Cefaclor
Summary
Cefaclor is a broad-spectrum, second-generation, beta-lactam antibiotic belonging to the class of cephalosporins. The beta-lactam ring and the side chains (R1 and R2) are the sites of immunological recognition. Cross-reactivity is frequently attributed to the aminobenzene side chain (R1), which is shared between aminopenicillins (amoxicillin and ampicillin) and aminocephalosporins (cefaclor and cephalexin). Hypersensitivity to cefaclor can present as immediate or delayed reactions. Frequent clinical manifestations include urticaria and angioedema, but severe systemic reactions (anaphylaxis) are also reported. Clinical history alone is not reliable for the diagnosis of cefaclor allergy, hence one or more among skin and blood tests for cefaclor sensitization and cefaclor provocation tests are required. Cefaclor skin testing and cefaclor-specific IgE determination are highly specific but lack diagnostic sensitivity for immediate allergic reactions. Risk factors of immediate cefaclor allergy are hypertension, liver disease, asthma, atopic dermatitis, urticaria, allergic conjunctivitis, and intake of non-steroidal anti-inflammatory drugs. Similar to other beta-lactams, alleged allergy to cefaclor is confirmed only in a small proportion of patients.
Epidemiology
Worldwide distribution
Alleged allergy to cephalosporin has a prevalence of 1-2% in general population. Among patients with a history of beta-lactam allergy, cefaclor was suspected in 4% of US-based patients, in 2% of Australia-based patients, and in 6% of pregnant Canadian patients. However, it is estimated that allergological work-up could delabel around 90% of patients labeled as beta-lactam allergic. This is possibly due to two reasons: inaccurate diagnosis and the gradual loss of sensitization with time. Hence, delabelling through allergological investigation is advised, considering the harms of false allergy labels.
The reported prevalence of adverse drug reactions for cephalosporins was 1.7% in the U.S. with an incidence of 0.8% for oral administrations. A survey on 3,999,290 individuals in San Diego during 2010–2012 involved 5269 individuals receiving 6459 courses of cefaclor; about 0.54% (35/6459) of new cefaclor reactions were reported in these individuals.
A retrospective study conducted in Korea found 6883 cases of adverse drug reactions attributed to cefaclor with an incidence rate of 1.92/10,000 individuals, including 1.17/10,000 individuals for hypersensitivity reactions, and 0.38/10,000 individuals for anaphylactic reactions.
A prospective study was conducted in Italy with 236 patients, of whom 216 had a history of immediate cephalosporin reaction. Cefaclor allergy was found in 19/236 subjects, of whom 5/19 showed positive skin tests, 2/19 had elevated serum specific IgE (sIgE) to cefaclor, and 7/19 were positive for both tests.
Another study conducted retrospectively on 476 French patients with alleged cephalosporin allergy found 22.3% (106/476) patients having confirmed cephalosporin allergy, of which 33% (35/106) concerned cefaclor, cefalexin, cefadroxil, and cefatrizine.
A retrospective study conducted in Korea on 47 patients with a history of cefaclor allergy reported elevated cefaclor sIgE in 89.4 % (42/47) patients, while skin tests were positive in 61.5% (8/13) of patients and oral provocation tests for cefaclor were positive in 100% (11/11).
An Australia-based study conducted on 564 subjects with a history of beta-lactam allergy found 90 patients with primary cephalosporin allergy. Of these 90 patients, 55 had a history of IgE-mediated reaction. Cephalosporin allergy was confirmed in 24/55 patients through sIgE or skin testing. Cefaclor sIgE was found in 4 patients.
Risk factors
Risk and predictive factors contribute to the stratification of patients’ risk of having genuine beta-lactam allergy, and thus to the choice of the diagnostic strategy.
Females and patients with penicillin allergy are at higher risk of cephalosporin allergy. A study found hypertension, liver disease, asthma, atopic dermatitis, urticaria, allergic conjunctivitis, and intake of non-steroidal anti-inflammatory drugs to be associated with immediate cefaclor allergy.
