Drug Safety

, Volume 13, Issue 6, pp 343–358 | Cite as

Tolerability of Fluoroquinolone Antibiotics

Past, Present and Future
  • Peter Ball
  • Glenn Tillotson
Review Article Drug Experience


New fluoroquinolones have been in clinical use for 10 years and have an excellent record of safety and tolerance. The main elements of their adverse reaction profile were predictable from human experience with precursor naphthyridines and quinolones, and from toxicological studies in animals. Thus gastrointestinal reactions (1 to 5%), skin disturbances (less than 2.5%) and central nervous system (CNS) effects (usually around 1 to 2%) were anticipated. Individual group members exhibit particular properties in relation to their chemical structures, for example the phototoxicity associated with 8-halogenation of the nucleus and found to be a particular problem with lomefloxacin and sparfloxacin. Other members, for example ofloxacin, are linked to a higher than usual incidence of CNS reactions and psychological disturbance. However, despite increasing usage, none of the present group have been implicated in joint damage in children, which had been a major concern following reports of this effect in juvenile animals in chronic toxicity studies. Furthermore, intravenous formulations appear to have no associated increase in toxicity. Crystalluria with associated renal damage, originally thought likely to limit intravenous dosage, has not proved to be a problem in humans. Clinically significant interactions may occur but, as with those involving various NSAIDs and potentially leading to convulsions, they have been defined and are thus avoidable.

Postmarketing surveillance studies and prescription event monitoring have largely confirmed the limited adverse reaction profile defined during clinical trials. However, some unexpected reactions have appeared after launch, most notably the episodes of haemolysis, renal failure and hypoglycaemia which led to the withdrawal of temafloxacin. These effects have not been observed with other fluoroquinolones. However, severe tendinitis appears to be a group effect, albeit rare, and anaphylactoid reactions have been reported with several of the fluoroquinolone group, often in AIDS patients.

The new fluoroquinolones are essentially a well tolerated group of antibacterials, the benefits of which clearly outweigh their disadvantages in a wide range of indications. Clinical efficacy has been a larger determinant of which members have succeeded in the marketplace than potential toxicity. However, the lesser potential for adverse effects of some of the class, e.g. norfloxacin, ofloxacin and ciprofloxacin, has undoubtedly led to their more widespread use. For others, e.g. enoxacin, limited clinical utility and a perception of increased toxicity have resulted in sidelining. There remains the potential for development of safer and yet more active fluoroquinolones via chemical manipulation both of the nucleus and the side chain substituents.


Adis International Limited Ofloxacin Levofloxacin Norfloxacin Nalidixic Acid 
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  1. 1.
    Domagala JM. Structure-activity and structure-side-effect relationships for the quinolone antibacterials. J Antimicrob Chemother 1994; 33: 685–706PubMedGoogle Scholar
  2. 2.
    Schluter G. Ciprofloxacin: review of potential toxicologic effects. Am J Med 1987; 82 Suppl. 4A: 91–3Google Scholar
  3. 3.
    Cahal DA. Reactions to nalidixic acid. BMJ 1965; 2: 590PubMedGoogle Scholar
  4. 4.
    Boreus LO, Sundstrom B. Intracranial hypertension in a child during treatment with nalidixic acid. BMJ 1967; 2: 744PubMedGoogle Scholar
  5. 5.
    Mathew TH. Nalidixic acid. Med J Aust 1966; 2: 243Google Scholar
  6. 6.
    Tafani O, Mazoli M, Landini G, et al. Fatal acute immune haemolytic anaemia caused by nalidixic acid. BMJ 1982; 285: 936–7PubMedGoogle Scholar
  7. 7.
    Janknegt R. Drug interactions with quinolones. J Antimicrob Chemother 1990; 26 Suppl. D: 7–29PubMedGoogle Scholar
  8. 8.
