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The discovery and development of ciprofloxacin is that rare case of an actual groundbreaking new drug development, opening up an entire new class of antibiotics for further research, development, and marketing.

Ciprofloxacin (Cipro) was the first fluoroquinolone to be on the market. It was discovered in 1981 by Bayer, the German-based drug and chemical company. In 1987 Cipro was approved by the FDA in the United States as the first oral broad-spectrum antibiotic of this class. An intravenous formulation followed in 1991. Cipro has been extensively studied and its safety profile is well documented in more than 32,000 publications.

• Urinary tract infections: urethritis (infection of the urethra), cystitis (infection of the bladder ), pyelonephritis (infection of the kidneys).
• Acute uncomplicated cystitis in women
• Chronic bacterial prostatitis
• Lower respiratory infections (pneumonia, bronchitis, tracheobronchitis). Ciprofloxacin is not a drug of first choice in the treatment of pneumonia secondary to Streptococcus pneumoniae.
• Acute sinusitis (inflammation of the paranasal sinuses).
• Skin and skin structure infections: cellulitis (infection of the dermis and subcutaneous tissue), erysipelas (superficial form of cellulitis), folliculitis (inflammation of the hair follicles, if the infection of the follicle is deeper and involves more follicles, it moves into the furuncle and carbuncle), furuncles, carbuncles, abscesses, impetigo (large vessicles or honey-crusted sores), infected ulcers and infected burns and other.
• Bone and joint infections: septic (infectious) arthritis (infection in the fluid and tissues of a joint), osteomyelitis (bone infection).
• Complicated intra-abdominal infections (used in combination with metronidazole). Complicated intra-abdominal infections are defined by the FDA as those in which an operation would not remove all of the infected tissue. Intra-abdominal infections include: intra-abdominal abscess, peritonitis (infection of the abdominal cavity and its lining), cholecystitis, cholangitis, diverticulitis and some other.
• Infectious diarrhea: Escherichia coli infection, Campylobacter infection, and shigellosis.
• Typhoid fever (enteric fever) .
• STDs: uncomplicated cervical and urethral gonorrhea
• Complicated urinary tract iInfections and pyelonephritis in children (1 to 17 years of age)
• Inhalational anthrax (post-exposure) to reduce the incidence or progression of disease following exposure to aerosolized Bacillus anthracis (in adults and children)

Ciprofloxacin is not effective in the treatment of syphilis.

• Chlamydia infections 2, 3.
  In general, ciprofloxacin is not the best option for Chlamydia infections. Although it has good activity ahgainst Chlamydia in laboratory environment, ciprofloxacin even in high dosages of 2 g daily is insufficient for treatment of chlamydial infection and often results in relapsing infection 3. Doxycycline and azithromycin are more effective options for Chlamydia.
• Mycoplasma infections 15.
  Ciprofloxacin is not the optimal antibiotic for pneumonia caused by Mycoplasma pneumoniae 16, however it may be effective for genital Micoplasma infections.
• Gonorrhea in adolescents 23.
  Single 500-mg dose of ciprofloxacin is among the treatment regimens recommended by Centers for Disease Control and Prevention (CDC) to treat uncomplicated gonorrhea infection in adolescents.
• Pelvic inflammatory disease (PID) 11-13 .
  PID is the infection of the upper female reproductive organs. PID can affect the cervix (cervicitis), uterus (endometritis), fallopain tubes (salpingitis) and ovaries (oophoritis). Ciprofloxacin is not an optimal effective treatment for pelvic inflammatory disease if used alone 14.
• Inflammatory bowel diseases (IBD) 9-10.
  The research suggests that ciprofloxacin produces anti-inflammatory effect on intestinal inflammation.
• Chronic ear disease 30-31.
  Chronic suppurative otitis media is a common and potentially dangerous chronic ear disease that is difficult to treat, because the most common infecting organisms are often resistant to many antibiotics. Ciprofloxacin is an effective treatment for suppurative chronic otitis media in adults. The research study demonstrated that ciprofloxacin can also effectively treat suppurative otitis media in children.
• Salmonellosis 22.
  In severe salmonellosis, short treatment with ciprofloxacin is safe and promotes rapid recovery.
• Legionnaires' disease (Legionella pneumonia) 29.
  Legionnaires' disease is a pneumonia caused by bacteria Legionella pneumophila. Intravenous ciprofloxacin is effective treatment of Legionella pneumonia.
• Cystic fibrosis 26.
  Cystic fibrosis (mucoviscidosis) is a hereditary disease that mainly affects the lungs and digestive system. Antibiotics are often used to treat cystic fibrosis. Some antibiotics may be prescribed to help prevent infections, while others may be prescribed to help fight infections. Fluoroquinolones are effective against most gram-positive and gram-negative organisms. They are the only class of oral antibiotics effective against P. aeruginosa. According to the studies, Ciprofloxacin may be safe and effective abtibiotic in young persons with bronchopulmonary exacerbation of cystic fibrosis.
• Tuberculosis 27-28.
  Ciprofloxacin may be an effective option for tuberculosis in persons who cannot use conventional anti-tuberculosis medications or for multidrug-resistant tuberculosis.
• Cat-scratch disease in adults 17.
  Cat scratch fever is a usually benign infectious disease caused by the intracellular parasite Bartonella. Ciprofloxacin appears to be an effective treatment for cat-scratch disease.
  
