Pharmacokinetics and tissue penetration of ciprofloxacin

Crump, B J; Wise, R.; Dent, John G.

doi:10.1128/aac.24.5.784

Cited by 242 publications

(125 citation statements)

References 8 publications

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“…Serum concentrations above this level have been obtained in humans by oral drug administration (3,6). Therefore, these new quinolones should prove to be effective in the therapy of systemic infections caused by this organism.…”

Section: Discussionmentioning

confidence: 99%

Activities of pefloxacin and ciprofloxacin in experimentally induced Pseudomonas pneumonia in neutropenic guinea pigs

Gordin¹,

Hackbarth²,

Scott³

et al. 1985

Antimicrob Agents Chemother

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Pefloxacin and ciprofloxacin are two new quinoline carboxylic acid derivatives that have activity in vitro against a wide range of gram-negative bacteria, including Pseudomonas aeruginosa. Using a well-standardized model of Pseudomonas pneumonia in neutropenic guinea pigs, we tested the efficacy in vivo of these new agents. Both were highly effective in increasing survival and decreasing bacterial counts in the lungs of surviving animals. Pefloxacin and ciprofloxacin were significantly better (P < 0.05) than aminoglycosides or beta-lactams tested in prior studies with this model, and they were as effective as combination therapy with aminoglycosides and beta-lactams. Resistance to either ciprofloxacin or pefloxacin did not emerge during the study period. Further studies with these drugs in the therapy of Pseudomonas sp. infections are warranted.Pefloxacin and ciprofloxacin are two new quinoline carboxylic acid derivatives (12,15). Although structurally similar to nalidixic acid, the spectrum of activity of pefloxacin and ciprofloxacin includes Enterobacteriaceae, Pseudomonas sp., and many gram-positive cocci. Both drugs are well absorbed orally, have serum half-lives of 8.6 and 3.9 h, respectively, and reach concentrations in serum well above the MIC for many bacterial species (3, 6). Extensive in vitro studies have shown that ciprofloxacin has a MIC90 of -1 g/ml, whereas pefloxacin has a MIC90 of .2 ,ug/ml for many of the above-mentioned bacteria (2,5,14). It is of special interest that both of these antimicrobial agents are highly active against Pseudomonas aeruginosa, including multiply drug-resistant strains (2, 11).The purpose of this study was to examine the effectiveness of pefloxacin and ciprofloxacin against induced P. aeruginosa pneumonia in neutropenic guinea pigs. MATERIALS AND METHODSCiprofloxacin was obtained from Miles Pharmaceuticals, West Haven, Conn. Pefloxacin mesylate was obtained from Rhone-Poulenc, Paris, France.The MIC of each agent for the P5 strain of P. aeruginosa was determined in Mueller-Hinton broth supplemented with Mg2+ and Ca2+ by the macro-tube dilution method, using a standard inoculum of 5 log10 CFU/ml (13). The MBC was defined as the lowest concentration of drug that killed 99.9% of the original inoculum.Time-kill studies were performed with each antimicrobial agent, using concentrations which approximated the serum concentrations at peak levels. Logarithmic-phase organisms were added to supplemented Mueller-Hinton broth containing 12 ,ug of pefloxacin per ml, 4 ,ug of ciprofloxacin per ml, or no antibiotic and were incubated at 35°C. Samples were removed and quantitatively cultured before and after 4, 8, and 24 h of incubation.To determine the serum half-life (t412) of each drug and develop the therapeutic regimens, preliminary drug dosing studies were performed in groups of five normal guinea pigs. Blood was obtained by cardiac puncture 0.5, 1, 2, 3, 4, 6, and 8 h after an intramuscular injection of pefloxacin (25 mg/kg) or ciprofloxacin (either 10 or 20 mg/kg). Concentratio...