    Blum MD, Graham DJ, McCloskey CA. Temafloxacin syndrome: review of 95 cases. Clin Infect Dis 1994; 18: 946–50PubMedGoogle Scholar
  9. 9.
    Jungst G, Mohr R. Overview of post-marketing experience with ofloxacin in Germany. J Antimicrob Chemother 1988; 22 Suppl. C: 167–75PubMedGoogle Scholar
  10. 10.
    Wijnands WJA, Vree TB, van Herwaarden CLA. The influence of quinolone derivatives on theophylline clearance. Br J Clin Pharmacol 1986; 22: 677–83PubMedGoogle Scholar
  11. 11.
    Polk R. Drug-drug interactions with ciprofloxacin and other fluoroquinolones. Am J Med 1989; 87 Suppl. 5A: 76–81Google Scholar
  12. 12.
    Davis R, Bryson HM. Levofloxacin: a review of its antibacterial activity, pharmacokinetics and therapeutic efficacy. Drugs 1994; 47: 677–700PubMedGoogle Scholar
  13. 13.
    Ball P. Long term use of quinolones and their safety. Rev Infect Dis 1989; 11 Suppl. 5: S1365–70PubMedGoogle Scholar
  14. 14.
    Kennedy N, Fox R, Uiso L, et al. Safety profile of ciprofloxacin during long-term therapy for pulmonary tuberculosis. J Antimicrob Chemother 1993; 32: 897–902PubMedGoogle Scholar
  15. 15.
    Ball AP. Ciprofloxacin: an overview of adverse experiences. J Antimicrob Chemother 1986; 18 Suppl. D: 187–93PubMedGoogle Scholar
  16. 16.
    Norrby SR, Pernet AG. Assessment of adverse events during drug development: experience with temafloxacin. J Antimicrob Chemother 1991; 20 Suppl. C: 111–9Google Scholar
  17. 17.
    Geddes AM. Safety of fleroxacin in clinical trials. Am J Med 1993; 94 Suppl. 3A: S201–3Google Scholar
  18. 18.
    Bruch K, Blomer R. Efficacy and safety of ofloxacin in elderly patients. Int J Clin Pharm Res 1987; 7: 195–8Google Scholar
  19. 19.
    Pernet AG. Temafloxacin: a safe antibiotic for the elderly, patients with co-morbidities, and other special populations. Am J Med 1991; 91 Suppl. 6A: 162–5Google Scholar
  20. 20.
    Sawada M, Saishu Y, Hayashi S, et al. Post-marketing surveillance of levofloxacin in Japan. [abstract 2256]. 19th International Congress of Chemotherapy. Can J Infect Dis 1995: 6 Suppl. C: 385CGoogle Scholar
  21. 21.
    Fass RJ. Adverse reactions associated with quinolones. Quinolones Bull 1987; 3: 5–6Google Scholar
  22. 22.
    Wang C, Sabbaj J, Corrado M, et al. World-wide experience with norfloxacin: efficacy and safety. Scand J Infect Dis Suppl 1986; 48: 81–9PubMedGoogle Scholar
  23. 23.
    Gonzalez JP, Henwood JM. Pefloxacin: a review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs 1989; 37: 628–68PubMedGoogle Scholar
  24. 24.
    Schacht P, Arcieri G, Branolte J, et al. Worldwide clinical data on efficacy and safety of ciprofloxacin. Infection 1988; 16 Suppl. 1: 29–43Google Scholar
  25. 25.
    Rizk E. The US clinical experience with lomefloxacin, a new once-daily fluoroquinolone. Am J Med 92;Suppl. 4A: 130S–5SGoogle Scholar
  26. 26.
    Carbon C, Rubinstein E. Sparfloxacin monograph. Chester: Adis International Ltd, 1994Google Scholar
  27. 27.
    Urinary Tract Infection Study Group. Coordinated multicenter study of norfloxacin versus trimethoprim-sulphamethoxazole treatment of symptomatic urinary tract infection. J Infect Dis 1987; 155: 170–7Google Scholar
  28. 28.
