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Ceftaroline Desensitization Procedure in a Pregnant Patient With Multiple Drug Allergies

Ceftaroline Desensitization Procedure in a Pregnant Patient With Multiple Drug Allergies BRIEF R EP ORT [3–5]. When evaluating an inpatient with a history of multiple Ceftaroline Desensitization drug allergies to antibiotics, exonerating a reported drug allergy Procedure in a Pregnant Patient is challenging. Validated skin testing for immediate, type I HSR exists only for PCN, where the antigenic determinants have With Multiple Drug Allergies been identified [3–5]. Skin testing to most other drugs, although 1,2,a 1,2,3,a 1,2,4 not validated, may be performed using a nonirritating concen- James L. Kuhlen, Jr Kimberly G. Blumenthal, Caroline L. Sokol, 1,2 2,5 5,6 Diana S. Balekian, Ana A. Weil, Christy A. Varughese, tration (NIC) [5, 6] when this value has been previously 2,3,5,7 1,2 Erica S. Shenoy, and Aleena Banerji established. A drug graded challenge, or test dose, can be Division of Rheumatology, Allergy, and Immunology, Department of Medicine, performed when the reaction is unlikely to have an immuno- 2 3 Massachusetts General Hospital, Harvard Medical School, Medical Practice globulin (Ig)E-mediated mechanism or if skin testing is nega- Evaluation Center, Massachusetts General Hospital, Center for Immunology and tive [5–7]. A desensitization protocol can be used to safely Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Department of Medicine, Massachusetts General Hospital, Division of Infectious administer a drug if there is a history of IgE-mediated HSR, Diseases, Department of Medicine, Massachusetts General Hospital, positive skin testing, or if cross-reactivity within a drug class 6 7 Department of Pharmacy, Massachusetts General Hospital, and Infection is unknown and no reasonable alternative treatment options Control Unit, Massachusetts General Hospital, Boston are available [5, 6, 8, 9]. Given the lack of validated tools available to evaluate drug Validated skin testing is lacking for many drugs, including allergies, we report the case of a patient with history of multi- ceftaroline. The cross-reactivity between ceftaroline and ple β-lactam antibiotic allergies and methicillin-resistant other β-lactam antibiotics is unknown. We report a case of Staphylococcus aureus (MRSA) pneumonia treated with a pregnant patient with cystic fibrosis and multiple drug al- ceftaroline. She reported a history of HSR to both PCN and lergies who required ceftaroline for methicillin-resistant Staphylococcus aureus pneumonia and underwent an uncom- an advanced-generation cephalosporin and was managed plicated empiric desensitization procedure. safely using a desensitization procedure to ceftaroline. We discuss the chemical structure of ceftaroline and how Keywords. β-lactam; ceftaroline; cross-reactivity; desensiti- this might result in cross-reactivity with PCN and other zation procedure; drug allergy. cephalosporins. CASE PRESENTATION Adverse drug reactions (ADRs) account for 3%–6% of all hos- pital admissions and occur in 10%–15% of hospitalized patients A 29-year-old female G1P0 in her 12th week of pregnancy with [1]. Adverse drug reactions can be costly, life threatening, and ahistory of cystic fibrosis (CF) presented with cough and in- result in morbidity, prolonged hospitalization, and increased creased sputum production. She reported dyspnea on exertion, risk of mortality [1]. Approximately one quarter of all ADRs productive cough, sore throat, nasal congestion, and postnasal are attributed to drug hypersensitivity [2], with antibiotics rep- drip. In addition to CF, her medical history was notable for al- resenting the most frequently reported class of drugs causing lergic rhinitis, chronic rhinosinusitis with nasal polyposis, dia- hypersensitivity reactions (HSR). Penicillin (PCN) allergy betes mellitus, gastroesophageal reflux disease, pancreatic alone is documented in up to 15% of hospitalized patients insufficiency, and vitamin D deficiency. She had documented drug allergies to amoxicillin, piperacillin-tazobactam, cefepime, and vancomycin. On exam, she was tachycardic and hypoxemic Received 18 December 2014; accepted 27 February 2015. J. L. K. and K. G. B. contributed equally to this work. but hemodynamically stable. Auscultation identified crackles Correspondence: James L. Kuhlen