Fluoroquinolones. Levofloxacin vs. ciprofloxacin. Is the choice obvious? Review article
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Published:
Jun 30, 2025
Keywords:
fluoroquinolones, adverse reactions, neuropathy, ciprofloxacin, levofloxacin, safety, toxicity
Main Article Content
Abstract
The fluoroquinolone class of antibacterial agents are among the most frequently prescribed drugs, with utility in a broad range of bacterial infections. Although very useful agents, the fluoroquinolones as a class are associated with a number of adverse events, some with considerable clinical significance. In the past 15–20 years, tolerability concerns have led to restrictions on the use of the fluoroquinolones and, in some instances, even to their withdrawal. Adverse events commonly associated with the fluoroquinolones include gastrointestinal and central nervous system toxicity (most frequently headache and dizziness), as well as other adverse events including ECG abnormalities (for example QT interval prolongation), disrupted glucose metabolism, phototoxicity, tendon and joint disorders, hypersensitivity and skin disorders, and hepatic toxicity. These differences may be explained, at least in part, by structural differences. Furthermore, many of the fluoroquinolone-associated adverse effects and toxicities occur more frequently in patients with pre-existing risk factors, or in certain subpopulations. Overall, it appears that levofloxacin is relatively well tolerated, with low rates of clinically important adverse events such as central nervous system toxicity, cardiovascular toxicity and dysglycaemia.
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Wiatr, T., Chłosta, P., & Chłosta, M. (2025). Fluoroquinolones. Levofloxacin vs. ciprofloxacin. Is the choice obvious?. Medycyna Faktow (J EBM), 18(2(67), 227-232. https://doi.org/10.24292/01.MF.0225.09
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References
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14. Humphries RM, Hindler JA, Shaffer K et al. Evaluation of ciprofloxacin and levofloxacin disk diffusion and etest using the 2019 Enterobacteriaceae CLSI breakpoints. J Clin Microbiol. 2019; 57(3): https://doi.org/10.1128/jcm.01797-18.
15. Cao D, Shen Y, Huang Y et al. Levofloxacin Versus Ciprofloxacin in the Treatment of Urinary Tract Infections: Evidence-Based Analysis. Front Pharmacol. 2021; 12: 658095. https://doi.org/10.3389/fphar.2021.658095.
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24. Richard GA, Klimberg IN, Fowler C et al. A combined analysis of two studies comparing levofloxacin with two other fluoroquinolones for the treatment of acute pyelonephritis (Abstract LM3) In: Program and Abstracts of the 36th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 15-18, 1996; New Orleans, LA.
25. Habib MP, Gentry LO, Rodriguez-Gomez G et al. Multi-center, randomized study comparing efficacy and safety of oral levofloxacin and cefaclor in treatment of acute bacterial exacerbation of chronic bronchitis. Infect Dis Clin Pract. 1998; 7: 101-9.
26. 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: 69-74.
27. North DS, Fish DN, Redington JJ. Levofloxacin, a second-generation fluoroquinolone. Pharmacotherapy. 1998; 18: 915-35.
28. Davis R, Bryson HM. Levofloxacin. A review of its antibacterial activity, pharmacokinetics and therapeutic efficacy. Drugs. 1994; 47: 677-700.
29. Wagai N, Yoshida M, Takayama S. Phototoxic potential of the new quinolone antibacterial agent levofloxacin in mice. Arzneimittelforschung. 1992; 42: 404-5.
30. Lipsky BA, Baker CA. Fluoroquinolone toxicity profiles: a review focusing on newer agents. Clin Infect Dis. 1999; 28: 352-64.
31. Richard GA, Childs S, Fowler C et al. A comparison of levofloxacin and ciprofloxacin for the treatment of complicated urinary tract infections. Clin Infect Dis. 1996; 23: 913 abstract 293.
32. Richard GA, Klimberg IN, Fowler CL et al. Levofloxacin versus ciprofloxacin versus lemofloxacin in acute pyelonephritis. Urology. 1998; 51: 51-5.
33. Öztürk R, Murt A. Epidemiology of urological infections: a global burden. World J Urol. 2020; 38(11): 2669-79.
34. Mongioi L, Calogero AE, Vicari E et al. The role of carnitine in male infertility. Andrology. 2016; 4(5): 800-7. https://doi.org/10.1111/andr.12191.
35. Zhang ZC, Jin FS, Liu DM et al. Safety and efficacy of levofloxacin versus ciprofloxacin for the treatment of chronic bacterial prostatitis in Chinese patients. Asian J Androl. 2012; 14(6): 870-4. https://doi.org/10.1038/aja.2012.48.