    Rubinstein E, Potgieter P, Davey P, et al. The use of fluoroquinolones in neutropenic patients: analysis of adverse effects. J Antimicrob Chemother 1994; 34: 7–19PubMedGoogle Scholar
  29. 29.
    Echols RM, Oliver MK. Ciprofloxacin safety relative to temafloxacin and lomefloxacin. In: Einhorn J, Nord CE, Norrby SR, editors. Recent advances in chemotherapy. Proceedings of the 18th International Congress of Chemotherapy; American Society for Microbiology; 1993 Jun 27–Jul 2: Washington (DC). Washington (DC): American Society for Microbiology, 1994: 349–50Google Scholar
  30. 30.
    Marutani K, Matsumoto M, Otabe Y, et al. Reduced phototoxicity of a fluoroquinolone antibacterial agent with a methoxy group at the 8 position in mice irradiated with long-wavelength UV light. Antimicrob Agents Chemother 1993; 37: 2217–33PubMedGoogle Scholar
  31. 31.
    Iravani A. Efficacy of lomefloxacin as compared to norfloxacin in the treatment of uncomplicated urinary tract infections in adults. Am J Med 1992; 92 Suppl. 4A: 75–81SGoogle Scholar
  32. 32.
    Yasuda S, Sakakibara N, Sakai Y, et al. Lomefloxacin-induced photodermatosis. Hifubyo Shinryo 1992; 14: 1081–4Google Scholar
  33. 33.
    Reiter C, Pfeiffer M, Hullmann R, et al. Integrated safety profile of intravenous ciprofloxacin. In: Garrard C, editor. Ciprofloxacin i.v.: defining its role in serious infections. Berlin: Springer-Verlag, 1994: 131–43Google Scholar
  34. 34.
    Schacht P, Hullmann R, Reiter C, et al. Challenges in the development of intravenous ciprofloxacin. Infect Med 1992; 9 Suppl. B: 73–84Google Scholar
  35. 35.
    Echols R. The selection of appropriate dosages for intravenous ciprofloxacin. J Antimicrob Chemother 1993; 31: 783–7PubMedGoogle Scholar
  36. 36.
    Wolfson JS, Hooper DC. Overview of fluoroquinolone safety. Am J Med 1991; 91 Suppl. 6A: 153–61SGoogle Scholar
  37. 37.
    Blomer R, Bruch K, Krauss H, et al. Safety of ofloxacin: adverse drug reactions reported during Phase-II studies in Europe and Japan. Infection 1986; 14 Suppl. 4: S332–4PubMedGoogle Scholar
  38. 38.
    Dan M, Samra Z. Clostridium difficile colitis associated with ofloxacin therapy. Am J Med 1989; 87: 479PubMedGoogle Scholar
  39. 39.
    Ehrenpreis ED, Lievens MW, Craig RM. Clostridium difficile associated diarrhoea after norfloxacin. J Clin Gastroenterol 1990; 12: 188–9PubMedGoogle Scholar
  40. 40.
    Cain DB, O’Connor ME. Pseudomembranous colitis associated with ciprofloxacin. Lancet 1990; 336: 946PubMedGoogle Scholar
  41. 41.
    Golledge CL, Carson CF, O’Neill GL, et al. Ciprofloxacin and Clostridium difficile-associated diarrhoea. J Antimicrob Chemother 1992; 30: 141–7PubMedGoogle Scholar
  42. 42.
    Lopez-Navidad A, Domingo P, Cadafalch J, et al. Norfloxacin-induced hepatotoxicity. J Hepatol 1990; 11: 277–8PubMedGoogle Scholar
  43. 43.
    Blum A. Ofloxacin-induced acute severe hepatitis [letter]. South Med J 1991; 84: 1158PubMedGoogle Scholar
  44. 44.