• Brucellosis 19-20.
  Brucellosis (also known as undulant fever or Malta fever) is infectious disease transmitted from animals to humans and exists worldwide. It is caused by bacteria Brucella. Despite the high in vitro (in test-tube) activity of antibiotic against brucella, the treatment of brucellosis frequently results in therapeutic failures and relapse of infection 18. Combination of ciprofloxacin with rifampicin may be quite effective for serious cases of this disease 20.
• Cholera 21.
  Cholera is an extreme diarrheal disease caused by the bacterium Vibrio cholerae. Single-dose ciprofloxacin is an effective treatment of severe cholera in adults and children.
• Tularemia 24.
  Tularemia (rabbit fever) is a serious infectious disease caused by the bacterium Francisella tularensis. Oral ciprofloxacin may be an effective alternative to injection therapy.

• Advantages:
• Ease of use - twice daily dosing.
• Broad spectrum of antibacterial activity.
• Ciprofloxacin is the only fluoroquinolone currently approved for post-exposure prophylaxis of anthrax.
• Excellent bioavailability both orally and intravenously. Oral ciprofloxacin is 70-80% bioavailable, meaning that a 500 mg oral dose gives plasma concentrations in the same range as a 400 mg IV dose.
• Good tissue penetration (especially in kidneys, gallbladder, liver, lungs, gynecological tissue, and prostatic tissue).
• Inexpensive and is available in generic version.
• Does not cause a significant prolongation in the QT interval 1.
• Most effective antibiotic against P. aeruginosa (bacteria that causes infections of the pulmonary tract, external ear, urinary tract, burns, and wounds and is the most frequent colonizer of medical devices (e.g.catheters)), which is becoming increasingly resistant to antibiotic treatment.
• Experience is favorable and extensive for nosocomial pneumonia, osteomyelitis, neutropenic fever, travelers diarrhea, chronic prostatitis and UTIs.
• Disadvantages:
• Poor activity against Streptococcus pneumoniae (major cause of pneumonia and meningitis).
• Several serious drug interactions (e.g. theophylline, propranolol). Ciprofloxacin can inhibit (prevent the activity) one of the pathways that is used to eliminate medications from the body. This pathway, called CYP1A2, works through an enzyme in the liver known as cytochrome P450 1A2. If CYP1A2 is inhibited, and the dose of these medications is not reduced, the medicine could accumulate in the body to levels that could cause serious adverse drug reactions.
• Widespread use of Ciprofloxacin, often inappropriate, resulted in increasing rates of microbal resistance (development of resistance in P. aeruginosa, Salmonella, Neisseria gonorrhoeae).
• Tendon damage. Achilles tendon is the most susceptible, however other tendons also may be affected. Usually, spontaneous tendon rupture occurs during or shortly after a course of antibiotic, but symptoms may occur months after taking the medication. Risk factors for tendon damage include use of corticosteroids, hypercholesterolemia, gout, rheumatoid arthritis, advanced age, long-term dialysis, and renal transplantation.
• Peripheral neuropathy (peripheral nervous system side effects). The symptoms of neuropathy include pain, burning, tingling, numbness, and/or weakness, or is found to have deficits in light touch, pain, temperature, position sense, vibratory sensation, and/or motor strength. Ciprofloxacin should be stopped if person experiences these symptoms in order to prevent the development of an irreversible condition.
• Phototoxicity.
• Severe allergic reactions.
• Crystalluria (crystals in the urine). Ciprofloxacin may induce calculi (kidney stones) via urinary supersaturation. The risk is higher when urinary pH is greater than 7.3 and antibiotic doses are greater than 1000 mg.
• Absorption of the drug may be significantly reduced by dairy products. Ciprofloxacin should not be taken with dairy or calcium-fortified juices alone. However, it may be taken with a meal that contains these products (eg. cereal with milk).
• Decrease the metabolism of caffeine ( the half-life of caffeine significantly increases) 7.
• Rare cases of vision disturbance 8.
• Ciprofloxacin may delay the fracture healing 25. The research data suggest that use of ciprofloxacin during early fracture repair may compromise the clinical course of fracture-healing.

