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BackgroundIn Clostridioides difficile infection (CDI), the relationship between clinical, microbial, and temporal/epidemiological trends, disease severity and adverse outcomes is incompletely understood. In a follow-up to our study from 2010–2013, we evaluate stool toxin levels and C. difficile polymerase chain reaction (PCR) ribotypes. We hypothesized that elevated stool toxins and infection with ribotype 027 associate with adverse outcomes.MethodsIn 565 subjects at the University of Michigan with CDI diagnosed by positive testing for toxins A/B by enzyme immunoassay (EIA) or PCR for the tcdB gene, we quantified stool toxin levels via a modified cell cytotoxicity assay (CCA), isolated C. difficile by anaerobic culture, and performed PCR ribotyping. Severe CDI was defined by Infectious Diseases Society of America (IDSA) criteria, and primary outcomes were all-cause 30-day mortality and a composite of colectomy, intensive care unit admission, and/or death attributable to CDI within 30 days. Analyses included bivariable tests and logistic regression.Results199 samples were diagnosed by EIA; 447 were diagnosed by PCR. Toxin positivity associated with IDSA severity but not primary outcomes. In 2016, compared with 2010–2013, ribotype 106 newly emerged, accounting for 10.6% of strains, ribotype 027 fell from 16.5% to 9.3%, and ribotype 014–027 remained stable at 18.9%. Ribotype 014–020 associated with IDSA severity and 30-day mortality (P = .001).ConclusionsToxin positivity by EIA and CCA associated with IDSA severity but not with subsequent adverse outcomes. The molecular epidemiology of C. difficile has shifted, which may have implications for the optimal diagnostic strategy for and clinical severity of CDI.

149 Background: A complete family history is critical in identifying cancer patients who should be referred to genetic counseling and testing. Despite the importance of a detailed family history, defined as any cancer diagnoses in first- or second-degree relatives and their age at diagnosis, only about one third of cancer patients have a complete family history documented in their medical record. The Michigan Oncology Quality Consortium (MOQC), a physician-led consortium of oncology practices across the state of Michigan, selected documentation of a complete family history in oncology patients as a quality measure. The purpose of this study was to identify clinical and non-clinical factors associated with the quality of the family history. Methods: Beginning in 2020, MOQC began collecting completeness of documentation of cancer family history from the medical oncology records of patients with invasive cancer from MOQC practices twice per year in the Quality Oncology Practice Initiative (QOPI) database. QOPI data from 2020 and 2021 were combined for analyses. A multivariate model was built to determine the clinical and non-clinical factors, including age, sex, race, ethnicity, and cancer diagnosis, associated with documentation of a complete family history. Results: Between January 2020 and December 2021, 10,800 patients’ records were abstracted. Of these, 30% had a complete family history documented in their medical record. Factors independently and significantly associated with not having a complete family history included increasing age and Black race. Patients with breast cancer (AOR 1.94, 95% CI 1.72, 2.19) and colorectal cancer (AOR 1.2, 95% CI 1.05, 1.37) were more likely to have a complete family history than all others. Patients with prostate, pancreas, or endometrial cancer—all of which are associated with cancer syndromes—were no more likely than other patients to have a complete family history. Sex and ethnicity were not significantly associated with documentation of a complete family history. Conclusions: Patients may qualify for genetic testing based on family history alone. It is therefore crucial that clinicians know a patient’s complete family history to identify those patients eligible for genetic risk assessment. We have identified gaps in the quality of the family history with increasing age, in Black patients, and, except for breast and colorectal cancer, in patients with cancers associated with an inherited susceptibility. Our findings highlight an opportunity to improve care.[Table: see text]

