Clostridium Difficile Recurrence Research Articles

Design, Synthesis and Biological Evaluation of Novel PEG-Rakicidin B1 Hybrid as Clostridium difficile (CD) Targeted Anti-Bacterial Agent.

Rakicidin B1 was isolated and purified from the culture broth of a marine Streptomyces sp. as a potent anti-cancer agent, and lately the compound and its derivatives have firstly been found to possess anti-Clostridium difficile (CD) activity but with high cytotoxicity. Herein, following our previous discovery on anti-CD activity of Rakicidin B1, structure modification was performed at the OH position of Rakicidin B1 and a new Rakicidin B1-PEG hybrids FIMP2 was facilely designed and synthesized by conjugating the PEG2000 with the scaffolds of Rakicidin B1 via the linkage of carbamate. The cytotoxicity of the FIMP2 was first evaluated against three different cancer cell lines, including HCT-8 cells, PANC-1, and Caco-2, with IC50 values at 0.519 μM, 0.815 μM, and 0.586 μM, respectively. Obviously, as compared with a positive control group treated with Rakicidin B1, the IC50 value of FIMP2 increased by nearly 91-fold, 50-fold, and 67-fold, suggesting that the PEGylation strategy significantly reduced the cytotoxicity of FIMP2. Thus, this preliminary result may be beneficial to increase its safety index (SI) value due to the decreased cytotoxicity of FIMP2. In addition, this decreased cytotoxicity of FIMP2 was further confirmed based on a zebrafish screening model in vivo. Thereafter, the anti-CD activity of FIMP2 was evaluated in vivo, and its efficacy to treat CDI was found to be better than that of vancomycin. The mortality and recurrence rate of FIMP2 is not as low compared with that of vancomycin; these results demonstrated that compound FIMP2 is a new, promising anti-CD agent with significant efficacy against CD recurrence with low cytotoxicity towards bodies.

Fecal Transplant for Recurrent Clostridium difficile Colitis in CF-LVAD Supported Patients

<h3>Purpose</h3> Clostridium difficile (CD) colitis may result in diarrhea with fluid shifts and hypovolemia as well as sepsis in patients supported on LVAD therapy. Treatment of CD with fecal transplant has utilized for patients with recurrent CD. Use of fecal transplant (FT) for treatment of CD in the LVAD population has not been described. <h3>Methods</h3> A retrospective study was conducted on LVAD patients implanted at a single center from 2010 to 2020 to identify those with CD that proceeded with FT. Patient characteristics, infection history, and subsequent medical course were collected and analyzed. The primary outcome was efficacy in a small cohort of LVAD-supported patients with CD. <h3>Results</h3> Patients identified (n=2) included an LVAD patient implanted as destination therapy (DT) and an LVAD patient who later underwent heart transplant. Prior to FT, both patients were trialed on courses of oral vancomycin for treatment of CD. Both patients developed recurrent CD despite oral vancomycin and were deemed to be failures of response. Patients underwent FT 379 and 1533 days after LVAD implant. FT occurred 301 days and 1749 days after initial CD diagnosis. All patients tolerated fecal transplant without complications. Following FT, the patient supported with DT LVAD did not have CD recurrence after last follow up of 481 days, and the patient initially supported with LVAD had one CD recurrence after 663 days (after heart transplant). <h3>Conclusion</h3> These data provide initial evidence of treatment safety and response to FT in patients supported on CF-LVAD therapy who have previously failed antibiotic therapy. FT may represent an effective therapy for treatment of CD in LVAD patients similar to the general population, but multi-institutional datasets should confirm efficacy.

Recurrence of Clostridium Difficile and Cytomegalovirus Infections in Patients with Ulcerative Colitis Who Undergo Ileal Pouch-Anal Anastomosis.

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. 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. 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. 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.

Gold Nanoclusters as an Antibacterial Alternative Against Clostridium difficile.

