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Klebsiella oxytoca is a gram-negative bacterium found in fecal microbiota and known to cause several infections in humans, including antibiotic-associated hemorrhagic colitis. We present here a case of colitis caused by K. oxytoca toxin-producing strains that evolved in chronic diarrhea successfully treated by fecal microbiota transplant., Competing Interests: Potential conflicts of interest. L.-C. F. reports travel support from the Faculty of Medicine and Health Sciences of the University of Sherbrooke and has issued or pending patents for Clostridium difficile toxins A and/or B antigen and epitope antibody (PCT/CA2016/050170; WO/2016/131157 #62118450). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Clostridium difficile is the most common cause of healthcare-associated infectious diarrhea and colitis, and carries the potential for high morbidity, particularly in frail patient populations. The purpose of this study was to utilize a large nationally representative database in order to report 1.) the incidence of CDC in patients with operative lower extremity fractures, 2.) risk factors for the development of CDC, 3.) the association of CDC with length of stay (LOS), readmission, and 30-day mortality rates., Methods: The ACS-NSQIP (2015-2019) was queried for patients who underwent surgical fixation of lower extremity fractures. A backward elimination multivariate regression model was used to identify risk factors for CDC. Chi squared and multivariate regression that controlled for preoperative variables and comorbidities were used to compare outcomes in patients with and without CDC., Results: 95,532 patients were included, 681 (0.71%) of whom developed CDC. Risk factors for CDC were advanced age, ASA class ≥ 3, smoking, dialysis, anemia, hypoalbuminemia, preoperative SIRS, preoperative wound infections, preoperative sepsis, and the use of spinal anesthesia or MAC/IV sedation. Patients with CDC had significantly increased 30-day mortality rates (10.6% vs 4.4%; OR 1.80, 95% CI 1.41-2.31), readmission (34.2% vs 7.5%; OR 5.13, 95% CI 4.36-6.05, and length of stay (7.5 days vs 5.3 days) compared to patients without CDC., Conclusion: The incidence of CDC in lower extremity orthopedic trauma patients was 0.71%. An occurrence of CDC was associated with approximately a 2.5 times increase in 30-day mortality, five times the readmission rate, and a longer hospital stay compared to patients without CDC. Mitigating the spread of c. diff through improved antibiotic stewardship and prompt treatment of CDC is paramount to decreasing the burden this infection imposes on orthopedic trauma patients and the healthcare system., Competing Interests: Declaration of Competing Interest The authors report no relevant conflicts of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Patients with ulcerative colitis (UC) are at increased risk for infections such as Clostridium difficile and cytomegalovirus (CMV) colitis due to chronic immunosuppression. These patients often undergo multiple surgeries putting them at risk for recurrence of the infection. However, rates of recurrence in this setting and outcomes are not well understood., Aim: The aim of this study is to determine rates of recurrence of C difficile and CMV infection in patients undergoing multistage UC surgeries and effects of antibiotic prophylaxis on outcomes., Methods: All patients with UC who underwent IPAA between 2001 and 2017 (at two tertiary referral centers were identified. History of C. difficile or CMV colitis prior to any surgery and recurrence after IPAA was noted RESULTS: A total of 633 patients with UC who underwent IPAA were identified, of whom 8.1% patients had C. difficile and 2.7% had CMV infections. 9.8% of C. difficile and 5.9% of CMV patients recurred after IPAA. Rates of abdominal sepsis (14.7% vs. 12.7%), 90-day mortality (0% vs. 0.4%), pouchitis (36.8% vs. 45.0%), or return to stoma (7.4% vs. 5.4%) were similar between patients who did or did not have infections. In patients with C. difficile infection prior to first surgery, none of the patients who received prophylaxis had recurrent infection., Conclusions: Rates of C. difficile and CMV infections remain high in patients undergoing surgery for UC, with substantial minority developing recurrent infection during subsequent surgical procedures. Antibiotic prophylaxis in patients with a history of C difficile may reduce the rate of recurrent infection., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Abstract: In the last three decades, the dramatic worldwide increase in incidence and severity of Clostridioides difficile infection (CDI) (formerly Clostridium difficile infection) has made CDI a global public health challenge. Surgery is a known risk factor for development of CDI yet surgery is also a treatment option in severe cases of CDI. The World Society of Emergency Surgery guidelines for management of CDI in surgical patients were published in 2015. In 2019, the guidelines were revised and updated according to the grading of recommendations assessment, development and evaluation methodology. This executive summary is intended to consolidate knowledge on the management of CDI focusing on aspects that a general and emergency surgeon should know about the prevention and the management of CDI, by providing a practical and concise version of the original guidelines., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The impact of inflammatory bowel disease (IBD) activity on long-term outcomes after liver transplantation (LT) for primary sclerosing cholangitis (PSC) is unknown. We examined the impact of post-LT IBD activity on clinically significant outcomes., Methods: One hundred twelve patients undergoing LT for PSC from 2 centers were studied for a median of 7 years. Patients were divided into 3 groups according to their IBD activity after LT: no IBD, mild IBD, and moderate to severe IBD. Patients were classified as having moderate to severe IBD if they met at least 1 of 3 criteria: (i) Mayo 2 or 3 colitis or Simple Endoscopic Score-Crohn's Disease ≥7 on endoscopy; (ii) acute flare of IBD necessitating steroid rescue therapy; or (iii) post-LT colectomy for medically refractory IBD., Results: Moderate to severe IBD at any time post-transplant was associated with a higher risk of Clostridium difficile infection (27% vs 8% mild IBD vs 8% no IBD; P = 0.02), colorectal cancer/high-grade dysplasia (21% vs 3% both groups; P = 0.004), post-LT colectomy (33% vs 3% vs 0%) and rPSC (64% vs 18% vs 20%; P < 0.001). Multivariate analysis revealed that moderate to severe IBD increased the risk of both rPSC (relative risk [RR], 8.80; 95% confidence interval [CI], 2.81-27.59; P < 0.001) and colorectal cancer/high-grade dysplasia (RR, 10.45; 95% CI, 3.55-22.74; P < 0.001)., Conclusions: Moderate to severe IBD at any time post-LT is associated with a higher risk of rPSC and colorectal neoplasia compared with mild IBD and no IBD. Patients with no IBD and mild IBD have similar post-LT outcomes. Future prospective studies are needed to determine if more intensive treatment of moderate to severe IBD improves long-term outcomes in patients undergoing LT for PSC., (© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background & Aims: The protease plasmin is an important wound healing factor, but it is not clear how it affects gastrointestinal infection-mediated damage, such as that resulting from Clostridioides difficile. We investigated the role of plasmin in C difficile-associated disease. This bacterium produces a spore form that is required for infection, so we also investigated the effects of plasmin on spores., Methods: C57BL/6J mice expressing the precursor to plasmin, the zymogen human plasminogen (hPLG), or infused with hPLG were infected with C difficile, and disease progression was monitored. Gut tissues were collected, and cytokine production and tissue damage were analyzed by using proteomic and cytokine arrays. Antibodies that inhibit either hPLG activation or plasmin activity were developed and structurally characterized, and their effects were tested in mice. Spores were isolated from infected patients or mice and visualized using super-resolution microscopy; the functional consequences of hPLG binding to spores were determined., Results: hPLG localized to the toxin-damaged gut, resulting in immune dysregulation with an increased abundance of cytokines (such as interleukin [IL] 1A, IL1B, IL3, IL10, IL12B, MCP1, MP1A, MP1B, GCSF, GMCSF, KC, TIMP-1), tissue degradation, and reduced survival. Administration of antibodies that inhibit plasminogen activation reduced disease severity in mice. C difficile spores bound specifically to hPLG and active plasmin degraded their surface, facilitating rapid germination., Conclusions: We found that hPLG is recruited to the damaged gut, exacerbating C difficile disease in mice. hPLG binds to C difficile spores, and, upon activation to plasmin, remodels the spore surface, facilitating rapid spore germination. Inhibitors of plasminogen activation might be developed for treatment of C difficile or other infection-mediated gastrointestinal diseases., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

