Postoperative outcomes after receipt of ertapenem antimicrobial prophylaxis for colon surgery: a multicenter retrospective cohort study.

OBJECTIVE: To evaluate postoperative outcomes among patients undergoing colon surgery who receive perioperative prophylaxis with ertapenem compared to other antibiotic regimens. DESIGN AND SETTING: Multicenter retrospective cohort study among adults undergoing colon surgery in seven hospitals across three health systems from 1/1/2010 to 9/1/2015. METHODS: Generalized linear mixed logistic regression models were applied to assess differential odds of select outcomes among patients who received perioperative prophylaxis with ertapenem compared to other regimens. Postoperative outcomes of interest included surgical site infection (SSI), Clostridioides difficile infection (CDI) and clinical culture positivity for carbapenem-resistant Enterobacteraciae (CRE). Inverse probability weights were applied to account for differing covariate distributions across ertapenem and non-ertapenem groups. RESULTS: A total of 2,109 patients were included for analysis. The odds of postoperative SSI was 1.56 times higher among individuals who received ertapenem than among those receiving other perioperative antimicrobial prophylaxis regimens in our cohort (46 [3.5%] vs 20 [2.5%]; IPW-weighted OR 1.56, [95% CI, 1.08-2.26], P = .02). No statistically significant differences in odds of postoperative CDI (24 [1.8%] vs 16 [2.0%]; IPW-weighted OR 1.07 [95% CI, .68-1.68], P = .78) were observed between patients who received ertapenem prophylaxis compared to other regimens. Clinical CRE culture positivity was rare in both groups (.2%-.5%) and did not differ statistically. CONCLUSIONS: Ertapenem use for perioperative prophylaxis was associated with increased odds of SSI among patients undergoing colon surgery in our study population, though no differences in CDI or clinical CRE culture positivity were identified. Further study and replication of these findings are needed.

Gut microbiome correlates of recurrent urinary tract infection: a longitudinal, multi-center study.

Background: Urinary tract infections (UTI) affect approximately 250 million people annually worldwide. Patients often experience a cycle of antimicrobial treatment and recurrent UTI (rUTI) that is thought to be facilitated by a gut reservoir of uropathogenic Escherichia coli (UPEC). Methods: 125 patients with UTI caused by an antibiotic-resistant organism (ARO) were enrolled from July 2016 to May 2019 in a longitudinal, multi-center cohort study. Multivariate statistical models were used to assess the relationship between uropathogen colonization and recurrent UTI (rUTI), controlling for clinical characteristics. 644 stool samples and 895 UPEC isolates were interrogated for taxonomic composition, antimicrobial resistance genes, and phenotypic resistance. Cohort UTI gut microbiome profiles were compared against published healthy and UTI reference microbiomes, as well as assessed within-cohort for timepoint- and recurrence-specific differences. Findings: Risk of rUTI was not independently associated with clinical characteristics. The UTI gut microbiome was distinct from healthy reference microbiomes in both taxonomic composition and antimicrobial resistance gene (ARG) burden, with 11 differentially abundant taxa at the genus level. rUTI and non-rUTI gut microbiomes in the cohort did not generally differ, but gut microbiomes from urinary tract colonized patients were elevated in E. coli abundance 7-14 days post-antimicrobial treatment. Corresponding UPEC gut isolates from urinary tract colonizing lineages showed elevated phenotypic resistance against 11 of 23 tested drugs compared to non-colonizing lineages. Interpretation: The gut microbiome is implicated in UPEC urinary tract colonization during rUTI, serving as an ARG-enriched reservoir for UPEC. UPEC can asymptomatically colonize the gut and urinary tract, and post-antimicrobial blooms of gut E. coli among urinary tract colonized patients suggest that cross-habitat migration of UPEC is an important mechanism of rUTI. Thus, treatment duration and UPEC populations in both the urinary and gastrointestinal tract should be considered in treating rUTI and developing novel therapeutics. Funding: This work was supported in part by awards from the U.S. Centers for Disease Control and Prevention Epicenter Prevention Program (grant U54CK000482; principal investigator, V.J.F.); to J.H.K. from the Longer Life Foundation (an RGA/Washington University partnership), the National Center for Advancing Translational Sciences (grants KL2TR002346 and UL1TR002345), and the National Institute of Allergy and Infectious Diseases (NIAID) (grant K23A1137321) of the National Institutes of Health (NIH); and to G.D. from NIAID (grant R01AI123394) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (grant R01HD092414) of NIH. R.T.'s research was funded by the Deutsche Forschungsgemeinschaft (DFG; German Research Foundation; grant 402733540). REDCap is Supported by Clinical and Translational Science Award (CTSA) Grant UL1 TR002345 and Siteman Comprehensive Cancer Center and NCI Cancer Center Support Grant P30 CA091842. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.

