By Linda Paul PharmD BCPS 1 Disclosure I have no financial relationships or conflicts of interest to disclose 2 Pharmacist Objectives 3 Pharmacy Technician Objectives 4 What percentage of the US population is considered allergic to Penicillin ID: 651082
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Slide1
Clinical Impact of Penicillin or Cephalosporin Allergy
By Linda Paul, PharmD, BCPS
1Slide2
DisclosureI have no financial relationships or conflicts of interest to disclose.
2Slide3
Pharmacist Objectives
3Slide4
Pharmacy Technician
Objectives
4Slide5
What percentage of the US population is considered allergic to Penicillin?
10%30%50%70%
5
Picture Adapted: hudsonvalleygeologist.blogspot.comSlide6
6
Epidemiology
Picture Adapted: https://penallergytest.com/pst-clinical-facts/Slide7
Incidence and ImplicationPenicillin 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 antibioticsAdded 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
7Slide8
Implication Additional implication
Increased risk of multi-drug resistant pathogensIncreased 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 allergicWaning 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
.
Clev
Clinc
Journ
Med
. 2015; 82 (5): 295-299
8Slide9
Gell and Coombs Classification of Drug Allergy
Type of Reaction
Hypersensitivity
Mediated byTime of onsetExamples
IgE-mediated
Type IIgE antibodiesWithin 1 hour
AnaphylaxisNon-
IgE
-mediated
Type II
Cytotoxic
Hours to days
Hemolytic anemia
Non-
IgE
-mediated
Type III
Immune complex
7-21 days
Serum sickness
Non-
IgE
-mediated
Type IV
Cell-mediated
Days to weeks
Maculopapular rash
SJS, TEN
Gonzalez-Estrada et al
.
Clev
Clinc
Journ Med. 2015; 82 (5): 295-2999Slide10
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
10
Bhattacharya, S. J Adv Pharm
Technol Res. 2010; 1(1): 11–17Slide11
Cross-reactivity Cross-reactivity among beta-lactam antibiotics are due to similarity in the R-side chain
11
Solensky
, R, et al. Ann Allergy Asthma
Immunol
. 2010; 273 (105): 47-48Slide12
Cross-reactivity between PCN and Beta-lactam Antibiotics
Beta-lactam Antibiotics
Cross-reactivity rateAminopenicillins
<2 %
Cephalosporins1st generation2
nd generation3rd generation
4th generation
0.5% - 3%
0.5%
- 4%
<0.5%
<0.2%
No data
Monobactams
0%
Carbapenems
<1%
1.
Pichichero
, M, et al.
Ann Allergy Asthma
Immunol
. 2014; 112: 404-412
2. Gonzalez-Estrada et al
.
Clev
Clinc
Journ
Med
. 2015; 82 (5): 295-299
12Slide13
Cross-reactivity between CEPH and Beta-lactam Antibiotics
Beta-lactam Antibiotics
Cross-reactivity rate
PCNs
~ 2%
Aminopenicillins
Depends on similarity
in the R-side chain
Cephalosporins
Depends
on similarity in R- side chain
Monobactams
*
< 1 %
Carbapenems
<
1 %
*
Avoid
aztreonam
if pt. has had previous reaction to ceftazidime
Pichichero
, M, et al.
Ann Allergy Asthma Immunol
. 2014; 112: 404-412
13Slide14
Cross Reactivity Based On Side-chain Similarity14
7-Position side chain
Related
Cephaloridine (1st ), Cephalothin (1st ), Penicillin G
RelatedCefaclor
(2nd), Cephalexin (1st
), Cefadroxil (1st), Amoxicillin, Ampicillin
Related
Cefepime
(4
th
),
Ceftizoxime
(3
rd
),
Cefpirome
(4
th
), Cefotaxime (3
rd
),
Cefpodoxime
(3
rd
), Ceftriaxone (3
rd
)
Bhattacharya
, S. J Adv Pharm
Technol
Res. 2010; 1(1):
11–17
Ledford, D.
J Allergy Clin Immunol Pract. 2015; 3: 1006-7Slide15
Cross Reactivity Based On Side-chain Similarity15
3-Position side chain
RelatedCefadroxil
(1st ), Cephalexin (1st )Related
Cefmetazole (2nd), Cefoperazone
(3rd), Cefotetan (2
nd)Related
Cefotaxime (3
rd
),
Cephalothin
(1
st
)
Related
Ceftibuten
(3
rd
),
Ceftizoxime
(3
rd
)
Related
Cefuroxime (2
nd
),
Cefoxitin
(2
nd
)
Related
Cefdinir
(3
rd), Cefixime (3rd)Bhattacharya, S. J Adv Pharm Technol Res. 2010; 1(1): 11–17Ledford, D. J Allergy Clin Immunol Pract. 2015; 3: 1006-7Slide16
What is the Clinical Impact?