Jr, MD, Massachusetts General Hospital, Cox 201 Allergy over the bilateral upper lung fields; radiographic images were Associates, Boston, MA 02114 (jkuhlen@partners.org). not obtained given the patient’s pregnancy. Laboratory evalua- Open Forum Infectious Diseases © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases tion included normal renal function. A sputum Gram stain re- Society of America. This is an Open Access article distributed under the terms of the Creative vealed abundant polymorphonuclear lymphocytes and few Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/ by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any squamous cells with a culture growth of few Pseudomonas aer- medium, provided the original work is not altered or transformed in any way, and that the work uginosa and abundant MRSA. The Infectious Diseases service is properly cited. For commercial re-use, please contact journals.permissions@oup.com. DOI: 10.1093/ofid/ofv027 was consulted and recommended ceftaroline as the optimal BRIEF REPORT OFID 1 � � treatment given the predominance of MRSA and ceftaroline’s MRSA disease, including MRSA pneumonia, is accumulating presumed safety in pregnancy (class B), compared with that [11–14]. of vancomycin and linezolid (both class C), and the patient’s reported allergy to vancomycin [10]. Given the patient’s multi- Ceftaroline: Adverse Reactions, Structure, and Potential ple allergies to β-lactam antibiotics, Allergy/Immunology (AI) Cross-Reactivity was consulted. The patient reported 3 prior reactions to PCN Cross-reactivity of ceftaroline with PCNs and other cephalo- and cephalosporins. Her first reaction was in childhood, char- sporins is reported; however, the exact risk of cross-reactivity acterized by immediate respiratory distress requiring an emer- is unknown [12]. Previously reported reactions to ceftaroline gency room treatment after receiving amoxicillin. At age 21, she include the following: positive Coomb’s test without hemoly- experienced diffuse urticaria after piperacillin-tazobactam ad- sis (11%); pruritus (3%–4%); rash (3%); vomiting (2%); elevat- ministration. Four months before her admission, she developed ed transaminases (2%); anaphylaxis (<2%); eosinophilia, diffuse urticaria after cefepime administration while hos- thrombocytopenia, or neutropenia (<2%); and urticaria pitalized for a CF exacerbation. From the allergy history, AI (<2%) [11, 13]. These reactions occur at a similar incidence consultation determined these reactions were most likely IgE- compared with other advanced-generation cephalosporins mediated and felt that the patient was at high risk for subse- [9, 13]. Prior studies evaluating allergy to β-lactam antibiotics quent PCN and cephalosporin allergic reactions. In light of have not included ceftaroline, and although NIC to many the clinical urgency to treat the MRSA pneumonia with associ- cephalosporins have been reported, there is no validated or ated hypoxemia aggressively in the setting of pregnancy, the published NIC for ceftaroline [14, 15]. Although ceftaroline lack of data on a NIC for ceftaroline, and the unknown cross- has been in use for over 4 years with existing reports of HSR reactivity between cefepime and ceftaroline, the patient was [13, 16], desensitization to ceftaroline has only recently been treated with ceftaroline using a 12-step drug desensitization described [15]. procedure that took approximately 5 hours to complete (Sup- In cephalosporin allergy, cross-reactivity exists; up to 37% of plementary Table 1) [3]. Before the desensitization, written patients who react to one cephalosporin react to a different informed consent was obtained. According to hospital policy, cephalosporin [16]. Data suggest that cephalosporin allergy is the patient’s desensitization procedure was conducted in an in- mediated by development of IgE antibodies against antigenic tensive care unit bed with orders for as-needed antiallergic determinants that are unique to cephalosporins (side chains medications including antihistamines, oral and parenteral ste- or R groups) or to determinants that are shared with other roids, and epinephrine. The patient tolerated the desensitization β-lactam drugs (eg, β-lactam ring) [17]. In later-generation procedure without adverse effects. She completed 14 days of cephalosporins, allergy is thought to be due to the R groups intravenous ceftaroline (600 milligrams twice daily) without rather than the β-lactam ring [17]. This is supported by clinical complications and returned to her baseline pulmonary status. data showing <1% cross-reactivity between PCNs and later- A full-term healthy male child was born 6 months after her generation cephalosporins [18]. admission. Ceftaroline contains a bicyclic ring with a 4-member β- lactam ring joined to a 6-member cephem ring (Figure 1) Indications for Cephalosporins and Ceftaroline [12]. Ceftaroline’s R1 group is defined by 2 parts: the 7-alpha- Cephalosporins are first-line antimicrobial treatment for iminoethoxy group and an aminothiadiazole group [12]. many common infections, including urinary tract infections, Ceftaroline’s R2 group is a 1,3-thiazole ring [12]. Structurally, healthcare-associated pneumonia, methicillin-sensitive S aureus ceftaroline’s R groups are less likely to be cross-reactive with (MSSA) bacteremia, endocarditis, and osteomyelitis. Hyper- other cephalosporins with 2 key exceptions: ceftobiprole medo- sensitivity reactions to cephalosporin antibiotics occur in caril, the other 5th-generation cephalosporin, and cefclidine, a 0.0001%–3% of administrations, with anaphylaxis comprising 4th-generation cephalosporin. Ceftobiprole medocaril is likely 0.0001%–0.1% of these HSR [4]. Patients with chronic or to be cross-reactive based on an identical R1 group. Cefclidine’s recurrent infections requiring repeat courses of antibiotics, R1 group differs from ceftaroline, containing 1 less carbon (7-α- such as those with CF, are at increased risk of HSR [9, 10]. iminomethoxyl group as opposed to iminoethoxy group), mak- Ceftaroline fosamil, a relatively new anti-MRSA “5th genera- ing cross-reactivity possible. More importantly, ceftaroline’sR tion” cephalosporin, was approved in the United States groups are dissimilar from those of the most commonly used in 2010 for treatment of complicated skin and soft tissue cephalosporins in the United States, including cephalexin, cefa- infections (SSTIs) and community-acquired pneumonia. Cef- zolin, ceftriaxone, ceftazidine, and cefepime, and is therefore taroline demonstrates activity against organisms including less likely to cause a reaction when administered in patients MRSA, MSSA, PCN-resistant Streptococcus pneumoniae,and with reported allergy to any of these antibiotics. Haemophilus influenzae [7, 11]. In addition to treating MRSA Although this structural information suggests that the patient SSTIs, postmarketing experience in the treatment of invasive would have likely tolerated ceftaroline, because of her poor 2 OFID BRIEF REPORT � � Figure 1. Chemical structure of β-lactam antibiotics. The chemical structures of ceftaroline as well as other β-lactam antibiotics to which the patient was allergic (amoxicillin, piperacillin, and cefepime). All structures contain a central β-lactam ring with distinct R groups. respiratory status and pregnancy, we determined that the safest dose (for ceftaroline, 0.0002 mg/mL). The only other published approach was administration of ceftaroline by desensitization. ceftaroline desensitization protocol used 14 steps, initiated at 0.0004 mg/mL, and took 3.75 hours to complete [15]. Protocols are chosen based on a patient’s risk of HSR, with the slowest CONCLUSIONS protocols recommended for patients at highest risk of HSR. Based on its structural properties, we hypothesize that cef- We report a case of ceftaroline desensitization in a patient with taroline may be tolerated in patients with a PCN or cephalospo- multiple β-lactam antibiotic allergies. The patient’s antibiotic rin allergy, although clinical data are needed to confirm these treatment plan was complicated by a well documented PCN hypotheses. In addition, more research to define a skin-testing and cephalosporin allergy, lack of validated skin testing to ceftaro- protocol should be established and validated to improve the care line, poor respiratory status, and need for aggressive therapy with of patients with multiple allergies to PCN and cephalosporin no reasonable alternative treatment options. Ceftaroline was con- antibiotics. sidered the optimal therapy given the patient’s diagnosis of MRSA pneumonia. Although the literature supports the safety of vanco- mycin in pregnancy despite its class C classification [19–23], our Supplementary Material patient additionally had a reported allergy to