Correspondence
Imipenem in Patients with Immediate Hypersensitivity to Penicillins
N Engl J Med 2006; 354:2835-2837June 29, 2006
- Article
To the Editor:
It is considered potentially harmful to administer imipenem–cilastatin to patients with IgE-mediated hypersensitivity to penicillins1 because of a 47.4 percent rate of cross-reactivity (9 of 19 subjects) found in a single study2 on the basis of positive skin tests involving imipenem reagents.
Between 1997 and 2005, we studied 112 consecutive patients with such hypersensitivity, diagnosed as previously described,3 in order to assess the cross-reactivity with imipenem–cilastatin and to evaluate the allergic responses to imipenem–cilastatin in patients who had negative skin tests. Our patients had had a total of 143 immediate reactions to penicillins. All patients had positive skin tests for at least one of the penicillin reagents tested; 45 (40.2 percent) had positive specific IgE assays (Table 1Table 1
Clinical Characteristics of Patients and Results of Allergologic Tests.).All 112 patients underwent skin testing with imipenem–cilastatin at a concentration of 0.5 mg per milliliter of normal saline for each component, which is half the concentration that produced a positive response to a skin test in a patient who had had an anaphylactic reaction to imipenem–cilastatin.4 One patient (0.9 percent) had a positive skin test. Of the 111 patients with a negative skin test, 110 agreed to undergo imipenem–cilastatin challenges. We administered intramuscular doses of different fractions of the therapeutic dose (500 mg of imipenem plus 500 mg of cilastatin) at one-hour intervals: 1/100 of the dose in the first hour, 1/10 in the second hour, and the full dose in the third hour. No patient had a clinical reaction.
Our data did not confirm the previously published2 rate of cross-reactivity between penicillins and imipenem–cilastatin. However, all patients evaluated by Saxon et al.2 had reacted to penicillin, whereas only 9 of our 112 patients (8.0 percent) had such a reaction (Table 1). Moreover, we used the parent drug imipenem–cilastatin for skin testing, whereas Saxon et al.2 also used imipenemoyl–polylysine and imipenemoate. Unlike them, we challenged patients who had negative skin tests for imipenem–cilastatin.
Our rate of positive responses to skin tests with imipenem–cilastatin (0.9 percent) is lower than that to skin tests with cephalosporins (10.9 percent), with which we had previously3 assessed 128 patients allergic to penicillin, and lower than the 4.4 percent rate of cross-reactivity between penicillins and cephalosporins calculated in a review.5
We think the practice of avoiding imipenem–cilastatin in patients allergic to penicillin should be reconsidered. In patients who require treatment with imipenem–cilastatin, prophylactic skin tests can be useful. In patients with a penicillin allergy who have negative skin tests for imipenem–cilastatin, we suggest a graded challenge until further studies fully establish the negative predictive value of skin testing. Since affinity maturation IgE antibodies to imipenem may be produced after challenges, we also recommend repeating imipenem–cilastatin skin tests when patients need to be reexposed, in order to exclude such sensitization.
Antonino Romano, M.D.
Marinella Viola, M.D.
Università Cattolica del Sacro Cuore, 00168 Rome, Italy
antoninoromano@h-columbus.it Rosa-Maria Guéant-Rodriguez, M.D.
Université Henri Poincaré, 54500 Nancy, FranceFrancesco Gaeta, M.D.
Università Cattolica del Sacro Cuore, 00168 Rome, ItalyRosa Pettinato, M.D.
Istituto di Ricovero e Cura a Carattere Scientifico Oasi Maria, Santissima, 94018 Troina, ItalyJean-Louis Guéant, M.D., Ph.D.
Université Henri Poincaré, 54500 Nancy, FranceSupported by grants from the Italian Ministry for University, Scientific, and Technological Research for the skin testing and challenges and from the French Ministry for National Education, Research, and Technology for the biologic and statistical analyses.
