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Ciprofloxacin

Ciprofloxacin is a fluoroquinolone antibiotic used to treat a number of bacterial infections.

A second-generation fluoroquinolone with a broad spectrum of activity that usually results in the death of the bacteria.

It is active against some Gram-positive and many Gram-negative bacteria.

It functions by inhibiting a type II topoisomerase (DNA gyrase) and topoisomerase IV, necessary to separate bacterial DNA, thereby inhibiting cell division. 

Bacterial DNA fragmentation will occur as a result of inhibition of the enzymes.

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.

Tradename Cipro

Pregnancy category AU: B3

Drug class Fluoroquinolone

Bioavailability 70%

Protein binding 30%

Metabolism- Liver-CYP1A2

Elimination half-life-3.5 hours

Excretion,Kidney

Common side effects include nausea, vomiting, and diarrhea.

Severe side effects include an increased risk of tendon rupture, hallucinations, and nerve damage.

In people with myasthenia gravis, there is worsening muscle weakness.

It appears to be safe during breastfeeding.

It is used to treat a wide variety of infections: infections of bones and joints, endocarditis, gastroenteritis, malignant otitis externa, respiratory tract infections, cellulitis, urinary tract infections, prostatitis, anthrax, and chancroid.

Ciprofloxacin only treats bacterial infections.

It is not considered a first-line agent for 

acute sinusitis, lower respiratory tract infections and uncomplicated gonorrhea.

Has an important role for the treatment of serious infections, especially those likely to be caused by Gram-negative bacteria, including Pseudomonas aeruginosa. 

Cprofloxacin in combination with metronidazole is one of several first-line antibiotic regimens recommended  

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.

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.

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.

Ciprofloxacin for the treatment of gonorrhea is regarded as obsolete due to resistance development.

Ciprofloxacin is pregnancy category: no adequate and well-controlled studies in human pregnancy exist, and for which animal studies have suggested the potential for harm to the fetus, but potential benefits may warrant use of the drug in pregnant women despite potential risks. 

Therapeutic doses during pregnancy are unlikely to pose a substantial teratogenic risk, but the data are insufficient to state no risk exists.

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 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.

Fluoroquinolones have been reported as present in a mother’s milk and thus passed on to the nursing child.

The risk of serious adverse reactions, including articular damage, in infants nursing from mothers taking ciprofloxacin, should be considered.

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 

Complicated urinary tract infections and pyelonephritis due to Escherichia coli,but never as first-line agents.

Recommendations by the American Academy of Pediatrics note the systemic use of ciprofloxacin in children should be restricted to infections caused by multidrug-resistant pathogens or when no safe or effective alternatives are available.

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: Escherichia coli, Haemophilus influenzae, Klebsiella pneumoniae, Legionella pneumophila, Moraxella catarrhalis, Proteus mirabilis, and Pseudomonas aeruginosa.

It is less effective against Gram-positive bacteria: methicillin-sensitive Staphylococcus aureus, Streptococcus pneumoniae, and Enterococcus faecalis than newer fluoroquinolones.

Resistance to ciprofloxacin and other fluoroquinolones may evolve rapidly, even during a course of treatment:

Numerous pathogens, including enterococci, Streptococcus pyogenes and Klebsiella pneumoniae exhibit resistance.

Contraindications include:

Taking tizanidine together

May exacerbate myasthenia gravis muscle weakness.

Also  considered to be contraindicated in children, except for the indications outlined, 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 can involve the tendons, muscles, joints, nerves, and the central nervous system.

Most adverse events are mild or moderate in severity, abate soon after the drug is discontinued, and require no treatment.

The drug was stopped because of an adverse event in 1% of people treated with the oral agent.

The most frequently reported drug-related events; nausea (2.5%), diarrhea (1.6%), abnormal liver function tests (1.3%), vomiting (1%), and rash (1%).

It has a boxed warning in the United States due to an increased risk of tendinitis and tendon rupture.

Tendinitis and tendon rupture is especially likely to occur in people who are older than 60 years, who also use corticosteroids, and in people with kidney, lung, or heart transplants.

