Antimicrob Agents Chemother. 1999 May;43(5):1291-3.
Antimicrobial activities and postantibiotic effects of clarithromycin, 14-hydroxy-clarithromycin, and azithromycin [Zithromax] in epithelial cell lining fluid against clinical isolates of haemophilus influenzae and Streptococcus pneumoniae.

Bergman KL, Olsen KM, Peddicord TE, Fey PD, Rupp ME.

Department of Pharmacy Practice, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA.

The antimicrobial activity of concentrations of selected macrolides found in epithelial cell lining fluid was investigated. Clarithromycin demonstrated greater potency and a significantly longer postantibiotic effect (PAE) than azithromycin [Zithromax] against Streptococcus pneumoniae. Azithromycin [Zithromax] displayed greater potency, faster killing, and a longer PAE than clarithromycin against Haemophilus influenzae. Drug concentrations in epithelial cell lining fluid similar to those found in tissue did not improve the synergistic potential of 14-hydroxy-clarithromycin and indicate that a maximal PAE may exist despite increasing concentrations of drug.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10223956&dopt=Abstract Zithromax azithromycin




Diagn Microbiol Infect Dis. 2001 Mar;39(3):181-5.
Comparative serum bactericidal activity of clarithromycin and azithromycin [Zithromax] against macrolide-sensitive and resistant strains of Streptococcus pneumoniae.

Stein GE, Schooley S.

Michigan State University, Department of Medicine, Division of Infectious Diseases, B-320 Life Sciences Bldg., East Lansing, MI 48824, USA.

The serum pharmacodynamics of clarithromycin and azithromycin [Zithromax] were studied against isolates of S. pneumoniae, including efflux resistant (M. phenotype) strains, by analyzing their serum bactericidal activity (SBA) over time. Normal healthy subjects were given a single 500 mg oral dose of these macrolides and serum samples were collected over 12 hrs. Paired isolates with MICs ranging from 0.25 ug/ml to 8.0 ug/ml were analyzed. Prolonged (at least 6 hrs) SBA was observed with clarithromycin for strains with MICs < or = 2.0 ug/ml. No SBA was observed in strains with MICs >or = 4.0 ug/ml. Azithromycin [Zithromax] exhibited SBA for at least 6 hrs for strains up to a MIC = 0.5 ug/ml. No SBA was observed for isolates with MICs > or = 1.0 ug/ml. In contrast to azithromycin, clarithromycin exhibited SBA for at least one-half of its normal dosing interval against S. pneumoniae strains well above its current susceptibility breakpoint concentration of 0.25 microg/ml. These findings may have relevance to the ongoing debate as to the appropriate susceptibility breakpoints for the newer macrolides.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11337186&dopt=Abstract Zithromax azithromycin

uthct.edu

Ninety-two patients were assessable in 3 consecutive, open, noncomparative, prospective, controlled, single-center trials of the use of multidrug regimens that contain azithromycin [Zithromax] for treating pulmonary Mycobacterium avium complex (MAC) disease. Azithromycin [Zithromax] was provided at a dose of 300-600 mg per day with oral companion drugs administered daily (regimen A, 29 patients); 600 mg 3 times weekly (t.i.w.), with oral companion drugs administered daily (regimen B, 20 patients); and 600 mg (t.i.w.), with oral companion drugs administered t.i.w. (regimen C, 43 patients). All regimens included rifabutin (or rifampin) and ethambutol as companion drugs as well as initial streptomycin. Treatment success was defined as 12 months of negative cultures while on therapy. Treatment failure was defined as sputum culture positivity after at least 6 months of therapy. Of the patients in each regimen who reached study end points, 17 of 29 (59%) were in regimen A, 11 of 20 (55%) were in regimen B, and 28 of 43 (65%) were in regimen C met the treatment success criterion. There were no statistically significant differences in outcome between the 3 regimens. These studies demonstrate the effectiveness of daily and t.i.w. regimens containing azithromycin [Zithromax] for treatment of MAC lung disease.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11340525&dopt=Abstract Zithromax azithromycin




Am J Vet Res. 2001 May;62(5):687-91.
Inoculation of two genotypes of Hemobartonella felis (California and Ohio variants) to induce infection in cats and the response to treatment with azithromycin.

Westfall DS, Jensen WA, Reagan WJ, Radecki SV, Lappin MR.

Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins 80523, USA.

OBJECTIVES: To describe clinical and laboratory findings associated with cats experimentally infected by inoculation with the 2 recognized genotypes of Hemobartonella felis (small variant, Hfsm; large variant, Hflg) and to determine the response of cats to treatment with azithromycin. ANIMALS: 18 young adult domestic shorthair cats of both sexes. PROCEDURES: Cats were inoculated with H felis and monitored weekly, using CBC counts and a polymerase chain reaction (PCR) designed to detect both genetic variants of H felis. Beginning 26 days after inoculation, 11 cats were administered azithromycin [Zithromax] (15 mg/kg of body weight, PO, q 12 h, for 7 days). RESULTS: Inoculation resulted in coinfection with Hflg and Hfsm, and both variants were detected by PCR. Clinical abnormalities and anemia were most severe in Hflg- and dual-infected cats. Results of PCR and CBC were positive for H felis in 112/112 (100%) and 42/112 (37.5%), respectively, samples collected after inoculation. Administration of azithromycin [Zithromax] had little effect on clinical variables, including anemia. All cats, regardless of treatment with azithromycin, had positive results for the PCR at the end of the study period. CONCLUSIONS AND CLINICAL RELEVANCE: In these cats, Hflg was more pathogenic than Hfsm, and coinfection with both variants was detected. Results of the PCR were superior to results of CBC for detecting infection with H felis. Azithromycin [Zithromax] administered at the dose and duration reported here was not efficacious for the treatment of cats with hemobartonellosis.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11341386&dopt=Abstract Zithromax azithromycin




Mol Pharmacol. 2001 Jun;59(6):1441-5.
Insights into the mechanism of azithromycin [Zithromax] interaction with an Escherichia coli functional ribosomal complex.

