supercable.es

The activity of azithromycin [Zithromax] against 225 clinical strains of Acinetobacter baumannii isolated consecutively from 26 Spanish hospitals in November 2000 was studied. The MICs of azithromycin [Zithromax] were determined by microdilution, according to the NCCLS guidelines. The bactericidal activity of azithromycin [Zithromax] against 15 clonally unrelated A. baumannii strains with different antimicrobial susceptibility patterns was tested using the subculture method. The killing-curves method was also performed against five strains with different susceptibility to azithromycin. The MIC(50) and MIC(90) of azithromycin [Zithromax] were 32 and 64 mg/l, respectively. Moderate bactericidal activity was observed in 14 out of the 15 strains evaluated by the subculture method (MBCs from 1 to 4 dilution steps higher than the MICs) and by the killing-curve method. For three strains the number of CFU/ml was reduced 1 to 1.4 log by concentrations of azithromycin [Zithromax] equivalent to 1 and 4 times their MICs. lt is concluded that azithromycin [Zithromax] has moderate bactericidal activity against the strains of A. baumannii evaluated.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12973458&dopt=Abstract Zithromax azithromycin




J Antimicrob Chemother. 1992 Jan;29(1):27-33.
Influence of outer membrane mutations on susceptibility of Escherichia coli to the dibasic macrolide azithromycin.

Farmer S, Li ZS, Hancock RE.

Department of Microbiology, University of British Columbia, Vancouver, Canada.

Azithromycin [Zithromax] differs chemically from erythromycin by having an extra positive charge created by the presence of a methyl-substituted nitrogen in the 15-membered macrolide ring. This results in substantially increased potency against Gram-negative bacteria. Therefore, the possibility was considered that azithromycin [Zithromax] was taken across the outer membrane of Escherichia coli by the self-promoted uptake route, which is utilized by other cationic antibiotics including polymyxins and aminoglycosides. Azithromycin, like polymyxin B and gentamicin, demonstrated equal activity against porin-sufficient and porin-deficient E. coli strains but its MIC was increased eight-fold by magnesium supplementation. Nevertheless, an outer membrane-altered mutant DC2 was eight-fold more susceptible than its parent strain UB1005 to azithromycin, indicating that the outer membrane was a permeability barrier to this macrolide. A mutant SC9252 which had an alteration in the self-promoted uptake of polymyxin and gentamicin, was more resistant to azithromycin, polymyxin and gentamicin compared to its parent SC9251. Further azithromycin, like polymyxin B and gentamicin, was capable of weakly permeabilizing cells to the hydrophobic fluorophor 1-N-phenyl-naphthylamine, a process antagonized by Mg2+. The monobasic macrolide erythromycin on the other hand was less affected by the SC9252 mutation, less effectively antagonized by Mg2+, and was a far less effective permeabilizer than dibasic azithromycin. These data are consistent with the hypothesis that the improved efficacy of azithromycin [Zithromax] compared to erythromycin against E. coli reflects its better access to the self-promoted uptake pathway due to its additional positive charge.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1310670&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 1992 Jan;36(1):10-6.
Potentiation of antibacterial activity of azithromycin [Zithromax] and other macrolides by normal human serum.

Pruul H, McDonald PJ.

Department of Microbiology and Infectious Diseases, Flinders Medical Centre, Bedford Park, Australia.

The interaction of azithromycin [Zithromax] with normal human serum was examined in relation to serum protein binding, MIC, and kinetics of killing of bacteria. While the binding of azithromycin [Zithromax] to serum proteins is low (8.5% at a concentration of 0.01 mM in 95% serum), the presence of 40% serum during the MIC test decreased MICs by 26-fold for serum-resistant Escherichia coli and 15-fold for Staphylococcus aureus. Erythromycin had a similar but lesser effect, while roxithromycin was less active against S. aureus in the presence of serum. The rate of killing of E. coli and S. aureus by azithromycin [Zithromax] was increased in the presence of serum. The enhancement of antibiotic activity by serum was pH independent, and heat inactivation and preabsorption with homologous bacteria failed to inhibit enhancement by serum. The macromolecular incorporation of [3H]thymidine by E. coli continuously exposed to 2 micrograms of azithromycin [Zithromax] per ml (0.25x the MIC) and 40% serum was decreased by 80% at pH 7.8 and by 48% at pH 7.2, while azithromycin [Zithromax] alone failed to inhibit incorporation. Inhibition of nucleic acid biosynthesis at pH 7.2 in the presence of serum was also detected with sub-MICs of erythromycin, norfloxacin, and gentamicin but not roxithromycin. A diffusible serum factor was shown to interact with azithromycin [Zithromax] to inhibit the growth of E. coli in an agar diffusion assay to detect antibiotic-serum synergy.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1317141&dopt=Abstract Zithromax azithromycin




J Antibiot (Tokyo). 1992 Apr;45(4):527-34.
Synthesis and antibacterial activity of O-methylazithromycin [Zithromax] derivatives.

Kobrehel G, Lazarevski G, Dokic S, Kolacny-Babic L, Kucisec-Iepes N, Cvrlje M.

PLIVA, Research and Development, Zagreb, Yugoslavia.

