Drugs

, Volume 37, Issue 5, pp 628–668 | Cite as

Pefloxacin

A Review of its Antibacterial Activity, Pharmacokinetic Properties and Therapeutic Use
  • John P. Gonzalez
  • Julian M. Henwood
Drug Evaluation

Summary

Synopsis

Pefloxacin is a fluorinated quinolone that is structurally related to nalidixic acid. It can be administered both orally and intravenously, and has a broad spectrum of in vitro activity against Gram-negative organisms and staphylococci. The pharmacokinetic profile of pefloxacin is characterised by high bioavailability after oral administration, a long half-life and good penetration of tissue and body fluids.

Data from mainly non-comparative studies suggest that pefloxacin has the potential for use in a variety of serious or difficult-to-treat and nosocomially acquired infections in hospitalised and immunocompromised patients. Such infections have included respiratory tract, urogenital tract, and bone and joint infections, septicaemia and surgical infections, in addition to severe Gram-negative infections in neutropenic cancer patients. Pefloxacin demonstrates comparable efficacy with ampicillin combined with gentamicin in upper gynaecological tract infections, ceftazidime in nosocomially acquired Gram-negative infections and co-trimoxazole (trimethoprim + sulphamethoxazole) in uncomplicated urinary tract infections and typhoid fever.

Although the place of pefloxacin in this new and expanding class of 4-quinolone antibacterial drugs has yet to be defined and it appears to be a well-tolerated and useful drug for the treatment of serious infections in hospitalised patients, further studies are awaited with interest for confirmation of these preliminary results.

Antibacterial Activity

Pefloxacin is a fluorinated quinolone which is structurally related to nalidixic acid. Most species of Enterobacteriaceae are susceptible or moderately susceptible to pefloxacin (MIC90 ≤ 2 mg/L); Providencia rettgeri is only moderately susceptible to the drug. For most species of Enterobacteriaceae the potency of pefloxacin was equivalent to that of enoxacin, ofloxacin, norfloxacin and cefotaxime, less than that of ciprofloxacin, and greater than that of nalidixic acid, ampicillin, amikacin, gentamicin and ceftazidime. Pefloxacin is a potent inhibitor of Neisseria gonorrhoeae and N. meningitidis, while strains of Acinetobacter are susceptible or moderately susceptible to the drug. Branhamella catarrhalis and Campylobacter species are susceptible or moderately susceptible to pefloxacin as well as to the other 4-quinolones tested. Haemophilus ducreyi is highly susceptible (MIC90 ≤ 0.12 mg/L) while H. influenzae is susceptible to pefloxacin. The activity of pefloxacin against Pseudomonas aeruginosa (MIC90 2 to 16 mg/L) is similar to that of enoxacin and norfloxacin, but less than that of ciprofloxacin and ofloxacin. For other species of Pseudomonas the susceptibility to pefloxacin is variable, with MIC90 values ranging from 1 to 64 mg/L. Other Gram-negative species including Aeromonas hydrophila, Legionella, Plesiomonas, Capnocytophaga, Agrobacter and Vibrio species are susceptible to pefloxacin, but Gardnerella vaginalis is resistant.

Staphylococcal strains, including Staphylococcus epidermidis and isolates of Staphylococcus aureus resistant to other antibacterials, are susceptible or moderately susceptible to pefloxacin, but there is an increasing percentage of resistant strains emerging. Streptococcus species including enterococci have only moderate sensitivity to pefloxacin, with MIC90 values ranging from 3.1 to 32 mg/L. Other Gram-positive species such as Listeria monocytogenes and Nocardia asteroides are resistant, whereas Mycobacterium tuberculosis and some other species of mycobacteria are usually only moderately susceptible to pefloxacin. Pefloxacin is inactive against most anaerobic species, including Bacteroides, Clostridium and Fusobacterium.

Pefloxacin is not active against Chlamydia trachomatis, Mycoplasma hominis and Ureaplasma urealyticum, with MIC90 values of 2 to 8, 16 and 2 to 8 mg/L, respectively; ofloxacin and ciprofloxacin are generally more active than pefloxacin in inhibiting these species.

Bacterial resistance to non-quinolone drugs such as penicillin, oxacillin and methicillin has little influence on the in vitro activity of pefloxacin but there is cross resistance, as shown using nalidixic acid-resistant isolates. Inoculum size has only a minor influence on the in vitro activity of pefloxacin but acidic pH and addition of calcium or magnesium ions has been shown to reduce its activity. Pefloxacin is rapidly bactericidal and has shown no synergistic in vitro effects in combination with other antibacterials, including cephalosporins and aminoglycosides, against Gram-negative and Gram-positive isolates. Amikacin, ceftazidime and piperacillin prevented the emergence of resistance to pefloxacin. Pefloxacin inhibits DNA gyrase activity, preventing the supercoiling of DNA and so interfering with bacterial replication, but alternative mechanisms of action such as the capacity to penetrate the bacterial membrane probably also contribute to its antibacterial effects.

Pefloxacin was shown to have good in vivo activity against S. aureus infections in mice, P. aeruginosa infections in neutropenic guinea-pigs, Escherichia coli-induced endocarditis, mice infected with Mycobacterium leprae and guinea-pig legionellosis.

Pharmacokinetic Properties

After administration of single oral doses of pefloxacin 400mg, to healthy volunteers, maximum plasma concentrations of 3.84 to 6.6 mg/L occur within 60 to 90 minutes. In a multiple-dose study both intravenous and oral routes of administration of pefloxacin 400mg produced approximate maximum plasma concentrations of 10 mg/L and AUC values were similar after both routes, indicative of complete bioavailability. Steady-state concentrations were achieved within 48 hours. Plasma trough concentrations 2 to 3 days after the start of multiple-dose 400mg administration were 2.1 to 3.8 mg/L, which are higher than the MIC90s for the majority of susceptible pathogens.

The volume of distribution has been calculated to range from 1.7 to 1.9 L/kg. Tissue pefloxacin concentrations are equivalent or higher than plasma concentrations for blister fluid, bone, brain, cardiac tissue, cerebrospinal fluid, prostate, saliva and sputum. Pefloxacin effectively penetrates extravascular spaces and is only 20 to 30% protein bound.

Pefloxacin is metabolised extensively to form the principal N-demethyl pefloxacin (norfloxacin) and N-oxide metabolites. Following single-dose administration of radiolabelled pefloxacin 70% and 25% of radioactivity was detected in urine and faeces, respectively, within 7 days. Only 8 to 9% of an administered dose appears in the urine as unchanged pefloxacin. Total urinary recovery of parent drug and metabolites was 59% of an administered dose, and renal clearance was 0.6 L/h and was independent of the route of administration. In addition, biliary excretion of pefloxacin and its metabolites also occurs. The elimination half-life following administration of single oral doses of pefloxacin 400mg ranged from 8.6 to 13 hours, increasing to approximately 14 to 15 hours after multiple dosing. In patients with impaired hepatic function plasma clearance of pefloxacin was reduced as further indicated by an increase in elimination half-life. In contrast, studies have shown impaired renal function to have minimal influence on the pharmacokinetics of pefloxacin. However, further studies are needed to verify whether alteration of dosage or dosing interval of pefloxacin is necessary in patients with renal dysfunction.

