What are the recommended betalactam (beta-lactam) antibiotics for treating bacterial infections?

Beta-Lactam Antibiotics for Bacterial Infections

Beta-lactam antibiotics remain the cornerstone of empiric and targeted therapy for most bacterial infections, with specific agent selection based on infection site, severity, and local resistance patterns. 1

Community-Acquired Pneumonia

Outpatient Treatment (Mild Disease)

• Amoxicillin (1.5-4 g/day) or amoxicillin-clavulanate (1.75-4 g/250 mg/day) are first-line beta-lactam options for patients without recent antibiotic exposure 1
• High-dose amoxicillin-clavulanate (4 g/250 mg/day) should be used when drug-resistant Streptococcus pneumoniae (DRSP) is suspected, particularly in patients with recent antibiotic use, immunodeficiency, or frequent daycare exposure 1
• Alternative oral beta-lactams include cefpodoxime, cefuroxime axetil, or cefdinir, though these have lower calculated bacteriologic efficacy (85-91%) compared to high-dose amoxicillin-clavulanate (97-99%) 1

Inpatient Non-ICU Treatment

• A beta-lactam plus a macrolide is strongly recommended 1
• Preferred beta-lactams: cefotaxime, ceftriaxone, or ampicillin 1
• Ertapenem is acceptable for selected patients with risk factors for gram-negative pathogens (excluding Pseudomonas aeruginosa) 1

ICU Treatment

• A beta-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam) plus either azithromycin or a fluoroquinolone is strongly recommended 1
• For suspected Pseudomonas infection: use an antipseudomonal beta-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) plus either ciprofloxacin or levofloxacin 750 mg 1

Beta-Lactam Allergy Alternatives

• Respiratory fluoroquinolones (levofloxacin 750 mg daily or moxifloxacin) are the primary alternative 2
• For severe ICU infections: aztreonam plus a respiratory fluoroquinolone 2

Acute Bacterial Rhinosinusitis

Adults with Mild Disease

• High-dose amoxicillin-clavulanate (4 g/250 mg/day) achieves 91% calculated clinical efficacy and 99% bacteriologic efficacy 1
• Standard amoxicillin (1.5-4 g/day) provides 87-88% clinical efficacy but only 91-92% bacteriologic efficacy 1
• Alternative beta-lactams: cefpodoxime (87% efficacy), cefuroxime axetil (85% efficacy), or cefdinir (83% efficacy) 1

Adults with Moderate Disease or Recent Antibiotic Use

• High-dose amoxicillin-clavulanate (4 g/250 mg/day) or ceftriaxone 1 g IM/IV daily for 5 days 1
• Both achieve 91% clinical efficacy and 99% bacteriologic efficacy 1

Pediatric Patients

• High-dose amoxicillin-clavulanate (90 mg/6.4 mg per kg per day) or high-dose amoxicillin (90 mg/kg per day) for children without recent antibiotic exposure 1
• Alternative beta-lactams: cefpodoxime proxetil, cefuroxime axetil, or cefdinir 1

Febrile Neutropenia

High-Risk Patients

• Monotherapy with an antipseudomonal beta-lactam is recommended: piperacillin-tazobactam, cefepime, ceftazidime, or a carbapenem (meropenem or imipenem-cilastatin) 1
• Piperacillin-tazobactam demonstrated the lowest mortality (RR 0.56; 95% CI 0.34-0.92) and lowest adverse event rate (RR 0.25; 95% CI 0.12-0.53) among beta-lactams 1
• Cefepime showed higher mortality compared to other beta-lactams (RR 1.39-1.44) in systematic reviews 1

High-Risk Patients with Complications

• Add aminoglycosides or vancomycin to the beta-lactam when antimicrobial resistance is suspected, for clinically unstable patients, or in centers with high resistant pathogen rates 1

Low-Risk Patients

• Oral amoxicillin-clavulanate plus ciprofloxacin for outpatient treatment 1

Hospital-Acquired and Ventilator-Associated Pneumonia

Empiric Therapy

• Antipseudomonal beta-lactams are first-line: piperacillin-tazobactam, cefepime, imipenem, or meropenem 1
• Combination with an aminoglycoside or fluoroquinolone is recommended for severe cases 1

Duration

• 7-8 days of therapy is adequate for most patients 1
• Shorter courses result in significantly more antibiotic-free days (MD 4.02 days; 95% CI 2.26-5.78) and reduced recurrence of VAP due to multidrug-resistant organisms (OR 0.44; 95% CI 0.21-0.95) 1

Multidrug-Resistant Organisms

Carbapenem-Resistant Enterobacterales (CRE)

• Ceftazidime-avibactam 2.5 g IV q8h is first-line for bloodstream infections, pneumonia, and complicated urinary tract infections 1
• Alternative beta-lactam combinations: meropenem-vaborbactam 4 g IV q8h or imipenem-cilastatin-relebactam 1.25 g IV q6h 1
• For complicated intra-abdominal infections: ceftazidime-avibactam 2.5 g q8h plus metronidazole 500 mg q6h 1

Extended-Spectrum Beta-Lactamase (ESBL) Producers

• Carbapenems remain the treatment of choice for serious ESBL infections 3
• These enzymes inactivate third-generation cephalosporins but remain sensitive to beta-lactamase inhibitors like clavulanic acid 3

Key Clinical Considerations

Resistance Patterns

• Amoxicillin-clavulanate is the most active oral beta-lactam against S. pneumoniae, including most penicillin-nonsusceptible strains 4
• Third-generation oral cephalosporins (cefdinir, cefpodoxime) exhibit more balanced activity against respiratory pathogens compared to earlier generation cephalosporins 4
• Beta-lactams are active against many gram-positive, gram-negative, and anaerobic organisms, but only against beta-lactamase-negative isolates unless combined with a beta-lactamase inhibitor 5, 6

Pharmacokinetics

• Most beta-lactams have a serum half-life of 1-2 hours, requiring frequent dosing 7
• Ceftriaxone has an 8-10 hour half-life, allowing once-daily dosing 7
• Beta-lactams achieve 50-80% of serum concentrations in peripheral tissues, with good penetration except to cerebrospinal fluid 7

Treatment Duration

• Continue therapy for a minimum of 48-72 hours beyond clinical improvement or bacterial eradication 5
• For Streptococcus pyogenes infections, treat for at least 10 days to prevent acute rheumatic fever 5

Common Pitfalls

• Never use macrolide monotherapy for pneumonia due to increasing resistance rates 1
• Avoid empiric use of antipseudomonal beta-lactams without specific risk factors, as this promotes resistance 1
• In beta-lactam allergic patients, clarify the type of reaction—immediate Type I hypersensitivity versus other side effects—as patients may tolerate specific beta-lactams 1, 2
• Switch from IV to oral therapy when patients are hemodynamically stable, improving clinically, and able to ingest medications 1