Ciprofloxacin versus Trimethoprim/Sulfamethoxazole (TMP-SMX)

Based on "Antibiotic and Chemotherapy"
written by Roger G. Finch

Main differences between Ciprofloxacin and TMP-SMZ

  Ciprofloxacin TMP-SMX
Brand names • Cipro®
• Cipro XR®
• ProQuin XR®
• Bactrim®
• Bactrim DS®
• Septra®
• Septra DS®
Drug class Fluoroquinolone antibiotic Combination of dihydrofolate reductase inhibitor and sulfonamide antibiotic,
folate-antagonist anti-infectives
Half-life 4 hours sulfamethoxazole 10 hours
trimethoprim 8-10 hours
Elimination 65% is excreted in the urine as unchanged drug
30% as unchanged drug in the feces
Primarily by the kidneys through glomerular filtration and tubular secretion. Urine concentrations are higher than blood concentrations.
Metabolized in the liver
Spectrum of activity Gram-negative aerobic bacteria, some atypical bacteria. Gram-positive and Gram-negative aerobic bacteria and some protozoa.
Good activity against Pseudomonas aeruginos Pseudomonas aeruginosa is resistant.
Side Effects & Toxicities Phototoxicity
Risk of tendinitis and tendon rupture
Possibility of CNS effects, QT interval prolongation
Severe hypersensitivity reactions related to sulfonamide component 2.
Hematologic toxicity
Hyperkalemia and hyponatremia
Renal damage from crystalluria
Special populations Pregnancy Category C,
possible risk of arthropathy.

Pregnancy Category C,
antifolate effects, may cause kernicterus in neonates.

Caution in patient with possible folate deficiency.
Children Approved for use in children only for life-threatening infections Approved for use in children >2 months of age.
Drug interactions Inhibits cytochrome P450 CYP3A4.
May cause serious drug interactions with antiarrhythmic agents, warfarin, tizanidine, theophylline.
May cause accumulation of drugs metabolized by cytochrome P450 2C8 or 2C9.
May inhibit warfarin clearance and prolong the prothrombin time.
May increase digoxin concentrations, especially in elderly.
Possible potentiation of hypoglycemic effects of sulfonylureas and repaglinide 2.

Urinary tract infection

Ciprofloxacin and Trimethoprim/Sulfamethoxazole are equally effective for treatment of urinary tract infections.

Urinary E. coli is more frequently resistant to trimethoprim-sulfamethoxazole than to ciprofloxacin 6.

Ciprofloxacin is less toxic and better tolerated. Fewer patients prematurely discontinue ciprofloxacin than trimethoprim/sulfamethoxazole because of side effects.

Results of randomized double-blind study of ciprofloxacin and co-trimoxazole in urinary tract infection 3. Ciprofloxacin TMP-SMX
Regimen 100-250 mg twice a day for 5 days. 960 mg twice a day for 5 days.
Cure rates at 28 days

Results of controlled, double-blind comparison of ciprofloxacin versus trimethoprim-sulfamethoxazole for community-acquired urinary tract infections 4. Ciprofloxacin TMP-SMX
Regimen 250 mg twice daily for 10 days 160/800 mg twice daily for 10 days
Success rate
7 of 103
6 of 100
Adverse reactions rate

Results of comparison of ciprofloxacin and co-trimoxazole for uncomplicated urinary tract infection in women 5. Ciprofloxacin TMP-SMX
Regimen 250 mg twice daily for 10 days 160/800 mg twice daily for 10 days
Eradication rate
100% (31 of 31 patients)
Complete resolution of clinical symptoms
100% (31 of 31 patients)
Relapsed rate
6.5% (2 of 31 patients)
18% (6 of 34 patients)
Overall cure rates
Tolerability   increase in adverse side effects

Results of randomized, open-label, study of ciprofloxacin versus trimethoprim-sulfamethoxazole for older women with acute urinary tract infection 7. Ciprofloxacin TMP-SMX
Regimen 250 mg/5 mL twice daily for 10 days. 160/800 mg/20 mL twice daily for 10 days.
Clinical resolution of symptoms
Eradication of pretreatment bacterial isolates posttherapy rate
Posttherapy clinical resolution for the intent-to-treat population
Incidence of adverse effects
Incidence of premature discontinuation due to adverse effects

See also:


Ciprofloxacin is more effective than trimethoprim-sulfamethoxazole for pyelonephritis 1.

