The incidence and prevalence of non-tuberculous mycobacterial (NTM) infections have been increasing worldwide and lately led to an emerging public health problem. Among rapidly growing NTM, Mycobacterium abscessus is the most pathogenic and drug resistant opportunistic germ, responsible for disease manifestations ranging from “curable” skin infections to only “manageable” pulmonary disease. Challenges in M. abscessus treatment stem from the bacteria’s high-level innate resistance and comprise long, costly and non-standardized administration of antimicrobial agents, poor treatment outcomes often related to adverse effects and drug toxicities, and high relapse rates. Drug resistance in M. abscessus is conferred by an assortment of mechanisms. Clinically acquired drug resistance is normally conferred by mutations in the target genes. Intrinsic resistance is attributed to low permeability of M. abscessus cell envelope as well as to (multi)drug export systems. However, expression of numerous enzymes by M. abscessus, which can modify either the drug-target or the drug itself, is the key factor for the pathogen’s phenomenal resistance to most classes of antibiotics used for treatment of other moderate to severe infectious diseases, like macrolides, aminoglycosides, rifamycins, β-lactams and tetracyclines. In 2009, when M. abscessus genome sequence became available, several research groups worldwide started studying M. abscessus antibiotic resistance mechanisms. At first, lack of tools for M. abscessus genetic manipulation severely delayed research endeavors. Nevertheless, the last 5 years, significant progress has been made towards the development of conditional expression and homologous recombination systems for M. abscessus. As a result of recent research efforts, an erythromycin ribosome methyltransferase, two aminoglycoside acetyltransferases, an aminoglycoside phosphotransferase, a rifamycin ADP-ribosyltransferase, a β-lactamase and a monooxygenase were identified to frame the complex and multifaceted intrinsic resistome of M. abscessus, which clearly contributes to complications in treatment of this highly resistant pathogen. Better knowledge of the underlying mechanisms of drug resistance in M. abscessus could improve selection of more effective chemotherapeutic regimen and promote development of novel antimicrobials which can overwhelm the existing resistance mechanisms. This article reviews the currently elucidated molecular mechanisms of antibiotic resistance in M. abscessus, with a focus on its drug-target-modifying and drug-modifying enzymes.
contributed equally. Author order was determined both alphabetically and in order of increasing seniority.
Introduction: Recurrent strokes make up 25% of the annual stroke incidence with 10% of the Veteran population suffering a recurrent stroke within 1 year. The role of adherence to a post-stroke medication regimen and its effect on stroke recurrence is unknown. Methods: Veterans evaluated in a vascular neurology specialty clinic from July 2010 to June 2016 underwent a detailed medical chart review and assessment of medication adherence to stroke prevention medications including anti-thrombotic use, anti-coagulants, anti-hypertensives, lipid-lowering therapy, and anti-hyperglycemic therapy. Medication adherence was measured by 90d refill history with >75% medication possession ratio (MPR) indicating adherence. A Framingham Stroke Risk Profile (FSRP) Score was calculated for each patient. Relative risk calculations were generated using a bivariate analysis and means compared via t-test. Results: 162 of 245 patients who were newly referred to the clinic underwent a detailed chart review and medication adherence profile. In this cohort, 93.8% were male and ranged in age between 35-94 years old (mean 69.2±10.2). The mean age of first stroke was 62.9±10.5 and the frequency of recurrent stroke was 26.5% (43 patients). The median time to recurrent stroke was 2.59 years. The average FSRP score for all subjects was 0.087±0.09 and did not differ between those with or without a recurrent stroke (0.103 vs. 0.082, p= 0.18). The rate of medication adherence in all subjects was 69.8% and differed greatly between those without and with a recurrent stroke, 79.0% vs. 44.2%, respectively. Median time to recurrent stroke was 2.59 years in those with MPR >75% and 1.91 years in those with MPR <75%. Strict adherence with a stroke prevention medication regimen was associated with a lower risk of recurrent stroke (relative risk = 0.34, 95% CI 0.21-0.57, p -value <0.0001) while poor adherence, was associated with a 2.91-fold increased risk ( p -value <0.0001) of recurrent stroke in the Veteran population. Conclusion: In this high-risk Veteran population, strict adherence with a stroke prevention medication regimen is associated with a lower risk of recurrent stroke. Efforts to measure and encourage medication adherence in patients with prior stroke may reduce the risk of recurrence.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.