What is the coverage and dosage of cefexime (a third-generation cephalosporin antibiotic) for a typical adult patient with uncomplicated urinary tract infection (UTI) and no known allergies to cephalosporins, considering factors such as renal function and potential cross-reactivity with penicillins?

Coverage of Cefixime

Cefixime is an oral third-generation cephalosporin with excellent coverage against common Gram-negative uropathogens (E. coli, Proteus mirabilis) and respiratory pathogens (H. influenzae, M. catarrhalis, S. pyogenes), but has limited activity against Staphylococcus aureus and no activity against Pseudomonas aeruginosa or Enterococcus species. 1

Spectrum of Antibacterial Activity

Gram-Negative Coverage

• Highly active against Enterobacteriaceae, particularly Escherichia coli and Proteus mirabilis, making it suitable for uncomplicated urinary tract infections 1, 2
• Excellent activity against respiratory pathogens including Haemophilus influenzae (including beta-lactamase producing strains), Moraxella catarrhalis, and many Enterobacteriaceae 1, 2
• Resistant to hydrolysis by many beta-lactamases, providing stability against common resistance mechanisms 2
• No activity against Pseudomonas aeruginosa, which is a critical limitation for empiric therapy in nosocomial infections 2

Gram-Positive Coverage

• Active against Streptococcus pyogenes (Group A Streptococcus), indicated for pharyngitis and tonsillitis 1
• Moderate activity against Streptococcus pneumoniae, though approximately 10% lower efficacy than comparators for otitis media caused by this organism 1
• Little to no activity against Staphylococcus aureus, limiting its use in skin and soft tissue infections where staphylococcal coverage is needed 2
• Inactive against Enterococcus species, MRSA, and most Enterobacter species 3

Organisms NOT Covered

• Pseudomonas aeruginosa - completely inactive 2
• Enterococcus species - no coverage 3
• MRSA and methicillin-resistant staphylococci - no coverage 3
• ESBL-producing organisms - not effective 3
• Bacteroides fragilis and anaerobes - inadequate coverage 3

FDA-Approved Indications and Dosing

Adult Dosing

• Standard dose: 400 mg orally once daily for most infections 1
• Uncomplicated gonorrhea: 400 mg as a single oral dose 1
• May be administered without regard to food 1

Pediatric Dosing (≥6 months)

• 8 mg/kg/day orally, administered as a single daily dose or divided into 4 mg/kg every 12 hours 1
• For otitis media, must use the oral suspension formulation (not capsules), as suspension achieves higher peak blood levels necessary for middle ear penetration 1

Renal Dosing Adjustments

• CrCl ≥60 mL/min: Normal dose (400 mg daily) 1
• CrCl 21-59 mL/min OR on hemodialysis: 260 mg daily 1
• CrCl ≤20 mL/min OR on peritoneal dialysis: 172 mg daily 1
• Neither hemodialysis nor peritoneal dialysis removes significant drug, so no supplemental dosing needed 1

Clinical Positioning and Limitations

Current Guideline Recommendations

• NOT recommended as first-line therapy for uncomplicated cystitis by the European Association of Urology, which prefers fosfomycin, nitrofurantoin, and pivmecillinam 3
• WHO 2024 guidelines explicitly acknowledge lack of evidence to recommend cefixime for UTI treatment despite older recommendations 3
• Beta-lactams generally have inferior efficacy and more adverse effects compared to preferred UTI antimicrobials 3

When Cefixime May Be Considered

• Uncomplicated cystitis in non-pregnant women when first-line agents (nitrofurantoin, fosfomycin, TMP-SMX) are contraindicated or unavailable AND local resistance rates to cefixime are <20% 3
• Uncomplicated urinary tract infections caused by susceptible E. coli or P. mirabilis 1
• Otitis media (must use suspension formulation) 1
• Pharyngitis/tonsillitis due to S. pyogenes (though penicillin remains drug of choice) 1
• Acute exacerbations of chronic bronchitis due to S. pneumoniae or H. influenzae 1

Critical Contraindications

• Should NOT be used for pyelonephritis or febrile UTIs, as agents primarily excreted in urine without adequate serum/tissue levels are inappropriate for kidney parenchymal infections 3
• Should NOT be used for post-cesarean infections, as it lacks adequate coverage for the polymicrobial flora (including anaerobes and staphylococci) typical of these infections 4
• Should NOT be used for nosocomial infections, where broader coverage including Pseudomonas and resistant organisms is required 5

Antibiotic Stewardship Concerns

Collateral Damage

• Beta-lactams like cefixime are associated with disruption of protective periurethral and vaginal microbiota, potentially promoting more rapid UTI recurrence 3
• Cephalosporins are more likely than other antibiotic classes to cause C. difficile infection and alter fecal microbiota 3

Duration of Therapy

• For S. pyogenes infections (pharyngitis/tonsillitis), administer for at least 10 days to ensure eradication and prevent rheumatic fever complications 1
• For uncomplicated UTI, typical duration is 3-7 days, though specific data for cefixime are limited 3

Common Pitfalls to Avoid

• Do not substitute capsules for suspension in otitis media - the suspension formulation is required for adequate middle ear penetration 1
• Do not use for suspected or confirmed Pseudomonas infections - cefixime has no activity 2
• Do not use empirically for nosocomial UTIs - resistance patterns and need for broader coverage make other agents preferable 5
• Do not use for polymicrobial infections requiring anaerobic coverage - cefixime lacks activity against B. fragilis and other anaerobes 3
• Ensure proper dose adjustment in renal impairment - failure to adjust can lead to drug accumulation 1