1. New approach to Cefazolin
Penicillin allergic patients and surgical prophylaxis
New approach to Cefazolin

2. Is changing to
“Cefazolin can be safely administered to patients with history of allergy to penicillins including anaphylaxis, EXCEPT in those with severe delayed skin reactions – e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS.”
If cefazolin 2g IV is ordered for a patient <80kg, not a big deal!
If CeFAZolin allergic:

3. Objectives Explain differences between beta-lactams
Explain cross reactivity
For specific types of beta-lactam
Explain the new approach to surgical prophylaxis

5. Beta-lactam Ring

6. Four different Classes of Beta-lactam
Penicillin
Cephalosporin
Four different Classes of Beta-lactam
All Unique Central Structure
Carbapenem (e.g. meropenem)
Monobactam

7. Penicillin
Cephalosporin
Side Chains make the difference within the classes and are responsible for most allergic reactions
Carbapenem (e.g. meropenem)
Monobactam

8. So Reactions aren’t about Classes
Similar C-7 Position Side Chain – Cross Reactivity Possible Within Group
Similar C-3 Position Side Chain – Cross Reactivity Possible Within Group
Penicillins
Group 1
Penicillin G
Group 2
Amoxicillin
Ampicillin
Group 3
N/A
Group 3 N/A
Cephalosporins
Cefoxitin
Cephalothin
Cefaclor
Cefadroxil
Cefprozil
Cephalexin
Cefotaxime
Ceftizoxime
Ceftriaxone
Cefepime
Cefuroxime
Note that Cefazolin is not here: It has unique side chains that are not found in any other beta-lactams

9. Of 1000 people reporting a penicillin allergy
General Population
Of 1000 people reporting a penicillin allergy
The real occurrence of allergy in children is lower at around 6% (or 60 in 1000 with a reported allergy). Most reactions are minor such as mild delayed rashes
Only 100 will have their allergy confirmed
Of the 100 people with a true allergy to penicillin there is a low likelihood of reaction to another beta-lactam
Infographics taken from INESSS “Outil D’aide à la Décision en cas D’allergy aux pénicillines`, Juin 2017

10. Similar Cephalosporins
people might react if given a cephalosporin that shares structural similarity with the involved penicillin
Different Cephalosporins
1-2 people might react if given a cephalosporin that does not shares structural similarity with the involved penicillin
Carbapenems
Less than 1 person is likely to react to a carbapenem
Infographics taken from INESSS “Outil D’aide à la Décision en cas D’allergy aux pénicillines`, Juin 2017

12. What is the math? If my patient is labelled as penicillin allergic:
10% chance patient is actually allergic
1% chance of reaction if given cephalosporin with a similar side chain
0.1% chance (1/1000) of reaction if given cefazolin

13. Why so many wrong allergies on profile?
After 10 years, 80% of people lose allergy
Older drugs weren’t pure
Many had contaminants
Hard to know what is allergy and what isn’t if rash present
Many drugs are often given together, unable to tell which drug caused reaction

14. Beta-Lactams are Better
Use of alternatives antibiotics results in:
Worse efficacy
2-7x more infections
Increased toxicity
2x time the readmission rate
3x times the C. diff and kidney injury rate
Slower OR flow-through
E.g. Vancomycin takes longer to infuse
? Increased resistance
Blumenthal KG. Plos One 2016; DOI: /journal.pone
Less likely to receive optimal antibiotic therapy for MSSA bacteremia (47% vs. 80%, p<0.001)
MacFadden DR et al. Clin Infect Dis 2016; 63:
35% inpatients did not received preferred β-lactam therapy
↑ readmission, CDI and AKI (OR 3.53, 95% CI )
Jeffres MN et al. J Allergy Clin Immunol 2016; 137:
22% inpatients did not receive a β-lactam for G- BSI
Resulted in ↑clinical failure (38 vs. 27%, p=0.03), inadequate empiric therapy based on blood culture results (75 vs. 92%, p<0.001)
Koliscak LP et al. Antimicrob Agents Chemother 2013; 12:
Use of monotherapy with non-β-lactam results in suboptimal treatment of G- infections >25% of time
Combination therapy tends to result in more AE and resistance (e.g. to FQ)
Murphy J et al. J Oral Maxillofac Surg 2017; 75:
Use of clindamycin alternative therapy vs. β-lactam therapy (e.g. cefazolin) resulted in ↑SSIs (OR 7.0, p<0.002)
SSI clindamycin 50% vs. cefazolin 25% vs. amp-sulbactam 19%
Blumenthal KG et al. Clin Infect Dis 2018; 66:
Prescribed less cefazolin (12 vs. 92%, p<0.001) and more clindamycin (49 vs. 3%, p<0.001), vancomycin (35 vs. 3%, P<0.001), gentamicin (24 vs. 3%, P<0.001)
Use of alternative antibiotics resulted in more SSI (OR 1.51, 95% CI )- ↑50%

15. What About Severe Reactions?
Anaphylaxis is the most predictable reaction
Anaphylaxis to penicillin is NOT a contraindication to cefazolin
Delayed mild rashes may occur (not a true allergy)
The benefits of beta-lactams outweighs the risk
Severe delayed reactions are poorly understood
Stevens-Johnson, Toxic Epidermal Necrolysis

16. How do I know? Signs of severe delayed infection:
Reaction was more than 72 hours after drug started
There were systemic signs of reaction
Fever, hypotension
Skin sloughing
Organs failed (e.g. kidneys, liver)
Patient required hospitalization

17. How likely are severe reactions?
SJS-TENS occurs in 5-10/million population
Neutropenia is generally reversible and occurs after several weeks of therapy
Serum sickness is very rare and usually occurs after multiple doses of medication

18. If this is such a great idea . . .
Why isn’t everybody doing it?

19. They are: 6 Provinces have adopted guidelines

20. Summary CeFAZolin is safe with almost all penicillin allergies
Severe delayed reactions excluded (for now)
We are starting education in the OR because
It’s where we use the most ceFAZolin
It supports OR flow-through
This reduces adverse events and surgical infections
We are making sure this is safe moving forward