Continuing Education Activity

Ciprofloxacin is an antibiotic agent in the fluoroquinolone class used to treat bacterial infections such as urinary tract infections and pneumonia. Ciprofloxacin has FDA approval for the treatment of urinary tract infections, sexually transmitted infections (gonorrhea and chancroid), skin, bone and joint infections, prostatitis, typhoid fever, gastrointestinal infections, lower respiratory tract infections, anthrax, plague, and salmonellosis. Ciprofloxacin is an appropriate treatment option in patients with mixed infections or patients with predisposing factors for Gram-negative infections. This activity covers ciprofloxacin, which is a broad-spectrum quinolone antibiotic that members of the interprofessional team need to review its indications, coverage, contraindications, and adverse event profile to optimally manage patients with infectious disease.

Objectives:

• Identify the mechanism of action of ciprofloxacin.
• Summarize the types of infections and bacterial coverage of ciprofloxacin, where it would be effective in a target population.
• Recognize the interactions and adverse events associated with ciprofloxacin therapy.
• Review the importance of improving care coordination amongst interprofessional team members to improve outcomes for a patient with infectious disease that would respond to ciprofloxacin therapy.

Indications

Ciprofloxacin is an antibiotic agent in the fluoroquinolone class used to treat bacterial infections such as urinary tract infections and pneumonia. Ciprofloxacin is FDA approved for the treatment of urinary tract infections, sexually transmitted infections (gonorrhea and chancroid), skin, bone and joint infections, prostatitis, typhoid fever, gastrointestinal infections, lower respiratory tract infections, anthrax, plague, and salmonellosis.[1] For respiratory tract infections, ciprofloxacin should not be a first-line empirical therapy if penicillin-susceptible Streptococcus pneumoniae is the primary pathogen. Ciprofloxacin is an appropriate treatment option in patients with mixed infections or patients with predisposing factors for Gram-negative infections. Ciprofloxacin was patented in 1983 by Bayer A.G. and approved in 1987 by the United States Food and Drug Administration (USFDA).[2]

Mechanism of Action

Ciprofloxacin is a bactericidal antibiotic of the fluoroquinolone drug class. It inhibits DNA replication by inhibiting bacterial DNA topoisomerase and DNA-gyrase. Of the fluoroquinolone class, ciprofloxacin is the most potent against gram-negative bacilli bacteria (notably, the Enterobacteriaceae such as Escherichia coli, Salmonella spp., Shigella spp., and Neisseria).[3] Ciprofloxacin also has effectiveness against some gram-positive bacteria. Ciprofloxacin is the most active against Pseudomonas aeruginosa, among the quinolones.[4] Progressively decreasing susceptibility among P. aeruginosa has been reported in Europe, North and South America, predominantly in the hospital or nursing home settings with identifiable risk factors. Ciprofloxacin is readily absorbed but typically does not achieve complete absorption. The bioavailability of oral ciprofloxacin is 70 to 80%.[4] Ciprofloxacin is one of the few oral antibiotics able to treat P. aeruginosa infections.

Administration

Ciprofloxacin is available both orally and intravenously.

Ciprofloxacin is administered orally twice daily for 7 to 14 days or at least two days after signs and symptoms of the infection is over.

The recommended oral dose regimen is 250 mg twice daily to treat mild to moderate, and 500 mg twice daily for severe or complicated urinary tract infections. Therapy for mild to moderate respiratory tract or skin and soft-tissue infections require 500mg twice-daily dosing, while a dosage of 750mg twice daily is recommended for severe or complicated infections. Ciprofloxacin should be given with food to minimize gastrointestinal upset. 

