether a single model of height-based dosage would be applicable in more than one setting. METHODS: Data on height, weight, age, and gender of 5558 children aged 6 months to15 years were obtained from Kongwa and Rombo, Tanzania; Malakal, Sudan; Jareng, The Gambia; and Daboya, Ghana. Models for predicting weight by measuring height were developed that incorporated country-specific parameters. Doses of azithromycin [Zithromax] assumed suspension of 40 mg/mL and 250-mg tablets that could be halved. Tolerance limits were defined as 15 to 30 mg/kg. RESULTS: A regression model, predicting log weight as a function of log height, was the best fit and explained 94% of the variance. In children less than 1 year of age or 60 cm in height, dose determined by weight was preferred. Dosage by height resulted in more than 97% of children receiving doses within the tolerance limits. Children aged 1 to 2 years were the group most likely to be over- or undermedicated, but this occurred in only 6% of this age group. CONCLUSIONS: Height-based determination of dosage of azithromycin [Zithromax] in trachoma control programs appears to be feasible, using the height-based schedule proposed. One model was adequate for all the countries in the study. Further expansion to other countries is warranted.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12657580&dopt=Abstract Zithromax azithromycin

vet.ksu.edu

Azithromycin [Zithromax] is the first of a class of antibiotics classified as azalides. Six ball pythons (Python regius) were given a single dose of azithromycin [Zithromax] at 10 mg/kg p.o. and i.v. in a crossover design. Serial blood samples were collected for unchanged azithromycin [Zithromax] and to determine, if possible, the structure and number of circulating azithromycin [Zithromax] metabolites. After a 4-month wash-out period, the snakes were given azithromycin [Zithromax] p.o. as a single dose of 10 mg/kg for the study of azithromycin [Zithromax] metabolism and metabolite tissue distribution. Bile, liver, lung, kidney, and skin samples were analyzed for the metabolites identified from the first experiment. Unchanged azithromycin [Zithromax] accounted for 80, 68, and 60% of the total material at 12, 24, and 48 h postadministration in plasma, independent of route of administration. At both 24 and 72 h postadministration, azithromycin [Zithromax] accounted for 70% of total azithromycin- associated material in bile. In liver and kidney, unchanged azithromycin [Zithromax] accounted for 40% of the total azithromycin-associated material; this doubled in lung and skin. Fifteen metabolites were positively or tentatively identified in plasma, bile, or tissues of all snakes. Four of these possible metabolites: 3'-desamine-3-ene-azithromycin, descladinose dehydroxy-2-ene-azithromycin, 3'-desamine-3-ene descladinose-azithromycin, and 3'-N-nitroso,9a-N-desmethyl-azithromycin [Zithromax] are unique to this species. Descladinose-azithromycin, 3'-N-desmethyl,9a-N-desmethyl-azithromycin, and 3'-N-desmethyl, 3'-O-desmethyl-azithromycin [Zithromax] were the only metabolites identified in skin. Kidney tissue contained a greater number of metabolites than liver tissue, with 3'-N-didesmethyl-azithromycin [Zithromax] being identified only in the kidney. Compared with the dog and cat, a greater number of metabolites were identified in ball python plasma. The percentage of unchanged azithromycin [Zithromax] in bile is not different between the three species.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12667181&dopt=Abstract Zithromax azithromycin

focusanswers.com

To identify factors associated with antimicrobial resistance, data were analyzed from 27,828 isolates of Streptococcus pneumoniae submitted to the Tracking Resistance in the United States Today (TRUST) surveillance program during 4 consecutive respiratory seasons. From the 1998-1999 season to the 2001-2002 season, the prevalence of azithromycin [Zithromax] resistance increased by 4.8% to 27.5%, the prevalence of penicillin resistance increased by 3.7% to 18.4%, the prevalence of ceftriaxone resistance increased by 0.5% to 1.7%, and the prevalence of levofloxacin resistance increased by 0.3% to 0.9%. Isolates recovered from patients <18 years of age and lower respiratory tract specimens had elevated rates of penicillin, azithromycin, and trimethoprim-sulfamethoxazole resistance (P<.00001); penicillin resistance correlated with coresistance to trimethoprim-sulfamethoxazole (87.3%), azithromycin [Zithromax] (76.3%), ceftriaxone (9.1%), and levofloxacin (1.3%) (P<.00001). Only 62 (0.2%) of 27,828 isolates were concurrently resistant to penicillin and levofloxacin. Minimum inhibitory concentrations (MICs) of penicillin correlated strongly with MICs of ceftriaxone (R2=0.90), trimethoprim-sulfamethoxazole (R2=0.53), and azithromycin [Zithromax] (R2=0.41). Patient age, specimen source, and penicillin resistance were factors associated with antimicrobial resistance, particularly for nonfluoroquinolone antimicrobial agents.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12684907&dopt=Abstract Zithromax azithromycin