IID 09: Allergies to Beta Lactams and Other Antibiotics Flashcards
(56 cards)
1
Q
Type I Hypersensitivity Reaction
- Mechanism
- Onset
- Clinical Manifestations
A
IgE mediated
- mechanism: Ag → cross-linking of IgE bound to mast cells → release of vasoactive mediators
- onset: 0-2 hours
- clinical manifestations: anaphylaxis, urticaria, angioedema, respiratory distress, hypotension
2
Q
Type II Hypersensitivity Reaction
- Mechanism
- Onset
- Clinical Manifestations
A
cytotoxic
- mechanism: Ab directed (IgG, IgM) against cell-surface Ag → cell destruction via antibody-dependent cell-mediated cytotoxicity (ADCC) or complement
- onset: 10 hours to weeks
- clinical manifestations: anemia, thrombocytopenia
3
Q
Type III Hypersensitivity Reaction
- Mechanism
- Onset
- Clinical Manifestations
A
immune complex
- mechanism: Ag-Ab complexes deposited at various sites induces mast cell degranulation → damages tissue
- onset: 1-3 weeks
- clinical manifestations: serum sickness (fever, urticaria, vasculitis, arthritis/arthralgia)
4
Q
Type IV Hypersensitivity Reaction
- Mechanism
- Onset
- Clinical Manifestations
A
T-cell mediated
- mechanism: memory TH1 cells release cytokines that recruit and activate macrophages
- onset: 2-14 days
- clinical manifestations: maculopapular rash, Stevens Johnson Syndrome
5
Q
What are the patient-related factors that influence the likelihood of allergic drug reactions?
A
- age – males before puberty, females after puberty
- sex
- genetic
- prior reactions to the drug
- multiple drug allergies
- pharmacogenomics
6
Q
What are the drug-related factors that influence the likelihood of allergic drug reactions?
A
- route of exposure – topical > oral > IV (skin has many immune cells that act as first line of defence)
- molecular weight
- severity of reaction influenced by the dose and duration
7
Q
What information is needed to assess a patient’s drug allergy status?
A
- when the reaction occurred – and how soon it occurred after taking the drug
- what type of reaction – and characteristics of it
- did they go to the hospital visit – what did they do/give (ie. epinephrine means anaphylaxis, stop taking medication)
- route
- family history
- other antibiotics taken
- any other non-drug allergies
8
Q
Beta Lactam Antibiotics
What is the best way to evaluate IgE-mediated penicillin allergy?
A
skin testing
9
Q
Beta Lactam Antibiotics – Penicillins
What are the antigenic components of penicillins?
A
beta lactam ring and R side chain
10
Q
Beta Lactam Antibiotics – Penicillins
What is cross-reactivity between penicillins due to?
A
shared Ag determinants:
- core: beta lactam ring
- R side chain
if patient has allergy to penicillin – should avoid all penicillins
11
Q
Beta Lactam Antibiotics
Describe amoxicillin/ampicillin rashes.
A
- non-immunologic rash
- non-pruritic
- flat, blotchy, appears over days
12
Q
Beta Lactam Antibiotics
What is the incidence of amoxicillin/ampicillin rashes greater with?
A
- concomitant viral infections (incidence 69-100%)
- chronic lymphocytic leukemia (CLL)
- hyperuricemia
- concomitant allopurinol
(not associated with an increased risk for future intolerance to penicillins)
13
Q
Beta Lactam Antibiotics – Cephalosporins
Which generation results in more allergic reactions?
A
increased with 1st and 2nd generation vs. 3rd generation
- 3rd generation side chains thought to have less immunogenicity
14
Q
Beta Lactam Antibiotics – Cephalosporins
Is there cross-reactivity between cephalosporins?
