Ciprofloxacin, sold under the brand name Cipro among others, is a fluoroquinolone antibiotic used to treat a number of bacterial infections. This includes bone and joint infections, intra-abdominal infections, certain types of infectious diarrhea, respiratory tract infections, skin infections, typhoid fever, and urinary tract infections, among others. For some infections it is used in addition to other antibiotics. It can be taken by mouth, as eye drops, as ear drops, or intravenously.
Common side effects include nausea, vomiting, and diarrhea. Severe side effects include tendon rupture, hallucinations, and nerve damage. In people with myasthenia gravis, there is worsening muscle weakness. Rates of side effects appear to be higher than some groups of antibiotics such as cephalosporins but lower than others such as clindamycin. Studies in other animals raise concerns regarding use in pregnancy. No problems were identified, however, in the children of a small number of women who took the medication. It appears to be safe during breastfeeding. It is a second-generation fluoroquinolone with a broad spectrum of activity that usually results in the death of the bacteria.
Ciprofloxacin was patented in 1980 and introduced by Bayer in 1987. It is on the World Health Organization's List of Essential Medicines. The World Health Organization classifies ciprofloxacin as critically important for human medicine. It is available as a generic medication. In 2023, it was the 155th most commonly prescribed medication in the United States, with more than 3million prescriptions.
Medical uses Ciprofloxacin is used to treat a wide variety of infections, including infections of bones and joints, endocarditis, bacterial gastroenteritis, malignant otitis externa, bubonic plague, respiratory tract infections, cellulitis, urinary tract infections, prostatitis, anthrax, and chancroid.
Ciprofloxacin occupies an important role in treatment guidelines issued by major medical societies for the treatment of serious infections, especially those likely to be caused by Gram-negative bacteria, including Pseudomonas aeruginosa. For example, ciprofloxacin in combination with metronidazole is one of several first-line antibiotic regimens recommended by the Infectious Diseases Society of America for the treatment of community-acquired abdominal infections in adults. It also features prominently in treatment guidelines for acute pyelonephritis, complicated or hospital-acquired urinary tract infection, acute or chronic prostatitis, certain types of endocarditis, certain skin infections, and prosthetic joint infections.
In other cases, treatment guidelines are more restrictive, recommending in most cases that older, narrower-spectrum drugs be used as first-line therapy for less severe infections to minimize fluoroquinolone-resistance development. For example, the Infectious Diseases Society of America recommends the use of ciprofloxacin and other fluoroquinolones in urinary tract infections be reserved to cases of proven or expected resistance to narrower-spectrum drugs such as nitrofurantoin or trimethoprim/sulfamethoxazole. The European Association of Urology recommends ciprofloxacin as an alternative regimen for the treatment of uncomplicated urinary tract infections, but cautions that the potential for "adverse events have to be considered".
Although approved by regulatory authorities for the treatment of respiratory infections, ciprofloxacin is not recommended for respiratory infections by most treatment guidelines due in part to its modest activity against the common respiratory pathogen Streptococcus pneumoniae. "Respiratory quinolones" such as levofloxacin, having greater activity against this pathogen, are recommended as first line agents for the treatment of community-acquired pneumonia in patients with important co-morbidities and in patients requiring hospitalization (Infectious Diseases Society of America 2007). Similarly, ciprofloxacin is not recommended as a first-line treatment for acute sinusitis.
Ciprofloxacin is approved for the treatment of gonorrhea in many countries, but this recommendation is widely regarded as obsolete due to resistance development.
Pregnancy An expert review of published data on experiences with ciprofloxacin use during pregnancy concluded therapeutic doses during pregnancy are unlikely to pose a substantial teratogenic risk (quantity and quality of data=fair), but the data is insufficient to state that no risks exist. Exposure to quinolones, including levofloxacin, during the first-trimester is not associated with an increased risk of stillbirths, premature births, birth defects, or low birth weight.
Two small post-marketing epidemiology studies of mostly short-term, first-trimester exposure found that fluoroquinolones did not increase risk of major malformations, spontaneous abortions, premature birth, or low birth weight.
Breastfeeding Fluoroquinolones have been reported as present in a mother's milk and thus passed on to the nursing child.
Children Oral and intravenous ciprofloxacin are approved by the FDA for use in children for only two indications due to the risk of permanent injury to the musculoskeletal system: Inhalational anthrax (postexposure) Complicated urinary tract infections and pyelonephritis due to Escherichia coli, but never as first-line agents.
Spectrum of activity Its spectrum of activity includes most strains of bacterial pathogens responsible for community-acquired pneumonias, bronchitis, urinary tract infections, and gastroenteritis. Ciprofloxacin is particularly effective against Gram-negative bacteria (such as Escherichia coli, Haemophilus influenzae, Klebsiella pneumoniae, Legionella pneumophila, Moraxella catarrhalis, Proteus mirabilis, and Pseudomonas aeruginosa), but is less effective against Gram-positive bacteria (such as methicillin-sensitive Staphylococcus aureus, Streptococcus pneumoniae, and Enterococcus faecalis) than newer fluoroquinolones.
