From the Guidelines
For patients with a penicillin allergy, alternative antibiotics such as cefdinir, cefuroxime, or ceftriaxone are recommended due to their low cross-reactivity with penicillin 1. When considering alternatives to penicillin, it's essential to assess the severity of the allergy and the specific infection being treated.
- Cefdinir, cefuroxime, and ceftriaxone are highly unlikely to be associated with cross-reactivity with penicillin allergy due to their distinct chemical structures 1.
- For patients with non-severe penicillin allergies, cephalosporins such as cefdinir (14 mg/kg per day in 1 or 2 doses) or cefuroxime (30 mg/kg per day in 2 divided doses) may be suitable alternatives 1.
- In cases where cephalosporins are not appropriate, doxycycline or a respiratory fluoroquinolone (levofloxacin or moxifloxacin) may be considered as alternative agents for empiric antimicrobial therapy 2.
- Clindamycin (30–40 mg/kg per day in 3 divided doses) plus a third-generation oral cephalosporin (cefixime or cefpodoxime) is also a recommended combination therapy for adults with a history of non–type I hypersensitivity to penicillin 2. It's crucial to note that many patients who report penicillin allergies may not have true allergies, and the choice of alternative should be based on the infection type, local resistance patterns, patient factors, and the nature of the allergic reaction to penicillin.
- The use of macrolide antibiotics and trimethoprim-sulfamethoxazole is not recommended for initial therapy of acute bacterial rhinosinusitis (ABRS) due to high resistance rates 2.
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. Pharyngitis/Tonsillitis ... 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)
Alternatives to penicillin in patients with a penicillin allergy are:
- Doxycycline: for syphilis, and other infections
- Azithromycin: for pharyngitis/tonsillitis, and other infections 3, 4
From the Research
Alternatives to Penicillin in Patients with Penicillin Allergy
- Aztreonam, a monobactam antibiotic, may be a safe alternative for managing Gram-negative infections in penicillin-allergic patients 5.
- Cephalosporins can be used in penicillin-allergic patients, but the risk of cross-reactivity varies depending on the generation of cephalosporin and the specific penicillin allergy 6, 7, 8.
- First-generation cephalosporins have a higher cross-reactivity with penicillins, while third- and fourth-generation cephalosporins have a lower risk of cross-reactivity 6, 7.
- The overall cross-reactivity rate between penicillins and cephalosporins is approximately 1% when using first-generation cephalosporins or cephalosporins with similar R1 side chains 6.
- Patients allergic to several penicillins are more likely to develop an allergic reaction to cephalosporins due to sensitization to similar structural characteristics (nuclear and R1 side-chain) 7.
- Other beta-lactam antibiotics, such as carbapenems and monobactams, may also be safe alternatives in penicillin-allergic patients, but the risk of cross-reactivity should be assessed on a case-by-case basis 9.
Considerations for Selecting Alternative Antibiotics
- The selection of an alternative antibiotic should be based on the specific type of infection, the severity of the penicillin allergy, and the patient's medical history 8, 9.
- Skin testing, patch testing, and graded challenge may be used to diagnose penicillin allergy and assess the risk of cross-reactivity with other antibiotics 9.
- Desensitization may be used in some cases where treatment with penicillins is essential, but this should be done under close medical supervision 9.