Moxifloxacin
Moxifloxacin
Generic Name
Moxifloxacin
Mechanism
Moxifloxacin interferes with bacterial DNA replication by dual inhibition of DNA gyrase (topoisomerase II) and topoisomerase IV.
• *Gyrase* inhibition predominates in Gram‑negative bacteria, while *topoisomerase IV* inhibition is the primary target in most Gram‑positive organisms, leading to rapid bactericidal activity.
• The compound has a high affinity for the DNA‑enzyme complex, producing double‑strand breaks and preventing transcription/replication.
Pharmacokinetics
- Absorption: Oral bioavailability ≈ 80 % (fast, 1–2 h).
- Distribution: Extensive; volume of distribution ~ 7 L/kg. Penetrates well into lungs, CSF, bone, and abscess fluid.
- Metabolism: Primarily hepatic via oxidation to inactive metabolites; minimal glucuronidation.
- Elimination: Renal clearance ~ 60 % unchanged; half‑life 6–8 h (shorter in renal impairment).
- Drug interactions: Competitive inhibition of CYP 1A2, CYP 2D6, and CYP 3A4; caution with P‑gp substrates.
Indications
- Community‑acquired bacterial pneumonia (CAP).
- Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) when bacterial infection suspected.
- Vaginal and intra‑uterine abscesses.
- Skin and soft‑tissue infections (SSTIs), including cellulitis and wound infections.
- Community‑acquired urinary tract infections (UTIs) in certain settings.
- Intra‑abdominal infections (abdominal sepsis) when broad coverage is required.
Contraindications
- Contraindications: Hypersensitivity to fluoroquinolones; G‑lactam allergy may accompany cross‑reactivity.
- Warnings:
- Tendinopathies and tendon rupture; avoid in athletes, those >60 yr, or concurrent steroid use.
- QT prolongation; beware of cardiac disease, electrolyte disturbances, and concomitant QT‑extending drugs.
- CNS effects (tremors, seizures, hallucinations).
- Caution in pregnancy (Category B) and breastfeeding; infant nursing may require a pause if the infant is 2–3 days old.
Dosing
| Infection | Adult Dose (IV) | Adult Dose (PO) | Duration (typical) |
| CAP, AECOPD | 400 mg q 24 h | 400 mg q 24 h (≤50 kg: 320 mg) | 7–14 days |
| SSTI | 400 mg q 24 h | 400 mg q 24 h | 5–14 days |
| Abscesses | 400 mg q 24 h | 400 mg q 24 h | 7–10 days |
| UTI | 400 mg q 24 h | 400 mg q 24 h | 5–7 days |
| Renal impairment (CrCl 30–59 mL/min) | 200 mg q 24 h | 200 mg q 24 h | Adjust per above |
• IV infusion over 30–60 min avoids rapid peak levels.
• Weight‑based adjustment when <50 kg.
Adverse Effects
- Common (≤10 %): GI upset, nausea, vertigo, headache, altered taste, rash.
- Serious (≤1 %):
- Tendon rupture (especially in elderly, concurrent steroids).
- QT prolongation leading to torsades de pointes.
- Severe CNS reactions (seizures, psychosis).
- Hypersensitivity (rash, eosinophilic pneumonia).
- Rare: aortic dissection, retinal detachment.
Monitoring
- Baseline QT interval and electrolytes (K⁺, Mg²⁺).
- Renal function: serum creatinine, CrCl at baseline, then every 3–5 days when dosing.
- Blood glucose in diabetic patients (fluoroquinolones can alter glucose).
- Tendon assessment if high‑risk (elderly, concurrent steroids).
- Liver transaminases if prolonged therapy (>7 days).
Clinical Pearls
- Rapid tissue penetration: Moxifloxacin achieves peak concentrations in lung tissue within 1–2 h, providing robust coverage for CAP.
- Dual target inhibition makes it effective against *Pseudomonas aeruginosa* and MRSA—rare for fluoroquinolones.
- Avoid in pediatric patients <18 years due to risk of musculoskeletal toxicity; consider alternatives.
- Drug‑drug interactions: Concomitant use with oral hypoglycemics can impair glucose monitoring; avoid if insulin therapy is initiated concomitantly.
- Stomach irritation: Administer with a meal to reduce GI side‑effects, unless contraindicated by hepatic dysfunction.
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• *Prepared for medical students and clinicians seeking an evidence‑based overview of moxifloxacin’s pharmacology, indications, and safety profile.*