Background: Critically ill infants with congenital heart disease (CHD) are often prescribed stress ulcer prophylaxis (SUP) to prevent upper gastrointestinal bleeding, despite the low incidence of stress ulcers and limited data on the safety and efficacy of SUP in infants. Recently, SUP has been associated with an increased incidence of hospital-acquired infections, community-acquired pneumonia, and necrotizing enterocolitis. The objective of this pilot study is to investigate the feasibility of performing a randomized controlled trial to assess the safety and efficacy of withholding SUP in infants with congenital heart disease admitted to the cardiac intensive care unit., Methods: A single center, prospective, double-blinded, randomized placebo-controlled pilot feasibility trial will be performed in infants with CHD admitted to the cardiac intensive care unit and anticipated to require respiratory support for > 24 h. Patients will be randomized to receive a histamine-2 receptor antagonist (H2RA) or placebo until they are discontinued from respiratory support. Randomization will be performed within 2 strata defined by admission type (medical or surgical) and age (neonate, age < 30 days, or infant, 1 month to 1 year). Allocation will be a 1:1 ratio using permuted blocks to ensure balanced allocations across the two treatment groups within each stratum. The primary outcomes include feasibility of screening, consent, timely allocation of study drug, and protocol adherence. The primary safety outcome is the rate of clinically significant upper gastrointestinal bleeding. The secondary outcomes are the difference in the relative and absolute abundance of the gut microbiota and functional microbial profiles between the two study groups. We plan to enroll 100 patients in this pilot study., Discussion: Routine use of SUP to prevent upper gastrointestinal bleeding in infants is controversial due to a low incidence of bleeding events and concern for adverse effects. The role of SUP in infants with CHD has not been examined, and there is equipoise on the risks and benefits of withholding this therapy. In addition, this therapy has been discontinued in other neonatal populations due to the concern for hospital-acquired infections and necrotizing enterocolitis. Furthermore, exploring changes to the microbiome after exposure to SUP may highlight the mechanisms by which SUP impacts potential microbial dysbiosis of the gut and its association with hospital-acquired infections. Assessment of the feasibility of a trial of withholding SUP in critically ill infants with CHD will facilitate planning of a larger multicenter trial of safety and efficacy of SUP in this vulnerable population., Trial Registration: ClinicalTrials.gov , NCT03667703. Registered 12 September 2018, https://clinicaltrials.gov/ct2/show/NCT03667703?term=SUPPRESS+CHD&draw=2&rank=1 . All WHO Trial Registration Data Set Criteria are met in this manuscript.

This study was a retrospective chart review from January 1, 2015 through June 30, 2017, comparing the incidence of Clostridium difficile-associated diarrhea (CDAD) in patients taking select broad spectrum antibiotics with probiotics versus without probiotics. The purpose was to determine if probiotic use was associated with a reduction in the incidence of CDAD. A total of 5,574 hospital encounters were reviewed, showing a 0.96% incidence of CDAD in patients receiving a probiotic compared to a 2.19% incidence of CDAD in patients with no probiotic (risk ratio = 0.442; P = .00743). These findings show probiotic use was associated with a statistically significant lower incidence of positive C. difficile test results compared to no probiotic use., (Copyright © 2019. Published by Elsevier Inc.)

Background: During the last two decades, there has been a worldwide increase in frequency and severity of infections with Clostridium difficile (CDI). Solid organ transplant (SOT) recipients receiving immunosuppressing medications are especially at risk., Methods: We collected data from immunocompromised pediatric patients, including kidney and liver transplant recipients, at our tertiary pediatric care center in Germany. For this, we performed a retrospective review of institutional databases and analyzed data from all children who underwent diagnostic tests for CDI in a 3-year study period., Results: A total of 797 diagnostic tests in 343 patients were performed. We found 104 infection episodes in 69 patients (42% female, ages 12 days-20 years). Children after SOT accounted for 20% of all detected CDI patients in our series. Median time of CDI onset after transplantation was 588 days. Overall antibiotic exposure was identified as the major risk factor, particularly in immunocompromised children after SOT (exposure in > 95% of all cases)., Conclusions: The occurrence of CDI in the pediatric SOT population contributes to a greater length of stay and higher hospital charges. However, only very few severe complications from CDI were observed in our cohort. A potentially fulminant course of CDI can be prevented in most cases if timely diagnosis and treatment are carried out.