Therapeutic Trials

The majority of clinical trials with oral or intravenous pefloxacin have been conducted in hospitalised patients with a range of infectious conditions including nosocomially acquired infections, serious or difficult-to-treat infections, and infections in immunocompromised patients. In most cases these studies have been carried out under non-blind conditions and with limited comparisons to other antibacterial drugs.

In the treatment of patients with respiratory tract infections pefloxacin 800 to 1200mg daily produced clinical cure rates of 58 to 70% and bacteriological eradication rates ranging from 70 to 94%. Resistant strains of S. pneumoniae and P. aeruginosa were responsible for some of the treatment failures, and 3 studies reported superinfections in 7.5, 22 and 25% of patients. Gynaecological infections, as well as complicated upper or lower urinary tract infections, pelvic infections associated with the genital tract, and acute gonococcal infections were responsive in 72 to 94% of patients treated with pefloxacin 800 to 1200mg daily. In 2 comparative studies pefloxacin 800mg daily was as effective as daily ampicillin 2g combined with gentamicin 180 to 240mg in upper gynaecological tract infections, producing clinical cure rates of 93.3 and 94.4%, respectively, and as effective as co-trimoxazole 160/800mg twice daily in uncomplicated urinary tract infections.

In the treatment of chronic osteitis, chronic osteomyelitis and other bone and joint infections, treatment with pefloxacin 400mg twice a day for up to 18 months produced a clinical cure in 87 to 100% of patients. In a limited number of immunologically compromised patients successful results have been obtained with pefloxacin in non-comparative trials in the prophylaxis and treatment of fever or infections, particularly those caused by Gram-negative bacteria. In patients with septicaemia of varying focal origin caused by Staphylococcus aureus, streptococci, Enterobacteriaceae and Pseudomonas aeruginosa, treatment with pefloxacin 800 to 1200mg daily produced a favourable response in 76 to 100% of patients and eradication of 86 to 96% of bacteriological isolates.

Pefloxacin 800mg was as effective as co-trimoxazole 320/1600mg in the treatment of typhoid fever with both drugs resulting in a clinical cure in 100% of patients, but pefloxacin produced a more rapid onset of apyrexia than co-trimoxazole allowing a shortening of the treatment time. In the treatment of patients with nosocomially acquired Gram-negative infections, which included urinary tract infections, bronchopneumonia, deep soft tissue phlegmon, osteoarticular infections, intra-abdominal infections, chronic otitis media and acute cholangitis, pefloxacin 400mg every 8 or 12 hours was similar in efficacy to ceftazidime 2g every 8 hours and cefotaxime 1g 4 times a day.

Adverse Effects

Pefloxacin is generally well tolerated, with most adverse effects being of mild to moderate severity and transient in nature. Gastrointestinal disturbances were the most frequent adverse effects experienced, accounting for over 50% of 186 reactions reported in a survey of 1437 patients. Nausea, vomiting, gastralgia, skin reactions and neurological reactions were the most frequently cited adverse effects, and 3% of patients withdrew from therapy as a result of adverse reactions. Photosensitivity developed in 0.83% of patients in this survey, and in a long term study 11 of 36 patients developed pruriginous and erythematous eruptions on the face and forearms after exposure to sunlight.

Minor changes in laboratory values following pefloxacin treatment have been reported, but these were generally not considered to be drug related. Pefloxacin does not adversely affect the gastrointestinal microflora through selection of resistant species.

Dosage and Administration

The recommended dosage of pefloxacin is 400mg administered twice a day orally with meals or intravenously. Parenteral pefloxacin should be administered as a 1-hour intravenous infusion, with the drug mixed with a 5% glucose solution and not saline. Where appropriate a loading dose of 800mg may be used on starting treatment to achieve steady-state concentrations of the drug. In patients with reduced hepatic function dosage adjustments should be made. Patients with impaired renal function may also require dosage adjustment.

As a result of the pharmacokinetic interactions between pefloxacin and theophylline, it is recommended that theophylline concentrations should be monitored in those patients receiving concomitant treatment. In addition, patients receiving pefloxacin and coumarin should have their clotting times monitored. The absorption of pefloxacin may be reduced by the concomitant administration of antacids, especially those containing aluminium or magnesium ions. A reduction in pefloxacin clearance and an increase in its elimination half-life occur with concomitant cimetidine administration.

Pefloxacin is contraindicated in children or adolescents in the growing phase and the drug should not be administered to pregnant women or nursing mothers.