vancomycin, which Supplementary material is available online at Open Forum Infectious led to the selection of ceftaroline as the preferred therapy. Without Diseases (http://OpenForumInfectiousDiseases.oxfordjournals.org/). knowing the cross-reactivity of ceftaroline and cefepime or cef- taroline and PCN, drug desensitization was recommended and Acknowledgments tolerated. Similar to another recent report of ceftaroline desensi- Disclaimer. The content is solely the responsibility of the authors and tization [15], we were unable to tell whether the patient’s tolerance does not necessarily represent the official views of the National Institutes of of ceftaroline was due to lack of cross-reactivity or the result of a Health. Financial support. This work was supported by departmental successful desensitization procedure. funds. K. G. B. is supported by the National Institute of Allergy and Infec- The patient’s desensitization protocol was similar to previ- tious Diseases, National Institutes of Health (Award Number NIAID T32 ously published desensitizations [5, 8, 9], using a 12-step proto- HL116275); C. L. S. is supported by National Institutes of Health and the col beginning with a dilution of 1:100 000 of the therapeutic Asthma and Allergy Foundation of America; D. S. B. is supported by the BRIEF REPORT OFID 3 � � National Institute of Allergy and Infectious Diseases, National Institutes of 11. Pasquale TR, Tan MJ, Trienski TL, File TM Jr. Methicillin-resistant Health (Award Number NIAID T32 HL116275); A. A. W. is supported by Staphylococcus aureus nosocomial pneumonia patients treated with cef- National Institutes of Health (Award Number NIAID T32 AI070611976); taroline: retrospective case series of 10 patients. J Chemother 2015: and E. S. S. is supported by the National Institute of Allergy and Infectious 27:29–34. Diseases, National Institutes of Health (NIAID K01AI110524). 12. Laboratories F. TEFLARO® (ceftaroline fosamil) injection for intrave- Potential conflicts of interest. All authors: No reported conflicts. nous (IV) use. 2010:22. All authors have submitted the ICMJE Form for Disclosure of Potential 13. Stryjewski ME, Jones RN, Corey GR. Ceftaroline: clinical and microbi- Conflicts of Interest. Conflicts that the editors consider relevant to the con- ology experience with focus on methicillin-resistant Staphylococcus au- tent of the manuscript have been disclosed. reus after regulatory approval in the USA. Diagn Microbiol Infect Dis 2014; 81:183–8. 14. Casapao AM, Davis SL, Barr VO, et al. Large retrospective evaluation of References the effectiveness and safety of ceftaroline fosamil therapy. Antimicrob 1. Thong BY, Tan TC. Epidemiology and risk factors for drug allergy. Br J Agents Chemother 2014; 58:2541–6. Clin Pharmacol 2011; 71:684–700. 15. Jones JM, Richter LM, Alonto A, Leedahl DD. Desensitization to cef- 2. Kelly WN. Potential risks and prevention, part 1: fatal adverse drug taroline in a patient with multiple medication hypersensitivity reactions. events. Am J Health Syst Pharm 2001; 58:1317–24. Am J Health Syst Pharm 2015; 72:198–202. 3. Lee CW, Matulonis UA, Castells MC. Carboplatin hypersensitivity: a 6- 16. Daulat S, Solensky R, Earl HS, et al. Safety of cephalosporin administra- h 12-step protocol effective in 35 desensitizations in patients with gyne- tion to patients with histories of penicillin allergy. J Allergy Clin Immu- cological malignancies and mast cell/IgE-mediated reactions. Gynecol nol 2004; 113:1220–2. Oncol 2004; 95:370–6. 17. Pichichero ME. A review of evidence supporting the American 4. Kelkar PS, Li JT. Cephalosporin allergy. N Engl J Med 2001; 345:804–9. Academy of Pediatrics recommendation for prescribing cephalosporin 5. Drug allergy: an updated practice parameter. Ann Allergy Asthma Im- antibiotics for penicillin-allergic patients. Pediatrics 2005;115: munol 2010; 105:259–73. 1048–57. 6. Blumenthal KG, Saff RR, Banerji A. Evaluation and management of a 18. Pichichero ME, Zagursky R. Penicillin and cephalosporin allergy. Ann patient with multiple drug allergies. Allergy Asthma Proc 2014; Allergy Asthma Immunol 2014;112:404–12. 35:197–203. 19. Reyes MP, Ostrea EM, Cabinian AE, et al. Vancomycin during pregnan- 7. Iammatteo M, Blumenthal KG, Saff R, et al. Safety and outcomes of test cy: does it cause hearing loss or nephrotoxicity in the infant? Am J Ob- doses for the evaluation of adverse drug reactions: a 5-year retrospective stet Gynecol 1989; 161:977–81. review. J Allergy Clin Immunol Pract 2014; 2:768–74. 