Background: Clostridioides (formerly Clostridium) difficile infection (CDI) is associated with significant morbidity and mortality, including frequent hospitalizations. However, the impact of CDI after hospital discharge is poorly understood. The purpose of this study was to assess patient discharge disposition and understand CDI-related risk factors for nonhome discharge., Methods: Using a nationally representative database of Veterans Health Administration (VHA) patients (2003-2014) and a validation database from hospitalized non-VHA patients in Houston, Texas, admission and discharge disposition was obtained for patients with CDI and matched controls. Incidence of and clinical/microbiologic risk factors for nonhome discharge were assessed using these databases., Results: A total of 15173 VHA patients with CDI and 48599 non-CDI control patients originally admitted from the community were included. Significantly more patients with CDI were discharged to a nonhome location compared with controls (18% vs 8%; P < .0001), most commonly hospice/death (12%) or nursing home/long-term care facility (6%). Results were confirmed using a propensity-matched analysis and a validation cohort of 1941 hospitalized patients with CDI in Houston, Texas. Age, comorbidities, severe CDI, and ribotypes F027, F001, and F053-163 were associated with a nonhome discharge (P < .05 for all)., Conclusions: Hospitalized patients with CDI frequently required a higher level of medical care residence at discharge compared with non-CDI patients. Risk factors for discharge to a higher level of care included CDI disease severity and variables associated with recurrent CDI., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objective: To evaluate the role of antibiotic prophylaxis with oral ciprofloxacin prior to urinary catheter removal after radical prostatectomy in preventing urinary tract infection (UTI)., Materials and Methods: Patients undergoing radical prostatectomy were prospectively enrolled and randomized to either the antibiotic prophylaxis group (2 doses of oral ciprofloxacin prior to urinary catheter removal) or the control group (no antibiotics given prior to urinary catheter removal). Neither patients nor study providers were blinded to the group. The primary objective was to assess for development of UTI. The secondary objective was to assess for development of Clostridium difficile (C diff) enterocolitis. Continuous variables were compared using a 2-sample t test. Categorical variables were compared using Pearson's chi-squared test or Fisher's exact test., Results: One hundred seventy-five patients were enrolled and randomized (90 control and 85 antibiotic prophylaxis). After randomization, 4 patients were excluded and 4 patients withdrew voluntarily. One hundred sixty-seven patients (84 control and 83 antibiotic prophylaxis) completed the study and were available for analysis. There were no significant differences in baseline characteristics, perioperative data, or complications. There was no significant difference in the rate of UTI between the control group and antibiotic prophylaxis group (5.95% vs. 6.02%, P = 1). There was also no significant difference in the rates of C diff infection between the control and the antibiotic prophylaxis groups (3.57% vs. 0%, P = 0.21)., Conclusions: In this prospective, randomized, controlled trial, the use of antibiotic prophylaxis with oral ciprofloxacin prior to urinary catheter removal after radical prostatectomy did not decrease the rate of UTI, and was not associated with an increased incidence of C diff enterocolitis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

In the last three decades, Clostridium difficile infection (CDI) has increased in incidence and severity in many countries worldwide. The increase in CDI incidence has been particularly apparent among surgical patients. Therefore, prevention of CDI and optimization of management in the surgical patient are paramount. An international multidisciplinary panel of experts from the World Society of Emergency Surgery (WSES) updated its guidelines for management of CDI in surgical patients according to the most recent available literature. The update includes recent changes introduced in the management of this infection., Competing Interests: Not applicable.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

The most common cause of antibiotic-associated diarrhea is Clostridium difficile infection (CDI). Recurrent C. difficile infection (rCDI) often occurs after successful treatment of CDI. Due to the increased incidence and the difficulty in treating rCDI, it is becoming an important clinical issue. Identifying risk factors is helpful for early detection, treatment, and prevention of rCDI. Advanced age, use of antibiotics, gastric acid suppression, and infection with a hypervirulent strain are currently regarded as the major risk factors for rCDI. Several treatment modalities, including vancomycin, fidaxomicin, and fecal microbiota transplant (FMT), are suggested for rCDI treatment. However, there is currently no definitive treatment method with sufficient evidence for rCDI. Recent studies have focused on FMT and have shown positive results for rCDI. Prevention of rCDI by measures such as hand washing and isolation of patients is very important. However, these preventive measures are often overlooked in clinical practice. Here, we review the risk factors, treatment, and prevention of rCDI.

Background: Clostridium difficile-associated diarrhea (CDAD) is common during hematopoietic stem-cell transplantation (HSCT) and is associated with increased morbidity and mortality. We evaluated fidaxomicin for prevention of CDAD in HSCT patients., Methods: In this double-blind study, subjects undergoing HSCT with fluoroquinolone prophylaxis stratified by transplant type (autologous/allogeneic) were randomized to once-daily oral fidaxomicin (200 mg) or a matching placebo. Dosing began within 2 days of starting conditioning or fluoroquinolone prophylaxis and continued until 7 days after neutrophil engraftment or completion of fluoroquinolone prophylaxis/clinically-indicated antimicrobials for up to 40 days. The primary endpoint was CDAD incidence through 30 days after study medication. The primary endpoint analysis counted confirmed CDAD, receipt of CDAD-effective medications (for any indication), and missing CDAD assessment (for any reason, including death) as failures; this composite analysis is referred to as "prophylaxis failure" to distinguish from the pre-specified sensitivity analysis, which counted only confirmed CDAD (by toxin immunoassay or nucleic acid amplification test) as failure., Results: Of 611 subjects enrolled, 600 were treated and analyzed. Prophylaxis failure was similar in fidaxomicin and placebo recipients (28.6% vs 30.8%; difference 2.2% [-5.1, 9.5], P = .278). However, most failures were due to non-CDAD events. Confirmed CDAD was lower in fidaxomicin vs placebo recipients (4.3% vs 10.7%; difference 6.4% [2.2, 10.6], P = .0014). Drug-related adverse events occurred in 15.0% of fidaxomicin recipients and 20.0% of placebo recipients., Conclusions: While no difference was demonstrated between arms in the primary analysis, results of the sensitivity analysis demonstrated that fidaxomicin significantly reduced the incidence of CDAD in HSCT recipients., Clinical Trials Registration: NCT01691248.

