Adverse reactions associated with oral and parenteral use of cephalosporins: a retrospective population-based analysis.
Abstract
Background Few studies have provided population-based, route-specific data on allergy to cephalosporin or incidence of serious adverse drug reactions (ADRs).Objective We investigated the incidence of new reports of cephalosporin-associated "allergy" and serious ADRs.Methods We identified all members of the Kaiser Permanente Southern California health plan given cephalosporins (from January 1, 2010, through December 31, 2012), all new reports of cephalosporin-associated allergy, and all serious ADRs.Results There were 622,456 health plan members exposed to 901,908 courses of oral cephalosporins and 326,867 members exposed to 487,630 courses of parenteral cephalosporins over the 3-year study period. New reports of allergy to cephalosporin were more frequent among women (0.56%; 95% CI, 0.54% to 0.57%) than among men (0.43%; 95% CI, 0.41% to 0.44%) per course (P < .0001). The most frequent serious cephalosporin-associated ADRs were Clostridium difficile infection within 90 days (0.91%), nephropathy within 30 days (0.15%), and all-cause death within 1 day (0.10%). None correlated with history of drug allergy. Physician-documented cephalosporin-associated anaphylaxis occurred with 5 oral exposures (95% CI, 1/1,428,571-1/96,154) and 8 parenteral exposures (95% CI, 1/200,000-1/35,971) (P = .0761). There were 3 documented cephalosporin-associated serious cutaneous adverse reactions (95% CI, 0-1 in 217,291). All were associated with the use of another antibiotic at the same time as cephalosporin.Conclusions Cephalosporins are widely and safely used, even in individuals with a history of penicillin allergy. Physician-documented cephalosporin-associated anaphylaxis and serious cutaneous adverse reactions are rare compared with C difficile infection within 90 days, nephropathy within 30 days, and all-cause death within 1 day.
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Anaphylaxis secondary to cephalosporins is extremely rare among persons who report a penicillin allergy and is estimated to occur at a rate of one per 52,000 persons.
“Moreover, anaphylaxis secondary to cephalosporins is extremely rare among persons who report a penicillin allergy and is estimated to occur at a rate of one per 52,000 persons (652).”
From Sexually Transmitted Infections Treatment Guidelines, 2021 (2021) · cites this paper as [652]
Cross-reactivity between penicillin allergy and third-generation cephalosporins is low.
“even though the cross-reactivity between penicillin allergy and third-generation cephalosporins is low (652–654).”
From Sexually Transmitted Infections Treatment Guidelines, 2021 (2021) · cites this paper as [652]
Data from the Kaiser health care system reported that among 3,313 patients with self-reported cephalosporin allergy who received a cephalosporin (mostly first generation), no cases of anaphylaxis were reported.
“Data from the Kaiser health care system reported that among 3,313 patients with self-reported cephalosporin allergy who received a cephalosporin (mostly first generation), no cases of anaphylaxis were reported (652).”
From Sexually Transmitted Infections Treatment Guidelines, 2021 (2021) · cites this paper as [652]
Third-generation cephalosporins (e.g., ceftriaxone and cefixime) have lower cross-reactivity with IgE-mediated penicillin-allergic patients (<1%) compared with first- and second-generation cephalosporins (range: 1%-8%).
“Third-generation cephalosporins (e.g., ceftriaxone and cefixime) have lower cross-reactivity with IgE-mediated penicillin-allergic patients (<1%) compared with first- and second-generation cephalosporins (range: 1%–8%).”
From Sexually Transmitted Infections Treatment Guidelines, 2021 (2021) · cites this paper as [652]
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Why Was There Ever a Warning Not to Use Cephalosporins in the Setting of a Penicillin “Allergy”?
