Lecture 15 Beta-lactam Cross Sensitivty/allergy Testing Flashcards
What is a Type I beta-lactam hypersensitivity reaction?
it is immediate - Gell and Coombs immunopathic classification system,
onset within 30 minutes all the way to 3 days,
S&S: urticaria, laryngeal edema, angioedema, bronchoconstriction, allergic rhinitis, diarrhea,
can also be with or without hypotension and CV collapse,
are anaphylactic reactions (onset <1 hour) - occur in 0.2% of 10,000 tx courses of which 10% are fatal ⇒ happen due to interaction between penicillin determinants and pre-formed IgE bound to mast cells or basophils,
epinephrine is tx of choice for acute, and beta-blockers can increase risk of fatality
What is a Type II beta-lactam hypersensitivity reaction?
it is a cytotoxic response - onset after 3 days,
usually only happens with high dose tx,
penicillin determinants become bound to cells causing their destruction by IgG, IgM via complement activation,
S&S: hemolytic anemia, leukopenia, neutropenia, agranulocytosis, thrombocytopenia,
may occur immediately with future admin if pre-existing Abs therefore future admin not recommended
What is a Type III beta-lactam hypersensitivity reaction?
it is immune complexes,, onset in 7-14 days,
rare,
IgG, IgM complexes with penicillin haptens, these complexes lodge in tissue sites including complement activation and neutrophil response causing further damage,
S&S: interstitial nephritis, serum sickness, allergic vasculitis, possibly drug fever
What is a Type IV beta-lactam hypersensitivity reaction?
it is cell mediated,, onset is delayed,
sensitized T-cells release cytokines that activate macrophages or cytotoxic Tc cells which mediate direct cellular damage,
S&S: contact dermatitis from drug sensitized T-cells (onset 1-2 days),
also maculopapular rash, morbilliform drug eruptions ⇒ considered Type IV rxn, onset >3 days, occurs in ⇒ 3% receiving penicillin, 0.2-9.5% receiving ampicillin/amoxicillin, 90-100% of ampicillin tx with Epstein-Barr virus, cytomegalovirus, lymphocytic leukemia,
may resolve with continued use
What is the risk of penicillin hypersensitivity reactions for different ages, and how does rechallenging work?
4-6x greater risk if previous penicillin rxn,
most common in 20-49 yrs, older adults and smaller children have reduced risk,
Rechallenging: only 10% with hx of allergy will have rxn if rechallenged, when tested 80-90% of pt with hx of allergy will have (-) skin tests,
may not have been true rxn, may have been predictable rxn, or an effect of underlying illness,
patients with Type I penicillin allergy tend to lose penicillin-specific IgE Abs over time
What do cephalosporin hypersensitivity rxn look like?
not as common as penicillin rxn,
most often maculopapular rash with eosinophilia, occasionally fever (1-7%), anaphylaxis and urticaria reported (0.0001-0.1%)
What is an example of the effect of side chain in beta-lactam cross allergies?
12-38% pt allergic to amoxicillin but able to tolerate penicillin reacted to cefadroxil as it has an identical R group,
amoxicillin allergic pt should avoid cefadroxil, cefprozil, or undergo rapid induction of drug tolerance,
ampicillin allergic pt should avoid cephalexin
What are examples of beta-lactams which have similar R side chains, and therefore may present higher risk of cross-allergies?
Group 1: penicillin and cefoxitin,
Group 2: amoxicillin, cefadroxil, cefprozil, ampicillin, cephalexin,
Group 3: cefotaxime, ceftriaxone, cefepime,
Group 4: cefuroxime, cefoxitin,
Group 5: ceftazidime, aztreonam, ceftolozane
For a patient that experienced a severe non-IgE mediated allergic reaction to penicillins, how should it be managed for further treatment in the future?
all beta-lactams should be avoided if hx of this including: hemolytic anemia, serum sickness, interstitial nephritis, hepatitis, SJS, toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic sx (DRESS), exfoliative dermatitis, acute generalized exanthematous pustulosis (AGEP)
For a patient that experienced a true IgE-mediated reaction to a cephalosporin, with respiratory difficulty, hypotension, or hives, how should future tx be managed?
avoid that cephalosporin, avoid penicillins/cephalosporins with similar side chains,, cause use other cephalosporins/penicillins with dissimilar side chains (or carbapenem if appropriate)
How can penicillin skin testing be used?
is 99% predictive if both major and minor determinants used (only predicts Type I IgE-mediated rxn, and SHOULD ONLY BE USED for these reactions),
major determinant benzylpenicilloyl polylysine is commercially available while minor determinant mix penicilloate and penilloate isn’t,
fatalities have occurred when done improperly, should only be done by qualified allergist with tx for anaphylaxis available
What is graded challenge for antibiotics?
give 1/100 of therapeutic dose, if no rxn ⇒ 30-60 min later give 1/10 dose, if no rxn ⇒ 30-60 min later give full dose,
procedure should be abandoned and patient treated at first sign of any allergic rxn,
if pt requires med at later point it should only be admin through formal desensitization,, pt with severe non-IgE mediated reactions are not candidates for this
When can antibiotic desensitization be used for tx?
only in pt with severe IgE-mediated rxn and/or (+) skin test and when there are no alternatives (ex. syphilis in pregnancy),
oral desensitization is safer and recommended than injectable,
effectiveness if usually lost within 2 days after cessation of penicillin therapy therefore therapy must start immediately after desensitization and would need to be redone if the antibiotic was needed again in the future