    Villeneuve J-P, Davies C, Cote J. Suspected ciprofloxacin-induced hepatotoxicity. Ann Pharmacother 1995; 29: 257–9PubMedGoogle Scholar
  45. 45.
    Jick SS, Jick H, Dean AD. A follow-up safety study of ciprofloxacin users. Pharmacotherapy 1993; 13: 461–4PubMedGoogle Scholar
  46. 46.
    Jungst G, Mohr R. Side effects of ofloxacin in clinical trials and post-marketing surveillance. Drugs 1987; 34 Suppl. 1: 144–9PubMedGoogle Scholar
  47. 47.
    Maesen FPV, Teengs JP, Baur C, et al. Quinolones and raised plasma concentrations of theophylline. Lancet 1984; ii: 530Google Scholar
  48. 48.
    Davey PG. Overview of drug interactions with the quinolones. J Antimicrob Chemother 1988; 22 Suppl. C: 97–107PubMedGoogle Scholar
  49. 49.
    FDA Anti-Infective Advisory Committee: March 31, Sept 23, 1993 — lomefloxacinGoogle Scholar
  50. 50.
    Inman W, Kubota K, Pearce G, et al. PEM Report Number 4. Pharmacoepidemiol Drug Saf 1993; 2: 341–64Google Scholar
  51. 51.
    Report. Norfloxacin and convulsions. Aust Adverse Drug Reactions Bull, 1990 MayGoogle Scholar
  52. 52.
    Chapuis L, Cardranel JF, Nordmann P, et al. Grand mal seizures as a complication of treatment with pefloxacin in patients with cirrhosis. J Hepatol 1993; 19: 383–4PubMedGoogle Scholar
  53. 53.
    Fink MP, Snydman DR, Niederman MS, et al. Treatment of severe pneumonia in hospitalised patients: results of a multi-center, randomised, double-blind trial comparing intravenous ciprofloxacin with imipenem-cilastatin. Antimicrob Agents Chemother 1994; 38: 547–57PubMedGoogle Scholar
  54. 54.
    Traeger SM, Bonfiglio MF, Wilson J, et al. Seizures associated with ofloxacin therapy. Clin Infect Dis. In PressGoogle Scholar
  55. 55.
    Kohler RB, Arkins N, Tack KJ. Accidental overdose of ofloxacin with benign outcome. Antimicrob Agents Chemother 1991; 35: 1239–40PubMedGoogle Scholar
  56. 56.
    Boles JM, Gentric A, Garre M, et al. Massive intoxication by flumequine. Presse Med 1985; 14: 1668PubMedGoogle Scholar
  57. 57.
    Fourtillan JB, Granier J, Saint-Sal IB, et al. Pharmacokinetics of ofloxacin and theophylline alone and in combination. Infection 1986; 14 Suppl. 1: 67–9Google Scholar
  58. 58.
    Okimoto N, Niki Y, Soejimza R. Effect of levofloxacin on serum concentration of theophylline. Chemotherapy (Tokyo) 1992; 40 Suppl. 3: 68–74Google Scholar
  59. 59.
    Takagi K, Yamaki K, Masayuki N, et al. Effect of the new quinolone, sparfloxacin, on the pharmacokinetics of theophylline in asthmatic patients. Antimicrobial Agents Chemother 1991; 35: 1137–41Google Scholar
  60. 60.
    Grasela TH, Dreis MW. An evaluation of the quinolone-theophylline interaction using the FDA spontaneous reporting system. Arch Intern Med 1992; 152: 617–21PubMedGoogle Scholar
  61. 61.
    Mulder GJ, Nagelkerke JF, Roeline TB, et al. Inhibition of the oxidative mechanism of theophylline in isolated rat hepatocytes by the quinolone antibiotic enoxacin and its metabolite oxo-enoxacin, but not by ofloxacin. Biochem Pharmacol 1988; 37: 2565–8PubMedGoogle Scholar
  62. 62.