Our aim was to study Clostridium difficile infection (CDI) in peripartum women in France and compare them to cases published in the literature. We characterize these infections regarding clinico-biological features and specific risk factors in order to raise awareness for obstetricians and midwifes. Eight antepartum and six post-partum CDI cases were retrospectively studied in 6 French centers during the period between 2008 and 2013. In addition, 59 literature cases were reviewed. Cases were identified with CDI clinical symptoms associated to characteristic imagery or detection of C. difficile toxins. The key risk factors of CDI (antibiotherapy, hospitalization) and other risk factors (cesarean section, obstetric complications, corticotherapy, and underlying disease) were retrospectively collected. Most of the cases were exposed to at least one key risk factor of CDI: previous exposure to antibiotics and/or hospitalization. The post-partum cases often had cesarean section: 67% (4/6) in French cases and 89% (31/35) in literature cases. Metronidazole was the most used antibiotic. Relapses occurred in two French cases and in nine published cases. Two French cases and 15 literature cases were reported to have complications (pseudomembranous colitis, toxic megacolon, death…). Diverse C. difficile PCR ribotypes were involved, but the BI/NAP1/027 strain was not detected in the French case series contrary to the literature cases. The delay for diagnosis CDI could be long and peripartum CDI could be severe. In case of unexplained diarrhea in pregnant women, clinicians need to consider CDI and ask for research of C. difficile and its toxins in stool.

The bacterium originally named Bacillus difficilis was later renamed Clostridium difficile because of the difficulty associated with its isolation in the laboratory. C. difficile causes human-associated diarrhea, which is now known as C. difficile infection (CDI), a major cause of nosocomial infection mainly occurring in developed countries. Changes in antibiotic patterns in its strains produce toxins that are responsible for the high mortality rates associated with CDI; therefore, the epidemiology and severity of CDI have recently changed. Apart from CDI, C. difficile also causes opportunistic infections of the human gut usually when the normal gut flora are disrupted by broad-spectrum antibiotics. By disrupting normal gut flora, spores of C. difficile germinate and traverse the gut mucosa through flagellar binding to the mucosal epithelium where several proteins are involved in the binding of C. difficile. Proper diagnostic techniques have to be applied to ensure early identification of CDI and prompt treatment administered because false results may lead to inappropriate treatment and increase risk of cross-infection. This review discusses the epidemiology and pathogenicity of this bacterium with concern for its changing pattern over the years. Further details on the diagnosis of CDI are elaborated upon, mainly focusing on the limits of and challenges in molecular diagnosis.

Study Design: A retrospective study of prospectively collected data., Objective: The aim of this study was to utilize a large national database with post-hospitalization follow-up data [National Surgical Quality Improvement Program (NSQIP)] to determine the incidence, risk factors, timing, and clinical impact of Clostridium difficile colitis in spine surgery patients., Summary of Background Data: Recent literature has suggested an increased incidence of C. difficile infections. However, there has been a lack of large cohort studies defining the incidence and impact of C. difficile colitis in patients undergoing spine surgery., Methods: Patients who underwent spine surgical procedures in the 2015 NSQIP database were identified. The primary outcome was a diagnosis of C. difficile colitis within the 30-day postoperative period. Independent risk factors for development of C. difficile colitis were identified using multivariate regression. Postoperative length of stay and rate of 30-day readmission were compared between patients who did and did not develop C. difficile colitis., Results: A total of 23,981 patients who underwent spine surgical procedures were identified. The incidence of C. difficile colitis was approximately 0.11% [95% confidence interval (95% CI), 0.07-0.16]. Of the cases that developed C. difficile colitis, 70% were diagnosed postdischarge and 88% had not had a pre-existing infection diagnosed. Independent risk factors for the development of C. difficile colitis were combined anterior/posterior lumbar fusion procedures [odds ratio (OR) = 12.29, 95% CI = 2.22-68.13, P = 0.010], greater age (most notably ≥76 years old, OR = 10.31, 95% CI = 3.06-34.76, P < 0.001), hypoalbuminemia (OR = 6.40, 95% CI = 2.49-16.43, P < 0.001), and anemia (OR = 2.39, 95% CI = 1.13-5.05, P = 0.023). The development of C. difficile colitis was associated with greater length of stay (2.2 vs. 12.5 days; P < 0.001) and increased 30-day readmission (OR = 8.21, 95% CI = 3.14-21.45, P < 0.001)., Conclusion: C. difficile was diagnosed in 0.11% of patients undergoing spine surgery. The majority of these cases occurred after discharge and in patients not having prior infection diagnoses. High-risk patients should be monitored and targeted with preventative interventions accordingly., Level of Evidence: 3.

Introduction: Our main objective was a revision of clinical, microbiological and epidemiological results of Clostridium difficile-associated infection in paediatric patients (2010-2015). We compared the diagnoses performed by detection of toxins in feces and those performed by real-time PCR., Methods: This retrospective study included 82 paediatric patients. Detection of toxigenic C. difficile was performed sequentially, in diarrheal feces and under clinical request., Results: A total of 39% of the patients were attended at Haematology-oncology Unit and >50% of them had previously received cephalosporins. Fever associated with diarrhea was more frequent in the group of toxin detection, whereas not receiving specific antibiotic treatment was more frequent in the group of positive PCR, without statistically significant differences., Conclusions: We highlight the presence of C. difficile infection in children under 2years old. A diagnostic testing in selected paediatric patients would be advisable when there is clinical suspicion of infection., (Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