Keywords

Quinolones Ceftazidime Norfloxacin Nalidixic Acid Antimicrobial Chemotherapy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aldridge KE, Schiro DD, Sanders CV. Pefloxacin (RB 1589): an in vitrocomparison with other oral antimicrobial agents and imipenem. Current Therapeutic Research 40: 1103–1113, 1986Google Scholar
  2. Appelbaum PC, Spangler SK, Sollenberger L. Susceptibility of non-fermentative Gram-negative bacteria to ciprofloxacin, norflox-acin, amifloxacin, pefloxacin and cefpirome. Journal of Antimicrobial Chemotherapy 18: 675–679, 1986PubMedCrossRefGoogle Scholar
  3. Arlet G, Sanson-Le Pors MJ, Casin IM, Ortenberg M, Perol Y. In vitrosusceptibility of 96 Capnocytophagastrains, including a β-lactamase producer, to new β-lactam antibiotics. Antimicrobial Agents and Chemotherapy 31: 1283–1284, 1987PubMedCrossRefGoogle Scholar
  4. Arpi M, Gahrn-Hansen B, Sogaard P, Bentzon MW. Comparative in vitroactivities of pefloxacin, ofloxacin, enoxacin and ciprofloxacin against 256 clinical isolates. Acta Pathologica Microbiologica et Immunologica Scandinavica Section B 95: 141–146, 1987Google Scholar
  5. Auckenthaler R, Michéa-Hamzehpour M, Pechère JC. In-vitroactivity of newer quinolones against aerobic bacteria. Journal of Antimicrobial Chemotherapy 17 (Suppl. B): 29–39, 1986PubMedGoogle Scholar
  6. Badet B, Hughes P, Kohiyama M, Forterre P. Inhibition of DNA replication in vitroby pefloxacin. FEBS Letters 145: 355–359, 1982PubMedCrossRefGoogle Scholar
  7. Baran R, Brun P. Photoonycholysis induced by the fluoroquinolones pefloxacine and ofloxacine. Dermatologica 173: 185–188, 1986PubMedCrossRefGoogle Scholar
  8. Barre J, Houin G, Tillement JP. Dose-dependent pharmacokinetic study of pefloxacin, a new antibacterial agent, in humans. Journal of Pharmaceutical Sciences 73: 1379–1382, 1984PubMedCrossRefGoogle Scholar
  9. Barry AL, Gardiner RV, Packer RR. Resistance to ten different fluoroquinolone antibiotics following in vitro exposures to nalidixic acid. Diagnostic Microbiology and Infectious Disease 6: 77–79, 1987PubMedCrossRefGoogle Scholar
  10. Barry AL, Jones RN. Cross resistance among cinnoxin, ciprofloxacin, DJ-6783, enoxacin, nalidixic acid, norfloxacin and oxolinic acid after in vitroselection of resistant populations. Antimicrobial Agents and Chemotherapy 25: 775–777. 1984PubMedCrossRefGoogle Scholar
  11. Barry AL, Jones RN. Comparative in vitroactivity of amifloxacin and five other fluoroquinolone antimicrobial agents and preliminary criteria for the disk susceptibility test. European Journal of Clinical Microbiology 6: 179–182, 1987PubMedCrossRefGoogle Scholar
  12. Bayer AS, Greenberg DP, Yih J. Correlates of therapeutic efficacy in experimental methicillin-resistant Staphylococcus aureusendocarditis. Chemotherapy 34: 46–55, 1988PubMedCrossRefGoogle Scholar
  13. Bernard E, Dellamonica P, Etesse H, Garraffo R, Beziau H, et al. Efficacy of ofloxacin and pefloxacin for the treatment of bone infections. Reviews of Infectious Diseases 10 (Suppl. 1): 188–189, 1988Google Scholar
  14. Beun GDM, Debrus-Palmans LL, Daniels-Bosman MSM, Blijham GH. Therapy with pefloxacin in febrile neutropenic patients. Reviews of Infectious Diseases 10 (Suppl. 1): 236, 1988CrossRefGoogle Scholar
  15. Benzakour M, Lagarde C, Benevent D, Mourier M, Denis F. Peritonitis during continuous ambulatory peritoneal dialysis. Nephron 50: 175–176, 1988PubMedCrossRefGoogle Scholar
  16. Boerema JBJ. New 4-quinolones in the treatment of urinary tract infections. Pharmaceutisch Weekblad Scientific Edition 8: 46–52, 1986PubMedCrossRefGoogle Scholar
  17. Boerema JBJ, Pauwels R, Scheepers J, Crombach W. Efficacy and safety of pefloxacin in the treatment of patients with complicated urinary tract infections. Journal of Antimicrobial Chemotherapy 17 (Suppl. B): 103–109, 1986PubMedGoogle Scholar
  18. Bouanchaud DH, Rolin O. Bactericidal activity of pefloxacin compared with ten other antibiotics on Staphylococcus aureusand Pseudomonas aeruginosa.Drugs Under Experimental and Clinical Research 10: 669–676, 1984Google Scholar
  19. Brion N, Lessana A, Mosset F, Lefevre JJ, Montay G. Penetration of pefloxacin in human heart valves. Journal of Antimicrobial Chemotherapy 17 (Suppl. B): 89–92, 1986PubMedGoogle Scholar
  20. Buré A, Desplaces N, Pangon B, Dournon E. In vitroactivity of ciprofloxacin, pefloxacin and ofloxacin against Legionella.14th International Congress of Chemotherapy, Tokyo, June 23–28, 1985Google Scholar
  21. Campoli-Richards DM, Monk JP, Price A, Benfield P, Todd PA, et al. Ciprofloxacin: a review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs 35: 373–447, 1988PubMedCrossRefGoogle Scholar
  22. Cantet P, Renaudin H, Quentin C, Bebear C. Activité comparée in vitrode sept quinolones sur Ureaplasma urealyticum.Pathologie Biologie 31: 501–503, 1983PubMedGoogle Scholar
  23. Cardey J, Silvain C, Bouquet S, Breux JP, Becq-Giraudon B, et al. Oral pharmacokinetics and ascitic fluid penetration of pefloxacin in cirrhosis. European Journal of Clinical Pharmacology 33: 469–472, 1987PubMedCrossRefGoogle Scholar
  24. Chin N-X, Novelli A, Neu HC. In vitroactivity of lomefloxacin (SC-47111; NY-198), a difluoroquinolone 3-carboxylic acid, compared with those of other quinolones. Antimicrobial Agents and Chemotherapy 32: 656–662, 1988PubMedCrossRefGoogle Scholar
  25. Clarke AM, Zemcov SJV, Campbell ME. In-vitroactivity of pefloxacin compared to enoxacin, norfloxacin, gentamicin and new β-lactams. Journal of Antimicrobial Chemotherapy 15: 39–44, 1985PubMedCrossRefGoogle Scholar
  26. Coignard S, Renard C, Lortat-Jacob A. Diffusion de la pefloxacine dans le tissu osseux humain. Médecine et Maladies Infectieuses 7: 471–474, 1986CrossRefGoogle Scholar
  27. Contrepois A, Daldoss C, Pangon B, Garaud J-J, Kecir M, et al. Pefloxacin in rabbits: protein binding, extravascular diffusion, urinary excretion and bactericidal effect in experimental endocarditis. Journal of Antimicrobial Chemotherapy 14: 51–57, 1984PubMedCrossRefGoogle Scholar
  28. Courvalin P, Derlot E, Chabbert YA. Cross resistance to quinolone derivatives of Enterobacteriaceae and Pseudomonasmutants selected on pefloxacin and ciprofloxacin. 24th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, 1984Google Scholar
  29. Cullmann W, Stieglitz M, Baars B, Opferkuch W. Comparative evaluation of recently developed quinolone compounds — with a note on the frequency of resistant mutants. Chemotherapy (Basel) 31: 19–28, 1985Google Scholar
