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ObjectivesThe Intermountain Risk Score (IMRS), composed using published sex-specific weightings of parameters in the complete blood count (CBC) and basic metabolic profile (BMP), is a validated predictor of mortality. We hypothesised that IMRS calculated from prepandemic CBC and BMP predicts COVID-19 outcomes and that IMRS using laboratory results tested at COVID-19 diagnosis is also predictive.DesignProspective observational cohort study.SettingPrimary, secondary, urgent and emergent care, and drive-through testing locations across Utah and in sections of adjacent US states. Viral RNA testing for SARS-CoV-2 was conducted from 3 March to 2 November 2020.ParticipantsPatients aged ≥18 years were evaluated if they had CBC and BMP measured in 2019 and tested positive for COVID-19 in 2020.Primary and secondary outcome measuresThe primary outcome was a composite of hospitalisation or mortality, with secondary outcomes being hospitalisation and mortality separately.ResultsAmong 3883 patients, 8.2% were hospitalised and 1.6% died. Subjects with low, mild, moderate and high-risk IMRS had the composite endpoint in 3.5% (52/1502), 8.6% (108/1256), 15.5% (152/979) and 28.1% (41/146) of patients, respectively. Compared with low-risk, subjects in mild-risk, moderate-risk and high-risk groups had HR=2.33 (95% CI 1.67 to 3.24), HR=4.01 (95% CI 2.93 to 5.50) and HR=8.34 (95% CI 5.54 to 12.57), respectively. Subjects aged ConclusionsIMRS, a simple risk score using very basic laboratory results, predicted COVID-19 hospitalisation and mortality. This included important abilities to identify risk in younger adults with few diagnosed comorbidities and to predict risk prior to SARS-CoV-2 infection.

Background Multisystem inflammatory syndrome in adults (MIS-A) was reported in association with the coronavirus disease 2019 (COVID-19) pandemic. MIS-A was included in the list of adverse events to be monitored as part of the emergency use authorizations issued for COVID-19 vaccines. Methods Reports of MIS-A patients received by the Centers for Disease Control and Prevention (CDC) after COVID-19 vaccines became available were assessed. Data collected on the patients included clinical and demographic characteristics and their vaccine status. The Vaccine Adverse Events Reporting System (VAERS) was also reviewed for possible cases of MIS-A. Results From 14 December 2020 to 30 April 2021, 20 patients who met the case definition for MIS-A were reported to CDC. Their median age was 35 years (range, 21–66 years), and 13 (65%) were male. Overall, 16 (80%) patients had a preceding COVID-19-like illness a median of 26 days (range 11–78 days) before MIS-A onset. All 20 patients had laboratory evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Seven MIS-A patients (35%) received COVID-19 vaccine a median of 10 days (range, 6–45 days) before MIS-A onset; 3 patients received a second dose of COVID-19 vaccine 4, 17, and 22 days before MIS-A onset. Patients with MIS-A predominantly had gastrointestinal and cardiac manifestations and hypotension or shock. Conclusions Although 7 patients were reported to have received COVID-19 vaccine, all had evidence of prior SARS-CoV-2 infection. Given the widespread use of COVID-19 vaccines, the lack of reporting of MIS-A associated with vaccination alone, without evidence of underlying SARS-CoV-2 infection, is reassuring., Seven of 20 MIS-A patients received COVID-19 vaccination before illness onset. All patients had evidence of prior SARS-CoV-2 infection. Given widespread COVID-19 vaccinations in the United States, the lack of reporting of MIS-A associated with vaccination alone is reassuring.

Background SARS-CoV-2 reinfection and reactivation has mostly been described in case reports. We therefore investigated the epidemiology of recurrent COVID-19 SARS-CoV-2. Methods Among patients testing positive for SARS-CoV-2 between March 11 and July 31, 2020 within an integrated healthcare system, we identified patients with a recurrent positive SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) assay ≥60 days after an initial positive test. To assign an overall likelihood of COVID-19 recurrence, we combined quantitative data from initial and recurrent positive RT-PCR cycle thresholds—a value inversely correlated with viral RNA burden— with a clinical recurrence likelihood assigned based on independent, standardized case review by two physicians. “Probable” or “possible” recurrence by clinical assessment was confirmed as the final recurrence likelihood only if a cycle threshold value obtained ≥60 days after initial testing was lower than its preceding cycle threshold or if the patient had an interval negative RT-PCR. Results Among 23,176 patients testing positive for SARS-CoV-2, 1,301 (5.6%) had at least one additional SARS-CoV-2 RT-PCRs assay ≥60 days later. Of 122 testing positive, 114 had sufficient data for evaluation. The median interval to the recurrent positive RT-PCR was 85.5 (IQR 74–107) days. After combining clinical and RT-PCR cycle threshold data, four patients (3.5%) met criteria for probable COVID-19 recurrence. All four exhibited symptoms at recurrence and three required a higher level of medical care compared to their initial diagnosis. After including six additional patients (5.3%) with possible recurrence, recurrence incidence was 4.3 (95% CI 2.1–7.9) cases per 10,000 COVID-19 patients. Conclusions Only 0.04% of all COVID-19 patients in our health system experienced probable or possible recurrence; 90% of repeat positive SARS-CoV-2 RT-PCRs were not consistent with true recurrence. Our pragmatic approach combining clinical and quantitative RT-PCR data could aid assessment of COVID-19 reinfection or reactivation by clinicians and public health personnel.