Background: With the increased demand for primary total hip arthroplasty (THA) and corresponding rise in revision procedures, it is imperative to understand the factors contributing to the development of Clostridium difficile colitis. We aimed to provide a detailed analysis of: (1) the incidence of; (2) the demographics, lengths of stay, and total costs for; and (3) the risk factors and mortality associated with the development of C. difficile colitis after revision THA., Methods: The National Inpatient Sample database was queried for all individuals diagnosed with a periprosthetic joint infection and who underwent all-component revision THA between 2009 and 2013 (n = 40,876). Patients who developed C. difficile colitis during their inpatient hospital stay were identified. Multilevel logistic regression analysis was conducted to assess the association between hospital- and patient-specific characteristics and the development of C. difficile colitis., Results: The overall incidence of C. difficile colitis after revision THA was 1.7%. These patients were significantly older (74 vs 65 years), had greater lengths of hospital stay (19 vs 9 days), accumulated greater costs ($51,641 vs $28,282), and were more often treated in an urban hospital compared to their counterparts who did not develop C. difficile colitis (P < .001 for all). Patients with colitis also had a significantly higher in-hospital mortality compared to those without (5.6% vs 1.4%; P < .001)., Conclusion: While C. difficile colitis infection is an uncommon event following revision THA, it can have potentially devastating consequences. Our analysis demonstrates that this infection is associated with a longer hospital stay, higher costs, and greater in-hospital mortality., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Tilvalline is a pyrrolo[4,2]benzodiazepine derivative produced by the pathobiont Klebsiella oxytoca and is the causative toxin in antibiotic associated hemorrhagic colitis (AAHC). Heterologous expression of the tilivalline biosynthetic gene cluster along with in vitro reconstitution of the respective NRPS (NpsA, ThdA, NpsB) was employed to reveal a nonenzymatic indole incorporation via a spontaneous Friedel-Crafts-like alkylation reaction. Furthermore, the heterologous system was used to generate novel tilivalline derivatives by supplementation of respective anthranilate and indole precursors. Finally, it could be shown that salicylic and acetylsalicylic acid inhibit the biosynthesis of tilivalline in K. oxytoca liquid culture, presumably by blocking the peptidyl carrier protein ThdA, pointing toward a potential application in combination therapy to prevent or alleviate the symptoms of AAHC.

Background: Despite the implementation of enhanced recovery pathways (ERP), morbidity following colorectal surgery remains high. The aim of the present study was to estimate the impact of postoperative complications on excess hospital length of stay (LOS) in patients undergoing elective colorectal resection., Methods: A retrospective study of patients undergoing elective colorectal surgery at a single institution from 2003 to 2010 was performed. Patients managed by an ERP were compared to conventional care (CC), matched by propensity score radius matching. Complications were defined a priori. Excess (independent effect on LOS from multivariate analysis) and attributable (absolute number of additional bed days) LOS of common postoperative complications determined the impact of complications on bed utilization. Multivariate analysis was performed using multiple linear regression., Results: A total of 810 propensity-score-matched patients were included (ERP = 472, CC = 338). Complications were significantly lower in the ERP group compared to the CC group (20 vs. 31%, p < 0.001). Median LOS decreased from 7 days in the CC group to 5 days in the ERP group [adjusted decrease in mean LOS of 2.8 days (95% CI 0.8, 4.8)]. Anastomotic leak, myocardial infarction and C. difficile infection had the highest excess LOS for both the ERP and CC groups. However, impaired gastrointestinal function had a higher impact on the absolute number of hospital bed days in the ERP group, as high as anastomotic leak (72.7 vs. 73.5 days respectively), while in the CC group the impact of gastrointestinal dysfunction was less of that of anastomotic leak (50.6 vs. 78.9 days respectively)., Conclusions: In the setting of an ERP, postoperative complications have significant impact on total bed utilization. Impaired gastrointestinal function, given its high incidence, accounted for almost the same number of additional hospital bed days as anastomotic leak in the ERP group and is a target for quality improvement.

Competing Interests: Competing interests: None declared.

Aim: Using a prospective analysis to assess the success of faecal bacteriotherapy (FBT) in antibiotic-associated colitis due to Clostridium difficile. To analyse whether any of the factors according to which the treated patients can be categorized has a statistically significant effect on the therapeutic outcome., Materials and Methods: During the 2-year study period (2015-2016), 71 patients received FBT. After treatment, the patients were followed up by means of clinic visits or by phone. If colitis did not recur within eight weeks of follow-up, the treatment was considered successful., Results: The overall success rate was 76%, with statistically insignificant decline in recurrences. Subgroup analysis did not show any statistically significant difference in the success rate between the routes of administration, i.e. through a naso-enteral feeding tube and rectal enema. Likewise, there were no statistically significant differences in the success rate between the types of prior antibiotic therapy or between using fresh and cryo-stored stool suspension. No unexpected adverse event or lethality occurred during the study period., Conclusions: Faecal bacteriotherapy is a successful and safe therapeutic alternative for recurrent C. difficile infections.

Introduction and Aims: Clostridium difficile infection is the main cause of hospital-acquired diarrhea, and the clinical and endoscopic findings in those patients have been studied very little in Mexico. The aim of the present study was to describe those findings., Materials and Methods: A prospective cohort study was conducted that included patients with hospital-acquired diarrhea associated with Clostridium difficile diagnosed through polymerase chain reaction. The hypervirulent NAP027 strain was also determined. The clinical and endoscopic findings in the study patients, as well as the variables associated with severity, were analyzed., Results: Of the 127 patients with hospital-acquired diarrhea, 97 were excluded from the study due to lack of colonoscopy. The remaining 39 study patients had a mean age of 48 years, and their most common signs/symptoms were abdominal pain (49%), mucus in stools (41%), and blood in stools (10%). The most common alterations in the laboratory results were leukocytosis in 49%, fecal leukocytes (61%), and hypoalbuminemia (67%). The main risk factor was antibiotic use in 62%, and ceftriaxone was the most widely used. The hypervirulent strain was present in 54% of the cases. Endoscopic abnormalities were found in 87% of the patients. Thirty-eight percent presented with pseudomembranous colitis, with lesions in the left colon in 53%, and in the right colon in 13%. No association was found between proton-pump inhibitor use and Clostridium difficile-associated diarrhea. There was a significant association between hypoalbuminemia (< 3.3g/dL) and a greater risk for severe colitis, with a RR of 8.2 (p=0.008)., Conclusions: Pseudomembranous colitis lesions associated with the hypervirulent Clostridium difficile strain were predominant in the left colon. Hypoalbuminemia was a significant severity predictor., (Copyright © 2017 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.)

Competing Interests: Interessenkonflikt: Der Autor hat Vortragshonorare und Reisegrants von Astellas erhalten.

