Hospital-acquired Diarrhea Research Articles

Oral teicoplanin for successful treatment of severe refractory Clostridium difficile infection

Clostridium difficile is the leading cause of hospital-acquired diarrhoea. There is no defined protocol for treating severe Clostridium difficile infection (CDI) refractory to vancomycin or vancomycin and metronidazole combination therapy. The aim of this study was to evaluate the rate of clinical cure, time to resolution of diarrhoea and recurrence rate in patients with severe refractory CDI treated with oral teicoplanin. A one-year prospective study was carried out in the Clinic for Infectious and Tropical Diseases, Clinical Center Serbia. Patients with severe and complicated CDI who failed to respond to oral vancomycin and intravenous metronidazole combination therapy were enrolled. They were given oral teicoplanin 100 mg bi-daily. Patients were followed for recurrence for eight weeks. Nine patients with a mean age of 70.8±9.4 years were analyzed. All patients had pseudomembranous colitis, and five had complicated disease. In four patients intracolonic delivery of vancomycin was also performed in addition to oral vancomycin and intravenous metronidazole prior to initiating teicoplanin, but without improvement. After teicoplanin initiation all patients achieved clinical cure. The mean time to resolution of diarrhoea after teicoplanin introduction was 6.3±4.5 days. There was no statistically significant difference in time to resolution of diarrhoea according to initial leucocyte count, age over 65 years, the presence of ileus, complicated disease and the use of concomitant antibiotic therapy (p = 0.652, 0,652, 0.374, 0.374, and 0,548, respectively). None of the patients experienced recurrence. Oral teicoplanin might be a potential treatment for severe and complicated refractory CDI, but further studies are required.

Clinical significance of direct cytotoxicity and toxigenic culture in Clostridium difficile infection

BackgroundClostridium difficile infection (CDI) is the leading cause of hospital-acquired diarrhoea in developed countries. Although an optimal diagnosis is crucial, laboratory diagnostics remain challenging. Currently, the reference methods are direct cytotoxicity assay and toxigenic culture; however there is controversy in the interpretation of discordant results of these tests. ObjectiveThe aim of our study was to determine the clinical significance of detecting C. difficile only by toxigenic culture with a negative direct cytotoxicity assay. MethodsWe conducted a prospective study in which patients aged >2 years with CDI were enrolled and monitored at least 2 months after their last episode. Samples were tested by both cytotoxicity assay and toxigenic culture. ResultsDuring the 6-month study period, we identified 169 episodes meeting CDI criteria that had been tested by both assays, out of which 115 were positive for both cytotoxicity assay and toxigenic culture, and 54 CDI episodes (31.9%) were positive only by toxigenic culture. Overall, patients median age was 71.3, 50.9% were male and the most frequent underlying disease was malignancy. The comparison of CDI episodes positive for both assays and by toxigenic culture only revealed the following, respectively: mild CDI (77.4% vs 94.4%; p = 0.008), severe CDI (21.7% vs 5.6%; p = 0.008), severe complicated (0.9% vs 0.0%; p = 1.000), pseudomembranous colitis (1.7% vs 1.9% p = 1.000), recurrence (17.4% vs 14.8%; p = 0.825), overall mortality (8.7% vs 7.4%; p = 1.000) and CDI related mortality (2.6% vs 0%; p = 0.552). ConclusionCDI episodes positive by cytotoxicity assay were more severe than those positive only by toxigenic culture, however there were a significant proportion of CDI cases (31.9%) that would have been missed if only cytotoxicity had been considered as clinically significant for CDI treatment, including severe CDI cases. Our data suggest that a positive test by toxigenic culture with a negative result for cytotoxicity should not be interpreted as colonization.

Treating Clostridium difficile infections: Should fecal microbiota transplantation be reclassified from investigational drug to human tissue?