36. Bundrick W, Heron SP, Ray P et al. Levofloxacin versus ciprofloxacin in the treatment of chronic bacterial prostatitis: a randomized double-blind multicenter study. Urology. 2003; 62(3): 537-41. https://doi.org/10.1016/s0090-4295(03)00565-x.
37. Lee DS, Lee SJ, Choe HS. Community-acquired urinary tract infection by Escherichia coli in the era of antibiotic resistance. Biomed Res Int. 2018; 1: https://doi.org/10.1155/2018/7656752.
38. Craig WA. State-of-the-Art clinical article: pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis. 1998; 26(1): 1-10. https://doi.org/10.1086/516284.
39. Naber KG. Which fluoroquinolones are suitable for the treatment of urinary tract infections? Int J Antimicrob Agents. 2001; 17(4): 331-41. https://doi.org/10.1016/s0924-8579(00)00362-9.
40. Drusano GL, Preston SL, Van Guilder M et al. A population pharmacokinetic analysis of the penetration of the prostate by levofloxacin. Antimicrob Agents Chemother. 2000; 44(8): 2046-51. https://doi.org/10.1128/aac.44.8.2046-2051.2000.
41. Wagenlehner FME, Kinzig-Schippers M, Sörgel F et al. Concentrations in plasma, urinary excretion and bactericidal activity of levofloxacin (500mg) versus ciprofloxacin (500mg) in healthy volunteers receiving a single oral dose. Int J Antimicrob Agents. 2006; 28(6): 551-9. https://doi.org/10.1016/j.ijantimicag.2006.07.026.
42. Stahlmann R, Lode HM. Risks associated with the therapeutic use of fluoroquinolones. Expert Opin Drug Saf. 2013; 12(4): 497-505. https://doi.org/10.1517/14740338.2013.796362.
43. Klausner HA, Brown P, Peterson J et al. A trial of levofloxacin 750 mg once daily for 5 days versus ciprofloxacin 400 mg and/or 500 mg twice daily for 10 days in the treatment of acute pyelonephritis. Curr Med Res Opin. 2007; 23(11): 2637-45. https://doi.org/10.1185/030079907x233340.
44. Peterson J, Kaul S, Khashab M et al. A double-blind, randomized comparison of levofloxacin 750 mg once-daily for five days with ciprofloxacin 400/500 mg twice-daily for 10 days for the treatment of complicated urinary tract infections and acute pyelonephritis. Urology. 2008; 71(1): 17-22. https://doi.org/10.1016/j.urology.2007.09.002.
45. Martin SJ, Sahloff EG, Close SJ. Evaluation and cost assessment of fluoroquinolones in community-acquired respiratory infections. Expert Opin Pharmacother. 2002; 3(9): 1251-66.
2. Flores-Mireles AL, Walker JN, Caparon M et al. Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nat Rev Microbiol. 2015; 13(5): 269-84. https://doi.org/10.1038/nrmicro3432.
3. Stamm WE, Norrby SR. Urinary tract infections: disease panorama and challenges. J Infect Dis. 2001; 183(Suppl 1): S1-4. https://doi.org/10.1086/318850.
4. Zusso M, Lunardi V, Franceschini D et al. Ciprofloxacin and levofloxacin attenuate microglia inflammatory response via TLR4/NF-kB pathway. J Neuroinflammation. 2019; 16(1): 148. https://doi.org/10.1186/s12974-019-1538-9.
5. Rambaran KA, Seifert CF. Ciprofloxacin vs. levofloxacin for prophylaxis in recipients of hematopoietic stem cell transplantation. J Oncol Pharm Pract. 2019; 25(4): 884-90. https://doi.org/10.1177/1078155218787286.
6. Karampela I, Dalamaga M. Could respiratory fluoroquinolones, levofloxacin and moxifloxacin, prove to be beneficial as an adjunct treatment in COVID-19? Arch Med Res. 2020; 51(7): 741-2. https://doi.org/10.1016/j.arcmed.2020.06.004.
7. Bader MS, Loeb M, Brooks AA. An update on the management of urinary tract infections in the era of antimicrobial resistance. Postgrad Med. 2017; 129(2): 242-58. https://doi.org/10.1080/00325481.2017.1246055.
8. Chu CM, Lowder JL. Diagnosis and treatment of urinary tract infections across age groups. Am J Obstet Gynecol. 2018; 219(1): 40-51. https://doi.org/10.1016/j.ajog.2017.12.231.
