Ciprofloxacin
Ciprofloxacin
Generic Name
Ciprofloxacin
Mechanism
Ciprofloxacin interferes with bacterial DNA replication by dual inhibition of:
• DNA gyrase (Topoisomerase II) – essential for supercoiling and unwinding of DNA.
• Topoisomerase IV – critical for chromosome segregation during cell division.
Binding to the gyrase‑DNA complex stabilizes the cleaved complex, leading to double‑stranded DNA breaks and bacterial death (bactericidal). Fluoroquinolones also have a modest antibiofilm effect, though this is less clinically significant.
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Pharmacokinetics
- Absorption: Oral → 70–80 % bioavailable; food decreases absorption by ~25 % (take on empty stomach).
- Distribution: Extensive – volumes of distribution (Vd) ~18 L/m²; penetrates well into tissues (skin, bone, lung, prostate) and fluids (urine, synovial, CSF ≈ 50–60 % of serum).
- Metabolism: Minimal hepatic metabolism; ~55 % unchanged in urine, ~30 % excreted unchanged via bile/duodenum.
- Elimination: Primarily renal (≈60 %); half‑life ~4 h in normal renal function, prolonged with impairment (1‑2 h to >6 h depending on GFR).
- Protein binding: 20–30 %.
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Indications
| Indication | Typical Use |
| Lower Respiratory Tract Infections (e.g., community‑acquired pneumonia) | 500 mg PO BID (or IV 400 mg Q12h) 10–14 days |
| Upper Respiratory Tract / Sinusitis | 250–500 mg PO BID, 5–10 days |
| Urinary Tract Infections (severe, complicated) | 500 mg PO/IV BID, 7–14 days |
| Intraabdominal / Abdominal (peri‑operative) | 500–750 mg IV Q12h, 7‑10 days |
| Skin & Soft‑Tissue Infections | 500 mg PO/IV BID, 7‑10 days |
| Severe Gram‑negative Infections (sepsis, meningitis) | 500 mg IV Q12h, adjust per renal function |
| Gonorrhea (including ceftriaxone‑resistant strains) | 500 mg PO single dose |
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Contraindications
- Allergy to ciprofloxacin or any fluoroquinolone component.
- Pregnancy (Category C) – avoid unless no alternatives.
- Pediatrics and Young Children (growth/toxicity concerns).
- Myasthenia Gravis – risk of exacerbation.
- Severe Renal Dysfunction (CrCl <30 mL/min) – dose adjustment required.
- History of Tendinopathy / Rupture – dose reduction, monitor.
- QT‑interval prolongation disorders – avoid if possible; monitor ECG in high‑risk patients.
- Epilepsy – may lower seizure threshold.
- Concurrent use of probenecid – increases ciprofloxacin levels.
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Dosing
| Condition | Dose | Route | Frequency | Duration |
| Adults – uncomplicated UTI | 500 mg | PO/IV | BID | 7–14 days |
| Adults – complicated UTI | 500–750 mg | PO/IV | BID | 14–21 days |
| Adults – CAP | 500 mg | PO/IV | BID | 10–14 days |
| Adults – SSTI | 500 mg | PO/IV | BID | 7–10 days |
| Adults – sepsis, meningitis | 500 mg | IV | Q12h | 14–21 days |
| Renal adjustment (CrCl 20‑40 mL/min) | 500 mg | PO/IV | Q12h | 7–14 days |
| Renal adjustment (CrCl <20 mL/min) | 250 mg | PO/IV | Q12h | 7–14 days |
• Start with a loading dose of 750 mg IV for severe infections.
• Avoid taking with dairy milk or calcium‑fortified juices.
• Use a fast‑acting carb‑hydrate if GI upset occurs.
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Adverse Effects
| Category | Illustrative Examples |
| GI | Nausea, vomiting, diarrhea, dyspepsia, abdominal cramping |
| Central Nervous System | Headache, dizziness, insomnia, paresthesias, anxiety, seizures (rare) |
| Musculoskeletal | Tendinopathy, tendon rupture (extensor tendon > Achilles) especially in older adults or concurrent steroids |
| Cardiovascular | QT prolongation, ventricular arrhythmias (rare) |
| Metabolic | Hyperglycemia, hypoglycemia, hypokalemia (via renal tubular effect) |
| Allergic | Rash, pruritus, anaphylaxis (rare) |
| Increased Serum Creatinine | Transient, due to decreased tubular secretion |
| Photosensitivity | Sunburn‑like reaction, especially in tropical climates |
| Dermatologic | Stevens‑Johnson syndrome, toxic epidermal necrolysis (rare; severe) |
| Hepatotoxicity | Elevated transaminases; monitor AST/ALT in prolonged therapy |
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Monitoring
- Renal Function: serum creatinine / eGFR at baseline, Day 3–5, and before each dose change.
- Liver Enzymes: AST/ALT baseline, then periodically if therapy >2 weeks.
- Electrolytes: K⁺, Mg²⁺, Ca²⁺ when at risk (e.g., chronic diuretic use).
- ECG: baseline in patients with QT‑prolonging comorbidities or concomitant drugs.
- Symptoms of Tendinopathy: educate patients to report tendon pain, swelling, or weakness.
- Signs of CNS Toxicity: monitor for agitation, confusion, seizures (especially in elderly).
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Clinical Pearls
- Avoid the “fluoroquinolone warning” only for susceptible infections; the benefits outweigh risks when used appropriately.
- Food interaction: give ciprofloxacin 2 h before or after meals containing iron, magnesium, calcium, or aluminum to maintain absorption.
- Tendon monitoring: best to prescribe for the shortest duration (≤14 days) in older adults on steroids; if tendon pain arises, discontinue immediately.
- Renal dose adjustment is critical; *recalc* using CrCl formula as patients age or receive nephrotoxic drugs (e.g., NSAIDs, aminoglycosides).
- Combination therapy: consider adding a beta‑lactam or azithromycin for severe pneumonia to broaden coverage and reduce emergence of resistance.
- Prevent ophthalmic adverse events: recommend sunglasses in sunny climates; avoid prolonged exposure in photosensitive individuals.
- Resistant strains: test cultures promptly and use susceptibility data to switch if MIC >1 µg/mL.
- Drug–drug interactions: avoid concurrent use of doxycycline, warfarin, or theophylline due to potential for QT prolongation.
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• Ciprofloxacin remains a cornerstone for treating Gram‑negative bacterial infections, but judicious use, attention to dosing in renal impairment, and vigilance for tendinopathy and CNS effects are essential for safe and effective therapy.