What are the first-line antibiotics to give to a patient with a bacterial infection?

First-Line Antibiotic Selection for Bacterial Infections

For most common bacterial infections, amoxicillin or amoxicillin-clavulanate should be the first-line choice, with specific alternatives based on infection site, severity, and local resistance patterns. 1, 2, 3

General Framework: The AWaRe Classification

The WHO AWaRe framework guides antibiotic selection to optimize effectiveness while minimizing resistance 1:

• Access antibiotics (first-line): Amoxicillin, amoxicillin-clavulanate, penicillin, cephalexin, doxycycline, trimethoprim-sulfamethoxazole 1
• Watch antibiotics (second-line/specific indications): Fluoroquinolones, third-generation cephalosporins, macrolides 1
• Reserve antibiotics (last-resort only): Carbapenems, linezolid, colistin 1

Infection-Specific First-Line Recommendations

Respiratory Tract Infections

Community-Acquired Pneumonia:

• Low severity (outpatient): Amoxicillin monotherapy 2
• Moderate severity (hospitalized): Amoxicillin plus azithromycin 2, 4
• High severity (ICU): Beta-lactam/beta-lactamase inhibitor (ampicillin-sulbactam or piperacillin-tazobactam) plus azithromycin 2
• Suspected Pseudomonas: Piperacillin-tazobactam or carbapenem plus ciprofloxacin or levofloxacin 2

Acute Bacterial Rhinosinusitis:

• Mild disease, no recent antibiotics: High-dose amoxicillin-clavulanate (1.75-4 g/250 mg daily) or amoxicillin (1.5-4 g daily) 1, 3
• Moderate disease or recent antibiotic use: High-dose amoxicillin-clavulanate (90 mg/6.4 mg per kg daily in children) 1
• Beta-lactam allergy: Doxycycline, trimethoprim-sulfamethoxazole, or azithromycin (note: 20-25% bacterial failure rate expected) 1, 3

Skin and Soft Tissue Infections

Non-purulent cellulitis:

• Benzylpenicillin, phenoxymethylpenicillin, cefazolin, or cephalexin 1

Purulent infections (likely Staphylococcus aureus):

• Dicloxacillin, cefazolin, cephalexin, or clindamycin 1
• If MRSA suspected: Trimethoprim-sulfamethoxazole, doxycycline, or clindamycin 1

Necrotizing fasciitis:

• Clindamycin plus piperacillin-tazobactam (with or without vancomycin) OR ceftriaxone plus metronidazole (with or without vancomycin) 1, 3

Animal bites:

• Oral: Amoxicillin-clavulanate 1
• Intravenous: Ampicillin-sulbactam or piperacillin-tazobactam 1

Urinary Tract Infections

Acute uncomplicated cystitis:

• Trimethoprim-sulfamethoxazole or nitrofurantoin 1
• Alternative: Fluoroquinolones (reserve for complicated cases) 1

Acute pyelonephritis:

• Fluoroquinolones or third-generation cephalosporins 1

Genitourinary Infections

Gonococcal urethritis:

• Ceftriaxone 1 g IM/IV single dose PLUS azithromycin 1 g oral single dose 1

Non-gonococcal urethritis (Chlamydia):

• Doxycycline 100 mg twice daily for 7 days OR azithromycin 1-1.5 g oral single dose 1

Acute bacterial prostatitis:

• First-line: Piperacillin-tazobactam, ceftriaxone, or ciprofloxacin for 2-4 weeks (92-97% success rate) 5

Chronic bacterial prostatitis:

• Levofloxacin or ciprofloxacin for minimum 4 weeks 5

Acute epididymitis:

• If sexually transmitted: Ceftriaxone plus doxycycline 1
• If urinary pathogen: Fluoroquinolone or third-generation cephalosporin 1

Intra-Abdominal Infections

Community-acquired, mild-moderate:

• Amoxicillin-clavulanate, ampicillin-sulbactam, or ceftriaxone plus metronidazole 1, 2

Severe or healthcare-associated:

• Piperacillin-tazobactam, ertapenem, or ceftriaxone plus metronidazole 1

Enteric Fever (Typhoid)

Fully susceptible Salmonella typhi:

• Fluoroquinolone (ciprofloxacin, ofloxacin, or gatifloxacin) 1

Multidrug-resistant strains:

• Azithromycin or ceftriaxone 1

Quinolone-resistant:

• Azithromycin or ceftriaxone 1

Critical Pitfalls to Avoid

Inappropriate empiric coverage leads to worse outcomes: Studies demonstrate that inadequate initial antibiotic therapy increases mortality from 17.7% to 42% in infected patients 1. Prior antibiotic exposure is a major risk factor for receiving inadequate therapy 1.

Beta-lactam allergy overcalling: Distinguish true Type I hypersensitivity (anaphylaxis, angioedema) from minor reactions (rash). Patients with non-severe reactions may tolerate alternative beta-lactams 1. True penicillin allergy requires alternative classes, but expect higher failure rates (20-25%) with macrolides or trimethoprim-sulfamethoxazole 1, 3.

Fluoroquinolone overuse: Reserve fluoroquinolones for specific indications (complicated UTI, severe pneumonia with Pseudomonas risk, prostatitis) rather than routine use to preserve effectiveness and minimize resistance 1.

Inadequate dosing in severe infections: For critically ill patients, beta-lactams should maintain plasma concentrations above MIC for ≥70% of dosing interval 2. Consider extended infusions (3-4 hours) or continuous infusions for high-MIC organisms 2.

Administration Principles for Optimal Outcomes

Timing matters: Initiate antibiotics immediately for suspected bacterial sepsis or severe infections 1, 2.

Reassess at 48-72 hours: De-escalate based on clinical response and culture results 2. Procalcitonin <0.5 ng/mL or >80% decrease from peak supports discontinuation in lower respiratory tract infections 2.

Loading doses for severe infections: Vancomycin requires loading dose followed by continuous infusion to achieve early target concentrations 2.