Drug Safety

, Volume 24, Issue 3, pp 199–222 | Cite as

A Risk-Benefit Assessment of Levofloxacin in Respiratory, Skin and Skin Structure, and Urinary Tract Infections

Review Article


As a class, the quinolone antibacterials can no longer be assumed to be both effective and relatively free of significant adverse effects. Recent safety issues with newer generation fluoroquinolones, and concerns regarding drug-use associated bacterial resistance have made all drugs in this class subject to intense scrutiny and further study. Levofloxacin is a second generation fluoroquinolone with a post marketing history of well tolerated and successful use in a variety of clinical situations.

Quinolones as a class cause a variety of adverse effects, including phototoxicity, seizures and other CNS disturbances, tendonitis and arthropathies, gastrointestinal effects, nephrotoxicity, prolonged QTc interval and torsade de pointes, hypo- or hyperglycaemia, and hypersensitivity reactions. Levofloxacin has been involved in only a few case reports of adverse events, which include QTc prolongation, seizures, glucose disturbances, and tendonitis.

Levofloxacin has been shown to be effective at dosages of 250mg to 500mg once-daily in clinical trials in the management of acute maxillary sinusitis, acute bacterial exacerbations of chronic bronchitis, community-acquired pneumonia, skin and skin structure infections, and urinary tract infections. There are data suggesting that levofloxacin may promote fluoroquinolone resistance among the Streptococcus pneumoniae, and that clinical failures may result from this therapy. Other data suggest that fluoroquinolones with lower potency against Pseudomonas aeruginosa than ciprofloxacin, such as levofloxacin, may drive class-wide resistance to this pathogen.

Levofloxacin is an effective drug in many clinical situations, but its cost is significantly higher than amoxicillin, erythromycin, or first and second generation cefalosporins. Because of the propensity to select for fluoroquinolone resistance in the pneumococcus and potentially other pathogens, levofloxacin should be an alternative agent rather than a drug-of-choice in routine community-acquired respiratory tract, urinary tract, and skin or skin structure infections. In areas with increasing pneumococcal β-lactam resistance, levofloxacin may be a reasonable empiric therapy in community-acquired respiratory tract infections. Similarly, in patients with risk factors for infectious complications or poor outcome, levofloxacin may be an excellent empiric choice in severe community-acquired respiratory tract infections, urinary tract infections, complicated skin or skin structure infections, and nosocomial respiratory and urinary tract infections. Better clinical data are needed to identify the true place in therapy of the newer fluoroquinolones in common community-acquired and nosocomial infections. Until then, these agents, including levofloxacin, might best be reserved for complicated infections, infection recurrence, and infections caused by β-lactam or macrolide-resistant pathogens.


Ofloxacin Levofloxacin Sparfloxacin Clinical Success Rate Lomefloxacin 
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.


  1. 1.
    Andriole V. The future of the fluoroquinolones. Drugs 1999; 58Suppl. 2: 1–5PubMedCrossRefGoogle Scholar
  2. 2.
    Domagala JM. Structure-activity and structure-side effect relationships for the quinolone antibacterials. J Antimicrob Chemother 1994; 33: 685–706PubMedCrossRefGoogle Scholar
  3. 3.
    Blondeau JM. Expanded activity and utility of the new fluoroquinolones: a review. Clin Ther 1000; 21: 3–30CrossRefGoogle Scholar
  4. 4.
    Wise R, Brenwald NP, Andrews JM, et al. The activity of the methylpiperazinyl fluoroquinolone CG 5501: a comparison with other fluoroquinolones. J Antimicrob Chemother 1997; 39: 447–452PubMedCrossRefGoogle Scholar
  5. 5.
    Ednie LM, Jacons MR, Applebaum PC. Activities of gatifloxacin compared to those of seven other agents against anaerobic organisms. Antimicrob Agents Chemother 1998; 42: 2459–62PubMedGoogle Scholar
  6. 6.
    Bergan T. Pharmacokinetics of the fluoroquinolones. In: Andriole VT, editor. The Quinolones, 2nd ed. New York (NY): Academic Press, 1998, 143–82Google Scholar
  7. 7.
    Wolfson JS, Hooper DC. Overview of fluoroquinolone safety. Am J Med 1991; 91Suppl. 6A: 153S–61SPubMedCrossRefGoogle Scholar
  8. 8.
