What are the recommended third-generation oral antibiotics (e.g. cefixime, ceftibuten) and their dosing regimens for treating infections?

Third-Generation Oral Antibiotics and Their Dosing Regimens

Cefixime is the primary recommended third-generation oral cephalosporin with a standard adult dose of 400 mg once daily for most infections, while ceftibuten is an alternative option at 400 mg once daily.

Available Third-Generation Oral Cephalosporins

Cefixime

• Standard adult dosing: 400 mg orally once daily 1
• Specific indications and dosing:
  • Uncomplicated urinary tract infections: 400 mg once daily 1
  • Pharyngitis/tonsillitis: 400 mg once daily for at least 10 days 1
  • Acute bronchitis: 400 mg once daily 1
  • Uncomplicated gonorrhea: 400 mg as a single dose 2

Ceftibuten

• Standard adult dosing: 400 mg orally once daily 3
• Specific indications:
  • Acute uncomplicated or complicated urinary tract infections 3
  • Acute or chronic lower respiratory tract infections 3
  • Acute otitis media (pediatric): 9 mg/kg/day 3

Pediatric Dosing

Cefixime

• Standard pediatric dosing: 8 mg/kg/day 1
• Can be administered as a single daily dose or divided into two doses (4 mg/kg every 12 hours) 1
• Available as oral suspension in two concentrations: 100 mg/5 mL and 200 mg/5 mL 1
• Weight-based dosing chart available in FDA labeling 1

Ceftibuten

• Standard pediatric dosing: 9 mg/kg/day once daily 3, 4

Special Populations

Renal Impairment

• Cefixime dose adjustment:
  • Normal dose for creatinine clearance ≥60 mL/min
  • For creatinine clearance 21-59 mL/min: reduced dose (approximately 65% of normal)
  • For creatinine clearance ≤20 mL/min or patients on hemodialysis/peritoneal dialysis: further reduced dose (approximately 43% of normal) 1

Clinical Efficacy

Cefixime

• Effective for uncomplicated urogenital and anorectal gonococcal infections with cure rates of 97.1-97.4% 2
• Clinical cure rates for:
  • Lower UTIs: 96% 5
  • Upper UTIs: 92% 5
  • Respiratory infections: 88-93% 5
  • ENT infections: approximately 95% 5

Ceftibuten

• Similar efficacy to other agents (cefaclor, cotrimoxazole) for urinary tract infections 3
• Comparable to cefaclor for lower respiratory tract infections 3
• At least as effective as cefaclor and amoxicillin/clavulanic acid for acute otitis media in children 3

Antimicrobial Spectrum and Resistance Considerations

• Both cefixime and ceftibuten have broad-spectrum activity against gram-negative pathogens and streptococci 3, 6
• Ceftibuten shows greater stability against extended-spectrum beta-lactamases compared to some other cephalosporins 3
• Neither has significant activity against Staphylococcus aureus or Pseudomonas aeruginosa 6

Safety and Tolerability

• Most common adverse effects are gastrointestinal:
  • Cefixime: diarrhea (16%), nausea (7%), loose stools (6%), abdominal pain (3%), dyspepsia (3%), and vomiting 1
  • Ceftibuten: mild to moderate gastrointestinal disturbances in 5-10% of patients 3

Clinical Pearls and Pitfalls

• Pitfall: Inadequate dosing for streptococcal infections

  • Solution: Ensure treatment for at least 10 days for Streptococcus pyogenes infections 1

• Pitfall: Using oral suspension and tablets/capsules interchangeably for otitis media

  • Solution: For otitis media, use only the suspension form of cefixime, as it results in higher peak blood levels than tablets/capsules at the same dose 1

• Pitfall: Failure to adjust dosing in renal impairment

  • Solution: Always assess renal function and adjust dosing accordingly 1

• Pitfall: Using quinolones instead of cephalosporins for gonorrhea

  • Solution: Due to increasing resistance, cephalosporins are preferred over quinolones for gonorrhea treatment 2

The once-daily dosing regimen of both cefixime and ceftibuten offers a significant advantage for outpatient treatment, potentially improving medication adherence compared to antibiotics requiring multiple daily doses.