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Allergic Cross-Reactivity Among -Lactam Antibiotics (In patients with penicillin allergies)

Allergic Cross-Reactivity Among -Lactam Antibiotics (In patients with penicillin allergies). Tracey ngo COH Medicine Rotation Western University of Health Sciences College of Pharmacy May 3, 2011. Overview. Patient case Background Penicillin Allergies

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Allergic Cross-Reactivity Among -Lactam Antibiotics (In patients with penicillin allergies)

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  1. Allergic Cross-ReactivityAmong-Lactam Antibiotics(In patients with penicillin allergies) Tracey ngo COH Medicine Rotation Western University of Health Sciences College of Pharmacy May 3, 2011

  2. Overview • Patient case • Background • Penicillin Allergies • Structural differences among beta lactam antibiotics • Historical data on allergic cross reactivity • Current data on allergic cross reactivity rate: cephalosporin, carbapenem, and monobactam • IDSA guidelines for Febrile Neutropenia • Treatment for patients with penicillin allergies • Conclusion • Recommendation

  3. Learning Objectives • Distinguish between IgE and non IgE mediated allergic reactions • Describe factors that affect cross reactivity • List the cross reactivity rate among the beta lactam antibiotics in patients with penicillin allergies • Make recommendations for patients with penicillin allergies

  4. Patient Case • YK is a 36 y/o Asian male with a hx of refractory non-Hodgkin’s lymphoma (NHL) who is currently on cycle #1 of a clinical trial drug SGN 75. • HPI: • Diagnosed with Hodgkin’s lymphoma stage 2A on Feb, 2010 which progressed to large B-cell NHL • Subjectives: • SOB, chest pain, significant cough, intermittent fever, and tingling & numbness in R arm to hand • Objectives: • Weight 74 kg, height 168 cm • Physical Exam: • Head and Neck: shows clear oropharynx. A large mass in the R cervical to supraclavicular areas • Lungs: coarse BS and occasional rhonchi. Diminished BS in the R, but air movement is present • EXTREMITIES: Shows 1+ ankle edema. • I/O: 1860/925 • Current Admission on 4/25/11 to COH for pain control

  5. Patient Case (continue) • PMH: • Hypertriglyceridemia, sleep apnea • SH: • Smoked <1/2 pack per day x 20 yrs but quit in 2010 • Occasional drinker • FH: • Maternal family: multiple cancers including leukemia but no lymphoma • Details unavailable

  6. Patient Case (Pertinent Values) • CBC: • WBC: 10.3 • Hgb/Hct: 9.9/30.7 • Platelet: 65, 000 • Vital Signs: • Temperature 37.2°C • HR 119 • RR 16 • BP 108/73 • O2 sat 99% • Pain Scale: 6-9/10

  7. Patient Case (continue) • Current Medications: • Ceftazidime 2g IV Q8H PRNtemp • Cefazolin 2g IV Q8H PRNtemp • Fentanyl (100mcg/hr) 1 patch Q72H • Fentanyl PCA • Basal: 25 mcg/hr • Bolus: 25 mcg Q15 min • Xopenex 1 puff Q6H (COH TEAM) • Benzonatate 200mg PO Q8H for cough • Hycodan 5ml PO Q4HPRN for cough • Acetaminophen 650 mg PO Q4H PRN temp >38°C • Allergies: • Penicillin G (hives and throat swelling)

  8. PICO • P: adult with a penicillin allergy • I: beta lactam antibiotics • C: n/a • O: allergic cross reactivity rate • Question: what is the allergic cross reactivity rate among the beta lactam antibiotics in an adult with a penicillin allergy?

  9. Background -Penicillin Allergy in ~10% of the population -In a patient with penicillin allergy, historical data suggest cross reactivity rate: Cephalosporin: 5-15% carbapenem: 50% Aztreonam: 1-2% Torres MJ, Blanca M (2010). The complex clinical picture of B-lactam hypersensitivity: penicillins, cephalosporins, monobactams, carbapenems, and clavams. Med Clin N Am 94:805-820

  10. Structural Similarities Penicillin Cephalosporin Carbapenem Monobactam (Aztreonam) http://en.wikipedia.org/wiki/Beta-lactam_antibiotic

  11. Cross-Reactivity with Cephalosporin Based on the review by Petz in 1978, the cross reactivity rate of cephalosporin in patients with penicillin allergies was estimated as 6.2% Petz LD (1978) Immunologic cross-reactivity between penicillins and cephalosporins: a review. J Infect Dis 137: S74-S79

