Infectious Diseases Society of America 2022 Guidance on the Treatment of Extended-Spectrum β-lactamase Producing Enterobacterales (ESBL-E), Carbapenem-Resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with Difficult-to-Treat Resistance (DTR-P. aeruginosa)

Background: The Infectious Diseases Society of America (IDSA) is committed to providing up-to-date guidance on the treatment of antimicrobial-resistant infections. The initial guidance document on infections caused by extended-spectrum β-lactamase producing Enterobacterales (ESBL-E), carbapenem-resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P. aeruginosa) was published on 17 September 2020. Over the past year, there have been a number of important publications furthering our understanding of the management of ESBL-E, CRE, and DTR-P. aeruginosa infections, prompting a rereview of the literature and this updated guidance document. Methods: A panel of 6 infectious diseases specialists with expertise in managing antimicrobial-resistant infections reviewed, updated, and expanded previously developed questions and recommendations about the treatment of ESBL-E, CRE, and DTR-P. aeruginosa infections. Because of differences in the epidemiology of resistance and availability of specific anti-infectives internationally, this document focuses on the treatment of infections in the United States. Results: Preferred and alternative treatment recommendations are provided with accompanying rationales, assuming the causative organism has been identified and antibiotic susceptibility results are known. Approaches to empiric treatment, duration of therapy, and other management considerations are also discussed briefly. Recommendations apply for both adult and pediatric populations. Conclusions: The field of antimicrobial resistance is highly dynamic. Consultation with an infectious diseases specialist is recommended for the treatment of antimicrobial-resistant infections. This document is current as of 24 October 2021. The most current versions of IDSA documents, including dates of publication, are available at www.idsociety.org/practice-guideline/amr-guidance/

Infectious Diseases Society of America Guidance on the Treatment of Extended-Spectrum β-lactamase Producing Enterobacterales (ESBL-E), Carbapenem-Resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with Difficult-to-Treat Resistance (DTR-P. aeruginosa)

Background: Antimicrobial-resistant infections are commonly encountered in US hospitals and result in significant morbidity and mortality. This guidance document provides recommendations for the treatment of infections caused by extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E), carbapenem-resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P. aeruginosa). Methods: A panel of 6 infectious diseases specialists with expertise in managing antimicrobial-resistant infections formulated common questions regarding the treatment of ESBL-E, CRE, and DTR-P. aeruginosa infections. Based on review of the published literature and clinical experience, the panel provide recommendations and associated rationale for each recommendation. Because of significant differences in the molecular epidemiology of resistance and the availability of specific anti-infective agents globally, this document focuses on treatment of antimicrobial-resistant infections in the United States. Results: Approaches to empiric treatment selection, duration of therapy, and other management considerations are briefly discussed. The majority of guidance focuses on preferred and alternative treatment recommendations for antimicrobial-resistant infections, assuming that the causative organism has been identified and antibiotic susceptibility testing results are known. Treatment recommendations apply to both adults and children. Conclusions: The field of antimicrobial resistance is dynamic and rapidly evolving, and the treatment of antimicrobial-resistant infections will continue to challenge clinicians. This guidance document is current as of 17 September 2020. Updates to this guidance document will occur periodically as new data emerge. Furthermore, the panel will expand recommendations to include other problematic gram-negative pathogens in future versions. The most current version of the guidance including the date of publication can be found at www.idsociety.org/practice-guideline/amr-guidance/

Infectious Diseases Society of America Guidance on the Treatment of AmpC β-Lactamase-Producing Enterobacterales, Carbapenem-Resistant Acinetobacter baumannii, and Stenotrophomonas maltophilia Infections

The Infectious Diseases Society of America (IDSA) is committed to providing up-to-date guidance on the treatment of antimicrobial-resistant infections. A previous guidance document focused on infections caused by extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E), carbapenem-resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P. aeruginosa). Here, guidance is provided for treating AmpC β-lactamase-producing Enterobacterales (AmpC-E), carbapenem-resistant Acinetobacter baumannii (CRAB), and Stenotrophomonas maltophilia infections. A panel of 6 infectious diseases specialists with expertise in managing antimicrobial-resistant infections formulated questions about the treatment of AmpC-E, CRAB, and S. maltophilia infections. Answers are presented as suggested approaches and corresponding rationales. In contrast to guidance in the previous document, published data on the optimal treatment of AmpC-E, CRAB, and S. maltophilia infections are limited. As such, guidance in this document is provided as "suggested approaches"based on clinical experience, expert opinion, and a review of the available literature. Because of differences in the epidemiology of resistance and availability of specific anti-infectives internationally, this document focuses on the treatment of infections in the United States. Preferred and alternative treatment suggestions are provided, assuming the causative organism has been identified and antibiotic susceptibility results are known. Approaches to empiric treatment, duration of therapy, and other management considerations are also discussed briefly. Suggestions apply for both adult and pediatric populations. The field of antimicrobial resistance is highly dynamic. Consultation with an infectious diseases specialist is recommended for the treatment of antimicrobial-resistant infections. This document is current as of 17 September 2021 and will be updated annually. The most current version of this document, including date of publication, is available at www.idsociety.org/practice-guideline/amr-guidance-2.0/