PURPOSE: Electronic clinical decision support (CDS) for treatment of community-acquired pneumonia (ePNa) is associated with improved guideline adherence and decreased mortality. How rural providers respond to CDS developed for urban hospitals could shed light on extending CDS to resource-limited settings. METHODS: ePNa was deployed into 10 rural and critical access hospital emergency departments (EDs) in Utah and Idaho in 2018. We reviewed pneumonia cases identified through ICD-10 codes after local deployment to measure ePNa utilization and guideline adherence. ED providers were surveyed to assess quantitative and qualitative aspects of satisfaction. FINDINGS: ePNa was used in 109/301 patients with pneumonia (36%, range 0%−67% across hospitals) and was associated with appropriate antibiotic selection (93% vs 65%, P < .001). Fifty percent of survey recipients responded, 87% were physicians, 87% were men, and the median ED experience was 10 years. Mean satisfaction with ePNa was 3.3 (range 1.7–4.8) on a 5-point Likert scale. Providers with a favorable opinion of ePNa were more likely to favor implementation of additional CDS (P = .005). Satisfaction was not associated with provider type, age, years of experience or experience with ePNa. Ninety percent of respondents provided qualitative feedback. The most common theme in high and low utilization hospitals was concern about usability. Compared to high utilization hospitals, low utilization hospitals more frequently identified concerns about adaptation for local needs. CONCLUSIONS: ePNa deployment to rural and critical access EDs was moderately successful and associated with improved antibiotic use. Concerns about usability and adapting ePNa for local use predominated the qualitative feedback.

Coronavirus disease (COVID-19) is a potentially fatal illness with no proven therapy beyond excellent supportive care. Treatments are urgently sought. Adaptations to traditional trial logistics and design to allow rapid implementation, evaluation of trials within a global trials context, flexible interim monitoring, and access outside traditional research hospitals (even in settings where formal placebos are unavailable) may be helpful. Thoughtful adaptations to traditional trial designs, especially within the global context of related studies, may also foster collaborative relationships among government, community, and the research enterprise. Here, we describe the protocol for a pragmatic, active comparator trial in as many as 300 patients comparing two current "off-label" treatments for COVID-19-hydroxychloroquine and azithromycin-in academic and nonacademic hospitals in Utah. We developed the trial in response to local pressures for widespread, indiscriminate off-label use of these medications. We used a hybrid Bayesian-frequentist design for interim monitoring to allow rapid, contextual assessment of the available evidence. We also developed an inference grid for interpreting the range of possible results from this trial within the context of parallel trials and prepared for a network meta-analysis of the resulting data. This trial was prospectively registered (ClinicalTrials.gov Identifier: NCT04329832) before enrollment of the first patient.Clinical trial registered with www.clinicaltrials.gov (NCT04329832).

Background Because both diarrhea due to other causes and gastrointestinal colonization with toxigenic Clostridioides difficile are common in HSCT, there is a possibility of false-positive diagnoses of C difficile infections (CDI). Methods We estimated the probability of a patient being colonized by toxigenic C difficile by testing non-diarrheal surveillance stools from 223 HSCT recipients and the probability that a specimen submitted for C difficile testing was not CDI by determining the number of clinical tests that returned negative from this cohort. The number of expected false-positive CDI was estimated using these probabilities and compared with observed clinical test results. Results The expected false-positive and the observed numbers of positive clinical results were similar. The 20 patients diagnosed with CDI were also similar to 142 patients with diarrhea and C difficile-negative stools in number of stools on day of testing, associated symptoms, and the recorded number of days to formed stools. C difficile colonization was most commonly detected during the first week and CDI during the second. Retrospective analysis of 837 patients showed that 18 stools were submitted for each diagnosis of CDI. Ribotyping of the surveillance samples showed 17 ribotypes. Conclusions Although several assumptions could impact the accuracy of our false-positive CDI estimates, it appears that many HSCT recipients diagnosed with CDI may actually represent colonized status and an alternative cause of diarrhea. Diagnostic stewardship, including limiting CDI diagnoses to patients with positive toxin and restricting stool submissions to patients with more severe symptoms, may decrease the number of false-positive diagnoses.