Tendon rupture can occur during therapy or even months after discontinuation of the medication.

In one study fluoroquinolones were associated with a 1.9-fold increase in tendon problems, 3.2 increase in those over 60 years of age and 6.2 in those over the age of 60 who were also taking corticosteroids. 

0.08% cases of Achilles tendon rupture were identified in fluoroquinone users.

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.

It is lipophilic, and has the ability to cross the blood–brain barrier.

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 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.

Black box warning exists: 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.

Clostridium difficile-associated diarrhea is a serious adverse effect of ciprofloxacin.

Children and the elderly are at a much greater risk of experiencing adverse reactions.

Overdose of ciprofloxacin may result in reversible renal toxicity. 

Treatment of overdose:  emptying of the stomach by induced vomiting or gastric lavage, as well as administration of antacids containing magnesium, aluminium, or calcium to reduce drug absorption. 

Renal function and urinary pH should be monitored, and support includes adequate hydration and urine acidification if necessary to prevent crystalluria. 

Hemodialysis or peritoneal dialysis can only remove less than 10% of ciprofloxacin.

Ciprofloxacin can interact with certain foods and several other drugs leading to undesirable increases or decreases in the serum levels or distribution of one or both drugs.

It should not be taken with antacids containing magnesium or aluminum, highly buffered drugs or with supplements containing calcium, iron, or zinc. 

It should be taken two hours before or six hours after these products. 

Magnesium or aluminum antacids turn ciprofloxacin into insoluble salts that are not readily absorbed by the intestinal tract, reducing peak serum concentrations by 90% or more, leading to therapeutic failure. 

It should not be taken with dairy products or calcium-fortified juices alone, as peak serum concentration and the area under the serum concentration-time curve can be reduced up to 40%. 

Ciprofloxacin inhibits the drug-metabolizing enzyme CYP1A2 and thereby can reduce the clearance of drugs metabolized by that enzyme: tizanidine, theophylline, caffeine, methylxanthines, clozapine, olanzapine, and ropinirole. 

Central nervous system adverse effects, including seizure risk, may be increased when NSAIDs are combined with quinolones: this interaction may involve a synergistic increased antagonism of GABA neurotransmission.

Altered serum levels of the antiepileptic drugs phenytoin and carbamazepine have been reported in patients receiving concomitant ciprofloxacin.

Ciprofloxacin is a potent inhibitor of CYP1A2, CYP2D6, and CYP3A4.

 It is available as immediate-release tablets, extended-release tablets, an oral suspension, and as a solution for intravenous administration. 

When administered over one hour as an intravenous infusion, ciprofloxacin rapidly distributes into the tissues, with levels in some tissues exceeding those in the serum. 

Its ability to penetrate into the central nervous system is relatively modest, with cerebrospinal fluid levels normally less than 10% of peak serum concentrations. 

The serum half-life of ciprofloxacin is about 4–6 hours, with 50–70% of an administered dose being excreted in the urine as unmetabolized drug. 

An additional 10% is excreted in urine as metabolites. 

Urinary excretion is virtually complete 24 hours after administration. 

Dose adjustment is required in the elderly and in those with renal impairment.

Ciprofloxacin is weakly bound to serum proteins at 20–40%.

It is an inhibitor of the drug-metabolizing enzyme cytochrome P450 1A2, which leads to the potential for clinically important drug interactions with drugs metabolized by that enzyme.

Ciprofloxacin is about 70% orally available when administered orally, so a slightly higher dose is needed to achieve the same exposure when switching from IV to oral administration.

The extended release oral tablets allow once-daily administration by releasing the drug more slowly in the gastrointestinal tract. 

These tablets contain 35% of the administered dose in an immediate-release form and 65% in a slow-release matrix. 

Maximum serum concentrations are achieved between 1 and 4 hours after administration.

Ciprofloxacin is the most widely used of the second-generation quinolones.

Ciprofloxacin for systemic administration is available as immediate-release tablets, as extended-release tablets, as an oral suspension, and as a solution for intravenous infusion. 

It is also available for local administration as eye drops and ear drops.

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