Changes in the Association Between Diagnostic Testing Method, Polymerase Chain Reaction Ribotype, and Clinical Outcomes From Clostridioides difficile Infection: One Institution's Experience.

BACKGROUND: In 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. METHODS: In 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. RESULTS: 199 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). CONCLUSIONS: Toxin 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.

Anti-toxin antibody is not associated with recurrent Clostridium difficile infection.

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.

Low Tidal Volume Ventilation Use in Acute Respiratory Distress Syndrome.

OBJECTIVE: Low tidal volume ventilation lowers mortality in the acute respiratory distress syndrome. Previous studies reported poor low tidal volume ventilation implementation. We sought to determine the rate, quality, and predictors of low tidal volume ventilation use. DESIGN: Retrospective cross-sectional study. SETTING: One academic and three community hospitals in the Chicago region. PATIENTS: A total of 362 adults meeting the Berlin Definition of acute respiratory distress syndrome consecutively admitted between June and December 2013. MEASUREMENTS AND MAIN RESULTS: Seventy patients (19.3%) were treated with low tidal volume ventilation (tidal volume < 6.5 mL/kg predicted body weight) at some time during mechanical ventilation. In total, 22.2% of patients requiring an FIO2 greater than 40% and 37.3% of patients with FIO2 greater than 40% and plateau pressure greater than 30 cm H2O received low tidal volume ventilation. The entire cohort received low tidal volume ventilation 11.4% of the time patients had acute respiratory distress syndrome. Among patients who received low tidal volume ventilation, the mean (SD) percentage of acute respiratory distress syndrome time it was used was 59.1% (38.2%), and 34% waited more than 72 hours prior to low tidal volume ventilation initiation. Women were less likely to receive low tidal volume ventilation, whereas sepsis and FIO2 greater than 40% were associated with increased odds of low tidal volume ventilation use. Four attending physicians (6.2%) initiated low tidal volume ventilation within 1 day of acute respiratory distress syndrome onset for greater than or equal to 50% of their patients, whereas 34 physicians (52.3%) never initiated low tidal volume ventilation within 1 day of acute respiratory distress syndrome onset. In total, 54.4% of patients received a tidal volume less than 8 mL/kg predicted body weight, and the mean tidal volume during the first 72 hours after acute respiratory distress syndrome onset was never less than 8 mL/kg predicted body weight. CONCLUSIONS: More than 12 years after publication of the landmark low tidal volume ventilation study, use remains poor. Interventions that improve adoption of low tidal volume ventilation are needed.

Prevention of colonization and infection by Klebsiella pneumoniae carbapenemase-producing enterobacteriaceae in long-term acute-care hospitals.

BACKGROUND: Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae (hereafter "KPC") are an increasing threat to healthcare institutions. Long-term acute-care hospitals (LTACHs) have especially high prevalence of KPC. METHODS: Using a stepped-wedge design, we tested whether a bundled intervention (screening patients for KPC rectal colonization upon admission and every other week; contact isolation and geographic separation of KPC-positive patients in ward cohorts or single rooms; bathing all patients daily with chlorhexidine gluconate; and healthcare-worker education and adherence monitoring) would reduce colonization and infection due to KPC in 4 LTACHs with high endemic KPC prevalence. The study was conducted between 1 February 2010 and 30 June 2013; 3894 patients were enrolled during the preintervention period (lasting from 16 to 29 months), and 2951 patients were enrolled during the intervention period (lasting from 12 to 19 months). RESULTS: KPC colonization prevalence was stable during preintervention (average, 45.8%; 95% confidence interval [CI], 42.1%-49.5%), declined early during intervention, then reached a plateau (34.3%; 95% CI, 32.4%-36.2%; P<.001 for exponential decline). During intervention, KPC admission prevalence remained high (average, 20.6%, 95% CI, 19.1%-22.3%). The incidence rate of KPC colonization fell during intervention, from 4 to 2 acquisitions per 100 patient-weeks (P=.004 for linear decline). Compared to preintervention, average rates of clinical outcomes declined during intervention: KPC in any clinical culture (3.7 to 2.5/1000 patient-days; P=.001), KPC bacteremia (0.9 to 0.4/1000 patient-days; P=.008), all-cause bacteremia (11.2 to 7.6/1000 patient-days; P=.006) and blood culture contamination (4.9 to 2.3/1000 patient-days; P=.03). CONCLUSIONS: A bundled intervention was associated with clinically important and statistically significant reductions in KPC colonization, KPC infection, all-cause bacteremia, and blood culture contamination in a high-risk LTACH population.

