Serum sickness-like reaction to cefaclor: lack of in vitro cross-reactivity with loracarbef.
OBJECTIVE
A lymphocyte-based in vitro rechallenge technique was used to examine the potential for cross-reactivity between loracarbef and cefaclor in children who had had adverse reactions to cefaclor.


METHODS
The study cohort included 10 patients (2.2 +/- 1.1 years old) with a serum sickness-like reaction to cefaclor, five patients (4.1 +/- 4.6 years old) with immediate-type hypersensitivity reactions to the drug, and five patients (1.5 +/- 0.9 years old) who had a delayed hypersensitivity reaction to cefaclor without joint involvement (i.e., not a serum sickness-like reaction). Peripheral blood mononuclear cells were isolated from each patient and were exposed to cefaclor, loracarbef, and the metabolites of each generated with phenobarbital-induced murine hepatic microsomes.


RESULTS
Among patients with cefaclor-associated serum sickness-like reactions, lymphocyte killing (expressed as percentage cell kill above baseline) in the presence of cefaclor metabolites (83.6% +/- 42.2%) was significantly (p < 0.02) higher than that observed among the patients with either immediate-type (1.1% +/- 2.4%) or delayed hypersensitivity (0%) reactions. In contrast, loracarbef did not produce significant in vitro cytotoxicity among any of the patient subgroups. Our in vitro evidence was supported at therapeutic rechallenge with loracarbef among three children with cefaclor-associated serum sickness-like reactions who tolerated a full course of therapy without adverse reactions.


CONCLUSIONS
The metabolite-mediated cytotoxicity associated with cefaclor among patients who had had serum sickness-like reactions after therapeutic administration of the drug was not shared with loracarbef. The extent to which the apparent lack of in vitro cross-reactivity between cefaclor and loracarbef may be predictive of clinical cross-reactivity is not known.
Kearns
G L
GL
Department of Pediatrics, University of Missouri-Kansas City, USA.
Wheeler
J G
JG
Rieder
M J
MJ
Reid
J
J
D002433:Cefaclor / Q000009:adverse effects*; D016923:Cell Death / Q000187:drug effects; D002511:Cephalosporins / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D004342:Drug Hypersensitivity / Q000209:etiology* / Q000276:immunology; D005260:Female; D006801:Humans; D007223:Infant; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D015203:Reproducibility of Results
D002511:Cephalosporins; D002433:Cefaclor