Ciprofloxacin

Ciprofloxacin is a widely used fluoroquinolone with the strongest Gram-negative activity of the oral class, including Pseudomonas aeruginosa. It is used for urinary, gastrointestinal, bone, joint and some respiratory infections, and for anthrax and plague. Resistance is common and serious adverse effects restrict its use in minor infection.

Classification. Fluoroquinolone, second generation.

Mechanism. Inhibits DNA gyrase and topoisomerase IV, blocking DNA replication; bactericidal, concentration-dependent.

Spectrum. Enterobacterales, Pseudomonas aeruginosa, Haemophilus, Neisseria, Campylobacter, Salmonella, Shigella, Vibrio cholerae, Bacillus anthracis, Yersinia pestis, Brucella and atypical bacteria in part. Weak against pneumococci and streptococci, enterococci and anaerobes. Resistance is high in Escherichia coli, Salmonella Typhi, Campylobacter and gonococci.

Pharmacokinetics. Oral bioavailability about 70%, reduced by cations. Half-life 4 hours. Protein binding 20 to 40%. Wide tissue penetration. Renal and non-renal clearance; CYP1A2 inhibitor.

Maximum 1.5 g daily orally or 1.2 g daily IV in adults.

Adults, oral. 250 to 750 mg every 12 hours. IV 400 mg every 8 to 12 hours over 60 minutes. Switch to oral once improving.

• Uncomplicated cystitis (when other options are unsuitable): 250 to 500 mg every 12 hours for 3 days.
• Pyelonephritis and complicated urinary tract infection: 500 mg every 12 hours for 7 days (400 mg IV every 12 hours).
• Prostatitis: 500 mg every 12 hours for 28 days.
• Typhoid and paratyphoid (when susceptible): 500 mg every 12 hours for 7 to 14 days. Resistance is widespread, and azithromycin or ceftriaxone is used when resistance is likely.
• Infective diarrhoea (severe, invasive): 500 mg every 12 hours for 3 days. Cholera: 1 g as a single dose.
• Bone and joint infection, Pseudomonas infection: 750 mg every 12 hours (400 mg IV every 8 hours), usually with a second active agent.
• Anthrax and plague: 500 mg orally every 12 hours or 400 mg IV every 8 to 12 hours. Inhalational anthrax post-exposure usually needs 60 days.
• Gonorrhoea: not advised unless susceptibility is proven.
• Neutropenic fever (oral, low risk): 750 mg every 12 hours with amoxicillin clavulanate.

Children. Use only for complicated urinary tract infection, pulmonary Pseudomonas infection in cystic fibrosis, anthrax, plague and similar when alternatives are not suitable. Oral 10 to 20 mg/kg every 12 hours (maximum 750 mg a dose); IV 6 to 10 mg/kg every 8 hours (maximum 400 mg a dose). Cholera 20 mg/kg as a single dose (maximum 1 g).

Alternatives. Nitrofurantoin, fosfomycin, trimethoprim, ceftriaxone, azithromycin, levofloxacin.

Boxed-warning level risks. Tendinitis and tendon rupture, peripheral neuropathy, central nervous system effects, exacerbation of myasthenia gravis, and an association with aortic aneurysm and dissection. Use for minor infection is discouraged.

Contraindications. Fluoroquinolone hypersensitivity; previous tendon disorder with a fluoroquinolone; concurrent tizanidine; myasthenia gravis (relative).

Adverse effects. Nausea, diarrhoea, headache, dizziness, insomnia, photosensitivity.

Serious adverse effects:

• Tendon rupture (higher with age over 60 years, corticosteroids and transplant)
• QT prolongation and torsades de pointes
• Dysglycaemia (especially in diabetes on sulphonylureas)
• Peripheral neuropathy, seizures and psychosis
• Aortic aneurysm or dissection
• Hepatotoxicity, Clostridioides difficile infection, severe skin reactions
• Cartilage damage in growing animals

Interactions.

• Magnesium, aluminium, calcium, iron and zinc products and sucralfate reduce absorption: take ciprofloxacin 2 hours before or 6 hours after.
• Tizanidine (contraindicated), theophylline and caffeine (toxicity), warfarin (INR rise), clozapine, duloxetine, methotrexate, ciclosporin, sulphonylureas (hypoglycaemia).
• QT-prolonging drugs, corticosteroids (tendon risk), NSAIDs (seizure risk).

Common prescribing errors. Use for uncomplicated infection when safer drugs work, giving with dairy, antacids or iron, no dose adjustment in renal impairment, and use for pneumococcal pneumonia.

Special groups.

• Pregnancy: avoid unless no safe alternative exists.
• Breastfeeding: avoid if possible; a short course is acceptable when essential.
• Older adults: higher risk of tendon rupture, delirium and QT prolongation; use lower doses.
• Kidney impairment: creatinine clearance 30 to 50 mL/min 250 to 500 mg every 12 hours; 5 to 29 mL/min 250 to 500 mg every 18 hours; haemodialysis 250 to 500 mg every 24 hours after dialysis. IV: 200 to 400 mg every 18 to 24 hours when creatinine clearance is under 30 mL/min.
• Liver impairment: no adjustment in mild to moderate disease; use with caution in severe disease.
• Region: widely available and affordable in East Africa. Resistance is high in urinary Escherichia coli and in Salmonella Typhi, so culture results should decide use.

Preparation. Oral tablets with water, with or without food, away from dairy alone and from cations. IV: infuse over 60 minutes at 1 to 2 mg/mL in 0.9% sodium chloride or 5% glucose; rapid infusion causes venous irritation.

Baseline and monitoring. - Baseline: medication review for tizanidine, QT drugs and cations; ECG in cardiac risk; glucose in diabetes; creatinine; pregnancy status. - During treatment: ask about tendon pain, paraesthesia and mood; glucose in diabetes on insulin or sulphonylureas.

Stop rules. Stop at first tendon pain, new neuropathic symptoms, severe hypoglycaemia, psychiatric symptoms, seizure, rash or palpitations.

Referral and escalation. Refer for tendon rupture, neuropathy, aortic symptoms, resistant Pseudomonas infection and bone or joint infection.