Ciprofloxacin is a synthetic bactericidal antibiotic that inhibits bacterial nuclear DNA synthesis, so that bacteria rapidly die. The target is the enzyme DNA gyrase (topoisomerase II), which is responsible for the supercoiling and uncoiling of the DNA. Supercoiling of the DNA allows the long DNA molecule to fit into the cell. Uncoiling of the structure is the initiative step for replication, transcription, and repair of the DNA. Thus, prolonged inhibition will lead to the death of the cell.

Ciprofloxacin half-life is 3-5 hours. So it take about 15-24 hours to clear out of the system.

While there are no controlled studies of ciprofloxacin use in pregnant women to show safety, an expert review of published data on experiences with ciprofloxacin use during pregnancy by TERIS - the Teratogen Information System - concluded that therapeutic doses during pregnancy are unlikely to produce substantial teratogenic risk, but the data are insufficient to state that there is no risk (information from FDA Center for Drug Evaluation and Research) 5.

Long-term therapy.

• One publication described 6 pregnant women exposed to longer durations of ciprofloxacin therapy (3 weeks to 3 months) who delivered normal babies 5.
• There has also been a case report of a pregnant woman exposed to three weeks of ciprofloxacin therapy during early third trimester who delivered a normal baby 5.

Ciprofloxacin is excreted into breast milk but is considered as "usually compatible with breastfeeding" by the American Academy of Pediatrics.

Clinical reports, histopathologic (microscopic examination of tissue) findings, and an experimental animal model support a relationship between fluoroquinolone use and tendon ruptures. In some cases changes in tendon tissue associated with fluoroquinolones may not be completely reversible.

According to reports from France, fluoroquinolones associated with tendon ruptures include, in decreasing order of risk, pefloxacin, ofloxacin, norfloxacin, and ciprofloxacin. The risk associated with pefloxacin has been estimated to be 1 case per 23,130 treatment days, and for ciprofloxacin, 1 case per 779,600 treatment days 6.

Like other fluoroquinolones, ciprofloxacin may result in false positive opiate screen (JAMA 2001;286:3115-9).

