Dr. Casey and I have shown that the otitis media dose of azithromycin is inferior for the treatment of strep throat (Clin. Infect. Dis. 2005;40:1748–55). If you accidentally prescribe the lower dose for strep throat and the child develops rheumatic fever, you may have a lawsuit on your hands.
In adolescents and adults with strep throat, this means that you need two of the standard “Z-PAKs” in order to give a high enough dose for eradication. The Z-PAKs label doesn't say this because our data showing inferiority weren't published until after the product was approved for treating strep throat. Thus, in this case you won't get sued if you just prescribe one pack, … but there's a better chance the patient will be cured if you prescribe two.
I hope I've convinced you that 5-day treatment is a viable option for strep throat, because the guidelines from AAP and other organizations aren't likely to change any time soon. Guidelines should be based on data, but the current guideline writers prefer to harken back to penicillin studies done in the 1940s and 1950s, when rheumatic fever was still prevalent. However, a recommendation for 10 days of cephalosporin or amoxicillin for treating strep throat is currently under discussion. It stands to reason: The only way to prevent rheumatic fever is to eradicate strep, and these drugs do that better than penicillin!
Keep in mind too that at the time those old studies were done, penicillin cured 95% of strep bacteria. Today that number is just 65%, because of the bombardment of antimicrobials we've been using for the last several decades. The newer literature suggests it's time for change.
I have performed clinical trials, received honoraria, and/or served as a consultant for Abbott Laboratories and Pfizer Inc.