    Hasegawa T, Nadai M, Kuzuya T, et al. The possible mechanism of interaction between xanthines and quinolone. J Pharm Pharmacol 1990; 42: 767–72PubMedGoogle Scholar
  63. 63.
    Sarkar M, Polk RE, Guzelian PS, et al. In vitro effect of fluoroquinolones on theophylline metabolism in human liver microsomes. Antimicrob Agents Chemother 1990; 34: 594–9PubMedGoogle Scholar
  64. 64.
    Morikawa K, Nagata O, Kubo S, et al. Unusual CNS toxic action of new quinolones. [abstract 255] In: Program and Abstracts of the 27th Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society for Microbiology; 1987; Washington (DC), 141Google Scholar
  65. 65.
    Hori S, Shimada J, Saito A, et al. Effect of new 4-quinolones on gamma-amino butyric acid receptor binding. [abstract 396]. In: Program and Abstracts of the 25th Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society for Microbiology; 1985; MinneapolisGoogle Scholar
  66. 66.
    Christ W. Central nervous system toxicity of quinolones: human and animal findings. J Antimicrob Chemother 1990; 26 Suppl. B: 219–25PubMedGoogle Scholar
  67. 67.
    Furuhama K, Akahane K, Tawara K, et al. Interaction of the new quinolone antibacterial agent levofloxacin with fenbufen in mice. Arzneimittelforschung 1992; 42: 406–8Google Scholar
  68. 68.
    Davey PG, Charter M, Kelly S, et al. Ciprofloxacin and sparfloxacin penetration into human brain tissue and their activity as antagonists of GABA receptor of rat vagus nerve. Antimicrob Agents Chemother 1994; 38: 1356–62PubMedGoogle Scholar
  69. 69.
    Hori S, Shimada J, Saito A, et al. Comparison of the inhibitory effects of new quinolones on γ-aminobutyric acid receptor binding in the presence of anti-inflammatory drugs. Rev Infect Dis 1989; 11 Suppl. 5: 1397–8Google Scholar
  70. 70.
    Halliwell RF, Davey PG, Lambert JJ. Antagonism of GABA receptors by 4-quinolones. J Antimicrob Chemother 1993; 31: 457–62PubMedGoogle Scholar
  71. 71.
    Dimpfel W, Spuler M, Dalhoff A, et al. Hippocampal activity in the presence of quinolones and fenbufen. in vitro. Antimicrob Agents Chemother 1991; 35: 1142–6PubMedGoogle Scholar
  72. 72.
    Bowie WR, Willets V, Jewesson PJ. Adverse reactions in a dose ranging study with a new long acting fluoroquinolone. Antimicrob Agents Chemother 1989; 33: 1778–82PubMedGoogle Scholar
  73. 73.
    Stille W, Harder S, Mieke S, et al. Decrease of caffeine elimination in man during co-administration of 4-quinolones. J Antimicrob Chemother 1987; 20: 729–34PubMedGoogle Scholar
  74. 74.
    Arcieri G, August R, Becker N, et al.Overview of clinical experience with ciprofloxacin. Eur J Clin Microbiol 1986; 5: 214–9Google Scholar
  75. 75.
    Winrow AP, Supramaniam G. Benign intracranial hypertension after ciprofloxacin administration. Arch Dis Child 1990; 65: 1165–6PubMedGoogle Scholar
  76. 76.
    Hooper DC, Wolfson JS. Adverse effects. In: Hooper DC, Wolfson JS, editors. Quinolone antimicrobial agents. 2 ed. Washington (DC): American Society for Microbiology, 1993; 489–512Google Scholar
  77. 77.
    Wainwright NJ, Collins P, Ferguson J. Photosensitivity associated with antibacterial agents. Drug Saf 1993; 9: 437–40PubMedGoogle Scholar
  78. 78.
    Zelickson AS. Phototoxic reaction with nalidixic acid. JAMA 1964; 190: 556PubMedGoogle Scholar
  79. 79.
