Download - Module 3 (of 3): Allergy Review * Allergy to β-lactam Antibiotics By Keith Teelucksingh, PharmD Infectious Disease Pharmacist, Kaiser Permanente Vallejo.

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Module 3 (of 3): Allergy Review *

Allergy to β-lactam AntibioticsBy Keith Teelucksingh, PharmD

Infectious Disease Pharmacist, Kaiser Permanente VallejoWith contributions from Linh Van, PharmD

Infectious Disease Pharmacist, Kaiser Permanente Oakland

See Notes

Goal The goal of this presentation is to provide

pharmacists with up-to-date information regarding penicillin allergy and the cross reactivity with related antibiotics.

Objectives

After completing this module, the participant will be able to:

1. Describe the different types of allergy (per Gell Coombs classification) as they relate to penicillin and the β-lactam-related antibiotics.

2. Be able to identify clinical situations where it is safe or unsafe to use β-lactam-related antibiotics given a patient’s allergy history.

Allergy to the β-lactam antibiotics

There are several classification schemes. They can be applied to other drug classes but are best characterized for the β-lactam antibiotics: Gell and Coombs

Based on immunopathologic reactions (all of which have been seen w/β-lactam antibiotics).

Levine Reactions specific to penicillin (PCN)

according to time of onset.

Gell Coombs Classification

Type I: IgE mediation Type II: Antibody mediation Type III: Immune complex mediation Type IV: Delayed hypersensitivity

reaction

Type I: IgE mediation Serious and life threatening

Can include erythema, pruritis, urticaria (hives), angioedema, bronchospasm, hypotension, arrhythmias.

Mechanism Interaction of β-lactam antigens with

preformed β-lactam specific IgE bound to mast cells causes release of histamine, proteases, prostaglandins, leukotrienes.

Type I (cont’d)

Time course Usually starts <15 min after drug administration,

can also occur >1 hour after but less common. Pearl:

If patient has type I hypersensitivity to PCN, unless patient has tolerated before, probably judicious to avoid cephalosporins. If unable to get specific history as to what type of rash occurred and in what timeframe, err on the side of caution.

If PCN use is absolutely indicated, consult allergy for skin testing (e.g., PCN for neurosyphilis).

Type II: Antibody Mediation

Reactions Hemolysis, thrombocytopenia, neutropenia,

interstitial nephritis Mechanism

Result when β-lactam specific cytotoxic antibodies (usually IgG or IgM) become attached to circulating blood cells or renal interstitial cells that have β-lactam antigens bound to their cell surface. The antibody-antigen complex can activate complement system (resulting in cell lysis), neutrophil or macrophage attachment (leading to cell injury).

Type II (cont’d)

Time course Usually longer term, > 7 days

Pearl Long term, high-dose β-lactam treatment

predisposes to this reaction (nafcillin for endocarditis, high-dose Zosyn® for Pseudomonal infection).

Type III: Immune Complex Mediation

Serum-sickness like reaction Mechanism

β-lactam specific IgG or IgM antibodies may form circulating complexes with β-lactam antigens. These complexes can fix complement and lodge in tissue sites, possibly causing serum sickness/drug fever.

Type III (cont’d)

Time course: 6–21 days after exposure Pearl

Best example is classic serum-sickness like reaction seen with cefaclor.

Signs/symptoms: fever, arthralgia, lymphadenopathy, skin eruption

Type IV: Delayed Hypersensitivity

Delayed hypersensitivity reaction Contact dermatitis, delayed non-urticarial

rashes. Mechanism

T-cell mediated release of cytokines causing tissue inflammation and injury.

Type IV (cont’d)

Time course: not well defined Pearl/example

Penicillin was available topically in the past, but high rate of dermatitis led to its discontinuation as a marketed product.

Idiopathic Reactions

Not included in Gell Coombs classification since pathogenesis is not well defined.

Examples Maculopapular reactions (rash, etc.)

Occurs in 2 percent to 3 percent of penicillin courses, usually late in treatment.

