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Infectious Diseases Society of America Guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections

September 8,  2020

Pranita D. Tamma, Samuel L. Aitken, Robert A. Bonomo, Amy J. Mathers, David van Duin, and Cornelius J. Clancy with  thanks to  Helen Boucher, Vance Fowler, and Cynthia Sears for their guidance in the development of this document

Published by IDSA on September 8, 2020: https://www.idsociety.org/practice-guideline/amr-guidance/ 


The rise in antimicrobial resistance (AMR) continues to be a global crisis [1, 2]. Collectively, antimicrobial resistant pathogens caused more than 2.8 million infections and over 35,000 deaths annually in the United States from 2012 through 2017, according to the 2019 Centers for Disease Control and Prevention (CDC) Antibiotic Resistant Threats Report [2]. The selection of effective antibiotics for the treatment of infections by resistant pathogens is challenging [3]. Although there has been an increase in the availability of novel antibiotics to combat resistant infections in recent years [3], resistance to a number of these agents has been observed [4]. Three groups of antimicrobial resistant Gram-negative bacteria pose particular therapeutic challenges: (1) extended-spectrum β-lactamase producing Enterobacterales (ESBL-E), (2) carbapenem-resistant Enterobacterales (CRE), and (3) Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P. aeruginosa) [5]. These pathogens have been designated urgent or serious threats by the CDC [2]. They are encountered in US hospitals of all sizes and cause a wide range of serious infections that carry significant morbidity and mortality. Treatment options against ESBL-E, CRE, and DTR-P. aeruginosa infections remain limited despite approval of new antibiotics. There is often uncertainty about the precise role(s) of new agents in clinical practice [6-8].

The Infectious Diseases Society of America (IDSA) identified the development and dissemination of clinical practice guidelines and other guidance products for clinicians as a top initiative in its 2019 Strategic Plan [9]. IDSA acknowledged that the ability to address rapidly evolving topics such as AMR was limited by prolonged timelines needed to generate new or updated clinical practice guidelines. As an alternative and complement to comprehensive clinical practice guidelines, IDSA endorsed developing more narrowly focused guidance documents for the treatment of specific infectious processes. Guidance documents will address specific clinical questions for difficult-to-manage infections that are not covered by present guidelines. The documents will be prepared by a small team of experts based on a comprehensive (but not necessarily systematic) review of the literature. Additionally, such guidance documents will not include a formal grading of the evidence, unlike IDSA guidelines, which utilize the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework. Over time, guidance documents may be transitioned to a GRADE format. Content will be disseminated on multiple platforms and updated as new data emerge. Treatment of antimicrobial resistant Gram-negative bacterial infections was chosen as the initial topic for a guidance document.

The overarching goal of this guidance document is to assist clinicians – including those with and without infectious diseases expertise – in selecting antibiotic therapy for infections caused by ESBL-E, CRE, and DTR-P. aeruginosa. Future iterations of this document will address other resistant pathogens. Although brief descriptions of notable clinical trials, resistance mechanisms, and susceptibility testing methods are included, this guidance is not meant to provide a comprehensive review of these topics. The document is framed as answers to a series of clinical questions, each of which can stand on its own. Because of significant differences in the molecular epidemiology of resistance and availability of specific anti-infectives globally, the document focuses on treatment recommendations for antimicrobial resistant infections in the United States.

Source: https://www.idsociety.org/practice-guideline/amr-guidance/