Clostridioides difficile infection (CDI) is a health care-associated infection associated with significant morbidity and cost, with highly varied risk across populations. More effective, risk-based prevention strategies are needed. Here, we investigate risk factors for hospital-associated CDI in a large integrated health system. In a retrospective cohort of all adult admissions to 21 Intermountain Healthcare hospitals from 2006 to 2012, we identified all symptomatic (i) hospital-onset and (ii) health care-facility-associated, community-onset CDI. We then evaluated the risk associated with antibiotic exposure, including that of specific agents, using multivariable logistic regression. A total of 2,356 cases of CDI among 506,068 admissions were identified (incidence, 46.6 per 10,000). Prior antibiotic use was the dominant risk factor, where for every antibiotic day of therapy prior to the index admission, the odds of subsequent CDI increased by 12.8% (95% confidence interval [CI], 12.2 to 13.4%; P < 0.0001). This was a much stronger association than was inpatient antibiotic exposure (odds ratio [OR], 1.007 [95% CI, 1.005 to 1.009]; P < 0.0001). The highest-risk antibiotics included second-generation and later cephalosporins (especially oral), carbapenems, fluoroquinolones, and clindamycin, while doxycycline and daptomycin were associated with a lower CDI risk. We concluded that cumulative antibiotic exposure prior to admission is the greatest contributor to the risk of subsequent CDI. Most classes of antibiotics carry some risk, which varies by drug and route. This information may be useful for antimicrobial stewardship efforts.

Background More data are needed regarding the incidence, risk factors, and outcomes for Clostridioides difficile infection (CDI) and colonization in patients undergoing an autologous hematopoietic stem cell transplantation (AHSCT). Methods We studied 472 consecutive patients admitted for a first AHSCT and conducted a prospective C difficile stool surveillance and ribotyping analysis in a subset of 94 patients. Results Clostridioides difficile infection was diagnosed in 7% of patients for an incidence of 3.4 CDI/1000 inpatient days, recurrent/reinfection CDI was rare. CDI was increased in patients who were colonized on admission, had required a recent pre-admission inpatient stay for fever and/or serious infection, or received empiric therapy with a carbapenem or extended-spectrum penicillin. CDI was associated with a longer length of stay and higher hospital costs. Twelve of 94 patients (13%) were found to have colonization on admission; CDI was diagnosed in 27% of these vs 1% in those with initial negative stools. Colonization in the hospital for those negative on admission was infrequent. C difficile ribotyping showed a predominance of 014/020. Conclusions Clostridioides difficile infection is a significant infection in patients receiving a first AHSCT. The risk factors identified may be useful in designing preventive interventions.

Objective:To compare the effects of empiric carbapenems versus cycling cefepime and piperacillin/tazobactam on the rates of vancomycin-resistantEnterococcus(VRE) colonization, bloodstream infections, and outcomes of patients admitted with acute leukemia.Design:Retrospective clinical study with VRE molecular strain typing and gastrointestinal microbiome comparison.Setting:A regional referral center for acute leukemia.Patients:342 consecutive patients admitted with newly diagnosed acute leukemia.Methods:In September 2015, we changed our empiric antibiotic of choice for neutropenic fever from a carbapenem to the cycling regimen. We studied 214 consecutive patients during the carbapenem period and 128 during the cycling period. Surveillance for VRE stool colonization was conducted weekly. Representative stool samples were analyzed for VRE MLST types and changes in the composition and diversity of the fecal microbiota.Results:The change in empiric antibiotics was associated with a significant decrease in VRE colonization (hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.27–0.66), a switch in the dominant VRE MLST types on the unit, and some modifications in the gastrointestinal microbiome. There were no differences in total gram-positive or gram-negative BSIs. During the carbapenem period, we observed higher absolute numbers ofCandidaspp and fewer ESBL BSIs, but these did not reach statistical significance. Patients during the carbapenem period had longer lengths of stay and durations of severe neutropenia and 10% higher hospital cost.Conclusions:Carbapenem-sparing empiric antibiotic regimens may have advantages related to VRE ecology, gastrointestinal dysbiosis, duration of neutropenia, cost and length of stay.