Eosinophilia Stevens-Johnson syndrome Exfoliative dermatitis

Choosing an Antibiotic

Always note the REACTION to a given drug

Nausea, vomiting, GI upset are NOT allergic reactions.

Rash reactions: Need to either clarify type of rash and onset

or err on side of caution and use alternative agents with low chance of cross reactivity.

Cross-Reactivity

If patient is allergic to:

Can this be used?

1. Penicillin Penicillin-class drug(amoxicillin, ampicillin, etc.)

2. Penicillin Cephalosporin

3. Cephalosporin Penicillin

4. Penicillin Carbapenem

Penicillin – Penicillin Class

If patient has IgE mediated reaction to penicillin, likely to have similar reaction to ampicillin, amoxicillin, dicloxacillin and piperacillin.

Patients with allergy to penicillin may be prone to allergic reactions to drugs in general.

Aztreonam seems to be safe to use even in patients with Type I reactions. Use caution in patients with ceftazidime allergy, since these drugs have the same side chain. Reactions still can occur but tend to be very rare.

Penicillin – Cephalosporin Incidence may have been higher with

earlier preparations of cephalosporins . In general, patients with documented Type

I reactions to penicillin should not be challenged with a cephalosporin unless there is documentation that patient has tolerated cephalosporins in the past.

No good answer at this time.

Cephalosporin - Penicillin Allergic reactions to cephalosporins in the

general population tend to be rare. Chance of cross-reactivity between patients with

cephalosporin allergy being exposed to penicillin may be higher (50 percent) with first-generation cephalosporins than that with second or third generation (~10 percent).

For example, if a patient is allergic to cefazolin and exposed to a penicillin-class drug, s/he may be more likely to have an allergic reaction. If the patient is allergic to either cefuroxime or ceftriaxone, s/he may be less likely to have an allergic reaction to a penicillin-class drug.

Penicillin – Carbapenem Incidence was thought to be close to 50

percent. Emerging data suggests that carbapenems

may be safe to use in patients with Type I penicillin allergy.

Some data to suggest that patients with type IV reactions to penicillins will have a ~5 percent chance of cross-reaction with carbapenems (imipenem).

References Chen, S. Serum sickness. http://emedicine.com Weiss, M., Adkinson, N. Chapter 24: β-lactam Allergy. Mandell, Bennett &

Dolin. Principles and Practice of Infectious Disease. 7th ed. 2009. Robinson, et al. Practical aspects of choosing an antibiotic for patients with a

reported allergy to an antibiotic. Clin Infect Dis. 2002 Jul 1;35(1):26-31. Patriarca, et al. Tolerability of aztreonam in patients with IgE-mediated

hypersensitivity to beta-lactams. Int J Immunopathol Pharmacol. 2008 Apr-Jun;21(2):375-9.

Schiavino, et al.Cross-reactivity and tolerability of imipenem in patients with delayed-type, cell-mediated hypersensitivity to beta-lactams. Allergy 2009 Apr 14.

Romano, et al. Brief communication: tolerability of meropenem in patients with IgE-mediated hypersensitivity to penicillin. Ann Intern Med. 2007 Feb 20;146(4):266-9

Prescott, et al. Incidence of carbapenem-associated allergic-type reactions among patients with versus patients without a reported penicillin allergy. Clin Infect Dis. 2004 Apr 15;38(8):1102-7

Acknowledgments

Thank you to the following individuals for their support of and/or assistance with this program:

Dan Dong, Pharm D, Area Pharmacy Director Kaiser Permanente East Bay Service Area

Kathleen Hiroshima, Pharm D, Drug Information Services Kaiser Permanente California Regions

Matangi Venkateswaran, Pharm D, Inpatient Quality-Clinical Supervisor, Kaiser Permanente Central Valley Service Area

Sam S Lee, Pharm D, Inpatient Pharmacy Supervisor Kaiser Permanente Santa Rosa

Conclusion *

This concludes Module 3 of the Review of Basic Principles and Selected Antimicrobials.Upon completion of Modules 1, 2 and 3, you may proceed to the post-test and evaluation.

Thank you for participating in this continuing education program.

See Notes