Clinical outcomes in patients infected with ertapenem-only-resistant Enterobacterales versus multi-carbapenem-resistant Enterobacterales.

BACKGROUND: Use of anti-carbapenem-resistant Enterobacterales (anti-CRE) agents such as ceftazidime/avibactam has been associated with improved clinical outcome in cohorts that primarily include patients infected with CRE that are resistant to meropenem (MCRE). OBJECTIVES: To clarify whether patients with CRE resistant to ertapenem but susceptible to meropenem (ertapenem-only-resistant Enterobacterales; EORE) benefit from therapy with anti-CRE agents. METHODS: Patients treated for CRE infection in hospitals in the USA between 2016 and 2019 and enrolled in the CRACKLE-2 study were included. The primary outcome was the desirability of outcome ranking (DOOR) assessed at 30 days after index cultures. RESULTS: The EORE group included 213 patients and the MCRE group included 643. The demographics were similar between the groups except for the patients' race and origin before admission. The MCRE group received anti-CRE agents for definitive therapy significantly more frequently compared with the EORE group (30% versus 5% for ceftazidime/avibactam). We did not observe a significant difference between the groups in the adjusted DOOR probability of a more desirable outcome for a randomly selected patient in the EORE group compared with the MCRE group (52.5%; 95% CI, 48.3%-56.7%). The MCRE group had a similar proportion of patients who died at 30 days (26% versus 21%) and who were discharged to home (29% versus 40%), compared with the EORE group. CONCLUSIONS: Patients with clinical EORE infection rarely received anti-CRE agents, but attained similar outcomes compared with patients with MCRE infection. The findings support current IDSA treatment guidance for meropenem- or imipenem-based therapy for treatment of EORE infections.

Carbapenem-resistant Acinetobacter baumannii complex in the United States-An epidemiological and molecular description of isolates collected through the Emerging Infections Program, 2019.

BACKGROUND: Understanding the epidemiology of carbapenem-resistant A. baumannii complex (CRAB) and the patients impacted is an important step toward informing better infection prevention and control practices and improving public health response. METHODS: Active, population-based surveillance was conducted for CRAB in 9 U.S. sites from January 1 to December 31, 2019. Medical records were reviewed, isolates were collected and characterized including antimicrobial susceptibility testing and whole genome sequencing. RESULTS: Among 136 incident cases in 2019, 66 isolates were collected and characterized; 56.5% were from cases who were male, 54.5% were from persons of Black or African American race with non-Hispanic ethnicity, and the median age was 63.5 years. Most isolates, 77.2%, were isolated from urine, and 50.0% were collected in the outpatient setting; 72.7% of isolates harbored an acquired carbapenemase gene (aCP), predominantly blaOXA-23 or blaOXA-24/40; however, an isolate with blaNDM was identified. The antimicrobial agent with the most in vitro activity was cefiderocol (96.9% of isolates were susceptible). CONCLUSIONS: Our surveillance found that CRAB isolates in the U.S. commonly harbor an aCP, have an antimicrobial susceptibility profile that is defined as difficult-to-treat resistance, and epidemiologically are similar regardless of the presence of an aCP.

Evaluation of hospital-onset bacteraemia and fungaemia in the USA as a potential healthcare quality measure: a cross-sectional study.

BACKGROUND: Hospital-onset bacteraemia and fungaemia (HOB) is being explored as a surveillance and quality metric. The objectives of the current study were to determine sources and preventability of HOB in hospitalised patients in the USA and to identify factors associated with perceived preventability. METHODS: We conducted a cross-sectional study of HOB events at 10 academic and three community hospitals using structured chart review. HOB was defined as a blood culture on or after hospital day 4 with growth of one or more bacterial or fungal organisms. HOB events were stratified by commensal and non-commensal organisms. Medical resident physicians, infectious disease fellows or infection preventionists reviewed charts to determine HOB source, and infectious disease physicians with training in infection prevention/hospital epidemiology rated preventability from 1 to 6 (1=definitely preventable to 6=definitely not preventable) using a structured guide. Ratings of 1-3 were collectively considered 'potentially preventable' and 4-6 'potentially not preventable'. RESULTS: Among 1789 HOB events with non-commensal organisms, gastrointestinal (including neutropenic translocation) (35%) and endovascular (32%) were the most common sources. Overall, 636/1789 (36%) non-commensal and 238/320 (74%) commensal HOB events were rated potentially preventable. In logistic regression analysis among non-commensal HOB events, events attributed to intravascular catheter-related infection, indwelling urinary catheter-related infection and surgical site infection had higher odds of being rated preventable while events with neutropenia, immunosuppression, gastrointestinal sources, polymicrobial cultures and previous positive blood culture in the same admission had lower odds of being rated preventable, compared with events without those attributes. Of 636 potentially preventable non-commensal HOB events, 47% were endovascular in origin, followed by gastrointestinal, respiratory and urinary sources; approximately 40% of those events would not be captured through existing healthcare-associated infection surveillance. DISCUSSION: Factors identified as associated with higher or lower preventability should be used to guide inclusion, exclusion and risk adjustment for an HOB-related quality metric.