A
yes – side chains
- NOT beta lactam ring
15
Q
Beta Lactam Antibiotics – Cephalosporins
1st Generation Cross-Reactivity
A
- cefazolin does not have a similar side chain to any other cephalosporin
- other 1st generation cephalosporins (cephalexin and cefadroxil) will cross-react with each other and some 2nd generation cephalosporins
16
Q
Beta Lactam Antibiotics – Cephalosporins
2nd Generation Cross-Reactivity
A
cefaclor and cefprozil
- cross-react with each other
- cross-react with 1st generation cephalosporins – cephalexin, cefadroxil
cefoxitin and cefuroxime
- cross-react with each other
17
Q
Beta Lactam Antibiotics – Cephalosporins
3rd/4th Generation Cross-Reactivity
A
- cefotaxime, ceftriaxone, and cefipime cross-react with each other
18
Q
Penicillin-Cephalosporin Cross-Reactivity
What are the antigenic components?
A
- cross-reactivity due to similarities with side chains – NOT due to beta-lactam ring
- if a patient has anaphylaxis to penicillin → cephalosporin with different side chains are safe (less clear if ‘similarities’ with side chains)
19
Q
Penicillin-Cephalosporin Cross-Reactivity
What cephalosporins do amoxicillin and ampicillin cross-react with?
A
- 1st generation: cephalexin, cefadroxil
- 2nd generation: ceflacor, cefprozil
20
Q
Penicillin-Cephalosporin Cross-Reactivity
What cephalosporins does penicillin cross-react with?
A
- cefoxitin (2nd generation)
21
Q
Penicillin-Cephalosporin Cross-Reactivity
What cephalosporins do cloxacillin and piperacillin/tazobactam cross-react with?
A
none – no cross-reactivity with cephalosporins
22
Q
Beta Lactam Antibiotics – Carbapenems
What are the antigenic components of carbapenems?
A
beta-lactam ring
23
Q
Beta Lactam Antibiotics – Carbapenems
What is the cross-reactivity of carbapenems?
A
if react to one carbapenem → react to all carbapenems
24
Q
Penicillin-Carbapenem Cross-Reactivity
A
- cross-reactivity: ‘very low,’ < 1% or lower (issues with studies)
- considered safe to give carbapenems to a person with anaphylaxis to penicillins
25
Penicillin-Carbapenem Cross-Reactivity
What are the antigenic components?
- beta-lactam ring?
- side chains very different → antigenic components likely very different
26
Beta Lactams
Type II Reactions
drug specific – avoid offending agent
27
Beta Lactams
Type III Reactions
avoid all beta lactams
28
Beta Lactams
Type IV Reactions
avoid all beta lactams
29
Sulfonamides
What are some sulfonamides? (6)
- antimicrobials (sulfamethoxazole)
- diuretics (hydrochlorothiazide, furosemide)
- celecoxib
- oral hypoglycemics
- carbonic anhydrase inhibitors (acetazolamide)
- triptans (sumatriptan, etc.)
30
Sulfonamides
Is there cross-reactivity between antimicrobial sulfa and non-antimicrobial sulfa drugs?
- not well quantified
- likely very low due to differences in chemical structure
31
Sulfonamides
What is the Type 1 reaction mechanism?
- IgE has NO affinity for the sulfonamide group
- has some affinity for other parts of the sulfamethoxazole molecule
- some drugs share these parts but no evidence of cross-reactivity (dapsone, benzocaine, acebutolol, procainamide)
32
Sulfonamides
What are allergic reactions with non-antibiotic sulfas?
predisposition to allergic reactions vs. cross reactivity with sulfa antibiotics
33
Sulfonamides
Describe non-Type 1 reactions.
- via direct cytotoxicity or types II, III, or IV reactions
- clinical presentations vary widely
- delayed cutaneous reactions (fever → rash):
morbilliform eruptions (bumpy, patches), erythema multiforme (red, patches), Stevens Johnson (can be fatal, or life-altering with significant morbidity), TEN (toxic epidermal necrolysis)
34
Sulfonamides – Non-Type 1 Reactions
Sulfamethoxazole
produce reactive metabolites (hydroxylamines)
35
Sulfonamides – Non-Type 1 Reactions
Slow Acetylators, People with Glutathione Deficiency
increase risk
36
Sulfonamides
Is there cross-reactivity between sulfonamide antibiotics and non-antibiotics?
no
- sulfa moeity unfairly blamed and maligned
37
Trimethoprim-Sulfamethoxazole
Which patients have increased rates of ADRs?
