Drugs online research references
J Antimicrob Chemother. 2003 Jul;52(1):83-8. Epub 2003 May 29.
Pharmacodynamic activity of azithromycin against macrolide-susceptible and -resistant Streptococcus pneumoniae simulating clinically achievable free serum, epithelial lining fluid and middle ear fluid concentrations.
Zhanel GG, DeCorby M, Noreddin A, Mendoza C, Cumming A, Nichol K, Wierzbowski A, Hoban DJ.
Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, and Health Sciences Centre, MS673-820 Sherbrook Street, Winnipeg, Manitoba, Canada R3A 1R9. ggzhanel
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pcs.mb.ca
BACKGROUND: The association between macrolide resistance mechanisms and bacteriological eradication of Streptococcus pneumoniae remains poorly studied. The present study, using an in vitro pharmacodynamic model, assessed azithromycin activity against macrolide-susceptible and -resistant S. pneumoniae simulating clinically achievable free serum (S), epithelial lining fluid (ELF) and middle ear fluid (MEF) concentrations. MATERIALS AND METHODS: Two macrolide-susceptible [PCR-negative for both mef(A) and erm(B)] and six macrolide-resistant [five mef(A)-positive/erm(B)-negative displaying various degrees of macrolide resistance and one mef(A)-negative/erm(B)-positive] S. pneumoniae were tested. Azithromycin was modelled simulating a dosage of 500 mg/250 mg by mouth, once a day [free S: maximum concentration (Cmax) 0.2 mg/L, t1/2 68 h; free ELF Cmax 1.0 mg/L, t1/2 68 h] and 10 mg/kg by mouth, once a day (free MEF: Cmax 1.0 mg/L, t1/2 68 h) using a one compartment model. Starting inocula were 1 x 10(6) cfu/mL in Mueller-Hinton broth with 2% lysed horse blood. Sampling at 0, 2, 4, 6, 12, 24 and 48 h assessed the extent of bacterial killing (decrease in log10 cfu/mL versus initial inoculum). RESULTS: Free azithromycin concentrations in serum, ELF and MEF simulating time above the MIC (T > MIC) of 100% [area under the curve to MIC (AUC0-24/MIC] > or = 36.7] were bactericidal (> or = 3 log10 killing) at 24 and 48 h versus macrolide-susceptible S. pneumoniae. Against macrolide-resistant S. pneumoniae, free serum concentrations providing T > MIC of 0% or AUC0-24/MIC < or = 1.1 demonstrated no bacterial inhibition followed by regrowth at 24 and 48 h, whereas free ELF and MEF providing T > MIC of 0% or AUC0-24/MIC of 4.6 produced a bacteriostatic (0.2-0.5 log10 killing at 24 h) effect with a mef(A) strain with an azithromycin MIC of 2 mg/L. Against mef(A)-positive S. pneumoniae strains with azithromycin MICs > or = 4 mg/L, no bacterial killing occurred at any time point and rapid regrowth was observed simulating ELF or MEF T > MIC of 0% or AUC0-24/MIC < or = 2.3. CONCLUSION: Azithromycin serum, ELF and MEF concentrations rapidly eradicated macrolide-susceptible S. pneumoniae but did not eradicate macrolide-resistant S. pneumoniae regardless of resistance phenotype.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12775677&dopt=Abstract
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cdc.gov
BACKGROUND: Treatment of incubating syphilis with intramuscular benzathine penicillin in exposed sex partners is not always practical in the field, and exposed partners may not adhere to referrals for treatment at clinical facilities. The availability of a single-dose oral therapy could increase the number of partners treated and reduce future infections. GOAL: The goal of the study was to evaluate the cost-effectiveness of directly observed oral administration of azithromycin as an alternative to referral for treatment with benzathine penicillin. STUDY DESIGN: Using published probability and cost estimates, we constructed a decision-analysis model to compare the direct costs and effectiveness of field treatment with azithromycin (1-g single dose) versus referral for standard benzathine penicillin therapy. RESULTS: At public-sector pricing ($11.50 U.S. dollars), directly observed field treatment with azithromycin is cost-saving from both the program and healthcare system perspectives at efficacy levels as low as 75%. Azithromycin therapy is cost-saving at the wholesale price of $17.32 U.S. dollars (sachet formulation) when efficacy is at least 90%. The more expensive tablet formulation (average wholesale price of $27.89 U.S. dollars) is not cost-saving from a program perspective, but it remains cost-saving from a healthcare system perspective if efficacy rates are at least 90%. Azithromycin therapy (1-g single dose) will result in fewer cases of early syphilis among exposed partners, provided that the drug's efficacy is at least 87%. CONCLUSIONS: Azithromycin is a cost-effective alternative treatment for incubating syphilis in settings where standard intramuscular therapy is not practical.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12782951&dopt=Abstract
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