9. Bientinesi R, Murri R, Sacco E. Efficacy and safety of levofloxacin as a treatment for complicated urinary tract infections and pyelonephritis. Expert Opin Pharmacother. 2020; 21(6): 637-44. https://doi.org/10.1080/14656566.2020.1720647.
10. Choe HS, Lee SJ, Cho YH et al. Aspects of urinary tract infections and antimicrobial resistance in hospitalized urology patients in Asia: 10-Year results of the Global Prevalence Study of Infections in Urology (GPIU). J Infect Chemother. 2018; 24(4): 278-83. https://doi.org/10.1016/j.jiac.2017.11.013.
11. Kranz J, Schmidt S, Lebert C et al. The 2017 update of the German clinical guideline on epidemiology, diagnostics, therapy, prevention, and management of uncomplicated urinary tract infections in adult patients. Part II: therapy and prevention. Urol Int. 2018; 100 (3): 271-8. https://doi.org/10.1159/000487645.
12. Unnikrishnan R, El-Shafei A, Klein EA et al. For Single Dosing, Levofloxacin Is Superior to Ciprofloxacin When Combined With an Aminoglycoside in Preventing Severe Infections After Prostate Biopsy. Urology. 2015; 85(6): 1241-6.
13. Afriyie DK, Adu LB, Dzradosi M et al. Comparative in vitro activity of ciprofloxacin and levofloxacin against isolated uropathogens in Ghana: a pilot study. Pan Afr Med J. 2018; 30: 194. https://doi.org/10.11604/pamj.2018.30.194.15457.
14. Humphries RM, Hindler JA, Shaffer K et al. Evaluation of ciprofloxacin and levofloxacin disk diffusion and etest using the 2019 Enterobacteriaceae CLSI breakpoints. J Clin Microbiol. 2019; 57(3): https://doi.org/10.1128/jcm.01797-18.
15. Cao D, Shen Y, Huang Y et al. Levofloxacin Versus Ciprofloxacin in the Treatment of Urinary Tract Infections: Evidence-Based Analysis. Front Pharmacol. 2021; 12: 658095. https://doi.org/10.3389/fphar.2021.658095.
16. Thai T, Salisbury BH, Zito PM. Ciprofloxacin. 2023 Aug 28. In: StatPearls [Internet]. StatPearls Publishing, Treasure Island (FL) 2025 Jan–.
17. Segev S, Yaniv I, Haverstockg D et al. Safety of long-term ciprofloxacin: data analysis of controlled clinical trials and review. Clin Infect Dis. 1999; 28: 299-308.
18. Pryka R, Kowasksy S, Haverstock D. Efficacy and tolerability of twice-daily ciprofloxacin 750 mg in the treatment of patients with acute exacerbations of chronic bronchitis and pneumonia. Clin Ther. 1998; 20: 141-55.
19. Schacht P, Arcieri G, Hullman R. Safety of oral ciprofloxacin. An update based on clinical trial results. Am J Med. 1989; 87: 98S-102S.
20. Deamer RL, Prichard JG, Luman GJ. Hypersensitivity and anaphylactoid reactions to ciprofloxacin. Ann Pharmacother. 1992; 26: 1081-4.
21. Norrby SR. Levofloxacin. Expert Opin Pharmacother. 1999; 1: 109-19.
22. Martin SJ, Jung R, Garvin CG. A risk-benefit assessment of levofloxacin in respiratory, skin and skin structure, and urinary tract infections. Drug Saf. 2001; 24: 199-222.
23. File TM, Segreti J, Dunbar L et al. A multi-center randomized study comparing the efficacy and safety of IV and/or oral levofloxacin versus ceftriaxone and/or cefuroxime axetil in the treatment of adults with community-acquired pneumonia. Antimicrob Agents Chemother. 1997; 41: 1965-72.
24. Richard GA, Klimberg IN, Fowler C et al. A combined analysis of two studies comparing levofloxacin with two other fluoroquinolones for the treatment of acute pyelonephritis (Abstract LM3) In: Program and Abstracts of the 36th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 15-18, 1996; New Orleans, LA.
25. Habib MP, Gentry LO, Rodriguez-Gomez G et al. Multi-center, randomized study comparing efficacy and safety of oral levofloxacin and cefaclor in treatment of acute bacterial exacerbation of chronic bronchitis. Infect Dis Clin Pract. 1998; 7: 101-9.
