Drugs online research references
Antibiot Khimioter. 2002;47(7):6-12.
[Mechanisms of azithromycin accumulation and efflux in human polymorphonuclear leukocytes]
[Article in Russian]
Hand WI, Hand DL.
Department of Research Development and Internal Medicine, Texas Tech. University Health Sciences Center, Texas, USA.
Azithromycin achieves prolonged, high tissue concentrations in spite of low serum levels and obviously must be effective at tissue sites of infection. These unique features prompted us to evaluate the interactions of azithromycin and human polymorphonuclear leukocytes (PMN). Uptake of radiolabeled antibiotic by PMN was determined by a velocity-gradient centrifugation technique and expressed as the ratio of cellular to extracellular drug concentration (C/E). Azithromycin was massively accumulated by human PMN (C/E = 387.2 at 2 h). Uptake was not influenced by inhibitors of cellular metabolism, but phagocytosis slightly inhibited the entry of azithromycin into PMN. After removal of extracellular drug, the release (efflux) of azithromycin from PMN was extremely slow. Agents which neutralize lysosomal pH, preventing protonation and trapping of azithromycin, markedly increased antibiotic efflux. Active concentration and prolonged retention of azithromycin by phagocytic cells should allow delivery and subsequent release of accumulated drug at sites of infection.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12516190&dopt=Abstract
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Antimicrob Agents Chemother. 2003 Feb;47(2):524-8.
Activities of azithromycin and amphotericin B against Naegleria fowleri in vitro and in a mouse model of primary amebic meningoencephalitis.
Goswick SM, Brenner GM.
Department of Pharmacology, Oklahoma State University Center for Health Sciences, Tulsa, Oklahoma 74107-1898, USA.
Inhalation of fresh water containing the free-living ameba Naegleria fowleri may lead to a potentially fatal infection known as primary amebic meningoencephalitis. Amphotericin B is the only agent with established clinical efficacy in the treatment of primary amebic meningoencephalitis in humans, but therapy with this drug is often associated with adverse effects on the kidneys and other organs, and not all persons treated with amphotericin B have survived. We investigated the in vitro activity and in vivo efficacy of newer therapeutic agents in an attempt to identify other useful agents for treating primary amebic meningoencephalitis. Azithromycin has shown in vitro activity against Acanthamoeba spp. and in vivo activity against experimental toxoplasmosis. In our study, the MIC of azithromycin against N. fowleri was 13.4 micro M (10 micro g/ml), which was 123 times greater than the MIC of amphotericin B, which was 0.108 micro M (0.1 micro g/ml). Azithromycin protected 100% of mice infected with N. fowleri at a dose of 75 mg/kg/day for 5 days, whereas amphotericin B protected only 50% of mice at a dose of 7.5 mg/kg/day for 5 days, and all control mice died during the 28-day observation period. We conclude that azithromycin has both in vitro and in vivo activity versus N. fowleri and may be a useful addition to therapy for primary amebic meningoencephalitis.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12543653&dopt=Abstract
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Antimicrob Agents Chemother. 2003 Feb;47(2):739-46.
Influence of macrolide susceptibility on efficacies of clarithromycin and azithromycin against Streptococcus pneumoniae in a murine lung infection model.
Hoffman HL, Klepser ME, Ernst EJ, Petzold CR, Sa'adah LM, Doern GV.
Colleges of Pharmacy, University of Iowa, Iowa City, Iowa, USA.
We evaluated the activities of clarithromycin and azithromycin against 19 isolates of Streptococcus pneumoniae using a neutropenic lung infection model. The isolates included five susceptible isolates (clarithromycin and azithromycin MICs, </=0.12 micro g/ml), nine isolates exhibiting low-level, mefA-mediated resistance (clarithromycin and azithromycin MICs, 0.5 to 32 micro g/ml), and five isolates expressing high-level, ermB-mediated macrolide resistance (clarithromycin and azithromycin MICs, >/=64 micro g/ml). Infected mice were administered either saline (control), clarithromycin (4, 40, or 200 mg/kg of body weight twice daily or 200 mg/kg once daily), or azithromycin (4, 40, or 200 mg/kg once daily or 40 mg/kg twice daily) by oral gavage for 72 h. Mortality was assessed at regular intervals for 10 days, and survival in each group was compared to that of untreated controls. Animals infected with susceptible isolates demonstrated significant improvement in survival compared to the controls following treatment with either agent at doses of >/=40 mg/kg. In contrast, none of the regimens improved the survival of animals infected with isolates exhibiting high-level macrolide resistance. Among mice infected with strains expressing low-level resistance, significant improvement in survival compared to the controls was noted among isolates treated with clarithromycin at 40 (seven of nine isolates) and 200 (nine of nine isolates) mg/kg twice a day and with azithromycin at 40 (one of nine isolates) and 200 (three of nine isolates) mg/kg once a day. Animals infected with isolates of S. pneumoniae exhibiting low-level, mefA-mediated macrolide resistance responded to treatment with clarithromycin at rates similar to those observed among mice infected with fully susceptible isolates.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12543686&dopt=Abstract
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