Category Archives: C. diff. Research Community

Researchers Share Risk Factors for Recurrence of Clostridioides difficile (formally known as Clostridium difficile) Infection In Japan Real-World Analysis

 

 

 

 

Author information

Abstract

OBJECTIVE:

Recurrent Clostridioides (Clostridium) difficile infection (rCDI) is common and increases healthcare resource utilization. In this study, we assessed rCDI risk factors using an up-to-date, Japanese national hospital-based database.

METHODS:

C. difficile infection (CDI) episodes, occurring July 2014-June 2017, in patients aged ≥18 years were extracted from the database and a nested case-control analysis was performed. Cases were defined as rCDI episodes which required re-initiation of oral vancomycin or oral/intravenous metronidazole treatment within 8 weeks from the start of initial treatment. Cases were matched to 4 non-rCDI episodes at the timing of rCDI occurrence. Adjusted odds ratios (ORs) were estimated using multivariate conditional logistic regression model.

RESULTS:

Of 18,246 initial CDI episodes, 3250 (17.8%) had at least one rCDI. Approximately 90% of episodes occurred in inpatients and 65% were treated with metronidazole. Older age (<75 years vs 75-84 years and vs 85 + years) was associated with higher risk of rCDI (OR = 1.27, 95% confidence interval [1.15, 1.41] and 1.45 [1.30, 1.61], respectively). Use of systemic antibiotics (3.16 [2.90, 3.44]), probiotics (2.53 [2.32, 2.77]), chemotherapy (1.28 [1.08, 1.53]), or proton pump inhibitors (PPIs) (1.17 [1.07, 1.28]), and prior CDI history (1.22 [1.03, 1.43]) were also identified as rCDI risk factors. Vancomycin reduced the risk of rCDI compared with metronidazole treatment (0.83 [0.76, 0.91]).

CONCLUSION:

This large, multicenter, nationwide study confirmed that older age, PPIs, antibiotics, probiotics, chemotherapy, and prior CDI history are risk factors for rCDI in Japan. There was a 17% decrease of rCDI risk with vancomycin vs metronidazole treatment.

CLINICAL TRIAL REGISTRATION NUMBER:N/A.

To review article in its entirety click on the link below to be redirected:

https://www.ncbi.nlm.nih.gov/pubmed/30987950?dopt=Abstract&utm_source=dlvr.it&utm_medium=twitter

University of Virginia School of Medicine Researchers Find Why Certain Patients Are Highly Susceptible to C.diff. Infections

The new finding from the University of Virginia School of Medicine (UVA) explains why certain patients are highly susceptible

to C. diff infections, provides doctors with a way to predict disease severity and points to a new way to treat the often-deadly condition.

The UVA researchers found that the immune response to C. diff causes tissue damage and even death through a type of immune cell called Th17. This solves a longstanding mystery about why disease severity does not correlate with the amount of bacteria in the body but, instead, to the magnitude of the immune response. It also explains why patients with inflammatory bowel disease are more likely to suffer severe C. diff infections and more likely to die from them.

Lingering Effects

The bowel condition colitis, the researchers determined, has a lingering effect on the immune system, priming the patient for a worse C. diff infection.

While scientists have known that C. diff and other bacteria produce toxins that are harmful to the body, they assumed this was a simple matter: more toxin, more sickness.

But UVA’s research reveals that the truth is far more complex. Oftentimes, the type of immune response generated by the body can dictate the outcome of disease independent of bacterial toxin.

“When we, as a lab, started working on this, we were actively discouraged from working

on C. difficile because [some] people in the field thought, ‘Oh, this is a toxin-mediated disease. You don’t need to understand anything more than the fact that the bacteria make toxins,’” UVA’s Dr. William A. Petri Jr. said. “So, it’s been a wonderful opportunity for us because we went in and we sort of countered the prevailing wisdom. Yes, the toxins are important, but the toxins are important because they affect the immune system in dramatic ways.”

Inflammatory Bowel Disease

Seeking to understand why patients with inflammatory bowel disease are so susceptible to C. diff, researcher Mahmoud Saleh created a mouse model of colitis, one of the common forms of inflammatory bowel disease. He was able to determine that mice that recovered from colitis actually had changes in their immune system – an adaptive immune response. Immune cells known as Th17 cells had become hyper-charged, primed to cause a severe reaction to subsequent C. difficile infection. Even the same amount of the bacteria would now cause a dangerous, outsized response. “If we infect a month later, we see that these [T helper cells] alone can cause severe infection,” Saleh said. “So, these cells are sufficient for that increased severity of C. difficile infection.”