    Ortho McNeil Pharmaceuticals. Levaquin (levofloxacin) package insert. Raritan (NJ); Ortho McNeil, Dec 1996Google Scholar
  9. 9.
    Boccumini LE, Fowler CL, Campbell TA, et al. Photoreaction potential of orally administered levofloxacin in healthy subjects. Ann Pharmacother 2000; 34: 453–8PubMedCrossRefGoogle Scholar
  10. 10.
    Blum MD, Graham DJ, McCloskey CA. Temafloxacin syndrome: review of 95 cases. Clin Infect Dis 1994; 18: 949–50CrossRefGoogle Scholar
  11. 11.
    Finch RG. The withdrawal of temafloxacin: are there implications for other quinolones? Drug Saf 1993; 8: 9–11PubMedCrossRefGoogle Scholar
  12. 12.
    US Food and Drug Administration web site. Public Health Advisory. Trovan (trovafloxacin/altrovafloxacin mesylate). Available at: [Accessed 1999 Jun 9]
  13. 13.
    Stahlmann R, Lode H. Toxicity of quinolones. Drugs 1999; 58Suppl. 2: 37–48PubMedCrossRefGoogle Scholar
  14. 14.
    Stahlmann R. Safety profile of the quinolones. J Antimicrob Chemother 1990; 26Suppl. D: 31–44PubMedCrossRefGoogle Scholar
  15. 15.
    Paton JH, Reeves DS. Adverse reactions to the fluoroquinolones. Adverse Drug React Bull 1992; 153: 575–8CrossRefGoogle Scholar
  16. 16.
    Lode H. Potential interactions of the extended-spectrum fluoroquinolones with the CNS. Drug Saf 1999; 21: 123–35PubMedCrossRefGoogle Scholar
  17. 17.
    Akahane K, Sekiguchi, M, Une T. et al. Structure-epileptogenicity relationship of quinolones with special reference to their interaction with gamma-amino butyric acid receptor sites. Antimicrob Agents Chemother 1989; 33: 1704–8PubMedCrossRefGoogle Scholar
  18. 18.
    Yasuda H, Yoshida A, Masuda Y, et al. Levofloxacin-induced neurological adverse effects such as convulsion, involuntary movement (tremor, myoclonus and chorea like), visual hallucination in two elder patients. Nippon Ronen Igakkai Zasshi 1999; 36: 213–7PubMedCrossRefGoogle Scholar
  19. 19.
    Walton GD, Hon JK, Mulpur TG. Ofloxacin-induced seizure. Ann Pharmacother 1997; 31: 1475–7PubMedGoogle Scholar
  20. 20.
    Traeger SM, Bonfiglio MF, Wilson JA, et al. Seizures associated with ofloxacin therapy. Clin Infect Dis 1995; 21: 1504–6PubMedCrossRefGoogle Scholar
  21. 21.
    Davis BI, Maesen FPV. Clinical effectiveness of levofloxacin in patients with acute purulent exacerbation of chronic bronchitis: the relationship with in-vitro activity. J Antimicrob Chemother 1999; 43Suppl. C: 83–90CrossRefGoogle Scholar
  22. 22.
    Adelglass J, Jones TM, Ruoff G, et al. A multicenter, investigator- blinded, randomized comparison of oral levofloxacin and oral clarithromycin in the treatment of acute bacterial sinusitis. Pharmacotherapy 1998; 18(6): 1255–63PubMedGoogle Scholar
  23. 23.
    Adelglass J, DeAbate A, McElvaine P, et al. Comparison of the effectiveness of levofloxacin and amoxicillin-clavulanate for the treatment of acute sinusitis in adults. Otolaryngol Head Neck Sur 1999; 120: 320–7CrossRefGoogle Scholar
  24. 24.
    Sydnor TA, Kopp EJ, Anthony KE, et al. Open-label assessment of levofloxacin for the treatment of acute bacterial sinusitis in adults. Ann Allergy Asthma Immunol 1998; 80: 357–62PubMedCrossRefGoogle Scholar
  25. 25.
    DeAbate CA, Russell M, McElvaine P, et al. Safety and efficacy of oral levofloxacin versus cefuroxime axetil in acute bacterial exacerbation of chronic bronchitis. Resp Care 1997; 42(2): 206–13Google Scholar
  26. 26.