  30. Danan G, Montay G, Cunci R, Erlinger S. Pefloxacin kinetics in cirrhosis. Clinical Pharmacology and Therapeutics 38: 439–442, 1985PubMedCrossRefGoogle Scholar
  31. David C, Chaste A, Saison C, Combremont AG. Activité in vitrodes associations de la nétilmicine et de l’amikacine avec la fosfomycine et la péfloxacine sur trente et une souches de Staphylococcus aureusmeticilline-résistantes hétérogénes. Pathologie Biologie 36: 608–612, 1988PubMedGoogle Scholar
  32. Davies BI, Maesen FPV, Teengs JP, Baur C. The quinolones in chronic bronchitis. Pharmaceutisch Weekblad — Scientific Edition 8: 53–59, 1986aPubMedCrossRefGoogle Scholar
  33. Davies BI, Maesen FPV, Teengs JP, Baur C. Neue orale chinolon - Verbindungen bei chronischer bronchitis. Infection 14 (Suppl. 1): 73–78, 1986bCrossRefGoogle Scholar
  34. Davies S, Sparham PD, Spencer RC. Comparative in-vitroactivity of five fluoroquinolones against mycobacteria. Journal of Antimicrobial Chemotherapy 19: 605–609, 1987PubMedCrossRefGoogle Scholar
  35. Debbia E, Schito GC, Nicoletti G, Speciale A. In vitroactivity of pefloxacin against Gram-negative and Gram-positive bacteria in comparison with other antibiotics. Chemoterapia 6: 319–323, 1987Google Scholar
  36. Dellamonica P, Bernard E, Etesse H, Garraffo R. The diffusion of pefloxacin into bone and the treatment of osteomyelitis. Journal of Antimicrobial Chemotherapy 17 (Suppl. B): 93–102, 1986PubMedGoogle Scholar
  37. Delmee M, Avesani V. Comparative in vitroactivity of seven quinolones against 100 clinical isolates of Clostridium difficile.Antimicrobial Agents and Chemotherapy 29: 374–375, 1986PubMedCrossRefGoogle Scholar
  38. Denis F, Mournier M, Adenis JP. Intraocular penetration of pefloxacin into human and rabbit eyes. Aqueous humor and vitreous fluid. Pathologie Biologie 35: 772, 1987PubMedGoogle Scholar
  39. Desnottes JF, Diallo N, Moret G, Santonja R. Effects of subinhibitory concentrations of pefloxacin on the adherence of Staphylococcus aureusto human cells. Drugs Under Experimental and Clinical Research 13: 69–73, 1987PubMedGoogle Scholar
  40. Desnottes JF, Jacotot F, Bruel J, Bassoullet MT, Niel G. Effects of pefloxacin on phagocytosis function of rat macrophages and polymorphonuclear leucocytes. Journal of Antimicrobial Chemotherapy 17 (Suppl. B): 53–57, 1986PubMedGoogle Scholar
  41. Desplaces N, Gutmann L, Acar JF. Treatment of chronic osteomyelitis (CO.) due to Staphylococcusspp. or Gram-negative baeteria with a new quinolone: pefloxacin (PEF). 14th International Congress of Chemotherapy, Kyoto, June 23–28, 1985Google Scholar
  42. Desplaces N, Mamoudy P, Leonard P, Kitzis MD, Gutmann L. Pefloxacin in the treatment of bone and joint infections due to Enterobacteriaceae. 15th International Congress of Chemotherapy, Istanbul, July 20–25, 1987Google Scholar
  43. Dournon E, Rajagopalan P, Vilde JL, Pocidalo JJ. Efficacy of pefloxacin in comparison with erythromycin in the treatment of experimental guinea pig legionellosis. Journal of Antimicrobial Chemotherapy 17 (Suppl. B): 41–48, 1986PubMedGoogle Scholar
  44. Dow J, Chazal J, Frydman AM, Janny P, Woehrle R, et al. Transfer kinetics of pefloxacin into cerebro-spinal fluid after one hour iv infusion of 400mg in man. Journal of Antimicrobial Chemotherapy 17 (Suppl. B): 81–87, 1986PubMedGoogle Scholar
  45. Dow J, Frydman AM, Djebbar F, Gaillot J. Single- and multiple-dose pharmacokinetics of pefloxacin in elderly patients. Reviews of Infectious Diseases 10 (Suppl. 1): 107, 1988Google Scholar
  46. Dubreuil L, Devos J, Romond C, Bryskier A. Sensibilité des anaérobes stricts envers l’ofloxacine, la péfloxacine, l’énoxacine et la norfloxacine. Pathologie Biologie 33: 421–425, 1985PubMedGoogle Scholar
  47. Edlund C, Nord CE. Comparative in vitroactivities of ciprofloxacin, enoxacin, norfloxacin, ofloxacin and pefloxacin against Bacteroides fragilisand Clostridium difficile.Scandinavian Journal of Infectious Diseases 18: 149–151, 1986PubMedCrossRefGoogle Scholar
  48. Edlund C, Nord CE. A review on the impact of 4-quinolones on the normal oropharyngeal and intestinal human microflora. Infection 16: 8–12, 1988PubMedCrossRefGoogle Scholar
  49. Etesse-Carsenti H, Garraffo R, Giaume F, Barbarin A, Bernard E, et al. Cinétique de la diffusion de la péfloxacine dans le tissu osseux humain après perfusion unique de 800mg. Pathologie Biologie 36: 715–718, 1988PubMedGoogle Scholar
  50. Felmingham D, O’Hare MD, Robbins MJ, Wall RA, Williams AH, et al. Comparative in vitrostudies with 4-quinolone antimicrobials. Drugs Under Experimental and Clinical Research 11: 317–329, 1985PubMedGoogle Scholar
  51. Forsgren A, Schlossman SF, Tedder TF. 4-Quinolone drugs affect cell cycle progression and function of human lymphocyte in vitro.Antimicrobial Agents and Chemotherapy 31: 768–773, 1987PubMedCrossRefGoogle Scholar
  52. Fournier G, Mantz JM, Kopferschmitt J, Ghanassia JP. Pefloxacin in the impiric treatment of sepsis of various origin. 15th International Congress of Chemotherapy, Istanbul, July 20–25, 1987Google Scholar
  53. Freland C, Massoubre B, Drugeon HB. Sensibilité de Campylobacter pyloridisvis-à-vis des antibiotiques. Pathologie Biologie 35: 809–812, 1987PubMedGoogle Scholar
  54. Frydman AM, Le Roux Y, Lefebvre MA, Djebbar F, Fourtillan JB, et al. Pharmacokinetics of pefloxacin after repeated intravenous and oral administration (400mg bid) in young healthy volunteers. Journal of Antimicrobial Chemotherapy 17 (Suppl. B): 65–79, 1986PubMedGoogle Scholar
  55. Gevaudan MJ, Mallet MN, Gulian C, Terriou Ph, Lagier P, et al. Étude de la sensibilité de sept espèces de mycobactéries aux nouvelles quinolones. Pathologie 36: 477–481, 1988Google Scholar
  56. Giamarellou H, Galanakis N, Perdikaris G, Tsagaraki Ch. Comparative efficacy of pefloxacin versus ceftazidime in a variety of mostly nosocomial acquired Gram-negative infections. 17th Interscience Conference on Antimicrobial Agents and Chemotherapy, New York, 1987Google Scholar
  57. Gluckman E, Carazzana M, Devergie A, Meletis J, Arlet G, et al. Prevention des infections bactériennes apres greffe de moelle osseuse par antibiotiques oraux a large spectre absorbables (pefloxacine, penecilline) ou non absorbables (cephalosporines, gentamicine, bacitracine). Pathologie Biologie 36: 902–906, 1988PubMedGoogle Scholar
