Gordon H. Sun, MD, MS

April 29, 2014

Nonpenicillin Options

Alternative medical therapy for ABRS in the setting of penicillin allergy is highly contentious, and recommendations from existing clinical guidelines vary widely. The AAP guideline suggests that the risk for cross-reactive allergy to cephalosporins is low, and that certain second- or third-generation cephalosporins, such as cefuroxime and cefpodoxime, can be used as alternatives.[3]

The cross-reactive allergy rate between penicillins and cephalosporins is estimated at 0.1%,[5] substantially lower than the oft-cited figure of 10%-20%. This historical statistic may be attributed to the use of older first-generation cephalosporins before 1980, as well as suspected trace contamination of some first-generation cephalosporins with penicillin.[6] The AAP guideline does suggest the option of referring patients with penicillin allergy to an allergist for skin testing.

Both the AAP and IDSA guidelines suggest a combination of clindamycin and a third-generation cephalosporin and, of note, a fluoroquinolone as options.[2,3] Currently, the only US Food and Drug Administration (FDA)-approved indication for levofloxacin in the pediatric population is for the prevention of inhalational anthrax, owing to an increased incidence of musculoskeletal disorders, such as arthritis and tendinopathy. Given this substantial risk, clinicians should be very cautious in the use of fluoroquinolones in children.

Neither guideline recommends macrolides and trimethoprim/sulfamethoxazole as alternatives, citing unacceptably high bacterial resistance rates from epidemiologic studies.[7,8,9,10,11]

In contrast, the AAO-HNS guideline does suggest a macrolide or trimethoprim/sulfamethoxazole as alternatives for patients with penicillin allergy.[4] Although the guideline was intended for adults, the microbiology and drug resistance patterns of pediatric and adult patients with ABRS are similar: Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are the most common causative organisms.[12,13,14]

However, recently there has been particular concern about increasing resistance to azithromycin among several types of respiratory tract infections, including ABRS. The use of azithromycin has risen significantly over the past decade, even as prescription rates for other broader-spectrum antibiotics have remained stable.[15,16] Surveillance studies conducted in North America have found increased S pneumoniae and H influenzae resistance to azithromycin, diminishing its efficacy in treating common respiratory tract infections.[2,3,17,18] Globally, pneumococcal resistance to macrolides is now more common than resistance to penicillin.[19] In 2013, the Canadian Pediatric Society strongly recommended that azithromycin not be used to treat acute pharyngitis, otitis media, or community-acquired pneumonia (CAP).[18]


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