20. Bourget P, Fernandez H, Delouis C, Ribou F. Transplacental passage of 8. Hesterberg PE, Banerji A, Oren E, et al. Risk stratification for desensi- vancomycin during the second trimester of pregnancy. Obstet Gynecol tization of patients with carboplatin hypersensitivity: clinical presenta- 1991; 78(5 Pt 2):908–11. tion and management. J Allergy Clin Immunol 2009; 123:1262–7.e1. 21. MacCulloch D. Vancomycin in pregnancy. N Z Med J 1981; 93:93–4. 9. Castells MC, Tennant NM, Sloane DE, et al. Hypersensitivity reactions 22. Verani JR, McGee L, Schrag SJ. Prevention of perinatal group B strep- to chemotherapy: outcomes and safety of rapid desensitization in 413 tococcal disease–revised guidelines from CDC, 2010. MMWR Recomm cases. J Allergy Clin Immunol 2008; 122:574–80. Rep 2010; 59(RR–10):1–36. 10. File TM, Wilcox MH, Stein GE. Summary of ceftaroline fosamil clinical 23. ACOG Committee Opinion No. 485: Prevention of early-onset trial studies and clinical safety. Clin Infect Dis 2012; 55(Suppl 3): group B streptococcal disease in newborns. Obstet Gynecol 2011; 117: S173–80. 1019–27. 4 OFID BRIEF REPORT � � http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Open Forum Infectious Diseases Oxford University Press

Ceftaroline Desensitization Procedure in a Pregnant Patient With Multiple Drug Allergies

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Oxford University Press
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© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.
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DOI
10.1093/ofid/ofv027
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Abstract

BRIEF R EP ORT [3–5]. When evaluating an inpatient with a history of multiple Ceftaroline Desensitization drug allergies to antibiotics, exonerating a reported drug allergy Procedure in a Pregnant Patient is challenging. Validated skin testing for immediate, type I HSR exists only for PCN, where the antigenic determinants have With Multiple Drug Allergies been identified [3–5]. Skin testing to most other drugs, although 1,2,a 1,2,3,a 1,2,4 not validated, may be performed using a nonirritating concen- James L. Kuhlen, Jr Kimberly G. Blumenthal, Caroline L. Sokol, 1,2 2,5 5,6 Diana S. Balekian, Ana A. Weil, Christy A. Varughese, tration (NIC) [5, 6] when this value has been previously 2,3,5,7 1,2 Erica S. Shenoy, and Aleena Banerji established. A drug graded challenge, or test dose, can be Division of Rheumatology, Allergy, and Immunology, Department of Medicine, performed when the reaction is unlikely to have an immuno- 2 3 Massachusetts General Hospital, Harvard Medical School, Medical Practice globulin (Ig)E-mediated mechanism or if skin testing is nega- Evaluation Center, Massachusetts General Hospital, Center for Immunology and tive [5–7]. A desensitization protocol can be used to safely Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Department of Medicine, Massachusetts General Hospital, Division of Infectious administer a drug if there is a history of IgE-mediated HSR, Diseases, Department of Medicine, Massachusetts General Hospital, positive skin testing, or if cross-reactivity within a drug class 6 7 Department of Pharmacy, Massachusetts General Hospital, and Infection is unknown and no reasonable alternative treatment options Control Unit, Massachusetts General Hospital, Boston are available [5, 6, 8, 9]. Given the lack of validated tools available to evaluate drug Validated skin testing is lacking for many drugs, including allergies, we report the case of a patient with history of multi- ceftaroline. The cross-reactivity between ceftaroline and ple β-lactam antibiotic allergies and methicillin-resistant other β-lactam antibiotics is unknown. We report a case of Staphylococcus aureus (MRSA) pneumonia treated with a pregnant patient with cystic fibrosis and multiple drug al- ceftaroline. She reported a history of HSR to both PCN and lergies who required ceftaroline for methicillin-resistant Staphylococcus aureus pneumonia and underwent an uncom- an advanced-generation cephalosporin and was managed plicated empiric desensitization procedure. safely using a desensitization procedure to ceftaroline. We discuss the chemical structure of ceftaroline and how Keywords. β-lactam; ceftaroline; cross-reactivity; desensiti- this