Penetration of pefloxacin into cerebrospinal fluid of patients with meningitis

Wolff, Michel; Régnier, B.; Daldoss, C; Nkam, M; Vachon, F

doi:10.1128/aac.26.3.289

Cited by 71 publications

(18 citation statements)

References 3 publications

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“…Comparisons in the same laboratory of the ratio of AUC values for serum and blister fluid for norfloxacin, enoxacin, ciprofloxacin, and ofloxacin suggest approximately equivalent, excellent drug penetration (1,9,29,44 17), and peak enoxacin concentrations in sputa from patients with acute exacerbations of chronic bronchitis were 90% of peak serum concentrations (10). In the presence of meningeal inflammation, pefloxacin appears to penetrate well into the cerebrospinal fluid, reaching concentrations of 4.8 ± 0.79 ,ug/ml (44% that of serum) (47). Similar drug penetration into cerebrospinal fluid was also seen when pefloxacin was given after the recovery of patients from meningitis (47 [34][35][36]40).…”

Section: Introductionmentioning

confidence: 99%

“…In the presence of meningeal inflammation, pefloxacin appears to penetrate well into the cerebrospinal fluid, reaching concentrations of 4.8 ± 0.79 ,ug/ml (44% that of serum) (47). Similar drug penetration into cerebrospinal fluid was also seen when pefloxacin was given after the recovery of patients from meningitis (47 [34][35][36]40). Norfloxacin, when given with one exception (14) in doses of 400 mg orally twice daily, demonstratqd significantly higher (35,36) or equivalent rates of cure when compared in eight randomized, nonblinded studies to orally administered trimethoprim-sulfamethoxazole (14,16,18,19,36,40), amoxicillin (28), or nalidixic acid (35) ( Table 2).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The fluoroquinolones: pharmacology, clinical uses, and toxicities in humans

Hooper¹,

Wolfson²

1985

Antimicrob Agents Chemother

394

204

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The fluoroquinolones: pharmacology, clinical uses, and toxicities in humans

Hooper¹,

Wolfson²

1985

Antimicrob Agents Chemother

394

204

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“…For cerebrospinal fluid obtained from patients with meningitis, concentrations were 10 to 40% of concentrations in serum for ciprofloxacin (860), 40 to 90% for ofloxacin (171,742), and 60% for pefloxacin (862).…”

Section: Pharmacokinetic Properties In Healthy Personsmentioning

confidence: 99%

Fluoroquinolone antimicrobial agents

1989

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The fluoroquinolones, a new class of potent orally absorbed antimicrobial agents, are reviewed, considering structure, mechanisms of action and resistance, spectrum, variables affecting activity in vitro, pharmacokinetic properties, clinical efficacy, emergence of resistance, and tolerability. The primary bacterial target is the enzyme deoxyribonucleic acid gyrase. Bacterial resistance occurs by chromosomal mutations altering deoxyribonucleic acid gyrase and decreasing drug permeation. The drugs are bactericidal and potent in vitro against members of the family Enterobacteriaceae, Haemophilus spp., and Neisseria spp., have good activity against Pseudomonas aeruginosa and staphylococci, and (with several exceptions) are less potent against streptococci and have fair to poor activity against anaerobic species. Potency in vitro decreases in the presence of low pH, magnesium ions, or urine but is little affected by different media, increased inoculum, or serum. The effects of the drugs in combination with a beta-lactam or aminoglycoside are often additive, occasionally synergistic, and rarely antagonistic. The agents are orally absorbed, require at most twice-daily dosing, and achieve high concentrations in urine, feces, and kidney and good concentrations in lung, bone, prostate, and other tissues. The drugs are efficacious in treatment of a variety of bacterial infections, including uncomplicated and complicated urinary tract infections, bacterial gastroenteritis, and gonorrhea, and show promise for therapy of prostatitis, respiratory tract infections, osteomyelitis, and cutaneous infections, particularly when caused by aerobic gram-negative bacilli. Fluoroquinolones have also proved to be efficacious for prophylaxis against travelers' diarrhea and infection with gram-negative bacilli in neutropenic patients. The drugs are effective in eliminating carriage of Neisseria meningitidis. Patient tolerability appears acceptable, with gastrointestinal or central nervous system toxicities occurring most commonly, but only rarely necessitating discontinuance of therapy. In 17 of 18 prospective, randomized, double-blind comparisons with another agent or placebo, fluoroquinolones were tolerated as well as or better than the comparison regimen. Bacterial resistance has been uncommonly documented but occurs, most notably with P. aeruginosa and Staphylococcus aureus and occasionally other species for which the therapeutic ratio is less favorable. Fluoroquinolones offer an efficacious, well-tolerated, and cost-effective alternative to parenteral therapies of selected infections.

