What is the next step for oral antibiotic treatment if Cefixime (Cefixime) is not sufficient?

Stepping Up from Cefixime: Ceftriaxone with Azithromycin

If cefixime is insufficient, the next step is ceftriaxone 250 mg intramuscularly plus azithromycin 1 g orally as a single dose, which represents the current first-line treatment for gonorrhea. 1

Context: Why Cefixime Is No Longer First-Line

• Cefixime is no longer recommended as first-line therapy for gonorrhea due to declining susceptibility and documented treatment failures, particularly in Europe. 1, 2
• CDC surveillance data from 2006-2011 showed increasing minimum inhibitory concentrations (MICs) for cefixime, with 0.2% of isolates demonstrating decreased susceptibility. 1
• When cefixime is used as an alternative (only when ceftriaxone is unavailable), it must be combined with azithromycin 1 g orally or doxycycline 100 mg twice daily for 7 days, and a mandatory test-of-cure at 1 week is required. 1, 2

Recommended Step-Up Regimen

For Uncomplicated Urogenital, Anorectal, or Pharyngeal Gonorrhea:

• Ceftriaxone 250 mg intramuscularly as a single dose 1
• PLUS azithromycin 1 g orally as a single dose (preferred over doxycycline due to single-dose convenience and lower gonococcal resistance rates) 1

Rationale for Combination Therapy:

• Dual therapy with different mechanisms of action improves treatment efficacy and potentially delays emergence of cephalosporin resistance. 1
• Azithromycin is preferred over doxycycline because of substantially lower prevalence of gonococcal resistance to azithromycin compared to tetracycline among surveillance isolates. 1

Alternative Options (When Ceftriaxone Cannot Be Used)

If Severe Cephalosporin Allergy:

• Azithromycin 2 g orally as a single dose 1
• Mandatory test-of-cure at 1 week is required 1
• This is a last-resort option with less robust efficacy data

Critical Management Steps

Test-of-Cure Requirements:

• Always perform test-of-cure 1 week after treatment when using alternative regimens (cefixime or azithromycin monotherapy). 1, 2
• Ideally use culture; if unavailable, use NAAT with confirmatory culture if positive. 1
• All positive cultures should undergo phenotypic antimicrobial susceptibility testing. 1

Treatment Failure Protocol:

• If a patient fails recommended combination therapy (ceftriaxone + azithromycin), culture the specimen and perform antimicrobial susceptibility testing. 1
• Consult an infectious disease specialist or CDC (404-639-8659) within 24 hours. 1
• Re-treat with ceftriaxone 250 mg IM plus azithromycin 2 g orally. 1
• Ensure sex partners from preceding 60 days are evaluated and treated. 1

Common Pitfalls to Avoid

• Do not use cefixime as monotherapy for gonorrhea—it must always be combined with azithromycin or doxycycline when used as an alternative. 1, 2
• Do not use cefixime for dental infections—it has poor activity against Staphylococcus aureus and is inactive against anaerobes commonly involved in odontogenic infections. 3
• Do not skip the test-of-cure when using alternative regimens, as treatment failures have been documented. 1, 2
• Do not assume cefixime failure means ceftriaxone failure—ceftriaxone provides higher and more sustained bactericidal levels than oral cefixime. 1

For Non-Gonococcal Infections

If the question pertains to respiratory or urinary tract infections (not gonorrhea):

• Consider fluoroquinolones (ciprofloxacin, levofloxacin) for urinary tract infections if susceptibility allows. 4, 5
• Consider amoxicillin-clavulanate for respiratory infections requiring broader coverage. 5, 6
• Cefixime itself is effective for many respiratory and urinary infections at 400 mg daily, so "stepping up" may involve switching to parenteral therapy (ceftriaxone) or broader-spectrum agents depending on clinical response. 4, 5, 6