Pediatric issues
Beta-lactam antibiotics are the most prevalent medications that trigger allergic reactions in children. A retrospective cohort study on 83 pediatric patients (11 months to 12 years) with serum sickness-like reactions reported cephalosporin as the cause in 8.5% of cases. Cutaneous manifestations included erythema multiforme (38%), urticaria type (35%) and maculo-papular rashes (26%). Labial or palpebral edema was seen in 31%, fever was reported in 44.5% and edema with pain in hands and feet was found in 60% of all cases.
Route Of Exposure
Main
Cefaclor is only available for oral administration.
Clinical Relevance
Beat-lactam allergies are divided into two categories: immediate and delayed, each stemming from different immune responses. Immediate reactions happen within 1 to 6 hours of taking the drug, with symptom onset taking place during the first 15 minutes in 85% of patients and can range from urticaria to life-threatening anaphylaxis. Delayed reactions occur at least 6 hours after dosing, with a majority taking place 1 to 2 weeks after intake, and may present as benign maculopapular exanthema but severe, life-threatening presentations are also reported, such as DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) syndrome, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis.
A study identified 55 subjects with a history of cephalosporin-induced IgE-mediated hypersensitivity out of 564 subjects with a history of beta-lactam allergy. Clinical features of their reactions were erythema (36.3%), urticaria (30.9%), angioedema (21.8%), hypotension (16.3%), and bronchospasm (5.4%). Symptoms of nausea, vomiting and diarrhoea ocuured in 9% subjects.
A survey-based study reported 6883 cases of cefaclor and 15,024 cases of other cephalosporin-induced adverse drug reactions, of which cefaclor-induced manifestations were anaphylaxis (32.7%), urticaria (27%), and angioedema (7.7%). Severe adverse drug reactions such as disability, life-threatening conditions, prolonged hospitalization, death and others were found in 20.4% of cases of cefaclor hypersensitivity. Furthermore, another study with 459 cases of immediate cefaclor allergy found cutaneous manifestations in 73% of cases, followed by 61.2% cases of anaphylaxis, dyspnea/hypoxemia in 45.3%, angioedema in 31.8%, hypotension in 15.9 % cases, and 6.3% showing alternation in mental state. Similarly, a Korean study conducted on 47 patients with a history of immediate cefaclor hypersensitivity reported anaphylaxis as the most frequent (78.7%) manifestation of immediate reactions. Urticaria, along with/without angioedema, was found in 21.3% of cases. Moreover, anaphylaxis was also reported to be the most common (65.3%) clinical manifestation in a study of 1247 subjects with 193 patients having cefaclor allergy. Among the patients showing anaphylactic reactions, 9.5% patients had mild, 60.3% had moderate, and 30.2% had severe anaphylactic reactions.
A diagnosis of anaphylaxis to cefaclor was confirmed in two cases of adult female patients having a prior history of drug allergies. In both cases, a history of immediate reaction to cefaclor, skin prick tests positive for multiple allergens and a positive oral challenge with cefaclor were reported. Oral challenge with cefaclor resulted in vomiting, hypertension, itching and more severe symptoms at higher concentrations in the first case, while skin rash, breathing difficulty, chest tightness, edema and angioedema were reported in the second case.
A case series of immediate hypersensitive reactions to cefaclor in 7 females and 1 male was presented. Immediate reactions were manifested as angioedema, urticaria, generalized erythema and anaphylaxis.
Diagnostics
Clinical predictors for true beta-lactam allergies are lacking, hence suspected allergy cases need to be confirmed by specific IgE testing and if necessary, by an in vivo drug challenge test. Skin testing to cefaclor is not included in standard testing panels, but amoxicillin, which shares a similar R1 side chain with cefaclor, allows to identify R1-linked cross-reactivity. Serum specific IgE testing is safe, is not influenced by ongoing antihistamine medication and can be performed in primary care settings.
Serum-specific IgE (sIgE) tests or immunological assays that measure sIgE of beta-lactams have shown diagnostic performance comparable to skin tests. A study with 193 patients diagnosed with cefaclor allergy reported that a value of 0.11 kU/l of sIgE cefaclor was optimum for discriminating immediate cefaclor allergic reactions. The specificity and sensitivity for immediate cefaclor allergy at this cut-off were 81.6% and 80.2%.