• Ciprofloxacin (Cipro) versus Other Medications

• 1. Makaryus AN, Byrns K, Makaryus MN, Natarajan U, Singer C, Goldner B. Effect of ciprofloxacin and levofloxacin on the QT interval: is this a significant "clinical" event? South Med J. 2006 Jan;99(1):52-6. PubMed
• 2. Skerk V, Schonwald S, Krhen I, Banaszak A, Begovac J, Strugar J, Strapac Z, Vrsalovic R, Vukovic J, Tomas M. Comparative analysis of azithromycin and ciprofloxacin in the treatment of chronic prostatitis caused by Chlamydia trachomatis. Int J Antimicrob Agents. 2003 May;21(5):457-62. PubMed
• 3. Hooton TM, Rogers ME, Medina TG, Kuwamura LE, Ewers C, Roberts PL, Stamm WE. Ciprofloxacin compared with doxycycline for nongonococcal urethritis. Ineffectiveness against Chlamydia trachomatis due to relapsing infection. JAMA. 1990 Sep 19;264(11):1418-21.
• 5. CIPRO (Ciprofloxacin) Use by Pregnant and Lactating Women. FDA Center for Drug Evaluation and Research
• 6. Royer RJ. Adverse drug reactions with fluoroquinolones. Therapie. 1996 Jul-Aug;51(4):414-6.
• 7. D. P. Healy, R. E. Polk, L Kanawati, D. T. Rock, and M. L. Mooney. Interaction between oral ciprofloxacin and caffeine in normal volunteers. Antimicrob Agents Chemother. 1989 April; 33(4): 474–478. PubMed
• 8. Samarakoon N, Harrisberg B, Ell J. Ciprofloxacin-induced toxic optic neuropathy. Clin Experiment Ophthalmol. 2007 Jan-Feb;35(1):102-4. PubMed
• 9. Lahat G, Halperin D, Barazovsky E, Shalit I, Rabau M, Klausner J, Fabian I. Immunomodulatory effects of ciprofloxacin in TNBS-induced colitis in mice. Inflamm Bowel Dis. 2007 May;13(5):557-65
• 10. Kolios G, Manousou P, Bourikas L, Notas G, Tsagarakis N, Mouzas I, Kouroumalis E. Ciprofloxacin inhibits cytokine-induced nitric oxide production in human colonic epithelium. Eur J Clin Invest. 2006 Oct;36(10):720-9.
• 11. Maccato ML, Faro S, Martens MG, Hammill HA. Ciprofloxacin versus gentamicin/clindamycin for postpartum endometritis. J Reprod Med. 1991 Dec;36(12):857-61. PubMed
• 12. Arredondo JL, Diaz V, Gaitan H, Maradiegue E, Oyarzu'n E, Paz R, Reynal JL, Stamm W, Zambrano D. Oral clindamycin and ciprofloxacin versus intramuscular ceftriaxone and oral doxycycline in the treatment of mild-to-moderate pelvic inflammatory disease in outpatients. Clin Infect Dis. 1997 Feb;24(2):170-8. PubMed
• 13. Thadepalli H, Mathai D, Scotti R, Bansal MB, Savage E. Ciprofloxacin monotherapy for acute pelvic infections: a comparison with clindamycin plus gentamicin. Obstet Gynecol. 1991 Oct;78(4):696-702. PubMed
• 14. Crombleholme WR, Schachter J, Ohm-Smith M, Luft J, Whidden R, Sweet RL. Efficacy of single-agent therapy for the treatment of acute pelvic inflammatory disease with ciprofloxacin. Am J Med. 1989 Nov 30;87(5A):142S-147S. PubMed
• 15. Kenny GE, Hooton TM, Roberts MC, Cartwright FD, Hoyt J. Susceptibilities of genital mycoplasmas to the newer quinolones as determined by the agar dilution method. Antimicrob Agents Chemother. 1989 Jan;33(1):103-7.
• 16. Waites KB, Crabb DM, Duffy LB. Inhibitory and bactericidal activities of gemifloxacin and other antimicrobials against Mycoplasma pneumoniae. Int J Antimicrob Agents. 2003 Jun;21(6):574-7. PubMed
• 17. Holley HP Jr. Successful treatment of cat-scratch disease with ciprofloxacin. JAMA. 1991 Mar 27;265(12):1563-5. PubMed