OBJECTIVE Distinguishing recurrent Clostridium difficile infection (CDI), defined as CDI caused by the same genotype, from reinfection with a different genotype, has important implications for surveillance and clinical trials investigating treatment effectiveness. We validated the proposed 8-week period for distinguishing "same genotype CDI" from "different genotype CDI," and we aimed to identify clinical variables with distinctiveness to propose an improved definition. METHODS From January 2004 to December 2013, a cohort of all inpatients with CDI at the University Hospital Basel, Switzerland, was established, and respective strains were collected. In patients with a second episode of CDI, both strains were compared using polymerase chain reaction (PCR) ribotyping. The standard definition of recurrence (within 8 weeks after initial diagnosis) was evaluated for its performance to predict CDI caused by the same genotype. RESULTS Among 750 patients with CDI, 130 (17.3%) were diagnosed with recurrence or reinfection. Strains from both episodes were available from 106 patients. Identical strains were identified in 36 patients with recurrence (36 of 47) and 27 patients with reinfection (27 of 59). Sensitivity, specificity, and negative and positive predictive values of the standard definition were 56%, 74%, 53%, and 76%, respectively. An extended period of 20 weeks resulted in the best match for both sensitivity and specificity (83% and 58%, respectively), while none of the clinical characteristics revealed independent distinctive power. CONCLUSIONS Our results challenge the utility of the 8-week cutoff for distinguishing recurrent CDI from reinfection. An extended period of 20 weeks may result in improved overall performance characteristics, but this finding requires external validation. Infect Control Hosp Epidemiol 2017;38:891-896.

Diseases causing hematochezia range from benign to potentially life-threatening. Systematic pediatric data on the causes of hematochezia are scarce. We studied the underlying causes and long-term outcome of hematochezia in children. We further investigated the relevance of antibiotic-associated hemorrhagic colitis in children, especially if caused by Klebsiella oxytoca.Infants, children, and adolescents with hematochezia were recruited prospectively. Patients were grouped according to age (<1 year, 1-5 years, 6-13 years, >14 years). In addition to routine diagnostics, K oxytoca stool culture and toxin analysis was performed. We collected data on history, laboratory findings, microbiological diagnostic, imaging, final diagnosis, and long-term outcome.We included 221 patients (female 46%; age 0-19 years). In 98 (44%), hematochezia was caused by infectious diseases. Endoscopy was performed in 30 patients (13.6%). No patient died due to the underlying cause of hematochezia. The most common diagnoses according to age were food protein-induced proctocolitis in infants, bacterial colitis in young children, and inflammatory bowel disease in children and adolescents. Seventeen (7.7%) had a positive stool culture for K oxytoca. Antibiotic-associated colitis was diagnosed in 12 (5%) patients: 2 caused by K oxytoca and 2 by Clostridium difficile; in the remaining 8 patients, no known pathobiont was identified.Infections were the most common cause of hematochezia in this study. In most patients, invasive diagnostic procedures were not necessary. Antibiotic-associated hemorrhagic colitis caused by K oxytoca was an uncommon diagnosis in our cohort. Antibiotic-associated colitis with hematochezia might be caused by pathobionts other than C difficile or K oxytoca.

A 75-year-old man was admitted with abdominal pain and fresh rectal bleeding. Significantly, he had no risk factors for Clostridium difficile infection. An abdominal CT demonstrated colonic thickening, and flexible sigmoidoscopy identified pseudomembranous colitis-like lesions. After initial treatment as C. difficile colitis, a stool sample revealed Escherichia coli O157:H7 infection. Antibiotic therapy was stopped due to the risk of lysis-mediated toxin release, but unfortunately, the patient continued to deteriorate. He developed several of the severe sequelae of E. coli O157:H7 infection, including haemolytic-uraemic syndrome with an acute kidney injury necessitating haemofiltration, plus progressively severe seizures requiring escalating antiepileptic treatment and intubation for airway protection. After a prolonged intensive care admission and subsequent recovery on the ward, our patient was discharged alive., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Introduction and Aims: Evidence in Colombia and Latin America has been insufficient for establishing the clinical characteristics of patients with antibiotic-associated diarrhea (AAD). The present study attempts to describe the clinical characteristics of patients with AAD and to determine the presence of Clostridium difficile, utilizing the polymerase chain reaction (PCR) technique., Materials and Methods: Forty-three patients with AAD, managed at the Hospital Universitario San Ignacio in Bogotá, Colombia, were evaluated. Prospective patient information was collected, with respect to demographic characteristics, profile of the antibiotic management received, clinical manifestations, risk factors, and paraclinical reports. In addition, the real time PCR test for Clostridium difficile (Cepheid Xpert ® , Sunnyvale, CA, United States) was performed., Results: Patient mean age was 58 years (19.31 SD). The majority of the patients received 2 or more antibiotics (62.9%) and the beta-lactams were the most frequently used. Hospital stay ranged from 2 to 104 days with a median of 10 days. The most frequent clinical manifestations were abdominal pain and bloating, followed by fever and tachycardia. At the time of diagnosis, 23 patients had noninflammatory results in the stool sample analyses and 18 had kidney failure. The mean level of albumin was 2.4mg/dl (0.7 SD). The presence of Clostridium difficile was documented through PCR in 6 patients (13.95% of the cases)., Conclusions: AAD patients were characterized by a high frequency of severe comorbidities and prolonged hospital stay. The presence of Clostridium difficile in only 13.9% of the cases suggests that other causes of diarrhea in the hospitalized patient should be considered., (Copyright © 2017 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.)

Clostridium difficile infection is a growing concern in health care and is a worrisome complication in orthopaedics. The incidence and severity of this infection are increasing, although the incidence following orthopaedic surgery is comparatively lower than that seen in patients in most other surgical specialties. The typical geriatric orthopaedic patient may have many risk factors that increase the likelihood of C difficile infection, including advanced age, residence in a long-term care facility, multiple comorbidities, the use of perioperative antibiotics, and a long length of stay. Many antibiotics used for prophylaxis in orthopaedic procedures have been correlated with an increased incidence of C difficile infection. The indications for C difficile testing may vary, and diagnostic methods differ in sensitivity and specificity. The prevention of this infection is multifaceted and consists of practitioner and patient hand hygiene, antibiotic stewardship, contact precautions, and proper environmental cleaning. The main treatment options are metronidazole for mild cases and vancomycin for moderate to severe disease. Up to 40% of cases may have one or more recurrence. Further research is needed to identify novel therapeutic and prevention strategies for C difficile infection.