The researchers then looked at human samples to determine if their finding would hold true. It did, and they were able to use substances in the blood, including a protein known as interleukin 6 (IL-6), to predict disease severity. Patients with high amounts of IL-6 were almost eight times more likely to die from C. difficile than those with low levels.

Petri, of UVA’s Division of Infectious Diseases and International Health, explained: “Now we know from Mahmoud’s work that if I, as a physician, measure IL-6 in one of my patients with inflammatory bowel disease, I’ll be able to know how severe disease will be in that person and I can make the decision about whether the person needs to be admitted to the hospital … or even go to the intensive care unit.”

Preventing C. diff

The research also suggests a potential new way to treat or prevent severe C. difficile relapses. “We know that in mice by targeting T cells we protect from disease, and that leads to the question, could we do something similar and people to provide better therapy?” Petri said. “It is an interesting and terrible situation right now that C. diff is not resistant to antibiotics, but is resistant to treatment. And so even though we have very, very good antibiotics for this, the [body’s] response is so severe that even though we’re killing the bacteria with the antibiotics, patients are suffering from their own immune response.”

While more research will need to be done to create such a treatment, Petri and Saleh are proud to have solved a big mystery about C. difficile. “When you look at how much bacteria are growing or how much toxin is being produced, a lot of time there is no direct correlation,” Saleh said. “Now we know that what’s making that difference is this immune response.”

Findings Published

The researchers have published their findings in the scientific journal Cell Host & Microbe. The research team consisted of Saleh, Alyse L. Frisbee, Jhansi L. Leslie, Erica L. Buonomo, Carrie A Cowardin, Jennie Z. Ma, Morgan E. Simpson, Kenneth W. Scully, Mayuresh M. Abhyankar and Petri.

The research was supported by the National Institutes of Health, grants T32GM008715, T32AI007496, T32AI007496, T32AI07496, 5F31AI114203, 1R21AI114734 and 1R01AI124214; and the UVA Wagner Fellowship.

 

To review this article in its entirety – please click on the link below to be redirected:

https://news.virginia.edu/content/revealed-secret-superpower-makes-c-difficile-so-deadly?utm_source=dlvr.it&utm_medium=twitter

 

Researchers at Chinese University of Hong Kong Develop Fluorescent Microrobots to Detect C.diff.

Researchers at Chinese University of Hong Kong (CUHK) have developed fluorescent microrobots that can spot C. diff in a stool sample within a matter of minutes without relying on expensive laboratory equipment.

The technology relies on fungi spore-inspired microrobots that feature fluorescent functionalised carbon nanodots. When the microrobots encounter toxins produced by C. diff, the brightness of the fluorescence changes, something that can be detected with digital photo equipment.

The process is accelerated by the shape and structure of the microrobots, which spread throughout a diluted stool sample and quickly come in contact with as much as the present toxins as possible. This “active” process also helps to detect low concentrations of toxins, according to the researchers.

Additionally, because the microrobots have iron-based nanoparticles in their structure, they can be manipulated by an external magnetic field and gathered together for best visualization.

Study in journal Science Advances: Real-time tracking of fluorescent magnetic spore–based microrobots for remote detection of C. diff toxins

 

To read article in its entirety please click on the following link to be redirected. Thank you.

https://www.medgadget.com/2019/02/microrobots-take-minutes-to-detect-c-diff-in-stool-samples.html

Deinove Phase II DNV3837 for C.difficile Infection Clinical Trial To Begin Mid 2019

Deinove is preparing initiation of Phase II for DNV3837 in Clostridium difficile infections, with a key partner

  • The test design has been improved for a better assessment of DNV3837 effectiveness in treating Clostridium difficile infections,
  • This will be a multicenter trial, taking place mostly in the United States, where the prevalence of the disease is high,
  • DEINOVE has chosen Medpace as its Clinical Research Organization (CRO)1 to prepare and oversee the trial, notably because of their experience with the target disease,
  • The trial is scheduled to begin mid-2019,
  • This clinical program will be the focal point of DEINOVE’s antibiotic strategy in the coming months, as the Company has decided not to exercise its option on the NBTI program.

