β-lactam Allergies Flashcards
β-lactam Hypersensitivity
Reactions
Type I – Immediate hypersensitivity
manifestations
time it occurs
IgE mediated Gell and Coombs Immunopathic Classification System (Onset immediate – 30 minutes) (Late up to 72hr) Urticaria Laryngeal edema Angioedema Bronchoconstriction Allergic rhinitis Diarrhea
With or without
Hypotension
Cardiovascular collapse
β-lactam Hypersensitivity
Reactions
Type I – Immediate hypersensitivity
what mediates it
Anaphylactic reactions (onset < 1 hr)
Occur in 0.2% of 10,000 treatment courses of which 10% are fatal
Due to interaction between penicillin determinants and preformed IgE bound to mast cells or basophils
Patients at risk t1/2 IgE 10 - 1,000 days to indeterminate
Epinephrine is treatment of choice for acute treatment
Increased risk of fatality if patient taking β-blockers
we care cuz
can be fatal, penicillins are first line very effective, there are alternatives but needed for other organisms, few adverse effects
Urticaria
angioedema
which type of hypersens?
raised lesions in body
swelling of deeper dermis?, eyes, face, mouth, breathing difficulty
Type I
Type II – Cytotoxic Response
what mediates them?
time it occurs
Type II – Cytotoxic Response (> 72 hours)
Rare - usually only with high dose therapy
Penicillin determinants become bound to cells causing their destruction by IgG, IgM via complement activation
Hemolytic anemia, leukopenia, neutropenia, agranulocytosis, thrombocytopenia
May occur immediately with future administration if pre-existing antibodies therefore future administration not recommended
Type III – Immune Complexes
what mediates them?
time it occurs
(Onset 7-14 days)
Rare
IgG, IgM complexes with penicillin haptens
complexes lodge in tissue sites inducing complement
activation and neutrophil response causing further damage
interstitial nephritis, serum sickness, allergic vasculitis, and possibly drug fever
Type IV – Cell Mediated (Onset delayed)
Sensitized T-cells release cytokines that activate macrophages
or cytotoxic Tc cells which mediate direct cellular damage
Contact dermatitis from drug-sensitized T–cells
(onset 24 - 48hr)
all considered severe cutaneous rxns: do not rechallenge
DRESS 2-8 wks, resolution with stopping agent
SJS-TEN 4-28 day delay: <10% of body is SJS, > 30% is TEN
AGEP 24-48 hr: pustules
Maculopapular rash, morbilliform drug eruptions
Formerly considered to be idiopathic - now considered to be Type IV hypersensitivity
Onset > 72 hours
not to be stopped with this rxn, not true allergy
important to get hx odf allergy
Occurs in
3% receiving penicillin
0.2 - 9.5% receiving ampicillin or amoxicillin
90 - 100% of ampicillin treatments with Epstein-Barr Virus, Cytomegalovirus, Lymphocytic leukemia
Aminopenicillin Tx in patients with hyperuriciemia treated with allopurinol increases risk of rash from ~5 - 7.5% to ~15 - 20%
May resolve with continued use
Risk of Hypersensitivity Reactions
higher in which pt?
4 to 6-fold greater risk of reaction to penicillin if previous penicillin reaction
parenteral or high dose therapy ↑ risk
Hypersensitivity reactions most common age 20 - 49 yrs
Older adults and small children have reduced risk
but ↑ morbidity with older adult if reaction occurs
true allergy uncommon in young children
atopy does not ↑ incidence of reaction
History of Penicillin Allergy
no hx –> 2% actually allergic, 10% will claim
yes hx –? 65-93% neg skin test, treat with penicillin will lead to 1-3% cutaneous rxn only
7-35% pos skin test, higher risk 50-70% anaphylaxis, accelerated urticaria
see slide 20
Penicillin Allergy
Discrepancy due to several factors
Only 10% of those with a history of penicillin allergy will have allergic reaction if challenged (Mandel 2010)
When tested 80 – 90% of patients with a history of penicillin allergy will have negative skin tests
Discrepancy due to several factors
may not have been a true allergic reaction
may have been a predictable reaction or
effect of the underlying illness
Patients with type 1 penicillin allergy tend to lose penicillin-specific IgE antibodies over time. 10% per year, ppl will not react to pen antymore if true IgE mediated
- need to know when it happened, the longer it has been, the less likely it will happen
Penicillin/Cephalosporin
Cross-Hypersensitivity
Increasing evidence suggests most hypersensitivity
reactions to cephalosporins likely directed at the R group side chain rather than the β-lactam ring structure
R1 side chain of most 1st generation cephalosporins more structurally similar to some penicillins
Side chains of 3rd generation cephalosporins are dissimilar bto those of penicillins
hx of pen: could by core, but if only to R1, they may only react to amoxicillin
cephalosporins with diff side chains, it should be fine if IgE rxn
Examples of Effect of Side Chain
Cross-reactivity between amoxicillin and cephalosporins
with identical R group side chains was higher than for penicillin skin test-positive patients.
12 - 38% patients allergic to amoxicillin, but able to tolerate penicillin, reacted to cefadroxil (with identical R group)
Amoxicillin allergic patients should avoid (same R group) cefadroxil, cefprozil, or undergo rapid induction of drug tolerance
Ampicillin allergic patients should avoid cephalexin
if allergic to amoxicillin avoid:
ampicillin, cefadroxil, cefprozil, cephalexin
if allergic to penicillinavoid:
cefoxitine
Groups of β-lactams with
Similar Side Chains
cefazolin (1st gen has no cross-sensistivity)
cefexime is different ( maybe closest to G3)
group 1:
Penicillin
Cefoxitin
group 2: amox, ampicillin, cefadroxil, cephalexin, cefuroxime
group 3: cefotaxime, ceftriaxone, cefepime
group 4: cefuroxime, cefoxitin
group 5: ceftazdime, aztreonam, ceftolozane (Z’s EXCEPT cefprozil)