Bacterial resistance
As a result of its widespread use to treat minor infections readily treatable with older, narrower-spectrum antibiotics, many bacteria have developed resistance to this drug, leaving it significantly less effective than it would have been otherwise.
Resistance to ciprofloxacin and other fluoroquinolones may evolve rapidly, even during a course of treatment. Numerous pathogens, including enterococci, Streptococcus pyogenes, and Klebsiella pneumoniae (quinolone-resistant) now exhibit resistance.M Jacobs, Worldwide Overview of Antimicrobial Resistance. International Symposium on Antimicrobial Agents and Resistance 2005. Widespread veterinary usage of fluoroquinolones, particularly in Europe, has been implicated. Meanwhile, some Burkholderia cepacia, Clostridium innocuum, and Enterococcus faecium strains have developed resistance to ciprofloxacin to varying degrees.
Fluoroquinolones had become the class of antibiotics most commonly prescribed to adults in 2002. Nearly half (42%) of those prescriptions in the US were for conditions not approved by the FDA, such as acute bronchitis, otitis media, and acute upper respiratory tract infection.
Contraindications Contraindications include: Taking tizanidine at the same time Use by those who are hypersensitive to any member of the quinolone class of antimicrobial agents Use by those who are diagnosed with myasthenia gravis, as muscle weakness may be exacerbated
Ciprofloxacin is also considered to be contraindicated in children (except for the indications outlined above), in pregnancy, to nursing mothers, and in people with epilepsy or other seizure disorders.
Caution may be required in people with Marfan syndrome or Ehlers–Danlos syndrome.
Adverse effects Adverse effects can involve the tendons, muscles, joints, nerves, and the central nervous system.
Rates of adverse effects appear to be higher than with some groups of antibiotics such as cephalosporins but lower than with others such as clindamycin. Compared to other antibiotics some studies find a higher rate of adverse effects while others find no difference.
In clinical trials most of the adverse events were described as mild or moderate in severity, abated soon after the drug was discontinued, and required no treatment. Some adverse effects may be permanent. Ciprofloxacin was stopped because of an adverse event in 1% of people treated with the medication by mouth. The most frequently reported drug-related events, from trials of all formulations, all dosages, all drug-therapy durations, and for all indications, were nausea (2.5%), diarrhea (1.6%), abnormal liver function tests (1.3%), vomiting (1%), and rash (1%). Other adverse events occurred at rates of <1%.
Tendon problems Ciprofloxacin includes a boxed warning in the United States due to an increased risk of tendinitis and tendon rupture, especially in people who are older than 60 years, people who also use corticosteroids, and people with kidney, lung, or heart transplants. Tendon rupture can occur during therapy or even months after discontinuation of the medication. One study found that fluoroquinolone use was associated with a 1.9-fold increase in tendon problems. The risk increased to 3.2 in those over 60 years of age and to 6.2 in those over the age of 60 who were also taking corticosteroids. Among the 46,766 quinolone users in the study, 38 (0.08%) cases of Achilles tendon rupture were identified.
Cardiac arrhythmia The fluoroquinolones, including ciprofloxacin, are associated with an increased risk of cardiac toxicity, including QT interval prolongation, torsades de pointes, ventricular arrhythmia, and sudden death.
Nervous system Because Ciprofloxacin is lipophilic, it has the ability to cross the blood–brain barrier. The 2013 FDA label warns of nervous system effects. Ciprofloxacin, like other fluoroquinolones, is known to trigger seizures or lower the seizure threshold, and may cause other central nervous system adverse effects. Headache, dizziness, and insomnia have been reported as occurring fairly commonly in postapproval review articles, along with a much lower incidence of serious CNS adverse effects such as tremors, psychosis, anxiety, hallucinations, paranoia, and suicide attempts, especially at higher doses. Like other fluoroquinolones, it is also known to cause peripheral neuropathy that may be irreversible, such as weakness, burning pain, tingling or numbness.
Fluoroquinolones have already been reported for movement disorders. In this context, ciprofloxacin is especially associated with myoclonus, which derives the term "ciproclonus."
Cancer Ciprofloxacin is active in six of eight in vitro assays used as rapid screens for the detection of genotoxic effects, but is not active in in vivo assays of genotoxicity. Long-term carcinogenicity studies in rats and mice resulted in no carcinogenic or tumorigenic effects due to ciprofloxacin at daily oral dose levels up to 250 and 750 mg/kg to rats and mice, respectively (about 1.7 and 2.5 times the highest recommended therapeutic dose based upon mg/m2). Results from photo co-carcinogenicity testing indicate ciprofloxacin does not reduce the time to appearance of UV-induced skin tumors as compared to vehicle control.
Other The other black box warning is that ciprofloxacin should not be used in people with myasthenia gravis due to possible exacerbation of muscle weakness which may lead to breathing problems resulting in death or ventilator support. Fluoroquinolones are known to block neuromuscular transmission. There are concerns that fluoroquinolones including ciprofloxacin can affect cartilage in young children.
Clostridioides difficile-associated diarrhea is a serious adverse effect of ciprofloxacin and other fluoroquinolones; it is unclear whether the risk is higher than with other broad-spectrum antibiotics.