Rates of resistance and heteroresistance to newer ß-lactam/ß-lactamase inhibitors for carbapenem-resistant Enterobacterales.

Background: Heteroresistance (HR), the presence of antibiotic-resistant subpopulations within a primary isogenic population, may be a potentially overlooked contributor to newer ß-lactam/ß-lactamase inhibitor (BL/BLI) treatment failure in carbapenem-resistant Enterobacterales (CRE) infections. Objectives: To determine rates of susceptibility and HR to BL/BLIs ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam in clinical CRE isolates. Methods: The first CRE isolate per patient per year from two >500 bed academic hospitals from 1 January 2016 to 31 December 2021, were included. Reference broth microdilution (BMD) was used to determine antibiotic susceptibility, and population analysis profiling (PAP) to determine HR. Carbapenemase production (CP) was determined using the Carba NP assay. Results: Among 327 CRE isolates, 46% were Enterobacter cloacae, 38% Klebsiella pneumoniae and 16% Escherichia coli. By BMD, 87% to 98% of CRE were susceptible to the three antibiotics tested. From 2016 to 2021, there were incremental decreases in the rates of susceptibility to each of the three BL/BLIs. HR was detected in each species-antibiotic combination, with the highest rates of HR (26%) found in K. pneumoniae isolates with imipenem/relebactam. HR or resistance to at least one BL/BLI by PAP was found in 24% of CRE isolates and 65% of these had detectable CP. Conclusion: Twenty-four percent of CRE isolates tested were either resistant or heteroresistant (HR) to newer BL/BLIs, with an overall decrease of ∼10% susceptibility over 6 years. While newer BL/BLIs remain active against most CRE, these findings support the need for ongoing antibiotic stewardship and a better understanding of the clinical implications of HR in CRE.

Implementation of contact precautions for multidrug-resistant organisms in the post-COVID-19 pandemic era: An updated national Emerging Infections Network (EIN) survey.

OBJECTIVE: To understand how healthcare facilities employ contact precautions for patients with multidrug-resistant organisms (MDROs) in the post-coronavirus disease 2019 (COVID-19) era and explore changes since 2014. DESIGN: Cross-sectional survey. PARTICIPANTS: Emerging Infections Network (EIN) physicians involved in infection prevention or hospital epidemiology. METHODS: In September 2022, we sent via email an 8-question survey on contact precautions and adjunctive measures to reduce MDRO transmission in inpatient facilities. We also asked about changes since the COVID-19 pandemic. We used descriptive statistics to summarize data and compared results to a similar survey administered in 2014. RESULTS: Of 708 EIN members, 283 (40%) responded to the survey and 201 reported working in infection prevention. A majority of facilities (66% and 69%) routinely use contact precautions for methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) respectively, compared to 93% and 92% in 2014. Nearly all (>90%) use contact precautions for Candida auris, carbapenem-resistant Enterobacterales (CRE), and carbapenem-resistant Acinetobacter baumannii. More variability was reported for carbapenem-resistant Pseudomonas aeruginosa and extended-spectrum ß-lactamase-producing gram-negative organisms. Compared to 2014, fewer hospitals perform active surveillance for MRSA and VRE. Overall, 90% of facilities used chlorhexidine gluconate bathing in all or select inpatients, and 53% used ultraviolet light or hydrogen peroxide vapor disinfection at discharge. Many respondents (44%) reported changes to contact precautions since COVID-19 that remain in place. CONCLUSIONS: Heterogeneity exists in the use of transmission-based precautions and adjunctive infection prevention measures aimed at reducing MDRO transmission. This variation reflects a need for updated and specific guidance, as well as further research on the use of contact precautions in healthcare facilities.

Early Tecovirimat Treatment for Mpox Disease Among People With HIV.

