What are the first-line oral antibiotics for common bacterial infections?

First-Line Oral Antibiotics for Common Bacterial Infections

Amoxicillin remains the cornerstone first-line oral antibiotic for most common bacterial infections, with amoxicillin-clavulanate reserved for β-lactamase-producing organisms or treatment failures. 1, 2

Respiratory Tract Infections

Community-Acquired Pneumonia

For pneumococcal pneumonia in children under 3 years, amoxicillin 80-100 mg/kg/day in three divided doses is the reference treatment. 1 This dosing achieves adequate serum concentrations against Streptococcus pneumoniae, including strains with reduced penicillin susceptibility. 1

• In children over 3 years, the clinical and radiological picture guides therapy: amoxicillin for suspected pneumococcal infection, or a macrolide for atypical pathogens (Mycoplasma pneumoniae, Chlamydia pneumoniae). 1
• For adults with non-severe CAP, penicillin G, aminopenicillin plus macrolides, or co-amoxiclav plus macrolides are first-line options. 2
• For severe CAP, use a 3rd generation cephalosporin plus macrolides. 2

Acute Otitis Media

High-dose amoxicillin (80-90 mg/kg/day in 2 divided doses) is the recommended first-line treatment for AOM. 1 This provides effective coverage against common pathogens while maintaining a narrow microbiologic spectrum and favorable safety profile. 1

• Switch to high-dose amoxicillin-clavulanate (90 mg/kg/day of amoxicillin with 6.4 mg/kg/day of clavulanate in 2 divided doses, 14:1 ratio) if the child has taken amoxicillin in the previous 30 days, has concurrent conjunctivitis, or requires coverage for β-lactamase-producing Haemophilus influenzae or Moraxella catarrhalis. 1
• For penicillin allergy, cefdinir (14 mg/kg/day), cefuroxime (30 mg/kg/day), or cefpodoxime (10 mg/kg/day) are alternatives, as cross-reactivity with cephalosporins is lower than historically reported. 1
• After 48-72 hours of treatment failure, escalate to amoxicillin-clavulanate or ceftriaxone (50 mg IM/IV for 3 days). 1

Acute Sinusitis

For maxillary sinusitis, first-line therapy includes amoxicillin-clavulanate, 2nd generation cephalosporins (cefuroxime-axetil), or 3rd generation cephalosporins (cefpodoxime-proxetil, cefotiam-hexetil). 1 Pristinamycin is an alternative for β-lactam allergy. 1

• Reserve fluoroquinolones active against pneumococci (levofloxacin, moxifloxacin) for frontal, fronto-ethmoidal, or sphenoidal sinusitis, or for first-line treatment failures. 1
• Treatment duration is 7-10 days, though cefuroxime-axetil and cefpodoxime-proxetil have demonstrated efficacy in 5 days. 1

Acute Bronchitis

Antibiotics are generally not indicated for acute bronchitis, as 90% of cases are viral. 1

• In children under 3 years with fever >38.5°C persisting >3 days, consider amoxicillin, amoxicillin-clavulanate, cefuroxime-axetil, or cefpodoxime-proxetil for 5-8 days. 1
• In patients over 3 years, macrolides are preferred if treatment is warranted. 1

Skin and Soft Tissue Infections

Impetigo and Non-Purulent Infections

For impetigo, first-line oral antibiotics include dicloxacillin, cefalexin, erythromycin, clindamycin, or amoxicillin-clavulanate. 2

• For non-purulent cellulitis, benzylpenicillin, phenoxymethylpenicillin, clindamycin, nafcillin, cefazolin, or cefalexin provide adequate coverage against streptococci and methicillin-susceptible Staphylococcus aureus. 2

Purulent Infections (Suspected S. aureus)

For purulent skin infections likely caused by S. aureus, use dicloxacillin, cefazolin, clindamycin, cefalexin, doxycycline, or sulfamethoxazole-trimethoprim. 2

• For confirmed or suspected MRSA, vancomycin, linezolid, clindamycin, daptomycin, ceftaroline, doxycycline, or sulfamethoxazole-trimethoprim are first-line options. 2
• Linezolid demonstrates superior clinical cure rates compared to vancomycin (OR 1.41; 95% CI 1.03-1.95). 2

Necrotizing Fasciitis

For group A streptococcal necrotizing fasciitis, use clindamycin plus penicillin. 1 Clindamycin suppresses toxin production and modulates cytokine responses, while penicillin is added due to increasing macrolide resistance. 1

• For mixed polymicrobial necrotizing infections, use ampicillin-sulbactam (1.5-3.0 g every 6-8 hours) or piperacillin-tazobactam (3.37 g every 6-8 hours) plus clindamycin (600-900 mg every 8 hours) plus ciprofloxacin (400 mg every 12 hours). 1
• Alternative regimens include imipenem/cilastatin (1 g every 6-8 hours), meropenem (1 g every 8 hours), or ertapenem (1 g daily). 1

Intra-Abdominal Infections

For mild to moderate community-acquired intra-abdominal infections, amoxicillin-clavulanate is first-line therapy. 2 In children, ampicillin plus gentamicin plus metronidazole is an alternative. 2

• For severe infections, use cefotaxime or ceftriaxone plus metronidazole, or piperacillin-tazobactam. 2
• For hospital-acquired infections in critically ill patients, piperacillin, tigecycline, or a carbapenem (meropenem, imipenem, or doripenem) provides broader coverage. 2

Important Considerations and Common Pitfalls

Duration of therapy for most community-acquired infections is 5-7 days, with more severe infections requiring 10-14 days. 2 Clinical improvement should be evident within 3 days; patients should contact their physician if no improvement occurs. 2

Common pitfalls to avoid:

• Do not use fluoroquinolones as first-line therapy due to increasing resistance concerns and the need to preserve these agents for more serious infections. 1, 2
• Avoid using clindamycin for Bacteroides fragilis infections without checking local susceptibility patterns, as resistance varies geographically. 2
• Do not use broad-spectrum antibiotics for mild infections that could be treated with narrower-spectrum agents like amoxicillin. 2
• Ensure adequate MRSA coverage when purulent skin infections are present, as empiric β-lactam therapy alone will fail. 2
• Consider local resistance patterns when selecting antibiotics, as susceptibility varies by geographic region. 2

For penicillin-allergic patients, the cross-reactivity rate with cephalosporins is lower than the historically cited 10%, making cephalosporins reasonable alternatives in most cases. 1 However, for severe type I hypersensitivity reactions, avoid all β-lactams and use macrolides, fluoroquinolones, or other non-β-lactam alternatives. 1