10591 Background: Genetic testing allows patients and their families to identify hereditary cancer syndromes. Financial barriers to genetic testing are a major concern for patients offered genetic risk assessment. The cost of germline genetic testing has decreased substantially over the last several years. It is not clear, however, that oncologists are knowledgeable about the cost of genetic testing. The purpose of this study was to investigate oncologists’ knowledge of genetic testing costs. Methods: We deployed a survey to all oncologists who are members of the Michigan Oncology Quality Consortium, a physician-led quality improvement collaborative whose members represent 95% of the oncologists in Michigan. The modified Dillman method was used to achieve the maximum response rate. Responses were collected from December 2020 through May 2021. The responses to the question, “If a patient were to ask you how much it would cost for them to have clinical genetic testing for hereditary cancer syndromes, what would you tell them?” were independently coded by three investigators into one of three categories – correct and helpful, correct and not helpful, or incorrect and not helpful. We investigated associations between the number of years in practice and how important was cost as a barrier to genetic risk assessment. Results: The response rate to the survey was 61.2% (194/317). Only 25% of respondents provided an answer that was deemed to be both correct and helpful to a patient, for example “approximately $250 if out of pocket.” Nearly 40% of respondents gave an answer that was correct but was non-specific and would not help a patient decide about pursuing genetic testing. This category included responses such as deferring to a genetic counselor or that cost varies based on insurance. About 28% gave an incorrect response, such as “several thousand dollars” or responded, “I don’t know.” No associations were found between cost response category, number of years in practice, or reported responses that financial barriers play a role in referral patterns. Conclusions: The majority of oncologists in our statewide sample do not have an accurate understanding of the cost of germline genetic testing. Lack of precise information about the costs of testing may lead patients to believe that genetic testing is either not important or not within reach. Furthermore, providing incorrect information can have a downstream effect and prevent patients and their families from pursuing genetic counseling. Improving oncologists’ knowledge about the cost of testing may decrease barriers to uptake of genetic risk assessment. [Table: see text]

221 Background: A complete family history is essential in identifying patients who may benefit from genetic evaluation for hereditary cancer syndromes. Fewer than 40% of patients with cancer have a complete family history documented in their medical record. As part of a larger study of patient- and provider-focused interventions for increasing genetic testing, we conducted a survey of provider barriers to collecting and documenting a complete family history in a statewide, physician-led quality consortium of nearly all medical and gynecologic oncologists in Michigan. Methods: A novel survey instrument was created by adapting existing literature and clinician input. Surveys were mailed to medical and gynecologic oncologists with follow up electronic surveys sent to non-respondents. Questions addressed patient-specific barriers as well as known constraints faced by oncologists. Each barrier was rated from low to high using a 10-point Likert scale. Descriptive statistics, including mean scores and standard deviations (SD), were calculated. Results: Of 317 surveys sent, 194 (61.2%) were returned. Oncologists rated constraints on their time lower than lack of patient knowledge and understanding of their family history and its importance as a barrier. Open-ended responses indicated that the processes of collecting a family history (e.g. templates for collecting family history that omit age at diagnosis) and patients being overwhelmed at the time of consultation also interfered with collecting a complete family history. Conclusions: Oncologists perceive patient knowledge of their family history, including the ages of affected family members, and understanding of its importance as barriers to completion and documentation of a family history. Explaining the importance of the family history to patients, prompting new patients to provide their family history, and improving the process, including the timing of collection, may increase the proportion of oncology patients who have a complete family history collected and documented.[Table: see text]