- patients with HIV: 50-80% (rate ↑ as CD4 count ↓)
- other immunocompromised patients: 10%
38
Fluoroquinolones
Most reactions are either...
- immediate (IgE mediated, type I)
- delayed (cell-mediated, type IV)
but some severe types II-IV reported
39
Fluoroquinolones
Describe immediate reactions.
- some IgE, some non-IgE mechanisms
- unclear if skin testing useful
40
Fluoroquinolones
Describe cross-reactivity.
if allergic to one → avoid entire class
- frequent cross-reactivity but poorly described
41
What can be done to treat drug allergies?
- discontinue the medication
- treat adverse clinical signs and symptoms
- substitute (if necessary) a different agent
42
What can be used to treat adverse clinical signs and symptoms?
- H1 antagonists
- corticosteroids
- epinephrine
43
What information should be collected when investigating drug allergies?
- symptoms, physical findings
- what was the drug
- prior exposure
- timing of reaction
- description of reaction
- concomitant drugs
- how was the reaction managed
- receive same or related drug(s) since
- similar symptoms when not taking the drug?
- any concomitant medical condition that might promote reactions to certain drugs
44
What test can be used to confirm drug allergy investigations?
skin test
45
What does skin testing predict?
immediate, IgE-mediated reactions (type I) only
46
What CAN'T skin testing predict?
risk for non-IgE-mediated reactions (non-urticarial drug rashes)
47
What agents can be tested by skin testing?
- relevant allergenic metabolite(s) identified
- available for testing
48
What are the limitations of skin testing?
- for many drugs, the antigen is a metabolite – parent drug not useful
- predictive value unclear (sensitivity?)
- cannot use if patient has had a serious reaction (SJS/TEN, vasculitis, etc.)
- does not predict cross-reactions
- very rare, but systemic reactions can occur
49
Skin Testing
Describe the IgE-mediated reaction to penicillin.
- ↑ risk for IgE-mediated and non-IgE-mediated reactions with subsequent use
- tend to lose sensitivity if no exposure
- 50% skin test negative at 5 years
- 75-80% skin test negative after 10 years
50
Drug Challenge
- if history indicates unlikely allergic reactions or skin test negative
- to confirm: no reaction is expected
- used to exclude hypersensitivity where history vague/non-specific
- oral or IV
- generally start with 50% or smaller amount of normal dose then repeat with full dose
- monitoring
51
Allergy Management
- avoidance
- find non-cross-reacting drugs
- premedication: not useful – H1 antihistamines not effective in preventing anaphylactic shock, may mask early signs
- documentation
- patient education
- Medic-Alert® bracelet
- desensitization
52
When might desensitization be considered?
- if patient has history of allergic reaction to drug (swelling, anaphylaxis, shortness of breath)
- if no reasonable drug therapy alternatives
- if drug necessary for severe life-threatening infection
53
What does desensitization do?
can reduce risk of anaphylactic reactions
- but does NOT reduce risk of other types of reactions (exfoliative dermatitis, SJS)
54
What is the mechanism of desensitization?
unclear – possibly basophils and mast cells develop tolerance on exposure to antigen
55
Describe the desensitization process.
- in hospital
- resuscitation equipment and MD nearby
- discuss risks and benefits with patient
- prior to initiating: patient should be stable
- approximately 1/3 patients → mild transient allergic reaction during desensitization period and/or during treatment period
- once desensitization protocol begins, it should not be interrupted unless severe reaction occurs
- antihistamines and/or epinephrine to treat reactions
- lapse between doses of ≥ 24 hours may → reemergence of sensitivity
56
Summary
- good allergy history is essential
- penicillins – cross react with each other
- carbapenems – cross react with each other
- cephalosporins – depends on side chain
- cross reactivity between penicillin allergy and cephalosporins depends – side chain
- cross reactivity between penicillin allergy and carbapenem: none
- cefazolin – does not share side chain with any other beta lactam
