2435. The Impact of Treatment Strategy and Toxin Status on Outcomes of Patients with Clostridioides difficile Infections

Abstract Background Clostridioides difficile infection (CDI) is an important cause of morbidity and mortality and management continues to evolve. For laboratories that diagnose by detection of toxin gene, it is unclear whether reporting toxin production is additive to patient care. Furthermore, is there still a role for metronidazole (MNZ) given treatment guidelines now recommend vancomycin (VAN) as first-line therapy for non-severe cases? We analyzed cases of CDI in our hospital to assess outcomes of patients on MNZ vs. VAN and with or without toxin production. Methods A retrospective chart review of inpatients with CDI (based on detection of C. difficile toxin gene by PCR) was conducted between November 2017 and August 2018. Comparison of demographics and outcomes was performed in a) cases that were toxin-positive by enzyme immunoassay vs. negative and b) non-severe cases initially managed with MNZ vs. VAN. Results 76 patients were included (46 toxin-positive, 30 toxin-negative). Toxin-positive patients were older (mean age 77 vs. 62, p = 0.002) but had similar disease severity and initial treatment. A CDI recurrence occurred in 22% vs 0% in the toxin-positive cases (p = 0.006). Any CDI-related complication occurred in 23% of toxin-negative and 35% of toxin-positive cases (ns). After adjusting for toxin-status, age, and severity, the odds ratio of the composite outcome of any complication with toxin-positive CDI was not significant (OR 1.45 95% CI 0.45 -4.6, p = 0.52). There were 37 (49%) patients with non-severe CDI (27 MNZ, 10 VAN). Patients treated with VAN had higher stooling/day (6.3 vs 4.4, p = 0.04) and heart rate (p = 0.02). Initial MNZ use was associated with treatment escalation in 48% of cases compared with 10% in those treated with VAN alone (p = 0.03). CDI-associated mortality was higher in the VAN group (2/10 vs 0/27, p = 0.017). The rate of other complications was not significantly different. Conclusion Although no difference in the composite outcome of any CDI-related complication was detected between toxin positive vs negative patients, toxin-positivity may predict patients at risk for subsequent recurrence. Patients with non-severe CDI did not have increased risk of complications when managed with MNZ; however, they were more likely to require treatment escalation. Disclosures All authors: No reported disclosures.

Download Full-text

Effect of Average Blood Glucose Greater Than 140 mg/dL on Adverse Patient Outcomes in Adult Medical/Surgical Patients

INNOVATIONS in pharmacy ◽

10.24926/iip.v12i1.3577 ◽

2021 ◽

Vol 12 (1) ◽

pp. 10

Author(s):

Morgan Wynes ◽

Jaclyn Boyle

Keyword(s):

Blood Glucose ◽

Patient Outcomes ◽

Single Point ◽

Retrospective Chart Review ◽

Primary Objective ◽

Surgical Patients ◽

Composite Outcome ◽

Increased Risk ◽

Average Blood Glucose ◽

The Impact

Background: In hospitalized patients, hyperglycemia is defined as blood glucose greater than 140 mg/dL. Hyperglycemia can lead to the development of nosocomial infections as well as cardiovascular events. Despite these risks, current guidelines recommend blood glucose be maintained between 140-180 mg/dL. Previous studies have shown that elevated blood glucose levels are associated with increased patient mortality. However, these studies assessed blood glucose at a single point in time. Objective: The primary objective of this study is to determine the impact of average blood glucose >140 mg/dL on a composite outcome of intensive care unit transfer, death, length of stay > 4 days, development of nosocomial infection, or new cardiovascular event (myocardial infarction [MI], ischemic stroke, deep vein thrombosis [DVT], pulmonary embolism [PE], or new onset heart failure) occurring during patient admission. Methods: This single centered, randomized, case-control, retrospective chart review sorted adult medical/surgical patients into two groups, average blood glucose ≤140 mg/dL or >140 mg/dL, of 120 patients each. Results: Forty-seven (39.2%) patients in the >140 mg/dL group experienced the primary composite outcome versus 27 (22.5%) patients in the ≤140 mg/dL group (p=0.005). Secondary outcomes found that patients with diabetes in the >140 mg/dL group were more likely to experience the primary outcome than those in the ≤140 mg/dL group (41 (48.8%) vs 3 (13.6%) p=0.003). Conclusions: This study found that medical/surgical patients with an average blood glucose >140 mg/dL may be at an increased risk of developing adverse patient outcomes.