DEINOVE (Euronext Growth Paris: ALDEI), a French biotech company that uses a disruptive approach to develop innovative antibiotics and bio-based active ingredients for cosmetics and nutrition, is preparing the Phase II study that will test DNV3837, its most advanced antibiotic candidate, for use against Clostridium difficile infections (CDI). DEINOVE has chosen Medpace (NASDAQ: MEPD) to act as its CRO and to oversee the clinical trial scheduled to begin in 2019.

DNV3837 is a first-in-class antibiotic candidate targeting the treatment of Clostridium difficile infections (CDIs), a disease classified as a priority by the WHO and one of the leading causes of healthcare-associated infections2. DNV3837 has demonstrated a promising efficacy profile and acceptable tolerance in Phase I trials. The FDA3 has already approved the start of a Phase II study and has granted the DNV3837 program the Qualified Infectious Disease Product (QIDP) designation and Fast Track status4 for accelerated product development.

DEINOVE acquired the DNV3837 program in the 1st half of 2018. Since then, their clinical development team has worked with a group of healthcare experts in CDI to prepare for the start of a Phase II clinical trial whose purpose is to demonstrate the efficacy of DNV3837 in patients suffering from CDI. Several aspects of the trial design, which had been presented to the FDA prior to the acquisition, have been improved:

  • the target patient population was expanded and now covers moderate to severe CDIs for greater progressiveness in treatment assessment;
  • it will be a multicenter trial with a major part taking place in the United States, where there is greater prevalence and the regulatory authorities are looking for new treatment options.

The design of the trial has now been finalized for submission of the updated version to the FDA. The selection process of clinical investigation centers is underway. The trial is scheduled to begin mid-year.

DEINOVE has chosen Medpace to oversee the trial. Medpace is an internationally-recognized full-service CRO that notably has a great deal of experience in infectious diseases, especially gastrointestinal infections like CDIs.

Its mission includes support for the clinical trial’s design and set-up (protocol review, contacting the clinical investigation centers, etc.), gathering and analyzing data, and interacting with the FDA.

Georges Gaudriault, Scientific Director at DEINOVE, said: “Preparations for the Phase II clinical trial for DNV3837 are moving forward as planned and we are delighted to have executed such an agreement with Medpace for this trial’s oversight. Their experience in both the pathology and American regulatory procedures will help us to secure and maximize this trial’s progress.”

The DNV3837 program is followed by the AGIR program (backed by Bpifrance), whose aim is to add to the portfolio of new molecules from DEINOVE’s biodiversity. The option on the NBTI5 program will indeed not be exercised, as the data gathered during the assessment phase were not considered to be in line with DEINOVE’s expectations for pursuing the program.

Emmanuel Petiot, CEO of DEINOVE, added: “The antibiotics field is a priority for DEINOVE and the DNV3837 program is our spearhead. Furthermore, we have decided not to exercise our option on the NBTI program with REDX Pharma, insofar as our teams’ assessment showed obstacles to its development without further optimization. We want to respond quickly and effectively to the health emergency and the lack of innovative antibiotics, and we are focusing our efforts on those programs with the highest possible probability of success.”

 

DNV3837 – a prodrug of the DNV3681 molecule (also known as MCB3681) – is a narrow-spectrum, hybrid oxazolidinone-quinolone synthetic antibiotic, targeting only Gram-positive bacteria. It is developed as a highly active 1st line treatment targeting Clostridium difficile.

It has demonstrated significant efficacy and superiority to reference treatments (fidaxomicin in particular) against isolates of C. diff., regardless of their virulence (including the hyper virulent strain NAP1).

DNV3837 is administered intravenously and is able to cross the gastrointestinal barrier, allowing it to precisely target the infection site. Several Phase I trials (on approx. one hundred healthy volunteers) have shown a high concentration of the antibiotic in stools, a strong marker of its presence in the intestine. It has also demonstrated its ability to eliminate C. diff. bacteria without altering the gut microbiota in the long term, a definite advantage for patient prognosis. It has also shown an acceptable tolerance profile.

FDA granted the DNV3837 program with Qualified Infectious Disease Product (QIDP) designation and Fast Track status.

