Imipenem in Patients with Immediate Hypersensitivity to Penicillins
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《新英格兰医药杂志》
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 1).
Table 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, France
Francesco Gaeta, M.D.
Università Cattolica del Sacro Cuore
00168 Rome, Italy
Rosa Pettinato, M.D.
Istituto di Ricovero e Cura a Carattere Scientifico Oasi Maria
Santissima
94018 Troina, Italy
Jean-Louis Guéant, M.D., Ph.D.
Université Henri Poincaré
54500 Nancy, France
Supported 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.
References
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.
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.
Romano A, Guéant-Rodriguez RM, Viola M, Pettinato R, Guéant JL. Cross-reactivity and tolerability of cephalosporins in patients with immediate hypersensitivity to penicillins. Ann Intern Med 2004;141:16-22.
Chen Z, Baur X, Kutscha-Lissberg F, Merget R. IgE-mediated anaphylactic reaction to imipenem. Allergy 2000;55:92-93.
Kelkar PS, Li JT-C. Cephalosporin allergy. N Engl J Med 2001;345:804-809.
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 1).
Table 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, France
Francesco Gaeta, M.D.
Università Cattolica del Sacro Cuore
00168 Rome, Italy
Rosa Pettinato, M.D.
Istituto di Ricovero e Cura a Carattere Scientifico Oasi Maria
Santissima
94018 Troina, Italy
Jean-Louis Guéant, M.D., Ph.D.
Université Henri Poincaré
54500 Nancy, France
Supported 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.
References
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.
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.
Romano A, Guéant-Rodriguez RM, Viola M, Pettinato R, Guéant JL. Cross-reactivity and tolerability of cephalosporins in patients with immediate hypersensitivity to penicillins. Ann Intern Med 2004;141:16-22.
Chen Z, Baur X, Kutscha-Lissberg F, Merget R. IgE-mediated anaphylactic reaction to imipenem. Allergy 2000;55:92-93.
Kelkar PS, Li JT-C. Cephalosporin allergy. N Engl J Med 2001;345:804-809.