    Habib MP, Gentry LO, Rodriguez-Gomez G, et al. Multicenter, randomized study comparing efficacy and safety of oral levofloxacin and cefaclor in treatment of acute bacterial exacerbations of chronic bronchitis. Infect Dis Clin Pract 1998; 7: 101–9CrossRefGoogle Scholar
  27. 27.
    File TM, Segreti J, Dunbar L, et al. A multicenter, randomized study comparing the efficacy and safety of intravenous and/or oral levofloxacin versus ceftriaxone and/or cefuroxime axetil in treatment of adults with community-acquired pneumonia. Antimicrob Agents Chemother 1997; 41(9): 1965–72PubMedGoogle Scholar
  28. 28.
    Fogarty CM, Sullivan JG, Chattman MS, et al. Once a day levofloxacin in the treatment of mild to moderate and severe community-acquired pneumonia in adults. Infect Dis Clin Pract 1998; 7(8): 400–7CrossRefGoogle Scholar
  29. 29.
    Nicodemo AC, Robledo JA, Jasovich A, et al. A multicenter, double-blind, randomized study comparing the efficacy and safety of oral levofloxacin versus ciprofloxacin in the treatment of uncomplicated skin and skin structure infections. Int J Clin Pract 1998; 52(2): 69–74PubMedGoogle Scholar
  30. 30.
    Klimberg IW, Cox CE, Fowler CL, et al. A controlled trial of levofloxacin and lomefloxacin in the treatment of complicated urinary tract infection. Urology 1998; 51: 610–5PubMedCrossRefGoogle Scholar
  31. 31.
    Nichols RL, Smith JW, Gentry LO, et al. Multicenter, randomized study comparing levofloxacin and ciprofloxacin for uncomplicated skin and skin structure infections. Southern Med J 1997; 90(12): 1193–200PubMedCrossRefGoogle Scholar
  32. 32.
    Shah PM, Maesen FPV, Dolmann A, et al. Levofloxacin versus cefuroxime axetil in the treatment of acute exacerbation of chronic bronchitis: results of a randomized, double-blind study. J Antimicrob Chemother 1999; 43: 529–39PubMedCrossRefGoogle Scholar
  33. 33.
    Lasko B, Lau C, Saint-Pierre C, et al. Efficacy and safety of oral levofloxacin compared with clarythromycin in the treatment of acute sinusitis in adults; a multicentre, double-blind randomised study. J Int Med Res 1998; 26: 281–91PubMedGoogle Scholar
  34. 34.
    MacGowan AP, Wootton M, Holt HA. The antibacterial efficacy of levofloxacin and ciprofloxacin against Pseudomonas aeruginosa assessed by combining antibiotic exposure and bacterial susceptibility. J Antimicrob Chemother 1999; 43: 345–9PubMedCrossRefGoogle Scholar
  35. 35.
    Lipsky BA, Baker CA. Fluoroquinolone toxicity profiles: a review focusing on newer agents. Clin Inf Dis 1999; 28: 352–64CrossRefGoogle Scholar
  36. 36.
    Bischoff U, Schmidt C, Netzer R, et al. Effects of fluoroquinolones on HERG currents. Eur J Pharmacol 2000: 406: 341–3PubMedCrossRefGoogle Scholar
  37. 37.
    Li H, Fuentes-Garcia J, Towbin JA. Current concepts in long QT syndrome. Pediatr Cardiol 2000; 21: 542–50PubMedCrossRefGoogle Scholar
  38. 38.
    Rhone-Poulenc Rorer. Zagam (sparfloxacin) package insert. Collegeville (PA); Rhone-Poulenc Rorer, Nov 1999Google Scholar
  39. 39.
    Glaxo Wellcome. Raxar (grepafloxacin) package insert. Research Triangle Park (NC); Glaxo Wellcome, May 1998Google Scholar
  40. 40.
    Bayer Corporation. Avelox (moxifloxacin) package insert. West haven (CT); Bayer Corporation, Dec 1999Google Scholar
  41. 41.
    Andriole VT. Cardiotoxicity of antibiotics: what to make of a prolonged QTc-interval [abstract 1881]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17-20; Toronto, 542Google Scholar
  42. 42.
    Oberg KC, Bauman JL. QT interval prolongation and torsades de pointe due to erythromycin mactobionate. Pharmacotherapy 1995; 15: 687–92PubMedGoogle Scholar
  43. 43.
