Impact of an extended challenge on the effectiveness of ß-lactam hypersensitivity investigation.

BACKGROUND: Drug provocation tests (DPTs) are the gold standard in the diagnosis of ß-lactam hypersensitivity. However, no consensus exists on the need for extended provocation tests, even though the effectiveness of the short DPT is relatively low and there has been an increase in the relative incidence of nonimmediate hypersensitivity reactions. OBJECTIVE: To evaluate the effectiveness of a 7-day (extended) DPT compared with a 1-day-only (short) DPT in the management of hypersensitivity reactions to ß-lactam antibiotics. METHODS: Patients referred to the allergy clinic of the Sheba Medical Center for suspected ß-lactam hypersensitivity from January 2008 to December 2012 underwent in vivo skin tests and an immediate short DPT with the culprit drug. Unless an immediate reaction was clearly documented, patients were offered a 7-day, extended DPT. Long-term effectiveness, calculated as the subsequent use of the tested antibiotic, and satisfaction levels were assessed with a telephone questionnaire. RESULTS: Of 49 negative DPT results, 26 (53%) were long and 23 (47%) were short. A total of 78% of the patients who underwent the long DPT reported that they used the drug compared with 61% of those who underwent only the short DPT (P = .049). Most patients were very satisfied with the drug allergy evaluation process. CONCLUSIONS: An extended DPT protocol increased the effectiveness of the allergy workup in our center without compromising patient satisfaction and safety, and it should be recommended to patients with a history of nonimmediate reaction to ß-lactam.

Glucose intolerance in cystic fibrosis as a determinant of pulmonary function and clinical status.

BACKGROUND: Cystic fibrosis related diabetes (CFRD) is associated with a decrease in pulmonary function and nutritional status. We investigated the clinical significance of impaired glucose tolerance (IGT) in cystic fibrosis (CF) patients. METHODS: Fifty-five CF patients (aged 22.8 ± 9.2 years, 29 males, mean FEV1 67.9 ± 22% predicted, mean BMI-SDS -0.23 ± 1.1) underwent a 2-h Oral Glucose Tolerance Test (OGTT) with 30-min interval measurements of glucose and insulin. Additional clinical and laboratory data were obtained from the medical charts. RESULTS: Thirty-eight participants (69%) had normal glucose tolerance (NGT), 13 (23.7%) had IGT, and 4 (7.3%) had newly diagnosed CFRD. Compared to patients with NGT, patients with IGT had significantly lower BMI-SDS (-1.1 ± 0.8 vs. 0.1 ± 1.1, p<0.001), mean FEV1 (57 ± 19 vs. 74 ± 21% predicted, p<0.01), and albumin (3.9 ± 0.3 vs. 4.3 ± 0.2g/dl, p=0.004), and higher fibrinogen (376 ± 56 vs. 327 ± 48 g/dl, p=0.02). Patients with IGT had impaired ß-cell function, with reduced first phase insulin secretion, a delayed insulin peak, and significantly lower total insulin secretion, HOMA-%B and insulinogenic index. Seven patients had HbA1c in the "diabetic" range (≥6.5%; 47.5 mmol/mol), however, HbA1c was not a sensitive or specific marker of glucose tolerance status. CONCLUSIONS: IGT in CF patients is associated with increased inflammation and decreased nutritional status and pulmonary function.