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Clinical Impact of Penicillin or Cephalosporin Allergy

Clinical Impact of Penicillin or Cephalosporin Allergy. By Linda Paul, PharmD, BCPS. Disclosure. I have no financial relationships or conflicts of interest to disclose. Pharmacist Objectives. Pharmacy Technician Objectives.

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Clinical Impact of Penicillin or Cephalosporin Allergy

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  1. Clinical Impact of Penicillin or Cephalosporin Allergy By Linda Paul, PharmD, BCPS

  2. Disclosure I have no financial relationships or conflicts of interest to disclose.

  3. Pharmacist Objectives

  4. Pharmacy TechnicianObjectives

  5. What percentage of the US population is considered allergic to Penicillin? • 10% • 30% • 50% • 70% Picture Adapted: hudsonvalleygeologist.blogspot.com

  6. Epidemiology Picture Adapted: https://penallergytest.com/pst-clinical-facts/

  7. Incidence and Implication • Penicillin allergy is reported by 10% -15% of the U.S. population • Incidence of cephalosporin hypersensitivity reaction ranges from 1% to 3% • Major public health implication • Increased use of alternate antibiotics • Added health care cost 1. K.G. Blumenthal et al. Ann Allergy Asthma Immunol. 2015; 115: 294-300 2. DePestel, D, et al. J Am Pharm Assoc. 2008; 48:530-540

  8. Implication • Additional implication • Increased risk of multi-drug resistant pathogens • Increased risk of Clostridium difficile infection • After PCN skin testing, 90% -99% of patients with reported PCN allergy can tolerate PCNs • Mislabeling of a reaction (eg. diarrhea) as allergic • Waning of penicillin-specific IgE antibodies over time 1. K.G. Blumenthal et al. Ann Allergy Asthma Immunol. 2015; 115: 294-300 2. Gonzalez-Estrada et al. ClevClincJourn Med. 2015; 82 (5): 295-299

  9. Gell and Coombs Classification of Drug Allergy Gonzalez-Estrada et al. ClevClincJourn Med. 2015; 82 (5): 295-299

  10. Pathophysiology • All beta-lactam antibiotics share a common ring structure • They differ in their side chains (R group) • The core ring structure is metabolized • Major metabolite (penicilloyl) • Minor metabolite (penicilloate, penilloate) • Metabolites may trigger an immediate IgE-dependent response • Immunologic determinants of non penicillin B-lactam antibiotics are unknown Bhattacharya, S. J Adv Pharm Technol Res. 2010; 1(1): 11–17

  11. Cross-reactivity • Cross-reactivity among beta-lactam antibiotics are due to similarity in the R-side chain Solensky, R, et al. Ann Allergy Asthma Immunol. 2010; 273 (105): 47-48

  12. Cross-reactivity between PCN and Beta-lactam Antibiotics 1. Pichichero, M, et al. Ann Allergy Asthma Immunol. 2014; 112: 404-412 2. Gonzalez-Estrada et al. ClevClincJourn Med. 2015; 82 (5): 295-299

  13. Cross-reactivity between CEPH and Beta-lactam Antibiotics *Avoid aztreonam if pt. has had previous reaction to ceftazidime Pichichero, M, et al. Ann Allergy Asthma Immunol. 2014; 112: 404-412

  14. Cross Reactivity Based On Side-chain Similarity Bhattacharya, S. J Adv Pharm Technol Res. 2010; 1(1): 11–17 Ledford, D. J Allergy ClinImmunolPract. 2015; 3: 1006-7

  15. Cross Reactivity Based On Side-chain Similarity Bhattacharya, S. J Adv Pharm Technol Res. 2010; 1(1): 11–17 Ledford, D. J Allergy ClinImmunolPract. 2015; 3: 1006-7

  16. What is the Clinical Impact? Picture Adapted: https://penallergytest.com/pst-clinical-facts/

  17. Study Objective • To assess physician prescribing practices in patients with penicillin (PCN) or cephalosporin (CEPH) allergy

  18. Methods • Single center, retrospective, observational quality improvement project • Mission Trail Baptist Hospital (MTBH) between January 1, 2015 to June 30, 2015 • Patient population • Patients with PCN or CEPH allergy • Received antibiotics for > 1 day

  19. Methods • The following data were collected from the electronic medical record: • Allergic reaction and severity • Indication for treatment • Prescribed antibiotics, their dose, frequency and duration • Antibiotic cost was obtained from wholesaler ordering system • Drug of choice for various diseases was found in medical references and guidelines

  20. Demographics Patients discharged from MTBH from January-June 2015 (N = 3,247) • Inclusion Criteria: • Patients with PCN or CEPH allergy • Received antibiotics for > 1 day Patients meeting inclusion criteria (N = 265)

  21. Results • 265 (8.2%) of the 3,247 patients had a PCN or CEPH allergy and received antibiotics for > 1 day

  22. Results • The type of allergic reaction was not documented in 181 (67%) of the 265 patients

  23. Results • 48 (18.1%) of the 265 patients received a PCN or CEPH • In most of these patients, the type of allergic reaction was unknown

  24. Results • 217 (78.8%) of the 265 patients did not receive PCN or CEPH • 191 (88.0%) of the 217 had an indication for receiving PCN or CEPH as the preferred drug based on consensus guidelines

  25. Clinical Impact Of PCN/CEPH Allergy • Patients labeled PCN or CEPH allergy were either treated with • Less effective alternative • Broad-spectrum antibiotics * Antibiotic choices in Respiratory Infections