    Baker B, Dorian P, Sandor P, et al. Electrocardiographic effects of fluoxetine and doxepin in patients with major depressive disorder. J Clin Psychopharmacol. 1997; 17: 15–21PubMedCrossRefGoogle Scholar
  44. 44.
    van Haarst AD, van’t Klooster GA, van Gerven JM, et al. The influence of cisapride and clarithromycin on QT intervals in healthy volunteers. Clin Pharmacol Ther 1998; 64: 542–6PubMedCrossRefGoogle Scholar
  45. 45.
    Samaha FF. QTc interval prolongation and polymorphic ventricular tachycardia in association with levofloxacin [letter]. Am J Med 1999; 107: 28–9Google Scholar
  46. 46.
    Iannini PB, Kramer H, Circiumaru I, et al. QTc prolongation associated with levofloxacin [abstract 822]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17-20; Toronto, 477Google Scholar
  47. 47.
    Christ W, Lehnert T, Ulbrich B. Specific toxicologic aspects of the quinolones. Rev Infect Dis 1988; 10Suppl. 2: 16–28Google Scholar
  48. 48.
    Burkhardt JE, Walterspiel JN, Schaad UB. Quinolone arthorpathy in animals versus children. Clin Infect Dis 1997; 25: 1196–1204PubMedCrossRefGoogle Scholar
  49. 49.
    Alghasham AA, Nahata MC. Clinical use of fluoroquinolones in children. Ann Pharmacother 2000; 34: 347–59PubMedCrossRefGoogle Scholar
  50. 50.
    Lewis JR, Gums JG, Dickenseets DL. Levofloxacin-induced bilateral Achilles tendonitis. Ann Pharmacother 1999; 33: 792–795PubMedCrossRefGoogle Scholar
  51. 51.
    McGarvey WC, Singh D, Trevino SG. Partial Achilles tendon ruptures associated with fluoroquinolone antibiotics: a case report an literature review. Foot Ankle Int 1996; 17: 496–8PubMedGoogle Scholar
  52. 52.
    Zabraniecki L, Negrier I, Vergne P, et al. Fluoroquinolone indusced tendinopathy: report of 6 cases. J Rheumatol 1996 23: 516–20PubMedGoogle Scholar
  53. 53.
    Meyboom RH, Olsson S, Knol A, et al. Achilles tendonitis induced by pefloxacin and other fluoroquinolone derivatives. Drug Saf 1994 2: 185–9Google Scholar
  54. 54.
    Goa KL, Bryson HM, Markham A. Sparfloxacin: a review of its antibacterial activity, pharmacokinetic properties, clinical efficacy and tolerability in lower respiratory tract infectios. Drugs 1997; 53: 700–25PubMedCrossRefGoogle Scholar
  55. 55.
    Data on file, Ortho McNeil, Raritan, 1996Google Scholar
  56. 56.
    Casado BE, Vinas PG, Lauzurica VR, et al. Levofloxacin-induced tendonitis [letter]. Med Clin (Barc) 2000 114: 319Google Scholar
  57. 57.
    Hayem G, Carbon C. A reappraisal of quinolone tolerability: the experience of their musculoskeletal effects. Drug Saf 1995; 13: 338–42PubMedCrossRefGoogle Scholar
  58. 58.
    Takayama S, Hirohashi M, Kato M. et al. Toxicity of quinolone antimicrobial agents. J Tox Environ Health 1995; 45: 1–45CrossRefGoogle Scholar
  59. 59.
    Greenburg RN, Newman MT, Shariaty S, et al. Ciprofloxacin, lomefloxacin, or levofloxacin as treatment for chronic osteomyelitis. Antimicrob Agents Chemother 2000 44: 164–6CrossRefGoogle Scholar
  60. 60.
    Paily R. Quinolone drug rash in a patient with infectious mononucleosis. J Dermatol 2000; 27: 405–6PubMedGoogle Scholar
  61. 61.
    Piscitelli SC, Spooner K, Baird B, et al. Pharmacokinetics and safety of high-dose and extended-interval regimens of levofloxacin in human immunodeficiency virus-infected patients. Antimicrob Agents Chemother 1999 43: 2323–7PubMedGoogle Scholar
  62. 62.
    Goodwin SD, Gallis HA, Chow AT, et al. Pharmacokinetics and safety of levofloxacin in patients with human immunodeficiency virus infection. Antimicrob Agents Chemother 1994 38: 799–804PubMedCrossRefGoogle Scholar
  63. 63.