might result in cross-reactivity with PCN and other zation procedure; drug allergy. cephalosporins. CASE PRESENTATION Adverse drug reactions (ADRs) account for 3%–6% of all hos- pital admissions and occur in 10%–15% of hospitalized patients A 29-year-old female G1P0 in her 12th week of pregnancy with [1]. Adverse drug reactions can be costly, life threatening, and ahistory of cystic fibrosis (CF) presented with cough and in- result in morbidity, prolonged hospitalization, and increased creased sputum production. She reported dyspnea on exertion, risk of mortality [1]. Approximately one quarter of all ADRs productive cough, sore throat, nasal congestion, and postnasal are attributed to drug hypersensitivity [2], with antibiotics rep- drip. In addition to CF, her medical history was notable for al- resenting the most frequently reported class of drugs causing lergic rhinitis, chronic rhinosinusitis with nasal polyposis, dia- hypersensitivity reactions (HSR). Penicillin (PCN) allergy betes mellitus, gastroesophageal reflux disease, pancreatic alone is documented in up to 15% of hospitalized patients insufficiency, and vitamin D deficiency. She had documented drug allergies to amoxicillin, piperacillin-tazobactam, cefepime, and vancomycin. On exam, she was tachycardic and hypoxemic Received 18 December 2014; accepted 27 February 2015. J. L. K. and K. G. B. contributed equally to this work. but hemodynamically stable. Auscultation identified crackles Correspondence: James L. Kuhlen Jr, MD, Massachusetts General Hospital, Cox 201 Allergy over the bilateral upper lung fields; radiographic images were Associates, Boston, MA 02114 (jkuhlen@partners.org). not obtained given the patient’s pregnancy. Laboratory evalua- Open Forum Infectious Diseases © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases tion included normal renal function. A sputum Gram stain re- Society of America. This is an Open Access article distributed under the terms of the Creative vealed abundant polymorphonuclear lymphocytes and few Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/ by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any squamous cells with a culture growth of few Pseudomonas aer- medium, provided the original work is not altered or transformed in any way, and that the work uginosa and abundant MRSA. The Infectious Diseases service is properly cited. For commercial re-use, please contact journals.permissions@oup.com. DOI: 10.1093/ofid/ofv027 was consulted and recommended ceftaroline as the optimal BRIEF REPORT OFID 1 � � treatment given the predominance of MRSA and ceftaroline’s MRSA disease, including MRSA pneumonia, is accumulating presumed safety in pregnancy (class B), compared with that [11–14]. of vancomycin and linezolid (both class C), and the patient’s reported allergy to vancomycin [10]. Given the patient’s multi- Ceftaroline: Adverse Reactions, Structure, and Potential ple allergies to β-lactam antibiotics, Allergy/Immunology (AI) Cross-Reactivity was consulted. The patient reported 3 prior reactions to PCN Cross-reactivity of ceftaroline with PCNs and other cephalo- and cephalosporins. Her first reaction was in childhood, char- sporins is reported; however, the exact risk of cross-reactivity acterized by immediate respiratory distress requiring an emer- is unknown [12]. Previously reported reactions to ceftaroline gency room treatment after receiving amoxicillin. At age 21, she include the following: positive Coomb’s test without hemoly- experienced diffuse urticaria after piperacillin-tazobactam ad- sis (11%); pruritus (3%–4%); rash (3%); vomiting (2%); elevat- ministration. Four months before her admission, she developed ed transaminases (2%); anaphylaxis (<2%); eosinophilia, diffuse urticaria after cefepime administration while hos- thrombocytopenia, or neutropenia (<2%); and urticaria pitalized for a CF exacerbation. From the allergy history, AI (<2%) [11, 13]. These reactions occur at a similar incidence consultation determined these reactions were most likely IgE- compared with other advanced-generation cephalosporins mediated and felt that the patient was at high risk for subse- [9, 13]. Prior studies evaluating allergy to β-lactam antibiotics quent PCN and cephalosporin allergic reactions. In light of have not included ceftaroline, and although NIC to many the clinical urgency to treat the MRSA