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Fluoroquinolones

Author
David C Hooper, MD
Section Editor
Stephen B Calderwood, MD
Deputy Editor
Anna R Thorner, MD

INTRODUCTION

The fluoroquinolones have become an increasingly popular class of antibiotics for use in a variety of infections. Newer drugs in this class have been developed with a broader spectrum of activity including better coverage of gram-positive organisms and, in one case, even anaerobes. However, toxicities have been associated with some of these newer agents.

Fluoroquinolones available for systemic use include ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin, and ofloxacin.

Grepafloxacin was withdrawn from the worldwide market by the manufacturer in 1999 because of adverse cardiac events.

Sparfloxacin was withdrawn from most countries in 2001, primarily due to lack of sales [1].

Trovafloxacin was withdrawn worldwide between 1999 and 2000 because of the risk of hepatic toxicity.

                                    

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Literature review current through: Nov 2016. | This topic last updated: Thu May 26 00:00:00 GMT+00:00 2016.
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References
Top
  1. Mylan Zagam discontinued: Charges total $4.7 mil in fiscal third quarter. In: "The Pink Sheet" vol. 63 no. 6. F-D-C Reports, Inc. Chevy Chase, Maryland 2001. p.29.
  2. FDA Drug Shortages; Norfloxacin (Noroxin) tablets Discontinuation http://www.accessdata.fda.gov/scripts/drugshortages/dsp_ActiveIngredientDetails.cfm?AI=Norfloxacin (Noroxin) Tablets&st=d&tab=tabs-2 (Accessed on August 12, 2015).
  3. Drlica K, Zhao X. DNA gyrase, topoisomerase IV, and the 4-quinolones. Microbiol Mol Biol Rev 1997; 61:377.
  4. Hooper DC. Mechanisms of fluoroquinolone resistance. Drug Resist Updat 1999; 2:38.
  5. Tam VH, Louie A, Fritsche TR, et al. Impact of drug-exposure intensity and duration of therapy on the emergence of Staphylococcus aureus resistance to a quinolone antimicrobial. J Infect Dis 2007; 195:1818.
  6. Martínez-Martínez L, Pascual A, Jacoby GA. Quinolone resistance from a transferable plasmid. Lancet 1998; 351:797.
  7. Tran JH, Jacoby GA. Mechanism of plasmid-mediated quinolone resistance. Proc Natl Acad Sci U S A 2002; 99:5638.
  8. Robicsek A, Jacoby GA, Hooper DC. The worldwide emergence of plasmid-mediated quinolone resistance. Lancet Infect Dis 2006; 6:629.
  9. Pitout JD, Wei Y, Church DL, Gregson DB. Surveillance for plasmid-mediated quinolone resistance determinants in Enterobacteriaceae within the Calgary Health Region, Canada: the emergence of aac(6')-Ib-cr. J Antimicrob Chemother 2008; 61:999.
  10. Robicsek A, Strahilevitz J, Sahm DF, et al. qnr prevalence in ceftazidime-resistant Enterobacteriaceae isolates from the United States. Antimicrob Agents Chemother 2006; 50:2872.
  11. Robicsek A, Strahilevitz J, Jacoby GA, et al. Fluoroquinolone-modifying enzyme: a new adaptation of a common aminoglycoside acetyltransferase. Nat Med 2006; 12:83.
  12. Park CH, Robicsek A, Jacoby GA, et al. Prevalence in the United States of aac(6')-Ib-cr encoding a ciprofloxacin-modifying enzyme. Antimicrob Agents Chemother 2006; 50:3953.
  13. Périchon B, Courvalin P, Galimand M. Transferable resistance to aminoglycosides by methylation of G1405 in 16S rRNA and to hydrophilic fluoroquinolones by QepA-mediated efflux in Escherichia coli. Antimicrob Agents Chemother 2007; 51:2464.
  14. Zhao J, Chen Z, Chen S, et al. Prevalence and dissemination of oqxAB in Escherichia coli isolates from animals, farmworkers, and the environment. Antimicrob Agents Chemother 2010; 54:4219.