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“…Enoxacin and pefloxacin have similar pharmacological properties after oral administration; norfloxacin is absorbed much less (7,15). It has been shown that pefloxacin is widely distributed in human tissues and penetrates well in inflamed meninges (7,16). In this study we measured the serum levels of pefloxacin after intravenous administration.…”

mentioning

confidence: 99%

Bactericidal activity and killing rate of serum from volunteers receiving pefloxacin alone or in combination with amikacin

Auwera¹,

Klastersky²,

Lieppe³

et al. 1986

Antimicrob Agents Chemother

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Serum bactericidal activities (SBAs) were studied after intravenous administration of pefloxacin (8 mg/kg) and amikacin (7.5 mg/kg) alone or in combination to 15 human volunteers. About 10 strains each of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus Were tested. The serum levels of pefloxacin were measured microbiologically by using E. coli KP 1976-712 as the test organism at 0, 30, 60, 120, and 720 min after infusion; at 0, 30, 60, and 720 min these levels were 7 ± 1.4, 5 ± 0.8, 4.5 ± 0.7, and 2.1 ± 0.6 mg/liter (mean ± standard deviation), respectively, with a terminal half-life of 10 h. The serum levels of pefloxacin in the presence of amikacin were measured similarly; 1 % sodium polyanethol sulfonate was added to the agar to inactivate amikacin. Treatment with pefloxacin alone resulted in high SBAs against E. coli, K. pneumoniae strains susceptible to cephalothin, and Staphylococcus aureus at the peak concentration; 81 to 100% of the sera had SBAs of .1:8. However, treatment with pefloxacin alone resulted in low SBAs against K. pneumoniae strains resistant to cephalothin and P. aeruginosa; only 34% of the sera had SBAs of .1:8. At trough concentrations the percentages of sera with SBAs >1:8 were 75 to 83% (E. col), 9 to 27% (K. pneumoniae), 0% (P. aeruginosa), and 10% (S. aureus). The combination of pefloxacin plus amikacin was most often additive; the peak activity was due to amikacin, and the trough activity was due to pefloxacin. Occasionally antagonism occurred with P. aeruginosa, K. pneumoniae, and S. aureus strains. These observations were confirmed by the killing curves in pooled serum obtained at peak and trough levels. Regrowth was observed for seven strains of P. aeruginosa treated with pefloxacin alone; amikacin seemed to prevent this phenomenon.Gram-negative infections are still a major cause of morbidity and death in burned patients and in cancer patients, especially when they are neutropenic (11). Treatment of these infections often consists of the administration of a broad-spectrum ,-lactam antibiotic combined or not combined with an aminoglycoside (4). Pefloxacin is a new fluorinated quinoline carboxylic acid derivative which has a high in vitro activity against members of the Enterobacteriaceae, Pseudomonas aeruginosa, and some gram-positive cocci (12, 13). The purpose of the present investigation was to evaluate the efficacy, as measured by titration of serum bactericidal activity (SBA) and rate of bactericidal activity in serum, or parenteral administration of pefloxacin used alone or in combination with amikacin against selected gramnegative and gram-positive pathogens. The SBA has been shown to predict the outcome of bacteremic infections in cancer patients, whether they are granulocytopenic or not (10). Moreover, the usefulness of the serum killing rate assay was recently validated in an animal model of endocarditis (2). An 8-h time kill study with single 1:2 dilutions of serum samples was used to measure the rate of bactericidal activity. ...

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Penetration of pefloxacin into cerebrospinal fluid of patients with meningitis

Cited by 71 publications

References 3 publications

The fluoroquinolones: pharmacology, clinical uses, and toxicities in humans

The fluoroquinolones: pharmacology, clinical uses, and toxicities in humans

Fluoroquinolone antimicrobial agents

Bactericidal activity and killing rate of serum from volunteers receiving pefloxacin alone or in combination with amikacin

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