Ciprofloxacin


Article Author:
Tony Thai


Article Editor:
Patrick Zito


Editors In Chief:
David Wood
Andrew Wilt
Mary Cataletto


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Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Patrick Le
Anoosh Zafar Gondal
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Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
12/17/2018 10:39:20 AM

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 treatment of urinary tract infections, sexually transmitted diseases (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 70-80%.[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 250mg twice daily to treat mild to moderate, and 500mg 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 400mg every 8 hours for severe, life-threatening infections.[1] A 50% reduction in the total daily dosage is recommended in patients with severe renal impairment (creatinine clearance = 1.2 L/h). Ciprofloxacin is administered intravenously by slow infusion over 60 minutes. It is important 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 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] 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] It was observed that it can induce dose- and time-dependent growth inhibition and apoptosis of various carcinoma, osteosarcoma, and leukemia cell lines.[15].  

Ciprofloxacin also has a potential effect 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.


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Ciprofloxacin - Questions

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A 5-year-old girl presents to the emergency department with complaints of urinary frequency and urgency. Urine analysis reveals numerous gram-negative bacteria. Which of the following drugs is not appropriate for this patient?



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In which of the following infections is ciprofloxacin NOT useful?



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Ciprofloxacin inhibits which of the following?



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Which of the following medications can be used with ciprofloxacin?



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What is the mechanism of action of ciprofloxacin?



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Which of the following is associated with rupture of the Achilles tendon?



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To which drug class does ciprofloxacin belong?



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A 13-year-old boy presents with a new-onset urinary hesitancy and frequency for 3 days. Patient has no prior medical history. He denies being sexually active. Which of the following antimicrobial agents is contraindicated in this patient?



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Ciprofloxacin - References

References

Kaplan YC,Koren G, Use of ciprofloxacin during breastfeeding. Canadian family physician Medecin de famille canadien. 2015 Apr     [PubMed]
Abd-Elsayed A,Elsharkawy H,Sakr W, A severe interaction between Tizanidine and Ciprofloxacin. Journal of clinical anesthesia. 2015 Dec     [PubMed]
Samarei R, Comparison of local and systemic ciprofloxacin ototoxicity in the treatment of chronic media otitis. Global journal of health science. 2014 Sep 18     [PubMed]
Herold C,Ocker M,Ganslmayer M,Gerauer H,Hahn EG,Schuppan D, Ciprofloxacin induces apoptosis and inhibits proliferation of human colorectal carcinoma cells. British journal of cancer. 2002 Feb 1     [PubMed]
Wiseman LR,Balfour JA, Ciprofloxacin. A review of its pharmacological profile and therapeutic use in the elderly. Drugs     [PubMed]
Shimatsu K,Subramaniam S,Sim H,Aronowitz P, Ciprofloxacin-induced tendinopathy of the gluteal tendons. Journal of general internal medicine. 2014 Nov     [PubMed]
Smith N,Fackrell R,Henderson E, Ciprofloxacin-associated bilateral iliopsoas tendon rupture: a case report. Age and ageing. 2016 Sep     [PubMed]
Shybut TB,Puckett ER, Triceps Ruptures After Fluoroquinolone Antibiotics: A Report of 2 Cases. Sports health. 2017 Sep/Oct     [PubMed]
Cozzani E,Chinazzo C,Burlando M,Romagnoli M,Parodi A, Ciprofloxacin as a Trigger for Bullous Pemphigoid: The Second Case in the Literature. American journal of therapeutics. 2016 Sep-Oct     [PubMed]
Fasugba O,Gardner A,Mitchell BG,Mnatzaganian G, Ciprofloxacin resistance in community- and hospital-acquired Escherichia coli urinary tract infections: a systematic review and meta-analysis of observational studies. BMC infectious diseases. 2015 Nov 25     [PubMed]
LeBel M, Ciprofloxacin: chemistry, mechanism of action, resistance, antimicrobial spectrum, pharmacokinetics, clinical trials, and adverse reactions. Pharmacotherapy. 1988     [PubMed]
Kaguelidou F,Turner MA,Choonara I,Jacqz-Aigrain E, Ciprofloxacin use in neonates: a systematic review of the literature. The Pediatric infectious disease journal. 2011 Feb     [PubMed]
Sharma PC,Jain A,Jain S,Pahwa R,Yar MS, Ciprofloxacin: review on developments in synthetic, analytical, and medicinal aspects. Journal of enzyme inhibition and medicinal chemistry. 2010 Aug     [PubMed]
Blondeau JM, Expanded activity and utility of the new fluoroquinolones: a review. Clinical therapeutics. 1999 Jan     [PubMed]
Davis R,Markham A,Balfour JA, Ciprofloxacin. An updated review of its pharmacology, therapeutic efficacy and tolerability. Drugs. 1996 Jun     [PubMed]
Campoli-Richards DM,Monk JP,Price A,Benfield P,Todd PA,Ward A, Ciprofloxacin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs. 1988 Apr     [PubMed]
Aranha O,Wood DP Jr,Sarkar FH, Ciprofloxacin mediated cell growth inhibition, S/G2-M cell cycle arrest, and apoptosis in a human transitional cell carcinoma of the bladder cell line. Clinical cancer research : an official journal of the American Association for Cancer Research. 2000 Mar     [PubMed]

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