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.

Transmission of Carbapenem-Resistant Klebsiella pneumoniae in US Hospitals.

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKp) is the most prevalent carbapenem-resistant Enterobacterales in the United States. We evaluated CRKp clustering in patients in US hospitals. METHODS: From April 2016 to August 2017, 350 patients with clonal group 258 CRKp were enrolled in the Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae, a prospective, multicenter, cohort study. A maximum likelihood tree was constructed using RAxML. Static clusters shared ≤21 single-nucleotide polymorphisms (SNP) and a most recent common ancestor. Dynamic clusters incorporated SNP distance, culture timing, and rates of SNP accumulation and transmission using the R program TransCluster. RESULTS: Most patients were admitted from home (n = 150, 43%) or long-term care facilities (n = 115, 33%). Urine (n = 149, 43%) was the most common isolation site. Overall, 55 static and 47 dynamics clusters were identified involving 210 of 350 (60%) and 194 of 350 (55%) patients, respectively. Approximately half of static clusters were identical to dynamic clusters. Static clusters consisted of 33 (60%) intrasystem and 22 (40%) intersystem clusters. Dynamic clusters consisted of 32 (68%) intrasystem and 15 (32%) intersystem clusters and had fewer SNP differences than static clusters (8 vs 9; P = .045; 95% confidence interval [CI]: -4 to 0). Dynamic intersystem clusters contained more patients than dynamic intrasystem clusters (median [interquartile range], 4 [2, 7] vs 2 [2, 2]; P = .007; 95% CI: -3 to 0). CONCLUSIONS: Widespread intrasystem and intersystem transmission of CRKp was identified in hospitalized US patients. Use of different methods for assessing genetic similarity resulted in only minor differences in interpretation.

Risk Factors for Community Colonization With Extended-Spectrum Cephalosporin-Resistant Enterobacterales (ESCrE) in Botswana: An Antibiotic Resistance in Communities and Hospitals (ARCH) Study.

BACKGROUND: The epidemiology of extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) in low- and middle-income countries (LMICs) is poorly described. Identifying risk factors for ESCrE colonization is critical to inform antibiotic resistance reduction strategies because colonization is typically a precursor to infection. METHODS: From 15 January 2020 to 4 September 2020, we surveyed a random sample of clinic patients at 6 sites in Botswana. We also invited each enrolled participant to refer up to 3 adults and children. All participants had rectal swabs collected that were inoculated onto chromogenic media followed by confirmatory testing. Data were collected on demographics, comorbidities, antibiotic use, healthcare exposures, travel, and farm and animal contact. Participants with ESCrE colonization (cases) were compared with noncolonized participants (controls) to identify risk factors for ESCrE colonization using bivariable, stratified, and multivariable analyses. RESULTS: A total of 2000 participants were enrolled. There were 959 (48.0%) clinic participants, 477 (23.9%) adult community participants, and 564 (28.2%) child community participants. The median (interquartile range) age was 30 (12-41) and 1463 (73%) were women. There were 555 cases and 1445 controls (ie, 27.8% of participants were ESCrE colonized). Independent risk factors (adjusted odds ratio [95% confidence interval]) for ESCrE included healthcare exposure (1.37 [1.08-1.73]), foreign travel [1.98 (1.04-3.77]), tending livestock (1.34 [1.03-1.73]), and presence of an ESCrE-colonized household member (1.57 [1.08-2.27]). CONCLUSIONS: Our results suggest healthcare exposure may be important in driving ESCrE. The strong links to livestock exposure and household member ESCrE colonization highlight the potential role of common exposure or household transmission. These findings are critical to inform strategies to curb further emergence of ESCrE in LMICs.

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.

Advancing Diagnostic Stewardship for Healthcare-Associated Infections, Antibiotic Resistance, and Sepsis.

Diagnostic stewardship means ordering the right tests for the right patient at the right time to inform optimal clinical care. Diagnostic stewardship is an integral part of antibiotic stewardship efforts to optimize antibiotic use and improve patient outcomes, including reductions in antibiotic resistance and treatment of sepsis. The Centers for Disease Control and Prevention's Division of Healthcare Quality Promotion hosted a meeting on improving patient safety through diagnostic stewardship with a focus on use of the laboratory. At the meeting, emerging issues in the field of diagnostic stewardship were identified, awareness of these issues among stakeholders was raised, and strategies and interventions to address the issues were discussed-all with an emphasis on improved outcomes and patient safety. Here, we summarize the key takeaways of the meeting including needs for diagnostic stewardship implementation, promising future avenues for diagnostic stewardship implementation, and areas of needed research.

