PubMed · 7694059
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S Heinzl. 1993. [Lora and the steer].. https://pubmed.ncbi.nlm.nih.gov/7694059/
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OBJECTIVES: 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. STUDY DESIGN: 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. CONCLUSION: 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.
PAE and CERT values of cefaclor, loracarbef and cefuroxime (0.1-100 x MIC) were established for 8 E. coli, 3 K. pneumoniae and 2 P. mirabilis isolates. Cell enumeration was by impedance (IMP) monitoring in combination with either bioluminescence (BIOL) or viable counting (VC). Morphology was determined by interference contrast microscopy. After 2 h exposure to cefaclor, loracarbef and cefuroxime; concentration-dependent differences in counts were seen by BIOL and VC, varying from a mean value of 0.07 x log10 after exposing the P. mirabilis isolates to 0.1 x MIC cefaclor to a mean value of 2.24 x log10 after exposing the E. coli strains to 100 x MIC cefuroxime. Higher concentrations gave rise to fragile morphological forms including spheroplasts and lower concentrations to less fragile forms such as long bacilli. The longest PAE and CERT values were obtained after exposing the E. coli strains to 100 x MIC cefaclor with mean values of 4.07 and 4.87 h, respectively. Corresponding values were PAE and CERT values of 2.17 and 2.60 h for 100 x cefuroxime and 3.45 and 2.91 h for 100 x MIC loracarbef. By the Student's t-test, PAE values determined by IMP/BIOL and IMP/VC were found to be significantly different, whereas CERT values were found not to be significantly different. PAE and CERT are concentration dependent and vary with specific antibiotic/organism combinations.