What are the oral beta-lactam (β-lactam) antibiotics?

Oral β-Lactam Antibiotics

Oral β-lactam antibiotics include penicillins (with and without β-lactamase inhibitors) and cephalosporins, representing the most widely prescribed class of antibacterial agents for outpatient infections. 1

Penicillins

Aminopenicillins

• Amoxicillin is the most active oral β-lactam against streptococci, including pneumococci, with excellent bioavailability 1, 2
• Ampicillin is less well-absorbed than amoxicillin but shares similar antimicrobial activity 1

Aminopenicillins with β-Lactamase Inhibitors

• Amoxicillin-clavulanate combines amoxicillin with clavulanic acid to preserve activity against β-lactamase-producing organisms 1, 3
• High-dose formulations (4 g amoxicillin/250 mg clavulanate daily for adults; 90 mg/kg amoxicillin with 6.4 mg/kg clavulanate daily for children) are FDA-approved for resistant pathogens 1
• Amoxicillin-clavulanate is the most potent oral β-lactam against penicillin-nonsusceptible Streptococcus pneumoniae 4, 5

Cephalosporins

First-Generation Oral Cephalosporins

• Cephalexin has narrow antimicrobial spectrum and is among the least potent oral cephalosporins 4
• Cefaclor similarly has limited spectrum and potency compared to newer agents 1, 4

Second-Generation Oral Cephalosporins

• Cefuroxime axetil has activity against penicillin-susceptible S. pneumoniae and retains some activity against penicillin-intermediate strains 1, 4
• Cefprozil demonstrates similar activity profile to cefuroxime axetil 1, 4

Third-Generation (Extended-Spectrum) Oral Cephalosporins

• Cefdinir is highly active against penicillin-susceptible S. pneumoniae, methicillin-susceptible Staphylococcus aureus, and Moraxella catarrhalis 1, 4
• Cefpodoxime proxetil is the most potent oral cephalosporin against Haemophilus influenzae and has excellent activity against M. catarrhalis 1, 4
• Cefixime has strong activity against H. influenzae and M. catarrhalis but limited gram-positive coverage 1
• Cefditoren is a newer third-generation oral cephalosporin available in the United States 6

Fourth-Generation Oral Cephalosporins

• Loracarbef has limited activity and is among the least potent oral β-lactams 1

Key Clinical Considerations

Spectrum Limitations

• Oral cephalosporins are inherently less active than amoxicillin against S. pneumoniae, with baseline MICs fourfold higher 1
• Cephalosporins are actively absorbed in the gastrointestinal tract, limiting achievable concentrations regardless of dose 1
• Third-generation oral cephalosporins exhibit more balanced spectrums against respiratory pathogens compared to earlier generation agents 4

Resistance Considerations

• β-lactamase production is the primary resistance mechanism, making β-lactamase inhibitor combinations critical for certain infections 7, 8
• Empirical overuse of amoxicillin-clavulanate may select for extended-spectrum β-lactamase (ESBL) producing organisms 5

Common Pitfalls

• Never use oral cephalosporins as first-line for pneumococcal infections when amoxicillin is an option, as cephalosporins have inferior intrinsic activity 1
• Avoid assuming all oral β-lactams have equivalent activity—third-generation agents have significantly broader spectrum than first-generation 4
• Do not overlook that clavulanate absorption is enhanced when taken with food, while amoxicillin absorption is unaffected 3