Drugs online research references
Zentralbl Bakteriol. 1998 May;287(4):343-6.
Outer membrane proteins of Klebsiella pneumoniae after exposure to ciprofloxacin.
Hostacka A, Karelova E.
Institute of Preventive and Clinical Medicine, Bratislava, Slovakia.
Suppression of bacterial growth of two Klebsiella pneumoniae strains after a short time exposure to ciprofloxacin at suprainhibitory concentrations was found (postantibiotic effect-PAE). PAEs induced by ciprofloxacin at 2 x MIC were 4.1 h and 5.3 h for the strains tested, the concentration of 4 x MIC manifested a suppression of the bacterial growth which lasted 5.9 h and 6.3 h. Delay of regrowth of K. pneumoniae strains exposed to suprainhibitory concentrations of quinolones was shown also by other authors. New information concerning the outer membrane protein profile of K. pneumoniae after PAE has been found. SDS-PAGE analysis revealed that outer membrane protein patterns isolated from K. pneumoniae strains treated with a suprainhibitory concentration of ciprofloxacin did not show apparent changes as compared to controls.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9638864&dopt=Abstract
Clin Pharmacol Ther. 1984 Sep;36(3):384-8.
Multiple-dose ciprofloxacin kinetics in normal subjects.
Aronoff GE, Kenner CH, Sloan RS, Pottratz ST.
To determine multiple-dose kinetics of the quinoline carboxylic acid derivative ciprofloxacin, we gave 12 normal subjects ciprofloxacin, 250 mg by mouth every 12 hr for 13 doses. Plasma concentrations were measured by HPLC after the first, seventh, and thirteenth doses. Peak and trough plasma concentrations were measured daily. Ciprofloxacin was rapidly absorbed from the gastrointestinal tract and reached maximum serum concentrations about 1 hr after dosing. Ciprofloxacin elimination t1/2 increased from 3.71 hr after the first dose to 6.51 hr after the thirteenth dose (P less than 0.05). Apparent plasma clearance decreased from 0.823 to 0.629 l/kg/hr because of decreased nonrenal clearance. Drug cumulation did not occur throughout the experiment. We conclude that concentrations of ciprofloxacin in excess of the minimum inhibitory concentrations for many important pathogens can be achieved in plasma and that controlled clinical trials of ciprofloxacin efficacy in selected systemic infections are warranted.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6467798&dopt=Abstract
Antimicrob Agents Chemother. 1996 Aug;40(8):1768-74.
Gyrase mutations in laboratory-selected, fluoroquinolone-resistant mutants of Mycobacterium tuberculosis H37Ra.
Kocagoz T, Hackbarth CJ, Unsal I, Rosenberg EY, Nikaido H, Chambers HF.
Department of Medicine, University of California, San Francisco 94110, USA.
To characterize mechanisms of resistance to fluoroquinolones by Mycobacterium tuberculosis, mutants of strain H37Ra were selected in vitro with ofloxacin. Their quinolone resistance-determining regions for gyrA and gyrB were amplified and sequenced to identify mutations in gyrase A or B. Three types of mutants were obtained: (i) one mutant (TKp1) had no mutations in gyrA or gyrB; (ii) mutants that had single missense mutations in gyrA, and (iii) mutants that had two missense mutations resulting in either two altered gyrase A residues or an altered residue in both gyrases A and B. The TKp1 mutant had slightly reduced levels of uptake of [14C]norfloxacin, which was associated with two- to fourfold increases in the MICs of ofloxacin, ciprofloxacin, and sparfloxacin. Gyrase mutations caused a much greater increase in the MICs of fluoroquinolones. For mutants with single gyrA mutations, the increases in the MICs were 4- to 16-fold, and for mutants with double gyrase mutations, the MICs were increased 32-fold or more compared with those for the parent. A gyrA mutation in TKp1 secondary mutants was associated with 32- to 128-fold increases in the MICs of ofloxacin and ciprofloxacin compared with the MICs for H37Ra and an eight-fold increase in the MIC of sparfloxacin. Sparfloxacin was the most active fluoroquinolone tested. No sparfloxacin-resistant single-step mutants were selected at concentrations of > 2.5 micrograms/ml, and high-level resistance (i.e., MIC, > and = 5 micrograms/ml) was associated with two gyrase mutations. Mutations in gyrB and possibly altered levels of intracellular accumulation of drug are two additional mechanisms that may be used by M. tuberculosis in the development of fluoroquinolone resistance. Because sparfloxacin is more active in vitro and selection of resistance appears to be less likely to occur, it may have important advantage over ofloxacin or ciprofloxacin for the treatment of tuberculosis.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8843279&dopt=Abstract
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