Implementing nasal povidone-iodine decolonization to reduce infections in hemodialysis units: a qualitative assessment.

BACKGROUND: A substantial proportion of patients undergoing hemodialysis carry Staphylococcus aureus in their noses, and carriers are at increased risk of S. aureus bloodstream infections. Our pragmatic clinical trial implemented nasal povidone-iodine (PVI) decolonization for the prevention of bloodstream infections in the novel setting of hemodialysis units. OBJECTIVE: We aimed to identify pragmatic strategies for implementing PVI decolonization among patients in outpatient hemodialysis units. DESIGN: Qualitative descriptive study. SETTING: Outpatient hemodialysis units affiliated with five US academic medical centers. Units varied in size, patient demographics, and geographic location. INTERVIEWEES: Sixty-six interviewees including nurses, hemodialysis technicians, research coordinators, and other personnel. METHODS: We conducted interviews with personnel affiliated with all five academic medical centers and conducted thematic analysis of transcripts. RESULTS: Hemodialysis units had varied success with patient recruitment, but interviewees reported that patients and healthcare personnel (HCP) found PVI decolonization acceptable and feasible. Leadership support, HCP engagement, and tailored patient-focused tools or strategies facilitated patient engagement and PVI implementation. Interviewees reported both patients and HCP sometimes underestimated patients' infection risks and experienced infection-prevention fatigue. Other HCP barriers included limited staffing and poor staff engagement. Patient barriers included high health burdens, language barriers, memory issues, and lack of social support. CONCLUSION: Our qualitative study suggests that PVI decolonization would be acceptable to patients and clinical personnel, and implementation is feasible for outpatient hemodialysis units. Hemodialysis units could facilitate implementation by engaging unit leaders, patients and personnel, and developing education for patients about their infection risk.

Impact of deceased organ donor marijuana use on donor culture positivity and solid organ transplant recipient outcomes.

With the increasing prevalence of marijuana use in the US, many deceased organ donors have a history of marijuana use, raising concerns about infectious risks to transplant recipients. We performed a multicenter retrospective cohort study in which exposed donors were those with recent marijuana use (in the prior 12 months) and unexposed donors were those with no recent marijuana use. Primary outcomes included the following: (1) positive donor cultures for bacteria or fungi, (2) recipient infection due to bacteria or fungi within 3 months posttransplant, and (3) recipient graft failure or death within 12 months posttransplant. Multivariable regression was used to evaluate the relationship between donor marijuana use and each outcome. A total of 658 recipients who received organs from 394 donors were included. Recent marijuana use was not associated with donor culture positivity (aOR: 0.84, 95% CI: 0.39-1.81, P = .65), recipient infection (aHR: 1.02, 95% CI: 0.76-1.38, P = .90), or recipient graft failure or death (aHR: 1.65, 95% CI: 0.90-3.02, P = .11). Our data suggest that organs from donors with a history of recent marijuana use do not pose significant infectious risks in the early posttransplant period.

Impact of measurement and feedback on chlorhexidine gluconate bathing among intensive care unit patients: A multicenter study.