5 References1
Bernstein IL ,Gruchalla RS ,Lee RE , et al. Executive summary of disease management of drug hypersensitivity: a practice parameter. Ann Allergy Asthma Immunol 1999;83:665-700
CrossRef | Medline2
Saxon A ,Adelman DC ,Patel A ,Hajdu R ,Calandra GB . Imipenem cross-reactivity with penicillin in humans. J Allergy Clin Immunol 1988;82:213-217
CrossRef | Web of Science | Medline3
Romano A ,Gueant-Rodriguez RM ,Viola M ,Pettinato R ,Gueant JL . Cross-reactivity and tolerability of cephalosporins in patients with immediate hypersensitivity to penicillins. Ann Intern Med 2004;141:16-22
Web of Science | Medline4
Chen Z ,Baur X ,Kutscha-Lissberg F ,Merget R . IgE-mediated anaphylactic reaction to imipenem. Allergy 2000;55:92-93
CrossRef | Web of Science | Medline5
Kelkar PS ,Li JT-C . Cephalosporin allergy. N Engl J Med 2001;345:804-809
Full Text | Web of Science | Medline
- Citing Articles (30)
Citing Articles
1
Philippe Lagacé-Wiens, Ethan Rubinstein. (2012) Adverse reactions to β-lactam antimicrobials. Expert Opinion on Drug Safety1-19
CrossRef2
Astrid Mayr, Cornelia Lass-Flörl. (2011) Non–Culture-Based Methods for the Diagnosis of Invasive Candidiasis. Current Fungal Infection Reports 5:3, 151-156
CrossRef3
A. Liu, L. Fanning, H. Chong, J. Fernandez, D. Sloane, M. Sancho-Serra, M. Castells. (2011) Desensitization regimens for drug allergy: state of the art in the 21st century. Clinical & Experimental Allergyno-no
CrossRef4
Marc H Scheetz, Maureen K Bolon, John S Esterly, Pavani Reddy, Michael Postelnick, Todd A Lee. (2011) Life-Years Gained with Meropenem over Ciprofloxacin in Penicillin-Allergic Patients with Gram-Negative Bacilli Sepsis: Results of a Probabilistic Model. Pharmacotherapy 31:5, 469-479
CrossRef5
M. T. Krishna, A. P. Huissoon. (2011) Clinical immunology review series: an approach to desensitization. Clinical & Experimental Immunology 163:2, 131-146
CrossRef6
Antonino Romano, Francesco Gaeta, Rocco Luigi Valluzzi, Cristiano Caruso, Gabriele Rumi, Philippe Jean Bousquet. (2010) IgE-mediated hypersensitivity to cephalosporins: Cross-reactivity and tolerability of penicillins, monobactams, and carbapenems. Journal of Allergy and Clinical Immunology 126:5, 994-999
CrossRef7
(2010) Drug Allergy: An Updated Practice Parameter. Annals of Allergy, Asthma & Immunology 105:4, 259-273.e78
CrossRef8
Phillip Lieberman, Richard A. Nicklas, John Oppenheimer, Stephen F. Kemp, David M. Lang, David I. Bernstein, Jonathan A. Bernstein, A. Wesley Burks, Anna M. Feldweg, Jordan N. Fink, Paul A. Greenberger, David B.K. Golden, John M. James, Stephen F. Kemp, Dennis K. Ledford, Phillip Lieberman, Albert L. Sheffer, David I. Bernstein, Joann Blessing-Moore, Linda Cox, David A. Khan, David Lang, Richard A. Nicklas, John Oppenheimer, Jay M. Portnoy, Christopher Randolph, Diane E. Schuller, Sheldon L. Spector, Stephen Tilles, Dana Wallace. (2010) The diagnosis and management of anaphylaxis practice parameter: 2010 Update. Journal of Allergy and Clinical Immunology 126:3, 477-480.e42
CrossRef9
Maria J. Torres, Miguel Blanca. (2010) The Complex Clinical Picture of β-Lactam Hypersensitivity: Penicillins, Cephalosporins, Monobactams, Carbapenems, and Clavams. Medical Clinics of North America 94:4, 805-820
CrossRef10
So Hee Lee, Heung Woo Park, Sae Hoon Kim, Yoon Seok Chang, Sun Sin Kim, Sang Heon Cho, Kyung Up Min, You Young Kim. (2010) The Current Practice of Skin Testing for Antibiotics in Korean Hospitals. The Korean Journal of Internal Medicine 25:2, 207
CrossRef11
Bernard Yu-Hor Thong. (2010) Update on the Management of Antibiotic Allergy. Allergy, Asthma and Immunology Research 2:2, 77
CrossRef12
D. Schiavino, E. Nucera, C. Lombardo, M. Decinti, L. Pascolini, G. Altomonte, A. Buonomo, G. Patriarca. (2009) Cross-reactivity and tolerability of imipenem in patients with delayed-type, cell-mediated hypersensitivity to
-lactams. Allergy 64:11, 1644-1648
CrossRef13
Eric V. Granowitz, Richard B. Brown. 2009. Adverse Reactions to Antibiotics inCriticalCare. , 542-556.