Guidelines recommend a switch from intravenous to oral antibiotics once patients who are hospitalized with pneumonia achieve clinical stability. However, little evidence guides the selection of an oral antibiotic for patients with health care-associated pneumonia, especially where no microbiological diagnosis is made.To compare outcomes between patients who were transitioned to broad- versus narrow-spectrum oral antibiotics after initially receiving broad-spectrum intravenous antibiotic coverage.We performed a secondary analysis of an existing database of adults with community-onset pneumonia admitted to seven Utah hospitals. We identified 220 inpatients with microbiology-negative health care-associated pneumonia from 2010 to 2012. After excluding inpatient deaths and treatment failures, 173 patients remained in which broad-spectrum intravenous antibiotics were transitioned to an oral regimen. We classified oral regimens as broad-spectrum (fluoroquinolone) versus narrow-spectrum (usually a β-lactam). We compared demographic and clinical characteristics between groups. Using a multivariable regression model, we adjusted outcomes by severity (electronically calculated CURB-65), comorbidity (Charlson Index), time to clinical stability, and length of intravenous therapy.Age, severity, comorbidity, length of intravenous therapy, and clinical response were similar between the two groups. Observed 30-day readmission (11.9 vs. 21.4%; P = 0.26) and 30-day all-cause mortality (2.3 vs. 5.3%; P = 0.68) were also similar between the narrow and broad oral antibiotic groups. In multivariable analysis, we found no statistically significant differences for adjusted odds of 30-day readmission (adjusted odds ratio, 0.56; 95% confidence interval, 0.06-5.2; P = 0.61) or 30-day all-cause mortality (adjusted odds ratio, 0.55; 95% confidence interval, 0.19-1.6; P = 0.26) between narrow and broad oral antibiotic groups.On the basis of analysis of a limited number of patients observed retrospectively, our findings suggest that it may be safe to switch from broad-spectrum intravenous antibiotic coverage to a narrow-spectrum oral antibiotic once clinical stability is achieved for hospitalized patients with health care-associated pneumonia when no microbiological diagnosis is made. A larger retrospective study with propensity matching or regression-adjusted test of equivalence or ideally a prospective comparative effectiveness study will be necessary to confirm our observations.

Background Contaminated surfaces and colonization pressure are risk factors for vancomycin-resistant Enterococcus (VRE) colonization in intensive care units (ICUs). Whether these apply to modern units dedicated to the care of hematologic malignancies and hematopoietic stem cell transplant (HSCT) procedures is unknown. Methods We reviewed the records of 780 consecutive admissions for acute leukemia, autologous HSCT, or allogeneic HSCT in which the patient was at risk for hospital-acquired VRE and underwent weekly surveillance. We also obtained staff and room cultures, observed staff behavior, and performed VRE molecular strain typing on selected isolates. Results The overall rate of VRE colonization was 11.4 cases/1,000 patient days. Cultures of room surfaces revealed VRE isolates in 10% of terminally cleaned rooms. A prior VRE-colonized room occupant did not increase risk, and paired isolates from 20 patients and prior occupants were indistinguishable on molecular typing in only 1 pair. VRE colonization pressure was significantly associated with acquisition. Cultures of unit personnel and shared equipment were negative except for weighing scales. Observation of unit clinical personnel showed high compliance for hand sanitation and but less so for gowns. Conversely, ancillary staff showed poor compliance. Conclusions Transmission of VRE from room surfaces seems to be an infrequent event. Encouraging adherence to surveillance, disinfection, and contact isolation protocols may decrease VRE colonization rates.

Recurrent Clostridium difficile infection (CDI) is a consequence of intestinal dysbiosis and is particularly common following hematopoietic stem cell transplantation (HSCT). Fecal microbiota transplantation (FMT) is an effective method of treating CDI by correcting intestinal dysbiosis by passive transfer of healthy donor microflora. FMT has not been widely used in immunocompromised patients, including HSCT recipients, owing to concern for donor-derived infection. Here, we describe initial results of an FMT program for CDI at a US HSCT center. Seven HSCT recipients underwent FMT between February 2015 and February 2016. Mean time post HSCT was 635 days (25-75 interquartile range [IQR] 38-791). Five of the patients (71.4%) were on immunosuppressive therapy at FMT; 4 had required long-term suppressive oral vancomycin therapy because of immediate recurrence after antibiotic cessation. Stool donors underwent comprehensive health and behavioral screening and laboratory testing of serum and stool for 32 potential pathogens. FMT was administered via the naso-jejunal route in 6 of the 7 patients. Mean follow-up was 265 days (IQR 51-288). Minor post-FMT adverse effects included self-limited bloating and urgency. One patient was suspected of having post-FMT small intestinal bacterial overgrowth. No serious adverse events were noted and all-cause mortality was 0%. Six of 7 (85.7%) patients had no recurrence; 1 patient recurred at day 156 post FMT after taking an oral antibiotic and required repeat FMT, after which no recurrence has occurred. Diarrhea was improved in all patients and 1 patient with gastrointestinal graft-versus-host disease was able to taper off systemic immunosuppression after FMT. With careful donor selection and laboratory screening, FMT appears to be a safe and effective therapy for CDI in HSCT patients and may confer additional benefits. Larger studies are necessary to confirm safety and efficacy and explore other possible effects.

