Drugs online research references
Antimicrob Agents Chemother. 1999 Aug;43(8):2027-31.
Activity of telithromycin (HMR 3647) against anaerobic bacteria compared to those of eight other agents by time-kill methodology.
Credito KL, Ednie LM, Jacobs MR, Appelbaum PC.
Department of Pathology, Hershey Medical Center, Hershey, Pennsylvania 17033, USA.
Time-kill studies examined the activities of telithromycin (HMR 3647), erythromycin A, azithromycin, clarithromycin, roxithromycin, clindamycin, pristinamycin, amoxicillin-clavulanate, and metronidazole against 11 gram-positive and gram-negative anaerobic bacteria. Time-kill studies were carried out with the addition of Oxyrase in order to prevent the introduction of CO(2). Macrolide-azalide-ketolide MICs were 0.004 to 32.0 microg/ml. Of the latter group, telithromycin had the lowest MICs, especially against non-Bacteroides fragilis group strains, followed by azithromycin, clarithromycin, erythromycin A, and roxithromycin. Clindamycin was active (MIC </= 2.0 microg/ml) against all anaerobes except Peptostreptococcus magnus and Bacteroides thetaiotaomicron, while pristinamycin MICs were 0.06 to 4.0 microg/ml. Amoxicillin-clavulanate had MICs of </=1.0 microg/ml, while metronidazole was active (MICs, 0.03 to 2.0 microg/ml) against all except Propionibacterium acnes. After 48 h at twice the MIC, telithromycin was bactericidal (>/=99.9% killing) against 6 strains, with 99% killing of 9 strains and 90% killing of 10 strains. After 24 h at twice the MIC, 90, 99, and 99.9% killing of nine, six, and three strains, respectively, occurred. Lower rates of killing were seen at earlier times. Similar kill kinetics relative to the MIC were seen with other macrolides. After 48 h at the MIC, clindamycin was bactericidal against 8 strains, with 99 and 90% killing of 9 and 10 strains, respectively. After 24 h, 90% killing of 10 strains occurred at the MIC. The kinetics of clindamycin were similar to those of pristinamycin. After 48 h at the MIC, amoxicillin-clavulanate showed 99.9% killing of seven strains, with 99% killing of eight strains and 90% killing of nine strains. At four times the MIC, metronidazole was bactericidal against 8 of 10 strains tested after 48 h and against all 10 strains after 24 h; after 12 h, 99% killing of all 10 strains occurred.
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OBJECTIVE: The purpose of this study was to characterize the pharmacokinetics of orally administered azithromycin 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 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 levels were determined quantitatively with high-pressure liquid chromatography with electrochemical detection. RESULTS: All participants tolerated the preoperative azithromycin without significant adverse reactions. Peak maternal serum azithromycin levels occurred within 6 hours of drug administration. Although high serum levels of azithromycin 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 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 (>5000 ng/mL) were noted similarly during the initial 72 hours after drug administration. Umbilical arterial and venous serum azithromycin 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 concentrations were undetectable for all time points. CONCLUSION: Azithromycin 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 may have potential use for the treatment of perinatal infections.
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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 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 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 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.
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