The Michigan Genetic Hereditary Testing (MiGHT) study's innovative approaches to promote uptake of clinical genetic testing among cancer patients: a study protocol for a 3-arm randomized controlled trial.

BACKGROUND: Although most cancers are sporadic, germline genetic variants are implicated in 5-10% of cancer cases. Clinical genetic testing identifies pathogenic germline genetic variants for hereditary cancers. The Michigan Genetic Hereditary Testing (MiGHT) study is a three-arm randomized clinical trial that aims to test the efficacy of two patient-level behavioral interventions on uptake of cancer genetic testing. METHODS: The two interventions being tested are (1) a virtual genetics navigator and (2) motivational interviewing by genetic health coaches. Eligible participants are adults with a diagnosis of breast, prostate, endometrial, ovarian, colorectal, or pancreatic cancer who meet the National Comprehensive Cancer Network (NCCN) criteria for genetic testing. Participants are recruited through community oncology practices affiliated with the Michigan Oncology Quality Consortium (MOQC) and have used the Family Health History Tool (FHHT) to determine testing eligibility. The recruitment goal is 759 participants, who will be randomized to usual care or to either the virtual genetics navigator or the motivational interviewing intervention arms. The primary outcome will be the proportion of individuals who complete germline genetic testing within 6 months. DISCUSSION: This study addresses patient-level factors which are associated with the uptake of genetic testing. The study will test two different intervention approaches, both of which can help address the shortage of genetic counselors and improve access to care. TRIAL REGISTRATION: This study has been approved by the Institutional Review Board of the University of Michigan Medical School (HUM00192898) and registered in ClinicalTrials.gov (NCT05162846).

A quantitative approach for the analysis of clinician recognition of acute respiratory distress syndrome using electronic health record data.

IMPORTANCE: Despite its efficacy, low tidal volume ventilation (LTVV) remains severely underutilized for patients with acute respiratory distress syndrome (ARDS). Physician under-recognition of ARDS is a significant barrier to LTVV use. We propose a computational method that addresses some of the limitations of the current approaches to automated measurement of whether ARDS is recognized by physicians. OBJECTIVE: To quantify patient and physician factors affecting physicians' tidal volume selection and to build a computational model of physician recognition of ARDS that accounts for these factors. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, electronic health record data were collected for 361 ARDS patients and 388 non-ARDS hypoxemic (control) patients in nine adult intensive care units at four hospitals between June 24 and December 31, 2013. METHODS: Standardized tidal volumes (mL/kg predicted body weight) were chosen as a proxy for physician decision-making behavior. Using data-science approaches, we quantified the effect of eight factors (six severity of illness, two physician behaviors) on selected standardized tidal volumes in ARDS and control patients. Significant factors were incorporated in computational behavioral models of physician recognition of ARDS. RESULTS: Hypoxemia severity and ARDS documentation in physicians' notes were associated with lower standardized tidal volumes in the ARDS cohort. Greater patient height was associated with lower standardized tidal volumes (which is already normalized for height) in both ARDS and control patients. The recognition model yielded a mean (99% confidence interval) physician recognition of ARDS of 22% (9%-42%) for mild, 34% (19%-49%) for moderate, and 67% (41%-100%) for severe ARDS. CONCLUSIONS AND RELEVANCE: In this study, patient characteristics and physician behaviors were demonstrated to be associated with differences in ventilator management in both ARDS and control patients. Our model of physician ARDS recognition measurement accounts for these clinical variables, providing an electronic approach that moves beyond relying on chart documentation or resource intensive approaches.