Successful treatment of life-threatening community-acquired pneumonia requires appropriate empiric antibiotic coverage. But using conventional diagnostic techniques, a microbiological diagnosis is often not achieved. The diagnostic usefulness of tracheal aspirate at the time of intubation in patients with severe pneumonia has not been well studied.The purpose of this study was to evaluate the use of tracheal aspirate culture in identifying pneumonia pathogens.We identified all patients older than 18 years of age with International Classification of Disease, Ninth Revision codes and radiographic evidence of pneumonia seen in the emergency departments at 2 university-affiliated Utah hospitals from December 2009 to November 2010 and from December 2011 to November 2012. Patients intubated within 24 hours of arrival were then identified electronically. Postintubation orders instructed respiratory therapists to obtain tracheal aspirate for culture. All culture results were reviewed individually and defined as positive if a pneumonia pathogen was identified. Results of other microbiology studies were obtained from the electronic medical record.Of 2,011 patients with pneumonia, 94 were intubated and 84 had a tracheal aspirate obtained. Of these 84 patients, 47 (56%) had a pulmonary pathogen identified by tracheal aspirate culture, 80 also had blood cultures, and 71 underwent Pneumococcal and Legionella urinary antigen testing. A microbiological diagnosis was made in 55 patients (65.5%) by any diagnostic method. In 39% of patients (32 of 82), the tracheal aspirate culture was the only positive test, resulting in a unique microbiological diagnosis in patients who would have otherwise been classified as "culture negative."Tracheal aspirate cultures obtained as part of routine care identified a plausible pneumonia pathogen in more than one-half of emergency department adult patients with severe pneumonia requiring intubation. Tracheal aspirate culture offers important additive diagnostic value to other routine tests.

QuestionIs broad-spectrum antibiotic use associated with poor outcomes in community-onset pneumonia after adjusting for confounders?MethodsWe performed a retrospective, observational cohort study of 1995 adults with pneumonia admitted from four US hospital emergency departments. We used multivariable regressions to investigate the effect of broad-spectrum antibiotics on 30-day mortality, length of stay, cost and Clostridioides difficile infection (CDI). To address indication bias, we developed a propensity score using multilevel (individual provider) generalised linear mixed models to perform inverse-probability of treatment weighting (IPTW) to estimate the average treatment effect in the treated. We also manually reviewed a sample of mortality cases for antibiotic-associated adverse events.Results39.7% of patients received broad-spectrum antibiotics, but drug-resistant pathogens were recovered in only 3%. Broad-spectrum antibiotics were associated with increased mortality in both the unweighted multivariable model (OR 3.8, 95% CI 2.5–5.9; pConclusionBroad-spectrum antibiotics appear to be associated with increased mortality and other poor outcomes in community-onset pneumonia.

To guide rational antibiotic selection in community-onset pneumonia, we previously derived and validated a novel prediction tool, the Drug-Resistance in Pneumonia (DRIP) score. In 2015, the DRIP score was integrated into an existing electronic pneumonia clinical decision support tool (ePNa).We conducted a quasi-experimental, pre-post implementation study of ePNa with DRIP score (2015) vs ePNa with health-care-associated pneumonia (HCAP) logic (2012) in ED patients admitted with community-onset pneumonia to four US hospitals. Using generalized linear models, we used the difference-in-differences method to estimate the average treatment effect on the treated with respect to ePNa with DRIP score on broad-spectrum antibiotic use, mortality, hospital stay, and cost, adjusting for available patient-level confounders.We analyzed 2,169 adult admissions: 1,122 in 2012 and 1,047 in 2015. A drug-resistant pathogen was recovered in 3.2% of patients in 2012 and 2.8% in 2015; inadequate initial empirical antibiotics were prescribed in 1.1% and 0.5%, respectively (P = .12). A broad-spectrum antibiotic was administered in 40.1% of admissions in 2012 and 33.0% in 2015 (P .001). Vancomycin days of therapy per 1,000 patient days in 2012 were 287.3 compared with 238.8 in 2015 (P .001). In the primary analysis, the average treatment effect among patients using the DRIP score was a reduction in broad-spectrum antibiotic use (OR, 0.62; 95% CI, 0.39-0.98; P = .039). However, the average effects for ePNa with DRIP on mortality, length of stay, and cost were not statistically significant.Electronic calculation of the DRIP score was more effective than HCAP criteria for guiding appropriate broad-spectrum antibiotic use in community-onset pneumonia.

Background The frequency, risk factors, and outcomes for Clostridioides difficile infection (CDI) in patients with newly diagnosed acute leukemia (AL) admitted for induction therapy are unclear. Methods We studied 509 consecutive patients with AL admitted between 2006 and 2017 and conducted a prospective C difficile surveillance and ribotyping analysis in a subset of these. Results The incidence of CDI was 2.2/1,000 inpatient days during induction, and CDI was rare after discharge. CDI was highest in patients with acute myelogenous leukemia. A hospitalization shortly before admission and administration of a greater number of antibiotics increased the risk for CDI. No single class of antibiotics conveyed an increased risk. All cases were successfully treated, and CDI was not associated with an increase in length of stay, costs, or mortality. In a subgroup analysis, 16% of patients with acute myelogenous leukemia and 4% with other leukemia types were colonized on admission. Colonization was associated with a higher risk of CDI. Ribotyping of available isolates showed 27 different strain types with 014/020 and 027 being the most frequent. Conclusions The number of antibiotics administered are a major risk factor for CDI in patients with AL. However, CDI appears to have minimal clinical impact in this population.

