Ciprofloxacin (Cipro®)

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

History

The discovery of ciprofloxacin was an important medical breakthrough and it opened the door for further research, development, and marketing of new class of antibiotics.

Ciprofloxacin was the first fluoroquinolone brought to 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.

FDA approved uses

• 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. Ciprofloxacin 500 mg twice daily for 28 days provides one of the most cost effective treatments for chronic bacterial prostatitis 33.
• Lower respiratory infections (pneumonia, bronchitis, tracheobronchitis). Ciprofloxacin is not a drug of first choice in the treatment of pneumonia secondary to Streptococcus pneumoniae. Ciprofloxacin has poor activity against S. pneumoniae, and its use has been associated with the rapid emergence of resistance in pneumococci 12.
• Acute sinusitis (inflammation of the paranasal sinuses). However, ciprofloxacin is not recommended by IDSA Guideline due to limited activity against Streptococcus pneumoniae.
• 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, 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: 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 infections 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 FDA-approved for inhalational anthrax and complicated UTI and pyelonephritis in children.

Ciprofloxacin is NOT effective in the treatment of syphilis.

Off-label & Investigational uses

• Chlamydia infections 2, 3.
  In general, ciprofloxacin is not the best option for Chlamydia infections. Although it has good activity against Chlamydia in laboratory environment, ciprofloxacin even in high dosages of 2 g daily is insufficient for treatment 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 recommended treatments by Centers for Disease Control and Prevention (CDC) for 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 monotherapy is not an optimal treatment for pelvic inflammatory disease 14, but it is often used in combination with other antimicrobial agents.
• 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 help prevent or fight infections in persons with cystic fibrosis. 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 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. Brucellosis 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.

Spectrum of activity

Gram-negative bacteria:

• Campylobacter jejuni
• Citrobacter koseri (diversus)
• Citrobacter freundii
• Enterobacter cloacae
• Escherichia coli
• Haemophilus influenzae
• Haemophilus parainfluenzae
• Klebsiella pneumoniae
• Moraxella catarrhalis
• Morganella morganii
• Neisseria gonorrhoeae
• Proteus mirabilis
• Proteus vulgaris
• Providencia rettgeri
• Providencia stuartii
• Pseudomonas aeruginos -- best activity among Fluoroquinolones
• Salmonella typhi
• Serratia marcescens
• Shigella boydii, Shigella dysenteriae, Shigella flexneri, Shigella sonnei

Note: Ciprofloxacin has the strongest Gram-negative activity of the quinolones.

Gram-positive bacteria:
Ciprofloxacin has only moderate activity against Gram-positive bacteria such as Streptococcus pneumoniae and Enterococcus faecalis.

Anaerobic bacteria:
Most anaerobic bacteria are not susceptible.

Other:
Ciprofloxacin is active against Bacillus anthracis.

Moderate activity against atypical bacteria, but good activity against Legionella pneumophila.

Ciprofloxacin "pros" and "cons"

Advantages:

• Ease of use - twice daily regimen.
• 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).
• Unique characteristic of ciprofloxacin is its excellent penetration into prostate tissue, with concentrations above those reached in most other tissue22.
• 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.
• Experience is favorable and extensive for nosocomial pneumonia, osteomyelitis, neutropenic fever, travelers diarrhea, chronic prostatitis and UTIs.
• Inexpensive and is available as generic version.

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 is not reduced, the medicine could accumulate in the body to levels that could cause serious adverse reactions.
• Widespread use of Ciprofloxacin, often inappropriate, resulted in increasing rates of microbial resistance (development of resistant strains in P. aeruginosa, Salmonella, Neisseria gonorrhoeae).
• Tendon damage. Achilles tendon is the most susceptible, however other tendons (e.g. gluteal tendons36) 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 a person experiences these symptoms in order to prevent the development of an irreversible condition.
• Phototoxicity 34.
• 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 may be significantly reduced by dairy products. Ciprofloxacin should not be taken with dairy or calcium-fortified juices alone.
• Decreases 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 experimental research suggests that use of ciprofloxacin during early fracture repair may compromise the process of fracture-healing.

Mode of action

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.

Time for Ciprofloxacin to clear out the system

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

Ciprofloxacin during pregnancy and lactation

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 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.

Tendinopathy and Tendon damage

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.

Effects on tests

Like other fluoroquinolones, ciprofloxacin may result in false positive opiate screen35.

Further reading

• Ciprofloxacin (Cipro) versus other medications
• Ciprofloxacin vs Azithromycin
• Ciprofloxacin vs Levofloxacin
• Ciprofloxacin (Cipro®) vs Nitrofurantoin (Macrobid®)
• Ciprofloxacin vs Trimethoprim/ Sulfamethoxazole

References

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• 2. Skerk V, Schonwald S, Krhen I, Banaszak A, Begovac J, Strugar J, Strapac Z, Vrsalovic R, Vukovic J, Tomas M. Ciprofloxacin in chronic prostatitis caused by Chlamydia trachomatis. Int J Antimicrob Agents. 2003 May;21(5):457-62. PubMed
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• Shimatsu K, Subramaniam S, Sim H, Aronowitz P. Ciprofloxacin-induced tendinopathy of the gluteal tendons. J Gen Intern Med. 2014 Nov;29(11):1559-62

Published: March 31, 2008
Last updated: July 20, 2017