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Evaluation of the Potential Risk Factors for Drug-Induced Anaphylaxis in Adult Patients
Demir, S., Erdenen, F., Gelincik, A. A., Ünal, D., Olgaç, M., Coşkun, R., Çolakoğlu, B., & Büyüköztürk, S. (2018) · International Archives of Allergy and Immunology · doi:10.1159/000494130 · Cited by 19 · see citing works
Bukowski, B. R., Torres-Ramirez, R. J., Devine, D., Chiu, Y.-F., Carli, A. V., Maalouf, D. B., Goytizolo, E. A., Miller, A. O., & Rodríguez, J. A. (2024) · The Journal of Arthroplasty · doi:10.1016/j.arth.2024.04.058 · Cited by 18 · see citing works
Pyelonephritis treatment in the community emergency department: Cephalosporins vs. first-line agents
Vogler, S., & Pavich, E. (2018) · The American Journal of Emergency Medicine · doi:10.1016/j.ajem.2018.08.016 · Cited by 18 · see citing works
Management of Penicillin Allergy in the Perioperative Setting
Sexton, M. E., & Kuruvilla, M. E. (2024) · Antibiotics · doi:10.3390/antibiotics13020157 · Cited by 17 · see citing works
Chan, K. H., Whittam, B. M., Moser, E. A. S., Cain, M. P., & Bennett, W. E. (2016) · Journal of Pediatric Urology · doi:10.1016/j.jpurol.2016.10.017 · Cited by 17 · see citing works
Large Health System Databases and Drug Hypersensitivity
Chiriac, A. M., & Macy, E. M. (2019) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2019.04.014 · Cited by 17 · see citing works
The association of penicillin allergy with outcomes after open ventral hernia repair
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Choi, J.-Y., Choi, J.-H., Kim, M. G., & Rhie, S. J. (2021) · Pharmaceuticals · doi:10.3390/ph14050425 · Cited by 15 · see citing works
Classifying cephalosporins: from generation to cross-reactivity
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Recent Progress and Novel Perspectives of Electrochemical Sensor for Cephalosporins Detection
Wang, Q., Wang, D., Wang, J., Cui, Y., & Xu, H. (2019) · International Journal of Electrochemical Science · doi:10.20964/2019.09.15 · Cited by 14 · see citing works
Tackling the Patient with Multiple Drug “Allergies”: Multiple Drug Intolerance Syndrome
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Stonerock, D., Hallo‐Carrasco, A., Edwards, M. A., Porter, S. B., Epps, K. L., & Gonzalez‐Estrada, A. (2023) · American Journal of Health-System Pharmacy · doi:10.1093/ajhp/zxad023 · Cited by 14 · see citing works
Promoting β-lactam utilization through suppression of electronic medical record cross-allergy alerts
Boesch, T. S., Eischen, E., Ries, A., Quinn, A., Dave, A., & Beezhold, D. W. (2022) · American Journal of Health-System Pharmacy · doi:10.1093/ajhp/zxac040 · Cited by 13 · see citing works
Moral, L., Toral, T., Muñoz, C., Marco, N., García‐Avilés, B., Murcia, L., Forniés, M. J., González, M. C., Canals, F., Bragado, E., et al. (2024) · Pediatric Allergy and Immunology · doi:10.1111/pai.14096 · Cited by 13 · see citing works
Cephalosporin Allergy: Updates on Diagnostic Testing
Chow, T. G., Brunner, E. S., & Khan, D. A. (2024) · Current Allergy and Asthma Reports · doi:10.1007/s11882-024-01171-9 · Cited by 13 · see citing works
Clinical Outcomes of Failing to Dose-Reduce Cephalosporin Antibiotics in Older Adults with CKD
Bathini, L., Jandoc, R., Kuwornu, J. P., McArthur, E., Weir, M. A., Sood, M. M., Battistella, M., Muanda, F. T., Liu, A., Jain, A. K., et al. (2019) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.10710918 · Cited by 12 · see citing works
Antibiotic hypersensitivity in cystic fibrosis – Low frequency of anaphylaxis over 16 000 courses
Kowalik, A., de Monestrol, I., Sorjonen, K., Brockow, K., & Gülen, T. (2022) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.15434 · Cited by 11 · see citing works
Cefazolin-induced hemolytic anemia: a case report and systematic review of literature
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Update in Therapeutics: Prophylactic Antibiotics in Open Fractures
Samai, K., & Vilella, A. L. (2018) · Journal of Trauma Nursing · doi:10.1097/jtn.0000000000000348 · Cited by 11 · see citing works
Thellier, C., Subtil, D., Chambure, D. P. D., Grandbastien, B., Catteau, C., Beaugendre, A., Poitrenaud, D., Prévötat, A., Richart, P., Faure, K., et al. (2019) · International Journal of Obstetric Anesthesia · doi:10.1016/j.ijoa.2019.07.005 · Cited by 10 · see citing works