Early investigation can be performed with specific IgE determination in acute samples obtained at the time of an immediate reaction. Specific IgE testing is recommended as the first-line investigation in high-risk patients, e.g. having experienced severe immediate reactions to beta-lactams. A clearly positive IgE test can be considered sufficient for the diagnosis of beta-lactam allergy in patients with an evocative clinical history, especially anaphylaxis
If specific IgE tests are negative, additional examinations with skin and drug provocation test become necessary.
Conversely, USA practice parameter recommends skin testing over blood IgE testing due to lower diagnostic sensitivity of the latter.
Prevention And Therapy
Avoidance
The reaction to cefaclor could be transient immunologically but clinically it could be persistent. Therefore, it is usually recommended to avoid the culprit cephalosporin along with similar beta-lactams. However, the rate of real-world cross-reactivity might be lower than inferred from chemical structures.
Cross-Reactivity
Cross-reactivity to cephalosporin allergy is attributed to the R1 side chain, which is the major antigenic component. The most common side chain, aminobenzene, is found among the aminopenicillin group (amoxicillin and ampicillin) and aminocephalosporins (cefaclor and cephalexin). Cross-reactivity can also involve only a part of R1 side chain or a combination of R1 (aminobenzyl) and R2 (chloro, methy or ester) groups. However, cephalosporin allergy in patients with penicillin allergy showed variation depending on the side chain similarity. On the other hand, allergic cross-reactivity between cephalosporins and carbapenems or aztreonam was found to be low.
Explained Results
Allergen information
Cefaclor is a semi-synthetic, broad-spectrum, second-generation cephalosporin
Clinical information
Cefaclor hypersensitivity reactions with a demonstrated adaptive immune mechanism are termed cefaclor allergy. Immediate ampicillin allergy (1-6 hours after administration) is IgE-dependent, while delayed ampicillin allergy (>6 hours after administration) is T cell-dependent. Like other beta-lactams, confirmed cefaclor allergy represents around 10% of patients with a label of cefaclor allergy, prompting recommendations for proactive allergy delabeling after risk stratification.
Cross-reactivity
Cefaclor carries a risk of cross reactivity with potential clinical relevance with aminopenicillins (amoxicillin and ampicillin) and aminocephalosporins (cephalexin).
References
- Baldo, B. A. and N. H. Pham (2013). β-Lactam Antibiotics. Drug Allergy: 129-181.
- Brockow, K., W. Pfutzner, B. Wedi, G. Wurpts, A. Trautmann, B. Kreft, T. Buhl, M. Sulk, A. Recke, K. Scherer, S. Wohrl, I. Neustadter, R. Treudler, C. Querbach and M. Worm (2025). "Recommendations on how to proceed in case of suspected allergy to penicillin/beta-lactam antibiotics: Position paper of the German Society for Allergology and Clinical Immunology (DGAKI) in cooperation with the German Society for Pediatric Allergology (GPA), Austrian Society for Allergology and Immunology (OGAI) and the Swiss Society for Allergology and Immunology (SGAI)." Allergol Select 9: 28-39.
- Caruso, C., R. L. Valluzzi, S. Colantuono, F. Gaeta and A. Romano (2021). "beta-Lactam Allergy and Cross-Reactivity: A Clinician's Guide to Selecting an Alternative Antibiotic." J Asthma Allergy 14: 31-46.
- Castells, M., D. A. Khan and E. J. Phillips (2019). "Penicillin Allergy." N Engl J Med 381(24): 2338-2351.
- Del Pozzo-Magana, B. R., A. Abuzgaia, B. Murray, M. J. Rieder and A. Lazo-Langner (2021). "Paediatric serum sickness-like reaction: A 10-year retrospective cohort study." Paediatr Child Health 26(7): 428-435.
- Demoly, P., N. F. Adkinson, K. Brockow, M. Castells, A. M. Chiriac, P. A. Greenberger, D. A. Khan, D. M. Lang, H. S. Park, W. Pichler, M. Sanchez-Borges, T. Shiohara and B. Y. Thong (2014). "International Consensus on drug allergy." Allergy 69(4): 420-437.
- Dona, I., M. Salas, E. Moreno, M. Ferrer, C. Mayorga and M. J. Torres (2025). "An algorithm for the diagnosis of beta-lactam allergy, 2024 update." Allergy 80(2): 633-637.
