If a patient with streptococcal pharyngitis does not improve after 48 hours of azithromycin, what is an appropriate next step?

• A. Wait another 24 hours for improvement.
• B. A penicillin or cephalosporin with beta-lactamase coverage should be considered.
• C. Switch to a different macrolide antibiotic.
• D. Begin doxycycline.

Answer: (B)

When a patient with streptococcal pharyngitis does not improve after 48 hours on azithromycin, the next step is to switch to a penicillin-based therapy or a cephalosporin with beta-lactamase coverage. The reasoning is that Streptococcus pyogenes is typically susceptible to penicillin, so a beta-lactam antibiotic is likely to be effective even if a macrolide has failed due to resistance. Using a cephalosporin with beta-lactamase coverage also guards against possible co-infection with beta-lactamase–producing organisms, providing broader, more reliable bacterial eradication. Waiting longer or sticking with another macrolide would not address potential resistance, and doxycycline is not always appropriate as a first-line option for streptococcal pharyngitis due to safety and efficacy considerations in certain populations.