Download Full-text

Gastrostomy Tubes Placed in Children With Neurologic Impairment: Associated Morbidity and Mortality

Journal of Child Neurology ◽

10.1177/08830738211000179 ◽

2021 ◽

pp. 088307382110001

Author(s):

Jody L. Lin ◽

Joseph Rigdon ◽

Keith Van Haren ◽

MyMy Buu ◽

Olga Saynina ◽

...

Keyword(s):

Severe Pneumonia ◽

Sensitivity Analyses ◽

Tube Placement ◽

Composite Outcome ◽

Eligibility Criteria ◽

Risk Of Death ◽

Cox Proportional Hazard ◽

Neurologic Impairment ◽

Increased Risk ◽

The Impact

Background: Gastrostomy tube (G-tube) placement for children with neurologic impairment with dysphagia has been suggested for pneumonia prevention. However, prior studies demonstrated an association between G-tube placement and increased risk of pneumonia. We evaluate the association between timing of G-tube placement and death or severe pneumonia in children with neurologic impairment. Methods: We included all children enrolled in California Children’s Services between July 1, 2009, and June 30, 2014, with neurologic impairment and 1 pneumonia hospitalization. Prior to analysis, children with new G-tubes and those without were 1:2 propensity score matched on sociodemographics, medical complexity, and severity of index hospitalization. We used a time-varying Cox proportional hazard model for subsequent death or composite outcome of death or severe pneumonia to compare those with new G-tubes vs those without, adjusting for covariates described above. Results: A total of 2490 children met eligibility criteria, of whom 219 (9%) died and 789 (32%) had severe pneumonia. Compared to children without G-tubes, children with new G-tubes had decreased risk of death (hazard ratio [HR] 0.47, 95% confidence interval [CI] 0.39-0.55) but increased risk of the composite outcome (HR 1.21, CI 1.14-1.27). Sensitivity analyses using varied time criteria for definitions of G-tube and outcome found that more recent G-tube placement had greater associated risk reduction for death but increased risk of severe pneumonia. Conclusion: Recent G-tube placement is associated with reduced risk of death but increased risk of severe pneumonia. Decisions to place G-tubes for pulmonary indications in children with neurologic impairment should weigh the impact of severe pneumonia on quality of life.

Download Full-text

Temporal Variations in Patterns of Clostridioides difficile Strain Diversity and Antibiotic Resistance in Thailand

Antibiotics ◽

10.3390/antibiotics10060714 ◽

2021 ◽

Vol 10 (6) ◽

pp. 714

Author(s):

Supapit Wongkuna ◽

Tavan Janvilisri ◽

Matthew Phanchana ◽

Phurt Harnvoravongchai ◽

Amornrat Aroonnual ◽

...

Keyword(s):