BackgroundClostridium difficile infection (CDI) has become one of the most important factors threatening human health, and about 20–30% antibiotic-related diarrhea cases and almost all pseudomembranous enteritis cases are related to CDI. The high recurrence of Clostridium difficile (C. difficile) and the emergence of drug resistance make clinical treatment of CDI difficult. Therefore, there is an urgent need to develop a non-antibiotic-alternative therapy against CDI. Gold nanoclusters (AuNCs) can better interact with bacteria due to its ultrasmall size. The aim of the present study was to explore whether AuNCs could be used as an antibacterial agent to kill C. difficile.MethodsAuNCs and C. difficile were co-cultivated in an anaerobic atmosphere to evaluate the bactericidal effect of AuNCs. The bacterial growth rate was estimated by using two concentrations of AuNCs (50 and 100 μM). The damage of AuNCs to C. difficile is detected by SYTOX Green staining methods and SEM image analysis. The mechanism of AuNCs on C. difficile was explored by reactive oxygen species (ROS) detection. The toxic effect of AuNCs on human cells was evaluated by MTT method.ResultsAuNCs (100 μM) killed C. difficile drastically. AuNCs increased the release of ROS by about 5 fold and destroyed the membrane integrity of C. difficile cells without causing significant toxic effect on human cells.ConclusionAuNCs showed great potential as an alternative to traditional antibiotics in killing C. difficile and may prove to be an alternative to treat CDI.

Clostridium difficile: A Frequent Infection in Children After Intestinal Transplantation.

Organ transplantation (Tx) is a risk factor for Clostridium difficile infection (CDI). After intestinal transplantation (ITx), few data are available on the impact of this graft infection and the possible induction of rejection. We included retrospectively all children after ITx in our unit, with at least 1 year of graft survival. All samples positive for Clostridium difficile (CD) and its toxin were considered. Among the 57 ITx recipients (60 Txs), 22 children (39%) developed culture-proven CDI, 12 after isolated small bowel Tx, 9 after liver-small bowel Tx, and 1 after multivisceral Tx. Twenty patients had diarrhea, 8 bloody stools, 4 fever, and 1 hypothermia. Nine were hospitalized for an average of 6.5 days (2-20) and 4 with severe dehydration. Nine (40%) had received antibiotics for an average of 19 days (7-60) before CDI. Two patients were asymptomatic. CDI was treated with metronidazole in 12 children, vancomycin in 6, and both in 3. Three children presented mild-to-severe rejections. Two patients presented concomitantly CDI and rejection. The third patient presented a rejection with severe complications 4 years after CDI. Recurrence of toxinogenic CD was observed in 9 children, in 7 associated with clinical symptoms. During the last follow-up, the stool number was the same as before CDI except for 1 patient with ongoing infection. CDI is more prevalent in children after ITx compared with other organ Tx; it is most often symptomatic but mildly or moderately severe. Standard antibiotics efficiently control the symptoms. Induction of rejection is a rare event.

Medical students\u2019 perception on fecal microbiota transplantation

BackgroundFecal microbiota transplantation (FMT) has become an emergent method in the therapy of several intestinal diseases, mainly in Clostridium difficile recurrence. The training of FMT in medical schools is at its beginning and in countries where FMT is only occasionally carried out, it is important to know the perception of medical students on FMT.MethodsWe undertook a survey of 3rd year medical students not exposed to official academic information on FMT in order to find out their knowledge, beliefs and attitude toward FMT. A number of 80 students were asked to fill a dedicated online questionnaire.Results52 out of 80 third year medical students anonymously filled the questionnaire (65% response rate). 34% of respondents reported to have at least a medium level of knowledge regarding FMT. The top indication for FMT identified by 76.9% was C. difficile infection; however, 60% believed FMT to be a promising therapy for a high number of conditions and while almost all respondents (98.1%) would recommend it, 88.4% would explore other options first. Colonoscopy was considered the optimal method of delivery by 42.3%. Only 39% of participants believed that patients would accept FMT, however 71% considered that a more socially acceptable name for the procedure and anonymous donors would increase acceptance rate. The risk of transmitting a disease undetected by donor stool screening procedures to the recipient was the most worrying side effect considered by 75% of respondents. 54% believed that more research is required for FMT to enter clinical practice and 55.7% of respondents would enroll patients in controlled clinical trials.ConclusionsMedical students not exposed to educational information on FMT seem to be somewhat well informed about this method and would recommend it to their patients. Students, however, need to know more on the indications of FMT.

