What is the first-line antibiotic treatment for bacterial infections?

First-Line Antibiotic Treatment for Bacterial Infections

The first-line antibiotic choice depends critically on the infection site and patient age, but amoxicillin stands as the most broadly recommended Access group antibiotic across multiple common bacterial infections, particularly for respiratory tract infections in both children and adults. 1

WHO AWaRe Framework for Antibiotic Selection

The WHO categorizes antibiotics into three groups to guide appropriate empiric therapy: 2

• Access group antibiotics (amoxicillin, ampicillin, benzylpenicillin, gentamicin, cloxacillin) should be the default first-line choices—these are narrow-spectrum agents with favorable risk-benefit ratios and lower resistance potential 2
• Watch group antibiotics (fluoroquinolones, carbapenems, third-generation cephalosporins) carry greater toxicity concerns and resistance potential, reserved for second-line therapy or specific indications 2
• Reserve group antibiotics should only be used when other alternatives have failed or documented multidrug resistance exists 2

Infection-Specific First-Line Recommendations

Community-Acquired Pneumonia (CAP)

For mild to moderate CAP, amoxicillin is the reference first-line treatment based on non-inferiority to other classes and low resistance potential. 1

• Low severity (outpatient, no comorbidities): Amoxicillin 3 g/day in adults 1; 80-100 mg/kg/day in children <3 years 1
• Moderate severity: Amoxicillin plus a macrolide (clarithromycin preferred over erythromycin due to fewer adverse events) 1
• High severity/ICU: Ceftriaxone or cefotaxime plus clarithromycin as first-line; piperacillin-tazobactam or respiratory fluoroquinolone (levofloxacin) as alternatives 1
• Children >3 years with atypical features: Macrolide monotherapy is reasonable for suspected Mycoplasma or Chlamydia 1

The evidence shows no mortality difference between β-lactam monotherapy, β-lactam-macrolide combination, or fluoroquinolone monotherapy in randomized trials, supporting the use of narrower-spectrum amoxicillin. 1

Intra-Abdominal Infections

For non-severe community-acquired intra-abdominal infections, amoxicillin-clavulanic acid is the first-choice option. 1

• Non-severe infections: Amoxicillin-clavulanic acid (first choice); ciprofloxacin plus metronidazole (second choice) 1
• Severe infections: Cefotaxime or ceftriaxone plus metronidazole (first choice); piperacillin-tazobactam (alternative first choice); meropenem (second choice) 1

Ciprofloxacin was preferred over levofloxacin for parsimony and to preserve levofloxacin for multidrug-resistant tuberculosis treatment. 1

Skin and Soft Tissue Infections

For impetigo and non-purulent cellulitis, oral dicloxacillin or cefalexin are first-line choices targeting Staphylococcus aureus and streptococci. 1

• Impetigo: Dicloxacillin, cefalexin, or amoxicillin-clavulanic acid 1
• Non-purulent cellulitis: Benzylpenicillin, phenoxymethylpenicillin, or cloxacillin 1
• Purulent infections (likely S. aureus): Dicloxacillin, cefazolin, or clindamycin 1
• Suspected MRSA: Vancomycin, linezolid, or clindamycin (though linezolid showed better clinical cure rates than vancomycin in meta-analysis) 1

Neonatal Sepsis

For early-onset neonatal sepsis, ampicillin plus gentamicin is the WHO-recommended first-line empiric treatment, providing coverage against Group B Streptococcus, E. coli, and Listeria. 1, 3

• Early-onset sepsis: Ampicillin plus gentamicin (or benzylpenicillin plus gentamicin, or amoxicillin plus gentamicin) 1, 3
• Late-onset/nosocomial sepsis: Amikacin plus cloxacillin (first choice); cefotaxime or ceftriaxone (second choice) 1, 3
• Suspected MRSA or resistant Gram-negatives: Vancomycin plus ceftazidime 3

Critical pitfall: If no clinical improvement occurs after 48-72 hours on initial therapy, immediately escalate to amikacin plus cloxacillin (or vancomycin if MRSA suspected)—never wait beyond 72 hours. 4

COPD Exacerbations

For hospitalized patients with COPD exacerbations, antibiotics reduce treatment failure and mortality, though outpatient benefit is less clear. 1

• Antibiotics reduce treatment failure in inpatients (RR 0.77) and in-hospital death (RR 0.22) 1
• First-line antibiotics (amoxicillin, ampicillin, trimethoprim-sulfamethoxazole, doxycycline) showed lower treatment success than second-line agents (amoxicillin-clavulanic acid, macrolides, cephalosporins, quinolones) in meta-analysis 1

Critical Timing Considerations

• Septic shock: Initiate antibiotics within 1 hour 3
• Sepsis without shock: Initiate within 3 hours 3
• Blood cultures: Obtain before antibiotics but never delay treatment waiting for results 3

Common Pitfalls to Avoid

• Azithromycin avoidance: Not recommended due to increased cardiovascular events compared to other macrolides 1
• Fluoroquinolone caution: Associated with tendon, muscle, joint, nerve, and CNS adverse events—reserve for severe infections or resistant pathogens 1
• Local resistance patterns: Initial empiric choices must reflect institutional antibiograms, as less than one-quarter of neonates globally receive WHO-recommended antibiotics due to local resistance 3, 4
• Tigecycline: Not recommended for intra-abdominal infections due to FDA boxed warning regarding higher mortality rates 1