  58. Gordin FM, Hackbarth CJ, Scott KG, Sande MA. Activities of pefloxacin and ciprofloxacin in experimentally induced Pseudomonaspneumonia in neutropenic guinea pigs. Antimicrobial Agents and Chemotherapy 27: 452–454, 1985PubMedCrossRefGoogle Scholar
  59. Griggs D, Lister D, Andrews JM, Wise R. Pharmacokinetics and inflammatory-fluid penetration of pefloxacin. Reviews of Infectious Diseases 10 (Suppl. 1): 98, 1988Google Scholar
  60. Guelpa-Lauras C-C, Perani EG, Giroir A-M, Grosset JH. Activities of pefloxacin and ciprofloxacin against Mycobacterium lepraein the mouse. International Journal of Leprosy 55: 70–77, 1987Google Scholar
  61. Guy H, Caillot D, Solary E, Bielefeld Ph, Portier H, et al. Association d’une céphalosporine de troisième génération (céfo-taxime ou ceftazidime) et d’une nouvelle quinolone (péfloxacine) dans le traitement des épisodes fébriles des malades neutropéniques (37 cas). La Presse Médicale 16: 2172–2175, 1987PubMedGoogle Scholar
  62. Hajji M, El Molaghri N, Benbachir M, Marhoum El Filali K, Himmich H. Prospective randomised comparative trial of pefloxacin versus cotrimoxazole in the treatment of typhoid fever in adults. European Journal of Clinical Microbiology and Infectious Diseases 7: 361–363, 1988CrossRefGoogle Scholar
  63. Henwood JM, Monk JP. Enoxacin: a review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs 36: 32–66, 1988PubMedCrossRefGoogle Scholar
  64. Höffler D, Schäfer I, Koeppe P, Sörgel F. Pharmacokinetics of pefloxacin in normal and impaired renal function. Arzneimittel-Forschung 38: 739–743, 1988PubMedGoogle Scholar
  65. Høiby N. Clinical uses of nalidixic acid analogues: the fluoroquinolones. European Journal of Clinical Microbiology 5: 138–140, 1986PubMedCrossRefGoogle Scholar
  66. Holmes B, Brogden RN, Richards DM. Norfloxacin: a review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs 30: 482–513, 1985PubMedCrossRefGoogle Scholar
  67. Hooper DC, Wolfson JS, Ng EY, Swartz MN. Mechanisms of action and resistance to ciprofloxacin. American Journal of Medicine 82 (Suppl. 4A): 12–20, 1987PubMedGoogle Scholar
  68. Husson MO, Izard D, Bouillet L, Leclerc H. In vitro activity of pefloxacin. Drugs Under Experimental and Clinical Research 12: 313–317, 1986PubMedGoogle Scholar
  69. Inoue S, Ohue T, Yanogishi J, Nakamura S, Shimizu M. Mode of incomplete cross-resistance among pipemidic, piromidic and nalidixic acids. Antimicrobial Agents and Chemotherapy 14: 240–245, 1978PubMedCrossRefGoogle Scholar
  70. Janin N, Meugnier H, Desnottes JF, Woehrle R, Fleurette J. Recovery of pefloxacin in saliva and feces and its action on oral and fecal floras of healthy volunteers. Antimicrobial Agents and Chemotherapy 31: 1665–1668, 1987PubMedCrossRefGoogle Scholar
  71. Joly-Guillou ML, Bergogne-Berezin E. In vitroactivity of antimicrobial agents against Acinetobacter calcoaceticus.Drugs Under Experimental and Clinical Research 12: 949–952, 1986PubMedGoogle Scholar
  72. Jones BM, Geary I, Lee ME, Duerden BI. Activity of pefloxacin and thirteen other antimicrobial agents in vitroagainst isolates from hospital and genitourinary infections. Journal of Antimicrobial Chemotherapy 17: 739–746, 1986PubMedCrossRefGoogle Scholar
  73. Jorgensen JH, Doern GV, Thonsberry C, Preston DA, Redding JS, et al. Susceptibility of multiply resistant Haemophilus influenzaeto newer antimicrobial agents. Diagnostic Microbiology and Infectious Disease 9: 27–32, 1988PubMedCrossRefGoogle Scholar
  74. Jungers P, Ganeval D, Hannedouche T, Prieur B, Montay G. Steady-state levels of pefloxacin and its metabolites in patients with severe renal impairment. European Journal of Clinical Pharmacology 33: 463–467, 1987PubMedCrossRefGoogle Scholar
  75. Kayser FM. The quinolones: mode of action and mechanisms of resistance. Research and Clinical Forums 7: 17–27, 1985Google Scholar
  76. King A, Phillips I. The comparative in-vitroactivity of pefloxacin. Journal of Antimicrobial Chemotherapy 17 (Suppl. B): 1–10, 1986PubMedCrossRefGoogle Scholar
  77. Korinek AM, Montay G, Bianchi A, Guggiari M, Grob R, et al. Penetration of pefloxacin into human brain tissue. Reviews of Infectious Diseases 10 (Suppl. 1): 257, 1988Google Scholar
  78. Lambert T, Megraud F, Gerbaud G, Courvalin P. Susceptibility of Campylobacter pyloridisto 20 antimicrobial agents. Antimicrobial Agents and Chemotherapy 30: 510–511, 1986PubMedCrossRefGoogle Scholar
  79. Laredo Filho J. Efficacy and safety evaluation of pefloxacin in the treatment of chronic osteitis, with a prolonged follow-up. 15th International Congress of Chemotherapy, Istanbul, July 20–25, 1987Google Scholar
  80. Lauwers S, Vincken W, Naessens A, Pierard D. Efficacy and safety of pefloxacin in the treatment of severe infections in patients hospitalised in intensive care units. Journal of Antimicrobial Chemotherapy 17 (Suppl. B): 111–115, 1986PubMedGoogle Scholar
  81. Leleux A, Gerain J, Daneau M, Van der Auwera P, Meunier F. Pefloxacin for selective decontamination in neutropenic cancer patients (NCPTS). 15th International Congress of Chemotherapy, Istanbul, July 20–25, 1987Google Scholar
  82. Le Noc P, Croize J, Bryskier A. Activité antibactérienne in vitrodu cefpirome en association avec quatre aminoglycosides et deux fluoroquinolones. Pathologie Biologie 36: 762–767, 1988PubMedGoogle Scholar
  83. Limb DI, Dabbs DJW, Spence RC. In-vitroselection of bacteria resistant to the 4-quinolone agents. Journal of Antimicrobial Chemotherapy 19: 65–71, 1987PubMedCrossRefGoogle Scholar
  84. Lombard JY, Descotes J, Eyraud A, Evroux JC. Influence of pefloxacin on human neutrophil chemotactic response following oral treatment. Therapie 42: 17–20, 1987PubMedGoogle Scholar
  85. Lopitaux R, Hermet R, Sirot J, Filiu P, Terver S. Tolérance de la pefloxacine au cours du traitement d’une série d’infections ostéo-articulaires. Therapie 40: 349–352, 1985PubMedGoogle Scholar
  86. Lucet J-C, Tilly H, Lerebours G, Gres J-J, Piguet H. Neurological toxicity related to pefloxacin. Journal of Antimicrobial Chemotherapy 21: 811–812, 1988PubMedCrossRefGoogle Scholar
  87. Maesen FPV, Davies BI, Teengs JP. Pefloxacin in acute exacerbations of chronic bronchitis. Journal of Antimicrobial Chemotherapy 16: 379–388, 1985PubMedCrossRefGoogle Scholar
  88. Martin C, Charrel J, Mallet MN, Gouin F. Étude clinique et bactériologique d’une nouvelle quinolone, la péfloxacine, dans les infections sévères. Médecine et Maladies Infectieuses 16: 53–56, 1986CrossRefGoogle Scholar
