Diagnosis and Management of Immediate Hypersensitivity Reactions to Cephalosporins.

Diagnosis and Management of Immediate Hypersensitivity Reactions to Cephalosporins.

Clin Rev Allergy Immunol. 2013 Apr 2;
Dickson SD, Salazar KC

Cephalosporins are one of the most commonly prescribed classes of antibiotics. Immediate IgE-mediated hypersensitivity reactions have been reported with use of a specific cephalosporin, as a cross-reaction between different cephalosporins or as a cross-reaction to other ?-lactam antibiotics, namely, penicillin. Historically, frequent reports of anaphylaxis following administration of first- and second-generation cephalosporins to patients with a history of penicillin allergy led to the belief of a high degree of allergic cross-reactivity. More recent evidence reveals a significantly lower risk of cross-reactivity between penicillins and the newer-generation cephalosporins. The current thought is that a shared side chain, rather than the ?-lactam ring structure, is the determining factor in immunologic cross-reactivity. Understanding the chemical structure of these agents has allowed us to identify the allergenic determinants for penicillin; however, the exact allergenic determinants of cephalosporins are less well understood. For this reason, standardized diagnostic skin testing is not available for cephalosporins as it is for penicillin. Nevertheless, skin testing to the cephalosporin in question, using a nonirritating concentration, provides additional information, which can further guide the work-up of a patient suspected of having an allergy to that drug. Together, the history and the skin test results can assist the allergist in the decision to recommend continued drug avoidance or to perform a graded challenge versus an induction of tolerance procedure. HubMed – drug


Clinical Benefit of Delamanid (OPC-67683) in the Treatment of Multidrug-Resistant Tuberculosis Patients in China.

Cell Biochem Biophys. 2013 Apr 2;
Zhang Q, Liu Y, Tang S, Sha W, Xiao H

The cure rates are much lower for multidrug-resistant (MDR) tuberculosis (TB) patients. Delamanid (OPC-67683) has been evaluated in phase-II MDR-TB clinical trials. Herein, we reviewed MDR-TB cases in which treatment regimens, with/without delamanid, were administered. Thirty-eight patients were enrolled; 26 received delamanid-containing regimens (treatment group) while 12 received placebo-containing regimens (control group) for 56 days. Data regarding clinical/radio-microbiological characteristics, drug tolerability, and treatment outcomes were collected. We found that all patients had isolates resistant to a median of 5 (range 2-7) drugs; 24 (92.3 %) patients in treatment group and 11 (91.7 %) in control group had cavities. Culture conversion was obtained in 32 pulmonary TB cases (median 74.5 days). At data censure, 30/38 patients successfully completed therapy with documented negative cultures for at least 18 months before the end of treatment. Two patients (5 consecutive negative cultures) are still on treatment. Six patients had poor outcome (3 failures/2 lost/1 death). In 13 patients, adverse events were observed that included mental disorder, QT interval prolongation, and increased blood cortisol whereas only 3 patients stopped delamanid treatment because of adverse events. It was, therefore, concluded that delamanid was well-tolerated, had low rates of discontinuation, and could be effective for treating MDR-TB. HubMed – drug


FDA AD Drug Development Guidance.

J Nucl Med. 2013 Apr; 54(4): 16N

HubMed – drug


Drug shortages in Canadian anesthesia: a national survey.

Can J Anaesth. 2013 Apr 2;
Hall R, Bryson GL, Flowerdew G, Neilipovitz D, Grabowski-Comeau A, Turgeon AF,

BACKGROUND: Canadian physicians are faced with an increasing frequency of drug shortages. We hypothesized that drug shortages have a clinical impact on anesthesia care in Canada. METHODS: We conducted a self-administered survey of anesthesiologists in Canada using the membership list of the Canadian Anesthesiologists’ Society. For survey development, we identified key domains, including types of drug shortages, impact on the ability of anesthesia practitioners to provide general anesthesia care, and impact on patient outcomes. We undertook assessments of face validity, clinical sensibility, and content validity. Respondents were surveyed from January-April 2012. RESULTS: Completed valid questionnaires were submitted by 1,187 respondents (61.4%), and 779 (65.7%) of respondents described a shortage of one or more anesthesia or critical care drugs. Changes in anesthesia practice resulting from drug shortages were common; 586 (49%) respondents thought they had given an inferior anesthetic, and 361 (30%) reported administering medications with which they were unfamiliar. Respondents also reported that drug shortages were, at times, responsible for changes in the conduct of patient care, with 28 (2.4%) noting cancellation or postponement of surgery and 92 (7.8%) witnessing a drug error. One hundred sixty-five (13.9%) respondents regarded drug shortages as having prolonged recovery from anesthesia, and 124 (10.5%) viewed drug shortages as resulting in an increased number of postoperative complications, such as postoperative nausea and vomiting. INTERPRETATION: Drug shortages are common in anesthetic practice in Canada. This state of affairs may have a negative effect on how anesthesiologists practice anesthesia and may be associated with adverse patient outcomes. HubMed – drug