Fecal microbiota transplantation (FMT) has emerged as a highly effective treatment for Clostridium difficile infection (CDI), the most frequent cause of hospital-acquired infectious diarrhea in developed countries and the cause of nearly 30,000 annual deaths in the US. FMT is proving to be more effective at treating CDI than traditional antibacterial therapy, and reduces the exposure of valuable antibiotics to potential resistance. A systematic review to assess the efficacy of FMT for CDI treatment showed that across all studies for recurrent CDI, symptom resolution was observed in 85% of patients. The United States Food and Drug Administration currently classifies FMT as an investigational drug, which imparts overly restrictive regulations that are impossible to apply to FMT in the same manner as conventional drugs. Reclassification of FMT to a human cell, tissue, and cellular and tissue-based product could potentially expand access to this important treatment while maintaining rigorous safety standards.

Using a Novel Lysin To Help Control Clostridium difficile Infections.

As a consequence of excessive antibiotic therapies in hospitalized patients, Clostridium difficile, a Gram-positive anaerobic spore-forming intestinal pathogen, is the leading cause of hospital-acquired diarrhea and colitis. Drug treatments for these diseases are often complicated by antibiotic-resistant strains and a high frequency of treatment failures and relapse; therefore, novel nonantibiotic approaches may prove to be more effective. In this study, we recombinantly expressed a prophage lysin identified from a C. difficile strain, CD630, which we named PlyCD. PlyCD was found to have lytic activity against specific C. difficile strains. However, the recombinantly expressed catalytic domain of this protein, PlyCD1-174, displayed significantly greater lytic activity (>4-log kill) and a broader lytic spectrum against C. difficile strains while still retaining a high degree of specificity toward C. difficile versus commensal clostridia and other bacterial species. Our data also indicated that noneffective doses of vancomycin and PlyCD1-174 when combined in vitro could be significantly more bactericidal against C. difficile. In an ex vivo treatment model of mouse colon infection, we found that PlyCD1-174 functioned in the presence of intestinal contents, significantly decreasing colonizing C. difficile compared to controls. Together, these data suggest that PlyCD1-174 has potential as a novel therapeutic for clinical application against C. difficile infection, either alone or in combination with other preexisting treatments to improve their efficacy.

Ultrasound diagnosis of Clostridium difficile-associated diarrhea.

Clostridium difficile colitis is diagnosed using an immunoassay or polymerase chain reaction (PCR) assay for toxins A/B. Since ultrasound is frequently used as a screening test for hospitalized patients suffering from different abdominal morbidities, we searched for sonographic indicators of C. difficile infection (CDI). In a prospective and blinded case-control study, abdominal ultrasound was performed on hospitalized patients for whom stool samples were sent for C. difficile toxin immunoassay. All patients with positive toxin were included as the case group and patients with negative toxin comprised the control group. Sonographic parameters of both groups were compared. Demographic variables of the 67 patients in the toxin-positive group were similar to those of the 71 patients in the toxin-negative group. The sonographic parameters which were found to be associated with CDI included colonic wall thickening, appearing in 61 (91%) patients of the toxin-positive group versus 15 (21%) patients of the toxin-negative group (p < 0.001), and also internal ring (24 versus 0%, p < 0.001), external ring (15 versus 0%, p < 0.001), ascites (24 versus 10%, p < 0.001), and diminution of large bowel content (16 versus 1%, p < 0.001). Bowel wall thickening had high positive and negative predictive values (0.80 and 0.90, respectively), while the other features had only high positive predictive values (0.7-1.0). Abdominal ultrasound may contribute to the diagnosis of C. difficile colitis in patients developing hospital-acquired diarrhea.

Ferric Uptake Regulator Fur Control of Putative Iron Acquisition Systems in Clostridium difficile.