  89. Martin C, Gouin F, Fourrier F, Junginger W, Prieur BL. Pefloxacin in the treatment of nosocomial lower respiratory tract infections in intensive care patients. Journal of Antimicrobial Chemotherapy 21: 795–799, 1988PubMedCrossRefGoogle Scholar
  90. McEwan SR, Davey PG. Ciprofloxacin and tenosynovitis. Lancet 2: 900, 1988 au]Meunier F, Aoun M, Delbaye N, Van der Auwera P, Klastersky J. Therapy of Gram-negative bacillary septicaemia with pefloxacin in non neutropenic patients. 2nd International Symposium on New Quinolones, Geneva, August 25–27, 1988PubMedCrossRefGoogle Scholar
  91. Michéa-Hamzehpour M, Auckenthaler R, Regamey P, Pechère J-C. Resistance occurring after fluoroquinolone therapy of experimental Pseudomonas aeruginosaperitonitis. Antimicrobial Agents and Chemotherapy 31: 1803–1808, 1987PubMedCrossRefGoogle Scholar
  92. Michel-Briand Y, Uccelli V, Laporte J-M, Plesiat P. Elimination of plasmids from Enterobacteriaceae by 4-quinolone derivatives. Journal of Antimicrobial Chemotherapy 18: 667–674, 1986PubMedCrossRefGoogle Scholar
  93. Monk J-P, Campoli-Richards DM. Ofloxacin: a review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs 33: 346–391, 1987PubMedCrossRefGoogle Scholar
  94. Montay G, Goueffon Y, Roquet F. Absorption, distribution, metabolic fate and elimination of pefloxacin mesylate in mice, rats, dogs, monkeys and humans. Antimicrobial Agents and Chemotherapy 25: 463–472, 1984PubMedCrossRefGoogle Scholar
  95. Montay G, Jacquot C, Bariety C, et al. Pharmacokinetics of pefloxacin in renal insufficiency. European Journal of Clinical Pharmacology 29: 345, 1985PubMedCrossRefGoogle Scholar
  96. Montay G, Tassel JP. Improved high-performance liquid Chromatographic determination of pefloxacin and its metabolite nor-floxacin in human plasma and urine. Journal of Chromatography 339: 214–218, 1985PubMedCrossRefGoogle Scholar
  97. Morel C, Vergnaud M, Langeard V, Benard Y. Péfloxacine: diffusion dans le mucus bronchique. Pathologie Biologie 32: 516–519, 1985Google Scholar
  98. Moskowitz B, Djebbar F. Pefloxacin in the treatment of serious and/or difficult to treat infections. 15th International Congress of Chemotherapy, Istanbul, July 20–25, 1987Google Scholar
  99. NCCLS. Thornsberry C, et al. (Eds) Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically: approved standard. National Committee for Clinical Laboratory Standards Publication M7-A, Villanova Pa., NCCLS, 1985Google Scholar
  100. Neu HC, Chin NX, Labthavikul P, Saha G. In vitroactivity of pefloxacin compared to that of quinolones and other antimicrobial agents. Chemioterapia 3: 235–241, 1984PubMedGoogle Scholar
  101. Neuman M. Comparative pharmacokinetic parameters of new systemic fluoroquinolones: a review. Chemioterapia 6: 105–112, 1987PubMedGoogle Scholar
  102. Neuman M. Clinical pharmacokinetics of the newer antibacterial 4-quinolones. Clinical Pharmacokinetics 14: 96–121, 1988PubMedCrossRefGoogle Scholar
  103. Niki Y, Soejima R, Kawane H, Sumi M, Umeki S. New synthetic quinolone antibacterial agents and serum concentration of theophylline. Chest 92: 663–669, 1987PubMedCrossRefGoogle Scholar
  104. Nowicki M, Paucod JC, Bornstein N, Meugnier H, Isoard P, et al. Comparative efficacy of five antibiotics on experimental airborne legionellosis in guinea pigs. Journal of Antimicrobial Chemotherapy 22: 513–519, 1988PubMedCrossRefGoogle Scholar
  105. Pallavicini F, Antinori A, Federico G, Fantoni M, Nervo P. Influence of two quinolones, ofloxacin and pefloxacin, on human myelopoiesis in vitro.Antimicrobial Agents and Chemotherapy 33: 122–123, 19Google Scholar
  106. Pattyn SR, Van Caekenberghe DL, Verhoeven JR. In vitroactivity of five new quinolones against cultivable mycobacteria. European Journal of Clinical Microbiology 6: 572–573, 1987PubMedCrossRefGoogle Scholar
  107. Peixoto S. Pefloxacin versus ampicillin + gentamicin in the treatment of upper gynecological tract infections. 15th International Congress of Chemotherapy, Istanbul, July 20–25, 1987Google Scholar
  108. Periti P, Mazzei T, Nicoletti P. Comparative in vitroactivity of ciprofloxacin, ofloxacin and pefloxacin against resistant clinical isolates. Chemioterapia 6: 75–78, 1987PubMedGoogle Scholar
  109. Pfeiffer M, Treutner KP. Pefloxacin in the treatment of severe therapy-resistant infections in general surgery. 15th International Congress of Chemotherapy, Istanbul, July 20–25, 1987Google Scholar
  110. Piddock LJV, Diver JM, Wise R. Cross-resistance of nalidixic acid resistant Enterobacteriaceae to new quinolones and other antimicrobials. European Journal of Microbiology 5: 411–415, 1986CrossRefGoogle Scholar
  111. Piddock LJV, Wijnands WJA, Wise R. Quinolone/ureidopeni-cillin cross-resistance. Lancet 2: 907, 1987PubMedCrossRefGoogle Scholar
  112. Preheim LC, Cuevas TA, Roccaforte JS, Mellencamp MA, Bittner MJ. Oral ciprofloxacin in the treatment of elderly patients with complicated urinary tract infections due to trimethoprim/ sulphamethoxazole-resistant bacteria. American Journal of Medicine 82 (Suppl. 4A): 295–300, 1987PubMedGoogle Scholar
  113. Quentin C, Saivin S, Lafferriere C, Noury P, Bebear C. In vitroactivity of fosfomycin combined with rifampicin, pefloxacin and imipenem against staphylococci: a study by the time-kill curve method. Drugs Under Experimental and Clinical Research 13: 219–224, 1987PubMedGoogle Scholar
  114. Quentin R, Koubaa N, Cattier B, Gavignet M, Goudeau A. In vitroactivities of five new quinolones against 88 genital and neonatal Haemophilusisolates. Antimicrobial Agents and Chemotherapy 32: 147–149, 1988PubMedCrossRefGoogle Scholar
  115. Ramirez FJH, Loperena HH, Regalado AS, Sánchez CJ, Valdez AC. Estudio clinico abierto randomizado para determinar eficacia y seguridad de pefloxacina vs cefotaxima en el tratamiento de infecciones severas. Investigation Médica Internacional 15: 75–84, 1988Google Scholar
  116. Renaudin H, Quentin C, de Barbeyrac C, Bebear C. Activité in vitrode nouvelles quinolones sur les mycoplasmes pathogènes pour l’homme. Pathologie Biologie 36: 496–499, 1988PubMedGoogle Scholar
  117. Ridgway GL. Antimicrobial chemotherapy of chlamydial infection: where next? European Journal of Clinical Microbiology 5: 550–553, 1986PubMedCrossRefGoogle Scholar
