Epidemiology of Mycobacterial Infections

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications & trials

Abstract

This past fiscal year we had two major projects related to the above goals: 1) Amikacin exposure and susceptibility of macrolide-resistant Mycobacterium abscessus, in a patient cohort at NIH receiving long-term treatment: M. abscessus complex is associated with antibiotic resistance and poor treatment outcomes. We described within-patient changes in M. abscessus complex resistance to clarithromycin and amikacin. Patients with amikacin exposure and a >50 month interval between M. abscessus complex isolates were identified. Antimicrobial susceptibility testing was performed on first and last isolates by broth microdilution, and genetic markers of resistance were identified. Sixteen patients were identified with a median amikacin exposure of 2.3 years (range: 0.6-8.6). Fifteen patients also received macrolides (median: 7.2 years, range: 1.3-10.7). All initial isolates were resistant to clarithromycin (MIC8). Two patients had later susceptible isolates, which were of a different subspecies (M. massiliense) than the initial isolates (M. abscessus). All initial isolates were susceptible or intermediate resistant to amikacin, and only one patient had a resistant final isolate (MIC>64), accompanied by an AG mutation at position 1408 of the 16S rRNA. FEV1 decreased significantly over the study period, while smear quantity and the proportions of patients with elevated C-reactive protein or cavitary lesions all increased significantly. Despite prolonged, mostly inhaled amikacin exposure, development of amikacin resistance was uncommon in this patient population; however, disease progression continued. 2) Treatment regimens for MAC, using large electronic medical records database Treatment guidelines exist for pulmonary Mycobacterium avium complex (MAC) infection,although studies suggest poor concordance in clinician practice. Using a national database including hospital encounters of laboratory-confirmed MAC patients, we sought to characterise US treatment practices. We assessed patients in the Premier Healthcare Database from 2009 to 2013 with two or more MACpositive cultures or one MAC-positive culture and the International Classification of Diseases (9th revision) code for pulmonary nontuberculous mycobacteria (PNTM). Treatment was characterised by patient-, provider- and facility-level factors; significant differences were assessed ( p<0.05). Multilevel Poisson regression estimated adjusted relative risks (aRR) of receiving guidelines-based or macrolide resistance-promoting regimens.Of 1326 MAC patients, 645 (49%) received treatment: 10% received guidelines-based treatment and 18% resistance-associated therapy. Patients were more likely to receive guidelines-based therapy if they had multiple hospital encounters (aRR 1.5), codes for PNTM (aRR 5.7) or tuberculosis (aRR 4.5) or radiological procedures (aRR 10.9); multiple hospital encounters (aRR 0.8) or a tuberculosis code (aRR 0.1) were less likely to be associated with receiving resistance-promoting regimens. In hospital-based MAC patients, half received antibiotics active against MAC, a low proportion received therapy based on MAC guidelines and many received antibiotics that promote macrolide resistance. Improved implementation of guidelines-based treatment is needed to decrease use of regimens associated with macrolide resistance.