  12. Cross-Reactivity with Cephalosporin • Limitations of the study by Petz: • Allergy based on patient history-majority may be SE (N/V/D, nonspecific rash, idiopathic rxn) and not true allergies • Allergy was loosely defined • Not all were IgE mediated hypersensitivity reaction (only true allergic reactions) • Did not consider 3 fold increased risk of ADR to any unrelated drugs in PCN allergic patients • Early 1st gen-cephalosporin was produced by Cephalosporium spp mold contaminated with trace amounts of PCN (not seen with currently available cephalosporin) • Did not perform statistical analysis Petz LD (1978) Immunologic cross-reactivity between penicillins and cephalosporins: a review. J Infect Dis 137: S74-S79

  13. Cross-Reactivity with Cephalosporin • According to a review by Pichichero, the cross reactivity rate: • Based on the differences: • Chemical structure (S ring and side chain(s)) • Degradation process • Cross-reactivity between cephalosporin and penicillin should be minimal • Overall, the actual allergic cross reactivity among cephalosporin in penicillin allergic patients is <1% which is a lot lower than previously thought • However, the data is not statistically significant Pichichero ME (2005) A review of evidence supporting the American Academy of Pediatrics recommendation for prescribing cephalosporin antibiotics for penicillin-allergic patients. Pediatrics 115: 1048-1057

  14. Pichichero ME (2007) Use of selected cephalosporins in penicillin-allergic patients: a paradigm shift. Diagnostic Microbiology and Infectious Disease 57: 13S-18S

  15. Pichichero ME (2007) Use of selected cephalosporins in penicillin-allergic patients: a paradigm shift. Diagnostic Microbiology and Infectious Disease 57: 13S-18S

  16. Cross-Reactivity with Cephalosporin • Study Subjects: 534,810 • Record allergic reaction within 30 days • Allergic reaction defined as: • Anaphylaxis, urticaria, angioedema, erythema multiforme, laryngeal spasm, drug-induced dermatitis, and toxic epidermal necrolysis • Results: cross reactivity is ~1% Apter AJ, Kinman JL, Bilker WB, et al. Is there cross-reactivity between penicillins and cephalosporins? Am J Med. 2006; 119(4):354 e311-359

  17. Cross-Reactivity with Carbapenem Frumin J, Gallagher JC (2009). Allergic Cross Sensitivity Between Penicillin, Carbapenem, and Monobactam Antibiotics: What Are the Chances? The Annals of Pharmacotherapy 43: 304-315

  18. Cross-Reactivity with Carbapenem • Limitations of retrospective studies: • Broad definition of allergic rxn which included fever, rash, hematologic abnormalities (leukopenia or thrombocytopenia)not IgE mediated • Rely on patient history • No penicillin skin test80-90% of not true penicillin allergy Frumin J, Gallagher JC (2009). Allergic Cross Sensitivity Between Penicillin, Carbapenem, and Monobactam Antibiotics: What Are the Chances? The Annals of Pharmacotherapy 43: 304-315

  19. Cross-Reactivity with Carbapenem Frumin J, Gallagher JC (2009). Allergic Cross Sensitivity Between Penicillin, Carbapenem, and Monobactam Antibiotics: What Are the Chances? The Annals of Pharmacotherapy 43: 304-315

  20. Cross-Reactivity with Carbapenem • Recent prospective studies: • In penicillin allergic patients->negative carbapenem skin test • Indicates tolerabilityappears safe to use • Currently, no studies on doripenem or ertapenem cross reactivity Frumin J, Gallagher JC (2009). Allergic Cross Sensitivity Between Penicillin, Carbapenem, and Monobactam Antibiotics: What Are the Chances? The Annals of Pharmacotherapy 43: 304-315

  21. Cross-Reactivity with Monobactam • Clinically, no record of hypersensitivity reaction when receive IV aztreonam except in cystic fibrosis population • Cannot be generalized to the general population because CF population is more prone to developing hypersensitivity reaction to medications. • Difficult to assess if the hypersensitivity reaction is due to: • The cross sensitivity between penicillin and aztreonam • The high rate of generalized immune responsiveness in CF population • Most likely since the reaction was not immediate (not IgE mediated) Frumin J, Gallagher JC (2009). Allergic Cross Sensitivity Between Penicillin, Carbapenem, and Monobactam Antibiotics: What Are the Chances? The Annals of Pharmacotherapy 43: 304-315