Clostridium difficile infection (CDI) is a major cause of nosocomial diarrhea with the potential for significant morbidity and mortality. Colonization in a susceptible individual, with risk factors such as prior antibiotic use, advanced age, or medical comorbidities, may result in symptomatic infection. Although patients with a gynecologic malignancy may be at a higher risk of developing CDI due to an increased likelihood of having one or more risk factors, data do not consistently support the idea that chemotherapy or cancer itself are independently associated with CDI. For diagnosis of CDI, we recommended using a multi-step approach, with a highly sensitive initial rapid test such as the enzyme immunoassay (EIA) for glutamate dehydrogenase (GDH) or nucleic acid amplification testing (NAAT), followed by confirmatory testing with of the above two tests or EIA toxin A/B, which has high specificity. Treatment varies based on the severity of disease. We recommend vancomycin as first-line therapy for an initial episode of mild/moderate or severe CDI, with consideration of fidaxomicin for patients at particularly high risk for recurrence. Rectal vancomycin may play an adjunctive role for some severe cases, while surgical intervention is indicated for fulminant CDI if no improvement six or more days after initiating medical therapy. For non-severe recurrent disease, the initial treatment regimen should be repeated, while subsequent episodes are more appropriately treated with a tapered and pulsed dose of vancomycin, fidaxomicin, or fecal microbiota transplantation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background and Aims: Previous studies have reported that Clostridium difficile infection [CDI] is more common, and has a worse outcome, in patients with inflammatory bowel disease [IBD] than in those without. We have now reassessed the incidence and outcome of CDI in in-patients with and without IBD, and the outcomes of admissions for IBD patients with and without CDI., Methods: In-patients who had stool samples submitted for C. difficile testing [2007-2013] were collated. Two matched pools were generated: patients with IBD and CDI vs non-IBD patients with CDI [matched for age, sex and date] and patients with IBD and CDI vs IBD patients without CDI [matched for age and IBD type]. For each group, admission details, pre-admission and outcome data were compared., Results: Four per cent [1079/21035] of samples were positive for CDI; 5% [49] of these were from IBD in-patients. The incidence of CDI in IBD patients decreased from 8.7% in 2007/08 to 0.4% in 2012/13 [p < 0.0001]. Length of stay was shorter in IBD patients with CDI than in non-IBD CDI patients (hazard ratio [HR] 0.335 [0.218-0.513]) and was no different between IBD patients with and without CDI (HR 0.661 [0.413-1.06]). IBD patients were diagnosed with CDI earlier in their admission than non-IBD patients (HR 0.182 [0.093-0.246]). No differences in mortality were found., Conclusions: The incidence of CDI complicating IBD has fallen since 2007. CDI is no longer associated with worse short-term outcomes in patients with IBD than in those without. Patients with CDI and IBD have similar outcomes to those with IBD alone., (Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Study Objective: To compare the rates and severity of hospital-acquired Clostridium difficile infection (CDI) among patients taking proton pump inhibitors (PPIs) versus those not taking PPIs., Design: Retrospective, single-center, cohort study., Setting: Tertiary community hospital with a teaching service., Patients: A total of 41,663 patients with CDI who were hospitalized between January 2013 and May 2014; of those, 17,471 patients (41.9%) had received at least one dose of a PPI (PPI group), and 24,192 patients (58.1%) had no PPI exposure (control group)., Measurements and Main Results: A total of 348 patients had CDI during the study period, with 269 cases present on admission. Hospital-acquired CDI was defined as CDI diagnosis occurring on or after the third calendar day of admission. After excluding those patients with CDI on admission, 65 (0.38%) of 17,302 patients later developed CDI in the hospital in the PPI group compared with only 14 (0.058%) of 24,092 patients in the control group. Of these patients, 36 patients (0.21%) in the PPI group met the definition of severe CDI compared with 8 (0.03%) in the control group. This demonstrated an unadjusted relative risk (RR) of 6.46 (95% confidence interval [CI] 3.63-11.51, p<0.0001) of developing hospital-acquired CDI and an unadjusted RR of 6.27 (95% CI 2.91-13.48, p<0.0001) of developing severe CDI while taking a PPI. When evaluating only patients who developed severe-complicated CDI, there were 22 cases in the PPI group and 2 cases in the control group, demonstrating an unadjusted RR of 15.3 (95% CI 3.6-65.13, p=0.0002) of developing severe-complicated CDI. Confounding variables were similar between groups., Conclusion: PPI use was associated with an increase in both the rate and severity of hospital-acquired CDI., (© 2016 Pharmacotherapy Publications, Inc.)

Clostridium difficile infection is one of the most frequent among cancer patients. Its diagnosis is complicated by the fact that the symptoms of the infection and the side effects of the anticancer treatments could be similar. Chemotherapy itself might facilitate Clostridium difficile infection. Several risk factors are known but Clostridium difficile infection can develop in the absence of these. Neutreopenia is a risk factor for fatal Clostridium difficile infection and also the side effect of chemotherapy. Therefore, if symptoms of the potential infection develop (eg. diarrhoea more than three times a day, fever above 38.5 °C, colitis, rapid increase of serum creatinin) Clostridium difficile infection should be excluded. If the infection is confirmed it should be managed in the most efficient way. Orv. Hetil., 2016, 157(28), 1110-1116.

This report describes a case of Clostridium difficile ribotype 033 colitis in a patient treated with multiple antibiotics for KPC-producing Klebsiella pneumoniae pancreatitis. Diagnostic, clinical and therapeutic features are discussed. To the best of our knowledge, this is the first case of C. difficile ribotype 033 clinical infection reported from Italy.

High mobility group box1 (HMGB1), as a damage-associated inflammatory factor, contributes to the pathogenesis of numerous chronic inflammatory and autoimmune diseases. In this study, we explored the role of HMGB1 in CDI (Clostridium difficile infection) by in vivo and in vitro experiments. Our results showed that HMGB1 might play an important role in the acute inflammatory responses to C. difficile toxin A (TcdA), affect early inflammatory factors, and induce inflammation via the HMGB1-TLR4 pathway. Our study provides the essential information for better understanding the molecular mechanisms of CDI and the potential new therapeutic strategies for the treatment of this infection., (© The Author 2016. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Although Clostridium difficile infection is the cause of most cases of pseudomembranous colitis, clinicians should consider less common causes, especially if pseudomembranes are seen on endoscopy but testing remains negative for C difficile or if presumed C difficile infection does not respond to treatment. Histologic review of colonic mucosal biopsy specimens can provide clues to the underlying cause., (Copyright © 2016 Cleveland Clinic.)