OBJECTIVE: To assess whether measurement and feedback of chlorhexidine gluconate (CHG) skin concentrations can improve CHG bathing practice across multiple intensive care units (ICUs). DESIGN: A before-and-after quality improvement study measuring patient CHG skin concentrations during 6 point-prevalence surveys (3 surveys each during baseline and intervention periods). SETTING: The study was conducted across 7 geographically diverse ICUs with routine CHG bathing. PARTICIPANTS: Adult patients in the medical ICU. METHODS: CHG skin concentrations were measured at the neck, axilla, and inguinal region using a semiquantitative colorimetric assay. Aggregate unit-level CHG skin concentration measurements from the baseline period and each intervention period survey were reported back to ICU leadership, which then used routine education and quality improvement activities to improve CHG bathing practice. We used multilevel linear models to assess the impact of intervention on CHG skin concentrations. RESULTS: We enrolled 681 (93%) of 736 eligible patients; 92% received a CHG bath prior to survey. At baseline, CHG skin concentrations were lowest on the neck, compared to axillary or inguinal regions (P < .001). CHG was not detected on 33% of necks, 19% of axillae, and 18% of inguinal regions (P < .001 for differences in body sites). During the intervention period, ICUs that used CHG-impregnated cloths had a 3-fold increase in patient CHG skin concentrations as compared to baseline (P < .001). CONCLUSIONS: Routine CHG bathing performance in the ICU varied across multiple hospitals. Measurement and feedback of CHG skin concentrations can be an important tool to improve CHG bathing practice.

Severe acute respiratory coronavirus virus 2 (SARS-CoV-2) surface contamination in staff common areas and impact on healthcare worker infection: Prospective surveillance during the coronavirus disease 2019 (COVID-19) pandemic.

We prospectively surveyed SARS-CoV-2 RNA contamination in staff common areas within an acute-care hospital. An increasing prevalence of surface contamination was detected over time. Adjusting for patient census or community incidence of coronavirus disease 2019 (COVID-19), the proportion of contaminated surfaces did not predict healthcare worker COVID-19 infection on study units.

Clinical Outcomes and Risk Factors for Carbapenem-resistant Enterobacterales Bloodstream Infection in Solid Organ Transplant Recipients.

BACKGROUND: The clinical outcomes associated with, and risk factors for, carbapenem-resistant Enterobacterales (CRE) bloodstream infections (BSIs) in solid organ transplant (SOT) recipients remain ill-defined. METHODS: A multicenter retrospective cohort study was performed, including SOT recipients with an Enterobacterales BSI between 2005 and 2018. Exposed subjects were those with a CRE BSI. Unexposed subjects were those with a non-CRE BSI. A multivariable survival analysis was performed to determine the association between CRE BSI and risk of all-cause mortality within 60 d. Multivariable logistic regression analysis was performed to determine independent risk factors for CRE BSI. RESULTS: Of 897 cases of Enterobacterales BSI in SOT recipients, 70 (8%) were due to CRE. On multivariable analysis, CRE BSI was associated with a significantly increased hazard of all-cause mortality (adjusted hazard ratio, 2.85; 95% confidence interval [CI], 1.68-4.84; P < 0.001). Independent risk factors for CRE BSI included prior CRE colonization or infection (adjusted odds ratio [aOR] 9.86; 95% CI, 4.88-19.93; P < 0.001)' liver transplantation (aOR, 2.64; 95% CI, 1.23-5.65; P = 0.012)' lung transplantation (aOR, 3.76; 95% CI, 1.40-10.09; P = 0.009)' and exposure to a third-generation cephalosporin (aOR, 2.21; 95% CI, 1.17-4.17; P = 0.015) or carbapenem (aOR, 2.80; 95% CI, 1.54-5.10; P = 0.001) in the prior 6 months. CONCLUSIONS: CRE BSI is associated with significantly worse outcomes than more antibiotic-susceptible Enterobacterales BSI in SOT recipients.

Characterization of resistance to newer antimicrobials among carbapenem-resistant Klebsiella pneumoniae in the post-acute-care setting.

We assessed susceptibility patterns to newer antimicrobial agents among clinical carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates from patients in long-term acute-care hospitals (LTACHs) from 2014 to 2015. Meropenem-vaborbactam and imipenem-relebactam nonsusceptibility were observed among 9.9% and 9.1% of isolates, respectively. Nonsusceptibility to ceftazidime-avibactam (1.1%) and plazomicin (0.8%) were uncommon.

Risk factors for meticillin-resistant Staphylococcus aureus (MRSA) carriage in MRSA-exposed household pets.

