IID: L9 Allergies to Antimicrobial Agents

Allergic reactions are responsible for …% of ADRs

6-10

… reaction are ADRs not immune mediated but resemble allergic reactions

Pseudoallergic

What are 6 patient related factors influencing the likelihood of an allergic drug reaction?

Age, sex, genetic, prior reactions to the drug, multiple drug allergies, and pharmacogenomics

What are 5 drug related factors influencing the likelihood of an allergic drug reaction?

Route of exposure, molecular weight, dose, and duration

… % of patients reporting a penicillin allergy are confirmed to be allergic via .. testing

4-10, skin

After 10 years, only …% of people with an allergy to penicillin will continue to have a reaction

20

… testing is the best way to evaluate …-mediated penicillin allergy

Skin, IgE

Cross-reactivity between penicillins is due to which 2 shared antigenic determinants?

Beta lactam ring and R side chain

Amoxicillin/Ampicillin rash:

• Non-… rash

• Non-…

• Flat, …, appears over days

• Incidence greater with:

  • Concomitant … infections

  • Chronic Lymphocytic … (CLL)

  • Hyperuricemia

  • Concomitant allopurinol

• Not associated with an increased risk for future intolerance to penicillins

immunologic, pruritic, blotchy, viral, Leukemia

… is a … gen cephalosporin that does not have a similar side chain to any other cephalosporin

Cefazolin, 1st

Allergic reactions to cephalosporins is …%

1-3

Allergic reactions is increased with … and … gen vs … gen

1st, 2nd, 3rd

3rd gen side chains thought to have … immunogenicity

less

Cross reactivity between cephalosporins is due to the … and NOT the …

side chains, beta lactam ring

Other 1st gen cephalosporins such as … and … will cross react with each other and some 2nd gen cephs

cephalexin, cefadroxil

2nd gen cephs such as … and … will cross react with each other and some 1st gen cephs

cefaclor, cefprozil

2nd gen cephs such as … and … will cross react with other

cefoxitin, cefuroxime

3rd and 4th gen cephs such as …, …, and … will cross react with each other

cefotaxime, ceftriaxone, cefipime

… and … cross react with 1st generation: cephalexin, cefadroxil and 2nd generation: cefaclor, and cefprozil

Amoxicillin, ampicillin

… cross reacts with cefoxitin (2nd generation)

Penicillin

… and … has no cross reactivity with cephs

Cloxacillin, piperacillin/tazobactam

Allergic reactions for carbapenems are <…%

3

If react to one carbapenem → react to … carbapenems

all

Cross reactivity is very low between … and …

penicillins, carbapenems

Type II reactions: … specific

• Avoid offending agent

drug

Type IV reactions: avoid all …

beta lactams

Type III reactions: avoid all …

beta lactams

Sulfonamide drugs:

• … (sulfamethoxazole)

• … (hydrochlorothiazide, furosemide)

• Celecoxib

• Oral hypoglycemics

• Carbonic anhydrase inhibitors (acetazolamide)

• Triptans (sumatriptan, etc…)

Antimicrobials, Diuretics

Incidence of sulfa allergy:

• …% in patients receiving sulfa antibiotics

• …% in patients receiving non-antibiotic sulfa

5, 2

Cross reactivity between antimicrobial sulfa and non-antimicrobial sulfa drugs are likely very …

low

In type I reactions for sulfonamides, IgE has .. affinity for the sulfonamide group

no

In non-type I reactions:

• Via direct … or types II, III, or IV reactions

• … cutaneous reactions: fever → rash

• Sulfamethoxazole:

  • Produce reactive … (hydroxylamines)

• Slow …; people with glutathione deficiency: ↑ risk

cytotoxicity, Delayed, metabolites, acetylators

With trimethoprim-sulfamethoxazole, patients with HIV have an … rate of ADRs: …%

increased, 50-80

Fluoroquinolones

• Most reactions either:

  • … (IgE mediated, Type I)

  • … (cell-mediated, Type IV)

• Some severe types II-IV reported

• Immediate reactions:

  • Some IgE some non-IgE mechanisms

  • Unclear if … testing useful

• If allergic to one, avoid … class

• Frequent cross-reactivity but poorly described

Immediate, Delayed, skin, entire

What 3 things can you use to treat adverse clinical signs and symptoms?

H1 antagonists, corticosteroids, and epinephrine

Skin testing predicts …, …-mediated reactions (type I) only

• It cannot predict for …-mediated reactions (nonurticarial drug rashes)

immediate, IgE, non-IgE

Limitations in skin testing:

• For many drugs the antigen is a … – parent drug not useful

• Predictive value … (sensitivity?)

• Cannot use if patient has had a … reaction (SJS/TEN, vasculitis, etc…)

• Does not predict …-reactions

• Very rare but systemic reactions can occur

metabolite, unclear, serious, cross

H1 antihistamines not effective in preventing …

anaphylactic shock

Once … protocol begun should not be interrupted unless severe reaction occurs

• Lapse between doses of > … hours may lead to the reemergence of sensitivity

desensitization, 24