OBJECTIVETo identify modifiable risk factors for acquisition ofKlebsiella pneumoniaecarbapenemase-producing Enterobacteriaceae (KPC) colonization among long-term acute-care hospital (LTACH) patients.DESIGNMulticenter, matched case-control study.SETTINGFour LTACHs in Chicago, Illinois.PARTICIPANTSEach case patient included in this study had a KPC-negative rectal surveillance culture on admission followed by a KPC-positive surveillance culture later in the hospital stay. Each matched control patient had a KPC-negative rectal surveillance culture on admission and no KPC isolated during the hospital stay.RESULTSFrom June 2012 to June 2013, 2,575 patients were admitted to 4 LTACHs; 217 of 2,144 KPC-negative patients (10.1%) acquired KPC. In total, 100 of these patients were selected at random and matched to 100 controls by LTACH facility, admission date, and censored length of stay. Acquisitions occurred a median of 16.5 days after admission. On multivariate analysis, we found that exposure to higher colonization pressure (OR, 1.02; 95% CI, 1.01–1.04;P=.002), exposure to a carbapenem (OR, 2.25; 95% CI, 1.06–4.77;P=.04), and higher Charlson comorbidity index (OR, 1.14; 95% CI, 1.01–1.29;P=.04) were independent risk factors for KPC acquisition; the odds of KPC acquisition increased by 2% for each 1% increase in colonization pressure.CONCLUSIONSHigher colonization pressure, exposure to carbapenems, and a higher Charlson comorbidity index independently increased the odds of KPC acquisition among LTACH patients. Reducing colonization pressure (through separation of KPC-positive patients from KPC-negative patients using strict cohorts or private rooms) and reducing carbapenem exposure may prevent KPC cross transmission in this high-risk patient population.Infect Control Hosp Epidemiol2017;38:670–677

Clostridium difficile infection (CDI) recurs in ∼20% of patients. Prior studies indicated that antibody responses directed against the C. difficile toxins A and B were potentially associated with lower risk of recurrent CDI. Here we tested the hypothesis that circulating anti-toxin IgG antibody levels associate with reduced risk of recurrent CDI. A cohort study with prospective enrollment and retrospective data abstraction examined antibody levels in 275 adult patients at the University of Michigan with CDI. We developed an enzyme linked immunosorbent assay to detect IgG antibodies against toxin A and toxin B in sera obtained at the time of diagnosis. Logistic regression examined the relationship between antibody levels and recurrence, and sensitivity tests evaluated for follow-up and survivor biases, history of CDI, and PCR ribotype. Follow-up data were available for 174 subjects, of whom 36 (20.7%) had recurrence. Comparing antibody levels vs. recurrence and CDI history, anti-toxin A levels were similar, while anti-toxin B levels had a greater range of values. In unadjusted analysis, detection of anti-toxin A antibodies, but not anti-toxin B antibodies, associated with an increased risk of recurrence (OR 2.71 [1.06, 8.37], P = .053). Adjusting for confounders weakened this association. The results were the same in sensitivity analyses. We observed a borderline increased risk of recurrence in patients positive for anti-toxin A antibodies, and sensitivity analyses showed this was not simply a reflection of prior exposure status. Future studies are needed to assess how neutralizing antibody or levels after treatment associate with recurrence.

Background Clostridium difficile infection (CDI) is a major public health concern and frequently results in severe disease, including death. Predicting subsequent complications early in the course can help optimize treatments and improve outcomes. However, models based on clinical criteria alone are not accurate and/or do not validate. We hypothesized that inflammatory mediators from the stool would be biomarkers for severity and complications. Methods Subjects were included after testing positive for toxigenic C. difficile by the clinical microbiology laboratory via enzyme immunoassay (EIA) for glutamate dehydrogenase and toxins A/B, with reflex to tcdB gene PCR for discordants. Stool was thawed on ice, diluted 1:1 with PBS and protease inhibitor, centrifuged, and the supernatant was analyzed by a custom antibody-linked bead array with 17 inflammatory mediators. Measurements were normalized and log-transformed. IDSA severity was defined by serum white blood cell count > 15000 cells/µL or creatinine 1.5-fold above baseline. Primary 30-day outcomes were all-cause mortality and attributable disease-related complications (DRC): ICU admission, colectomy, and/or death. Analyses included principal components, permutational multivariate ANOVA (PERMANOVA), and logistic regression ± L1 regularization and 5-fold cross validation. The area under the receiver operator characteristic curve (AuROC) was computed. Results We included 225 subjects, with 124 females (55.1%), average age 58.5 (±17), and more PCR+ than toxin EIA+ (170 vs. 55, respectively). IDSA severity, death, and DRCs occurred in 79 (35.1%), 14 (6.2%), and 12 (5.3%) subjects, respectively. PCA and PERMANOVA showed IDSA severity (P = 0.009) but not death or DRCs associated with the panel (figure). Several inflammatory mediators associated with IDSA severity and death (table). Machine learning models had AuROCs of 0.77 (IDSA severity), 0.84 (death), and 0.7 (DRCs). Conclusion We found that specific inflammatory mediators from the stool of patients with CDI associate with severity and complications. These results are promising, but need replication in a larger dataset and should be incorporated into models that include clinical covariates prior to deployment. Disclosures All authors: No reported disclosures.