26. 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: 69-74.
27. North DS, Fish DN, Redington JJ. Levofloxacin, a second-generation fluoroquinolone. Pharmacotherapy. 1998; 18: 915-35.
28. Davis R, Bryson HM. Levofloxacin. A review of its antibacterial activity, pharmacokinetics and therapeutic efficacy. Drugs. 1994; 47: 677-700.
29. Wagai N, Yoshida M, Takayama S. Phototoxic potential of the new quinolone antibacterial agent levofloxacin in mice. Arzneimittelforschung. 1992; 42: 404-5.
30. Lipsky BA, Baker CA. Fluoroquinolone toxicity profiles: a review focusing on newer agents. Clin Infect Dis. 1999; 28: 352-64.
31. Richard GA, Childs S, Fowler C et al. A comparison of levofloxacin and ciprofloxacin for the treatment of complicated urinary tract infections. Clin Infect Dis. 1996; 23: 913 abstract 293.
32. Richard GA, Klimberg IN, Fowler CL et al. Levofloxacin versus ciprofloxacin versus lemofloxacin in acute pyelonephritis. Urology. 1998; 51: 51-5.
33. Öztürk R, Murt A. Epidemiology of urological infections: a global burden. World J Urol. 2020; 38(11): 2669-79.
34. Mongioi L, Calogero AE, Vicari E et al. The role of carnitine in male infertility. Andrology. 2016; 4(5): 800-7. https://doi.org/10.1111/andr.12191.
35. Zhang ZC, Jin FS, Liu DM et al. Safety and efficacy of levofloxacin versus ciprofloxacin for the treatment of chronic bacterial prostatitis in Chinese patients. Asian J Androl. 2012; 14(6): 870-4. https://doi.org/10.1038/aja.2012.48.
36. Bundrick W, Heron SP, Ray P et al. Levofloxacin versus ciprofloxacin in the treatment of chronic bacterial prostatitis: a randomized double-blind multicenter study. Urology. 2003; 62(3): 537-41. https://doi.org/10.1016/s0090-4295(03)00565-x.
37. Lee DS, Lee SJ, Choe HS. Community-acquired urinary tract infection by Escherichia coli in the era of antibiotic resistance. Biomed Res Int. 2018; 1: https://doi.org/10.1155/2018/7656752.
38. Craig WA. State-of-the-Art clinical article: pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis. 1998; 26(1): 1-10. https://doi.org/10.1086/516284.
39. Naber KG. Which fluoroquinolones are suitable for the treatment of urinary tract infections? Int J Antimicrob Agents. 2001; 17(4): 331-41. https://doi.org/10.1016/s0924-8579(00)00362-9.
40. Drusano GL, Preston SL, Van Guilder M et al. A population pharmacokinetic analysis of the penetration of the prostate by levofloxacin. Antimicrob Agents Chemother. 2000; 44(8): 2046-51. https://doi.org/10.1128/aac.44.8.2046-2051.2000.
41. Wagenlehner FME, Kinzig-Schippers M, Sörgel F et al. Concentrations in plasma, urinary excretion and bactericidal activity of levofloxacin (500mg) versus ciprofloxacin (500mg) in healthy volunteers receiving a single oral dose. Int J Antimicrob Agents. 2006; 28(6): 551-9. https://doi.org/10.1016/j.ijantimicag.2006.07.026.
42. Stahlmann R, Lode HM. Risks associated with the therapeutic use of fluoroquinolones. Expert Opin Drug Saf. 2013; 12(4): 497-505. https://doi.org/10.1517/14740338.2013.796362.
43. Klausner HA, Brown P, Peterson J et al. A trial of levofloxacin 750 mg once daily for 5 days versus ciprofloxacin 400 mg and/or 500 mg twice daily for 10 days in the treatment of acute pyelonephritis. Curr Med Res Opin. 2007; 23(11): 2637-45. https://doi.org/10.1185/030079907x233340.
44. Peterson J, Kaul S, Khashab M et al. A double-blind, randomized comparison of levofloxacin 750 mg once-daily for five days with ciprofloxacin 400/500 mg twice-daily for 10 days for the treatment of complicated urinary tract infections and acute pyelonephritis. Urology. 2008; 71(1): 17-22. https://doi.org/10.1016/j.urology.2007.09.002.
45. Martin SJ, Sahloff EG, Close SJ. Evaluation and cost assessment of fluoroquinolones in community-acquired respiratory infections. Expert Opin Pharmacother. 2002; 3(9): 1251-66.