- Garvey, L. H., D. G. Ebo, P. M. Mertes, P. Dewachter, T. Garcez, P. Kopac, J. J. Laguna, A. M. Chiriac, I. Terreehorst, S. Voltolini and K. Scherer (2019). "An EAACI position paper on the investigation of perioperative immediate hypersensitivity reactions." Allergy 74(10): 1872-1884.
- Genis, H., M. Li, M. Eng-Chong, A. Zaltz, J. Tarshis, M. Elligsen, J. A. Leis and P. W. Lam (2023). "Optimizing Cefazolin Prophylaxis in Obstetrical Patients with Reported Beta-Lactam Allergy Undergoing Cesarean Delivery." J Obstet Gynaecol Can 45(8): 574-580.
- Khan, D. A., A. Banerji, K. G. Blumenthal, E. J. Phillips, R. Solensky, A. A. White, J. A. Bernstein, D. K. Chu, A. K. Ellis, D. B. K. Golden, M. J. Greenhawt, C. C. Horner, D. Ledford, J. A. Lieberman, J. Oppenheimer, M. A. Rank, M. S. Shaker, D. R. Stukus, D. Wallace, J. Wang, E. Chief, D. A. Khan, D. B. K. Golden, M. Shaker, D. R. Stukus, C. Workgroup, D. A. Khan, A. Banerji, K. G. Blumenthal, E. J. Phillips, R. Solensky, A. A. White, R. Joint Task Force on Practice Parameters, J. A. Bernstein, D. K. Chu, A. K. Ellis, D. B. K. Golden, M. J. Greenhawt, C. C. Horner, D. Ledford, J. A. Lieberman, J. Oppenheimer, M. A. Rank, M. S. Shaker, D. R. Stukus, D. Wallace and J. Wang (2022). "Drug allergy: A 2022 practice parameter update." J Allergy Clin Immunol 150(6): 1333-1393.
- Lendal, V., S. Fransson, H. Mosbech, J. B. Boel, N. Kahlhofen, L. H. Blom, L. K. Poulsen and L. H. Garvey (2025). "Clinical Relevance of Specific IgE in Penicillin Allergy Investigation." Int Arch Allergy Immunol 186(4):303-310.
- Liang, E. H., L. H. Chen and E. Macy (2020). "Adverse Reactions Associated with Penicillins, Carbapenems, Monobactams, and Clindamycin: A Retrospective Population-based Study." J Allergy Clin Immunol Pract 8(4): 1302-1313 e1302.
- Macy, E. and R. Contreras (2015). "Adverse reactions associated with oral and parenteral use of cephalosporins: A retrospective population-based analysis." J Allergy Clin Immunol 135(3): 745-752 e745.
- Macy, E., W. W. Crawford, M. T. Nguyen, J. L. Adams, E. A. McGlynn and T. A. McCormick (2022). "Population-Based Incidence of New Ampicillin, Cephalexin, Cefaclor, and Sulfonamide Antibiotic "Allergies" in Exposed Individuals with and without Preexisting Ampicillin, Cephalexin, or Cefaclor "Allergies"." J Allergy Clin Immunol Pract 10(2): 550-555.
- Nam, Y. H., S. H. Lee, H. I. Rhyou, Y. S. Lee, S. H. Park, Y. H. Lee, Y. S. Shin, H. S. Park and Y. M. Ye (2018). "Proper Cut-off Levels of Serum Specific IgE to Cefaclor for Patients with Cefaclor Allergy." Yonsei Med J 59(8): 968-974.
- NIH-Pubchem. (2024). "Cefaclor-structure." Retrieved 04.01.2024.
- Noh, G., B. S. Kim, W. J. Kim, C. W. v, C. W. Ha and I. B. Choi (2018). "Immunotherapy Using IFN-Gamma for Cefaclor Allergy: Case Reports." Journal of Allergy & Therapy 09(02).
- Perez-Cantero, A. and J. Guarro (2020). "Sarocladium and Acremonium infections: New faces of an old opportunistic fungus." Mycoses 63(11): 1203-1214.
- Ramsey, A. (2022). "Cephalexin, Cefaclor, and Ampicillin: Points in the Picture of beta-Lactam Cross-Reactivity." J Allergy Clin Immunol Pract 10(2): 556-557.