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.

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.

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.

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.

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.

Attributable Cost of Healthcare-Associated Methicillin-Resistant Staphylococcus aureus Infection in a Long-term Care Center.

BACKGROUND: Studies have shown that healthcare-associated infections (HAIs) due to methicillin-resistant Staphylococcus aureus (MRSA) can lead to substantial healthcare costs in acute care settings. However, little is known regarding the consequences of these infections on patients in long-term care centers (LTCCs). The purpose of this study was to estimate the attributable cost of MRSA HAIs in LTCCs within the Department of Veterans Affairs (VA). METHODS: We performed a retrospective cohort study of patients admitted to VA LTCCs between 1 January 2009 and 30 September 2015. MRSA HAIs were defined as a positive clinical culture at least 48 hours after LTCC admission so as to exclude community-acquired infections. Positive cultures were further classified by site (sterile or nonsterile). We used multivariable generalized linear models and 2-part models to compare the LTCC and acute care costs between patients with and without an MRSA HAI. RESULTS: In our primary analysis, there was no difference in LTCC costs between patients with and without a MRSA HAI. There was, however, a significant increase in the odds of being transferred to an acute care facility (odds ratio, 4.40 [95% confidence interval {CI}, 3.40-5.67]) and in acute care costs ($9711 [95% CI, $6961-$12 462]). CONCLUSIONS: Our findings of high cost and increased risk of transfer from LTCC to acute care are important because they highlight the substantial clinical and economic impact of MRSA infections in this population.

Leveraging Existing and Soon-to-Be-Available Novel Diagnostics for Optimizing Outpatient Antibiotic Stewardship in Patients With Respiratory Tract Infections.

Respiratory tract infections (RTIs) drive many outpatient encounters and, despite being predominantly viral, are associated with high rates of antibiotic prescriptions. With rising antibacterial resistance, optimization of prescribing of antibiotics in outpatients with RTIs is a critical need. Fortunately, this challenge arises at a time of increasing availability of novel RTI diagnostics to help discern which patients have bacterial infections warranting treatment. Effective implementation of antibiotic stewardship is needed, but optimal approaches for ambulatory settings are unknown. Future research needs are reviewed in this summary of a research summit convened by the Infectious Diseases Society of America in the fall of 2019.

Risk Factors for Extended-Spectrum ß-lactamase-Producing Enterobacterales Bloodstream Infection Among Solid-Organ Transplant Recipients.

BACKGROUND: Approximately 40% of all Enterobacterales (EB) bloodstream infections (BSIs) among solid organ transplant recipients (SOTRs) are due to extended-spectrum ß-lactamase (ESBL)-producing organisms, but risk factors for such infections remain ill defined in this population. We sought to determine the risk factors for ESBL-EB BSIs among SOTRs. METHODS: A multicenter case-control study was performed. All SOTRs with an EB BSI at the Hospital of the University of Pennsylvania and University of Maryland Medical Center between 1 January 2007 and 30 June 2018 and at The Johns Hopkins Hospital between 1 January 2005 and 31 December 2015 were included. Cases were those with an ESBL-EB BSI. Controls were those with a non-ESBL-EB BSI. Multivariable logistic regression was performed to determine risk factors for ESBL-EB BSI. RESULTS: There were 988 episodes of EB BSI, of which 395 (40%) were due to an ESBL-EB. On multivariable analysis, the independent risk factors for ESBL-EB BSI included: ESBL-EB on prior culture (aOR, 12.75; 95% CI, 3.23-50.33; P < .001), a corticosteroid-containing immunosuppression regimen (aOR 1.30; 95% CI 1.03-1.65; P = .030), acute rejection treated with corticosteroids (aOR 1.18; 95% CI 1.16-1.19; P < .001), and exposure to third-generation cephalosporins (aOR 1.95; 95% CI 1.48-2.57; P < .001), echinocandins (aOR 1.61; 95% CI 1.08-2.40; P = .020), and trimethoprim-sulfamethoxazole (aOR 1.35; 95% CI 1.10-1.64; P = .003). CONCLUSIONS: We identified several novel risk factors that are uniquely important to the SOTR population, including exposure to trimethoprim-sulfamethoxazole and corticosteroid-containing immunosuppressive regimens. Further studies exploring these associations and testing interventions aimed at these modifiable risk factors among SOTRs are needed.

Antibiotic Utilization in Deceased Organ Donors.