  22. Cross-Reactivity with Monobactam • Exception: • Moss et al: cross reactivity rate in ceftazidime allergy patients and aztreonam is 16.7% • Bronchospasm and angioedema • Aztreonam and ceftazidime have the same side chain • Potential for cross reactivity exist in patients with a specific allergy to ceftazidime • avoid using aztreonam in these patients Ceftazidime Aztreonam Frumin J, Gallagher JC (2009). Allergic Cross Sensitivity Between Penicillin, Carbapenem, and Monobactam Antibiotics: What Are the Chances? The Annals of Pharmacotherapy 43: 304-315

  23. Cross-Reactivity with Monobactam Aztreonam Ceftazidime http://en.wikipedia.org/wiki/Beta-lactam_antibiotic

  24. Return to Patient Case Is cefazolin and ceftazidime appropriate for YK given his penicillin allergy? Pichichero ME (2007) Use of selected cephalosporins in penicillin-allergic patients: a paradigm shift. Diagnostic Microbiology and Infectious Disease 57: 13S-18S

  25. IDSA Guidelines for Febrile Neutropenia http://guidelinecentral.com/viewers/FeverNeutropenia.html

  26. Conclusion • In general, those with an immediate (IgE mediated) hypersensitivity reaction to penicillin should not receive any penicillin and its derivatives unless they undergo desensitization • Although recent studies stated that newer generations of cephalosporin may be used in patients with immediate hypersensitivity reaction to penicillin • However, this should be done cautiously since there is still a possible risk of allergic cross reaction in these patients. • According to IDSA guidelines cephalosporin should be avoided in patients with an immediate hypersensitivity reaction to penicillin.

  27. Penicillin Desensitization Solensky R. Hypersensitivity reactions to beta-lactam antibiotics. Clin Rev Allergy Immunol. Jun 2003;24(3):201-220

  28. Penicillin Desensitization Solensky R. Hypersensitivity reactions to beta-lactam antibiotics. Clin Rev Allergy Immunol. Jun 2003;24(3):201-220

  29. Let’s Vote Based on all the studies and data available, which option would you have chosen for YK? a. Ceftazidime and cefazolin b. Aztreonam and vancomycin c. Avoid all beta lactam antibiotics

  30. Recommendation • Even though the cross reactivity among cephalosporin and penicillin allergy is low (~1%) • Looking at the severity of YK’s hypersensitivity reaction to Penicillin G • Recommend against the use of cephalosporin • Based on the information from the different studies and IDSA guidelines for Febrile Neutropenia, I would recommend: • Aztreonam and vancomycin

  31. References • Apter AJ, Kinman JL, Bilker WB, et al. Is there cross-reactivity between penicillins and cephalosporins? Am J Med. 2006; 119(4):354 e311-359 • Frumin J, Gallagher JC (2009). Allergic Cross Sensitivity Between Penicillin, Carbapenem, and Monobactam Antibiotics: What Are the Chances? The Annals of Pharmacotherapy 43: 304-315 • http://en.wikipedia.org/wiki/Beta-lactam_antibiotic. Access April 30, 2011 • IDSA 2011 guidelines pocketcard on Febrile Neutropenia in Cancer Patients. http://guidelinecentral.com/viewers/FeverNeutropenia.html. Access April 20, 2011 • Petz LD (1978) Immunologic cross-reactivity between penicillins and cephalosporins: a review. J Infect Dis 137: S74-S79 • Pichichero ME (2005) A review of evidence supporting the American Academy of Pediatrics recommendation for prescribing cephalosporin antibiotics for penicillin-allergic patients. Pediatrics 115: 1048-1057 • Pichichero ME (2007) Use of selected cephalosporins in penicillin-allergic patients: a paradigm shift. Diagnostic Microbiology and Infectious Disease 57: 13S-18S • Solensky R. Hypersensitivity reactions to beta-lactam antibiotics. Clin Rev Allergy Immunol. Jun 2003;24(3):201-220 • Torres MJ, Blanca M (2010). The complex clinical picture of B-lactam hypersensitivity: penicillins, cephalosporins, monobactams, carbapenems, and clavams. Med Clin N Am 94:805-820

  32. Thank You

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