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Section: Discussionmentioning

confidence: 99%

Activities of pefloxacin and ciprofloxacin in experimentally induced Pseudomonas pneumonia in neutropenic guinea pigs

Gordin¹,

Hackbarth²,

Scott³

et al. 1985

Antimicrob Agents Chemother

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“…Blister fluid penetration studies show good penetration of these agents into extravascular fluids (1,19,48), but the ECF concentrations are virtually identical to those in serum (Table 1). Unlike tissue homogenate ratios, ECF concentrations are not twofold greater.…”

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confidence: 98%

Antibiotic tissue penetration and its relevance: impact of tissue penetration on infection response

Nix

Goodwin

Peloquin

et al. 1991

Antimicrob Agents Chemother

166

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“…The peak serum and inflammatory tissue levels of norfloxacin and ciprofloxacin are much in excess of the observed MICs of the compounds for N. gonorrhoeae (2,5). Rosoxa-cin has been shown to be effective for the treatment of gonorrhea, due to both penicillinase-negative strains and PPNGs (1,4,7,8).…”

mentioning

confidence: 99%

In vitro activities of the spectinomycin analog U-63366 and four quinolone derivatives against Neisseria gonorrhoeae

Peeters¹,

Dyck²,

Piot³

1984

Antimicrob Agents Chemother

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The in vitro activities of the new spectinomycin analog U-63366 and four new quinolone derivatives, rosoxacin, norfloxacin, ofloxacin, and ciprofloxacin, were compared with those of penicillin, tetracycline, thiamphenicol, cefotaxime, ceftriaxone, and spectinomycin against 222 beta-lactamase-negative and 25 betalactamase-positive Neisseria gonorrhoeae strains. U-63366 was more active than spectinomycin, inhibiting 90% of the strains at a concentration of 2 mg/liter. Among the quinolone derivatives, ciprofloxacin was the most active compound in vitro (90% MIC, 0.002 mg/liter), followed by ofloxacin (90% MIC, 0.008 mg/liter), norfloxacin (90% MIC, 0.015 mg/liter), and rosoxacin (90% MIC, 0.03 mg/liter).The emergence of penicillinase-producing isolates of Neisseria gonorrhoeae (PPNGs) and the high MIC of tetracycline among these strains have stimulated the search for alternative antimicrobial agents that are effective against infections with PPNGs as well as with gonococcal strains with reduced susceptibility to penicillin. Spectinomycin has been widely used for the treatment of PPNG infections, and spectinomycin-resistant PPNG strains are still rare (1). Until now, mainly second-and third-generation cephalosporins have been actively investigated as alternative drugs for PPNG infections, and they already are widely used in some countries. However, cefuroxime-resistant N. gonorrhoeae strains have been reported in the Netherlands (6), and isolates resistant to the newer cephalosporins may rapidly emerge (11).We report here on the activity of U-63366, a new spectinomycin analog, and four new quinolone derivatives against penicillinase-negative N. gonorrhoeae isolates and PPNGs.The These results agree with recently published in vitro susceptibilities (7,9,12).Although the MIC50 and MIC90 of the quinolones for the PPNGs were one to three dilutions higher than those for the penicillinase-negative isolates, the overall range of MICs of the four compounds was almost identical for both groups of strains. The slightly higher MICs for the PPNGs may be due to an overall lower susceptibility of these isolates, which were all acquired outside Belgium. PPNGs also exhibited slightly higher median MICs of ceftriaxone and U-63366 but not of cefotaxime and spectinomycin. In contrast, tetracycline and thiamphenicol were much less active against PPNGs, with an eightfold increase in the median MIC of both antibiotics. Thus, more than 50% of the PPNGs had MICs of tetracycline and thiamphenicol of .2 mg and .1 mg, respectively, per liter.The in vitro results suggest that the newer quinolones may be effective drugs for the treatment of gonococcal infection. The peak serum and inflammatory tissue levels of norfloxacin and ciprofloxacin are much in excess of the observed MICs of the compounds for N. gonorrhoeae (2,5). Rosoxa-cin has been shown to be effective for the treatment of gonorrhea, due to both penicillinase-negative strains and PPNGs (1,4,7,8). However, central nervous system side effects of a 200-mg single dose were found in up to ...

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Pharmacokinetics and tissue penetration of ciprofloxacin

Cited by 242 publications

References 8 publications

Activities of pefloxacin and ciprofloxacin in experimentally induced Pseudomonas pneumonia in neutropenic guinea pigs

Activities of pefloxacin and ciprofloxacin in experimentally induced Pseudomonas pneumonia in neutropenic guinea pigs

Antibiotic tissue penetration and its relevance: impact of tissue penetration on infection response

In vitro activities of the spectinomycin analog U-63366 and four quinolone derivatives against Neisseria gonorrhoeae

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