• 18. Al Dahouk S, Hagen RM, Nockler K, Tomaso H, Wittig M, Scholz HC, Vergnaud G, Neubauer H. Failure of a short-term antibiotic therapy for human brucellosis using ciprofloxacin. A study on in vitro susceptibility of Brucella strains. Chemotherapy. 2005 Oct;51(6):352-6. Epub 2005 Oct 14. PubMed
• 19. Agalar C, Usubutun S, Turkyilmaz R. Ciprofloxacin and rifampicin versus doxycycline and rifampicin in the treatment of brucellosis. Eur J Clin Microbiol Infect Dis. 1999 Aug;18(8):535-8. PubMed
• 20. Alp E, Koc RK, Durak AC, Yildiz O, Aygen B, Sumerkan B, Doganay M. Doxycycline plus streptomycin versus ciprofloxacin plus rifampicin in spinal brucellosis. BMC Infect Dis. 2006 Apr 11;6:72. PubMed
• 21. Saha D, Khan WA, Karim MM, Chowdhury HR, Salam MA, Bennish ML. Single-dose ciprofloxacin versus 12-dose erythromycin for childhood cholera: a randomised controlled trial. Lancet. 2005 Sep 24-30;366(9491):1085-93. PubMed
• 22. Moulin F, Sauve'-Martin H, Marc E, Lorrot MM, Soulier M, Ravilly S, Raymond J, Gendrel D. Ciprofloxacin after clinical failure of beta-lactam antibiotics in children with salmonellosis. Arch Pediatr. 2003 Jul;10(7):608-14. PubMed
• 23. Burstein GR, Berman SM, Blumer JL, Moran JS. Ciprofloxacin for the treatment of uncomplicated gonorrhea infection in adolescents: does the benefit outweigh the risk? Clin Infect Dis. 2002 Oct 15;35(Suppl 2):S191-9.
• 24. Johansson A, Berglund L, Gothefors L, Sjostedt A, Tarnvik A. Ciprofloxacin for treatment of tularemia in children. Pediatr Infect Dis J. 2000 May;19(5):449-53. PubMed
• 25. Huddleston PM, Steckelberg JM, Hanssen AD, Rouse MS, Bolander ME, Patel R. Ciprofloxacin inhibition of experimental fracture healing. J Bone Joint Surg Am. 2000 Feb;82(2):161-73.
• 26. Richard DA, Nousia-Arvanitakis S, Sollich V, Hampel BJ, Sommerauer B, Schaad UB. Oral ciprofloxacin vs. intravenous ceftazidime plus tobramycin in pediatric cystic fibrosis patients: comparison of antipseudomonas efficacy and assessment of safety with ultrasonography and magnetic resonance imaging. Cystic Fibrosis Study Group. Pediatr Infect Dis J. 1997 Jun;16(6):572-8. PubMed
• 27. Yang CK, Lin HC, Lee KY, Lin SM, Yu CT, Kuo HP. The effects of ciprofloxacin on chest radiographic regression in patients with drug intolerance or resistant tuberculosis. Chang Gung Med J. 2004 Apr;27(4):292-9. PubMed
• 28. Marinis E, Legakis NJ. In-vitro activity of ciprofloxacin against clinical isolates of mycobacteria resistant to antimycobacterial drugs. J Antimicrob Chemother. 1985 Oct;16(4):527-30.
• 29. Haranaga S, Tateyama M, Higa F, Miyagi K, Akamine M, Azuma M, Yara S, Koide M, Fujita J. Intravenous ciprofloxacin versus erythromycin in the treatment of Legionella pneumonia. Intern Med. 2007;46(7):353-7. Epub 2007 Apr 2. PubMed
• 30. Gehanno P. Multicenter study of the efficacy and safety of oral ciprofloxacin in the treatment of chronic suppurative otitis media in adults. The French Study Group. Otolaryngol Head Neck Surg. 1997 Jul;117(1):83-90. PubMed
• 31. Lang R, Goshen S, Raas-Rothschild A, Raz A, Ophir D, Wolach B, Berger I. Oral ciprofloxacin in the management of chronic suppurative otitis media without cholesteatoma in children: preliminary experience in 21 children. Pediatr Infect Dis J. 1992 Nov;11(11):925-9. PubMed

Published: March 31, 2008
Last updated: January 07, 2010