Clostridium difficile is an anaerobic, Gram-positive, spore-forming opportunistic pathogen and is the most common cause of hospital-acquired infectious diarrhea. Although iron acquisition in the host is a key to survival of bacterial pathogens, high levels of intracellular iron can increase oxidative damage. Therefore, expression of iron acquisition mechanisms is tightly controlled by transcriptional regulators. We identified a C. difficile homologue of the master bacterial iron regulator Fur. Using targetron mutagenesis, we generated a fur insertion mutant of C. difficile. To identify the genes regulated by Fur in C. difficile, we used microarray analysis to compare transcriptional differences between the fur mutant and the wild type when grown in high-iron medium. The fur mutant had increased expression of greater than 70 transcriptional units. Using quantitative reverse transcriptase PCR (qRT-PCR), we analyzed several of the Fur-regulated genes identified by the microarray and verified that they are both iron and Fur regulated in C. difficile. Among those Fur- and iron-repressed genes were C. difficile genes encoding 7 putative cation transport systems of different classes. We found that Fur was able to bind the DNA upstream of three Fur-repressed genes in electrophoretic mobility shift assays. We also demonstrate that expression of Fur-regulated putative iron acquisition systems was increased during C. difficile infection using the hamster model. Our data suggest that C. difficile expresses multiple iron transport mechanisms in response iron depletion in vitro and in vivo. Clostridium difficile is the most common cause of hospital-acquired infectious diarrhea and has been recently classified as an "urgent" antibiotic resistance threat by the CDC. To survive and cause disease, most bacterial pathogens must acquire the essential enzymatic cofactor iron. While import of adequate iron is essential for most bacterial growth, excess intracellular iron can lead to extensive oxidative damage. Thus, bacteria must regulate iron import to maintain iron homeostasis. We demonstrate here that C. difficile regulates expression of several putative iron acquisition systems using the transcriptional regulator Fur. These import mechanisms are induced under iron-limiting conditions in vitro and during C. difficile infection of the host. This suggests that during a C. difficile infection, iron availability is limited in vivo.

Epidemiology and mortality of Clostridium difficile infection: a 5-year retrospective laboratory-based study in a large teaching hospital in Northern Italy

Clostridium difficile represents the major infective causes of hospital-acquired infectious diarrhoea and one of the most common microorganisms responsible for health-care associated infection.

Prevalence of asymptomatic Clostridium difficile colonization in tertiary hospital patients in Australia

Despite the importance of C. difficile infection (CDI) as a cause of hospital-acquired diarrhea, few studies have investigated the prevalence of asymptomatic C. difficile colonization in a broad cross-section of the general hospital patient population over multiple years and seasons.

A chimeric protein comprising the glucosyltransferase and cysteine proteinase domains of toxin B and the receptor binding domain of toxin A induces protective immunity against Clostridium difficile infection in mice and hamsters

Clostridium difficile is the major cause of hospital-acquired infectious diarrhea and colitis in developed countries. The pathogenicity of C. difficile is mainly mediated by the release of 2 large potent exotoxins, toxin A (TcdA) and toxin B (TcdB), both of which require neutralization to prevent disease occurrence. We have generated a novel chimeric protein, designated mTcd138, comprised of the glucosyltransferase and cysteine proteinase domains of TcdB and the receptor binding domain of TcdA and expressed it in Bacillus megaterium. To ensure that mTcd138 is atoxic, 2 point mutations were introduced to the glucosyltransferase domain of TcdB, which essentially eliminates toxicity of mTcd138. Parenteral immunizations of mice and hamsters with mTcd138 induced protective antibodies to both toxins and provided protection against infection with the hyper-virulent C. difficile strain UK6.

Clostridium difficile infection in adult patients with acute myeloid leukemia: Incidence, recurrence, and outcomes.

e18020 Background: Clostridium difficile infection (CDI) is the most common cause of hospital-acquired diarrhea. Acute Myeloid Leukemia (AML) patients may have increased predisposition to CDI as we...

Identification of an epithelial cell receptor responsible for Clostridium difficile TcdB-induced cytotoxicity