BACKGROUND: Household pets can carry meticillin-resistant Staphylococcus aureus (MRSA) introduced to the home by their human companions. Specific factors promoting pet carriage of this pathogen have not been fully elucidated. OBJECTIVE: This study evaluated MRSA cultured from pets and the home environment in households where a human infected with MRSA had been identified, and aimed to determine potential risk factors for pet MRSA carriage. MATERIALS AND METHODS: Humans diagnosed with community-associated MRSA (CA-MRSA) skin or soft-tissue infection (SSTI) in the mid-Atlantic United States were identified. One hundred forty-two dogs and cats from 57 affected households were identified of which 134 (94.4%) pets and the household environment were sampled for bacterial culture, PCR confirmation and spa-typing for MRSA strain determination. Samples were obtained 3 months later from 86 pets. RESULTS: At baseline, 12 (9.0%) pets carried MRSA. Potential risk factors associated with carriage included pet bed (environmental) MRSA contamination, flea infestation and prior antimicrobial use in the pet. Pets tended to carry human-adapted MRSA strains and spa-types of MRSA isolates cultured from pets were concordant with strains cultured from the home environment in seven of eight homes (87.5%) at baseline. CONCLUSIONS AND CLINICAL RELEVANCE: Results may inform risk-based veterinary clinical recommendations and provide evidence for selective pet testing as a possible alternative to early removal of pets from the homes of humans infected with MRSA. MRSA contamination of the home environment is likely an important risk factor for pet MRSA carriage, and household interventions should be considered to reduce risk of MRSA carriage in exposed pets.

Risk Factors for Colistin-Resistant Carbapenem-Resistant Klebsiella pneumoniae in the Postacute Care Setting.

We assessed risk factors for colistin resistance among carbapenem-resistant Klebsiella pneumoniae (CRKP) from 375 patients in long-term acute care hospitals. Recent colistin or polymyxin B exposure was associated with increased odds of colistin resistance (adjusted odds ratio = 1.11 per day of exposure, 95% confidence interval = 1.03-1.19, P = .007).

Impact of deceased organ donor injection drug use on donor culture positivity and recipient outcomes.

BACKGROUND: Due to the ongoing opioid epidemic in the United States, deceased organ donors increasingly have a history of injection drug use (IDU), raising concerns about infectious risks to solid organ transplant (SOT) recipients. We sought to determine how recent IDU among deceased organ donors impacted donor culture results and recipient outcomes. METHODS: A retrospective cohort study was performed at three transplant centers. Exposed donors were those with "recent IDU" (in the prior 12 months). Primary outcomes included (1) positive donor cultures for bacteria or Candida species, (2) recipient bacterial or Candida infection within 3 months posttransplant, and (3) recipient graft failure or death within 12 months posttransplant. Mixed effects multivariable regression models were used to evaluate the relationship between recent donor IDU and each outcome. RESULTS: A total of 658 SOT recipients who received organs from 394 donors were included. Sixty-six (17%) donors had a history of recent IDU. Recent IDU in donors was associated with a significantly increased odds of donor culture positivity (aOR 3.65, 95% CI 1.06-12.60, p = .04) but was not associated with SOT recipient infection (aHR 0.98, 95% CI 0.71-1.36, p = .92) or graft failure or death (aHR 0.67, 95% CI 0.29-1.51, p = .33). CONCLUSION: Donors with recent IDU are more likely to have positive cultures, but their recipients' outcomes are unaffected, suggesting organs from donors with recent IDU may be safely utilized.

Persisting uropathogenic Escherichia coli lineages show signatures of niche-specific within-host adaptation mediated by mobile genetic elements.

Large-scale genomic studies have identified within-host adaptation as a hallmark of bacterial infections. However, the impact of physiological, metabolic, and immunological differences between distinct niches on the pathoadaptation of opportunistic pathogens remains elusive. Here, we profile the within-host adaptation and evolutionary trajectories of 976 isolates representing 119 lineages of uropathogenic Escherichia coli (UPEC) sampled longitudinally from both the gastrointestinal and urinary tracts of 123 patients with urinary tract infections. We show that lineages persisting in both niches within a patient exhibit increased allelic diversity. Habitat-specific selection results in niche-specific adaptive mutations and genes, putatively mediating fitness in either environment. Within-lineage inter-habitat genomic plasticity mediated by mobile genetic elements (MGEs) provides the opportunistic pathogen with a mechanism to adapt to the physiological conditions of either habitat, and reduced MGE richness is associated with recurrence in gut-adapted UPEC lineages. Collectively, our results establish niche-specific adaptation as a driver of UPEC within-host evolution.