Importance: Despite a lack of effectiveness data in humans, tecovirimat was widely prescribed to people with HIV (PWH) with mpox during the 2022 mpox epidemic, particularly PWH with low CD4+ T-cell counts or severe mpox clinical manifestations. Objective: To evaluate if PWH with mpox who were treated with tecovirimat within 7 days of symptom onset were less likely to have mpox disease progression. Design, Setting, and Participants: This cohort study included PWH diagnosed with mpox at 4 hospitals in Atlanta, Georgia, between June 1 and October 7, 2022. Patients were grouped according to whether they were treated with tecovirimat within 7 days of mpox symptom onset (early tecovirimat cohort) or they did not receive tecovirimat or received the drug 7 or more days after symptom onset (late or no tecovirimat cohort). Multivariable logistic regression models were used to identify factors associated with progression of mpox disease. The 2 cohorts were then matched 1:1 using propensity scores based on the identified factors, and mpox disease progression was compared. Exposures: Treatment with tecovirimat within 7 days of mpox symptom onset. Main Outcome and Measures: Progression of mpox disease, defined as the development of at least 1 severe mpox criterion established by the US Centers for Disease Control and Prevention, after symptom day 7. Results: After propensity score matching, a total of 112 PWH were included in the analysis; 56 received tecovirimat within 7 days of mpox symptom onset (early tecovirimat group) and 56 were either treated later or did not receive tecovirimat (late or no tecovirimat group). In the early tecovirimat group, the median (IQR) age was 35 (30-42) years; 54 individuals (96.4%) were cisgender men, 46 (82.1%) were Black individuals, and 10 (17.9%) were individuals of other races (American Indian or Alaska Native, Asian, Native Hawaiian or Other Pacific Islander, or White) or unknown race. In the late or no tecovirimat group, the median (IQR) age was 36 (32-43) years; 54 (96.4%) were cisgender men, 49 (87.5%) were Black individuals, and 7 (12.5%) were individuals of other races or unknown race. Mpox disease progression occurred in 3 PWH (5.4%) in the early tecovirimat group and in 15 PWH (26.8%) in the late or no tecovirimat group (paired odds ratio, 13.00 [95% CI, 1.71-99.40]; P = .002). Conclusion and Relevance: Results of this cohort study support starting tecovirimat in all PWH as soon as an mpox diagnosis is suspected. Additional research is warranted to confirm these findings.

Evaluating indwelling devices and other risk factors for mortality in invasive Carbapenem-resistant Enterobacterales infections in Georgia, 2012-2019.

Objective: Carbapenem-resistant Enterobacterales (CRE) infections are a public health threat due to the risk of transmission between patients and high associated mortality. We sought to identify risk factors for mortality in patients with invasive CRE infections and to specifically evaluate whether there was an association between indwelling medical devices and 90-day mortality. Design: Retrospective observational cohort study of patients infected with CRE in the eight-county metropolitan Atlanta area between 2012 and 2019. Methods: Patients with invasive CRE infections were identified via the Georgia Emerging Infections Program's active, population- and laboratory-based surveillance system and linked with the Georgia Vital Statistics database. We used bivariate analysis to identify risk factors for mortality and completed log binomial multivariable regression to estimate risk ratios (RR) for the association between indwelling devices and mortality. Results: In total, 154 invasive CRE infections were identified, with indwelling devices present in most patients (87.7%) around the time of infection. Admission to an intensive care unit was found to be associated with 90-day mortality (adjusted RR [aRR] 1.55, 95% CI 1.07, 2.24); however, the presence of any indwelling device was not associated with increased risk of 90-day mortality in multivariable analysis (aRR 1.22, 95% CI 0.55, 2.73). Having at least two indwelling devices was associated with increased mortality (aRR 1.79, 95% CI 1.05, 3.05). Conclusions: Indwelling devices were prevalent in our cohort but were not consistently associated with an increased risk of mortality. Further studies are needed to examine this relationship and the role of device removal.

Trends in Incidence of Carbapenem-Resistant Enterobacterales in 7 US Sites, 2016─2020.

Background: We described changes in 2016─2020 carbapenem-resistant Enterobacterales (CRE) incidence rates in 7 US sites that conduct population-based CRE surveillance. Methods: An incident CRE case was defined as the first isolation of Escherichia coli, Klebsiella spp., or Enterobacter spp. resistant to ≥1 carbapenem from a sterile site or urine in a surveillance area resident in a 30-day period. We reviewed medical records and classified cases as hospital-onset (HO), healthcare-associated community-onset (HACO), or community-associated (CA) CRE based on healthcare exposures and location of disease onset. We calculated incidence rates using census data. We used Poisson mixed effects regression models to perform 2016─2020 trend analyses, adjusting for sex, race/ethnicity, and age. We compared adjusted incidence rates between 2016 and subsequent years using incidence rate ratios (RRs) and 95% confidence intervals (CIs). Results: Of 4996 CRE cases, 62% were HACO, 21% CA, and 14% HO. The crude CRE incidence rate per 100 000 was 7.51 in 2016 and 6.08 in 2020 and was highest for HACO, followed by CA and HO. From 2016 to 2020, the adjusted overall CRE incidence rate decreased by 24% (RR, 0.76 [95% CI, .70-.83]). Significant decreases in incidence rates in 2020 were seen for HACO (RR, 0.75 [95% CI, .67-.84]) and CA (0.75 [.61-.92]) but not for HO CRE. Conclusions: Adjusted CRE incidence rates declined from 2016 to 2020, but changes over time varied by epidemiologic class. Continued surveillance and effective control strategies are needed to prevent CRE in all settings.