To read this article in its entirety please click on the following link to be redirected:

https://globenewswire.com/news-release/2019/01/31/1708049/0/en/Deinove-is-preparing-initiation-of-Phase-II-for-DNV3837-in-Clostridium-difficile-infections-with-a-key-partner.html

Patients Diagnosed With C. difficile Infection (CDI) Have Higher Readmission Rates

Elijah Verheyen, MD'Correspondence information about the author MD Elijah Verheyen

,

Vijay Dalapathi, MD

,

Shilpkumar Arora, MD

,

Kalpesh Patel, MD

,

Pavan Kumar Mankal, MD

,

Varun Kumar, MD

,

Edward Lung, MD

,

Donald P. Kotler, MD

,

Ari Grinspan, MD

Highlights

  • One in five patients admitted with C. difficile is readmitted within 30 days.
  • Recurrent C difficile is the leading cause of readmission.
  • Female sex, renal disease, and anemia increase C difficile readmission risk.
  • Discharge home, as opposed to facility, increases C difficile readmission risk.

Background

Clostridium difficile infection (CDI) is a leading cause of community-onset and healthcare–associated infection, with high recurrence rates, and associated high morbidity and mortality. We report national rates, leading causes, and predictors of hospital readmission for CDI.

Methods

Retrospective study of data from the 2013 Nationwide Readmissions Database of patients with a primary diagnosis of CDI and re-hospitalization within 30-days. A multivariate regression model was used to identify predictors of readmission.

Results

Of 38,409 patients admitted with a primary diagnosis of CDI, 21% were readmitted within 30-days, and 27% of those patients were readmitted with a primary diagnosis of CDI. Infections accounted for 47% of all readmissions. Female sex, anemia/coagulation defects, renal failure/electrolyte abnormalities and discharge to home (versus facility) were 12%, 13%, 15%, 36%, respectively, more likely to be readmitted with CDI.

Conclusions

We found that 1-in-5 patients hospitalized with CDI were readmitted to the hospital within 30-days. Infection comprised nearly half of these readmissions, with CDI being the most common etiology.

Predictors of readmission with CDI include female sex, history of renal failure/electrolyte imbalances, anemia/coagulation defects, and being discharged home. CDI is associated with a high readmission risk, with evidence of several predictive risks for readmission.

SOURCEhttps://www.ajicjournal.org/article/S0196-6553(19)30026-4/fulltext?utm_source=dlvr.it&utm_medium=twitter

C Diff Foundation Recognizes Rebiotix CEO Lee Jones with 2019 ‘Above and Beyond’ Award


C Diff Foundation Board presented Rebiotix CEO Lee Jones for Advocacy, Innovation in
C. difficile infection treatment

 

(NEW PORT RICHEY, Fla.) — The C. Diff Foundation Board of Directors announced that the 2019 “Above and Beyond” Award was presented to Rebiotix CEO Lee Jones in Roseville, Minnesota. The award, given to one recipient annually, is given to a person or organization that show extraordinary dedication to C. diff. patient safety, advocacy, and overall drive to improve the lives of those impacted by the infection.

“We are very proud to recognize Ms. Jones with our “Above and Beyond” award,” said C. Diff Foundation Founder and President, Nancy Caralla. “Lee’s dedication to the entire C.diff. community of patients, family members, and physicians hasn’t wavered since the founding of Rebiotix in 2011. She is a true example of what can happen when focusing on patient well-being drives new approaches to healthcare.”

The award was presented by the Foundation’s Vice President, Scott Battles at the Rebiotix office.

 

 

 

 

 

 

“It’s an honor to receive this award from the C. Diff Foundation,” said Ms. Jones. “The purpose of starting Rebiotix was to bring the power of the microbiome to the clinic in a scientifically sound, quality-controlled way to help patients. We stand with the Foundation in believing that patient well-being should be at the core of all that we do, from clinical trials to exploring new scientific landscapes within the microbiome space.”

About Rebiotix Inc.:

Rebiotix Inc., part of the Ferring Pharmaceuticals Group, is a late-stage clinical microbiome company focused on harnessing the power of the human microbiome to revolutionize the treatment of debilitating diseases. Rebiotix possesses a deep and diverse clinical pipeline, with its lead drug candidate, RBX2660, in Phase 3 clinical development for the prevention of recurrent Clostridium difficile (C. diff) infection. RBX2660 has been granted Fast Track, Orphan and Breakthrough Therapy designation from the FDA for its potential to prevent recurrent C. diff infection.

