Drugs online research references
Pediatr Infect Dis J. 2002 Jun;21(6):525-9.
Tendon or joint disorders in children after treatment with fluoroquinolones or azithromycin.
Yee CL, Duffy C, Gerbino PG, Stryker S, Noel GJ.
Johnson & Johnson Pharmaceutical Research and Development, L.L.C., Raritan, NJ 08869, USA.
BACKGROUND: Fluoroquinolones (FQs) have been infrequently used in children, largely because of concern that these agents can cause lesions of the cartilage in juvenile animals. However, the relevance of this laboratory observation to children treated with FQs is unknown. A retrospective, observational study was conducted to assess the incidence and relative risk of tendon or joint disorders (TJDs) that occur after use of selected FQs compared with azithromycin (AZ), a drug with no known effect on cartilage or tendons in humans or animals. METHODS: An automated database was searched to identify patients younger than 19 years who had been prescribed ofloxacin (OFX), levofloxacin, ciprofloxacin (CPX), or AZ. Potential cases of TJD occurring within 60 days of a prescription of one of the study drugs were identified based on assignment of a claims diagnosis consistent with a TJD within this period. Verified cases were identified by a blinded review of abstracts of medical records from subjects identified as potential cases. RESULTS: The incidence of verified TJD was 0.82% for OFX (13 of 1593) and CPX (37 of 4531) and was 0.78% for AZ (118 of 15,073). The relative risk of TJD for OFX and CPX compared with AZ was 1.04 (95% confidence interval, 0.55 to 1.84) and 1.04 (95% confidence interval, 0.72 to 1.51), respectively. The distributions of claims diagnoses and time to onset of TJD were comparable for all groups. The most frequently reported category of TJD involved the joint followed by tendon, cartilage and gait disorder. CONCLUSIONS: In this observational study involving more than 6000 FQ-treated children, the incidence of TJD associated with selected FQ use in children was <1% and was comparable with that of the reference group, children treated with AZ.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12182376&dopt=Abstract
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Antimicrob Agents Chemother. 2002 Sep;46(9):2956-62.
In vitro selection of resistance in Haemophilus influenzae by amoxicillin-clavulanate, cefpodoxime, cefprozil, azithromycin, and clarithromycin.
Clark C, Bozdogan B, Peric M, Dewasse B, Jacobs MR, Appelbaum PC.
Department of Pathology, Hershey Medical Center, Hershey, Pennsylvania 17033, USA.
Abilities of amoxicillin-clavulanate, cefpodoxime, cefprozil, azithromycin, and clarithromycin to select resistant mutants of Haemophilus influenzae were tested by multistep and single-step methodologies. For multistep studies, 10 random strains were tested: 5 of these were beta-lactamase positive. After 50 daily subcultures in amoxicillin-clavulanate, MICs did not increase more than fourfold. However, cefprozil MICs increased eightfold for one strain. Clarithromycin and azithromycin gave a >4-fold increase in 8 and 10 strains after 14 to 46 and 20 to 50 days, respectively. Mutants selected by clarithromycin and azithromycin were associated with mutations in 23S rRNA and ribosomal proteins L4 and L22. Three mutants selected by clarithromycin or azithromycin had alterations in ribosomal protein L4, while five had alterations in ribosomal protein L22. Two mutants selected by azithromycin had mutations in the gene encoding 23S rRNA: one at position 2058 and the other at position 2059 (Escherichia coli numbering), with replacement of A by G. One clone selected by clarithromycin became hypersusceptible to macrolides. In single-step studies azithromycin and clarithromycin had the highest mutation rates, while amoxicillin-clavulanate had the lowest. All resistant clones were identical to parents as observed by pulsed-field gel electrophoresis. The MICs of azithromycin for azithromycin-resistant clones were 16 to >128 micro g/ml, and those of clarithromycin for clarithromycin-resistant clones were 32 to >128 micro g/ml in multistep studies. For strains selected by azithromycin, the MICs of clarithromycin were high and vice versa. After 50 daily subcultures in the presence of drugs, MICs of amoxicillin-clavulanate and cefpodoxime against H. influenzae did not rise more than fourfold, in contrast to cefprozil, azithromycin, and clarithromycin, whose MICs rose to variable degrees.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12183253&dopt=Abstract
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hc-sc.gc.ca
Fifty-six azithromycin-resistant (MICs, 2.0 to 4.0 micro g/ml) Neisseria gonorrhoeae strains with cross-resistance to erythromycin (MICs, 2.0 to 64.0 micro g/ml), isolated in Canada between 1997 and 1999, were characterized, and their mechanisms of azithromycin resistance were determined. Most (58.9%) of them belonged to auxotype-serotype class NR/IB-03, with a 2.6-mDa plasmid. Based on resistance to crystal violet (MICs >or= 1 micro g/ml), 96.4% of these macrolide-resistant strains appeared to have increased efflux. Nine of the eleven strains selected for further characterization were found to have a promoter region mtrR mutation, a single-base-pair (A) deletion in the 13-bp inverted repeat, which is believed to cause overexpression of the mtrCDE-encoded efflux pump. The two remaining macrolide-resistant strains (erythromycin MIC, 64.0 micro g/ml; azithromycin MIC, 4.0 micro g/ml), which did not have the mutation in the mtrR promoter region, were found to have a C2611T mutation (Escherichia coli numbering) in the peptidyltransferase loop in domain V of the 23S rRNA alleles. Although mutations in domain V of 23S rRNA alleles had been reported in other bacteria, including E. coli, Streptococcus pneumoniae, and Helicobacter pylori, this is the first observation of these mutations associated with macrolide resistance in N. gonorrhoeae.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12183262&dopt=Abstract
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