    Boisvert A, Barbeau G. Nalidixic acid-induced photodermatitis after minimal sun exposure. Drug Intell Clin Pharm 1981; 15: 126–7PubMedGoogle Scholar
  80. 80.
    Ferguson J, Johnson BE. Ciprofloxacin induced photosensitivity: in vitro and in vivo studies. Br J Dermatol 1990; 123: 9–20PubMedGoogle Scholar
  81. 81.
    Ferguson J, Johnson BE. Clinical and laboratory studies of the photosensitising potential of norfloxacin, a 4-quinolone broad spectrum antibiotic. Br J Dermatol 1993; 128: 285–95PubMedGoogle Scholar
  82. 82.
    Paton JH, Reeves DS. Clinical features and management of adverse effects of quinolone antibacterials. Drug Saf 1991; 6: 8–27PubMedGoogle Scholar
  83. 83.
    Wagai N, Yoshida M, Takayama S. Phototoxic potential of the new quinolone antibacterial agent levofloxacin in mice. Arzneimittelforschung 1992; 42: 404–5Google Scholar
  84. 84.
    Burdge DR, Nakielna EM, Rabin HR. Photosensitivity associated with ciprofloxacin use in adult patients with cystic fibrosis. [letter]. Antimicrob Agents Chemother 1995; 39: 793PubMedGoogle Scholar
  85. 85.
    Baran R, Brun P. Photo-onycholysis induced by the fluoroquinolones pefloxacin and ofloxacin. Dermatologica 1986; 173: 185–8PubMedGoogle Scholar
  86. 86.
    Thorsteinsson SB, Bergan T, Oddsdottir S, et al. Crystalluria and ciprofloxacin, influence of urinary pH and hydration. Chemotherapy 1986; 32: 408–17PubMedGoogle Scholar
  87. 87.
    Swanson BN, Boppana VK, Vlasses PH, et al. Norfloxacin disposition after sequentially increasing oral doses. Antimicrob Agents Chemother 1983; 23: 284–8PubMedGoogle Scholar
  88. 88.
    Garlando F, Tauber MG, Joos B, et al. Ciprofloxacin-induced haematuria. Infection 1985; 13: 177–8PubMedGoogle Scholar
  89. 89.
    Mayer DG. Overview of toxicological studies. Drugs 1987; 34 Suppl. 1: 150–3PubMedGoogle Scholar
  90. 90.
    Hootkins R, Fenves AZ, Stephens MK. Acute renal failure secondary to oral ciprofloxacin therapy: a presentation of three cases and a review of the literature. Clin Nephrol 1989; 32: 75–8PubMedGoogle Scholar
  91. 91.
    Boelaert J, de Jaegere PP, Daneels R, et al. Case report of renal failure during norfloxacin therapy. [letter]. Clin Nephrol 1986; 25: 272PubMedGoogle Scholar
  92. 92.
    Rippelmeyer DJ, Synhavsky A. Ciprofloxacin and allergic interstitial nephritis. Ann Intern Med 1988; 109: 170PubMedGoogle Scholar
  93. 93.
    Rastogi S, Atkinson JLD, McCarthy JT. Allergic nephropathy associated with ciprofloxacin. Mayo Clin Proc 1990; 65: 987–9PubMedGoogle Scholar
  94. 94.
    Allon M, Lopez EJ, Min KW. Acute renal failure due to ciprofloxacin. Arch Intern Med 1990; 150: 2187–9PubMedGoogle Scholar
  95. 95.
    Lo WK, Rolston KVI, Rubenstein EB, et al. Ciprofloxacininduced nephrotoxicity in patients with cancer. Arch Intern Med 1993; 153: 1258–62PubMedGoogle Scholar
  96. 96.
    Rolston KVI, Rubenstein EB. Ciprofloxacin nephrotoxicity. [letter]. Arch Intern Med 1993; 153: 2706Google Scholar
  97. 97.
