What is the overview of second-generation cephalosporins (2nd gen cephalosporins) in treating bacterial infections?

Overview of Second Generation Cephalosporins

Second generation cephalosporins have moderate gram-positive coverage and improved gram-negative coverage compared to first generation agents, making them particularly valuable for treating mixed infections involving anaerobes and gram-negative bacteria. 1

Spectrum of Activity

Second generation cephalosporins can be divided into two main categories:

1. Traditional second generation cephalosporins:

   • Examples: cefuroxime, cefaclor
   • Moderate gram-positive coverage (less than first generation)
   • Improved gram-negative coverage against Haemophilus influenzae, Enterobacteriaceae
   • Limited anaerobic activity

2. Cephamycins (a subgroup of second generation):

   • Examples: cefoxitin, cefotetan
   • Similar gram-positive coverage
   • Enhanced activity against anaerobes, including Bacteroides fragilis 2

Antimicrobial Coverage

• Gram-positive organisms: Moderate activity against Staphylococcus aureus (methicillin-susceptible only), Streptococcus pneumoniae, and Streptococcus pyogenes (though less active than first generation agents) 1
• Gram-negative organisms: Active against Escherichia coli, Klebsiella species, Haemophilus influenzae (including β-lactamase producing strains), Proteus mirabilis 3, 4
• Anaerobes: Cephamycins like cefoxitin have significant activity against Bacteroides fragilis and other anaerobes 3

Clinical Applications

Second generation cephalosporins are particularly valuable in:

1. Respiratory tract infections: Particularly those caused by H. influenzae 5
2. Intra-abdominal infections: Cefoxitin is specifically indicated for intra-abdominal infections including peritonitis and abscesses due to its anaerobic coverage 5, 3
3. Mixed infections: Particularly useful for infections with mixed flora 1
4. Moderate diabetic foot infections: Cefoxitin is recommended for moderate diabetic foot infections due to its coverage of common pathogens 5
5. Skin and soft tissue infections: Effective against mixed aerobic and anaerobic infections 3
6. Gynecological infections: Cefoxitin is indicated for endometritis, pelvic cellulitis, and pelvic inflammatory disease 3

Specific Agents and Their Properties

Cefoxitin

• Mechanism: Highly stable in the presence of bacterial beta-lactamases (both penicillinases and cephalosporinases) 3
• Administration: Intravenous only
• Indications: Particularly valuable for intra-abdominal infections, gynecological infections, and mixed aerobic-anaerobic infections 5, 3
• Dosing: Typically administered every 6-8 hours due to shorter half-life 5

Cefuroxime

• Administration: Available in both oral (cefuroxime axetil) and parenteral forms
• Indications: Respiratory infections, sinusitis, and moderate infections with mixed flora 5
• Special property: Most active cephalosporin for beta-lactamase-producing Haemophilus influenzae 6

Cefaclor

• Administration: Oral only
• Pharmacokinetics: Well-absorbed after oral administration, with or without food (though peak concentrations are 50-75% lower when taken with food) 4
• Excretion: 60-85% excreted unchanged in urine within 8 hours 4
• Indications: Upper and lower respiratory tract infections, urinary tract infections, skin infections 4

Advantages and Limitations

Advantages

• Better stability against beta-lactamases compared to first generation agents 3
• Broader gram-negative coverage than first generation cephalosporins 1
• Anaerobic coverage with cephamycins (cefoxitin, cefotetan) 2
• Some agents available in both oral and parenteral forms (e.g., cefuroxime) 5

Limitations

• Less active against gram-positive organisms compared to first generation cephalosporins 1, 2
• Not active against Enterococcus species, methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and many Enterobacter species 3, 4
• Risk of cross-reactivity in patients with penicillin allergy (though less than previously thought)
• Potential for Clostridioides difficile infection 1

Clinical Pearls

• Second generation cephalosporins should be considered when treating infections likely to involve both gram-positive and gram-negative organisms, particularly when anaerobic coverage is needed (cephamycins) 5
• For intra-abdominal infections, cefoxitin is particularly valuable due to its anaerobic coverage 5, 3
• When treating respiratory infections where H. influenzae is suspected, cefuroxime may be preferred due to its enhanced activity against this organism 6
• Dosage adjustments are required in patients with renal impairment 1, 4
• Second generation cephalosporins are not appropriate for infections likely to involve MRSA, Pseudomonas, or Enterococcus 3, 4

Antimicrobial Stewardship Considerations

• Second generation cephalosporins should be used when their spectrum specifically matches the suspected pathogens rather than using broader spectrum agents 1
• Cephamycins like cefoxitin may be preferred over broader spectrum agents for mixed aerobic-anaerobic infections when susceptibility is likely 5, 3
• Duration of therapy should generally not exceed 7-14 days for most infections, with shorter durations appropriate for many uncomplicated infections with adequate source control 1