16
Picture Adapted: https://penallergytest.com/pst-clinical-facts/Slide17
Study Objective
17
To assess physician prescribing practices in patients with penicillin (PCN) or cephalosporin (CEPH) allergy Slide18
MethodsSingle center, retrospective, observational quality improvement project
Mission Trail Baptist Hospital (MTBH) between January 1, 2015 to June 30, 2015Patient population Patients with PCN or CEPH allergy
Received antibiotics for > 1 day
18Slide19
Methods
The following data were collected from the electronic medical record: Allergic reaction and severityIndication for treatment
Prescribed antibiotics, their dose, frequency and durationAntibiotic cost was obtained from wholesaler ordering systemDrug of choice for various diseases was found in medical references and guidelines
19Slide20
Demographics20
Patients discharged from MTBH from January-June 2015
(N = 3,247)
Inclusion Criteria: Patients with PCN or CEPH allergyReceived antibiotics for > 1 day
Patients meeting inclusion criteria
(N = 265)Slide21
Results
265 (8.2%) of the 3,247 patients had a PCN or CEPH allergy and received antibiotics for > 1 day
21Slide22
ResultsThe type of allergic reaction was not documented in 181 (67%) of the 265 patients
22Slide23
Results48 (18.1%) of the 265 patients received a PCN or CEPH
In most of these patients, the type of allergic reaction was unknown23Slide24
Results217 (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
24Slide25
Clinical Impact Of PCN/CEPH AllergyPatients labeled PCN or CEPH allergy were either treated withLess effective alternative
Broad-spectrum antibiotics25
Antibiotic choices*
Patients with PCN/CEPH Allergy
Levofloxacin73%
Meropenem22%
Vancomycin21%
Aztreonam
10%
* Antibiotic choices in Respiratory InfectionsSlide26
26Slide27
Cost Of Antibiotics By Infection
Infection
Preferred B-lactam
Prescribed Antibiotic*
Cost Δ /day**
CAP
Ceftriaxone
Levofloxacin
$2.05
HAP
Cefepime
Meropenem
$43.86
UTI (community)
Ceftriaxone
Levofloxacin
$2.05
UTI complicated (Health-care)
Cefepime
Aztreonam
$135.78
Diabetic Foot Infection
Piperacillin/
Tazobactam
Meropenem
$50.70
Intra-abdominal (Health-care)
Piperacillin/
Tazobactam
Meropenem
$50.70
27Slide28
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 guidelinesMost commonly used alternate antibiotics were either levofloxacin or
meropenemSome prescribing choices could be attributed to PCN allergy alternative in order sets
28Slide29
Limitations
Single center, observation, retrospective analysisLow rate of documented allergic reaction
Difficult to assess why some antibiotic choice were selected due to some patients presenting with multiple infections and comorbidities
29Slide30
Clinical Assessment and TestingDetailed History
Time course, character, severity of the reactionHistory of reaction to other B-lactam antibioticsPrevious skin testingSkin Testing
Graded Challenge/Test DoseDesensitization
30Blumenthal, K, et al. J allergy clin Immunol.
2017; 140 (1): 154-161. e6 Slide31
Algorithm for PCN Allergy31
Mild Reaction (Skin rash)
Type 1 reaction
Use CEPH (3rd /4
th/5th
generation) Or
Alternative agents by microbial coverage
Type II – IV reaction
Avoid PCN or CEPH
Or
Alternative agents by microbial coverage
Use
3
rd
,
4
th
or 5
th
generation CEPH (Full Dose)
Or
Use
Test Dose
PCN family or CEPH (1
st
or 2
nd
generation)
Blumenthal, K, et al.
J allergy
clin
Immunol
.
2017; 140 (1): 154-161. e6 Slide32
Algorithm for CEPH Allergy32
PCN Administration
CEPH Administration
Via graded challenge, give cephalosporin that does not share identical side chain
Give PCN via graded challenge
PCN Skin Testing
Negative: Give PCN
Positive: Alternate agent
OR
Alternate agent
OR
Blumenthal, K, et al.
J allergy
clin
Immunol
.
2017; 140 (1): 154-161. e6 Slide33
Take Away Points
33Slide34
Thank youDr. Manuel Estrada, MDDr. Kevin Purcell, MD,
PharmD, MHADr. Armando Garcia, PharmD
Dr. Andre Andalcio, PharmD, BCPS
34Slide35
Cross reactivity between PCN and CEPH antibiotics varies depending on the side chain and the generation of the cephalosporin.
35Slide36
Patients with documentation of a mild allergic reaction to penicillin could receive:36Slide37
Patient Case65-year-old male
C/C: Rash which developed on his left lower leg four days ago with increased swelling and erythemaVitals 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 sourceOn patient record, penicillin allergy is documentedNo family present on admission
Started on vancomycin and aztreonam
37Slide38
Patient ProgressionBlood culture positive for methicillin-sensitive Staphylococcus aureus
Sepsis determined to be due to MSSA bacteremia secondary to cellulitisAztreonam stopped, patient continued on vancomycinPatients remain in the ICU on pressors
Repeat blood culture is negative
38Slide39
Would you narrow the therapy to oxacillin or cefazolin based on his presentation/history
39Slide40
Pt’s allergy was a rash when he was a kid. What would be your recommendation?
40Slide41
ReferencesBlumenthal, 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:
294-300DePestel, D, Benninger, MS, et al.
J Am Pharm Assoc. 2008; 48:530-540Gonzalez-Estrada, Radojicic
, C. Clev
Clinc Journ
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
Clin
Immunol
Pract. 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
41Slide42
ReferencesSolomkin, J, Mazuski, J, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children.
Clin Infect Dis. 2010;50: 133-64Chang, c, Mahmood, M, et al. Overview of Penicillin Allergy. Clinic Rev
Allerg Immunol 2012; 43:84–97. DOI 10.1007/s12016-011-8279-6Frumin, 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
Clin
Immunol
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
42