  15. Kim HB, Wang M, Park CH, et al. oqxAB encoding a multidrug efflux pump in human clinical isolates of Enterobacteriaceae. Antimicrob Agents Chemother 2009; 53:3582.
  16. Coronado VG, Edwards JR, Culver DH, et al. Ciprofloxacin resistance among nosocomial Pseudomonas aeruginosa and Staphylococcus aureus in the United States. Infect Control Hosp Epidemiol 1995; 16:71.
  17. Polk RE, Johnson CK, McClish D, et al. Predicting hospital rates of fluoroquinolone-resistant Pseudomonas aeruginosa from fluoroquinolone use in US hospitals and their surrounding communities. Clin Infect Dis 2004; 39:497.
  18. Weber SG, Gold HS, Hooper DC, et al. Fluoroquinolones and the risk for methicillin-resistant Staphylococcus aureus in hospitalized patients. Emerg Infect Dis 2003; 9:1415.
  19. Neuhauser MM, Weinstein RA, Rydman R, et al. Antibiotic resistance among gram-negative bacilli in US intensive care units: implications for fluoroquinolone use. JAMA 2003; 289:885.
  20. Fox KK, Knapp JS, Holmes KK, et al. Antimicrobial resistance in Neisseria gonorrhoeae in the United States, 1988-1994: the emergence of decreased susceptibility to the fluoroquinolones. J Infect Dis 1997; 175:1396.
  21. Centers for Disease Control and Prevention (CDC). Update to CDC's sexually transmitted diseases treatment guidelines, 2006: fluoroquinolones no longer recommended for treatment of gonococcal infections. MMWR Morb Mortal Wkly Rep 2007; 56:332.
  22. Workowski KA, Bolan GA, Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep 2015; 64:1.
  23. Smith KE, Besser JM, Hedberg CW, et al. Quinolone-resistant Campylobacter jejuni infections in Minnesota, 1992-1998. Investigation Team. N Engl J Med 1999; 340:1525.
  24. Chen DK, McGeer A, de Azavedo JC, Low DE. Decreased susceptibility of Streptococcus pneumoniae to fluoroquinolones in Canada. Canadian Bacterial Surveillance Network. N Engl J Med 1999; 341:233.
  25. Hooper DC. Fluoroquinolone resistance among Gram-positive cocci. Lancet Infect Dis 2002; 2:530.
  26. Lautenbach E, Fishman NO, Bilker WB, et al. Risk factors for fluoroquinolone resistance in nosocomial Escherichia coli and Klebsiella pneumoniae infections. Arch Intern Med 2002; 162:2469.
  27. Eliopoulos GM, Eliopoulos CT. Activity in vitro of the quinolones. In: Quinolone antimicrobial agents, 2nd ed, Hooper DC, Wolfson JS (Eds), American Society for Microbiology, Washington, DC 1993. p.161.
  28. Wolfson JS, Hooper DC. Fluoroquinolone antimicrobial agents. Clin Microbiol Rev 1989; 2:378.
  29. Ji B, Lounis N, Maslo C, et al. In vitro and in vivo activities of moxifloxacin and clinafloxacin against Mycobacterium tuberculosis. Antimicrob Agents Chemother 1998; 42:2066.
  30. Miyazaki E, Miyazaki M, Chen JM, et al. Moxifloxacin (BAY12-8039), a new 8-methoxyquinolone, is active in a mouse model of tuberculosis. Antimicrob Agents Chemother 1999; 43:85.
  31. Burman WJ, Goldberg S, Johnson JL, et al. Moxifloxacin versus ethambutol in the first 2 months of treatment for pulmonary tuberculosis. Am J Respir Crit Care Med 2006; 174:331.
  32. Gillespie SH, Gosling RD, Uiso L, et al. Early bactericidal activity of a moxifloxacin and isoniazid combination in smear-positive pulmonary tuberculosis. J Antimicrob Chemother 2005; 56:1169.
  33. Nijland HM, Ruslami R, Suroto AJ, et al. Rifampicin reduces plasma concentrations of moxifloxacin in patients with tuberculosis. Clin Infect Dis 2007; 45:1001.