Antibiotic Resistance ◽

Antimicrobial Susceptibility ◽

Reference Strain ◽

Toxin Production ◽

Temporal Variations ◽

Toxin Gene ◽

Data Sets ◽

Clostridioides Difficile ◽

Life Threatening ◽

Susceptibility Profiles

Clostridioides difficile has been recognized as a life-threatening pathogen that causes enteric diseases, including antibiotic-associated diarrhea and pseudomembranous colitis. The severity of C. difficile infection (CDI) correlates with toxin production and antibiotic resistance of C. difficile. In Thailand, the data addressing ribotypes, toxigenic, and antimicrobial susceptibility profiles of this pathogen are scarce and some of these data sets are limited. In this study, two groups of C. difficile isolates in Thailand, including 50 isolates collected from 2006 to 2009 (THA group) and 26 isolates collected from 2010 to 2012 (THB group), were compared for toxin genes and ribotyping profiles. The production of toxins A and B were determined on the basis of toxin gene profiles. In addition, minimum inhibitory concentration of eight antibiotics were examined for all 76 C. difficile isolates. The isolates of the THA group were categorized into 27 A−B+CDT− (54%) and 23 A-B-CDT- (46%), while the THB isolates were classified into five toxigenic profiles, including six A+B+CDT+ (23%), two A+B+CDT− (8%), five A−B+CDT+ (19%), seven A−B+CDT− (27%), and six A−B−CDT− (23%). By visually comparing them to the references, only five ribotypes were identified among THA isolates, while 15 ribotypes were identified within THB isolates. Ribotype 017 was the most common in both groups. Interestingly, 18 unknown ribotyping patterns were identified. Among eight tcdA-positive isolates, three isolates showed significantly greater levels of toxin A than the reference strain. The levels of toxin B in 3 of 47 tcdB-positive isolates were significantly higher than that of the reference strain. Based on the antimicrobial susceptibility test, metronidazole showed potent efficiency against most isolates in both groups. However, high MIC values of cefoxitin (MICs 256 μg/mL) and chloramphenicol (MICs ≥ 64 μg/mL) were observed with most of the isolates. The other five antibiotics exhibited diverse MIC values among two groups of isolates. This work provides evidence of temporal changes in both C. difficile strains and patterns of antimicrobial resistance in Thailand.

Download Full-text

Abstract P305: Post-Stroke Aphasia as a Predictor of 30-Day Readmission Associated With Infection: A Retrospective Chart Review

Stroke ◽

10.1161/str.52.suppl_1.p305 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Emma M Loebel ◽

Mary Rojas ◽

Connor Mensching ◽

Danielle Wheelwright ◽

Laura K Stein

Keyword(s):

Chart Review ◽

Retrospective Chart Review ◽

Mount Sinai Hospital ◽

Index Admission ◽

Negative Consequences ◽

Medical Comorbidities ◽

Post Stroke ◽

Increased Risk ◽

Adjusted Model ◽

The Impact

Introduction: Studies have demonstrated that aphasia may negatively impact morbidity and mortality among ischemic stroke (IS) patients. However, the association between post-stroke aphasia and readmission with infection (RI) is poorly understood. We sought to assess the impact of aphasia on post-stroke RI. We hypothesized that aphasic patients are at increased risk of infection in the 30-day post-stroke period. Methods: We performed retrospective chart review of the Mount Sinai Hospital IS patients with 30-day all cause readmission from January 2016 - December 2019. All variables were abstracted from the index admission (IA) electronic medical records except for aspects related to the readmission (RA). Aphasia was present if a neurologist diagnosed the patient with acquired language dysfunction during IA. We performed chi square and logistic regression analyses to compare readmitted patients with and without aphasia at IA. Our fully adjusted model controlled for age, sex, medical comorbidities, NIHSS ≥ 8, IA LOS > 7, IA infection, discharge to facility. We completed all analyses with SPSS. Results: During IA, 36% (n=42) were diagnosed with aphasia. At IA, there were no significant differences in age (dichotomized at 65), sex, or medical comorbidities between aphasic and non-aphasic cohorts. However, more aphasic patients had admission NIHSS ≥ 8 (89% vs 35%, p<0.0001), LOS > 7 (76% vs 42%, p=0.0004), discharge to facility (79% vs 49%, p=0.0016), and RI (52% vs 19%, p=0.002). The presence of aphasia predicted RI in both unadjusted (OR=4.6, p<0.001) and adjusted (OR= 3.3, p=0.014) multivariate analyses. The Kappa inter-reliability ranged from 0.7-1.0 for the key variables included in our adjusted model. Conclusions: The adjusted odds of 30-day readmission with infection were significantly greater in those with diagnosis of aphasia at the time of index admission compared to those without. Our study provides preliminary evidence that the presence of aphasia may have negative consequences on a patient’s health beyond the language disturbance. Further study is needed to better understand the reasons and risk reduction strategies in this vulnerable population.