    Marchbanks CR. Drug-drug interactions with fluoroquinolones. Pharmacotherapy 1993; 13Suppl. 2: 23S–8SPubMedGoogle Scholar
  64. 64.
    Bryskier A, Chantot J-F. Classification and structure-activity relationships of fluoroquinolones. Drugs 1995; 49Suppl. 2: 16–28PubMedCrossRefGoogle Scholar
  65. 65.
    Gisclon LG, Curtin CR, Fowler CL, et al. Absence of a pharmacokinetic interaction between intravenous theophylline and orally administered levofloxacin. J Clin Pharmacol 1997 37: 744–50PubMedGoogle Scholar
  66. 66.
    Christ W. Central nervous system toxicity of quinolones: human and animal findings. J Antimicrob Chemother 1990; 26: 219–25PubMedCrossRefGoogle Scholar
  67. 67.
    Liao S, Palmer M, Fowler C, et al. Absence of an effect of levofloxacin on warfarin pharmacokinetics and anticoagulation in male volunteers. J Clin Pharmacol 1996 36: 1072–7PubMedCrossRefGoogle Scholar
  68. 68.
    Chien SC, Chow AT, Natarajan J, et al. Absence of age and gender effects on the pharmacokinetics of a single 500-milligram oral dose of levofloxacin in healthy subjects. Antimicrob Agents Chemother. 1997; 41(7): 1562–5PubMedGoogle Scholar
  69. 69.
    Doose DR, Walker SA, Chien SC, et al. Levofloxacin does not alter cyclosporine disposition. J Clin Pharmacol 1998 38: 90–3PubMedGoogle Scholar
  70. 70.
    Chien SC, Chow AT, Rogge MC, et al. Pharmacokinetics and safety of oral levofloxacin in human immunodeficiency virus-infected individuals receiving concomitant zidovudine. Antimicrob Agents Chemother 1997 41: 1765–9PubMedGoogle Scholar
  71. 71.
    Hooper DC, Wolfson JS. Mechanisms of bacterial resistance to quinolones. In: Hooper DC, Wolfson JS, editors. Quinolone antimicrobial agents. 2nd ed. Washington, DC: American Society for Microbiology; 1993: 97–118Google Scholar
  72. 72.
    Drlica K. Refining the fluoroquinolones. ASM News 1999; 65: 410–5Google Scholar
  73. 73.
    Nix DE, Shentag JJ. The quinolones: an overview and comparative appraisal of their pharmacokinetics and pharmacodynamics. J Clin Pharmacol 1988; 28: 169–78PubMedGoogle Scholar
  74. 74.
    Nau R, Kinzig M, Dreyaupt T, et al. Kinetics of ofloxacin and its metabolites in cerebrospinal fluid after a single intravenous infusion of 400 milligram of ofloxacin. Antimicrob Agents Chemother 1994 38: 1849–1953PubMedCrossRefGoogle Scholar
  75. 75.
    Rogge MC, Chien S-C, Wong F, et al. Single-dose pharmacokinetics of levofloxacin: influence of age and gender. In: Selected Posters Presented at the Fifth International Symposium on New Quinolones; 1994 Aug 25-27; Singapore. Raritan (NJ): The R.W. Johnson Pharmaceutical Research Institute, 1994: 44–5Google Scholar
  76. 76.
    Chien S-C, Wong FA, Fowler CL, et al. Double-blind evaluation of the safety and pharmacokinetics of multiple oral once-daily 750-milligram and 1-gram doses of levofloxacin in healthy volunteers. Antimicrob Agents Chemother 1998 42: 885–8PubMedGoogle Scholar
  77. 77.
    Preston SL, Drusano GL, Berman AL, et al. Pharmacodynamics of levofloxacin; A new paradigm for early clinical trials. JAMA 1998 279: 125–9PubMedCrossRefGoogle Scholar
  78. 78.
    Forrest A, Nix DE, Ballow CH, et al. Pharmacodynamics of intravenous ciprofloxacin in seriously ill patients. Antimicrob Agents Chemother 1993 37: 1073–81PubMedCrossRefGoogle Scholar
  79. 79.
    Jumbe NL, Louie A, Liu W, et al. Pharmacodynamics of levofloxacin with different organisms: one size does not fit all [abstract 291]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17-20; Toronto, 7Google Scholar
  80. 80.