Dinos GP, Michelinaki M, Kalpaxis DL.

Laboratory of Biochemistry, School of Medicine, University of Patras, GR-26500 Patras, Greece.

Azithromycin, a derivative of erythromycin with improved activity against Gram-negative bacteria, exhibits a marginal inhibition effect in a model system derived from Escherichia coli, in which a peptide bond is formed between puromycin and AcPhe-tRNA bound at the P-site of poly(U)-programmed ribosomes. This renders the study of azithromycin [Zithromax] interaction with Ac[(3)H]Phe-tRNA. poly(U). 70S ribosome complex (complex C) impossible, if we analyze its effect on peptide bond formation. To overcome this problem, we have used an alternative approach to investigate kinetically the azithromycin [Zithromax] interaction with complex C and to compare the azithromycin [Zithromax] binding properties with those of erythromycin. This approach was based on the ability of azithromycin [Zithromax] to compete with tylosin, a macrolide antibiotic strongly inhibiting the puromycin reaction. Detailed kinetic analysis revealed that the encounter complex CA between complex C and azithromycin [Zithromax] (A) undergoes a slow isomerization to a tighter complex C*A, which remains active toward puromycin. The determination of inhibition and isomerization rate constants enabled us to classify azithromycin [Zithromax] as a slow-binding ligand of ribosomes. Compared with erythromycin, azithromycin [Zithromax] is a better inducer and stabilizer of the C*A complex. This finding may explain the superiority of azithromycin [Zithromax] as inhibitor of translation in E. coli cells and many other Gram-negative bacteria.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11353804&dopt=Abstract Zithromax azithromycin




Zhonghua Jie He He Hu Xi Za Zhi. 1998 Sep;21(9):538-40.
[Inhibitory activity of azithromycin [Zithromax] on biofilm synthesis and synergism between azithromycin [Zithromax] and fleroxacin on Pseudomonas aeruginosa in biofilms]

[Article in Chinese]

Fang X, Liu Y, Chen Q, Wangrui.

Department of Pulmonary Disease, Chinese PLA General Hospital, Beijing 100853.

OBJECTIVE: The influence of azithromycin [Zithromax] (AZT) on the production of glycocalyx (GLX) from P. aeruginosa biofilms and synergism of antibacterial activities between AZT and fleroxacin (FLX) on P. aeruginosa were investigated. METHOD: GLX production was measured by using a L-tryptophan method and viable counts in biofilms was determined by using a methylthiazolyldiphenyltetrazolium(MTT) method. RESULT: GLX production was reduced significantly from 28.0 +/- 8.1 micrograms/ml at 0MIC to 21.8 +/- 8.2 micrograms/ml at 1/16MIC and 16.7 +/- 7.9 micrograms/ml at 1/4MIC respectively (P = 0.0002). 1/16MIC and 1/4MIC AZT showed no bactericidal activities to P. Aeruginosa in biofilms. Viable counts in biofilms were 6.2 +/- 0.61 Lg/cm2 at 0MIC, 6.1 +/- 0.4 Lg/cm2 at 1/16MIC and 6.2 +/- 0.4 Lg CFU/cm2 at 1/4 MIC respectively (P = 0.63). However, AZT could enhance bactericidal activity of FLX on P. aeruginosa in biofilms. When 1/4MIC FLX was combined with 1/16MIC and 1/4 MIC AZT, viable counts were reduced significantly from 6.1 +/- 0.5 Lg CFU/cm2 to 5.9 +/- 0.3 Lg CFU/cm2 and 5.8 +/- 0.4 Lg CFU/cm2 respectively (P = 0.02). When 1/2MIC FLX was combined with 1/16MIC and 1/4MICAZT, viable counts were reduced significantly from 6.3 +/- 0.7 Lg CFU/cm2 to 5.8 +/- 0.5 LgCFU/cm2 and 5.7 +/- 0.6 Lg CFU/cm2 respectively (P = 0.03). CONCLUSION: Because AZT did not have direct bactericidal activities on P. aeruginosa in biofilms but could inhibit GLX production, We considered that AZT could enhance antibacterial activities of FLX by enhancing permeability of FLX into biofilms.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11360505&dopt=Abstract Zithromax azithromycin

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We investigated the effects of azithromycin [Zithromax] and clarithromycin, two antibiotics that possess a broad spectrum of antimicrobial activity (including antimycobacterial activity), on interleukin-8 (IL-8) release from human whole blood leucocytes and lung macrophages. Ex vivo stimulation of leukocytes with either of the antibiotics (0.04-40 mg/L) significantly increased IL-8 secretion. Incubation of alveolar macrophages with different concentrations of azithromycin [Zithromax] or clarithromycin modified IL-8 production: it increased at a drug concentration of 4 mg/L and decreased at concentration of 400 mg/L. Our findings suggest that azithromycin [Zithromax] and clarithromycin may alter IL-8 production, thus enhancing the clinical effectiveness of these antibiotics.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11389120&dopt=Abstract Zithromax azithromycin