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, clinical situations in which phage therapy might be considered, dosing, route of administration, and outcomes. Large gaps in knowledge contribute to a heterogeneity in approach and lack of clear consensus in many important clinical areas. Here, 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, and 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.

This large-scale retrospective analysis (n ϭ 60,551) of the Premier inpatient database (1 January 2011 to 31 December 2014) found an overall prevalence of carbapenem-resistant Enterobacteriaceae strains of 2.3% (range, 0.9% to 5.8% by geographic region) among patients with infections due to Enterobacteriaceae. Ongoing monitoring and development of decision support tools/algorithms are needed for identification of high-risk patients.KEYWORDS bacterial drug resistance, anti-infective agents, carbapenems, bacterial infections, urinary tract infections, intra-abdominal infections, bacterial pneumonia, bacteremia A lthough the U.S. Centers for Disease Control and Prevention (CDC) identifies infections due to carbapenem-resistant Enterobacteriaceae (CRE) as an urgent public health threat (1), limited data exist regarding the true prevalence of these infections among adult hospitalized patients. Existing surveillance programs potentially underestimate prevalence owing to limited site participation and clinical specimen availability. This study sought to quantify the prevalence of carbapenem resistance in invasive infections due to Enterobacteriaceae among adult hospitalized patients within 9 geographic regions across the United States.(Preliminary results from this study were presented at the Society for Healthcare Epidemiology of America Spring 2015 Conference, 14 -17 May, 2015, Orlando, FL.) To accomplish the study objectives, a retrospective observational study was performed using hospital discharge data from approximately 178 U.S. health care facilities in the Premier research database with accessible microbiology results (see Appendix A in the supplemental material). In total, the Premier hospital database includes data from approximately 80 million admissions (Ͼ5 million added per year since 2011). Admissions data are provided by Ͼ500 participating acute care hospitals from across the United States and account for approximately 20% of all inpatient discharges in the nation (Premier Healthcare Database: Data that Informs and Performs, Premier, Inc., Charlotte, NC). The infective episode for a patient was included if all of the following criteria were met: (i) patient Ն18 years of age; (ii) inpatient discharge between 1 January 2011 and 31 December 2014; (iii) primary or secondary diagnosis at discharge using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), codes of complicated urinary tract infection (cUTI), complicated intra-abdominal infection (cIAI), hospital-associated pneumonia (HAP), or bloodstream infection (BSI) (see Appendix B in the supplemental material); (iv) positive culture for an Enterobacteriaceae strain obtained from a site consistent with the infection type (see Appendix C in the supplemental material); (v) receipt of antibiotic treatment on day of Enterobacteriaceae culture collection or Յ3 days after index Enterobacteriaceae culture; and (vi) available susceptibility data for the index isolate.Cohorts by infection type were not mutually excl...

The gut microbiome has been referred to as the “forgotten organ.” Although much about the gut microbiome remains incompletely understood, data on its clinical importance is emerging at rapid speed. Many practicing clinicians may be unaware of the essential role that the microbiome plays in both health and disease. This review aims to improve clinical understanding of the gut microbiome by discussing key terminology and foundational concepts. The role of a healthy microbiome in normal host function is described, as well as the consequences of a disrupted microbiome (i.e., dysbiosis). Management strategies to restore the gut microbiome from a disrupted to a healthy state are also briefly discussed. Lastly, we review emerging areas for therapeutic potential and opportunity to bring determinants of microbiome health from the bench to bedside.

Imipenem (IMI)/cilastatin/relebactam (REL) (I/R) is a novel β-lactam/β-lactamase inhibitor combination with expanded microbiologic activity against carbapenem-resistant non- Morganellaceae Enterobacterales (CR-NME) and difficult-to-treat (DTR) Pseudomonas aeruginosa . Relebactam, a bicyclic diazabicyclooctane, has no direct antimicrobial activity but provides reliable inhibition of many Ambler class A and class C enzymes.