Recurrent Clostridioides difficile infection (rCDI) may be mediated in part by secondary bile acids. Here we report salvage therapy with ursodeoxycholic acid (UDCA) to prevent rCDI in 16 high-risk patients. Patients on UDCA had a low observed recurrence rate (12.5%). Controlled trials are needed to confirm these observations.

Background Although several studies have documented adverse outcomes for vancomycin-resistant Enterococcus (VRE) colonization and infection in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients, data are inadequate for patients undergoing autologous (auto-)HSCT. Methods We conducted a retrospective cohort study of 300 consecutive patients receiving an auto-HSCT between 2006 and 2014. Patients had stool cultures for VRE on admission and weekly during hospitalization. Results Thirty-six percent of patients had VRE gastrointestinal (GI) colonization and 3% developed a VRE bloodstream infection (BSI), all of whom were colonized. VRE strain typing of BSI isolates showed that some patients shared identical patterns. Rates of colonization and BSI in colonized patients were similar to simultaneous patients undergoing allo-HSCT, except that the latter had a higher rate of colonization at admission. A diagnosis of lymphoma was associated with an increased risk of colonization. VRE BSI was associated with longer lengths of stay and possibly higher costs, but no decrease in overall survival, and colonized patients had no VRE infections during the year following discharge. Repeat stool cultures in patients subsequently undergoing allo-HSCT suggested that most, if not all, VRE-positive auto-HSCT patients lose their detectable GI colonization within a few months of discharge. Conclusion VRE colonization is frequent but carries a low risk for infection in patients undergoing auto-HSCT. However, these patients can serve as reservoirs for transmission to higher risk patients. Moreover, patients may remain colonized if proceeding to an allo-HSCT shortly after auto-HSCT, potentially increasing the risk of the allogeneic procedure.

OBJECTIVEWhile a direct relation between hospital construction and concomitant infection rates has been clearly established, few data are available regarding the environmental decontamination effects of renovation in which surfaces are replaced and regarding subsequent infection incidence.DESIGNRetrospective clinical study with vancomycin-resistant Enterococcus (VRE) molecular strain typing and environmental cultures.SETTINGA regional referral center for acute leukemia and hematopoietic stem-cell transplantation.PATIENTSOverall, 536 consecutive hospital admissions for newly diagnosed acute leukemia or a first autologous or allogeneic stem-cell transplantation were reviewed.INTERVENTIONDuring 2009–2010, our unit underwent complete remodeling including replacement of all surfaces. We assessed the effects of this construction on the incidence of hospital-acquired VRE colonization before, during, and after the renovation.RESULTSWe observed a sharp decrease in VRE colonization rates (hazard ratio, PCONCLUSIONSUnit reconstruction interrupted endemic transmission of VRE, which resumed with novel strains upon reopening. Contamination of environmental surfaces and shared equipment may play an important role in endemic transmission of VRE.Infect Control Hosp Epidemiol 2017;38:1055–1061

Bloodstream infection (BSI) to due vancomycin-resistant Enterococcus (VRE) is an important complication of hematologic malignancy. Determining when to use empiric anti-VRE antibiotic therapy in this population remains a clinical challenge.A single-center cohort representing 664 admissions for induction or hematopoietic stem-cell transplant (HSCT) from 2006 to 2014 was selected. We derived a prediction score using risk factors for VRE BSI and evaluated the model's predictive performance by calculating it for each of 16232 BSI at-risk inpatient days.VRE BSI incidence was 6.5% of admissions (2.7 VRE BSI per 1000 BSI at-risk days). Adjusted 1-year mortality and length of stay were significantly higher in patients with VRE BSI. VRE colonization (adjusted odds ratio [aOR] = 8.4; 95% confidence interval [CI] = 3.4-20.6; P.0001), renal insufficiency (aOR = 2.4; 95% CI = 1.0-5.8; P = .046), aminoglycoside use (aOR = 4.7; 95% CI = 2.2-9.8; P.0001), and antianaerobic antibiotic use (aOR = 2.8; 95% CI = 1.3-5.8; P = .007) correlated most closely with VRE BSI. A prediction model with optimal performance included these factors plus gastrointestinal disturbance, severe neutropenia, and prior beta-lactam antibiotic use. The score effectively risk-stratified patients (area under the receiver operating curve = 0.84; 95% CI = 0.79-0.89). At a threshold of ≥5 points, per day probability of VRE BSI was increased nearly 4-fold.This novel predictive score is based on risk factors reflecting a plausible pathophysiological model for VRE BSI in patients with hematological malignancy. Integrating VRE colonization status with risk factors for developing BSI is a promising method of guiding rational use of empiric anti-VRE antimicrobial therapy in patients with hematological malignancy. Validation of this novel predictive score is needed to confirm clinical utility.