Results of randomized comparison of ciprofloxacin and trimethoprim-sulfamethoxazole for acute uncomplicated pyelonephritis 1. Ciprofloxacin TMP-SMX
Regimen 500 mg twice per day for 7 days 160/800 mg twice per day for 14 days
Bacteriologic cure rates 99% (112 of 113) 89% (90 of 101)
Clinical cure rates 96% (109 of 113) 83% (92 of 111)
Adverse effects rate 24% of 191 patients 33% of 187 patients

Travelers' Diarrhea

Ciprofloxacin provides more effective prophylaxis for travelers' diarrhea than TMP/SMZ 8.

Results of randomized, double-blind, placebo-controlled comparison of trimethoprim/sulfamethoxazole versus ciprofloxacin for prevention of travelers' diarrhea 8. Ciprofloxacin TMP-SMX
Regimen 500 mg once daily 160/800 mg once daily
Number of patients who experienced diarrhea 5 of the 99 patients (5%) 14 of the 87 patients (16%)
Identification of bacterial pathogens   more frequently
Incidence of adverse reactions

Further reading


  • 1. Talan DA, Stamm WE, Hooton TM, Moran GJ, Burke T, Iravani A, Reuning-Scherer J, Church DA. Comparison of ciprofloxacin (7 days) and trimethoprim-sulfamethoxazole (14 days) for acute uncomplicated pyelonephritis in women: a randomized trial. JAMA. 2000 Mar 22-29;283(12):1583-90. PubMed
  • 2. Ho JM, Juurlink DN. Considerations when prescribing trimethoprim-sulfamethoxazole. CMAJ. 2011 Nov 8;183(16):1851-8.
  • 3. Williams AH, Grüneberg RN. Ciprofloxacin and co-trimoxazole in urinary tract infection. J Antimicrob Chemother. 1986 Nov;18
  • 4. Grubbs NC, Schultz HJ, Henry NK, Ilstrup DM, Muller SM, Wilson WR. Ciprofloxacin versus trimethoprim-sulfamethoxazole: treatment of community-acquired urinary tract infections in a prospective, controlled, double-blind comparison. Mayo Clin Proc. 1992 Dec;67(12):1163-8. PubMed
  • 5. Henry NK, Schultz HJ, Grubbs NC, Muller SM, Ilstrup DM, Wilson WR. Comparison of ciprofloxacin and co-trimoxazole in the treatment of uncomplicated urinary tract infection in women. J Antimicrob Chemother. 1986 Nov
  • 6. Sanchez GV, Master RN, Karlowsky JA, Bordon JM. In vitro antimicrobial resistance of urinary Escherichia coli isolates among U.S. outpatients from 2000 to 2010. Antimicrob Agents Chemother. 2012 Apr;56(4):2181-3. PubMed
  • 7. Gomolin IH, Siami PF, Reuning-Scherer J, Haverstock DC, Heyd A; Oral Suspension Study Group. Efficacy and safety of ciprofloxacin oral suspension versus trimethoprim-sulfamethoxazole oral suspension for treatment of older women with acute urinary tract infection. J Am Geriatr Soc. 2001 Dec;49(12):1606-13. PubMed
  • 8. Heck JE, Staneck JL, Cohen MB, Weckbach LS, Giannella RA, Hawkins J, Tosiello R. Prevention of Travelers' Diarrhea: Ciprofloxacin versus Trimethoprim/Sulfamethoxazole in Adult Volunteers Working in Latin America and the Caribbean. J Travel Med. 1994 Sep 1;1(3):136-142.

Published: April 01, 2014
Last updated: May 19, 2018


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