Low-Vt ventilation lowers mortality in patients with acute respiratory distress syndrome (ARDS) but is underused. Little is known about clinician attitudes toward and perceived barriers to low-Vt ventilation use and their association with actual low-Vt ventilation use.The objectives of this study were to assess clinicians' attitudes toward and perceived barriers to low-Vt ventilation (Vt6.5 ml/kg predicted body weight) in patients with ARDS, to identify differences in attitudes and perceived barriers among clinician types, and to compare attitudes toward and perceived barriers to actual low-Vt ventilation use in patients with ARDS.We conducted a survey of critical care physicians, nurses, and respiratory therapists at four non-ARDS Network hospitals in the Chicago region. We compared survey responses with performance in a cohort of 362 patients with ARDS.Survey responses included clinician attitudes toward and perceived barriers to low-Vt ventilation use. We also measured low-Vt ventilation initiation by these clinicians in 347 patients with ARDS initiated after ARDS onset as well as correlation with clinician attitudes and perceived barriers. Of 674 clinicians surveyed, 467 (69.3%) responded. Clinicians had positive attitudes toward and perceived few process barriers to ARDS diagnosis or initiation of low-Vt ventilation. Physicians had more positive attitudes and perceived fewer barriers than nurses or respiratory therapists. However, use of low-Vt ventilation by all three clinician groups was low. For example, whereas physicians believed that 92.5% of their patients with ARDS warranted treatment with low-Vt ventilation, they initiated low-Vt ventilation for a median (interquartile range) of 7.4% (0 to 14.3%) of their eligible patients with ARDS. Clinician attitudes and perceived barriers were not correlated with low-Vt ventilation initiation.Clinicians had positive attitudes toward low-Vt ventilation and perceived few barriers to using it, but attitudes and perceived process barriers were not correlated with actual low-Vt ventilation use, which was low. Implementation strategies should be focused on examining other issues, such as ARDS recognition and process solutions, to improve low-Vt ventilation use.

Objective.To identify differences in organizational culture and better understand motivators to implementation of abundle intervention to control Klebsiella pneumoniae carbapenemase–producing Enterobacteriaceae (KPC).Design.Mixed-methods study.Setting.Four long-term acute care hospitals (LTACHs) in Chicago.Participants.LTACH staff across 3 strata of employees (administration, midlevel management, and frontline clinical workers).Methods.Qualitative interviews or focus groups and completion of a quantitative questionnaire.Results.Eighty employees (frontline, 72.5%; midlevel, 17.5%; administration, 10%) completed surveys and participated in qualitative discussions in August 2012. Although 82.3% of respondents felt that quality improvement was a priority at their LTACH, there were statistically significant differences in organizational culture between staff strata, with administrative-level having higher organizational culture scores (ie, more favorable responses) than midlevel or frontline staff. When asked to rank the success of the KPC control program, mean response was 8.0 (95% confidence interval, 7.6–8.5), indicating a high level of agreement with the perception that the program was a success. Patient safety and personal safety were reported most often as personal motivators for intervention adherence. The most convergent theme related to prevention across groups was that proper hand hygiene is vital to prevention of KPC transmission.Conclusions.Despite differences in organizational culture across 3 strata of LTACH employees, the high degree of convergence in motivation, understanding, and beliefs related to implementation of a KPC control bundle suggests that all levels of staff may be able to align perspectives when faced with a key infection control problem and quality improvement initiative.