  26. Cost Of Antibiotics By Infection

  27. Study Summary • Reported prevalence of PCN/CEPH allergy at MTBH is less than 10% • Need accurate documentation of allergic reaction on patient records • Physicians prescribed a PCN or CEPH antibiotic in <20% of patients with an allergy • 88% of these patient had an indication for receiving beta-lactam antibiotics based on consensus guidelines • Most commonly used alternate antibiotics were either levofloxacin or meropenem • Some prescribing choices could be attributed to PCN allergy alternative in order sets

  28. Limitations • Single center, observation, retrospective analysis • Low rate of documented allergic reaction • Difficult to assess why some antibiotic choice were selected due to some patients presenting with multiple infections and comorbidities

  29. Clinical Assessment and Testing • Detailed History • Time course, character, severity of the reaction • History of reaction to other B-lactam antibiotics • Previous skin testing • Skin Testing • Graded Challenge/Test Dose • Desensitization Blumenthal, K, et al. J allergy clinImmunol. 2017; 140 (1): 154-161. e6

  30. Algorithm for PCN Allergy Mild Reaction (Skin rash) Type II – IV reaction Type 1 reaction Use 3rd, 4th or 5th generation CEPH (Full Dose) Or Use Test Dose PCN family or CEPH (1st or 2nd generation) Avoid PCN or CEPH Or Alternative agents by microbial coverage Use CEPH (3rd/4th/5th generation) Or Alternative agents by microbial coverage Blumenthal, K, et al. J allergy clinImmunol. 2017; 140 (1): 154-161. e6

  31. Algorithm for CEPH Allergy CEPH Administration PCN Administration Via graded challenge, give cephalosporin that does not share identical side chain Give PCN via graded challenge OR OR PCN Skin Testing Negative: Give PCN Positive: Alternate agent Alternate agent Blumenthal, K, et al. J allergy clinImmunol. 2017; 140 (1): 154-161. e6

  32. Take Away Points

  33. Thank you • Dr. Manuel Estrada, MD • Dr. Kevin Purcell, MD, PharmD, MHA • Dr. Armando Garcia, PharmD • Dr. Andre Andalcio, PharmD, BCPS

  34. Cross reactivity between PCN and CEPH antibiotics varies depending on the side chain and the generation of the cephalosporin.

  35. Patients with documentation of a mild allergic reaction to penicillin could receive:

  36. Patient Case • 65-year-old male • C/C: Rash which developed on his left lower leg four days ago with increased swelling and erythema • Vitals on admission: Temp 102.1F, blood pressure 93/50, pulse 102, respiratory rate 22, • Emergently intubated and admitted to the ICU with diagnosis of sepsis secondary to skin source • On patient record, penicillin allergy is documented • No family present on admission • Started on vancomycin and aztreonam

  37. Patient Progression • Blood culture positive for methicillin-sensitive Staphylococcus aureus • Sepsis determined to be due to MSSA bacteremia secondary to cellulitis • Aztreonam stopped, patient continued on vancomycin • Patients remain in the ICU on pressors • Repeat blood culture is negative

  38. Would you narrow the therapy to oxacillin or cefazolin based on his presentation/history

  39. Pt’s allergy was a rash when he was a kid. What would be your recommendation?

  40. References • Blumenthal, K, Shenoy, E, et al. Impact of a clinical guidelines for prescribing antibiotics to inpatients reporting penicillin or cephalosporin allergy. Ann Allergy Asthma Immunol. 2015; 115: 294-300 • DePestel, D, Benninger, MS, et al. J Am Pharm Assoc. 2008; 48:530-540 • Gonzalez-Estrada, Radojicic, C. ClevClincJourn Med. 2015; 82 (5): 295-299 • Bhattacharya, S. The Facts About Penicillin Allergy: A Review. J Adv Pharm Technol Res. 2010; 1(1): 11–17. • Solensky, R, Banerji, A, et al. Cephalosporin Administration to Patients with a History of Penicillin Allergy. Ann Allergy Asthma Immunol. 2010; 273 (105): 47-48 • Pichichero, M, Zagursky, R. Penicillin and Cephalosporin allergy. Ann Allergy Asthma Immunol. 2014; 112: 404-412 • Ledford, D. Cephalosporin side chain Cross-reactivity. J Allergy ClinImmunolPract. 2015;3:1006-7. • Robinson, J, Hammed, T, et al. Practical aspects of choosing an Antibiotics for Patients with a Reported Allergy to an Antibiotic. Clin Infect Dis. 2002; 35 (1): 26-31 • Gupta, K, Hooton, T, et al. International clinical practice guidelines for the treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women.Clin Infect Dis. 2011;52(5):e103–e120

  41. References • Solomkin, J, Mazuski, J, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children. Clin Infect Dis. 2010;50: 133-64 • Chang, c, Mahmood, M, et al. Overview of Penicillin Allergy. Clinic Rev AllergImmunol 2012; 43:84–97. DOI 10.1007/s12016-011-8279-6 • Frumin, J, Gallagher, J. Allergic Cross-Sensitivity Between Penicillin, Carbapenem, and Monobactam Antibiotics: What Are the Chances? Ann Pharmacother. 2009; 43:304-15 • Romano, A, Gaeta, F, et al. IgE-mediated hypersensitivity to cephalosporins: Cross-reactivity and tolerability of penicillins, monobactams, and carbapenems. J Allergy ClinImmunol 2010; 126: 994-998 doi:10.1016/j.jaci.2010.06.052 • Salkind, A, Cuddy, P, et al. Is This Patient Allergic to Penicillin? An Evidence-Based Analysis of the Likelihood of Penicillin Allergy. JAMA 2001; 285 (19): 2498-2504 • Gruchalla, R, Pirmohamed, M. Antibiotic Allergy. N Engl J Med 2006;354:601-9 • Solensky, R, Khan, D, et al. Drug Allergy: An Updated Practice Parameter. Ann Allergy Asthma Immunol. 2010; 273 (105): 47-48

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