Download Full-text

FliW and CsrA Govern Flagellin (FliC) Synthesis and Play Pleiotropic Roles in Virulence and Physiology of Clostridioides difficile R20291

Frontiers in Microbiology ◽

10.3389/fmicb.2021.735616 ◽

2021 ◽

Vol 12 ◽

Author(s):

Duolong Zhu ◽

Shaohui Wang ◽

Xingmin Sun

Keyword(s):

Bacterial Colonization ◽

Toxin Production ◽

Toxin Gene ◽

Clostridioides Difficile ◽

Significant Difference ◽

Assembly Factor ◽

Carbon Storage Regulator ◽

Transcription Suppression ◽

Post Transcriptional Regulation

Clostridioides difficile flagellin FliC is associated with toxin gene expression, bacterial colonization, and virulence, and is also involved in pleiotropic gene regulation during in vivo infection. However, how fliC expression is regulated in C. difficile remains unclear. In Bacillus subtilis, flagellin homeostasis and motility are coregulated by flagellar assembly factor (FliW), flagellin Hag (FliC homolog), and Carbon storage regulator A (CsrA), which is referred to as partner-switching mechanism “FliW-CsrA-Hag.” In this study, we characterized FliW and CsrA functions by deleting or overexpressing fliW, csrA, and fliW-csrA in C. difficile R20291. We showed that fliW deletion, csrA overexpression in R20291, and csrA complementation in R20291ΔWA (fliW-csrA codeletion mutant) dramatically decreased FliC production, but not fliC gene transcription. Suppression of fliC translation by csrA overexpression can be relieved mostly when fliW was coexpressed, and no significant difference in FliC production was detected when only fliW was complemented in R20291ΔWA. Further, loss of fliW led to increased biofilm formation, cell adhesion, toxin production, and pathogenicity in a mouse model of C. difficile infection (CDI), while fliW-csrA codeletion decreased toxin production and mortality in vivo. Our data suggest that CsrA negatively modulates fliC expression and FliW indirectly affects fliC expression through inhibition of CsrA post-transcriptional regulation. In light of “FliW-CsrA-Hag” switch coregulation mechanism reported in B. subtilis, our data also suggest that “FliW-CsrA-fliC/FliC” can regulate many facets of C. difficile R20291 pathogenicity. These findings further aid us in understanding the virulence regulation in C. difficile.

Download Full-text

RstA Is a Major Regulator ofClostridioides difficileToxin Production and Motility

mBio ◽

10.1128/mbio.01991-18 ◽

2019 ◽

Vol 10 (2) ◽

Cited By ~ 10

Author(s):

Adrianne N. Edwards ◽

Brandon R. Anjuwon-Foster ◽

Shonna M. McBride

Keyword(s):

Gene Expression ◽

Dna Binding ◽

Toxin Production ◽

Toxin Gene ◽

Dna Binding Domain ◽

Content Type ◽

Toxin Genes ◽

Clostridioides Difficile ◽

Species Specific ◽

Toxin Gene Expression

ABSTRACTClostridioides difficileinfection (CDI) is a toxin-mediated diarrheal disease. Several factors have been identified that influence the production of the two majorC. difficiletoxins, TcdA and TcdB, but prior published evidence suggested that additional unknown factors were involved in toxin regulation. Previously, we identified aC. difficileregulator, RstA, that promotes sporulation and represses motility and toxin production. We observed that the predicted DNA-binding domain of RstA was required for RstA-dependent repression of toxin genes, motility genes, andrstAtranscription. In this study, we further investigated the regulation of toxin and motility gene expression by RstA. DNA pulldown assays confirmed that RstA directly binds therstApromoter via the predicted DNA-binding domain. Through mutational analysis of therstApromoter, we identified several nucleotides that are important for RstA-dependent transcriptional regulation. Further, we observed that RstA directly binds and regulates the promoters of the toxin genestcdAandtcdB, as well as the promoters for thesigDandtcdRgenes, which encode regulators of toxin gene expression. Complementation analyses with theClostridium perfringensRstA ortholog and a multispecies chimeric RstA protein revealed that theC. difficileC-terminal domain is required for RstA DNA-binding activity, suggesting that species-specific signaling controls RstA function. Our data demonstrate that RstA is a transcriptional repressor that autoregulates its own expression and directly inhibits transcription of the two toxin genes and two positive toxin regulators, thereby acting at multiple regulatory points to control toxin production.IMPORTANCEClostridioides difficileis an anaerobic, gastrointestinal pathogen of humans and other mammals.C. difficileproduces two major toxins, TcdA and TcdB, which cause the symptoms of the disease, and forms dormant endospores to survive the aerobic environment outside the host. A recently discovered regulatory factor, RstA, inhibits toxin production and positively influences spore formation. Herein, we determine that RstA directly binds its own promoter DNA to repress its own gene transcription. In addition, our data demonstrate that RstA directly represses toxin gene expression and gene expression of two toxin gene activators, TcdR and SigD, creating a complex regulatory network to tightly control toxin production. This study provides a novel regulatory link betweenC. difficilesporulation and toxin production. Further, our data suggest thatC. difficiletoxin production is regulated through a direct, species-specific sensing mechanism.