    Ambrose PG, Grasela DM, Grasela TH, et al. Pharmacodynamics of fluoroquinolones against Streptococcus pneumoniae: Analysis of phase-III clinical trials [abstract 1387]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17-20; Toronto, 28Google Scholar
  81. 81.
    Morrissey I, Hoshino K, Sato K, et al. Mechanisms of differential activites of ofloxacin enantiomers. Antimicrob Agents Chemother 1996 40: 1775–84PubMedGoogle Scholar
  82. 82.
    Milatovic D, Schmitz F-J, Brisse V, et al. In vitro activities of sitafloxacin (DU-6859a) and six other fluoroquinolones against 8,796 clinical bacterial isolates. Antimicrob Agents Chemother 2000; 44: 1102–7PubMedCrossRefGoogle Scholar
  83. 83.
    Deshpande LM, Jones RN. Antimicrobial activity of advanced-spectrum fluoroquinolones tested against more than 2000 contemporary bacterial isolates of species causing community-acquired respiratory tract infections in the United States (1999). Diag Micro Inf Dis 2000; 37: 139–142CrossRefGoogle Scholar
  84. 84.
    Richard GA, Pittman W, Childs SJ, et al. Safety and efficacy of levofloxacin versus ciprofloxacin complicated urinary tract infections in adults. Pharm Ther 1998; Oct: 533–40Google Scholar
  85. 85.
    Shishido H, Furukawa K, Nagai H, et al. Oral levofloxacin 600 mg and 300 mg daily doses in difficult-to-treat respiratory infection. Drugs 1995; 49Suppl. 2: 433–5PubMedCrossRefGoogle Scholar
  86. 86.
    Tsang KWT, Chan WM, Ho PL, et al. A comparative study on the efficacy of levofloxacin and ceftazidime in acute exacerbation of bronchiectasis. Eur Respir J. 1999 14: 1206–9PubMedCrossRefGoogle Scholar
  87. 87.
    Rittenhouse B, Stinnett AA, Dulisse B, et al. An economic evaluation of levofloxacin versus cefuroxime axetil in the outpatient treatment of adults with community-acquired pneumonia. Am J Manag Care 2000 6: 381–9PubMedGoogle Scholar
  88. 88.
    Sato A, Ogawa H, Iwata M, et al. Clinical efficacy of levofloxacin in elderly patients with respiratory tract infections. Drugs 1995; 49Suppl 2: 428–9PubMedCrossRefGoogle Scholar
  89. 89.
    Kawai T. Clinical Evaluation of levofloxacin 200 mg 3 times daily in the treatment of bacterial lower respiratory infections. Drugs 1995; 49Suppl. 2: 416–7PubMedCrossRefGoogle Scholar
  90. 90.
    Norrby SR, Petermann W, Willcox PA, et al. A comparative study of levofloxacin and ceftriaxone in the treatment of hospitalized patients with pneumonia. Scand J Infect Dis 1998 30: 397–404PubMedCrossRefGoogle Scholar
  91. 91.
    Graham DR, Talan DA, Nichols RL, et al. A randomized open-label comparative trial of levofloxacin 750 mg once-daily versus intravenous ticarcillin/clavulanate with or without amoxicillin/clavulante for the treatment of complicated skin and skin structure infections [abstract 171]. Annual Meeting of the Infectious Disease Society of America; 2000 Sep 7-10; New OrleansGoogle Scholar
  92. 92.
    Geddes A, Thaler M, Schonwald S, et al. Levofloxacin in the empirical treatment of patients with suspected, bacteraemia/sepsis: comparison with imipenem/cilastatin in an open, randomized trial. J Antimicrob Chemother. 1999 44: 799–810PubMedCrossRefGoogle Scholar
  93. 93.
    Chen DK, McGreer A, De Azavedo JC, et al. Decreased susceptibility of Streptococcus pneumoniae to fluoroquinolones in Canada. N Engl J Med 1999; 341: 233–9PubMedCrossRefGoogle Scholar
  94. 94.
    Jones RN, Pfaller MA. In vitro activity of newer fluoroquinolones for respiratory tract infections and emerging patterns of antimicrobial resistance: data from the SENTRY Antimicrobial Surveillance Program. Clin Infect Dis 2000; 31Suppl. 2: S16–23PubMedCrossRefGoogle Scholar
  95. 95.
