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The erm(41) gene confers inducible macrolide resistance in Mycobacterium abscessus subsp. abscessus, calling into question the usefulness of macrolides for treating M. abscessus subsp. abscessus infections. With an extended incubation (14 days), isolates with MICs of ≥8 μg/ml are considered macrolide resistant by current CLSI guidelines. Our goals were to determine the incidence of macrolide susceptibility in U.S. isolates, the validity of currently accepted MIC breakpoints, and the erm(41) sequences associated with susceptibility. Of 349 isolates (excluding those with 23S rRNA gene mutations), 85 (24%) had clarithromycin MICs of ≤8 μg/ml. Sequencing of the erm(41) genes from these isolates, as well as from isolates with MICs of ≥16 μg/ml, including ATCC 19977T, revealed 10 sequevars. The sequence in ATCC 19977T was designated sequevar (type) 1; most macrolide-resistant isolates were of this type. Seven sequevars contained isolates with MICs of >16 μg/ml. The T28C substitution in erm(41), previously associated with macrolide susceptibility, was identified in 62 isolates (18%) comprising three sequevars, with MICs of ≤2 (80%), 4 (10%), and 8 (10%) μg/ml. No other nucleotide substitution was associated with macrolide susceptibility. We recommend that clarithromycin susceptibility breakpoints for M. abscessus subsp. abscessus be changed from ≤2 to ≤4 μg/ml and that isolates with an MIC of 8 μg/ml have repeat MIC testing or erm sequencing performed. Our studies suggest that macrolides are useful for treating approximately 20% of U.S. isolates of M. abscessus subsp. abscessus. Sequencing of the erm gene of M. abscessus subsp. abscessus will predict inducible macrolide susceptibility., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

This case is presented to: a) emphasize the importance of a careful history, including interviewing witnesses and considering a complete differential diagnosis when evaluating aviators with a history of an episode of altered consciousness; and b) demonstrate an appropriate use of literature review, subspecialty consultations, and U.S. Air Force Aeromedical Guidelines to arrive at an aeromedical disposition for an unusual case. A military aviator experienced an episode of syncope/near syncope, initially felt to be caused by a primary seizure or an arrhythmia. Subsequent thorough evaluation included careful history taking, extensive interviewing of witnesses, subspecialty consultations, review of appropriate literature and deliberation by a board of experienced military aeromedical physicians. Cardiac and neurologic diagnoses were considered but careful history and witness interviews revealed that the aviator had sustained an insect sting just minutes before the episode. Evaluation by allergy specialists, including skin testing, identified him as being hypersensitive to Hymenoptera stings. A diagnosis of hypersensitivity reaction to a Hymenoptera sting was determined to be the cause of the altered consciousness episode. Review of the literature revealed that immunotherapy for Hymenoptera sensitivity reduces the risk of future anaphylaxis to only 1-2% after maintenance dose is achieved. Consideration of the risk of future events and the success of rush immunotherapy resulted in a recommendation for a waiver to return the aviator to unrestricted flying duties. The importance of diligent history taking must never be forgotten. In this aviator it led to the correct diagnosis and definitive therapy. In addition, appropriate consideration of the literature and knowledge of outcome rates allowed a return to unrestricted flying for this aviator. If the original diagnosis of seizure or arrhythmia had been accepted, this aviator would have been disqualified without waiver and a valuable flying asset would have been lost.