- Rhyou, H. I., G. E. Doo, J. Yoon, C. Y. Ha, H. J. Nam, S. D. Woo, Y. Lee, Y. H. Nam and Y. M. Ye (2021). "Clinical characteristics and risk factors for cefaclor-induced immediate hypersensitivity: a retrospective observation at two university hospitals in Korea." Allergy Asthma Clin Immunol 17(1): 20.
- Rhyou, H. I., Y. H. Nam, S. C. Kim, G. E. Doo, C. Y. Ha, H. J. Nam, S. D. Woo, Y. Lee, J. H. Jang, H. Y. Lee and Y. M. Ye (2021). "Cefaclor-induced hypersensitivity: Differences in the incidence of anaphylaxis relative to other 2nd and 3rd generation cephalosporins." PLoS One 16(7): e0254898.
- Romano, A., M. Atanaskovic-Markovic, A. Barbaud, A. J. Bircher, K. Brockow, J. C. Caubet, G. Celik, J. Cernadas, A. M. Chiriac, P. Demoly, L. H. Garvey, C. Mayorga, A. Nakonechna, P. Whitaker and M. J. Torres (2020). "Towards a more precise diagnosis of hypersensitivity to beta-lactams - an EAACI position paper." Allergy 75(6): 1300-1315.
- Romano, A., F. Gaeta, R. L. Valluzzi, C. Caruso, G. Rumi and P. J. Bousquet (2010). "IgE-mediated hypersensitivity to cephalosporins: cross-reactivity and tolerability of penicillins, monobactams, and carbapenems." J Allergy Clin Immunol 126(5): 994-999.
- Romano, A., R. L. Valluzzi, C. Caruso, M. Maggioletti, D. Quaratino and F. Gaeta (2018). "Cross-Reactivity and Tolerability of Cephalosporins in Patients with IgE-Mediated Hypersensitivity to Penicillins." J Allergy Clin Immunol Pract 6(5): 1662-1672.
- Romano, A., R. L. Valluzzi, C. Caruso, A. Zaffiro, D. Quaratino and F. Gaeta (2021). "Evaluating Immediate Reactions to Cephalosporins: Time Is of the Essence." The Journal of Allergy and Clinical Immunology: In Practice 9(4): 1648-1657.e1641.
- Siew, L. Q. C., P. H. Li, T. J. Watts, I. Thomas, K. L. Ue, M. R. Caballero, K. Rutkowski, S. J. Till, P. Pillai and R. Haque (2019). "Identifying Low-Risk Beta-Lactam Allergy Patients in a UK Tertiary Centre." J Allergy Clin Immunol Pract 7(7): 2173-2181 e2171.
- Springer (2021). "Cefaclor." Reactions Weekly 1843(4): 97.
- Stone, C. A., Jr., J. A. Trubiano and E. J. Phillips (2021). "Testing Strategies and Predictors for Evaluating Immediate and Delayed Reactions to Cephalosporins." J Allergy Clin Immunol Pract 9(1): 435-444 e413.
- Touati, N., B. Cardoso, M. Delpuech, R. Bazire, N. El Kara, D. Ouali, P. Demoly and A. M. Chiriac (2021). "Cephalosporin Hypersensitivity: Descriptive Analysis, Cross-Reactivity, and Risk Factors." J Allergy Clin Immunol Pract 9(5): 1994-2000 e1995.
- Yoo, H. S., S. H. Kim, H. S. Kwon, T. B. Kim, Y. H. Nam, Y. M. Ye and H. S. Park (2014). "Immunologic evaluation of immediate hypersensitivity to cefaclor." Yonsei Med J 55(6): 1473-1483.
- Yuson, C., K. Kumar, A. Le, A. Ahmadie, T. Banovic, R. Heddle, F. Kette, W. Smith and P. Hissaria (2019). "Immediate cephalosporin allergy." Intern Med J 49(8): 985-993.
- Zagursky, R. J. and M. E. Pichichero (2018). "Cross-reactivity in beta-Lactam Allergy." J Allergy Clin Immunol Pract 6(1): 72-81 e71.
- Zhou, L., N. Dhopeshwarkar, K. G. Blumenthal, F. Goss, M. Topaz, S. P. Slight and D. W. Bates (2016). "Drug allergies documented in electronic health records of a large healthcare system." Allergy 71(9): 1305-1313.