Oral Antibiotic Similar to Rocephin (Ceftriaxone)
Cefixime is the standard oral cephalosporin alternative to ceftriaxone (Rocephin), recommended by the CDC as the primary oral substitute when parenteral therapy is not required. 1
Primary Oral Alternative: Cefixime
Cefixime 400 mg orally has an antimicrobial spectrum similar to ceftriaxone, though it does not provide as high or sustained bactericidal levels as ceftriaxone 125 mg IM 2, 1
In clinical trials for uncomplicated urogenital and anorectal gonococcal infections, cefixime achieved cure rates of 97.1-97.4%, compared to 98.9-99.1% for ceftriaxone 2, 1
The key advantage of cefixime is oral administration, making it suitable for outpatient therapy when parenteral treatment is not feasible 2
Cefixime demonstrates broad-spectrum activity against Enterobacteriaceae, Haemophilus influenzae, Streptococcus pyogenes, Streptococcus pneumoniae, and Moraxella catarrhalis, with high resistance to beta-lactamase degradation 3, 4
Critical Limitations of Cefixime
For pharyngeal infections, cefixime shows significantly higher failure rates (5.8%) compared to ceftriaxone-based regimens (1.8%), making it less appropriate for pharyngeal gonorrhea 1
Cefixime provides lower and less sustained bactericidal levels than ceftriaxone, limiting its use in serious infections requiring high tissue penetration 1
Like ceftriaxone, cefixime has poor activity against Staphylococcus aureus, enterococci, Listeria monocytogenes, and Pseudomonas species 3, 4
Alternative Oral Cephalosporins (Less Comparable)
Cefuroxime axetil is a second-generation oral cephalosporin but has more limited Gram-negative coverage and no activity against drug-resistant S. pneumoniae, making it substantially less comparable to ceftriaxone 5
Cefuroxime achieves only 70-85% coverage for H. influenzae and 50% coverage for M. catarrhalis based on pharmacokinetic/pharmacodynamic breakpoints, significantly inferior to cefixime 2, 5
Other oral cephalosporins (cefpodoxime, cefdinir) have been studied but do not meet minimum efficacy criteria or offer advantages over cefixime 2
Fluoroquinolone Alternatives (When Appropriate)
Levofloxacin 500-750 mg orally provides broader coverage than cefixime and can be considered when fluoroquinolone use is appropriate 6
Levofloxacin is active against multi-drug resistant S. pneumoniae (MDRSP), including isolates resistant to penicillin, second-generation cephalosporins, macrolides, tetracyclines, and trimethoprim/sulfamethoxazole 6
However, fluoroquinolones should not be used for gonorrhea in most U.S. regions due to widespread quinolone-resistant N. gonorrhoeae (QRNG) 2
Key Clinical Pitfall
Ceftriaxone has no oral formulation and cannot be given orally—it is not absorbed from the gastrointestinal tract and must be administered IV or IM 1
Prescribers must specifically order cefixime or another appropriate oral cephalosporin when oral therapy is intended; never assume ceftriaxone can be given orally 1
Dosing and Administration
Cefixime: 400 mg orally as a single dose for gonorrhea 2; 8 mg/kg/day (up to 400 mg) once or twice daily for other infections 3, 7
The 3-4 hour elimination half-life of cefixime permits once or twice daily dosing, improving compliance 3, 4, 8
Bioavailability of cefixime ranges from 40-52%, with linear pharmacokinetics over the 200-400 mg dose range 8