  118. Roche Y, Gougerot-Pocidalo M-A, Fay M, Etienne D, Forest N, et al. Comparative effects of quinolones on human mononuclear leucocyte functions. Journal of Antimicrobial Chemotherapy 19: 781–790, 1987PubMedCrossRefGoogle Scholar
  119. Rodante O. Clinical experience with pefloxacin in severe systemic infections in intensive care units. 14th International Congress of Chemotherapy, Kyoto, Jun 23–28, 1985Google Scholar
  120. Rolin O, Huet Y, Bouanchaud DH. Comparative efficacy of pefloxacin and six other antimicrobial agents on Staphylococcus aureusexperimental abscesses. Journal of Antimicrobial Chemotherapy 17 (Suppl. B): 49–52, 1986PubMedGoogle Scholar
  121. Ronco E, Pilliot J. A comparative study of the in vitroantista-phylococcal activity of norfloxacin and pefloxacin using 312hospital strains. Pathologie Biologie 33: 381–384, 1985PubMedGoogle Scholar
  122. Ruckdeschel G, Ehret W, Ahl A. Susceptibility of Legionellaspp. to quinolone derivatives and related organic acids. European Journal of Clinical Microbiology 3: 373, 1984PubMedCrossRefGoogle Scholar
  123. Salvanet A, Fisch A, Lafaix C, Montay G, Dubayle P, et al. Pefloxacin concentrations in human aqueous humour and lens. Journal of Antimicrobial Chemotherapy 18: 199–201, 1986PubMedCrossRefGoogle Scholar
  124. Sande M, Acar JF, Nishino T. A new quinolone compound: antimicrobial and clinical activity. 14th International Congress of Chemotherapy, Kyoto, June 23–28, 1985Google Scholar
  125. Sanson-Le Pors MJ, Casin IM, Thebault MC, Arlet G, Perol Y. In vitroactivities of U-63366, a spectinomycin analogue; roxithromycin (RU 28965), a new macrolide antibiotic; and five quinolone derivatives against Haemophilus ducreyi.Antimicrobial Agents and Chemotherapy 30: 512–513, 1986CrossRefGoogle Scholar
  126. Segev S, Pitlick SD, Rubinstein E. Pefloxacin for Gram-negative infections in compromised patients. 15th International Congress of Chemotherapy, Istanbul, July 20–25, 1987Google Scholar
  127. Segev S, Lev B, Barzilai A, Keren G. Pefloxacin in the treatment of severe infections. Reviews of Infectious Diseases 10 (Suppl. 1): 236–237, 1988CrossRefGoogle Scholar
  128. Simor AE, Ferro S, Low DE. Comparative in vitroactivities of six new fluoroquinolones and other oral antimicrobial agents against Campylobacter pylori.Antimicrobial Agents and Chemotherapy 33: 108–109, 1989PubMedCrossRefGoogle Scholar
  129. Smith CR. The adverse effects of fluoroquinolones. Journal of Antimicrobial Chemotherapy 19: 709–712, 1987PubMedCrossRefGoogle Scholar
  130. Smith JT. Mutational resistance to 4-quinolone antibacterial agents. European Journal of Clinical Microbiology 3: 347–350, 1984PubMedCrossRefGoogle Scholar
  131. Smith JT, Ratcliffe NT. Effect of pH and magnesium on the in vitro activity of ciprofloxacin. In Neu HC & Wenta H (Eds) Proceedings of the 1st International Ciprofloxacin Workshop, Amsterdam, pp. 12–16, Excerpta Medica, 1986Google Scholar
  132. Smith SM. In vitrocomparisons of A-56619, A-56620, amifloxacin, ciprofloxacin, enoxacin, norfloxacin, and ofloxacin against methicillin-resistant Staphylococcus aureus.Antimicrobial Agents and Chemotherapy 29: 325–326, 1986PubMedCrossRefGoogle Scholar
  133. Sörgel F, Koch U, Metz R, Staphan U. Cimetidine inhibits the hepatic metabolism of pefloxacin. 26th International Conference on Antimicrobial Agents and Chemotherapy, New Orleans, 28 September–1 October, 1986Google Scholar
  134. Sörgel F, Mahr G, Stephan U, Koch HU, Wiesemann HG. Absolute bioavailability and pharmacokinetics of pefloxacin in healthy volunteers. Reviews of Infectious Diseases 10 (Suppl. 1): 93, 1988Google Scholar
  135. Soussy CJ, Leclercq R, Duval J. Activité antibactérienne in vitrodes associations pipéracilline/quinolones. Pathologie Biologie 36: 357–360, 1988PubMedGoogle Scholar
  136. Stübner G, Weinrich W, Brands U. Study of the cerebrospinal fluid in patients with bacterial meningitis. Infection 14 (Suppl. 4): S254–S255, 1986CrossRefGoogle Scholar
  137. Sturm AW. Comparison of antimicrobial susceptibility patterns of fifty-seven strains of Haemophilus ducreyiisolated in Amsterdam from 1978 to 1985. Journal of Antimicrobial Chemotherapy 19: 187–191, 1987PubMedCrossRefGoogle Scholar
  138. Suerbaum S, Leving H, Kroll H-P, Gmeiner J, Opferkuch W. Influence of β-lactam antibiotics and ciprofloxacin on cell envelope of Escherichia coli.Antimicrobial Agents and Chemotherapy 31: 1106–1110, 19Google Scholar
  139. Suermondt G, Denamur E, Laurans G, Orfila J. Etude in vitrode trois fluoroquinolones sur Branhamella catarrhalis.Pathologie Biologie 36: 647–650, 19Google Scholar
  140. Texier-Maugein J, Mormède M, Fourche J, Bébéar C. In vitroactivity of four fluoroquinolones against eighty-six isolates of mycobacteria. European Journal of Clinical Microbiology 6: 584–586, 1987PubMedCrossRefGoogle Scholar
  141. Thabaut A, Meyran M. Comparative bactericidal activity of new quinolones and other antibiotics. International Symposium on New Quinolones, Geneva, 1986Google Scholar
  142. Thauvin C, Lemeland J-F, Humbert G, Fillastre J-P. Efficacy of pefloxacin-fosfomycin in experimental endocarditis caused by methicillin-resistant Staphylococcus aureus.Antimicrobial Agents and Chemotherapy 32: 919–921, 19Google Scholar
  143. Turgeon PL, Desrochers C, Mantha R. Comparative in vitroactivity of fluoroquinolones and other parenteral antimicrobial agents against urinary bacterial isolates and oxacillin-resistant Staphylococcus aureus.Current Therapeutic Research 41: 670–678, 1987bGoogle Scholar
  144. Turgeon PL, Gaudreau CL, Mantha R. Comparative in vitroactivity of four quinolones and four other agents against enteropathogens. Current Therapeutic Research 4: 584–588, 1987aGoogle Scholar
  145. Van der Auwera P. The immunomodulating effects of antibiotics. Current Opinion in Infectious Diseases 1: 363–374, 1988CrossRefGoogle Scholar
  146. Van der Auwera P, Grenier P, Glupczynski Y, Pierard D. In vitroactivity of lomefloxacin in comparison with pefloxacin and ofloxacin. Journal of Antimicrobial Chemotherapy, in press, 1989Google Scholar
  147. Van der Auwera P, Husson M, Klastersky J. Bactericidal activity and killing rate of serum in volunteers receiving pefloxacin alone or in combination with ceftazidime, piperacillin, or mezlocillin against Pseudomonas aeruginosa. Journal of Antimicrobial Chemotherapy 21: 49–55, 1988PubMedCrossRefGoogle Scholar