Medical students are increasingly seeking global health service-learning opportunities; however, the impact of these interventions is often not assessed. In this article, the authors describe a model for global health service-learning programs as well as a pilot tool for assessing program impacts on populations traditionally difficult to evaluate. Specifically, a group of medical students from the United States, in collaboration with local health officials and a global NGO, successfully implemented a training program for parteras, or traditional birth attendants, in Mexico. The training included educational objectives from the Ministry of Health. A pilot assessment tool was developed which included oral pretest and posttest self-reported knowledge and task-specific ability in 12 program-specific categories. The assessment was administered in an effort to determine educational impact: parteras, who were receptive to students as teachers, reported increased knowledge and skill in all topics except nutrition and postpartum care. The results of the assessment suggest that undergraduate medical students, when collaborating with a facilitating organization, community-based healthcare workers, and local ministries of health, can improve lay birth attendants’ confidence in basic obstetric knowledge and skills through global service-learning. Moreover, creative assessments are required to understand impacts on difficult to access populations.

Background The optimal diagnostic strategy for Clostridium difficile infection (CDI) is not known, and no test is shown to clearly differentiate colonization from symptomatic infection. We hypothesized that detection and/or quantification of stool toxins would associate with severe disease and adverse outcomes. Methods We conducted a retrospective cohort study among subjects with CDI diagnosed in 2016 at the University of Michigan. The clinical microbiology laboratory tested for glutamate dehydrogenase antigen and toxins A/B by enzyme immunoassay (EIA). Discordant results reflexed to PCR for the tcdB gene. Stool toxin levels were quantified via a modified cell cytotoxicity assay (CCA). C. difficile was isolated by anaerobic culture and ribotyped. Severe CDI was defined by the IDSA criteria: white blood cell count >15,000 cells/µL or a 1.5-fold increase in serum creatinine above baseline. The primary outcomes were all-cause 30-day mortality and a composite of colectomy, ICU admission, and/or death attributable to CDI within 30 days. Analysis included standard bivariable tests and adjusted models via logistic regression. Results From 565 adult patients, we obtained 646 samples; 199 (30.8%) contained toxins by EIA. Toxin positivity associated with IDSA severity (Table 1), but not our primary outcomes on unadjusted analysis. After adjustment for putative confounders, we still did not observe an association between toxin positivity and our primary outcomes. Stool toxin levels by CCA >6.4 ng/mL associated with IDSA severity (Table 1), but not the primary outcomes. Compared with the period from 2010 to 2013, the circulating ribotypes of C. difficile at our institution changed in 2016. Notably ribotype 106 newly emerged, accounting for 10.6% of strains, and ribotype 027 fell to 9.3% (Table 2). The incidence of ribotype 014-027 has remained stable at 18.9%, but this strain was associated with both IDSA severity and 30-day mortality (OR = 3.32; P = 0.001). Conclusion Toxin detection by EIA/CCA associated with IDSA severity, but this study was unable to confirm an association with subsequent adverse outcomes. The molecular epidemiology of C. difficile has shifted, and this may have implications for the optimal diagnostic strategy for CDI. Disclosures All authors: No reported disclosures.

We evaluated the effectiveness of daily chlorhexidine gluconate (CHG) bathing in decreasing skin carriage of Klebsiella pneumoniae carbapenemase–producing Enterobacteriaceae (KPC) among long-term acute care hospital patients. CHG bathing reduced KPC skin colonization, particularly when CHG skin concentrations greater than or equal to 128 μg/mL were achieved.