SARS-CoV-2 RNA persists on surfaces following terminal disinfection of COVID-19 hospital isolation rooms.

We evaluated the effect of terminal cleaning on SARS-CoV-2 RNA contamination of COVID-19 isolation rooms in an acute care hospital. SARS-CoV-2 RNA was detected on 32.1% of room surfaces after cleaning; the odds of contamination increased with month. The prevalence of elevated high-touch surface contamination was lower in terminally cleaned rooms than patient-occupied rooms.

Stopping Hospital Infections With Environmental Services (SHINE): A Cluster-randomized Trial of Intensive Monitoring Methods for Terminal Room Cleaning on Rates of Multidrug-resistant Organisms in the Intensive Care Unit.

BACKGROUND: Multidrug-resistant organisms (MDROs) frequently contaminate hospital environments. We performed a multicenter, cluster-randomized, crossover trial of 2 methods for monitoring of terminal cleaning effectiveness. METHODS: Six intensive care units (ICUs) at 3 medical centers received both interventions sequentially, in randomized order. Ten surfaces were surveyed each in 5 rooms weekly, after terminal cleaning, with adenosine triphosphate (ATP) monitoring or an ultraviolet fluorescent marker (UV/F). Results were delivered to environmental services staff in real time with failing surfaces recleaned. We measured monthly rates of MDRO infection or colonization, including methicillin-resistant Staphylococcus aureus, Clostridioides difficile, vancomycin-resistant Enterococcus, and MDR gram-negative bacilli (MDR-GNB) during a 12-month baseline period and sequential 6-month intervention periods, separated by a 2-month washout. Primary analysis compared only the randomized intervention periods, whereas secondary analysis included the baseline. RESULTS: The ATP method was associated with a reduction in incidence rate of MDRO infection or colonization compared with the UV/F period (incidence rate ratio [IRR] 0.876; 95% confidence interval [CI], 0.807-0.951; P = .002). Including the baseline period, the ATP method was associated with reduced infection with MDROs (IRR 0.924; 95% CI, 0.855-0.998; P = .04), and MDR-GNB infection or colonization (IRR 0.856; 95% CI, 0.825-0.887; P < .001). The UV/F intervention was not associated with a statistically significant impact on these outcomes. Room turnaround time increased by a median of 1 minute with the ATP intervention and 4.5 minutes with UV/F compared with baseline. CONCLUSIONS: Intensive monitoring of ICU terminal room cleaning with an ATP modality is associated with a reduction of MDRO infection and colonization.

Improving Outpatient Antibiotic Prescribing for Respiratory Tract Infections in Primary Care: A Stepped-Wedge Cluster Randomized Trial.

BACKGROUND: Inappropriate antibiotic prescribing is common in primary care (PC), particularly for respiratory tract diagnoses (RTDs). However, the optimal approach for improving prescribing remains unknown. METHODS: We conducted a stepped-wedge study in PC practices within a health system to assess the impact of a provider-targeted intervention on antibiotic prescribing for RTDs. RTDs were grouped into tiers based on appropriateness of antibiotic prescribing: tier 1 (almost always indicated), tier 2 (may be indicated), and tier 3 (rarely indicated). Providers received education on appropriate RTD prescribing followed by monthly peer comparison feedback on antibiotic prescribing for (1) all tiers and (2) tier 3 RTDs. A χ 2 test was used to compare the proportion of visits with antibiotic prescriptions before and during the intervention. Mixed-effects multivariable logistic regression analysis was performed to assess the association between the intervention and antibiotic prescribing. RESULTS: Across 30 PC practices and 185 755 total visits, overall antibiotic prescribing was reduced with the intervention, from 35.2% to 23.0% of visits (P < .001). In multivariable analysis, the intervention was associated with a reduced odds of antibiotic prescription for tiers 2 (odds ratio [OR] 0.57; 95% confidence interval [CI] .52-.62) and 3 (OR 0.57; 95% CI .53-.61) but not for tier 1 (OR 0.98; 95% CI .83-1.16). CONCLUSIONS: A provider-focused intervention reduced overall antibiotic prescribing for RTDs without affecting prescribing for infections that likely require antibiotics. Future research should examine the sustainability of such interventions, potential unintended adverse effects on patient health or satisfaction, and provider perceptions and acceptability.