Long-Term Efficacy of Oral Vancomycin Prophylaxis for the Prevention of Clostridium difficile Recurrence

Background: Limited evidence suggests that prophylactic oral vancomycin may be beneficial in preventing Clostridium difficile infection (CDI) recurrence, but long-term efficacy is unknown. Objective: To evaluate the long-term efficacy of oral vancomycin prophylaxis (OVP) in preventing CDI recurrence in subjects who require subsequent antibiotic exposure. Methods: A retrospective cohort study was conducted at a community hospital. A total of 91 subjects with a history of CDI between January 2013 and December 2015 who had a subsequent hospitalization requiring systemic antibiotics within 12 months were evaluated. Thirty-two subjects who received prophylaxis with oral vancomycin were compared to 59 subjects who did not receive prophylaxis. Results: CDI recurrence within 12 months was significantly lower in subjects receiving OVP compared to those who did not receive OVP (6.3% vs 28.8%; odds ratio [OR]: 0.16; 95% confidence interval [CI]: 0.04-0.77; P = .011) including patients whose previous CDI was an initial episode (3.7% [1/27] vs 28.3% [15/53]; OR: 10.3; 95% CI: 1.28-82.6; P = .009). Conclusion: Use of OVP in subjects with a history of CDI up to 12 months prior to subsequent antibiotic exposure appears to reduce the risk of CDI recurrence for up to 12 months.

▼ Bezlotoxumab for prevention of recurrence of Clostridium difficile infection

Clostridium difficile infection is a significant cause of infectious diarrhoea and is associated with considerable morbidity and mortality.1,2 Management of Clostridium difficile infection often requires treatment with antibiotics (metronidazole, vancomycin...

Efficacy of Oral Vancomycin, Oral Metronidazole, or IV Metronidazole Prophylaxis at Reducing the Risk of Clostridium difficile Recurrence

BackgroundSecondary prophylaxis (SP) for Clostridium difficile infection (CDI) with oral vancomycin or oral/IV metronidazole when initiating antibiotics is common, though few studies are available to support this practice. The purpose of this study was to assess the efficacy of prophylaxis within a year of index CDI.MethodsThis retrospective chart review looks at subsequent courses of antibiotics and CDI in patients with initial positive CDI testing in 2013–16. A positive CDI test within 90 days of antibiotics was a recurrence. The use of antibiotics for SP was noted, along with other factors associated with CDI relapse. Non-parametric and exact tests were used for univariate analysis. These variables were included in a multivariate proportional hazards model.ResultsWe found 597 antibiotic episodes in 230 patients. 130 episodes (21.8%) received SP. The difference of recurrence rates with and without antibiotics, 9.2 % vs 10.7%, was not statistically significant. No difference was seen when metronidazole was used, but vancomycin SP reduced the rate to 7.5% (6/80, P = 0.45). Probiotics were associated with a higher rate of recurrence (16.7 vs. 8.9%, P = 0.025). Proton pump inhibitors were also associated with a slightly higher rate of CDI recurrence (13.0% vs. 8.4%). The rate of relapse fell significantly with increasing time since the index case of CDI by logistic regression (P = 0.011). In multivariate regression, relapse was associated with shorter time from index CDI, shorter durations of antibiotics, and the use of probiotics.ConclusionThis retrospective study does not support the routine use of metronidazole in subsequent antibiotic courses following CDI. The use of probiotics paradoxically increased the rate of CDI relapse in this study. The limitations of this retrospective study do not eliminate the possibility of utility of vancomycin as prophylaxis, but this requires further evaluation.Disclosures All authors: No reported disclosures.