  34. Dooley K, Flexner C, Hackman J, et al. Repeated administration of high-dose intermittent rifapentine reduces rifapentine and moxifloxacin plasma concentrations. Antimicrob Agents Chemother 2008; 52:4037.
  35. Bozeman L, Burman W, Metchock B, et al. Fluoroquinolone susceptibility among Mycobacterium tuberculosis isolates from the United States and Canada. Clin Infect Dis 2005; 40:386.
  36. Gaba PD, Haley C, Griffin MR, et al. Increasing outpatient fluoroquinolone exposure before tuberculosis diagnosis and impact on culture-negative disease. Arch Intern Med 2007; 167:2317.
  37. Davis R, Bryson HM. Levofloxacin. A review of its antibacterial activity, pharmacokinetics and therapeutic efficacy. Drugs 1994; 47:677.
  38. Thomson KS, Chartrand SA, Sanders CC, Block SL. Trovafloxacin, a new fluoroquinolone with potent activity against Streptococcus pneumoniae. Antimicrob Agents Chemother 1997; 41:478.
  39. Gatifloxacin and moxifloxacin: two new fluoroquinolones. Med Lett Drugs Ther 2000; 42:15.
  40. Blondeau JM. A review of the comparative in-vitro activities of 12 antimicrobial agents, with a focus on five new respiratory quinolones'. J Antimicrob Chemother 1999; 43 Suppl B:1.
  41. Zhanel GG, Palatnick L, Nichol KA, et al. Antimicrobial resistance in respiratory tract Streptococcus pneumoniae isolates: results of the Canadian Respiratory Organism Susceptibility Study, 1997 to 2002. Antimicrob Agents Chemother 2003; 47:1867.
  42. von Eiff C, Peters G. In-vitro activity of ofloxacin, levofloxacin and D-ofloxacin against staphylococci. J Antimicrob Chemother 1996; 38:259.
  43. Dalhoff A, Schmitz FJ. In vitro antibacterial activity and pharmacodynamics of new quinolones. Eur J Clin Microbiol Infect Dis 2003; 22:203.
  44. Une T, Fujimoto T, Sato K, Osada Y. In vitro activity of DR-3355, an optically active ofloxacin. Antimicrob Agents Chemother 1988; 32:1336.
  45. Spangler SK, Jacobs MR, Appelbaum PC. Activity of CP 99,219 compared with those of ciprofloxacin, grepafloxacin, metronidazole, cefoxitin, piperacillin, and piperacillin-tazobactam against 489 anaerobes. Antimicrob Agents Chemother 1994; 38:2471.
  46. Malangoni MA, Song J, Herrington J, et al. Randomized controlled trial of moxifloxacin compared with piperacillin-tazobactam and amoxicillin-clavulanate for the treatment of complicated intra-abdominal infections. Ann Surg 2006; 244:204.
  47. Snydman DR, Jacobus NV, McDermott LA, et al. In vitro activities of newer quinolones against bacteroides group organisms. Antimicrob Agents Chemother 2002; 46:3276.
  48. Mant TG. Multiple-dose pharmacokinetics of lomefloxacin: rationale for once-a-day dosing. Am J Med 1992; 92:26S.
  49. Lode H, Höffken G, Boeckk M, et al. Quinolone pharmacokinetics and metabolism. J Antimicrob Chemother 1990; 26 Suppl B:41.
  50. Nightingale CH. Overview of the pharmacokinetics of fleroxacin. Am J Med 1993; 94:38S.
  51. Flor S. Pharmacokinetics of ofloxacin. An overview. Am J Med 1989; 87:24S.
  52. Chien SC, Rogge MC, Gisclon LG, et al. Pharmacokinetic profile of levofloxacin following once-daily 500-milligram oral or intravenous doses. Antimicrob Agents Chemother 1997; 41:2256.
  53. Sörgel F, Kinzig M. Pharmacokinetics of gyrase inhibitors, Part 1: Basic chemistry and gastrointestinal disposition. Am J Med 1993; 94:44S.
