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■ pharmacology update

Is This Patient -Allergic?

ANJLY SHETH, PHARMD; KELLY M. SMITH, PHARMD

bapenems (Table 1). Their exposure are most commonly Increased claims of hypersensitivity reactions are being broad spectrum of activity associated with the penicillin enables treatment and prophy- class. Cutaneous reactions are reported due to the inability to differentiate between the laxis of a multitude of commu- prominent whereas anaphylac- terms “allergic reaction” and “adverse effect.” nity- and hospital-acquired tic reactions are reported in infections. When used at rec- approximately 0.01% of ommended doses, beta lactams patients treated.1,5 The interac- any adverse effects of reaction resulting in little or no have a low toxicity profile, with tion between the degradation Mantibiotics often are change in patient management. the exception of allergic reac- product of penicillin, ben- incorrectly classified as hyper- Its intensity and occurrence is tions. Allergic reactions occur zylpenicillin and IgE antibodies sensitivity reactions. In fact, related to the size of the dose in 7-40 of every 1000 penicillin is responsible for anaphylactic up to 80%-90% of patients and occurs with a predictable treatment courses and can have reactions. who report a penicillin allergy frequency. In contrast, an aller- various manifestations.2 These Although the incidence of are not truly allergic. gic reaction is an immunologic reactions are most commonly systemic hypersensitivity reac- Increased claims of these reac- hypersensitivity occurring sec- classified according to hyper- tions is low, it is attributed to a tions have emerged from the ondary to an unusual sensitivi- sensitivity type and associated 9% fatality rate.1 Therefore, inability to differentiate ty to a drug. False claims of clinical reactions or time to patients with a known history between the terms “allergic allergies to often onset (Table 2). of an allergic reaction to peni- reaction” and “adverse effect,” result in therapeutic dilemmas, The bicyclic core of beta cillin should not be rechal- resulting in falsely elevated as cross-sensitivities among lactams is postulated to be the lenged with the drug. If uncer- claims of hypersensitivity agents must also be considered moiety most responsible for tainty exists regarding a reactions.1 when implementing appropri- hypersensitivity reactions.4 Of patient’s allergy status and An adverse effect is defined ate, effective therapy. It is this the four classes of beta-lactams penicillin use is essential, a as an expected, well-known patient population that poses currently available, the bicyclic penicillin skin test should be challenges to the clinician, who core is shared by , considered. In patients with a must balance optimal regimens , and carbapen- positive penicillin skin test, and From the University of Kentucky, with cost-effectiveness and ems, resulting in an increased who require penicillin therapy, Pharmacy Services and College of Pharmacy, Drug Information Center, minimization of potential frequency of cross-sensitivity desensitization should be per- Lexington, Ky. antimicrobial resistance. among these agents. formed. Reprint requests: Kelly M. Smith, Beta lactams are a widely PharmD, University of Kentucky used class of antibiotics con- PENICILLINS CEPHALOSPORINS Medical Center, Drug Information Center, 800 Rose St, Rm C-113, sisting of penicillins, cephalo- Hypersensitivity reactions A history of a penicillin Lexington, KY 40536-0293. sporins, , and car- from previous beta lactam allergy is a relative con-

JULY 2004 | Volume 27 • Number 7 719 ■ pharmacology update

traindication for the use of gic reactions to antibiotics, TABLE 1 cephalosporins. The cross- although evidence supporting a Classification of Beta Lactam Antibiotics sensitivity between cephalo- true allergy may be lacking. It Penicillins Cephalosporins sporins and penicillins is well- is prudent to obtain a detailed Natural First Generation documented in the literature history that includes concomi- Penicillin G and is estimated to be 10%. tant medications, age at reac- Penicillin V First and second generation tion, type of reaction, route of Cephalexin cephalosporins pose the great- administration, whether im- Second Generation est risk for cross-sensitivity to provement was noted after dis- penicillins compared to the continuation of the medication, Antistaphylococcal later generations secondary to and whether the patient had structural similarities of the been challenged by chemically 6 6 side chains. Interestingly, related agents. Availability of derivatives this information can be useful Carbenicillin show less cross-reactivity in making informed decisions Third Generation among themselves compared about appropriate with penicillin derivatives.1 To use. If the patient’s allergy sta- date, a skin test for allergy to tus is unclear and penicillin use cephalosporins has not been is indicated, a penicillin skin 6 proxetil developed. test should be considered. CARBAPENEMS REFERENCES The class is 1. Saxon A, Beall GN, Rohr AS, reserved for the treatment of Adelman DC. Immediate hyper- Moxalactam sensitivity reactions to beta-lac- serious multi-drug resistant tam antibiotics. Ann Intern Med. Fourth Generation bacterial infections. If their use 1987; 107:204-215. in penicillin-allergic patients is 2. Prescott WA, DePestel DD, considered, the risks and bene- Ellis JJ, Regal RE. Incidence of TABLE 2 carbapenem-associated aller- fits must be evaluated. Recent gic-type reactions among Classification of Hypersensitivity Reactions data indicate that penicillin patients with versus patients without a reported penicillin to Beta Lactam Antibiotics allergic patients are at a 5.2 allergy. Clin Infect Dis. 2004; Based on Their Time of Onset times higher risk for an allergic 38:1102-1107. reaction to a carbapenem com- 3. Weiss ME, Adkinson NF. Beta- Reaction Type Onset (Hours) Clinical Reactions pared to nonallergic patients.2 lactam allergy. In: Mandell GL, Immediate 0-1 Anaphylaxis Bennett JE, Dolin R, eds. Mandell, Douglas and Bennett’s Hypotension MONOBACTAMS Principles and Practice of Laryngeal edema Aztreonam, the sole beta Infectious Disease. 5th ed. Urticaria/angioedema Philadelphia, Pa: Churchill Wheezing lactam represented in the Livingstone; 2000:299-305. Accelerated 1-72 Urticaria/angioedema monobactam class, is not asso- 4. Yates AB, deShazo RD. Laryngeal edema ciated with cross-sensitivity Allergic and nonallergic drug reactions. South Med J. 2003; Late Ͼ72 Morbilliform rash reactions to the other beta lac- 96:1080-1087. Interstitial nephritis 1 tam antibiotics. Therefore, 5. Kelkar PS, Li JT. Cephalo- Hemolytic anemia aztreonam serves as a viable sporin allergy. N Engl J Med. Neutropenia treatment alternative in patients 2001; 345:804-809. Thrombocytopenia with a serious gram-negative 6. Salkind AR, Cuddy PG, Serum sickness Foxworth JW. Is this patient Drug fever infection. allergic to penicillin? An evi- Stevens-Johnson syndrome dence-based analysis of the Exfoliative dermatitis THE BOTTOM LINE likelihood of penicillin allergy. JAMA. 2001; 285:2498-2505. Many patients claim aller- Adapted from Mandell, Douglas and Bennett’s Principles and Practice of Infectious Disease. Copyright © 2000. Churchill Livingstone.3

Section Editor: Robert P. Rapp, PharmD

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