Pharmacotherapy in refractory anaphylaxis: when intramuscular epinephrine fails.

PURPOSE OF REVIEW: This review aims to provide an evidence-based overview of several pharmacotherapeutic options available for refractory anaphylaxis when intramuscular epinephrine, the drug of choice, fails to provide resolution of signs and symptoms. RECENT FINDINGS: The evidence base for the therapy of anaphylaxis is comparatively weak and is largely based on consensus expert recommendations and case reports. There is an increasing recognition that this is problematic. The level of evidence for epinephrine use in anaphylaxis is higher than for other agents. Recent systematic reviews have confirmed the lack of high-grade evidence to support use of antihistamines and corticosteroids in anaphylaxis, both of which statistically continue to be used more frequently than epinephrine. Newer pharmacotherapeutic agents have been proffered, but none has been evaluated with scientific rigor. SUMMARY: Some anaphylactic reactions are so severe that treatment is unsuccessful despite rapid recognition and treatment. Improving the evidence base for the various treatment modalities may further help minimize fatalities once anaphylaxis is recognized. Consensus expert recommendations and case reports suggest a number of pharmacotherapeutic agents that are worthy of high-quality scrutiny through randomized controlled studies in which both treatment and placebo arms receive intramuscular epinephrine injections.

Controlling the proliferation of Zygosaccharomyces bailii in ephedrine anti-phlegm cough mixture.

BACKGROUND AND OBJECTIVE: To explain a reported proliferation of Zygosaccharomyces bailii in a commercially available ephedrine anti-phlegm cough mixture preserved with 0.1% sodium benzoate, and to present a strategy for controlling its growth. METHODS: A yeast strain was isolated from the cough mixture and identified using biochemical tests, selective media and 18S rDNA sequencing. Preservative minimum inhibitory concentrations (MICs) were determined based on the broth microdilution technique. The cough mixture was reproduced using benzoate and a number of other candidate preservatives. Bottles were challenged with the yeast using the test for antimicrobial efficacy outlined in the monographs of the European Pharmacopoeia. RESULTS: The contaminating yeast was identified as Z. bailii. The yeast MIC value for benzoate was close to or above the concentration used in the commercially available cough mixture. Reintroduction of the strain into bottles preserved with benzoate or sorbate, gave an initial reduction in the inoculum concentration (>1 log) followed by growth to values close to those found in the contaminated product. Furthermore, yeast cells taken from bottles at the end of the challenge test, suffered no initial reduction in numbers and grew in fresh bottles of the product, possibly suggesting adaptation to weak-acid preservatives. Two paraben-based preservative systems passed the challenge test. CONCLUSION: Preservatives of the weak-acid type do not control the growth of Z. bailii in ephedrine cough mixture for reasons discussed in this article. If the raw juice used in production of the product cannot be treated to eliminate the yeast, other preservatives must be sought. We show that paraben-based systems are effective in this role, and these are discussed as possible replacements for benzoate in the cough mixture.