Drugs online research references
Eur J Clin Microbiol. 1984 Aug;3(4):333-8.
Comparative in vitro activity of five quinoline derivatives and five other antimicrobial agents used in oral therapy.
Hoogkamp-Korstanje JA.
The antibacterial activity of ciprofloxacin was compared to those of norfloxacin, pefloxacin, pipemidic acid, nalidixic acid, nitrofurantoin, sulfamethoxazole, trimethoprim, cephradine and amoxycillin. Agar dilution tests were performed with 631 clinical isolates from urinary and respiratory tract infections. Ciprofloxacin was found to be the most active drug tested against all gram-negative organisms and streptococci, with the exception of Streptococcus faecalis and Streptococcus pneumoniae. MIC 90 values of ciprofloxacin were as follows: for Enterobacteriaceae, 0.03-0.23 mg/l, Pseudomonas aeruginosa, 0.37 mg/l, Haemophilus influenzae, less than 0.015 mg/l, Staphylococcus aureus, 0.75 mg/l, Streptococcus pneumoniae, 1.89 mg/l, and Streptococcus faecalis, 0.95 mg/l. The inhibitory quotients for urine, serum and bronchial secretion showed that ciprofloxacin had the broadest spectrum of all agents tested and covered and clinically significant bacteria.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6237901&dopt=Abstract
al.mgh.harvard.edu
Mutations in the flqA (formerly ofx/cfx) resistance locus of Staphylococcus aureus were previously shown to be common after first-step selections for resistance to ciprofloxacin and ofloxacin and to map on the S. aureus chromosome distinctly from gyrA, gyrB, and norA.grlA and grlB, the genes for the topoisomerase IV of S. aureus, were identified from a genomic lambda library on a common KpnI fragment, and grlB hybridized specifically with the chromosomal SmaI A fragment, which contains the flqA locus. Amplification of grlA sequences (codons 1 to 251) by PCRs from nine independent single-step flqA mutants, one multistep mutant, and the parent strain identified mutations encoding a change from Ser to Phe at position 80 in four mutants, a novel change from Ala to either Glu or Pro at position 116 in three mutants, and no change in three mutants. In the multistep mutant, another resistance locus, flqC, was mapped by transformation to the chromosomal SmaI G fragment by linkage to omega(ch::Tn551)1051 (58%) and nov (97.9%), which encodes resistance to novobiocin. This fragment contains the gyrA gene, and flqC mutants had a mutation in gyrA encoding a change from Ser to Leu at position 84, a change previously found in resistant clinical isolates. In genetic outcrosses, the flqC (gyrA) mutation expressed resistance only in flqA mutants, including those with both types of grla mutations. The silent mutant allele of gyrA was present in a flqA background and expressed resistance only upon introduction of a grlA mutation. At fourfold the MIC of ciprofloxacin, the bactericidal activity of ciprofloxacin was reduced in a grlA mutant and was abolished in gyrA grlA double mutants. These findings provide direct genetic evidence that topoisomerase IV is the primary target of current fluoroquinolones in S. aureus and that this effect may result from the greater sensitivity of topoisomerase IV relative to that of DNA gyrase to these agents. Furthermore, resistance from an altered DNA gyrase requires resistant topoisomerase IV for its expression.
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microclinic.med.ub.es
Mutations in the parC gene, which encodes a subunit of topoisomerase IV, were determined in 21 epidemiologically unrelated clinical isolates of Acinetobacter baumannii. Our studies highlight the conserved sequences in the quinolone-resistance-determining region of the parC gene from A. baumannii and other bacteria. Nine of ten isolates with MICs of ciprofloxacin of > or = 32 mg/L showed a change of Ser80 to Leu and one showed a change of Glu84 to Lys. These results suggest that ParC from A. baumannii is a secondary target for quinolones and that mutations at residues Ser80 and Glu84, when combined with mutations at Ser83 of GyrA, may render A. baumannii highly resistant to quinolones.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9222045&dopt=Abstract
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