Penicillin or amoxicillin are considered the best first-line treatments for Strep throat. According to the CDC (Centers for Disease Control and Prevention) “ There has never been a report of a clinical isolate of group A strep that is resistant to penicillin”. For people with a penicillin allergy, treat Strep throat with either a narrow-spectrum cephalosporin (such as cephalexin or cefadroxil), clindamycin, azithromycin, or clarithromycin. Note that resistance to azithromycin and clarithromycin has been reported.