  54. Staib AH, Beermann D, Harder S, et al. Absorption differences of ciprofloxacin along the human gastrointestinal tract determined using a remote-control drug delivery device (HF-capsule). Am J Med 1989; 87:66S.
  55. Healy DP, Brodbeck MC, Clendening CE. Ciprofloxacin absorption is impaired in patients given enteral feedings orally and via gastrostomy and jejunostomy tubes. Antimicrob Agents Chemother 1996; 40:6.
  56. Montay G. Pharmacokinetics of sparfloxacin in healthy volunteers and patients: a review. J Antimicrob Chemother 1996; 37 Suppl A:27.
  57. Lubasch A, Keller I, Borner K, et al. Comparative pharmacokinetics of ciprofloxacin, gatifloxacin, grepafloxacin, levofloxacin, trovafloxacin, and moxifloxacin after single oral administration in healthy volunteers. Antimicrob Agents Chemother 2000; 44:2600.
  58. Allen A, Bygate E, Vousden M, et al. Multiple-dose pharmacokinetics and tolerability of gemifloxacin administered orally to healthy volunteers. Antimicrob Agents Chemother 2001; 45:540.
  59. Preston SL, Drusano GL, Berman AL, et al. Pharmacodynamics of levofloxacin: a new paradigm for early clinical trials. JAMA 1998; 279:125.
  60. Stass H, Kubitza D. Pharmacokinetics and elimination of moxifloxacin after oral and intravenous administration in man. J Antimicrob Chemother 1999; 43 Suppl B:83.
  61. Sörgel F, Kinzig M. Pharmacokinetics of gyrase inhibitors, Part 2: Renal and hepatic elimination pathways and drug interactions. Am J Med 1993; 94:56S.
  62. Outman WR, Nightingale CH. Metabolism and the fluoroquinolones. Am J Med 1989; 87:37S.
  63. Efthymiopoulos C, Bramer SL, Maroli A, Gambertoglio JG. Effect of renal impairment on the pharmacokinetics of grepafloxacin. Clin Pharmacokinet 1997; 33 Suppl 1:32.
  64. Fillastre JP, Montay G, Bruno R, et al. Pharmacokinetics of sparfloxacin in patients with renal impairment. Antimicrob Agents Chemother 1994; 38:733.
  65. Malone RS, Fish DN, Abraham E, Teitelbaum I. Pharmacokinetics of levofloxacin and ciprofloxacin during continuous renal replacement therapy in critically ill patients. Antimicrob Agents Chemother 2001; 45:2949.
  66. Fuhrmann V, Schenk P, Jaeger W, et al. Pharmacokinetics of moxifloxacin in patients undergoing continuous venovenous haemodiafiltration. J Antimicrob Chemother 2004; 54:780.
  67. Fillastre JP, Leroy A, Moulin B, et al. Pharmacokinetics of quinolones in renal insufficiency. J Antimicrob Chemother 1990; 26 Suppl B:51.
  68. Montay G, Gaillot J. Pharmacokinetics of fluoroquinolones in hepatic failure. J Antimicrob Chemother 1990; 26 Suppl B:61.
  69. Bar-Oz B, Moretti ME, Boskovic R, et al. The safety of quinolones--a meta-analysis of pregnancy outcomes. Eur J Obstet Gynecol Reprod Biol 2009; 143:75.
  70. Loebstein R, Addis A, Ho E, et al. Pregnancy outcome following gestational exposure to fluoroquinolones: a multicenter prospective controlled study. Antimicrob Agents Chemother 1998; 42:1336.
  71. Bradley JS, Jackson MA, Committee on Infectious Diseases, American Academy of Pediatrics. The use of systemic and topical fluoroquinolones. Pediatrics 2011; 128:e1034.
  72. Burkhardt JE, Walterspiel JN, Schaad UB. Quinolone arthropathy in animals versus children. Clin Infect Dis 1997; 25:1196.
