Despite the Safety of Preoperative Cefazolin for Patients With Non-anaphylactic Penicillin Allergy, 20% of Practitioners Avoid Its Use.

Cefazolin is commonly used for surgical site infection prophylaxis due to its low cost and effective coverage. However, it is controversial to use cefazolin in patients with a penicillin allergy despite the cross-reactivity between cefazolin and penicillin being only 1%. Ample literature shows that it is safe to use cefazolin in patients with non-anaphylactic penicillin allergies. However, there is often hesitation by anesthesiologists or orthopedists when prescribing this medication in this population. The current authors sent a 16-question survey to all the residency programs in the United States in anesthesiology and orthopedics asking physicians affiliated with these programs to answer a series of questions about their demographics, prescribing patterns, and knowledge of the cross-reactivity between penicillin and cefazolin. A total of 146 responses in each group, with 82.9% (n=121) of orthopedists and 78.8% (n=115) of anesthesiologists preferring cefazolin for patients with non-anaphylactic penicillin allergies. However, only 57.5% of anesthesiologists and 41.1% of orthopedists knew the correct cross-reactivity between cephalosporins and penicillin. If a provider knew the correct cross-reactivity between cefazolin and penicillin, he or she had an increased odds of prescribing cefazolin to patients with nonanaphylactic penicillin allergies (orthopedics odds ratio [OR], 4.77, P<.01; anesthesiologists OR, 3.59, P<.01). Therefore, this study supports that further education of orthopedic and anesthesia providers about the cross-reactivity between cefazolin and penicillin would lead to more evidence-based, cost-effective care. [Orthopedics. 2019; 42(5):e437-e442.].

Misconceptions Surrounding Penicillin Allergy: Implications for Anesthesiologists.

Administration of preoperative antimicrobial prophylaxis, often with a cephalosporin, is the mainstay of surgical site infection prevention guidelines. Unfortunately, due to prevalent misconceptions, patients labeled as having a penicillin allergy often receive alternate and less-effective antibiotics, placing them at risk of a variety of adverse effects including increased morbidity and higher risk of surgical site infection. The perioperative physician should ascertain the nature of previous reactions to aid in determining the probability of the prevalence of a true allergy. Penicillin allergy testing may be performed but may not be feasible in the perioperative setting. Current evidence on the structural determinants of penicillin and cephalosporin allergies refutes the misconception of cross-reactivity between penicillins and cefazolin, and there is no clear evidence of an increased risk of anaphylaxis in cefazolin-naive, penicillin-allergic patients. A clinical practice algorithm for the perioperative evaluation and management of patients reporting a history of penicillin allergy is presented, concluding that cephalosporins can be safely administered to a majority of such patients.

Selective hypersensitivity to cefazolin and contribution of the basophil activation test.

SUMMARY: The authors present 2 case reports of selective cefazolin hypersensitivity: a 49 year-old woman with a history of two perioperative reactions (urticaria and severe anaphylaxis) after the use of rocuronium, propophol and cefazolin; a 36 year-old pregnant woman who developed facial erythema, lips angioedema and hypotension immediately after administration of ropivacain, sufentanil, cefazolin, oxytocin and ephedrine. In both cases, intradermal skin tests were positive for cefazolin. A basophil activation test was performed for cefazolin, which was positive in one patient. Oral challenge tests with penicillin, amoxicillin and other cephalosporins were negative. This selective hypersensitivity to cefazolin may be associated with a R1-side chain different from other beta-lactams.

A statement on cefazolin immediate hypersensitivity: data from a large database, and focus on the cross-reactivities.

BACKGROUND: More perioperative cefazolin use has resulted in an increased risk of cefazolin-associated reactions. OBJECTIVE: The aim of this article is to study immediate reactions to cefazolin and attempt to determine possible allergic cross-reactivity with other ß-lactams using data from the Drug Allergy and Hypersensitivity Database (DAHD). METHODS: All 25 cefazolin-associated reactions in the DAHD were reviewed. The cases identified were then investigated according to the European Network for Drug Allergy (ENDA) recommendations by skin testing and challenges. RESULTS: A total of 10 individuals with proven IgE-mediated cefazolin hypersensitivity were identified between January 1999 and July 2009. All the index reactions were compatible with an acute IgE-mediated process, six with anaphylaxis, two with systemic allergic reactions without hypotension, and two with urticaria/angioedema. Cefazolin skin tests were positive in seven individuals and cefazolin challenges were positive in three more individuals. In the eight cefazolin allergic patients who had challenges with other ß-lactams, there was no positive reaction noted. CONCLUSION AND CLINICAL RELEVANCE: In this cohort of patients with IgE-mediated reactions to cefazolin, a majority tolerated amoxicillin and several patients tolerated other cephalosporins. This implies that the R1 side-chain may play an essential role in IgE-mediated reactions to cefazolin. No clear rule to predict cross-reactivity with other ß-lactams could be determined. More research on IgE-mediated hypersensitivity to cefazolin and other cephalosporins is needed.

