What is the appropriate second antibiotic for a patient with recurrent streptococcal pharyngitis (strep throat) and skin cellulitis, who has completed a course of penicillin?

From the Guidelines

For recurrent strep throat with cellulitis after a completed course of penicillin, I recommend clindamycin as a second-line antibiotic. The typical adult dosage is 300-450 mg orally every 6-8 hours for 10 days 1. For children, the dosage is 20-30 mg/kg/day divided into three or four doses 1.

Key Points to Consider

• Clindamycin is especially effective against both streptococcal infections and skin infections like cellulitis because it has excellent tissue penetration and is active against most strains of Group A Streptococcus, including those that may have developed resistance to penicillin 1.
• Alternatively, azithromycin (500 mg on day 1, then 250 mg daily for 4 more days for adults; 12 mg/kg once daily for 5 days for children) or cephalexin (500 mg orally four times daily for 10 days for adults; 25-50 mg/kg/day divided into four doses for children) could be effective options 1.
• These alternatives are particularly useful if the infection appears to be resistant to penicillin or if the patient has developed a recurrence shortly after treatment.
• Be aware that clindamycin carries a risk of Clostridioides difficile-associated diarrhea, so patients should be advised to contact their healthcare provider if they develop severe diarrhea during or after treatment.

Treatment Duration

• A 5-day course of antimicrobial therapy is as effective as a 10-day course, if clinical improvement has occurred by 5 days 1.
• However, for recurrent strep throat with cellulitis, a 10-day course of clindamycin may be necessary to ensure complete eradication of the infection 1.

From the FDA Drug Label

Pharyngitis/Tonsillitis In three double-blind controlled studies, conducted in the United States, azithromycin (12 mg/kg once a day for 5 days) was compared to penicillin V (250 mg three times a day for 10 days) in the treatment of pharyngitis due to documented Group A β-hemolytic streptococci (GABHS or S. pyogenes)

Azithromycin was clinically and microbiologically statistically superior to penicillin at Day 14 and Day 30 with the following clinical success (i.e., cure and improvement) and bacteriologic efficacy rates (for the combined evaluable patient with documented GABHS):

Three U. S. Streptococcal Pharyngitis Studies Azithromycin vs. Penicillin V EFFICACY RESULTS

Day 14Day 30

Bacteriologic Eradication: Azithromycin323/340 (95%)255/330 (77%)

Penicillin V242/332 (73%)206/325 (63%)

Clinical Success (Cure plus improvement): Azithromycin336/343 (98%)310/330 (94%)

Penicillin V284/338 (84%)241/325 (74%)

Azithromycin is a suitable option for the treatment of strep infection and skin cellulitis, as it has been shown to be effective in the treatment of pharyngitis due to documented Group A β-hemolytic streptococci (GABHS or S. pyogenes) 2.

• Clinical success rates for azithromycin were 98% at Day 14 and 94% at Day 30.
• Bacteriologic eradication rates for azithromycin were 95% at Day 14 and 77% at Day 30. Given that the patient has already completed a course of penicillin and the sore throat has returned, azithromycin may be considered as a second antibiotic option 2.

From the Research

Strep Infection and Skin Cellulitis Treatment

• The patient has completed a course of penicillin for strep infection, but the sore throat has returned, indicating the need for a second antibiotic 3.
• For uncomplicated superficial skin infections, including cellulitis, amoxicillin-clavulanate is often recommended as it offers the best guarantee of efficiency 4, 5.
• In cases of allergy to penicillin, alternative antibiotics such as first-generation cephalosporins, macrolides (if the strain is susceptible), or pristinamycine (after 6 years of age) can be considered 4.
• A network meta-analysis of randomized controlled trials found no significant differences in cure rates among various antibiotics for cellulitis, but ceftriaxone had the fewest gastrointestinal side effects 6.
• For erysipelas, pristinamycin showed the highest cure rates, but with a higher risk of rash 6.

Antibiotic Options for Cellulitis and Erysipelas

• Amoxicillin-clavulanate is a commonly recommended antibiotic for cellulitis and erysipelas due to its broad-spectrum activity and efficacy 4, 5.
• Cefaclor demonstrated a favorable profile for curative outcomes in cellulitis, while pristinamycin showed promising results in achieving cure rates for erysipelas 6.
• The choice of antibiotic should be based on the severity and type of infection, as well as the patient's medical history and potential allergies 4, 7.

Considerations for Antibiotic Treatment

• The majority of non-purulent, uncomplicated cases of cellulitis are caused by β-hemolytic streptococci or methicillin-sensitive Staphylococcus aureus, and targeted coverage with oral antibiotics such as penicillin, amoxicillin, or cephalexin is often sufficient 7.
• In cases of strep throat, antibiotics with narrow spectrums of activity are preferred to minimize unnecessary use and reduce the risk of resistance 3.
• The treatment of cellulitis and erysipelas should be guided by clinical guidelines and evidence-based recommendations to ensure optimal outcomes and minimize adverse effects 7, 5, 6.