The association between pre–hematopoietic stem cell transplantation (HSCT) vancomycin-resistant Enterococcus (VRE) colonization, HSCT-associated VRE bacteremia, and HSCT mortality is disputed. We studied 161 consecutive patients with acute leukemia who underwent HSCT at our hospital between 2006 and 2014, of whom 109 also received leukemia induction/consolidation on our unit. All inpatients had weekly VRE stool surveillance. Pre-HSCT colonization was not associated with increases in HSCT mortality but did identify a subgroup of HSCT recipients with a higher risk for VRE bacteremia and possibly bacteremia from other organisms. The major risk factor for pre-HSCT colonization was the number of hospital inpatient days between initial admission for leukemia and HSCT. One-third of evaluable patients colonized before HSCT were VRE-culture negative on admission for HSCT; these patients had an increased risk for subsequent VRE stool surveillance positivity but not VRE bacteremia. Molecular typing of VRE isolates obtained before and after HSCT showed that VRE strains frequently change. Postengraftment VRE bacteremia was associated with a much higher mortality than pre-engraftment VRE bacteremia. Pre-engraftment bacteremia from any organism was associated with an alternative donor and resulted in an increase in hospital length of stay and cost. Mortality was similar for pre-engraftment VRE bacteremia and pre-engraftment bacteremia due to other organisms, but mortality associated with post-engraftment VRE bacteremia was higher and largely explained by associated severe graft-versus-host disease and relapsed leukemia. These data emphasize the importance of distinguishing between VRE colonization before HSCT and at HSCT, between pre-engraftment and postengraftment VRE bacteremia, and between VRE bacteremia and bacteremia from other organisms.

Background CMV infection (CMV-I) remains an important complication of hematopoietic stem cell transplantation (HSCT). Methods This was a retrospective, single-center cohort study in HSCT recipients. Primary outcomes were adjusted cost and all-cause mortality. Secondary analyses investigated CMV risk factors and the effect of serostatus. Results Overall, 690 transplant episodes were included (allogeneic [n = 310]; autologous [n = 380]). All received preemptive CMV antiviral therapy at first detectable DNAemia. CMV-I occurred in 34.8% of allogeneic and 2.1% of autologous transplants; median time to onset was 45 days. In allogeneic HSCT recipients, the primary risk factor for CMV-I was CMV donor/recipient (D/R) serostatus. In a Markov multi-state model for allogeneic HSCT recipients, the hazard ratio for CMV-I and relapse was 1.5 (95% CI 0.8-2.8) and for CMV-I and mortality 2.4 (95% CI 0.9-6.5). In a multivariable model for all patients, CMV-I was associated with increased total cost (coefficient = 0.21, estimated incremental daily cost USD $500; P = 0.02). Cost was attenuated in allogeneic HSCT recipients (coefficient = 0.13, USD $699 vs $613, or $24 892 per transplant episode; P = 0.23). CMV disease (CMV-D) complicated 29.6% of CMV-I events in allogeneic HSCT recipients, but was not associated with an incrementally increased adjusted risk of mortality compared with CMV-I alone. CMV-I (56.4%) and CMV-D (19.8%) were significantly overrepresented in D-/R+ serostatus HSCT recipients, and mortality was higher in R+ HSCT recipients. Conclusions Despite early preemptive antiviral treatment, CMV-I impacts clinical outcomes and cost after HSCT, but the impact on cost is less pronounced in allogeneic HSCT recipients compared with autologous HSCT recipients.

To investigate potential differences in clinical presentation, histopathology, and outcomes of chronic invasive sinus aspergillosis (CISA) based on geographic region and species of Aspergillus isolated. A retrospective analysis of published cases of CISA with a comparison of North American and worldwide cases comprised a systematic search of the English language literature. Thirty-four articles were identified detailing 15 North American and 76 global cases of CISA with cranio-cerebral extension in clinically immunocompetent patients. North American patients with CISA were older, had a more rapidly progressive course, and appeared to have higher rates of treatment failure and mortality. Anatomic distribution and presenting symptoms were similar between the two groups. North American cases were mostly due to A. fumigatus, while A. flavus was the predominant pathogen worldwide. While granulomatous inflammation was a rare observation in North American cases, it was seen in the majority of cases worldwide. CISA due to A. fumigatus was encountered in older adults, was associated with a chronic inflammatory response, an accelerated clinical course, and a trend toward treatment failure and higher mortality. Patients with A. flavus were younger, demonstrated granulomatous inflammation, and pursued an indolent, clinically responsive course. Observed differences in clinical presentation, histopathology, and outcome might involve a complex interplay between the human host, Aspergillus species, and local climactic conditions.

Pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA) is associated with poor outcomes and frequently merits empirical antibiotic consideration despite its relatively low incidence. Nasal colonization with MRSA is associated with clinical MRSA infection and can be reliably detected using the nasal swab PCR assay. In this study, we evaluated the performance of the nasal swab MRSA PCR in predicting MRSA pneumonia. A retrospective cohort study was performed in a tertiary care center from January 2009 to July 2011. All patients with confirmed pneumonia who had both a nasal swab MRSA PCR test and a bacterial culture within predefined time intervals were included in the study. These data were used to calculate sensitivity, specificity, positive predictive value, and negative predictive value for clinically confirmed MRSA pneumonia. Four hundred thirty-five patients met inclusion criteria. The majority of cases were classified as either health care-associated (HCAP) (54.7%) or community-acquired (CAP) (34%) pneumonia. MRSA nasal PCR was positive in 62 (14.3%) cases. MRSA pneumonia was confirmed by culture in 25 (5.7%) cases. The MRSA PCR assay demonstrated 88.0% sensitivity and 90.1% specificity, with a positive predictive value of 35.4% and a negative predictive value of 99.2%. In patients with pneumonia, the MRSA PCR nasal swab has a poor positive predictive value but an excellent negative predictive value for MRSA pneumonia in populations with low MRSA pneumonia incidence. In cases of culture-negative pneumonia where initial empirical antibiotics include an MRSA-active agent, a negative MRSA PCR swab can be reasonably used to guide antibiotic de-escalation.

The Accreditation Council for Graduate Medical Education (ACGME) implemented work hour restrictions for physicians in training in 2003 that were revised July 1, 2011. Current published data are insufficient to assess whether such work hour restrictions will have long-term impact on residents’ education. We searched computer-generated reports of hospital in-patient census, continuity clinic census, in-training exam scores and first-year resident attendance at educational conferences for the academic years 2010–2011 (August 1, 2010—May 31, 2011) and 2011–2013 (August 1, 2011—May 31, 2013). During the first year of the study period, the residents’ inpatient internal medicine services admitted 1,754 patients; during this same period for academic years 2011–2012 and 2012–2013, the teaching services admitted 1,539 and 1,428 patients respectively, yielding a decrease of 16.4 %. Monthly, these services cared for a mean of 27.1 (27.1/175.4 [15.4 %]) fewer patients and 9.7 (9.7/34.4 [28.2 %]) fewer patients per intern than in the previous year. No statistical difference was observed regarding continuity clinic attendance and in-training exam scores. Residents in the years following work hours restrictions attended more educational conferences. Implementation of 2011 ACGME work hour regulations resulted in fewer patients seen by first-year residents in hospital, but did not affect in-training exam scores. Whether these findings will translate into differences in patient outcomes, and quality of care remains to be seen.

Invasive fungal infections are a significant complication of solid organ transplantation. Here we report the first case of concurrent invasive pulmonary fungal infection caused by Aspergillus fumigatus and Mucor species in a heart transplant recipient. Polymicrobial mold infection is rare but should be considered in solid organ transplant recipients who fail to respond to initial antifungal therapy targeting a single organism. It is also of interest that in addition to potent immunosuppression and prolonged voriconazole therapy, possible airway fungal colonization following hurricane Katrina cleaning efforts might have contributed to this dual invasive mold infection.

SummaryBackgroundThe 2005 ATS/IDSA guidelines defined healthcare-associated pneumonia (HCAP) as a novel category of pneumonia in patients with significant healthcare exposure in whom the risk of drug resistant bacteria may be higher. In this study, we compare clinical outcomes in patients with HCAP who were treated with guideline-concordant antibiotic regimens with those who were not.MethodsMedical records of 100 patients meeting HCAP criteria admitted to an academic tertiary care hospital between January 2009 and January 2011 were retrospectively reviewed. Cases were divided into guideline-concordant and guideline-discordant groups based on antibiotic therapy. Demographic, microbiological and clinical outcome data were compared for both groups.ResultsPatients in this cohort had multiple co-morbidities, severe pneumonia (mean PSI score 124.1), and significant mortality (22%). 21 of the 100 cases (21.0%) were culture positive, of which 11 (53.8%) represented drug-resistant pathogens. No statistically significant differences for any of the four clinical outcome measures were detected between the guideline-concordant therapy group and guideline-discordant group. In multivariate regression analysis controlling for possible confounders, similar results were observed, with the exception that length of stay was significantly longer (3.99 days, p