  148. Van der Auwera P, Klastersky J, Lieppe S, Husson M, Lauzon D, Pascual Lopez A. Bactericidal activity and killing rate of serum from volunteers receiving pefloxacin alone or in combination with amikacin. Antimicrobial Agents and Chemotherapy 29: 230–234, 1986PubMedCrossRefGoogle Scholar
  149. Van der Auwera P, Scorneaux B. In vitrosusceptibility of Campylobacter jejunito 27 antimicrobial agents and various combinations of β-lactams with clavulanic acid or sulbactam. Antimicrobial Agents and Chemotherapy 28: 37–40, 1985PubMedCrossRefGoogle Scholar
  150. Vanderdonckt J. Pefloxacin in the treatment of lower respiratory tract infections in geriatrics. Journal of International Medical Research 15: 234–239, 1987PubMedGoogle Scholar
  151. Vanderdonckt J, Cordier R, Hillebrand A. Clinical evaluation of pefloxacin in hospital acquired lower respiratory tract infections. 15th International Congress of Chemotherapy, Istanbul, July 20–25, 1987Google Scholar
  152. Vanhoof R, Hubrechts JM, Roebben E, Nyssen HJ, Nulens E, et al. The comparative activity of pefloxacin, enoxacin, ciprofloxacin and 13 other antimicrobial agents against enteropathogenic microorganisms. Infection 14: 294–298, 1986PubMedCrossRefGoogle Scholar
  153. Van Roosbroeck RJ, Provinciael DR, Van Caekenberghe DL. Activity of the newer quinolones against Chlamydia trachomatis.British Journal of Venereal Diseases 60: 350, 1984PubMedGoogle Scholar
  154. Van Saene JJM, Van Saene HKF, Geitz JN, Tanko-Smit NJPh, Lerk CF. Quinolones and colonisation resistance in human volunteers. Pharmaceutisch Weekblad — Scientific Edition 8: 67–71, 1986PubMedCrossRefGoogle Scholar
  155. Vargas FS, Fiss E, Cukier A, Maia F, Saad E, et al. Pefloxacin treatment of severe lower respiratory tract infections. 15th International Congress of Chemotherapy, Istanbul, July 20–25, 1987Google Scholar
  156. Verbist L. In-vitroactivity of pefloxacin against micro-organisms multiply resistant to β-lactam antibiotics and aminoglycosides. Journal of Antimicrobial Chemotherapy 17 (Suppl. B): 11–17, 1986PubMedGoogle Scholar
  157. Verschraegen G, Claeys G, Van den Abeele AM. Comparative in vitroactivity of the new quinolone fleroxacin (RO23-6240). European Journal of Clinical Microbiology and Infectious Diseases 7: 63–66, 1988CrossRefGoogle Scholar
  158. Vinceneux P, Weber P, Gaudin H, Boussougant Y. Diminution de l’absorption de la pefloxacine par les pausements gastriques. La Presse Medicale 15: 1826, 1986PubMedGoogle Scholar
  159. Wall RA, Mabey DCW, Bello CSS, Felmingham D. The comparative in-vitroactivity of twelve 4-quinolone antimicrobials against Haemophilus ducreyi.Journal of Antimicrobial Chemotherapy 16: 165–168, 1985PubMedCrossRefGoogle Scholar
  160. Webberley JM, Andrews JM, Ashby JP, McLeod A, Wise R. Pharmacokinetics and tissue penetration of orally administered pefloxacin. European Journal of Clinical Microbiology 6: 521–524, 1987PubMedCrossRefGoogle Scholar
  161. Webberley JM, Donovan I, Wise R, Ashby J. Intraperitoneal penetration of pefloxacin. European Journal of Clinical Microbiology and Infectious Diseases 7: 207–208, 1988CrossRefGoogle Scholar
  162. Weisser J, Wiedemann B. Elimination of plasmids by new 4-quinolones. Antimicrobial Agents and Chemotherapy 28: 700–702, 1985PubMedCrossRefGoogle Scholar
  163. Wijnands WJA. The fluoroquinolones in the treatment of lower respiratory tract infections. Pharmaceutical, clinical and bacteriological aspects. PhD thesis, University of Nijmegan, Nijmegan, 1987Google Scholar
  164. Wijnands WJA, Vree TB. Interaction between the fluoroquinolones and the bronchodilator theophylline. Journal of Antimicrobial Chemotherapy 22 (Suppl. C): 104–109, 1988Google Scholar
  165. Wijnands WJA, Vree TB, Baars AM, Van Herwaarden CLA. Steady-state kinetics of the quinolone derivatives ofloxacin, enoxacin, ciprofloxacin and pefloxacin during maintenance treatment with theophylline. Drugs 34 (Suppl. 1): 159–169, 1987PubMedCrossRefGoogle Scholar
  166. Wijnands WJA, Vree TB, Van Herwaarden CLA. The influence of quinolone derivatives on theophylline clearance. British Journal of Clinical Pharmacology 22: 677–683, 1986PubMedCrossRefGoogle Scholar
  167. Willems FThC, Boerema JBJ, Summeren TRKM. The in-vitrocomparative activity of quinolones against bacteria from urinary tract infections in general practice. Journal of Antimicrobial Chemotherapy 17: 69–73, 1986PubMedCrossRefGoogle Scholar
  168. Wittenberger R, Bauernfeind A. Treatment of urinary tract infections with pefloxacin: efficacy, safety and pharmacokinetics. 14th International Congress of Chemotherapy, Kyoto, June 23–28, 1985Google Scholar
  169. Wittke R, Schmidt P, Wipprecht H. Pefloxacin in the treatment of surgically related infections in the elderly. 15th International Congress of Chemotherapy, Istanbul, July 20–25, 1987Google Scholar
  170. Wolff M, Boutron L, Singlas E, Clair B, Decazes JM, et al. Penetration of ciprofloxacin into cerebrospinal fluid of patients with bacterial meningitis. Antimicrobial Agents and Chemotherapy 31: 899–902, 1987PubMedCrossRefGoogle Scholar
  171. Wolff M, Pangon B, Regnier B, Rouveix E, Bauchet J, et al. Traitement de septicémies et endocardites par la péfloxacine. La Presse Médicale 15: 471–474, 1986PubMedGoogle Scholar
  172. Wolff M, Regnier B, Nkam M, et al. Pefloxacin penetration into cerebrospinal fluid in patients with bacterial meningitis. Program and Abstracts of the 23rd ICAAC, Las Vegas, Oct 24–26, 1983Google Scholar
  173. Wolff M, Regnier B, Daldoss C, Nkam M, Vachon F. Penetration of pefloxacin into cerebrospinal fluid of patients with meningitis. Antimicrobial Agents and Chemotherapy 26: 289–291, 1984PubMedCrossRefGoogle Scholar
  174. Yamagishi J, Yoshida H, Yamayoshi M, Nakamura S. Nalidixic acid-resistant mutations of the gyrB gene of E. coli.Molecular and General Genetics 204: 367–373, 1986PubMedCrossRefGoogle Scholar
  175. Zuccarelli M, Simeon de Buochberg M, Maillols M, Armynot du Chatelet AM, Attisso MA. Cinétiques de bactericidie comparées de la ciprofloxacine, de l’ofloxacine et de la péfloxacine seules et en association sur des souches streptocoques du groupe D. Pathologie Biologie 36: 403–409, 1988PubMedGoogle Scholar

Copyright information

© ADIS Press Limited 1989

Authors and Affiliations

  • John P. Gonzalez
    • 1
  • Julian M. Henwood
    • 1
  1. 1.ADIS Press International LimitedManchester International Office CentreWythenshaweEngland

Personalised recommendations