  73. American Academy of Pediatrics. Antimicrobial agents and related therapy. In: Red Book: 2015 Report of the Committee on Infectious Diseases, 30th ed, Kimberlin DW, Brady MT, Jackson MA, Long SS (Eds), American Academy of Pediatrics, Elk Grove Village, IL 2015. p.871.
  74. Orenstein DM, Pattishall EN, Noyes BE, et al. Safety of ciprofloxacin in children with cystic fibrosis. Clin Pediatr (Phila) 1993; 32:504.
  75. Sendzik J, Lode H, Stahlmann R. Quinolone-induced arthropathy: an update focusing on new mechanistic and clinical data. Int J Antimicrob Agents 2009; 33:194.
  76. Pichichero ME, Arguedas A, Dagan R, et al. Safety and efficacy of gatifloxacin therapy for children with recurrent acute otitis media (AOM) and/or AOM treatment failure. Clin Infect Dis 2005; 41:470.
  77. Bradley JS, Kauffman RE, Balis DA, et al. Assessment of musculoskeletal toxicity 5 years after therapy with levofloxacin. Pediatrics 2014; 134:e146.
  78. Lipsky BA, Baker CA. Fluoroquinolone toxicity profiles: a review focusing on newer agents. Clin Infect Dis 1999; 28:352.
  79. Ball P, Mandell L, Niki Y, Tillotson G. Comparative tolerability of the newer fluoroquinolone antibacterials. Drug Saf 1999; 21:407.
  80. Glaxo withdraws Raxar following seven fatal cardiovascular AEs. "The Pink Sheet", November 1, 1999, p.17.
  81. McDonald LC, Killgore GE, Thompson A, et al. An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med 2005; 353:2433.
  82. Halliwell RF, Davey PG, Lambert JJ. Antagonism of GABAA receptors by 4-quinolones. J Antimicrob Chemother 1993; 31:457.
  83. Hori S, Shimada S. Effects of quinolones on the central nervous system. In: Quinolone antimicrobial agents, 2nd ed, Hooper DC, Wolfson JS (Eds), American Society for Microbiology, Washington, DC 1993. p.513.
  84. Sutter R, Rüegg S, Tschudin-Sutter S. Seizures as adverse events of antibiotic drugs: A systematic review. Neurology 2015; 85:1332.
  85. Etminan M, Brophy JM, Samii A. Oral fluoroquinolone use and risk of peripheral neuropathy: a pharmacoepidemiologic study. Neurology 2014; 83:1261.
  86. US Food and Drug Administration. FDA Drug Safety Communication: FDA requires label changes to warn of risk for possibly permanent nerve damage from antibacterial fluoroquinolone drugs taken by mouth or by injection. http://www.fda.gov/downloads/Drugs/DrugSafety/UCM365078.pdf (Accessed on August 16, 2013).
  87. United States Food and Drug Administration. Risk of fluoroquinolone-associated myasthenia gravis exacerbation — February 2011 label changes for fluoroquinolones. http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm247115.htm (Accessed on March 16, 2011).
  88. Norrby SR. Side-effects of quinolones: comparisons between quinolones and other antibiotics. Eur J Clin Microbiol Infect Dis 1991; 10:378.
  89. Stahlmann R. Safety profile of the quinolones. J Antimicrob Chemother 1990; 26 Suppl D:31.
  90. Rizk E. The U.S. clinical experience with lomefloxacin, a new once-daily fluoroquinolone. Am J Med 1992; 92:130S.
  91. Rubinstein E. Safety profile of sparfloxacin in the treatment of respiratory tract infections. J Antimicrob Chemother 1996; 37 Suppl A:145.
  92. Ferguson J. Fluoroquinolone photosensitization: A review of clinical and laboratory studies. Photochem Photobiol 1995; 62:954.
  93. Owens RC Jr, Ambrose PG. Antimicrobial safety: focus on fluoroquinolones. Clin Infect Dis 2005; 41 Suppl 2:S144.
  94. Avelox (moxifloxacin hydrochloride) prescribing information. Bayer HealthCare Pharmaceuticals, Inc. Wayne, NJ. http://www.avelox.com/html/pdf/avelox_prescribing.pdf (Accessed on November 05, 2009).