Download Full-text

Clinical impact of a pharmacist-led antimicrobial stewardship initiative evaluating patients with Clostridioides difficile colitis

Journal of Investigative Medicine ◽

10.1136/jim-2019-001173 ◽

2020 ◽

Vol 68 (4) ◽

pp. 888-892 ◽

Cited By ~ 1

Author(s):

Paige A Bishop ◽

Carmen Isache ◽

Yvette S McCarter ◽

Carmen Smotherman ◽

Shiva Gautam ◽

...

Keyword(s):

Clinical Outcomes ◽

Antimicrobial Stewardship ◽

Treatment Guidelines ◽

Clinical Success ◽

Audit And Feedback ◽

Healthcare Associated Infection ◽

Clostridioides Difficile ◽

Stewardship Program ◽

The Usa ◽

The Impact

Clostridioides difficile is the most common cause of healthcare-associated infection and gastroenteritis-associated death in the USA. Adherence to guideline recommendations for treatment of severe C. difficile infection (CDI) is associated with improved clinical success and reduced mortality. The purpose of this study was to determine whether implementation of a pharmacist-led antimicrobial stewardship program (ASP) CDI initiative improved adherence to CDI treatment guidelines and clinical outcomes. This was a single-center, retrospective, quasi-experimental study evaluating patients with CDI before and after implementation of an ASP initiative involving prospective audit and feedback in which guideline-driven treatment recommendations were communicated to treatment teams and documented in the electronic health record via pharmacy progress notes for all patients diagnosed with CDI. The primary endpoint was the proportion of patients treated with guideline adherent definitive regimens within 72 hours of CDI diagnosis. Secondary objectives were to evaluate the impact on clinical outcomes, including length of stay (LOS), infection-related LOS, 30-day readmission rates, and all-cause, in-hospital mortality. A total of 233 patients were evaluated. The proportion of patients on guideline adherent definitive CDI treatment regimen within 72 hours of diagnosis was significantly higher in the post-interventional group (pre: 42% vs post: 58%, p=0.02). No differences were observed in clinical outcomes or proportions of patients receiving laxatives, promotility agents, or proton pump inhibitors within 72 hours of diagnosis. Our findings demonstrate that a pharmacist-led stewardship initiative improved adherence to evidence-based practice guidelines for CDI treatment.

Download Full-text

Reorganisation of faecal microbiota transplant services during the COVID-19 pandemic

Gut ◽

10.1136/gutjnl-2020-321829 ◽

2020 ◽

Vol 69 (9) ◽

pp. 1555-1563 ◽

Cited By ~ 11

Author(s):

Gianluca Ianiro ◽

Benjamin H Mullish ◽

Colleen R Kelly ◽

Zain Kassam ◽

Ed J Kuijper ◽

...

Keyword(s):

Healthcare Professionals ◽

Faecal Microbiota ◽

Clostridioides Difficile ◽

Research Activities ◽

Increased Risk ◽

Recruitment And Selection ◽

Spread Of Infection ◽

The Impact

The COVID-19 pandemic has led to an exponential increase in SARS-CoV-2 infections and associated deaths, and represents a significant challenge to healthcare professionals and facilities. Individual countries have taken several prevention and containment actions to control the spread of infection, including measures to guarantee safety of both healthcare professionals and patients who are at increased risk of infection from COVID-19. Faecal microbiota transplantation (FMT) has a well-established role in the treatment of Clostridioides difficile infection. In the time of the pandemic, FMT centres and stool banks are required to adopt a workflow that continues to ensure reliable patient access to FMT while maintaining safety and quality of procedures. In this position paper, based on the best available evidence, worldwide FMT experts provide guidance on issues relating to the impact of COVID-19 on FMT, including patient selection, donor recruitment and selection, stool manufacturing, FMT procedures, patient follow-up and research activities.

