What is the difference between doxycycline and cefixime (cephalosporin antibiotic) in terms of treatment choice for various infections, considering patient factors such as allergies and impaired renal function?

Doxycycline vs Cefixime: Clinical Selection Guide

Doxycycline and cefixime serve fundamentally different clinical roles and are not interchangeable—doxycycline is a tetracycline antibiotic primarily used for atypical respiratory pathogens, sexually transmitted infections, and tick-borne diseases, while cefixime is a third-generation oral cephalosporin reserved mainly for gonorrhea (as second-line) and select urinary tract infections.

Antimicrobial Spectrum and Primary Indications

Doxycycline

• Covers atypical respiratory pathogens (Mycoplasma, Chlamydia pneumoniae) that cefixime cannot treat 1
• First-line for Chlamydia trachomatis at 100 mg twice daily for 7 days, which commonly co-infects with gonorrhea 1
• Essential for Lyme disease treatment (early localized and disseminated disease) at 100 mg twice daily 1
• Covers tick-borne illnesses including anaplasmosis and ehrlichiosis 1
• Effective against MRSA in skin/soft tissue infections (not covered by cefixime) 1
• Contraindicated in pregnancy, lactation, and children <8 years due to tooth discoloration 1

Cefixime

• Limited to specific Gram-negative coverage: excellent against Enterobacteriaceae and H. influenzae, but poor Gram-positive activity 1, 2
• Second-line for gonorrhea only: 400 mg orally plus azithromycin 1 g when ceftriaxone unavailable, with mandatory test-of-cure at 1 week 3
• Not recommended for pharyngeal gonorrhea due to 5.8% failure rate versus 1.8% for ceftriaxone 3
• Achieves lower bactericidal levels than ceftriaxone (97.1-97.4% cure rate vs 98.9-99.1%) 3
• Recent evidence shows treatment failure: cefixime 800 mg plus doxycycline failed noninferiority testing for pharyngeal gonorrhea (86% success vs 100% for ceftriaxone-azithromycin) 4
• Urinary tract infections: effective for uncomplicated UTI due to high urinary concentrations, comparable to co-trimoxazole or amoxicillin 2, 5
• No activity against Pseudomonas, Staphylococcus aureus, or atypical pathogens 2

Clinical Decision Algorithm

For Respiratory Tract Infections

• Acute bacterial rhinosinusitis with recent antibiotic use or moderate disease: Use amoxicillin-clavulanate 90 mg/6.4 mg/kg per day, NOT cefixime or doxycycline as monotherapy 1
• Atypical pneumonia suspected (Mycoplasma, Chlamydia): Doxycycline 100 mg twice daily 1
• Streptococcal pharyngitis: Neither agent is appropriate—use penicillin V or amoxicillin 1
• Acute bronchitis: Cefixime 400 mg once daily showed equivalent efficacy to cefuroxime but caused significantly more diarrhea (15% vs 5%, p=0.001) 6

For Sexually Transmitted Infections

• Uncomplicated gonorrhea: Ceftriaxone 250 mg IM plus azithromycin 1 g orally is first-line; cefixime 400 mg plus azithromycin 1 g is alternative only when ceftriaxone unavailable 1, 3
• Chlamydia co-infection (present in majority of gonorrhea cases): Doxycycline 100 mg twice daily for 7 days is preferred over single-dose azithromycin for chlamydial coverage 1
• Never use cefixime as monotherapy for gonorrhea—must combine with azithromycin 3

For Urinary Tract Infections

• Uncomplicated UTI: Cefixime 200 mg twice daily (preferred over 400 mg once daily due to less GI upset) is comparable to amoxicillin or co-trimoxazole 2, 5
• Complicated UTI: Cefixime only if sensitivity confirmed; requires testing due to resistant Gram-positive and non-fermenting organisms 5
• Doxycycline is not first-line for UTI treatment 1

Patient-Specific Factors

Renal Impairment

• Cefixime requires dose adjustment as 20% is renally excreted as active drug 2
• Doxycycline does not require adjustment and is safer in renal failure 1

Penicillin Allergy

• Cefixime has negligible cross-reactivity with penicillin as a third-generation cephalosporin 3
• Avoid cephalosporins in Type I hypersensitivity (anaphylaxis) to penicillin 1
• Doxycycline is safe alternative for penicillin-allergic patients in appropriate indications 1

Pregnancy and Pediatrics

• Doxycycline is contraindicated in pregnancy, lactation, and children ≤8 years 1
• Cefixime is safe in pregnancy and children when indicated 1, 2

Critical Pitfalls to Avoid

• Never confuse ceftriaxone with cefixime—ceftriaxone has no oral formulation and provides superior bactericidal levels 3
• Do not use cefixime for pharyngeal gonorrhea—documented high failure rates 3, 4
• Cefixime has no anti-pseudomonal activity—never use empirically in febrile neutropenia 3
• Cefixime lacks activity against S. pneumoniae and MRSA—inappropriate for most respiratory infections requiring Gram-positive coverage 1, 2
• Doxycycline cannot treat gonorrhea alone—only covers co-existing chlamydia 1
• Higher GI adverse effects with once-daily cefixime dosing—use 200 mg twice daily instead of 400 mg once daily 5, 6