Spatial and temporal effects on severe acute respiratory coronavirus virus 2 (SARS-CoV-2) contamination of the healthcare environment.

BACKGROUND: The spatial and temporal extent of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) environmental contamination has not been precisely defined. We sought to elucidate contamination of different surface types and how contamination changes over time. METHODS: We sampled surfaces longitudinally within COVID-19 patient rooms, performed quantitative RT-PCR for the detection of SARS-CoV-2 RNA, and modeled distance, time, and severity of illness on the probability of detecting SARS-CoV-2 using a mixed-effects binomial model. RESULTS: The probability of detecting SARS-CoV-2 RNA in a patient room did not vary with distance. However, we found that surface type predicted probability of detection, with floors and high-touch surfaces having the highest probability of detection: floors (odds ratio [OR], 67.8; 95% credible interval [CrI], 36.3-131) and high-touch elevated surfaces (OR, 7.39; 95% CrI, 4.31-13.1). Increased surface contamination was observed in room where patients required high-flow oxygen, positive airway pressure, or mechanical ventilation (OR, 1.6; 95% CrI, 1.03-2.53). The probability of elevated surface contamination decayed with prolonged hospitalization, but the probability of floor detection increased with the duration of the local pandemic wave. CONCLUSIONS: Distance from a patient's bed did not predict SARS-CoV-2 RNA deposition in patient rooms, but surface type, severity of illness, and time from local pandemic wave predicted surface deposition.

Impact of donor multidrug-resistant organisms on solid organ transplant recipient outcomes.

BACKGROUND: The impact of donor colonization or infection with multidrug-resistant organisms (MDROs) on solid organ transplant (SOT) recipient outcomes remains uncertain. We thus evaluated the association between donor MDROs and risk of posttransplant infection, graft failure, and mortality. METHODS: A multicenter retrospective cohort study was performed. All SOT recipients with a local deceased donor were included. The cohort was divided into three exposure groups: recipients whose donors had (1) an MDRO, (2) a non-MDRO bacterial or candidal organism, or (3) no growth on cultures. The primary outcomes were (1) bacterial or invasive candidal infection within 3 months and (2) graft failure or death within 12 months posttransplant. Mixed effect multivariable frailty models were developed to evaluate each association. RESULTS: Of 658 total SOT recipients, 93 (14%) had a donor with an MDRO, 477 (73%) had a donor with a non-MDRO organism, and 88 (13%) had a donor with no organisms on culture. On multivariable analyses, donor MDROs were associated with a significantly increased hazard of infection compared to those with negative donor cultures (adjust hazard ratio [aHR] 1.63, 95% CI 1.01-2.62, p = .04) but were not associated with graft failure or death (aHR 0.45, 95% CI 0.15-1.36, p = .16). CONCLUSIONS: MDROs on donor culture increase the risk of early posttransplant infection but do not appear to affect long-term graft or recipient survival, suggesting organ donors with MDROs on culture may be safely utilized. Future studies aimed at reducing early posttransplant infections associated with donor MDROs are needed.

The Impact of Centers for Medicare & Medicaid Services SEP-1 Core Measure Implementation on Antibacterial Utilization: A Retrospective Multicenter Longitudinal Cohort Study With Interrupted Time-Series Analysis.