CrossRef14
Mariana Castells. (2009) Rapid Desensitization for Hypersensitivity Reactions to Medications. Immunology and Allergy Clinics of North America 29:3, 585-606
CrossRef15
Birger Kränke, Werner Aberer. (2009) Skin Testing for IgE-Mediated Drug Allergy. Immunology and Allergy Clinics of North America 29:3, 503-516
CrossRef16
Marina Atanasković-Marković, Francesco Gaeta, Marija Gavrović-Jankulović, Tanja Čirković Veličković, Rocco Luigi Valluzzi, Antonino Romano. (2009) Tolerability of imipenem in children with IgE-mediated hypersensitivity to penicillins. Journal of Allergy and Clinical Immunology 124:1, 167-169
CrossRef17
P.-J. Bousquet, P. Demoly, A. Romano. (2009) Drug allergy and hypersensitivity: still a hot topic. Allergy 64:2, 179-182
CrossRef18
M. Blanca, A. Romano, M. J. Torres, J. Férnandez, C. Mayorga, J. Rodriguez, P. Demoly, P. J. Bousquet, H. F. Merk, M. L. Sanz, H. Ott, M. Atanasković-Marković. (2009) Update on the evaluation of hypersensitivity reactions to betalactams. Allergy 64:2, 183-193
CrossRef19
M. Blanca, A. Romano, M. J. Torres, J. Férnandez, C. Mayorga, J. Rodriguez, P. Demoly, P. J. Bousquet, H. F. Merk, M. L. Sanz, H. Ott, M. Atanasković-Marković. (2009) Update on the evaluation of hypersensitivity reactions to betalactams. Allergy
CrossRef20
Eric V. Granowitz, Richard B. Brown. (2008) Antibiotic Adverse Reactions and Drug Interactions. Critical Care Clinics 24:2, 421-442
CrossRef21
M. Atanasković-Marković, F. Gaeta, B. Medjo, M. Viola, B. Nestorović, A. Romano. (2008) Tolerability of meropenem in children with IgE-mediated hypersensitivity to penicillins. Allergy 63:2, 237-240
CrossRef22
Antonino Romano, Pascal Demoly. (2007) Recent advances in the diagnosis of drug allergy. Current Opinion in Internal Medicine 6:5, 443-447
CrossRef23
Karim Lakhal, Brice Lortat-Jacob, Catherine Neukirch, Olivier Pajot, Michel Wolff. (2007) Safe Use of Meropenem in a Patient with a Possible Nonimmediate Allergy to Imipenem. Pharmacotherapy 27:9, 1334-1338
CrossRef24
Javed Sheikh. (2007) Intrapartum anaphylaxis to penicillin in a woman with rheumatoid arthritis who had no prior penicillin allergy. Annals of Allergy, Asthma & Immunology 99:3, 287-289
CrossRef25
Judith A. Burrows, Lisa M. Nissen, Carl M.J. Kirkpatrick, Scott C. Bell. (2007) Beta-lactam allergy in adults with cystic fibrosis. Journal of Cystic Fibrosis 6:4, 297-303
CrossRef26
Stefan Wöhrl. (2007) Clinical work-up of adverse drug reactions. Expert Review of Dermatology 2:2, 217-231
CrossRef27
Mariana Castells. (2007) Desensitization for drug allergy. Current Opinion in Internal Medicine 6:1, 5-10
CrossRef28
(2007) Current awareness: Pharmacoepidemiology and drug safety. Pharmacoepidemiology and Drug Safety 16:1, i-xii
CrossRef29
M. Atanaskovic-Markovic, T. Cirkovic Velickovic, M. Gavrovic-Jankulovic, O. Vuckovic, B. Nestorovic. (2006) Authors reply to beta-lactam allergy in children. Pediatric Allergy and Immunology 17:8, 639-640
CrossRef30
P. L. B. Bruijnzeel. (2006) Imipenemgebruik door patiënten met een immediate-type overgevoeligheid voor penicilline. Medisch-Farmaceutische Mededelingen 44:10, 322-323
CrossRef