    Thornsberry C, Sahm DF. Resistance in respiratory tract pathogens; an international study 1997-1998. J Chemother 2000; 12 Suppl. 4: 16–20Google Scholar
  96. 96.
    Thornsberry C, Sahm DF. Antimicrobial resistance in respiratory tract pathogens; results of an international surveillance study. Chemotherapy 2000; 46Suppl. 1: 15–23PubMedCrossRefGoogle Scholar
  97. 97.
    Fishman NO, Suh B, Weigel LM, et al. Three levofloxacin treatment failures of pneumococcal respiratory tract infections [abstract 825]. 39th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1999 Sep 26-29; San FranciscoGoogle Scholar
  98. 98.
    Davidson RJ, De Azavedo J, Bast D, et al. Levofloxacin treatment failure of pneumococcal pneumonia and development of resistance during therapy [abstract 2103]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17-20; Toronto, 127Google Scholar
  99. 99.
    Weiss K, Restieri C, Davidson RJ, et al. Treatment failure and progression of resistance in an outbreak of fluoroquinolone-resistant (FQ) Streptococcus pneumoniae (Sp) [abstract 2104]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17-20; TorontoGoogle Scholar
  100. 100.
    Parker Cook DJ, Calder JAM, Fleckenstein P, et al. Fluoroquinolone resistance in mult-drug resistant Streptococcus pneumoniae in New York City [abstract 2105]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17-20; TorontoGoogle Scholar
  101. 101.
    Lister PD. Sanders CC. Pharmacodynamics of trovafloxacin, ofloxacin, and ciprofloxacin against Streptococcus pneumoniae in an in vitro pharmacokinetic model. Antimicrob Agents Chemother 1999; 43: 1118–23PubMedGoogle Scholar
  102. 102.
    Lister PD. Sanders CC. Pharmacodynamics of levofloxacin and ciprofloxacin against Streptococcus pneumoniae. J Antimicrob Chemother 1999; 43: 79–86PubMedCrossRefGoogle Scholar
  103. 103.
    Lacy MK, Lu W, Xu Z, et al. Pharmacodynamic comparison of levofloxacin, ciprofloxacin, and ampicillin against Streptococcus pneumoniae in an in vitro model of infection. Antimicrob Agents Chemother 1999 43: 672–7PubMedGoogle Scholar
  104. 104.
    Kays MB, Conklin M. Comparative in vitro activity and pharmacodynamics of five fluoroquinolones against clinical isolates of Streptococcus pneumoniae. Pharmacotheapyr 2000; 20: 1310–7CrossRefGoogle Scholar
  105. 105.
    Bauernfeind A. Pharmacodynamics of levofloxacin and ofloxacin against Streptococcus pneumoniae. J Antimicrob Chemother 1999; 43Suppl. C: 77–82PubMedCrossRefGoogle Scholar
  106. 106.
    Peterson LR, Postelnck M, Pozdol TL, et al. Management of fluoroquinolone resistance in Pseudomonas aeruginosa-Outcome of monitored use in a referral hospital. Int J Antimicrob Agents 1998; 10: 207–14PubMedCrossRefGoogle Scholar
  107. 107.
    Richard P, Delangle MH, Merrien D, et al. Fluoroquinolone usage and fluoroquinolone resistance: is there an association? Clin Infect Dis 1994 19: 54–9PubMedCrossRefGoogle Scholar
  108. 108.
    Richard P, Delangle MH, Raffi F, et al. Impact of fluoroquinolone administration on the emergence of fluoroquinolone-resistant gram-negative bacilli from gastrointestinal flora Clin Infect Dis 2001 32: 162–66PubMedCrossRefGoogle Scholar
  109. 109.
    Gerding DN, Larson TA, Hughes RA, et al. Aminoglycoside resistance and aminoglycoside usage: 10 years of experience in one hospital. Antimicrob Agents Chemother 1991 35: 1284–90PubMedCrossRefGoogle Scholar
  110. 110.
    Bartlett JG, Dowell SF, Mandell LA, et al. Practice guidelines for the management of community-acquired pneumonia in adults. Clin Infect Dis 2000 31: 347–82PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 2001

Authors and Affiliations

  1. 1.OhioThe University of Toledo, College of PharmacyToledoUSA
  2. 2.The University of Colorado Health Sciences Center, School of PharmacyDenverUSA
  3. 3.The University of Missouri-Kansas City, School of PharmacyKansas CityUSA

Personalised recommendations