Oral tetracyclines have been used in clinical practice for over 60 years. Overall, one of the most common indications for use of oral tetracyclines is for treatment of adult outpatients with lower respiratory tract infections, including community-acquired pneumonia (CAP). Despite the longstanding use of oral tetracyclines, practice patterns indicate that they are often considered after other guideline-concordant oral CAP treatment options (namely macrolides, fluoroquinolones, and β-lactams). However, there are growing resistance or safety concerns with the available oral agents listed for outpatients with CAP in the updated American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) CAP guidelines, especially among patients with comorbidities or notable risk factors for resistant pathogens. Given the need for alternative oral agents to macrolides, fluoroquinolones, and beta-lactams for adult outpatients with CAP, this review summarizes the literature on the use of oral tetracyclines (i.e., doxycycline, minocycline, and omadacycline) for this indication. As part of this review, we described their mechanism of action, common mechanisms of resistance, susceptibility profiles against common CAP pathogens, pharmacokinetics, pharmacodynamics, clinical data, and safety. The intent of the review is to highlight the important considerations when deciding between doxycycline, minocycline, and omadacycline for an adult outpatient with CAP in situations in which use of an oral tetracycline is warranted.

Study Objective Bloodstream infections (BSIs) are a significant cause of mortality. Use of a rapid multiplex polymerase chain reaction‐based blood culture identification panel (BCID) may improve antimicrobial utilization and clinical outcomes by shortening the time to appropriate therapy and de‐escalating antibiotics among patients on overly broad‐spectrum empiric therapy. The effect of BCID on clinical outcomes across varying institutional antimicrobial stewardship program (ASP) practices is unclear. This study evaluated clinical outcomes associated with the “real‐world” implementation of BCID in a national health system with varying ASP practices. Design National, multicenter, retrospective, pre–post quasi‐experimental study of hospitalized patients admitted from 2015 to 2020 to VHA facilities, which introduced the BCID for ≥1 year. Setting United States Veterans Health Administration (VHA) hospitals with BCID. Patients Hospitalized VHA patients with ≥1 blood culture positive for bacteria featured on the BCID panel. Intervention Comparison of outcomes between the pre‐ and post‐BCID implementation groups. Measurements Outcomes evaluated included early antimicrobial de‐escalation within 48 h, defined as reduction in antimicrobial spectrum scores, time to appropriate therapy, and 30‐day mortality. Main Results A total of 4138 patients (pre‐BCID, n = 2100; post‐BCID, n = 2038) met the study criteria. Implementation of BCID was associated with significant improvements in early antimicrobial de‐escalation (34.6%: pre‐BCID vs. 38.1%: post‐BCID; p = 0.022), which persisted after adjusting for other covariates (adjusted risk ratio [aRR], 1.11; 95% confidence interval [CI], 1.02–1.20; p = 0.011). Median time to appropriate therapy was shorter in the post‐BCID implementation group relative to the pre‐BCID group (9 h: pre‐BCID vs. 8 h: post‐BCID, respectively, p = 0.005), and a greater percentage of patients received early appropriate antimicrobial therapy within 48 h in the post‐BCID implementation group (91.7%: pre‐BCID vs. 93.8%: post‐BCID; p = 0.008). In the multivariable regression analysis, BCID implementation was significantly associated with a higher likelihood of appropriate therapy within 48 h (aRR, 1.02; 95% CI, 1.01–1.08; p = 0.020). There was no difference in 30‐day mortality between groups overall (12.6% pre‐BCID vs. 11.2% post‐BCID; p = 0.211). Conclusions In a “real‐world” clinical setting, the implementation of BCID was associated with clinical improvements in antimicrobial utilization. The BCID platform may serve as a useful adjunct for BSI management in facilities with ASP.

Among patients with methicillin-resistant Staphylococcus aureus bacteremia, vancomycin-associated acute kidney injury increased as a function of the day 2 area under the curve (AUC), even for daily AUCs within the recommended therapeutic range (400–600). Further data are needed to determine if daily AUCs <400 can be maintained without compromising efficacy.

In this multicenter study of adult patients who presented to the emergency department with an Enterobacterales complicated urinary tract infection (cUTI), high rates of resistance and co-resistance to commonly used oral antibiotics (fluoroquinolones, trimethoprim-sulfamethoxazole, nitrofurantoin, and third-generation cephalosporins) were observed.