Assessment of the Frequency of Dual Allergy to Penicillins and Cefazolin

Abstract

IMPORTANCE Cefazolin is the preoperative antibiotic of choice because it is safer and more efficacious than second-line alternatives. Surgical patients labeled as having penicillin allergy are less likely to prophylactically receive cefazolin and more likely to receive clindamycin or vancomycin, which results in higher rates of surgical site infections.OBJECTIVE To examine the incidence of dual allergy to cefazolin and natural penicillins.DATA SOURCES MEDLINE/PubMed, Web of Science, and Embase were searched without language restrictions for relevant articles published from database inception until July 31, 2020.STUDY SELECTION In this systematic review and meta-analysis, a search of MEDLINE/PubMed, Web of Science, and Embase was performed for articles published from database inception to July 31, 2020, for studies that included patients who had index allergies to a natural penicillin and were tested for tolerability to cefazolin or that included patients who had index allergies to cefazolin and were tested for tolerability to a natural penicillin. A total of 3228 studies were identified and 2911 were screened for inclusion.DATA EXTRACTION AND SYNTHESIS Data were independently extracted by 2 authors. Bayesian meta-analysis was used to estimate the frequency of allergic reactions. MAIN OUTCOMES AND MEASURESDual allergy to cefazolin and a natural penicillin. RESULTSSeventy-seven unique studies met the eligibility criteria, yielding 6147 patients. Cefazolin allergy was identified in 44 participants with a history of penicillin allergy, resulting in a dual allergy meta-analytical frequency of 0.7% (95% credible interval [CrI], 0.1%-1.7%; I 2 = 74.9%). Such frequency was lower for participants with unconfirmed (0.6%; 95% CrI, 0.1%-1.3%; I 2 = 54.3%) than for those with confirmed penicillin allergy (3.0%; 95% CrI, 0.01%-17.0%; I 2 = 88.2%). Thirteen studies exclusively assessed surgical patients (n = 3884), among whom 0.7% (95% CrI, 0%-3.3%; I 2 = 85.5%) had confirmed allergy to cefazolin. Low heterogeneity was observed for studies of patients with unconfirmed penicillin allergy who had been exposed to perioperative cefazolin (0.1%; 95% CrI, 0.1%-0.3%; I 2 = 13.1%). Penicillin allergy was confirmed in 16 participants with a history of cefazolin allergy, resulting in a meta-analytical frequency of 3.7% (95% CrI, 0.03%-13.3%; I 2 = 64.4%). The frequency of penicillin allergy was 4.4% (95% CrI, 0%-23.0%; I 2 = 75%) for the 8 studies that exclusively assessed surgical patients allergic to cefazolin.CONCLUSIONS AND RELEVANCE These findings suggest that most patients with a penicillin allergy history may safely receive cefazolin. The exception is patients with confirmed penicillin allergy in whom additional care is warranted.

Antibiotic Prophylaxis with Cefazolin Is Associated with Lower Shoulder Periprosthetic Joint Infection Rates Than Non-Cefazolin Alternatives

“…For surgical patients with an uncertain or self-reported penicillin allergy, preoperative testing is considered an integral aspect of antibiotic stewardship 51 . Subsequent investigations have demonstrated a positive effect of testing programs to confirm the safety of cephalosporins in those with negative penicillin skin tests 52,53 . Within orthopaedics, Wyles et al 19 evaluated 3,310 TJAs and reported that 97% of patients received clearance for cefazolin use after preoperative allergy testing.…”

Emerging Treatment Options for Acute Bacterial Skin and Skin Structure Infections and Bloodstream Infections Caused by Staphylococcus aureus: A Comprehensive Review of the Evidence

“… 9 , 16 , 27 The role of cefazolin as an alternative to antistaphylococcal penicillins for severe MSSA infections is much debated, with some authors suggesting it as a first-line alternative and others as a second-line option (in this latter case as an alternative to clindamycin for patients allergic to penicillins, supported by a lower than previously thought risk of allergic reactions to cefazolin in patients with self-reported penicillin allergy, although administration should be avoided in patients with previous systemic and/or severe reactions to penicillins). 9 , 15–17 , 27 , 28 For purulent S. aureus ABSSSI, such as abscesses, drainage remains the first therapeutic measure whenever feasible, and MRSA coverage (see below) should be considered for empiric therapy in severe cases while waiting for drug susceptibility test or molecular tests for mecA . 16 …”

Suspected allergy to Beta-Lactam antibiotics: An infectiological perspective

“…A corresponding meta-analysis found a very low cross-reaction with cefazolin in patients with presumed penicillin allergy and did not exclude the use of cefazolin even in cases of explicitly proven IgE-mediated penicillin allergy. However, administration should then only proceed under appropriate precautions under which an anaphylactic reaction can be controlled [ 21 ]. The German AWMF guideline on the diagnosis of suspected BLA hypersensitivity expresses it somewhat more cautiously, but also recommends the administration of a BLA with low risk of cross-reactivity under the precautions of a provocation test in cases of an urgent indication and after individual case assessment.…”

“…In a patient with a medical history of suspected type I reaction to, e.g., penicillin or ampicillin in the last 5- 10 years with limited cellulitis (even after 10 years, but after such a long, time type I reactions are often difficult to detect without intermediate re-exposure), parenteral therapy with cefazolin would be possible [ 9 , 21 , 28 ] as it is effective against S. aureus and recommended for limited cellulitis in guidelines [ 5 , 25 ] . Cefazolin would be better from an infectious-disease perspective than the macrolides or clindamycin (both of which would also be indicated for the case of penicillin allergy) [ 5 ].…”