A Critical Care Clinician Survey Comparing Attitudes and Perceived Barriers to Low Tidal Volume Ventilation with Actual Practice.

RATIONALE: 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. OBJECTIVES: The objectives of this study were to assess clinicians' attitudes toward and perceived barriers to low-Vt ventilation (Vt <6.5 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Modifiable Risk Factors for the Spread of Klebsiella pneumoniae Carbapenemase-Producing Enterobacteriaceae Among Long-Term Acute-Care Hospital Patients.

OBJECTIVE To identify modifiable risk factors for acquisition of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae (KPC) colonization among long-term acute-care hospital (LTACH) patients. DESIGN Multicenter, matched case-control study. SETTING Four LTACHs in Chicago, Illinois. PARTICIPANTS Each 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. RESULTS From 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. CONCLUSIONS Higher 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 Epidemiol 2017;38:670-677.

Duration of Colonization With Klebsiella pneumoniae Carbapenemase-Producing Bacteria at Long-Term Acute Care Hospitals in Chicago, Illinois.

Background. High prevalence of Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae has been reported in long-term acute care hospitals (LTACHs), in part because of frequent readmissions of colonized patients. Knowledge of the duration of colonization with KPC is essential to identify patients at risk of KPC colonization upon readmission and to make predictions on the effects of transmission control measures. Methods. We analyzed data on surveillance isolates that were collected at 4 LTACHs in the Chicago region during a period of bundled interventions, to simultaneously estimate the duration of colonization during an LTACH admission and between LTACH (re)admissions. A maximum-likelihood method was used, taking interval-censoring into account. Results. Eighty-three percent of patients remained colonized for at least 4 weeks, which was the median duration of LTACH stay. Between LTACH admissions, the median duration of colonization was 270 days (95% confidence interval, 91-∞). Conclusions. Only 17% of LTACH patients lost colonization with KPC within 4 weeks. Approximately half of the KPC-positive patients were still carriers when readmitted after 9 months. Infection control practices should take prolonged carriage into account to limit transmission of KPCs in LTACHs.

Modeling spread of KPC-producing bacteria in long-term acute care hospitals in the Chicago region, USA.

OBJECTIVE: Prevalence of bla KPC-encoding Enterobacteriaceae (KPC) in Chicago long-term acute care hospitals (LTACHs) rose rapidly after the first recognition in 2007. We studied the epidemiology and transmission capacity of KPC in LTACHs and the effect of patient cohorting. METHODS: Data were available from 4 Chicago LTACHs from June 2012 to June 2013 during a period of bundled interventions. These consisted of screening for KPC rectal carriage, daily chlorhexidine bathing, medical staff education, and 3 cohort strategies: a pure cohort (all KPC-positive patients on 1 floor), single rooms for KPC-positive patients, and a mixed cohort (all KPC-positive patients on 1 floor, supplemented with KPC-negative patients). A data-augmented Markov chain Monte Carlo (MCMC) method was used to model the transmission process. RESULTS: Average prevalence of KPC colonization was 29.3%. On admission, 18% of patients were colonized; the sensitivity of the screening process was 81%. The per admission reproduction number was 0.40. The number of acquisitions per 1,000 patient days was lowest in LTACHs with a pure cohort ward or single rooms for colonized patients compared with mixed-cohort wards, but 95% credible intervals overlapped. CONCLUSIONS: Prevalence of KPC in LTACHs is high, primarily due to high admission prevalence and the resultant impact of high colonization pressure on cross transmission. In this setting, with an intervention in place, patient-to-patient transmission is insufficient to maintain endemicity. Inclusion of a pure cohort or single rooms for KPC-positive patients in an intervention bundle seemed to limit transmission compared to use of a mixed cohort.

Understanding staff perceptions about Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae control efforts in Chicago long-term acute care hospitals.

OBJECTIVE: To identify differences in organizational culture and better understand motivators to implementation of a bundle 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.

The effectiveness of routine daily chlorhexidine gluconate bathing in reducing Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae skin burden among long-term acute care hospital patients.

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.