Rebiotix’s clinical pipeline also features RBX7455, a lyophilized, room temperature stable oral capsule formulation. Rebiotix is also targeting several other disease states with drug products built on its pioneering Microbiota Restoration Therapy(tm) platform. For more information on Rebiotix and its pipeline of human microbiome-directed therapies, visit https://www.rebiotix.com/

 

Researchers Present New Data that Brief NSAIDs Exposure Prior to a C.difficile Infection (CDI) Increases the Severity of the Infectious Colitis

ABSTRACT

Clostridium difficile infection (CDI) is a major public health threat worldwide. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with enhanced susceptibility to and severity of CDI; however, the mechanisms driving this phenomenon have not been elucidated. NSAIDs alter prostaglandin (PG) metabolism by inhibiting cyclooxygenase (COX) enzymes. Here, we found that treatment with the NSAID indomethacin prior to infection altered the microbiota and dramatically increased mortality and the intestinal pathology associated with CDI in mice. We demonstrated that in C. difficile-infected animals, indomethacin treatment led to PG deregulation, an altered proinflammatory transcriptional and protein profile, and perturbed epithelial cell junctions. These effects were paralleled by increased recruitment of intestinal neutrophils and CD4+ cells and also by a perturbation of the gut microbiota. Together, these data implicate NSAIDs in the disruption of protective COX-mediated PG production during CDI, resulting in altered epithelial integrity and associated immune responses.

IMPORTANCE Clostridium difficile infection (CDI) is a spore-forming anaerobic bacterium and leading cause of antibiotic-associated colitis. Epidemiological data suggest that use of nonsteroidal anti-inflammatory drugs (NSAIDs) increases the risk for CDI in humans, a potentially important observation given the widespread use of NSAIDs. Prior studies in rodent models of CDI found that NSAID exposure following infection increases the severity of CDI, but mechanisms to explain this are lacking. Here we present new data from a mouse model of antibiotic-associated CDI suggesting that brief NSAID exposure prior to CDI increases the severity of the infectious colitis. These data shed new light on potential mechanisms linking NSAID use to worsened CDI, including drug-induced disturbances to the gut microbiome and colonic epithelial integrity. Studies were limited to a single NSAID (indomethacin), so future studies are needed to assess the generalizability of our findings and to establish a direct link to the human condition.

INTRODUCTION

Clostridium difficile is the most commonly reported nosocomial pathogen in the United States and an urgent public health threat worldwide (1). C. difficile infection (CDI) manifests as a spectrum of gastrointestinal disorders ranging from mild diarrhea to toxic megacolon and/or death, particularly in older adults (2). The primary risk factor for CDI is antibiotic treatment, which perturbs the resident gut microbiota and abolishes colonization resistance (3). However, factors other than antibiotic exposure increase the risk for CDI and the incidence of cases not associated with the use of antimicrobials has been on the rise (4). Defining mechanisms whereby nonantibiotic factors impact CDI pathogenesis promises to reveal actionable targets for preventing or treating this infection.

Recently, several previously unappreciated immune system, host, microbiota, and dietary factors have emerged as modulators of CDI severity and risk. The food additive trehalose, for example, was recently shown to increase C. difficile virulence in mice, and the widespread adoption of trehalose in food products was implicated in the emergence of hypervirulent strains of C. difficile (5). Similarly, excess dietary zinc had a profound impact on severity of C. difficile disease in mice, and high levels of zinc altered the gut microbiota and increased susceptibility to CDI (6). Importantly, there is a growing body of evidence of the essential role of the innate immune response and inflammation in both protection against and pathology of CDI (79). Mounting a proper and robust inflammatory response is critical for successful clearance of C. difficile, and the immune response can be a key predictor of prognosis (3, 10). In this context, specific immune mediators can facilitate both protective and pathogenic responses through the activity of molecules such as interleukin-23 (IL-23) and IL-22, and an excessive and dysregulated immune response is believed to be one of the main factors behind postinfection complications.

Epidemiological data have established an association between the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and CDI (11). Muñoz-Miralles and colleagues demonstrated that the NSAID indomethacin (Indo) significantly increased the severity of CDI in antibiotic-treated mice when the NSAID was applied following inoculation and throughout the infection (12), and indomethacin exposure is associated with alterations in the structure of the intestinal microbiota (13, 14). NSAIDs are among the most highly prescribed and most widely consumed drugs in the United States (15), particularly among older adults (16), and have been implicated in causing spontaneous colitis in humans (17, 18). They act by inhibiting cyclooxygenase (COX) enzymatic activity, which prevents the generation of prostaglandins (PGs) and alters the outcome of subsequent inflammatory events. Prostaglandins, especially PGE2, are important lipid mediators that are highly abundant at sites of inflammation and infection and that support gastrointestinal homeostasis and epithelial cell (EC) health (19). NSAID use has been associated with shifts in the gut microbiota, in both rodents and humans (2023), but these shifts have not been explored in the context of CDI.

