The drug of choice for patients with a documented allergy to penicillin is Clindamycin.

- Penicillins are a commonly prescribed class of antibiotics, but some patients experience allergic reactions ranging from mild rash to severe anaphylaxis.
- For these patients, prescribing a beta-lactam antibiotic like amoxicillin or cephalexin is contraindicated due to the risk of cross-reactivity.
- Azithromycin, a macrolide antibiotic, is an alternative but is generally considered second-line due to emerging resistance and variable efficacy in some infections.
- Clindamycin is a lincosamide antibiotic that is effective against many gram-positive organisms and anaerobes, making it a preferred choice in patients with penicillin allergies.
- It has a different chemical structure than beta-lactams, so the risk of cross-allergy is minimal.
- Additionally, Clindamycin achieves good tissue penetration, particularly useful in infections of the oral cavity, bones, and soft tissues.

Key Points:
- Patients with penicillin allergy should avoid beta-lactam antibiotics.
- Clindamycin is the preferred alternative due to efficacy and low cross-reactivity.
- Azithromycin is an alternative but less preferred.
- Amoxicillin and cephalexin should be avoided in penicillin-allergic patients.

Reference: Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, 9th Edition, Volume 1, Chapter 45, p. 1203