    Hestin D, Hanesse B, Frimat L, et al. Norfloxacin induced nephrotic syndrome. Lancet 1995; 345: 732–3PubMedGoogle Scholar
  98. 98.
    Davis H, McGoodwin E, Greene Reed T. Anaphylactoid reactions reported after treatment with ciprofloxacin. Ann Intern Med 1989; 111: 1041–3PubMedGoogle Scholar
  99. 99.
    Wurtz RM, Abrams D, Becker S, et al. Anaphylactoid drug reactions to ciprofloxacin and rifampicin in HIV-infected patients. Lancet 1989; i: 955–6Google Scholar
  100. 100.
    Miller MS, Gaido F, Rourk MH, et al. Anaphylactoid reactions to ciprofloxacin in cystic fibrosis patients. Pediatr Infect Dis 1991; 10: 164–5Google Scholar
  101. 101.
    Kennedy CA, Goetz MB, Mathisen GE. Ciprofloxacin-induced anaphylactoid reactions in patients infected with the human immunodeficiency virus. West Med J 1990; 153: 563–4Google Scholar
  102. 102.
    Huminer D, Cohen JD, Majadla R, et al. Hypersensitivity vasculitis due to ofloxacin. BMJ 1989; 299: 303PubMedGoogle Scholar
  103. 103.
    Choe U, Rothschild BM, Laitman L. Ciprofloxacin-induced vasculitis. N Engl J Med 1989; 320: 257–8PubMedGoogle Scholar
  104. 104.
    Stubbings J, Sheehan-Dare R, Walton S, et al. Cutaneous vasculitis due to ciprofloxacin. BMJ 1992; 305: 29PubMedGoogle Scholar
  105. 105.
    Slama TG. Serum sickness-like illness associated with ciprofloxacin. Antimicrob Agents Chemother 1990; 34: 904–5PubMedGoogle Scholar
  106. 106.
    Ingham B, Brentnall DW, Dale EA, et al. Arthropathy induced by antibacterial fused N-alkyl-4-pyridone-3-carboxylic acids. Toxicol Lett 1977; 1: 21–6Google Scholar
  107. 107.
    Alfaham M, Holt ME, Goodchild MC. Arthropathy in a patient with cystic fibrosis taking ciprofloxacin. BMJ 1987; 295: 669Google Scholar
  108. 108.
    Schaad UB, Wedgwood J. Lack of quinolone-induced arthropathy in children. J Antimicrob Chemother 1992; 30: 414–6PubMedGoogle Scholar
  109. 109.
    Le Loet X, Fessard C, Noblet C, et al. Severe arthropathy in an adolescent treated with pefloxacin. [letter] J Rheumatol 1991; 18: 1941PubMedGoogle Scholar
  110. 110.
    Chevalier X, Albengress E, Voisin MC, et al. A case of destructive polyarthropathy in a 17-year-old youth following pefloxacin treatment. Drug Saf 1992; 7: 310–4PubMedGoogle Scholar
  111. 111.
    Dixey J, Redington AN, Butler RC, et al. The arthropathy of cystic fibrosis. Ann Rheum Dis 1988; 47: 2123Google Scholar
  112. 112.
    Pertuiset E, Lenoir G, Jehanne M, et al. Joint tolerance of pefloxacin and ofloxacin in children and teenagers with cystic fibrosis. Rev Rhum Mal Osteoartic 1989; 56: 735–40PubMedGoogle Scholar
  113. 113.
    Chysky V, Kapila K, Hullman R, et al. Safety of ciprofloxacin in children: worldwide experience based on compassionate use, emphasis on joint evaluation. Infection 1991; 19: 289–96PubMedGoogle Scholar
  114. 114.
    Schaad UB, Wedgwood-Krucko J. Nalidixic acid in children: retrospective matched case controlled study for cartilage toxicity. Infections 1987; 15: 165–8Google Scholar
  115. 115.
