What infections and patient groups are treated with amoxicillin administered twice daily (bid)?

Amoxicillin Twice Daily (BID) Dosing: Clinical Uses and Indications

Amoxicillin administered twice daily is indicated for acute otitis media, sinusitis, skin and soft tissue infections, respiratory tract infections, and animal/human bites, with dosing of 500 mg BID in adults and 45 mg/kg/day divided BID in children. 1

Primary Clinical Indications

Acute Otitis Media (AOM)

• High-dose amoxicillin 80-90 mg/kg/day divided into 2 doses is the first-line treatment for pediatric AOM, providing effective coverage against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis 1
• Adult dosing for AOM is 500 mg BID 1
• Twice-daily dosing demonstrates equivalent clinical efficacy to three-times-daily regimens (92% vs 95% favorable outcomes, p=0.25), with improved adherence due to simplified dosing schedules 2, 3
• The maximum adult dose is 1.0 g every 12 hours for resistant organisms 1

Acute Bacterial Sinusitis

• Adults: 500 mg BID is the standard regimen for uncomplicated sinusitis 1
• Pediatric patients: 45 mg/kg/day divided BID 1
• This dosing provides adequate coverage for the most common pathogens (S. pneumoniae, H. influenzae, M. catarrhalis), with 25-50% of S. pneumoniae strains showing penicillin resistance that can be overcome with higher doses 1

Skin and Soft Tissue Infections

Animal and Human Bites

• Amoxicillin-clavulanate 875/125 mg BID is specifically recommended for both animal and human bite wounds, providing coverage against Pasteurella multocida (animal bites) and Eikenella species (human bites) 1
• This formulation covers aerobic and anaerobic organisms commonly found in bite wounds 1

Erysipeloid

• Amoxicillin 500 mg three times daily (not BID) for 7-10 days is the recommended regimen 1

General Cellulitis

• For mild cellulitis without systemic signs, amoxicillin-clavulanate 875/125 mg BID provides coverage against streptococci and MSSA 1
• Treatment duration is typically 5-7 days, extended if infection has not improved 1

Respiratory Tract Infections

• Amoxicillin-clavulanate 875/125 mg BID for 7-14 days is recommended for respiratory infections including bronchitis and community-acquired pneumonia, with clinical success rates of 91.5-93% 4
• The BID regimen has significantly less severe diarrhea (1% vs 2%, p<0.05) compared to three-times-daily dosing due to reduced clavulanate exposure 4, 5

Special Patient Populations

Pediatric Dosing Considerations

• For children >3 months: 20-45 mg/kg/day divided every 12 hours 6
• For neonates and infants ≤3 months: maximum 30 mg/kg/day divided every 12 hours 6
• Children who received amoxicillin in the previous 30 days or those with concurrent conjunctivitis should receive amoxicillin-clavulanate instead of amoxicillin alone 1

Renal Impairment

• Dose reduction is required in patients with severe renal impairment (GFR <30 mL/min) 6

Critical Dosing Distinctions

When BID Dosing is NOT Appropriate

• Group A streptococcal pharyngitis: Standard treatment is amoxicillin 1000 mg once daily or penicillin V 500 mg BID (not amoxicillin BID) for 10 days 4
• Chronic streptococcal carriers: Require amoxicillin-clavulanate 500 mg BID (or 40 mg/kg/day in children divided TID) for 10 days 4
• Acute bacterial rhinosinusitis: Guidelines support 500 mg three times daily for 10 days rather than BID dosing 4

Advantages of BID Formulations

• Improved compliance: Twice-daily dosing reduces family-perceived problems with dosing schedules compared to three-times-daily regimens (31% vs 5.8% reporting difficulties) 2
• Reduced gastrointestinal side effects: Lower daily clavulanate dose in BID formulations (when using amoxicillin-clavulanate) results in fewer GI adverse effects, particularly in children 5
• Equivalent efficacy: Randomized trials confirm that BID dosing provides equivalent bacteriological and clinical efficacy to TID regimens for skin/soft tissue, urinary tract, respiratory infections, and otitis media 5

Common Pitfalls to Avoid

• Never substitute two 250 mg tablets for one 500 mg tablet, as this results in excessive clavulanate dosing and increased GI side effects 4
• Do not use first-generation cephalosporins (cephalexin, cefadroxil) for sinusitis due to poor H. influenzae coverage 1
• Complete the full course of therapy (typically 7-10 days) even if symptoms improve, to prevent treatment failure and resistance development 1, 4
• Avoid routine prophylactic use: Continuous amoxicillin prophylaxis (either once or twice daily) shows no benefit over placebo in preventing recurrent AOM episodes and may promote antibiotic resistance 7