What is the coverage and typical use of Cefixime, a (third-generation cephalosporin) antibiotic, in treating various bacterial infections?

Cefixime Coverage and Clinical Use

Cefixime is a third-generation oral cephalosporin with excellent activity against common respiratory and urinary tract pathogens including Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, Neisseria gonorrhoeae, and most Enterobacteriaceae, but it lacks clinically useful activity against Staphylococcus aureus, enterococci, Pseudomonas aeruginosa, and anaerobes like Bacteroides species. 1, 2

Spectrum of Antimicrobial Activity

Gram-Positive Coverage

• Cefixime inhibits 90% of S. pneumoniae and S. pyogenes at concentrations ≤0.25 mcg/mL 2
• No meaningful activity against staphylococci or enterococci, making it unsuitable for skin/soft tissue infections where these organisms predominate 2, 3
• Inactive against Listeria monocytogenes 3

Gram-Negative Coverage

• Excellent activity against H. influenzae, Branhamella catarrhalis, E. coli, Klebsiella pneumoniae, Proteus mirabilis, and N. gonorrhoeae at concentrations ≤0.25 mcg/mL 2
• Inhibits 90% of other Enterobacteriaceae at concentrations <1 mcg/mL, though some strains of Enterobacter, Citrobacter freundii, and Morganella morganii show reduced susceptibility 2
• Completely inactive against Pseudomonas aeruginosa and Acinetobacter species 2, 3
• Resistant to hydrolysis by many common plasmid and chromosomal β-lactamases 2, 4

Anaerobic Coverage

• Poor activity against Bacteroides fragilis and other anaerobes, limiting its use in mixed aerobic-anaerobic infections like intra-abdominal infections 2

FDA-Approved Indications

The FDA approves cefixime for patients ≥6 months of age for the following conditions 1:

• Uncomplicated urinary tract infections (400 mg daily in adults; 8 mg/kg/day in children) 1, 5
• Otitis media 1, 4
• Pharyngitis and tonsillitis 1, 4
• Acute exacerbations of chronic bronchitis 1
• Uncomplicated gonorrhea (cervical/urethral) 1

Clinical Use by Infection Type

Urinary Tract Infections

• Cefixime 400 mg once daily demonstrates comparable efficacy to co-trimoxazole or amoxicillin for acute uncomplicated cystitis 4
• High urinary concentrations are achieved with once-daily dosing due to renal excretion 6, 5
• Particularly useful during pregnancy due to high oral bioavailability, minimal fetal tissue penetration (<1%), and stable pharmacokinetics 5
• Effective for acute uncomplicated pyelonephritis in outpatient settings 5

Respiratory Tract Infections

• Comparable effectiveness to amoxicillin, amoxicillin-clavulanate, and cefaclor for acute lower respiratory tract infections 4
• Effective for acute tonsillitis and pharyngitis caused by S. pyogenes 4
• In pediatric acute otitis media, cefixime 8 mg/kg daily shows similar effectiveness to cefaclor 20-40 mg/kg daily and amoxicillin 40 mg/kg daily 4

Gonorrhea Treatment (Critical Limitations)

• The CDC recommends ceftriaxone 250 mg IM plus azithromycin 1 g orally as first-line therapy; cefixime 400 mg orally plus azithromycin 1 g orally is relegated to alternative status only when ceftriaxone is unavailable 7
• Cefixime provides lower and less sustained bactericidal levels than ceftriaxone, resulting in cure rates of only 97.1-97.4% for urogenital/anorectal gonorrhea versus 98.9-99.1% for ceftriaxone 8, 7
• Avoid cefixime for pharyngeal gonorrhea: failure rate of 5.8% versus 1.8% for ceftriaxone-based regimens, with overall efficacy of only 91% 7
• Mandatory test-of-cure at 1 week when cefixime is used due to declining susceptibility and elevated MICs 7
• Never use as monotherapy; must be combined with azithromycin 7

Key Clinical Advantages

Pharmacokinetic Benefits

• 3-hour elimination half-life permits once-daily or twice-daily dosing, improving compliance compared to multiple daily dosing regimens 4, 3
• High oral bioavailability 5
• Activity not reduced by serum, blood, or urine 2

Comparative Activity

• Superior in vitro activity to first-generation cephalosporins (cephalexin, cephradine, cefadroxil) and second-generation cefaclor against all bacteria except staphylococci 2
• Functions as the standard oral cephalosporin substitute for ceftriaxone when oral therapy is appropriate, though with important limitations 8

Critical Pitfalls and Contraindications

What Cefixime Does NOT Cover

• No empirical use in febrile neutropenia: lacks anti-pseudomonal activity essential for this population 9
• Avoid for suspected staphylococcal infections (skin/soft tissue infections, endocarditis) 2, 3
• Inadequate for mixed aerobic-anaerobic infections due to poor B. fragilis activity 2
• Never appropriate for Pseudomonas infections 2, 3

Prescribing Errors to Avoid

• Never confuse ceftriaxone with cefixime: ceftriaxone has no oral formulation and must be given IV or IM; prescribers intending oral therapy must specifically order cefixime 8
• Contraindicated in patients with known cephalosporin allergy 1
• Cross-reactivity with penicillin is negligible due to different chemical structures as a third-generation agent 6

Dosing Adjustments

• Dose adjustment required when creatinine clearance <60 mL/min due to renal elimination 1
• Safety and efficacy not established in infants <6 months 1

Adverse Effects

• Most common: diarrhea (16%), nausea (7%), loose stools (6%), abdominal pain (3%), dyspepsia (3%), vomiting 1
• Adverse effects are usually mild to moderate, transient, and occur in the first few days of treatment 4, 3
• Clostridioides difficile-associated diarrhea: evaluate if diarrhea develops 1
• Hypersensitivity reactions including shock and fatalities reported; discontinue if reaction occurs 1

Drug Interactions

• Elevated carbamazepine levels reported with concomitant administration 1
• Increased prothrombin time (with or without clinical bleeding) when administered with warfarin and anticoagulants 1