Download Full-text

The impact of age on approach-related complications with navigated lateral lumbar interbody fusion

Neurosurgical FOCUS ◽

10.3171/2020.6.focus20311 ◽

2020 ◽

Vol 49 (3) ◽

pp. E8

Author(s):

Yamaan S. Saadeh ◽

Clay M. Elswick ◽

Eleanor Smith ◽

Timothy J. Yee ◽

Michael J. Strong ◽

...

Keyword(s):

Risk Factor ◽

Elderly Patients ◽

Interbody Fusion ◽

Multivariable Analysis ◽

The Elderly ◽

Lumbar Interbody Fusion ◽

Related Complication ◽

Lateral Lumbar Interbody Fusion ◽

Increased Risk ◽

The Impact

OBJECTIVEAge is known to be a risk factor for increased complications due to surgery. However, elderly patients can gain significant quality-of-life benefits from surgery. Lateral lumbar interbody fusion (LLIF) is a minimally invasive procedure that is commonly used to treat degenerative spine disease. Recently, 3D navigation has been applied to LLIF. The purpose of this study was to determine whether there is an increased complication risk in the elderly with navigated LLIF.METHODSPatients who underwent 3D-navigated LLIF for degenerative disease from 2014 to 2019 were included in the analysis. Patients were divided into elderly and nonelderly groups, with those 65 years and older categorized as elderly. Ninety-day medical and surgical complications were recorded. Patient and surgical characteristics were compared between groups, and multivariate regression analysis was used to determine independent risk factors for complication.RESULTSOf the 115 patients included, 56 were elderly and 59 were nonelderly. There were 15 complications (25.4%) in the nonelderly group and 10 (17.9%) in the elderly group, which was not significantly different (p = 0.44). On multivariable analysis, age was not a risk factor for complication (p = 0.52). However, multiple-level LLIF was associated with an increased risk of approach-related complication (OR 3.58, p = 0.02).CONCLUSIONSElderly patients do not appear to experience higher rates of approach-related complications compared with nonelderly patients undergoing 3D navigated LLIF. Rather, multilevel surgery is a predictor for approach-related complication.

Download Full-text

Start low, go fast? Antipsychotic titration patterns at an inpatient psychiatric hospital

Mental Health Clinician ◽

10.9740/mhc.2020.09.275 ◽

2020 ◽

Vol 10 (5) ◽

pp. 275-281

Author(s):

Nina Vadiei ◽

Jonathan Chien ◽

Jude Enwereji ◽

Britt Myslinski ◽

Alexander Guzman

Keyword(s):

Psychiatric Hospital ◽

Treatment Guidelines ◽

Average Length ◽

Retrospective Chart Review ◽

Optimal Dose ◽

Primary Diagnosis ◽

Mental Illnesses ◽

Psychotic Symptoms ◽

Inpatient Setting ◽

The Impact

Abstract Introduction Antipsychotics are commonly used to treat psychotic symptoms and severe mental illnesses. Treatment guidelines recommend antipsychotics be titrated quickly to therapeutic effect in the acute setting but acknowledge that determining the optimal dose is complicated by a delay between treatment initiation and therapeutic response. The purpose of this study was to evaluate antipsychotic titration patterns in an inpatient psychiatric hospital. Methods This study is a retrospective chart review of adult patients admitted to a teaching hospital and initiated on an antipsychotic for treatment of psychosis between January and December 2018. Patients were excluded if they had substance-induced psychosis, delirium, were prescribed >1 antipsychotic, or had no antipsychotic dose changes. The primary outcome was the average titration rate of the newly initiated antipsychotic. Secondary outcomes included differences in titration rate between involuntary and voluntary admissions and other antipsychotic characteristics. Results Of 149 patients included, the majority had a primary diagnosis of schizophrenia. Antipsychotics were titrated on average every 2 days regardless of admission type. Eighteen percent of patients were titrated to guideline-recommended maximum doses, and it took, on average, 3 days for patients to reach their final dose during hospitalization. Average length of stay was 9 days, and 43.6% of patients were readmitted within 1 year. Discussion Antipsychotics are titrated rapidly in the inpatient setting despite a lack of evidence regarding the impact of titration rate on clinical outcomes. Further studies comparing slow versus rapid titration strategies are needed to elucidate the impact of this on patient outcomes.

Download Full-text