  95. Levaquin (levofloxacin) prescribing information. Ortho-McNeil-Janssen Pharmaceuticals, Inc. Raritan, NJ. http://www.levaquin.com/levaquin/shared/pi/levaquin.pdf#zoom=100 (Accessed on November 05, 2009).
  96. Cipro (ciprofloxacin hydrochloride) prescribing information. Bayer HealthCare Pharmaceuticals, Inc. Wayne, NJ. http://www.univgraph.com/bayer/inserts/ciprotab.pdf (Accessed on November 05, 2009).
  97. Noroxin (norfloxacin) prescribing information. Merck & Co, Inc. Whitehouse Station, NJ. http://www.merck.com/product/usa/pi_circulars/n/noroxin/noroxin_pi.pdf (Accessed on November 05, 2009).
  98. Adam D. Use of quinolones in pediatric patients. Rev Infect Dis 1989; 11 Suppl 5:S1113.
  99. Schaad UB, Wedgwood J. Lack of quinolone-induced arthropathy in children. J Antimicrob Chemother 1992; 30:414.
  100. Zabraniecki L, Negrier I, Vergne P, et al. Fluoroquinolone induced tendinopathy: report of 6 cases. J Rheumatol 1996; 23:516.
  101. van der Linden PD, Sturkenboom MC, Herings RM, et al. Fluoroquinolones and risk of Achilles tendon disorders: case-control study. BMJ 2002; 324:1306.
  102. van der Linden PD, Sturkenboom MC, Herings RM, et al. Increased risk of achilles tendon rupture with quinolone antibacterial use, especially in elderly patients taking oral corticosteroids. Arch Intern Med 2003; 163:1801.
  103. Melhus A, Apelqvist J, Larsson J, Eneroth M. Levofloxacin-associated Achilles tendon rupture and tendinopathy. Scand J Infect Dis 2003; 35:768.
  104. Khaliq Y, Zhanel GG. Fluoroquinolone-associated tendinopathy: a critical review of the literature. Clin Infect Dis 2003; 36:1404.
  105. http://www.fda.gov/Safety/MedWatch/SafetyInformation/Safety-RelatedDrugLabelingChanges/ucm121598.htm (Accessed on April 23, 2012).
  106. Wise BL, Peloquin C, Choi H, et al. Impact of age, sex, obesity, and steroid use on quinolone-associated tendon disorders. Am J Med 2012; 125:1228.e23.
  107. Mehlhorn AJ, Brown DA. Safety concerns with fluoroquinolones. Ann Pharmacother 2007; 41:1859.
  108. Kang J, Wang L, Chen XL, et al. Interactions of a series of fluoroquinolone antibacterial drugs with the human cardiac K+ channel HERG. Mol Pharmacol 2001; 59:122.
  109. Ball P. Quinolone-induced QT interval prolongation: a not-so-unexpected class effect. J Antimicrob Chemother 2000; 45:557.
  110. Crouch MA, Limon L, Cassano AT. Clinical relevance and management of drug-related QT interval prolongation. Pharmacotherapy 2003; 23:881.
  111. Jaillon P, Morganroth J, Brumpt I, Talbot G. Overview of electrocardiographic and cardiovascular safety data for sparfloxacin. Sparfloxacin Safety Group. J Antimicrob Chemother 1996; 37 Suppl A:161.
  112. Lapi F, Wilchesky M, Kezouh A, et al. Fluoroquinolones and the risk of serious arrhythmia: a population-based study. Clin Infect Dis 2012; 55:1457.
  113. Ray WA, Murray KT, Hall K, et al. Azithromycin and the risk of cardiovascular death. N Engl J Med 2012; 366:1881.
  114. Inghammar M, Svanström H, Melbye M, et al. Oral fluoroquinolone use and serious arrhythmia: bi-national cohort study. BMJ 2016; 352:i843.
  115. Factive (gemifloxacin mesylate) prescribing information. Oscient Pharmaceuticals. Waltham, MA. http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=6881 (Accessed on November 05, 2009).