pneumonia with associ- cephalosporins have been reported, there is no validated or ated hypoxemia aggressively in the setting of pregnancy, the published NIC for ceftaroline [14, 15]. Although ceftaroline lack of data on a NIC for ceftaroline, and the unknown cross- has been in use for over 4 years with existing reports of HSR reactivity between cefepime and ceftaroline, the patient was [13, 16], desensitization to ceftaroline has only recently been treated with ceftaroline using a 12-step drug desensitization described [15]. procedure that took approximately 5 hours to complete (Sup- In cephalosporin allergy, cross-reactivity exists; up to 37% of plementary Table 1) [3]. Before the desensitization, written patients who react to one cephalosporin react to a different informed consent was obtained. According to hospital policy, cephalosporin [16]. Data suggest that cephalosporin allergy is the patient’s desensitization procedure was conducted in an in- mediated by development of IgE antibodies against antigenic tensive care unit bed with orders for as-needed antiallergic determinants that are unique to cephalosporins (side chains medications including antihistamines, oral and parenteral ste- or R groups) or to determinants that are shared with other roids, and epinephrine. The patient tolerated the desensitization β-lactam drugs (eg, β-lactam ring) [17]. In later-generation procedure without adverse effects. She completed 14 days of cephalosporins, allergy is thought to be due to the R groups intravenous ceftaroline (600 milligrams twice daily) without rather than the β-lactam ring [17]. This is supported by clinical complications and returned to her baseline pulmonary status. data showing <1% cross-reactivity between PCNs and later- A full-term healthy male child was born 6 months after her generation cephalosporins [18]. admission. Ceftaroline contains a bicyclic ring with a 4-member β- lactam ring joined to a 6-member cephem ring (Figure 1) Indications for Cephalosporins and Ceftaroline [12]. Ceftaroline’s R1 group is defined by 2 parts: the 7-alpha- Cephalosporins are first-line antimicrobial treatment for iminoethoxy group and an aminothiadiazole group [12]. many common infections, including urinary tract infections, Ceftaroline’s R2 group is a 1,3-thiazole ring [12]. Structurally, healthcare-associated pneumonia, methicillin-sensitive S aureus ceftaroline’s R groups are less likely to be cross-reactive with (MSSA) bacteremia, endocarditis, and osteomyelitis. Hyper- other cephalosporins with 2 key exceptions: ceftobiprole medo- sensitivity reactions to cephalosporin antibiotics occur in caril, the other 5th-generation cephalosporin, and cefclidine, a 0.0001%–3% of administrations, with anaphylaxis comprising 4th-generation cephalosporin. Ceftobiprole medocaril is likely 0.0001%–0.1% of these HSR [4]. Patients with chronic or to be cross-reactive based on an identical R1 group. Cefclidine’s recurrent infections requiring repeat courses of antibiotics, R1 group differs from ceftaroline, containing 1 less carbon (7-α- such as those with CF, are at increased risk of HSR [9, 10]. iminomethoxyl group as opposed to iminoethoxy group), mak- Ceftaroline fosamil, a relatively new anti-MRSA “5th genera- ing cross-reactivity possible. More importantly, ceftaroline’sR tion” cephalosporin, was approved in the United States groups are dissimilar from those of the most commonly used in 2010 for treatment of complicated skin and soft tissue cephalosporins in the United States, including cephalexin, cefa- infections (SSTIs) and community-acquired pneumonia. Cef- zolin, ceftriaxone, ceftazidine, and cefepime, and is therefore taroline demonstrates activity against organisms including less likely to cause a reaction when administered in patients MRSA, MSSA, PCN-resistant Streptococcus pneumoniae,and with reported allergy to any of these antibiotics. Haemophilus influenzae [7, 11]. In addition to treating MRSA Although this structural information suggests that the patient SSTIs, postmarketing experience in the treatment of invasive would have likely tolerated ceftaroline, because of her poor 2 OFID BRIEF REPORT � � Figure 1. Chemical structure of β-lactam antibiotics. The chemical structures of ceftaroline as well as other β-lactam antibiotics to which the patient was allergic (amoxicillin, piperacillin, and cefepime). All structures contain a central β-lactam