Bezlotoxumab for the prevention of Clostridium difficile recurrence

ABSTRACTIntroduction: Clostridium difficile infection is a major economic and clinical burden, due to its high frequency of recurrence. Currently recommended treatments are not efficient for prevention and may contribute to the risk of recurrent infection. In recent years, research has focused on strategies to lessen this risk. Bezlotoxumab is a monoclonal antibody that prevents recurrences of C. difficile infection through the antagonism of toxin B.Areas covered: In this review, the authors discuss the burden of C. difficile infection and its recurrences, the mechanisms underlying the recurrences, and current C. difficile treatments. They subsequently analyze the strategic therapeutic rationale for bezlotoxumab use, as well as the supporting clinical evidence.Expert opinion: Bezlotoxumab is an attractive solution for reducing the unacceptable level of recurrence that occurs with the currently recommended C. difficile treatments and other alternative therapies under consideration. Even though bezlotoxumab has not been tested in large-scale trials exclusively in cases of already established recurrent C.difficile infection (rCDI), it has an advantage over current treatments in that it does not interfere with the patient’s gut flora while directly neutralizing the key virulence factor. Although cost remains an important factor against its widespread use, simpler administration, fewer side-effects, and better social acceptability justify its consideration for treating rCDI.

Risk factors and impact of Clostridium difficile recurrence on haematology patients.

The incidence of Clostridium difficile infection (CDI) in adults with malignancy is 7%-14% compared with 1%-2% in the general hospitalized population. Despite the increased incidence of CDI in this population, a major concern is the propensity of CDI to recur, leading to delays in therapy impacting outcomes. We conducted a retrospective case-control study to identify risk factors for recurrent CDI (rCDI) and to determine the impact of rCDI on adult patients with a haematological malignancy. Adult haematology patients with CDI from June 2010 to December 2014 were divided into two groups: rCDI and non-rCDI. Multivariable models using logistic regression were constructed to identify risk factors for rCDI. A total of 100 patients in our study yielded a 41% recurrence rate. CDI impacted chemotherapy significantly more in the rCDI group (53.7% versus 11.9%, P <0.001), primarily due to interruptions in established treatment plans (46.3% versus 10.3%, P <0.001). Risk factors for rCDI identified at index included salvage lymphoma chemotherapy (OR 9.64, 95% CI 1.02-91.15, P = 0.048) and severe CDI (OR 4.82, 95% CI 1.31-17.66, P = 0.018). Longitudinal risk factors included exposure to fluoroquinolones (OR 3.96, 95% CI 1.04-15.15, P = 0.044), ceftriaxone (OR 18.93, 95% CI 1.27-281.95, P = 0.033) and piperacillin/tazobactam (OR 10.4, 95% CI 1.81-59.64, P = 0.009). Haematology patients exhibit a higher rate of rCDI than general hospitalized patients. Utilization of this multivariable model to guide index CDI therapy at index may help to decrease the rCDI and prevent delays or interruptions in chemotherapy.

Clostridium difficile colonization and antibiotics response in PolyFermS continuous model mimicking elderly intestinal fermentation.