  116. Ciprofloxacin; US Food & Drug Administration (FDA) approved prescribing information. Revised January, 2015. US National Library of Medicine. www.dailymed.nlm.nih.gov.
  117. Teva-Norfloxacin; Health Canada Product Monograph. Revised May 21, 2015. Health Canada. http://webprod5.hc-sc.gc.ca/dpd-bdpp/index-eng.jsp.
  118. Norfloxacin; US Food & Drug Administration (FDA) approved prescribing information. Revised August, 2013. Drugs@FDA. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Label_ApprovalHistory#labelinfo.
  119. Paterson JM, Mamdani MM, Manno M, et al. Fluoroquinolone therapy and idiosyncratic acute liver injury: a population-based study. CMAJ 2012; 184:1565.
  120. Van Bambeke F, Tulkens PM. Safety profile of the respiratory fluoroquinolone moxifloxacin: comparison with other fluoroquinolones and other antibacterial classes. Drug Saf 2009; 32:359.
  121. Orman ES, Conjeevaram HS, Vuppalanchi R, et al. Clinical and histopathologic features of fluoroquinolone-induced liver injury. Clin Gastroenterol Hepatol 2011; 9:517.
  122. Chou HW, Wang JL, Chang CH, et al. Risk of severe dysglycemia among diabetic patients receiving levofloxacin, ciprofloxacin, or moxifloxacin in Taiwan. Clin Infect Dis 2013; 57:971.
  123. Bristol Tequin labeling update includes new indication, glucose warning. In: "The Pink Sheet" vol. 64 no. 43. F-D-C Reports, Inc. Chevy Chase, Maryland 2002. p.14.
  124. Hypoglycemia and hyperglycemia with fluroroquinolones. Med Lett Drugs Ther 2003; 45:64.
  125. Frothingham R. Glucose homeostasis abnormalities associated with use of gatifloxacin. Clin Infect Dis 2005; 41:1269.
  126. Park-Wyllie LY, Juurlink DN, Kopp A, et al. Outpatient gatifloxacin therapy and dysglycemia in older adults. N Engl J Med 2006; 354:1352.
  127. Aspinall SL, Good CB, Jiang R, et al. Severe dysglycemia with the fluoroquinolones: a class effect? Clin Infect Dis 2009; 49:402.
  128. Etminan M, Forooghian F, Brophy JM, et al. Oral fluoroquinolones and the risk of retinal detachment. JAMA 2012; 307:1414.
  129. Pasternak B, Svanström H, Melbye M, Hviid A. Association between oral fluoroquinolone use and retinal detachment. JAMA 2013; 310:2184.
  130. Kapoor KG, Hodge DO, St Sauver JL, Barkmeier AJ. Oral fluoroquinolones and the incidence of rhegmatogenous retinal detachment and symptomatic retinal breaks: a population-based study. Ophthalmology 2014; 121:1269.
  131. FDA Drug Safety Communication: FDA advises restricting fluoroquinolone antibiotic use for certain uncomplicated infections; warns about disabling side effects that can occur together. http://www.fda.gov/Drugs/DrugSafety/ucm500143.htm (Accessed on May 26, 2016).
  132. Radandt JM, Marchbanks CR, Dudley MN. Interactions of fluoroquinolones with other drugs: mechanisms, variability, clinical significance, and management. Clin Infect Dis 1992; 14:272.
  133. Polk RE, Healy DP, Sahai J, et al. Effect of ferrous sulfate and multivitamins with zinc on absorption of ciprofloxacin in normal volunteers. Antimicrob Agents Chemother 1989; 33:1841.
  134. Robson RA. The effects of quinolones on xanthine pharmacokinetics. Am J Med 1992; 92:22S.
  135. Stahlmann R, Schwabe R. Safety profile of grepafloxacin compared with other fluoroquinolones. J Antimicrob Chemother 1997; 40 Suppl A:83.
  136. Israel DS, Stotka J, Rock W, et al. Effect of ciprofloxacin on the pharmacokinetics and pharmacodynamics of warfarin. Clin Infect Dis 1996; 22:251.