Introduction
Ciprofloxacin is a broad-spectrum fluoroquinolone antibiotic that has been widely used in clinical practice since its approval in 1987. It remains an important therapeutic agent for treating various bacterial infections, particularly those caused by Gram-negative organisms. As a second-generation fluoroquinolone, ciprofloxacin demonstrates excellent activity against many pathogens while maintaining an acceptable safety profile when used appropriately.
Mechanism of Action
Ciprofloxacin exerts its bactericidal effect by inhibiting bacterial DNA gyrase (topoisomerase II) and topoisomerase IV enzymes. DNA gyrase is essential for DNA replication, transcription, and repair, while topoisomerase IV is critical for chromosome partitioning during cell division. By binding to these enzymes, ciprofloxacin causes double-stranded DNA breaks, leading to rapid bacterial cell death. This mechanism provides concentration-dependent killing activity against susceptible organisms.
Indications
FDA-approved indications include:
- Urinary tract infections (complicated and uncomplicated)
- Acute uncomplicated cystitis in females
- Chronic bacterial prostatitis
- Lower respiratory tract infections (acute exacerbations of chronic bronchitis, pneumonia)
- Acute sinusitis
- Skin and skin structure infections
- Bone and joint infections
- Infectious diarrhea
- Typhoid fever (enteric fever)
- Complicated intra-abdominal infections (in combination with metronidazole)
- Plague
- Post-exposure inhalation anthrax
- Neutropenic fever (in combination)
Dosage and Administration
Standard adult dosing:- Oral: 250-750 mg every 12 hours
- IV: 200-400 mg every 12 hours
- Urinary tract infections: 250-500 mg every 12 hours for 7-14 days
- Respiratory infections: 500-750 mg every 12 hours for 7-14 days
- Bone/joint infections: 500-750 mg every 12 hours for 4-8 weeks
- Anthrax: 500 mg every 12 hours for 60 days
- Renal impairment: Adjust dose for CrCl <50 mL/min
- Hepatic impairment: No adjustment needed
- Elderly: Consider renal function adjustments
- Pediatrics: Generally avoided except for specific indications (anthrax, plague)
Pharmacokinetics
- Absorption: Well absorbed orally (70-80% bioavailability), decreased by divalent cations
- Distribution: Wide tissue distribution, penetrates well into prostate, lung, and bone
- Metabolism: Partially metabolized in liver via CYP1A2
- Elimination: Renal excretion (40-50% unchanged), half-life 3-5 hours
- Protein binding: 20-40%
Contraindications
- Known hypersensitivity to ciprofloxacin or other quinolones
- Concurrent administration with tizanidine
- History of tendon disorders associated with quinolone use
Warnings and Precautions
Black Box Warnings:- Tendinitis and tendon rupture
- Exacerbation of myasthenia gravis
- Peripheral neuropathy
- CNS effects: seizures, increased intracranial pressure, psychosis
- QT prolongation and arrhythmias
- Hypersensitivity reactions
- Clostridium difficile-associated diarrhea
- Photosensitivity reactions
- Blood glucose disturbances
- Hepatotoxicity
Drug Interactions
Significant interactions:- Antacids, sucralfate, iron, zinc, calcium: Decreased absorption (separate by 2-4 hours)
- Theophylline: Increased theophylline levels
- Warfarin: Enhanced anticoagulant effect
- Probenecid: Decreased renal clearance of ciprofloxacin
- CYP1A2 substrates: Increased levels of tizanidine, theophylline, caffeine
- QT-prolonging drugs: Additive effects (antiarrhythmics, antipsychotics, antidepressants)
- Corticosteroids: Increased risk of tendon rupture
Adverse Effects
Common (≥1%):- Nausea (5.2%)
- Diarrhea (2.3%)
- Headache (1.7%)
- Abnormal liver function tests (1.3%)
- Rash (1.1%)
- Tendinitis and tendon rupture
- Peripheral neuropathy
- QT prolongation and torsades de pointes
- Seizures
- Hepatotoxicity
- Blood dyscrasias
- Severe hypersensitivity reactions
- Clostridium difficile-associated diarrhea
- Psychiatric reactions (anxiety, depression, psychosis)
Monitoring Parameters
- Clinical response to therapy
- Renal and hepatic function (baseline and during prolonged therapy)
- Signs of tendon inflammation or rupture
- Neurological symptoms
- Blood glucose in diabetic patients
- ECG monitoring in patients at risk for QT prolongation
- Signs of superinfection or C. difficile infection
- Therapeutic drug monitoring in special populations
Patient Education
- Complete the full course of therapy even if feeling better
- Take on empty stomach 1 hour before or 2 hours after meals
- Avoid antacids, calcium, iron, or zinc supplements within 2-4 hours of dose
- Maintain adequate hydration
- Report immediately any tendon pain, swelling, or inflammation
- Report numbness, tingling, or burning sensations
- Use sun protection due to photosensitivity risk
- Monitor blood glucose carefully if diabetic
- Report diarrhea that persists after treatment
- Avoid driving or operating machinery if experiencing dizziness or lightheadedness
- Inform all healthcare providers of ciprofloxacin use
References
1. FDA Prescribing Information: Ciprofloxacin (2023) 2. Gilbert DN, et al. The Sanford Guide to Antimicrobial Therapy. 52nd ed. 3. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 9th ed. 4. Flume PA, et al. Ciprofloxacin DPI in non-cystic fibrosis bronchiectasis. N Engl J Med. 2018. 5. Owens RC Jr, Ambrose PG. Antimicrobial safety: focus on fluoroquinolones. Clin Infect Dis. 2005. 6. Clinical Pharmacology [Internet]. Tampa (FL): Elsevier. Ciprofloxacin monograph. 7. USP DI: Drug Information for the Health Care Professional. Micromedex. 8. Lomaestro BM, Drusano GL. Pharmacodynamic evaluation of extending the administration time of ciprofloxacin. Pharmacotherapy. 2007.