An intravenous dosage of 200 to 400 mg twice daily is recommended for mild-to-moderate infections, and up to 400 mg every 8 hours for severe, life-threatening infections.[1] The recommendation is for a 50% reduction in the total daily dosage for patients with severe renal impairment (creatinine clearance = 1.2 L/hour). Ciprofloxacin is administered intravenously by slow infusion over 60 minutes. It is essential to maintain proper hydration and urine output. Usage of antacids should be avoided or at least administer ciprofloxacin either two hours before or six hours after antacids for both the immediate or the extended-release formulations. The oral suspension should not be administered through feeding tubes as the suspension may adhere to the tube. Topical ciprofloxacin is safe and an effective antibiotic used in the treatment of chronic otitis media compared to ciprofloxacin tablets.[5]

Adverse Effects

Adverse effects are mild at therapeutic doses and are mostly limited to gastrointestinal disruptions such as nausea and diarrhea. The serious adverse effects of ciprofloxacin include peripheral neuropathy, prolonged QT interval, seizures, and other CNS effects, hyper or hypoglycemia, photosensitivity, tendonitis.[6] Black box warnings include tendinitis and tendon rupture (associated with the fluoroquinolone class). The most common type of tendon rupture involves the Achilles tendon. There have also been reports of tendinopathies in the gluteal, iliopsoas, and triceps tendons.[7][8][9] Rare interactions include drug-induced bullous pemphigoid.[10]

Contraindications

Contraindications to ciprofloxacin include patients with documented hypersensitivity to the drug or components of the formulation. The concurrent administration of tizanidine for muscle spasms is also a contraindication. The pharmacokinetics of tizanidine are altered by CYP1A2 inhibition (ciprofloxacin), which leads to increased tizanidine levels and resulting in decreased psychomotor activity, blood pressure, and heart rate.[1][11] Avoid ciprofloxacin and its fluoroquinolone class in patients with myasthenia gravis because it may exacerbate muscle weaknesses.

Monitoring

Providers should monitor patients taking ciprofloxacin for symptoms of tendinitis, altered mental status, complete blood count, and renal and hepatic function in prolonged therapy. Other significant interactions with ciprofloxacin include theophylline (particularly with concurrent caffeine use), which acts on the CYP1A2 and raises theophylline levels.[1] There have been reports that the use of ciprofloxacin can lead to elevated cyclosporine serum levels. Oral absorption of ciprofloxacin decreases with antacids containing agents such as aluminum and magnesium.

Toxicity

The elimination half-life of ciprofloxacin ranges from 3.3 to 6.8 hours in the elderly, as compared with three to four hours in younger persons.[12] There is limited evidence suggesting ciprofloxacin excretion in breast milk.[13]. Clinical data indicate there is no significant evidence of osteoarticular toxicity in newborns and children. In these studies, the drug exposure of neonates and children was at much higher doses as compared to children whose exposure was via breastfeeding.[14] The use of ciprofloxacin with nursing mothers is acceptable with monitoring for possible GI adverse effects (diarrhea or candidiasis). Consider avoiding breastfeeding three to four hours after dosing.

Enhancing Healthcare Team Outcomes

Ciprofloxacin does not have a marketed indication for use in neonates worldwide; however, it is prescribed in neonates for life-threatening infections as salvage therapy for sepsis due to multi-drug resistance (mostly in Europe and developing countries). A systematic search of observational cohort studies and case reports suggest that the majority of clinical responses were positive, and there was a lack of serious adverse events, especially joint toxicity.[14] Ciprofloxacin has also attracted interest from the scientific community due to its apoptotic and antiproliferative activities in several cancer lines.[2] Researchers observed that it could induce dose- and time-dependent growth inhibition and apoptosis of various carcinoma, osteosarcoma, and leukemia cell lines.[15]

Ciprofloxacin also has potential benefits in bladder cancer management. In vitro studies on tumor cells made from transitional cell carcinoma of the bladder resulted in both a dose- as well as time-dependent inhibition of cell growth. These results were achieved by ciprofloxacin with concentrations that are easily attainable in the urine of patients.[16]. With appropriate use, ciprofloxacin can be less costly and more cost-effective than traditional parenteral regimens in selected clinical settings. Additional well-designed studies would be helpful in further defining the most cost-efficient use of this antimicrobial agent. However, in E. coli-associated urinary tract infections, there has been an increase in ciprofloxacin resistance more-so in the hospital versus the community setting.[17] Evaluation of the use of ciprofloxacin as empiric therapy should be on a case-by-case basis.