Antibiotic use in deceased organ donors has not been previously described. In a retrospective cohort of 440 donors, we found 427 (97%) received at least one antibiotic course, 312 (71%) received broad-spectrum antibiotics, and 61 (14%) received potentially redundant antibiotics during their terminal hospitalization, suggesting a need for stewardship.

Clinical prediction tool for extended-spectrum beta-lactamase-producing enterobacterales as the etiology of a bloodstream infection in solid organ transplant recipients.

BACKGROUND: Multidrug-resistant Gram-negative bacterial infections are increasingly common among solid organ transplant (SOT) recipients, leading to challenges in the selection of empiric antimicrobial therapy. We sought to develop a clinical tool to predict which SOT recipients are at high risk for extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales (EB) bloodstream infection (BSI). METHODS: A multicenter case-control study was performed. The source population included SOT recipients with an EB BSI between 2005 and 2018. Cases were those with ESBL-EB BSI; controls were those with non-ESBL EB BSI. The population was subdivided into derivation and validation cohorts based on study site. The predictive tool was developed in the derivation cohort through iterative multivariable logistic regression analyses that maximized the area under the receiver-operating curve (AUC). External validity was assessed using the validation cohort. RESULTS: A total of 897 SOT recipients with an EB BSI were included, of which 539 were assigned to the derivation cohort (135, 25% ESBL-EB) and 358 to the validation cohort (221, 62% ESBL-EB). Using multivariable analyses, the most parsimonious model that was predictive of ESBL-EB BSI consisted of 10 variables, which fell into four clinical categories: prior colonization or infection with EB organisms, recent antimicrobial exposures, severity of preceding illness, and immunosuppressive regimen. This model achieved an AUC of 0.81 in the derivation cohort and 0.68 in the validation cohort. CONCLUSIONS: Though further refinements are needed in additional populations, this tool shows promise for guiding empiric therapy for SOT recipients with EB BSI.

Comparing Propensity Score Methods Versus Traditional Regression Analysis for the Evaluation of Observational Data: A Case Study Evaluating the Treatment of Gram-Negative Bloodstream Infections.

BACKGROUND: Propensity score methods are increasingly being used in the infectious diseases literature to estimate causal effects from observational data. However, there remains a general gap in understanding among clinicians on how to critically review observational studies that have incorporated these analytic techniques. METHODS: Using a cohort of 4967 unique patients with Enterobacterales bloodstream infections, we sought to answer the question "Does transitioning patients with gram-negative bloodstream infections from intravenous to oral therapy impact 30-day mortality?" We conducted separate analyses using traditional multivariable logistic regression, propensity score matching, propensity score inverse probability of treatment weighting, and propensity score stratification using this clinical question as a case study to guide the reader through (1) the pros and cons of each approach, (2) the general steps of each approach, and (3) the interpretation of the results of each approach. RESULTS: 2161 patients met eligibility criteria with 876 (41%) transitioned to oral therapy while 1285 (59%) remained on intravenous therapy. After repeating the analysis using the 4 aforementioned methods, we found that the odds ratios were broadly similar, ranging from 0.84-0.95. However, there were some relevant differences between the interpretations of the findings of each approach. CONCLUSIONS: Propensity score analysis is overall a more favorable approach than traditional regression analysis when estimating causal effects using observational data. However, as with all analytic methods using observational data, residual confounding will remain; only variables that are measured can be accounted for. Moreover, propensity score analysis does not compensate for poor study design or questionable data accuracy.

Impact of deceased donor multidrug-resistant bacterial organisms on organ utilization.

The extent to which donor multidrug-resistant organisms (MDROs) affect organ utilization remains unclear. We performed a retrospective cohort study at 4 transplant centers between 2015 and 2016 to evaluate this question. All deceased donors who donated at least one organ were included. Exposed donors had at least one MDRO on culture. Unexposed donors had no MDRO-positive cultures. Only cultures obtained during the donor's terminal hospitalization were evaluated. Multivariable regression was used to determine the association between donor MDRO and (1) number of organs transplanted per donor and (2) the match run at which each organ was accepted. Subsequently, we restricted the analysis to donors with MDR-Gram-negative (GN) organisms. Of 440 total donors, 29 (7%) donors grew MDROs and 7 (2%) grew MDR-GNs. There was no significant association between donor MDRO and either measure of organ utilization. However, donor MDR-GNs were associated with a significant reduction in the number of organs transplanted per donor (incidence rate ratio 0.43, 95% confidence interval [CI] 0.39-0.48, P < .01), and organs were accepted significantly further down the match list (relative count 5.08, 95% CI 1.64-15.68, P = .01). Though donor MDR-GNs were infrequent in our study, their growing prevalence could meaningfully reduce the donor pool over time.