ring with distinct R groups. respiratory status and pregnancy, we determined that the safest dose (for ceftaroline, 0.0002 mg/mL). The only other published approach was administration of ceftaroline by desensitization. ceftaroline desensitization protocol used 14 steps, initiated at 0.0004 mg/mL, and took 3.75 hours to complete [15]. Protocols are chosen based on a patient’s risk of HSR, with the slowest CONCLUSIONS protocols recommended for patients at highest risk of HSR. Based on its structural properties, we hypothesize that cef- We report a case of ceftaroline desensitization in a patient with taroline may be tolerated in patients with a PCN or cephalospo- multiple β-lactam antibiotic allergies. The patient’s antibiotic rin allergy, although clinical data are needed to confirm these treatment plan was complicated by a well documented PCN hypotheses. In addition, more research to define a skin-testing and cephalosporin allergy, lack of validated skin testing to ceftaro- protocol should be established and validated to improve the care line, poor respiratory status, and need for aggressive therapy with of patients with multiple allergies to PCN and cephalosporin no reasonable alternative treatment options. Ceftaroline was con- antibiotics. sidered the optimal therapy given the patient’s diagnosis of MRSA pneumonia. Although the literature supports the safety of vanco- mycin in pregnancy despite its class C classification [19–23], our Supplementary Material patient additionally had a reported allergy to vancomycin, which Supplementary material is available online at Open Forum Infectious led to the selection of ceftaroline as the preferred therapy. Without Diseases (http://OpenForumInfectiousDiseases.oxfordjournals.org/). knowing the cross-reactivity of ceftaroline and cefepime or cef- taroline and PCN, drug desensitization was recommended and Acknowledgments tolerated. Similar to another recent report of ceftaroline desensi- Disclaimer. The content is solely the responsibility of the authors and tization [15], we were unable to tell whether the patient’s tolerance does not necessarily represent the official views of the National Institutes of of ceftaroline was due to lack of cross-reactivity or the result of a Health. Financial support. This work was supported by departmental successful desensitization procedure. funds. K. G. B. is supported by the National Institute of Allergy and Infec- The patient’s desensitization protocol was similar to previ- tious Diseases, National Institutes of Health (Award Number NIAID T32 ously published desensitizations [5, 8, 9], using a 12-step proto- HL116275); C. L. S. is supported by National Institutes of Health and the col beginning with a dilution of 1:100 000 of the therapeutic Asthma and Allergy Foundation of America; D. S. B. is supported by the BRIEF REPORT OFID 3 � � National Institute of Allergy and Infectious Diseases, National Institutes of 11. Pasquale TR, Tan MJ, Trienski TL, File TM Jr. Methicillin-resistant Health (Award Number NIAID T32 HL116275); A. A. W. is supported by Staphylococcus aureus nosocomial pneumonia patients treated with cef- National Institutes of Health (Award Number NIAID T32 AI070611976); taroline: retrospective case series of 10 patients. J Chemother 2015: and E. S. S. is supported by the National Institute of Allergy and Infectious 27:29–34. Diseases, National Institutes of Health (NIAID K01AI110524). 12. Laboratories F. TEFLARO® (ceftaroline fosamil) injection for intrave- Potential conflicts of interest. All authors: No reported conflicts. nous (IV) use. 2010:22. 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Hypersensitivity reactions 22. Verani JR, McGee L, Schrag SJ. Prevention of perinatal group B strep- to chemotherapy: outcomes and safety of rapid desensitization in 413 tococcal disease–revised guidelines from CDC, 2010. MMWR Recomm cases. J Allergy Clin Immunol 2008; 122:574–80. Rep 2010; 59(RR–10):1–36. 10. File TM, Wilcox MH, Stein GE. Summary of ceftaroline fosamil clinical 23. ACOG Committee Opinion No. 485: Prevention of early-onset trial studies and clinical safety. Clin Infect Dis 2012; 55(Suppl 3): group B streptococcal disease in newborns. Obstet Gynecol 2011; 117: S173–80. 1019–27. 4 OFID BRIEF REPORT � �

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Published: Jan 1, 2015

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