Background Clostridium difficile (CD), a spore-forming and toxin-producing bacterium, is the main cause for antibiotic-associated diarrhea in the elderly. Here we investigated CD colonization in novel in vitro fermentation models inoculated with immobilized elderly fecal microbiota and the effects of antibiotic treatments.MethodsTwo continuous intestinal PolyFermS models inoculated with different immobilized elder microbiota were used to investigate selected factors of colonization of CD in proximal (PC, model 1) and transverse-distal (TDC, model 1 and 2) colon conditions. Colonization of two CD strains of different PCR ribotypes, inoculated as vegetative cells (ribotype 001, model 1) or spores (ribotypes 001 and 012, model 2), was tested. Treatments with two antibiotics, ceftriaxone (daily 150 mg L−1) known to induce CD infection in vivo or metronidazole (twice daily 333 mg L−1) commonly used to treat CD, were investigated in TDC conditions (model 2) for their effects on gut microbiota composition (qPCR, 16S pyrosequencing) and activity (HPLC), CD spore germination and colonization, and cytotoxin titer (Vero cell assay).ResultsCD remained undetected after inoculating vegetative cells in PC reactors of model 1, but was shown to colonize TDC reactors of both models, reaching copy numbers of up to log10 8 mL−1 effluent with stable production of toxin correlating with CD cell numbers. Ceftriaxone treatment in TDC reactors showed only small effects on microbiota composition and activity and did not promote CD colonization compared to antibiotic-free control reactor. In contrast, treatment with metronidazole after colonization of CD induced large modifications in the microbiota and decreased CD numbers below the detection limit of the specific qPCR. However, a fast CD recurrence was measured only 2 days after cessation of metronidazole treatment.ConclusionsUsing our in vitro fermentation models, we demonstrated that stable CD colonization in TDC reactors can be induced by inoculating CD vegetative cells or spores without the application of ceftriaxone. Treatment with metronidazole temporarily reduced the counts of CD, in agreement with CD infection recurrence in vivo. Our data demonstrate that CD colonized an undisturbed microbiota in vitro, in contrast to in vivo observations, thus suggesting an important contribution of host-related factors in the protection against CD infection.Electronic supplementary materialThe online version of this article (doi:10.1186/s13099-016-0144-y) contains supplementary material, which is available to authorized users.

Epidemiology and outcome ofClostridium difficileinfections in patients hospitalized in Internal Medicine:findings from the nationwide FADOI-PRACTICE study.

Background Clostridium difficile (CD) is a leading cause of diarrhoea among hospitalized patients. The objective of this study was to evaluate the rate, the optimal diagnostic work-up, and outcome of CD infections (CDI) in Internal Medicine (IM) wards in Italy.MethodsPRACTICE is an observational prospective study, involving 40 IM Units and evaluating all consecutive patients hospitalized during a 4-month period. CDI were defined in case of diarrhoea when both enzyme immunoassay for GDH, and test for A/B toxin were positive. Patients with CDI were followed-up for recurrences for 4 weeks after the end of therapy.ResultsAmong the 10,780 patients observed, 103 (0.96 %) showed CDI, at admission or during hospitalization. A positive history for CD, antibiotics in the previous 4 weeks, recent hospitalization, female gender and age were significantly associated with CDI (multivariable analysis). In-hospital mortality was 16.5 % in CD group vs 6.7 % in No-CD group (p < 0.001), whereas median length of hospital stay was 16 (IQR = 13) vs 8 (IQR = 8) days (p < 0.001) among patients with or without CDI, respectively. Rate of CD recurrences was 14.6 %. As a post-hoc evaluation, 23 out of 34 GDH+/Tox- samples were toxin positive, when analysed by molecular method (a real-time PCR assay). The overall CD incidence rate was 5.3/10,000 patient-days.ConclusionsOur results confirm the severity of CDI in medical wards, showing high in-hospital mortality, prolonged hospitalization and frequent short-term recurrences. Further, our survey supports a 2–3 step algorithm for CD diagnosis: EIA for detecting GDH, A and B toxin, followed by a molecular method in case of toxin-negative samples.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1961-9) contains supplementary material, which is available to authorized users.

A Comparison of Clostridium difficile Recurrence Rates With Different Treatment Methods

A Comparison of Clostridium difficile Recurrence Rates With Different Treatment Methods