In this report, we deployed a mouse model of antibiotic-associated CDI to examine the impact of exposure to indomethacin prior to infection with C. difficile on disease severity, immune response, intestinal epithelial integrity, and the gut microbiota. These investigations revealed that even a brief exposure to an NSAID prior to C. difficile inoculation dramatically increased CDI severity, reduced survival, and increased pathological evidence of disease. Inhibition of PG biosynthesis by indomethacin altered the cytokine response and immune cell recruitment following CDI, enhancing intestinal tissue histopathology and allowing partial systemic bacterial dissemination by dismantling intestinal epithelial tight junctions (TJs). Additionally, indomethacin treatment alone significantly perturbed the structure of the gut microbiota. These findings support epidemiological data linking NSAID use and CDI and caution against the overuse of NSAIDs in patients at high risk for C. difficile, such as older adults.

RESULTS

Indomethacin worsens C. difficile Infection in Mice and Increases Mortality.To determine the extent to which preexposure to NSAIDs influences the natural course of CDI, mice were treated with indomethacin for 2 days prior to inoculation with C. difficile (Fig. 1A). We infected C57BL/6 female mice with 1 × 104 spores of C. difficile NAP1/BI/027 strain M7404 following 5 days of pretreatment with a broad-spectrum antibiotic, cefoperazone (Fig. 1A). This brief indomethacin treatment prior to CDI dramatically decreased cecum size and increased the mortality rate from 20% to 80% (Fig. 1C) but did not significantly impact weight loss (Fig. 1D). Mice pretreated with indomethacin and infected with C. difficile also displayed histopathological evidence of more-severe cecal tissue damage compared to mice infected with C. difficile that were not exposed to the drug (Fig. 1E). Indomethacin-exposed and infected mice exhibited no change in the burden of C. difficile in the cecum (Fig. 1F), but their livers harbored significantly greater loads of mixed aerobic and anaerobic bacteria (Fig. 1G), suggesting that indomethacin pretreatment compromised intestinal barrier function during CDI and fostered microbiota translocation to the liver.

FIG 1

Indomethacin worsens the effects of C. difficile infection in mice. (A) C57BL/6 mice were treated with cefoperazone for 5 days followed by 2 days of recovery and then challenged by gavage with 1 × 104 spores of NAP1 strain M7404. Animals received 2 doses of 10 mg/kg of body weight of indomethacin by gavage daily as indicated by the top arrows. (B) Representative picture illustrating the macroscopic effects of the different treatments in the cecum. Indo, indomethacin; Abx, antibiotic; C. diff, C. difficile. (C to E) Mice were monitored for survival (Kaplan-Meier curve) (C), weight loss (D), and histopathologic severity of colitis (E) (n = 13 to 15/group). (F and G) C. difficile bacterial burden was evaluated in the ceca of 12 mice/group (F) and total aerobic bacterial burden plus anaerobic bacterial burden in the liver of 5 mice/group (G) also at day 3 after infection, with the discontinuous line indicating the limit of detection. Path., pathology. **, P < 0.01 (by log rank [Mantel-Cox] test for survival [panel C] and by unpaired t test for weights [panel D]); *, P < 0.05 (1-way analysis of variance [ANOVA] test for histopathological scores [panel E]); **, P < 0.01 (Wilcoxon test with Bonferroni correction [panel G]). I, indomethacin; A, antibiotic.

Indomethacin alters the proportions of neutrophils and CD4+ T cells in mucosal-associated tissues during C. difficile infection…………………………………

 

Damian Maseda, Joseph P. Zackular, Bruno Trindade, Leslie Kirk, Jennifer Lising Roxas, Lisa M. Rogers, Mary K. Washington, Liping Du, Tatsuki Koyama, V. K. Viswanathan, Gayatri Vedantam, Patrick D. Schloss, Leslie J. Crofford, Eric P. Skaar, David M. Aronoff
Jimmy D. Ballard, Editor

TO READ THE ARTICLE IN ITS ENTIRETY PLEASE CLICK ON THE FOLLOWING LINK TO BE REDIRECTED:

https://mbio.asm.org/content/10/1/e02282-18