BACKGROUND: The impact of the US Centers for Medicare & Medicaid Services (CMS) Severe Sepsis and Septic Shock: Management Bundle (SEP-1) core measure on overall antibacterial utilization is unknown. METHODS: We performed a retrospective multicenter longitudinal cohort study with interrupted time-series analysis to determine the impact of SEP-1 implementation on antibacterial utilization and patient outcomes. All adult patients admitted to 26 hospitals between 1 October 2014 and 30 September 2015 (SEP-1 preparation period) and between 1 November 2015 and 31 October 2016 (SEP-1 implementation period) were evaluated for inclusion. The primary outcome was total antibacterial utilization, measured as days of therapy (DOT) per 1000 patient-days. RESULTS: The study cohort included 701 055 eligible patient admissions and 4.2 million patient-days. Overall antibacterial utilization increased 2% each month during SEP-1 preparation (relative rate [RR], 1.02 per month [95% confidence interval {CI}, 1.00-1.04]; P = .02). Cumulatively, the mean monthly DOT per 1000 patient-days increased 24.4% (95% CI, 18.0%-38.8%) over the entire study period (October 2014-October 2016). The rate of sepsis diagnosis/1000 patients increased 2% each month during SEP-1 preparation (RR, 1.02 per month [95% CI, 1.00-1.04]; P = .04). The rate of all-cause mortality rate per 1000 patients decreased during the study period (RR for SEP-1 preparation, 0.95 [95% CI, .92-.98; P = .001]; RR for SEP-1 implementation, .98 [.97-1.00; P = .01]). Cumulatively, the monthly mean all-cause mortality rate/1000 patients declined 38.5% (95% CI, 25.9%-48.0%) over the study period. CONCLUSIONS: Announcement and implementation of the CMS SEP-1 process measure was associated with increased diagnosis of sepsis and antibacterial utilization and decreased mortality rate among hospitalized patients.

Respiratory Microbiome Disruption and Risk for Ventilator-Associated Lower Respiratory Tract Infection.

BACKGROUND: Ventilator-associated lower respiratory tract infection (VA-LRTI) is common among critically ill patients and has been associated with increased morbidity and mortality. In acute critical illness, respiratory microbiome disruption indices (MDIs) have been shown to predict risk for VA-LRTI, but their utility beyond the first days of critical illness is unknown. We sought to characterize how MDIs previously shown to predict VA-LRTI at initiation of mechanical ventilation change with prolonged mechanical ventilation, and if they remain associated with VA-LRTI risk. METHODS: We developed a cohort of 83 subjects admitted to a long-term acute care hospital due to their prolonged dependence on mechanical ventilation; performed dense, longitudinal sampling of the lower respiratory tract, collecting 1066 specimens; and characterized the lower respiratory microbiome by 16S rRNA sequencing as well as total bacterial abundance by 16S rRNA quantitative polymerase chain reaction. RESULTS: Cross-sectional MDIs, including low Shannon diversity and high total bacterial abundance, were associated with risk for VA-LRTI, but associations had wide posterior credible intervals. Persistent lower respiratory microbiome disruption showed a more robust association with VA-LRTI risk, with each day of (base e) Shannon diversity <2.0 associated with a VA-LRTI odds ratio of 1.36 (95% credible interval, 1.10-1.72). The observed association was consistent across multiple clinical definitions of VA-LRTI. CONCLUSIONS: Cross-sectional MDIs have limited ability to discriminate VA-LRTI risk during prolonged mechanical ventilation, but persistent lower respiratory tract microbiome disruption, best characterized by consecutive days with low Shannon diversity, may identify a population at high risk for infection and may help target infection-prevention interventions.

Healthcare microenvironments define multidrug-resistant organism persistence.

BACKGROUND: Multidrug-resistant organisms (MDROs) colonizing the healthcare environment have been shown to contribute to risk for healthcare-associated infections (HAIs), with adverse effects on patient morbidity and mortality. We sought to determine how bacterial contamination and persistent MDRO colonization of the healthcare environment are related to the position of patients and wastewater sites. METHODS: We performed a prospective cohort study, enrolling 51 hospital rooms at the time of admitting a patient with an eligible MDRO in the prior 30 days. We performed systematic sampling and MDRO culture of rooms, as well as 16S rRNA sequencing to define the environmental microbiome in a subset of samples. RESULTS: The probability of detecting resistant gram-negative organisms, including Enterobacterales, Acinetobacter spp, and Pseudomonas spp, increased with distance from the patient. In contrast, Clostridioides difficile and methicillin-resistant Staphylococcus aureus were more likely to be detected close to the patient. Resistant Pseudomonas spp and S. aureus were enriched in these hot spots despite broad deposition of 16S rRNA gene sequences assigned to the same genera, suggesting modifiable factors that permit the persistence of these MDROs. CONCLUSIONS: MDRO hot spots can be defined by distance from the patient and from wastewater reservoirs. Evaluating how MDROs are enriched relative to bacterial DNA deposition helps to identify healthcare micro-environments and suggests how targeted environmental cleaning or design approaches could prevent MDRO persistence and reduce infection risk.