Impact of Clostridium difficile recurrence on hospital readmissions

The impact of recurrent Clostridium difficile infections (CDIs) on hospital readmissions is unknown. The objective of this study was to determine whether recurrent CDI was independently associated with the number of hospital readmissions and days readmitted. We performed a retrospective cohort study at an academic, urban, tertiary care hospital. Data were collected from electronic medical records and supplemented with chart review. CDI patients were followed for 180 days to ascertain the number of hospital readmissions and total days readmitted. Univariate and multivariable negative binomial regression models were used to evaluate factors, including CDI recurrence, associated with hospital readmissions. The study included 3,950 patients with CDI from 2003-2009, including 413 patients with recurrent CDI. Recurrent CDI patients were significantly more likely to have at least 1 readmission (85% vs 41%; P < .001) and had more days readmitted (mean = 18.6 vs 7.6; P < .001) than patients without recurrent CDI. In multivariable analysis, recurrent CDI was independently associated with number of readmissions (rate ratio = 2.54; 95% confidence interval [CI], 2.21-2.91) and days readmitted (rate ratio = 3.97; 95% CI, 3.11-5.08) after adjustment for demographics, comorbidities, and medications. Recurrent CDI patients are significantly more likely than patients without a recurrence to be readmitted and spend increased time readmitted to the hospital.

Clostridium difficile recurrence is a strong predictor of 30-day rehospitalization among patients in intensive care.

While incidence, mortality, morbidity, and recurrence rates of C. difficile infection (CDI) among the critically ill have been investigated, the impact of its recurrence on 30-day rehospitalization (ReAd), an important policy focus, has not been examined. Secondary analysis of a multicenter retrospective cohort study Patients Adult critically ill patients who survived their index hospitalization complicated by CDI METHODS: CDI was defined by diarrhea or pseudomembranous colitis and a positive assay for C. difficile toxins A and/or B. CDI recurrence (rCDI) was defined as diarrhea, positive C. difficile toxin and need for retreatment after cessation of therapy. Descriptive statistics and a logistic regression examined ReAd rates and characteristics, and factors that impact it. Among 287 hospital survivors, 76 (26.5%) required ReAd (ReAd+). At baseline, the ReAd+ group did not differ significantly from the ReAd- group based on demographics, comorbidities, APACHE II scores, or ICU type. ReAd+ patients were more likely to have hypotension at CDI onset (48.7% vs 34.1%, P=.025) and to require vasopressors (40.0% vs 27.1%, P=.038); they were less likely to require mechanical ventilation (56.0% vs 77.3%, P<.001). A far greater proportion of ReAd+ than ReAd- had developed a recurrence either during the index hospitalization or within 30 days after discharge (32.89% vs 2.84%, P<.001). In a logistic regression, rCDI was a strong predictor of ReAd+ (adjusted odd ratio, 15.33, 95% confidence interval, 5.68-41.40). Greater than 25% of all survivors of critical illness complicated by CDI require readmission within 30 days of discharge. CDI recurrence is a strong predictor of such rehospitalizations.

PIN25 - The Budget Impact of Using Fidaxomicin for Hospitalised Cdi Patients from the Danish Health Care Perspective

Analyse the budget impact in Region Hovedstaden in Denmark (Region H), if all Clostridium difficile (CDI) hospitalised patients received fidaxomicin instead of vancomycin during one year. The Danish national patient database provided the number of hospitalised patients and length of stay (LOS) for CDI patients (ICD-10: A047). A phase III trial provided the risk of a first and second CDI recurrence [Cornelly 2012]. Cost per hospital stay calculated by LOS multiplied by cost per bed day (DKK 6,000) plus drug costs, vancomycin (DKK 300), fidaxomicin (DKK 11,641). In Region H 840 CDI patients were hospitalised in 2012. Assuming the same outcome as the trial, the total number of CDI hospitalisations would decrease from 1,104 with vancomycin ( (23,2% risk of 1st recurrence (23.2% *840 = 195); 35.5% risk of 2nd recurrence (35.5%*195 = 69) ) to 930 with fidaxomicin ( (9.0% risk of 1st recurrence (9.0%*840=76); 19.7% risk of 2nd recurrence (19.7% *76= 15) ). Fidaxomicin prevents 174 hospitalisations compared to vancomycin. Assuming CDI is the primary diagnosis, with an average LOS of 9.0 days, the health care cost will increase by 2% with fidaxomicin. Assuming CDI is the secondary diagnosis, with an average LOS of 16.8 days, the health care cost will decrease by 6% with fidaxomicin. Assuming the average LOS for CDI patients is 13.3 days, the health care cost will decrease with 4%, and assuming LOS is 10 days, using fidaxomicin is cost neutral. In Region H, if all hospitalised CDI patients received fidaxomicin the number of recurrences decreases by 66% and the total number of cases decreases by 16%, compared to vancomycin usage. From the health care payer perspective fidaxomicin reduces recurrences, frees up available bed days, and may be cost neutral or cost saving depending on the assumed LOS, compared to vancomycin.