Effect of UV irradiation and magnetic field on immunometabolic effects of antibiotics immobilized in cell carriers.

The effects of UV and magnetic radiation on the immunometabolic activity of ampicillin and cephazolin immobilized in erythrocytic and leukocytic carriers were studied in intact Wistar rats and animals infected with staphylococci. Erythrocytic and leukocytic carriers with antibiotics were obtained. Injection of free antibiotics stimulated the immunosuppressive, pro-oxidant, and hepatotoxic effects, associated with staphylococcal infection. Treatment with antibiotics in erythrocytic and leukocytic carriers stimulated (to different degrees) the activity of the immune system and stabilized the parameters of LPO, antioxidant defense, cytolysis, and cholestasis. Ultraviolet irradiation and magnetic field modified (to different measures) the immunometabolic effects of ampicillin and cephazolin, immobilized in erythrocytic and leukocytic carriers, in animals with staphylococcal infection.

Anaphylaxis to cefazolin during labor secondary to prophylaxis for group B Streptococcus: a case report.

BACKGROUND: Anaphylaxis is an uncommon event during pregnancy, but if it does arise, it can lead to serious fetal consequences even if there are no serious long-term maternal complications. CASE: A parturient developed anaphylaxis in the labor unit shortly after intravenous cefazolin chemoprophylaxis had begun for perinatal group B streptococcal disease. Prompt treatment for anaphylaxis commenced, involving the administration of epinephrine and glucocorticoids, and an emergency cesarean section spared the mother serious morbidity, with a favorable perinatal outcome for the fetus. CONCLUSION: To the best of our knowledge, this case is the first reported one of anaphylaxis to cefazolin in pregnancy secondary to prophylaxis against for B Streptococcus. The case demonstrates that a life-threatening anaphylactic reaction can occur at any time during pregnancy and that all staff in a maternal unit should be familiar with the management of perinatal anaphylaxis.

Antigen specific quantification of sulfidoleukotrienes in patients allergic to Betalactam antibiotics.

BACKGROUND: After in vitro allergen-specific stimulation, basophils become activated and release sulfidoleukotrienes LTC4, LTD4 and LTE4. This can be detected by means of the CAST assay. We assessed the positivity criteria and the reliability of antigen-specific sulfidoleukotriene production (CAST) in the in vitro diagnosis of betalactam (BL) allergic patients. MATERIAL AND METHODS: We studied a sample of 67 patients (age 48.94 +/- 15.76 years) who had presented with anaphylaxis or urticaria-angioedema within the first 60 minutes after administration of Amoxicillin (54/67), Penicillin G (7/67), Cefuroxime (5/67) or Cefazoline (1/67). All of them had a positive skin test to at least one of the antigenic determinants of Penicillin. As control group 30 adults with negative skin tests who tolerated BL were included. All of them underwent skin tests, oral provocation tests, specific IgE (CAP-FEIA, Pharmacia) and CAST. RESULTS: Positivity criteria were established by means of ROC curves: a sLT release induced by Betalactams of at least 100 pg/ml and greater than or equal to 3 times the basal value. The overall sensitivity of CAST is 47.7% and specificity 83.3%. Sensitivity of specific IgE is 37.8% and specificity 83.3%. CONCLUSIONS: We have established validated positivity criteria for the CAST technique in patients allergic to Betalactams. This technique is a useful in vitro diagnostic method in patients with IgE-mediated allergy to Betalactam antibiotics.

Allergy to cefazolin: study of in vivo cross reactivity with other betalactams.

We present two cases of hypersensitivity to cefazolin (one anaphylaxis). The skin prick tests with cefazolin at therapeutic concentration were positive. For the in vitro study we used conjugates of cefazolin with human serum albumin, obtaining a positive result in the histamine release test in both patients. In one case, we demonstrated anticefazolin-specific IgE antibodies by RAST. The controls did not react to any of these tests. Finally, we carried out skin tests and challenge tests with other betalactam antibiotics, including benzylpenicillin, amoxicillin, aztreonam, cefuroxime and cefotaxime, showing in both patients good tolerance to all these drugs.

Influences of cephem antibiotics on the immune response in mice.

The effects of six cephem antibiotics, including ceftezole, cefmetazole, cefoxitin, cefotiam, cefoperazone, and cefotaxime, on murine humoral immunity were examined. In female BDF1 mice each cephem antibiotic was administered at a dose of 800 mg/kg/day i.v. for 7 consecutive days. Among the antibiotics tested, only ceftezole and cefoperazone induced a significant increase in serum total IgM, but not in serum total IgG. Especially in case of ceftezole, the mice developed splenomegaly due to the proliferation of IgM-producing cells in the germinal centers. The proliferation of splenic IgM-producing cells was also observed in female thymus-deficient Balb/c-nu/nu mice receiving intravenous ceftezole. Thus, the drug was indicated to enhance the polyclonal IgM production in mice by acting as a B cell mitogen. This is consistent with the in vitro finding that ceftezole exhibited a mitogenic effect on whole spleen cells from BDF1 mice, but not on B cell depleted spleen cells.