Antibacterial Resistance Leadership Group 2.0: Back to Business

In December 2019, the Antibacterial Resistance Leadership Group (ARLG) was awarded funding for another 7-year cycle to support a clinical research network on antibacterial resistance. ARLG 2.0 has 3 overarching research priorities: infections caused by antibiotic-resistant (AR) gram-negative bacteria, infections caused by AR gram-positive bacteria, and diagnostic tests to optimize use of antibiotics. To support the next generation of AR researchers, the ARLG offers 3 mentoring opportunities: the ARLG Fellowship, Early Stage Investigator seed grants, and the Trialists in Training Program. The purpose of this article is to update the scientific community on the progress made in the original funding period and to encourage submission of clinical research that addresses 1 or more of the research priority areas of ARLG 2.0

Considerations for the Use of Phage Therapy in Clinical Practice

Increasing antimicrobial resistance and medical device-related infections have led to a renewed interest in phage therapy as an alternative or adjunct to conventional antimicrobials. Expanded access and compassionate use cases have risen exponentially but have varied widely in approach, methodology, and clinical situations in which phage therapy might be considered. Large gaps in knowledge contribute to heterogeneity in approach and lack of consensus in many important clinical areas. The Antibacterial Resistance Leadership Group (ARLG) has convened a panel of experts in phage therapy, clinical microbiology, infectious diseases, and pharmacology, who worked with regulatory experts and a funding agency to identify questions based on a clinical framework and divided them into three themes: potential clinical situations in which phage therapy might be considered, laboratory testing, and pharmacokinetic considerations. Suggestions are provided as answers to a series of questions intended to inform clinicians considering experimental phage therapy for patients in their clinical practices

Clinical Impact of Ceftriaxone Resistance in Escherichia coli Bloodstream Infections: A Multicenter Prospective Cohort Study

Background: Ceftriaxone-resistant (CRO-R) Escherichia coli bloodstream infections (BSIs) are common. Methods: This is a prospective cohort of patients with E coli BSI at 14 United States hospitals between November 2020 and April 2021. For each patient with a CRO-R E coli BSI enrolled, the next consecutive patient with a ceftriaxone-susceptible (CRO-S) E coli BSI was included. Primary outcome was desirability of outcome ranking (DOOR) at day 30, with 50% probability of worse outcomes in the CRO-R group as the null hypothesis. Inverse probability weighting (IPW) was used to reduce confounding. Results: Notable differences between patients infected with CRO-R and CRO-S E coli BSI included the proportion with Pitt bacteremia score ≥4 (23% vs 15%, P =. 079) and the median time to active antibiotic therapy (12 hours [interquartile range {IQR}, 1-35 hours] vs 1 hour [IQR, 0-6 hours]; P <. 001). Unadjusted DOOR analyses indicated a 58% probability (95% confidence interval [CI], 52%-63%) for a worse clinical outcome in CRO-R versus CRO-S BSI. In the IPW-adjusted cohort, no difference was observed (54% [95% CI, 47%-61%]). Secondary outcomes included unadjusted and adjusted differences in the proportion of 30-day mortality between CRO-R and CRO-S BSIs (-5.3% [95% CI, -10.3% to -.4%] and -1.8 [95% CI, -6.7% to 3.2%], respectively), postculture median length of stay (8 days [IQR, 5-13 days] vs 6 days [IQR, 4-9 days]; P <. 001), and incident admission to a long-term care facility (22% vs 12%, P =. 045). Conclusions: Patients with CRO-R E coli BSI generally have poorer outcomes compared to patients infected with CRO-S E coli BSI, even after adjusting for important confounders

Antibiotic treatment of infections caused by carbapenem-resistant Gram-negative bacilli: an international ESCMID cross-sectional survey among infectious diseases specialists practicing in large hospitals

Objectives: To explore contemporary antibiotic management of infections caused by carbapenem-resistant Gram-negative bacteria in hospitals. Methods: Cross-sectional, internet-based questionnaire survey. We contacted representatives of all hospitals with more than 800 acute-care hospital beds in France, Greece, Israel, Italy, Kosovo, Slovenia, Spain and selected hospitals in the USA. We asked respondents to describe the most common actual practice at their hospital regarding management of carbapenem-resistant Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa through close-ended questions. Results: Between January and June 2017, 115 of 141 eligible hospitals participated (overall response rate 81.6%, country-specific rates 66.7%–100%). Most were tertiary-care (99/114, 86.8%), university-affiliated (110/115, 89.1%) hospitals and most representatives were infectious disease specialists (99/115, 86.1%). Combination therapy was prescribed in 114/115 (99.1%) hospitals at least occasionally. Respondents were more likely to consider combination therapy when treating bacteraemia, pneumonia and central nervous system infections and for Enterobacteriaceae, P. aeruginosa and A. baumannii similarly. Combination of a polymyxin with a carbapenem was used in most cases, whereas combinations of a polymyxin with tigecycline, an aminoglycoside, fosfomycin or rifampicin were also common. Monotherapy was used for treatment of complicated urinary tract infections, usually with an aminoglycoside or a polymyxin. The intended goal of combination therapy was to improve the effectiveness of the treatment and to prevent development of resistance. In general, respondents shared the misconception that combination therapy is supported by strong scientific evidence. Conclusions: Combination therapy was the preferred treatment strategy for infections caused by carbapenem-resistant Gram-negative bacteria among hospital representatives, even though high-quality evidence for carbapenem-based combination therapy is lacking. © 2018 European Society of Clinical Microbiology and Infectious Disease