A series of O-methylazithromycin [Zithromax] derivatives have been synthesized and their antibacterial activities were compared with those of azithromycin [Zithromax] (1). O-Methylation of 1 proceeded stepwise by the two main pathways beginning at the C-6 and C-11 hydroxyl groups, individually. Among O-methyl derivatives, 6-O-methylazithromycin [Zithromax] A (11) was slightly less active than 1. The methylation of the secondary hydroxyl group at the C-11 position resulted surprisingly in an increase of their in vitro activity. The antibacterial activities of novel azalides decreased with increasing the number of the methyl groups introduced.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1317368&dopt=Abstract Zithromax azithromycin




Am J Health Syst Pharm. 1999 Aug 1;56(15):1521-4.
Azithromycin [Zithromax] versus erythromycin for community-acquired pneumonia: a cost-minimization analysis.

Howard KB, Blumenschein K, Rapp RP.

The Ohio State University, Columbus, USA.

The costs of i.v. erythromycin versus azithromycin [Zithromax] (in terms of medication use and treatment of adverse effects) when these drugs were used with other antimicrobials to treat community-acquired pneumonia (CAP) were compared. The medical records of patients receiving i.v. azithromycin [Zithromax] or erythromycin as part of combination antimicrobial therapy for the treatment of CAP at a 473-bed level 1 trauma center in Kentucky were retrospectively reviewed. Data were collected for patients treated from December 1, 1997, through March 31, 1998. Patient data collected included occurrence of phlebitis or pain at the injection site, number of line changes due to phlebitis, and culture results. Cost data collected included drug acquisition cost, pharmacy cost of drug preparation, nursing time to administer the agent, cost of drug supplies, and cost of managing complications. Three time-and-motion studies were conducted to determine technician preparation time and pharmacist verification time. The medical records of 62 patients were identified and reviewed; 50 patients were enrolled in the study (25 in the azithromycin [Zithromax] group and 25 in the erythromycin group). The average total days of therapy was 5.1 for the azithromycin [Zithromax] group and 5.6 for the erythromycin group. The average total cost, including the cost of complications ($4.36 per patient in the erythromycin group), was $66.46 in the azithromycin [Zithromax] group and $96.56 in the erythromycin group. The difference in costs between the two groups was not significant. There was no significant cost difference between azithromycin- and erythromycin-containing combination antimicrobial therapy in the treatment of CAP.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10478989&dopt=Abstract Zithromax azithromycin




Arzneimittelforschung. 1992 Feb;42(2):156-9.
Disk diffusion sensitivity testing and antibacterial activity of azithromycin.

Davila D, Tambic T, Djokic S, Kolacny-Babic L.

Pliva Research Institute, Zagreb, Yugoslavia.

Azithromycin [Zithromax] (CAS 83905-01-5) disks with the selected loading (10, 15, 20 micrograms) were used for determination of the most suitable azithromycin [Zithromax] disk concentration. Estimation was carried out by means of the regression line related to the zone size inhibition. Testing was performed on a variety of freshly isolated gram-positive, gram-negative and anaerobic bacteria derived from various specimens collected from patients. Using the disk diffusion method with 10 micrograms of azithromycin [Zithromax] per disk in total 431 gram-positive, 875 gram-negative bacterial strains and 59 anaerobic bacteria were analysed. It was concluded that azithromycin [Zithromax] disk containing 10 micrograms is sufficient for determination of bacterial sensitivity.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1319164&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 1992 May;36(5):997-1001.
Synergistic activity of azithromycin [Zithromax] and pyrimethamine or sulfadiazine in acute experimental toxoplasmosis.

Derouin F, Almadany R, Chau F, Rouveix B, Pocidalo JJ.

Laboratoire de Parasitologie-Mycologie, Hopital Saint-Louis, Paris, France.

The efficacy of azithromycin [Zithromax] administered alone or combined with pyrimethamine or sulfadiazine was examined in a murine model of acute toxoplasmosis. Outbred Swiss mice acutely infected with tachyzoites of the virulent RH strain were treated for 10 days from day +1 postinfection. The efficacy of each regimen was assessed in terms of survival rates and sequential titration of parasites in blood, brain, and lungs by using a tissue culture method. Administration of azithromycin [Zithromax] at 300, 150, or 75 mg/kg of body weight per day resulted in prolonged survival relative to that of untreated controls; sequential examination of parasite burden showed early eradiaction of Toxoplasma gondii from the lungs, whereas dissemination to the brain was not prevented. A remarkable synergistic effect was observed when azithromycin [Zithromax] (150 mg/kg/day) was administered in combination with pyrimethamine or sulfadiazine at noncurative dosages, i.e., 12.5 and 200 mg/kg/day, respectively. In mice treated with azithromycin [Zithromax] plus sulfadiazine and azithromycin [Zithromax] plus pyrimethamine, parasite burdens in blood and organs, relapses after cessation of therapy, and mortality were all markedly reduced relative to mice treated with any of the agents alone. These results show that azithromycin, which is remarkably active on pulmonary Toxoplasma infection, significantly potentiates the curative effect of sulfadiazine or pyrimethamine.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1324642&dopt=Abstract Zithromax azithromycin