Gene Expression Profiles in Children With Suspected Sepsis.

STUDY OBJECTIVE: Sepsis recognition is a clinical challenge in children. We aim to determine whether peripheral blood gene expression profiles are associated with pathogen type and sepsis severity in children with suspected sepsis. METHODS: This was a prospective pilot observational study in a tertiary pediatric emergency department with a convenience sample of children enrolled. Participants were older than 56 days and younger than 18 years, had suspected sepsis, and had not received broad-spectrum antibiotics in the previous 4 hours. Primary outcome was source pathogen, defined as confirmed bacterial source from sterile body fluid or confirmed viral source. Secondary outcome was sepsis severity, defined as maximum therapy required for shock reversal in the first 3 hospital days. We drew peripheral blood for ribonucleic acid isolation at the sepsis protocol activation, obtained gene expression measures with the GeneChip Human Gene 2.0 ST Array, and conducted differential expression analysis. RESULTS: We collected ribonucleic acid samples from a convenience sample of 122 children with suspected sepsis and 12 healthy controls. We compared the 66 children (54%) with confirmed bacterial or viral infection and found 558 differentially expressed genes, many related to interferon signaling or viral immunity. We did not find statistically significant gene expression differences in patients according to sepsis severity. CONCLUSION: The study demonstrates feasibility of evaluating gene expression profiling data in children evaluated for sepsis in the pediatric emergency department setting. Our results suggest that gene expression profiling may facilitate identification of source pathogen in children with suspected sepsis, which could ultimately lead to improved tailoring of sepsis treatment and antimicrobial stewardship.

Risk factors for multidrug-resistant organisms among deceased organ donors.

Donor infection or colonization with a multidrug-resistant organism (MDRO) affects organ utilization and recipient antibiotic management. Approaches to identifying donors at risk of carrying MDROs are unknown. We sought to determine the risk factors for MDROs among transplant donors. A multicenter retrospective cohort study was conducted at four transplant centers between 2015 and 2016. All deceased donors who donated at least one organ were included. Cultures obtained during the donor's terminal hospitalization and organ procurement were evaluated. The primary outcome was isolation of an MDRO on culture. Multivariable Cox regression was used to determine risk factors associated with time to donor MDRO. Of 440 total donors, 64 (15%) donors grew an MDRO on culture. Predictors of an MDRO on donor culture included hepatitis C viremia (hazard ratio [HR] 4.09, 95% confidence interval [CI] 1.71-9.78, P = .002), need for dialysis (HR 4.59, 95% CI 1.09-19.21, P = .037), prior hematopoietic cell transplant (HR 7.57, 95% CI 1.03-55.75, P = .047), and exposure to antibiotics with a narrow gram-negative spectrum (HR 1.13, 95% CI 1.00-1.27, P = .045). This is the first study to determine risk factors for MDROs among deceased donors and will be important for risk stratifying potential donors and informing transplant recipient prophylaxis.

Whole-Genome Sequencing To Identify Drivers of Carbapenem-Resistant Klebsiella pneumoniae Transmission within and between Regional Long-Term Acute-Care Hospitals.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an antibiotic resistance threat of the highest priority. Given the limited treatment options for this multidrug-resistant organism (MDRO), there is an urgent need for targeted strategies to prevent transmission. Here, we applied whole-genome sequencing to a comprehensive collection of clinical isolates to reconstruct regional transmission pathways and analyzed this transmission network in the context of statewide patient transfer data and patient-level clinical data to identify drivers of regional transmission. We found that high regional CRKP burdens were due to a small number of regional introductions, with subsequent regional proliferation occurring via patient transfers among health care facilities. While CRKP was predicted to have been imported into each facility multiple times, there was substantial variation in the ratio of intrafacility transmission events per importation, indicating that amplification occurs unevenly across regional facilities. While myriad factors likely influence intrafacility transmission rates, an understudied one is the potential for clinical characteristics of colonized and infected patients to influence their propensity for transmission. Supporting the contribution of high-risk patients to elevated transmission rates, we observed that patients colonized and infected with CRKP in high-transmission facilities had higher rates of carbapenem use, malnutrition, and dialysis and were older. This report highlights the potential for regional infection prevention efforts that are grounded in genomic epidemiology to identify the patients and facilities that make the greatest contribution to regional MDRO prevalence, thereby facilitating the design of precision interventions of maximal impact.