Infectious Disease

IDSA guidance for treating resistant gram-negative infections

March 11, 2022

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Tamma reports no relevant financial disclosures. Please see the guidance for all other authors’ relevant financial disclosures.


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The Infectious Diseases Society of America published new guidance this week for the treatment of antimicrobial-resistant gram-negative infections.

The document includes guidance for the treatment of extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E), carbapenem-resistant Enterobacterales (CRE) and Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P. aeruginosa).

IDSA.  ISDA guidance on the treatment of antimicrobial-resistant gram-negative infections: Version 1.0.  Accessed on March 10, 2022.

Authors Pranita D tammaMD, director of the pediatric antimicrobial stewardship program and associate professor of pediatrics at Johns Hopkins Medicine, and colleagues noted that antimicrobial resistant (AMR) pathogens have caused more than 2.8 million infections and more than 35,000 deaths annually between 2012 and 2017. We spoke with Tamma about the guidance.

Healio: What prompted this new guidance?

tamma: The field of AMR continues to evolve relatively rapidly. We are continuing to learn about new resistance mechanisms and new treatment options. As such, we wanted to make sure the IDSA AMR guidance is as up to date as possible to capture important new additions to the literature. Because our understanding of AMR is changing so quickly, we have chosen to update the IDSA AMR guidance on an annual basis.

Healio: How was this guidance put together, and how did the process differ from the way clinical practice guidelines have historically been written?

tamma: The IDSA identified the development and dissemination of clinical practice guidelines as an important initiative. However, IDSA also acknowledged that the ability to address rapidly evolving topics such as AMR was limited by prolonged timelines needed to generate clinical practice guidelines, which are based on systematic literature reviews and employ rigorous GRADE methodology. As an alternative to practice guidelines, the IDSA endorsed developing guidance documents for select topics.

The IDSA AMR guidance documents are prepared by a small team that currently consists of five infectious diseases physicians and an infectious diseases pharmacist. We are all practicing clinicians who have cared for many patients infected with resistant pathogens and who are also very passionate about furthering the science in this area. Our objective was to address clinical management questions based on a comprehensive — but not necessarily systematic — review of the literature, clinical experience and our expert opinion. Through a series of virtual meetings, we developed commonly encountered treatment questions for each organism/resistance mechanism and addressed each question through a consensus approach.

Healio: Which infections are covered by the guidance, and which are not?

tamma: There are currently two different IDSA AMR guidance documents. The first IDSA AMR guidance, which is the one that has been recently updated, focuses on the treatment of ESBL-E, CRE and DTR-P. aeruginosa infections. The second IDSA AMR guidance includes treatment of AmpC-producing Enterobacterales (AmpC-E), carbapenem-resistant Acinetobacter baumannii (CRAB) and Stenotrophomonas maltophilia. Our plan is to update all six of these sections annually and, for the next version, to merge them into a single guidance document.

Healio: Among the treatment questions addressed by the guidance, are there a few common ones that you can highlight for readers?

tamma: This is a tough one because it feels like so much of the AMR guidance that focused on ESBL-E, CRE and DTR-P. aeruginosa has been updated. We received a lot of incredibly helpful feedback from the infectious diseases community about specific management questions they received or areas where there were conflicting viewpoints in the first version of the guidance, which we attempted to address in this updated version.

As a few examples, to the ESBL-E section, we added information on the role of doxycycline to treat ESBL cystitis and the role of the cephamycins to treat ESBL-E infections. Additionally, because new data have emerged from the MERINO trial — a randomized controlled trial comparing the outcomes of patients with ceftriaxone-resistant Escherichia coli and Klebisella pneumoniae bloodstream infections (so organisms presumed to be producing ESBLs) — we summarized the updated findings and gave our interpretation of how we believe the new findings should influence clinical decision-making.

In the CRE section, we have included updated information on the frequency of different carbapenemases in the US, more data on several clinical trials that have been published since the first guidance, added data related to common mechanisms of resistance to newer CRE agents, and gave more input on selecting between different CRE treatment agents.

Finally, to the P. aeruginosa section, we added guidance on the management of P. aeruginosa isolates that may be resistant to carbapenem agents but remain susceptible to some of the traditional beta-lactam agents — for example, cefepime — which is not an infrequent occurrence. We also added a question on the role of nebulized antibiotics for the treatment of DTR-P. aeruginosa. Finally, we added much more details about mechanisms of and the frequency of the emergence of resistance to newer beta-lactam agents, as well as more details on comparative effectiveness studies for the treatment of DTR-P. aeruginosa infections.

Healio: Do you have plans to add more GR.A.M-negative organisms to the guidance?

tamma: There are of course a large number of problematic bacteria that can exhibit antibiotic resistance. We have discussed the possibility of adding some other nonfermenting gram-negative organisms, such as Burkholderia cepacia or Achromobacter xylosoxidans, which can be particularly challenging to treat, but we haven’t made any final decisions yet. The difficulty with some of these rarer pathogens is that there is such a scarcity of robust treatment data available that it is difficult to offer treatment recommendations or even suggestions that are grounded in solid evidence. We certainly value the opinions of clinicians, and if there are some organisms that rise to the top that they would like for us to include in future iterations, we would love to receive feedback and are ready to get started.


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