Bassir, F., Varghese, S., Wang, L., Chin, Y. P., & Zhou, L. (2022) · Immunology and Allergy Clinics of North America · doi:10.1016/j.iac.2022.01.004 · Cited by 10 · see citing works
Advances in the Understanding of Drug Hypersensitivity: 2012 Through 2022
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Antibiotic-associated adverse drug events at a Japanese academic hospital
Kokado, R., Hagiya, H., Koyama, T., Matsui, E., Okuno, H., Morii, D., Hamaguchi, S., Yoshida, H., Miwa, Y., & Tomono, K. (2018) · Journal of Infection and Chemotherapy · doi:10.1016/j.jiac.2018.11.002 · Cited by 9 · see citing works
Menéndez, R., Cantón, R., García-Caballero, A., & Barberán, J. (2019) · Europe PMC (PubMed Central) · Cited by 10 · see citing works
Ratan, Y., Rajput, A., Pareek, A., Jain, V. K., Pareek, A., Gupta, M. M., & Kamal, M. A. (2023) · Current Pharmaceutical Biotechnology · doi:10.2174/1389201025666230908141543 · Cited by 9 · see citing works
Lillis, R., Barbee, L. A., McNeil, C. J., Newman, L. M., Fortenberry, J. D., Arango, S. A., & Zenilman, J. M. (2024) · Clinical Infectious Diseases · doi:10.1093/cid/ciae064 · Cited by 9 · see citing works
Multiple Drug Intolerance Syndrome
Macy, E. M. (2017) · Elsevier eBooks · doi:10.1016/b978-0-323-48551-7.00016-x · Cited by 9 · see citing works
Michaud, L., Yen, H. H., Engen, D. A., & Yen, D. (2023) · BMC Surgery · doi:10.1186/s12893-023-01931-w · Cited by 9 · see citing works
Approach for delabeling beta-lactam allergy in children
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Macy, E. M., Crawford, W., Nguyen, M. T., Adams, J., McGlynn, E. A., & McCormick, T. A. (2021) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2021.10.043 · Cited by 9 · see citing works
Barriers to and Facilitators of Delabelling of Antimicrobial Allergies: A Qualitative Meta-synthesis
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Is antibiotic prophylaxis necessary in mid-urethral sling surgery?
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Does the Penicillin Allergy Label Affect Outcomes of Complicated Odontogenic Infections?
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Cephalosporin-Induced Toxic Epidermal Necrolysis Treated with Intravenous Immunoglobulin
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Antibiotics for complicated urinary tract infection and acute pyelonephritis: A systematic review
Ong, L. T. (2020) · World Journal of Clinical Infectious Diseases · doi:10.5495/wjcid.v10.i3.33 · Cited by 6 · see citing works
Macy, E. M. (2018) · Springer eBooks · doi:10.1007/978-3-030-03395-8_10 · Cited by 6 · see citing works
Wren, C., Cowper, J., Greer, N. D., Goldin, L., & Perry, A. (2022) · Antibiotics · doi:10.3390/antibiotics11101312 · Cited by 5 · see citing works
- Authors
- Macy, E., & Contreras, R.
- Affiliations
- Kaiser Permanente (US)
- Corresponding author
- Macy, Eric
- ORCID
- Macy, Eric
- Venue
- Journal of Allergy and Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2015-03
- Volume
- 135
- Issue
- 3
- Pages
- 745-752.e5
- ISSN
- 0091-6749 (ISSN-L)
- OpenAlex
- W2098026142
- Cited by
- 153
- References
- 28
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 13 · 2023: 9 · 2022: 16 · 2021: 18 · 2020: 11 · 2019: 15 · 2018: 20 · 2017: 15 · 2016: 8 · 2015: 9 · 2014: 1
- FWCI
- 8.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Allergy and Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
- Health Sciences › Medicine › Pharmacology › Drug-Induced Adverse Reactions
- Life Sciences › Immunology and Microbiology › Applied Microbiology and Biotechnology › Antibiotic Use and Resistance
- Keywords
- cephalosporins, drug hypersensitivity, adverse drug reactions, anaphylaxis, Clostridium difficile infection, nephrotoxicity, antibiotic combinations, penicillin allergy, route of administration, Kaiser Permanente Southern California, drug safety, sex differences in allergy
- MeSH terms
- Administration, Oral, Adolescent, Adult, Anti-Bacterial Agents, California, Cephalosporins, Drug Hypersensitivity, Enterocolitis, Pseudomembranous, Female, Humans, Infusions, Parenteral, Male, Middle Aged, Nephritis, Retrospective Studies, State Health Plans, Clostridioides difficile
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