What is the appropriate co‑amoxiclav (amoxicillin + clavulanic acid) dose for an otherwise healthy adult with an uncomplicated upper respiratory tract infection, and how should it be adjusted for children, renal impairment, or severe penicillin allergy?

Co‑Amoxiclav Dosing for Upper Respiratory Tract Infection

Standard Adult Dosing for Uncomplicated URTI

For otherwise healthy adults with uncomplicated upper respiratory tract infection, co‑amoxiclav 875 mg/125 mg orally twice daily for 5–7 days is the recommended first‑line regimen, providing 90–92 % predicted clinical efficacy against the principal respiratory pathogens. 1

• The standard adult dose is 875 mg amoxicillin/125 mg clavulanate twice daily for most respiratory infections without risk factors. 1, 2
• An alternative regimen is 500 mg/125 mg three times daily, though twice‑daily dosing improves compliance. 3, 2
• Treatment duration should be 5–10 days or until the patient is symptom‑free for 7 consecutive days (typically 10–14 days total). 1
• Recent evidence supports shorter 5–7 day courses with comparable efficacy and fewer adverse effects compared with traditional 10‑day regimens. 1

High‑Dose Regimen for Risk Factors

• High‑dose co‑amoxiclav (2 g amoxicillin/125 mg clavulanate twice daily) is indicated when any of the following risk factors are present: 1
  • Recent antibiotic use within the past 4–6 weeks 3, 1
  • Age > 65 years 1
  • Moderate‑to‑severe symptoms 1
  • Comorbidities (diabetes, chronic cardiac/hepatic/renal disease) 1
  • Immunocompromised state 1
  • Close contact with daycare children 1
  • Smoking or exposure to smoke 1
  • High local prevalence of penicillin‑resistant Streptococcus pneumoniae (> 10 %) 1

Pediatric Dosing

• Standard pediatric dose: 45 mg/kg/day of amoxicillin component with 6.4 mg/kg/day clavulanate, divided into 2 doses for uncomplicated infections. 1
• High‑dose pediatric regimen: 80–90 mg/kg/day of amoxicillin component with 6.4 mg/kg/day clavulanate, divided into 2 doses, for children with risk factors: 1
  • Age < 2 years 1
  • Daycare attendance 1
  • Recent antibiotic use (past 4–6 weeks) 1
  • Incomplete Haemophilus influenzae type b vaccination 1
  • Regional prevalence of penicillin‑resistant S. pneumoniae > 10 % 1
  • Moderate‑to‑severe illness 1
  • Concurrent purulent otitis media 1
• Pediatric treatment duration: Minimum 10–14 days (longer than adult courses). 1
• Children weighing ≥ 40 kg should be dosed according to adult recommendations. 1, 2
• The 14:1 ratio of amoxicillin to clavulanate in the high‑dose pediatric formulation causes less diarrhea than other co‑amoxiclav preparations. 1

Renal Dose Adjustments

• Creatinine clearance 10–30 mL/min: 875 mg/125 mg once daily or 500 mg/125 mg every 12 hours, depending on infection severity. 2, 4
• Creatinine clearance < 10 mL/min: 875 mg/125 mg or 500 mg/125 mg every 24 hours, depending on severity. 2, 4
• Hemodialysis patients: 500 mg/125 mg or 250 mg/125 mg every 24 hours, with an additional dose both during and at the end of dialysis. 2, 4
• Patients with severe renal impairment (GFR < 30 mL/min) should not receive the 875 mg/125 mg formulation. 2
• The ratio of amoxicillin to clavulanate area‑under‑the‑curve increases markedly with declining renal function (from 4.9 at GFR 75 mL/min to 14.7 in hemodialysis patients), so standard dosing in renal failure leads to disproportionate amoxicillin accumulation. 4

Alternatives for Penicillin Allergy

• Non‑severe (non‑type I) penicillin allergy: Second‑ or third‑generation cephalosporins (cefuroxime‑axetil, cefpodoxime‑proxetil, cefdinir, cefprozil) for 10 days; cross‑reactivity is negligible. 1, 5
• Severe (type I/anaphylactic) penicillin allergy: Respiratory fluoroquinolones—levofloxacin 500 mg once daily for 10–14 days or moxifloxacin 400 mg once daily for 10 days—provide 90–92 % predicted efficacy against multidrug‑resistant pathogens. 1, 5
• Doxycycline 100 mg once daily for 10 days is an acceptable but suboptimal alternative (77–81 % predicted efficacy with a 20–25 % bacteriologic failure rate) and is contraindicated in children < 8 years. 1, 5

Administration and Tolerability

• Co‑amoxiclav may be taken without regard to meals, but absorption of clavulanate is enhanced when administered at the start of a meal. 2
• To minimize gastrointestinal intolerance, take at the start of a meal. 2
• Gastrointestinal adverse effects are common: diarrhea occurs in 40–43 % of patients, with severe diarrhea in 7–8 %. 1
• Two 250 mg/125 mg tablets are not equivalent to one 500 mg/125 mg tablet because both contain the same 125 mg clavulanate dose; therefore, do not substitute two 250 mg/125 mg tablets for one 500 mg/125 mg tablet. 2

Monitoring and Reassessment

• Reassess at 3–5 days: If no clinical improvement (persistent purulent drainage, unchanged symptoms, or worsening), switch to high‑dose co‑amoxiclav or a respiratory fluoroquinolone. 1
• Reassess at 7 days: Persistent or worsening symptoms warrant confirmation of diagnosis, exclusion of complications, and consideration of imaging or specialist referral. 1
• Expected timeline: Noticeable improvement should occur within 3–5 days of appropriate therapy, with complete resolution by 10–14 days. 1

Critical Pitfalls to Avoid

• Do not prescribe antibiotics for viral URTI (symptom duration < 10 days without severe features); 98–99.5 % of acute rhinosinusitis is viral and resolves spontaneously within 7–10 days. 1
• Ensure adequate treatment duration (minimum 5 days for adults, 10 days for children) to prevent relapse. 1
• Reserve fluoroquinolones for severe penicillin allergy or treatment failure; avoid routine first‑line use to prevent resistance. 1
• Hepatically impaired patients should be dosed with caution and hepatic function monitored at regular intervals. 2

Specific Indications by Pathology

Acute Bacterial Sinusitis

• Adults: Co‑amoxiclav 875 mg/125 mg twice daily for 5–7 days is first‑line therapy, except in cases with risk factors where high‑dose (2 g/125 mg twice daily) is recommended. 1
• Children: Standard co‑amoxiclav dosing (45 mg/kg/day) is first‑line, with high‑dose (80–90 mg/kg/day) for those with risk factors. 1
• Treatment duration is 5–7 days for adults, which is as effective as 10 days in most cases. 1

Non‑Severe Childhood Pneumonia

• First‑line treatment is amoxicillin 50 mg/kg in 2 divided doses for 5 days. 1
• High‑dose co‑amoxiclav (80–90 mg/kg/day amoxicillin component) is second‑line if amoxicillin fails. 1

Bronchiectasis Exacerbations

• For beta‑lactamase producing Haemophilus influenzae: 625 mg three times daily for 14 days. 1

Adjunctive Therapies (Add to All Patients)

• Intranasal corticosteroids (mometasone, fluticasone, budesonide) twice daily significantly reduce mucosal inflammation and accelerate symptom resolution; supported by strong evidence from multiple randomized controlled trials. 1
• Saline nasal irrigation 2–3 times daily provides symptomatic relief and enhances mucus clearance. 1
• Analgesics (acetaminophen or ibuprofen) for pain and fever control. 1