    Nuutinen M, Turtinen J, Uhari M. Growth and joint symptoms in children treated with nalidixic acid. Pediatr Infect Dis J 1994; 13: 798–800PubMedGoogle Scholar
  116. 116.
    Schaad UB, Stoupis C, Wedgwood J, et al. Clinical, radiologic and magnetic resonance monitoring for skeletal toxicity in paediatric patients with cystic fibrosis receiving a three month course of ciprofloxacin. Pediatr Infect Dis 1991; 10: 723–9Google Scholar
  117. 117.
    Schaad UB, Sander E, Wedgwood J, et al. Morphologic studies for skeletal toxicity after prolonged ciprofloxacin therapy in two juvenile cystic fibrosis patients. Pediatr Infect Dis J 1992; 11: 1047–9PubMedGoogle Scholar
  118. 118.
    Bethell DB, Hien TT, Phi LT, et al. The effects on growth of single short courses of fluoroquinolones. Arch Dis Child 1995; In pressGoogle Scholar
  119. 119.
    Schaad UB. Role of the new quinolones in paediatric practice. Pediatr Infect Dis J 1992; 11: 1043–6PubMedGoogle Scholar
  120. 120.
    Schaad UB, Salam MA, Aujard Y, et al. Use of fluoroquinolones in paediatrics: consensus report of an International Society of Chemotherapy commission. Pediatr Infect Dis J 1995; 14: 1–9PubMedGoogle Scholar
  121. 121.
    Royer RJ, Pierfitte C, Netter P. Features of tendon disorders with fluoroquinolones. Therapie 1994; 49: 75–6PubMedGoogle Scholar
  122. 122.
    Ribard P, Audisio F, Kahn MF, et al. Seven Achilles tendonitis including 3 complicated by rupture during fluoroquinolone therapy. J Rheumatol 1992; 19: 1479–81PubMedGoogle Scholar
  123. 123.
    Lee WT, Collins JF. Ciprofloxacin associated bilateral achilles tendon rupture. Aust NZ J Med 1992; 22: 500Google Scholar
  124. 124.
    Szrafman A, Chen M, Blum MD. More on fluoroquinolone antibiotics and tendon rupture. [letter] N Engl J Med 1995; 332: 193Google Scholar
  125. 125.
    Pierfitte C, Gillet P, Royer RJ. More on fluoroquinolone antibiotics and tendon rupture. [letter] N Engl J Med 1995; 332: 193PubMedGoogle Scholar
  126. 126.
    Moore B, Safrani M, Keesey J. Possible exacerbation of myasthenia gravis by ciprofloxacin. Lancet 1988; i: 882Google Scholar
  127. 127.
    Rauser EH, Ariano RE, Anderson BA. Exacerbation of myasthenia gravis by norfloxacin. Ann Pharmacother 1990; 24: 207–8Google Scholar
  128. 128.
    Azevedo E, Ribiero JA, Polona J, et al. Probable exacerbation of myasthenia gravis by ofloxacin. J Neurol 1993; 240: 508PubMedGoogle Scholar
  129. 129.
    Lumbiganon P, Pengsaa K, Sookpranee T. Ciprofloxacin in neonates and its possible adverse effect on the teeth. Pediatr Infect Dis J 1991; 10: 619–20PubMedGoogle Scholar
  130. 130.
    Davey PG, McDonald T. Postmarketing surveillance of quinolones, 1990 to 1992. Drugs 1993; 45 Suppl. 3: 46–53PubMedGoogle Scholar

Copyright information

© Adis International Limited 1995

Authors and Affiliations

  • Peter Ball
    • 1
  • Glenn Tillotson
    • 2
  1. 1.Infectious Diseases Unit (c/o Ward 7)Victoria HospitalKirkcaldy, FifeScotland
  2. 2.Bayer plcNewburyEngland

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