Background: In the management of hydrocephalus, the ventriculo-gallbladder shunt is justified in situations where the ventriculo-peritoneal shunt is not useful due to peritoneal involvement and/or when the ventriculo-auricular and ventriculo-pleural shunts are contraindicated., Clinical Case: A 27 year-old female with hydrocephalus at birth, managed with ventricle-peritoneal shunt, modified 3 times throughout her life due to repeated infections and other different reasons. She was admitted due to colitis caused by Clostridium difficile, presenting concomitant signs of intracranial hypertension and neurological impairment. This led to a review and change of the ventriculo-peritoneal shunt system, with distal dysfunction due to peritoneal thickening. Atrial and pleural shunts were not indicated because the risk of infection. As an alternative, it was decided to place the distal end of the catheter in the gallbladder. The patient recovered her neurological functions after the surgery., Conclusions: Drainage alternatives may be needed in 5% of patients with valvular shunt dysfunction. The ventriculo-gallbladder is a good and viable option because it has an absorptive capacity of 1500cc liquid daily, besides being an excellent drainage through the bile duct. The abdominal surgery is easy to perform, and it is an alternative option in the failure of the ventriculo-peritoneal shunt., (Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.)

Antibiotic therapy has long term consequences in the intestinal microbiome. Clostridium difficile has a well-known role in antibiotic-associated diarrhea, but in addition, persistent infection with this organism may increase the risk for developing inflammatory bowel disease. Here, recent literature on how the intestinal microbiome is altered by antibiotic therapy is presented., (© FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Critically ill patients in the intensive care unit (ICU) are at risk of clinically important gastrointestinal bleeding, and acid suppressants are frequently used prophylactically. However, stress ulcer prophylaxis may increase the risk of serious adverse events and, additionally, the quantity and quality of evidence supporting the use of stress ulcer prophylaxis is low. The aim of the SUP-ICU trial is to assess the benefits and harms of stress ulcer prophylaxis with a proton pump inhibitor in adult patients in the ICU. We hypothesise that stress ulcer prophylaxis reduces the rate of gastrointestinal bleeding, but increases rates of nosocomial infections and myocardial ischaemia. The overall effect on mortality is unpredictable., Methods/design: The SUP-ICU trial is an investigator-initiated, pragmatic, international, multicentre, randomised, blinded, parallel-group trial of stress ulcer prophylaxis with a proton pump inhibitor versus placebo (saline) in 3350 acutely ill ICU patients at risk of gastrointestinal bleeding. The primary outcome measure is 90-day mortality. Secondary outcomes include the proportion of patients with clinically important gastrointestinal bleeding, pneumonia, Clostridium difficile infection or myocardial ischaemia, days alive without life support in the 90-day period, serious adverse reactions, 1-year mortality, and health economic analyses. The sample size will enable us to detect a 20 % relative risk difference (5 % absolute risk difference) in 90-day mortality assuming a 25 % event rate with a risk of type I error of 5 % and power of 90 %. The trial will be externally monitored according to Good Clinical Practice standards. Interim analyses will be performed after 1650 and 2500 patients., Conclusion: The SUP-ICU trial will provide high-quality data on the benefits and harms of stress ulcer prophylaxis with a proton pump inhibitor in critically ill adult patients admitted in the ICU., Trial Registration: ClinicalTrials.gov Identifier: NCT02467621 .

Background: Systemic antibiotics vary widely in in vitro activity against Clostridium difficile. Some agents with activity against C. difficile (e.g., piperacillin/tazobactam) inhibit establishment of colonization in mice. We tested the hypothesis that piperacillin/tazobactam and other agents with activity against C. difficile achieve sufficient concentrations in the intestinal tract to inhibit colonization in patients., Methods: Point-prevalence culture surveys were conducted to compare the frequency of asymptomatic rectal carriage of toxigenic C. difficile among patients receiving piperacillin/tazobactam or other inhibitory antibiotics (e.g. ampicillin, linezolid, carbapenems) versus antibiotics lacking activity against C. difficile (e.g., cephalosporins, ciprofloxacin). For a subset of patients, in vitro inhibition of C. difficile (defined as a reduction in concentration after inoculation of vegetative C. difficile into fresh stool suspensions) was compared among antibiotic treatment groups., Results: Of 250 patients, 32 (13 %) were asymptomatic carriers of C. difficile. In comparison to patients receiving non-inhibitory antibiotics or prior antibiotics within 90 days, patients currently receiving piperacillin/tazobactam were less likely to be asymptomatic carriers (1/36, 3 versus 7/36, 19 and 15/69, 22 %, respectively; P = 0.024) and more likely to have fecal suspensions with in vitro inhibitory activity against C. difficile (20/28, 71 versus 3/11, 27 and 4/26, 15 %; P = 0.03). Patients receiving other inhibitory antibiotics were not less likely to be asymptomatic carriers than those receiving non-inhibitory antibiotics., Conclusions: Our findings suggest that piperacillin/tazobactam achieves sufficient concentrations in the intestinal tract to inhibit C. difficile colonization during therapy.

Background: Clostridium difficile infection (CDI) is the leading infectious cause of nosocomial diarrhea. Hospitalized patients are at increased risk of developing CDI because they are exposed to C. difficile spores through contact with the hospital environment and often receive antibiotics and other medications that can disrupt the integrity of the indigenous intestinal microbiota and impair colonization resistance. Using whole metagenome shotgun sequencing, we examined the diversity and composition of the fecal microbiota in a prospective cohort study of 98 hospitalized patients., Results: Four patients had asymptomatic C. difficile colonization, and four patients developed CDI. We observed dramatic shifts in the structure of the gut microbiota during hospitalization. In contrast to CDI cases, asymptomatic patients exhibited elevated relative abundance of potentially protective bacterial taxa in their gut at the onset of C. difficile colonization. Use of laxatives was associated with significant reductions in the relative abundance of Clostridium and Eubacterium; species within these genera have previously been shown to enhance resistance to CDI via the production of secondary bile acids. Cephalosporin and fluoroquinolone exposure decreased the frequency of Clostridiales Family XI Incertae Sedis, a bacterial family that has been previously associated with decreased CDI risk., Conclusions: This study underscores the detrimental impact of antibiotics as well as other medications, particularly laxatives, on the intestinal microbiota and suggests that co-colonization with key bacterial taxa may prevent C. difficile overgrowth or the transition from asymptomatic C. difficile colonization to CDI.