What are the oral antibiotic options for cellulitis in patients with a penicillin (Penicillin) allergy?

From the Guidelines

For patients with cellulitis who have a penicillin allergy, clindamycin is typically the first-line oral antibiotic choice, as recommended by the Infectious Diseases Society of America 1. The recommended adult dosage is 300-450 mg taken orally three times daily for 5-10 days, depending on the severity of the infection. Alternatively, doxycycline (100 mg twice daily) or trimethoprim-sulfamethoxazole (one double-strength tablet twice daily) can be used, particularly if MRSA is suspected, as supported by the 2011 guidelines 1. Some key points to consider when treating cellulitis in patients with a penicillin allergy include:

• Assessing the nature of the penicillin allergy, as true anaphylactic reactions require strict avoidance of beta-lactams, while less severe reactions might allow for certain alternatives.
• Treatment should be adjusted based on clinical response within 48-72 hours.
• If symptoms worsen, fever develops, or the affected area expands despite oral antibiotics, the patient should seek immediate medical attention as intravenous antibiotics may be necessary.
• The 2014 update by the Infectious Diseases Society of America also recommends considering the patient's individual risk factors, such as immunocompromised status or presence of systemic signs of infection, when selecting an antibiotic regimen 1. It's worth noting that the most recent and highest quality study, which is the 2014 update 1, provides more comprehensive guidance on the diagnosis and management of skin and soft tissue infections, but the recommendations for oral antibiotic options in patients with penicillin allergy remain consistent with the 2011 guidelines 1.

From the FDA Drug Label

Syphilis–early: Patients who are allergic to penicillin should be treated with doxycycline 100 mg, by mouth, twice a day for 2 weeks Syphilis of more than one year’s duration: Patients who are allergic to penicillin should be treated with doxycycline 100 mg, by mouth, twice a day for 4 weeks. Uncomplicated gonococcal infections in adults (except anorectal infections in men):100 mg, by mouth, twice a day for 7 days. The following in vitro data are available, but their clinical significance is unknown: Levofloxacin exhibits in vitro minimum inhibitory concentrations (MIC values) of 2 mcg/mL or less against most (≥ 90%) isolates of the following microorganisms; however, the safety and effectiveness of levofloxacin in treating clinical infections due to these bacteria have not been established in adequate and well-controlled clinical trials Streptococcus pneumoniae (including multi-drug resistant isolates [MDRSP] ) Streptococcus pyogenes

The oral antibiotic options for cellulitis in patients with a penicillin allergy are:

• Doxycycline: 100 mg, by mouth, twice a day
• Levofloxacin: may be effective against some bacteria that cause cellulitis, such as Streptococcus pneumoniae and Streptococcus pyogenes, but its effectiveness in treating clinical infections due to these bacteria has not been established in adequate and well-controlled clinical trials 2 3

From the Research

Oral Antibiotic Options for Cellulitis in Patients with Penicillin Allergy

• For patients with a penicillin allergy, alternative antibiotics such as trimethoprim-sulfamethoxazole and clindamycin can be used to treat cellulitis, as they have activity against community-associated methicillin-resistant Staphylococcus aureus (MRSA) 4.
• Cephalexin may not be the best option for patients with a penicillin allergy, as it has a lower success rate compared to trimethoprim-sulfamethoxazole and clindamycin in treating cellulitis, especially in cases with MRSA infections 4.
• However, it's worth noting that the cross-reactivity between penicillin and cephalosporins, such as cephalexin, is extremely low, estimated at 2% to 3% among patients with a verified penicillin allergy 5.
• In cases where there is no appropriate alternative antibiotic, desensitization can be performed, which involves temporary induction of drug tolerance through exposure to small amounts of the allergen until a therapeutic dose is achieved 5.

Considerations for Antibiotic Selection

• Clinicians should consider the severity of the cellulitis, the presence of MRSA, and the patient's allergy history when selecting an antibiotic 4, 6.
• Antibiotics with activity against community-associated MRSA, such as trimethoprim-sulfamethoxazole and clindamycin, are preferred empiric therapy for outpatients with cellulitis in the community-associated MRSA-prevalent setting 4.
• The use of cephalexin plus trimethoprim-sulfamethoxazole compared to cephalexin alone did not result in higher rates of clinical resolution of cellulitis in the per-protocol analysis, but further research may be needed to confirm these findings 7.