What is the next antibiotic for a patient who fails azithromycin (Zithromax, Zpak) treatment for sinus infection, and will adjunctive steroid therapy be beneficial?

From the Guidelines

If a patient fails to improve on azithromycin (Z-pak) for a sinus infection, the next antibiotic option would typically be amoxicillin-clavulanate (Augmentin) at a dose of 875/125 mg twice daily for 5-7 days, as recommended by the American College of Physicians and the Centers for Disease Control and Prevention 1. This provides broader coverage against beta-lactamase producing bacteria that may be resistant to azithromycin. For patients with penicillin allergies, doxycycline 100 mg twice daily for 5-7 days or levofloxacin 500 mg daily for 5-7 days are reasonable alternatives. Adding a short course of oral corticosteroids such as prednisone 20-40 mg daily for 5-7 days can indeed help reduce inflammation and provide symptomatic relief, especially in patients with significant congestion, facial pain, or pressure, as suggested by the Journal of Allergy and Clinical Immunology 1. Corticosteroids work by reducing the inflammatory response in the sinus mucosa, decreasing swelling and facilitating drainage. Nasal saline irrigation and intranasal corticosteroid sprays (such as fluticasone) should also be continued as adjunctive therapy. Some key points to consider when managing sinusitis include:

• Reserving antibiotic treatment for patients with persistent symptoms for more than 10 days, onset of severe symptoms or signs of high fever (>39 °C) and purulent nasal discharge or facial pain lasting for at least 3 consecutive days, or onset of worsening symptoms following a typical viral illness that lasted 5 days that was initially improving (double sickening) 1.
• Using supportive care, such as analgesics for pain and antipyretics for fever, as the primary management for most patients with acute rhinosinusitis 1.
• Considering referral to a specialist for patients who are seriously ill, who deteriorate clinically despite antibiotic therapy, or who have recurrent episodes 1.

From the FDA Drug Label

To evaluate the safety and efficacy of a high dose short course of levofloxacin, 780 outpatient adults with clinically and radiologically determined acute bacterial sinusitis were evaluated in a double-blind, randomized, prospective, multicenter study comparing levofloxacin 750 mg by mouth once daily for five days to levofloxacin 500 mg by mouth once daily for 10 days Clinical success rates (defined as complete or partial resolution of the pre-treatment signs and symptoms of ABS to such an extent that no further antibiotic treatment was deemed necessary) in the microbiologically evaluable population were 91.4% (139/152) in the levofloxacin 750 mg group and 88.6% (132/149) in the levofloxacin 500 mg group at the test-of-cure (TOC) visit (95% CI [-4. 2,10] for levofloxacin 750 mg minus levofloxacin 500 mg)

The next antibiotic to consider for a patient who fails on Z-pack (azithromycin) for a sinus infection could be levofloxacin.

• The 750 mg once daily for 5 days or 500 mg once daily for 10 to 14 days regimens are approved for the treatment of acute bacterial sinusitis (ABS).
• There is no direct information in the provided drug label about the use of steroids in conjunction with antibiotics for the treatment of sinus infections. 2

From the Research

Next Antibiotic Option

If a patient fails to respond to a Z-pack (azithromycin) for a sinus infection, the next antibiotic option may be:

• Amoxicillin-clavulanate, as studied in 3, 4, 5, 6
• Levofloxacin, as compared to amoxicillin-clavulanate in 3

Efficacy of Antibiotics

The efficacy of these antibiotics has been compared in several studies:

• Azithromycin was found to be as effective as amoxicillin-clavulanate in 4, 5, 6
• Levofloxacin was found to be as effective as amoxicillin-clavulanate in 3

Use of Steroids

The use of steroids in conjunction with antibiotics for sinus infections has been studied:

• A study found that short therapy with amoxicillin-clavulanate and corticosteroids was effective in acute sinusitis, with a therapeutic success rate of 80% and 85% in the 5-day and 10-day treatment groups, respectively 7
• However, the study also found that the 5-day treatment was not equivalent to the 10-day treatment, and that some risk factors (such as recurrence of sinusitis or previous surgical sinus drainage) may require longer treatment durations 7

Key Findings

Key findings from the studies include:

• Azithromycin and amoxicillin-clavulanate have similar efficacy in treating acute sinusitis 4, 5, 6
• Levofloxacin is a viable alternative to amoxicillin-clavulanate 3
• Steroids may be beneficial in conjunction with antibiotics for sinus infections, but further study is needed to define their indications 7