Clostridium difficile recurrence is characterized by pro-inflammatory peripheral blood mononuclear cell (PBMC) phenotype.

Clostridium difficile infection (CDI) is a prevalent nosocomial and increasingly community-acquired problem. Little is known about the productive cellular response in patients. We used flow cytometry to define inflammatory (Th1 and Th17) and regulatory [Foxp3(+) T-regulatory (Treg)] cells present in circulating peripheral blood mononuclear cells (PBMC) from CDI patients. We consented 67 inpatients that tested either positive or negative for CDI and 16 healthy controls and compared their PBMC phenotypes. PBMC were collected, isolated, and stained for CD3, CD8 and either IL17 (Th17), IFN-γ (Th1) or Foxp3 (Treg) and analysed using flow cytometry. Twenty thousand events were collected in the lymphocyte gate (gate 1) and T-cell phenotypes were defined. CDI patients who clear the primary initial infection have greater numbers of non-CD3 PBMC. CDI patients who develop recurrence of CDI have a greater percentage of CD3(+)CD8(+), CD3(+)CD4(+)Foxp3 and fewer low granular CD3(-)Foxp3(+) PBMC. These patients have greater numbers of IFN-γ-producing lymphocytes, as well as PBMC phenotypes represented by increased IFN-γ- and IL17-co-expressing CD4(+)CD3(+). This initial pro-inflammatory phenotype decreases with repeated recurrence, demonstrating importance of timing of sample collection and history of symptoms. Patients with a history of recurrence had increased Foxp3(+)CD3(+)CD4(+) and IL17(+)CD3(+)CD4(+) populations. Hence, CDI recurrence is hallmarked by greater numbers of circulating CD3(+) lymphocytes skewed towards a Th1/Th17 inflammatory population as well as possible immune plasticity (Th17/Treg).

Factors Affecting Recurrence of Clostridium difficile

SESSION TITLE: ICU Infections

Recurrence of Clostridium difficile infection among veterans with spinal cord injury and disorder

Recurrent Clostridium difficile (CDI) infection is a growing concern; however, there are little data on impact of recurrent CDI on those with spinal cord injury and disorder (SCI/D). Therefore, the objective of this study was to identify risk factors associated with recurrence of CDI among Veterans with SCI/D. This was a retrospective cohort study with data from outpatient, inpatient, and extended care settings at 83 Department of Veterans Affairs facilities from 2002 to 2009. Of 1,464 cases of CDI analyzed, 315 cases (21.5%) had a first recurrence of CDI. Multivariable regression demonstrated that risk factors significantly associated with increased recurrence were concomitant fluoroquinolone use (odds ratio [OR], 1.39; 95% confidence interval [CI]: 1.08-1.80), whereas concomitant tetracycline use (OR, 0.35; 95% CI: 0.14-0.90), and cerebrovascular accident (OR, 0.46; 95% CI: 0.25-0.85) were associated with decreased recurrence. A subanalysis in those with health care facility-onset CDI showed that increased length of stay postinitial CDI was a significant risk factor for recurrence as was concomitant use of fluoroquinolones and that tetracycline remained protective for recurrence. Concomitant fluoroquinolone use was a risk factor for the recurrence of CDI. In contrast, tetracyclines and cerebrovascular accident were protective. Length of stay greater than 90 days from the initial CDI episode was also a risk factor for recurrence among those with health care facility-onset CDI. Future studies should focus on effective strategies to prevent these risk factors among the SCI/D population.