Clostridium difficile is the leading cause of hospital-acquired diarrhea in the United States. The two main virulence factors of C. difficile are the large toxins, TcdA and TcdB, which enter colonic epithelial cells and cause fluid secretion, inflammation, and cell death. Using a gene-trap insertional mutagenesis screen, we identified poliovirus receptor-like 3 (PVRL3) as a cellular factor necessary for TcdB-mediated cytotoxicity. Disruption of PVRL3 expression by gene-trap mutagenesis, shRNA, or CRISPR/Cas9 mutagenesis resulted in resistance of cells to TcdB. Complementation of the gene-trap or CRISPR mutants with PVRL3 resulted in restoration of TcdB-mediated cell death. Purified PVRL3 ectodomain bound to TcdB by pull-down. Pretreatment of cells with a monoclonal antibody against PVRL3 or prebinding TcdB to PVRL3 ectodomain also inhibited cytotoxicity in cell culture. The receptor is highly expressed on the surface epithelium of the human colon and was observed to colocalize with TcdB in both an explant model and in tissue from a patient with pseudomembranous colitis. These data suggest PVRL3 is a physiologically relevant binding partner that can serve as a target for the prevention of TcdB-induced cytotoxicity in C. difficile infection.

Pseudomembranous colitis and toxic megacolon due to C. difficile in an inpatient hospitalized for home accident

Clostridium difficile infection (CDI) is the main cause of hospital-acquired diarrhea. It can result in symptoms ranging from moderate diarrhea to pseudomembranous colitis. Among the risk factors, there is antibiotic therapy, responsible for intestinal flora disruption.A 72-year-old man presented to the Emergency Room for a home accident, a fall, that resulted in a cranio-facial trauma and tibio-tarsal fracture. He was administered cefazolin. Then he underwent surgery and the antibiotic therapy was switched to teicoplanin + levofloxacin; three days after, he started having diarrhea and mild fever. Rifaximin was added. A further exacerbation prompted the replacement of antibiotic therapy with tazobactam-piperacillin and metronidazole. Owing to the detection in fecal examination of CDI signs, tazobactam-piperacillin were replaced with vancomicin. Due to the persistence of symptoms, the worsening of physical conditions and the onset of pseudomembranous colitis and toxic megacolon, fidaxomicin therapy was started, with symptom resolution in few days. A patient’s follow-up at five months post-treatment showed no CDI recurrence.

In vitro activity of surotomycin against contemporary clinical isolates of toxigenic Clostridium difficile strains obtained in Spain.

Clostridium difficile infection (CDI) is the leading cause of hospital-acquired diarrhoea in developed countries. Metronidazole and vancomycin are the mainstay of treatment, although they are associated with treatment failure and recurrence. Novel agents have emerged to address these shortcomings. We investigated the in vitro activity of a novel agent, surotomycin (formerly CB-183,315), and seven other antimicrobial agents against clinical C. difficile isolates. Antimicrobial susceptibility to surotomycin, fidaxomicin, metronidazole, vancomycin, clindamycin, rifaximin, moxifloxacin and tigecycline was determined for 100 contemporary clinical isolates of C. difficile collected in 2013. MICs were determined by agar dilution according to CLSI procedures. In addition, 10 strains with reduced susceptibility to metronidazole (n = 6) and vancomycin (n = 4) were also tested. Strains were PCR ribotyped. The MICs of surotomycin for the 100 isolates ranged from ≤0.06 to 2 mg/L, with a geometric mean (GM) of 0.31 mg/L and an MIC50/90 of 0.25/0.5 mg/L. The MIC range of surotomycin was 0.25-1 mg/L (GM = 0.45 mg/L) for isolates with reduced metronidazole susceptibility and 0.125-0.5 mg/L (GM = 0.25 mg/L) for isolates with reduced vancomycin susceptibility. The three most common ribotypes were 001 (31.0%), 014/020 (17.0%) and 078/126 (17.0%). Ribotype 014/020 exhibited the lowest MICs of surotomycin (GM = 0.22 mg/L); the highest MICs were for ribotype 078/126 (GM = 0.72 mg/L). Surotomycin exhibited potent in vitro activity against all the isolates tested, including those with elevated metronidazole and vancomycin MICs. The potential role of this agent in the treatment of CDI requires further clinical evaluation.

Toxin synthesis by Clostridium difficile is regulated through quorum signaling.

ABSTRACTClostridium difficile infection (CDI) is dramatically increasing as a cause of antibiotic- and hospital-associated diarrhea worldwide. C. difficile, a multidrug-resistant pathogen, flourishes in the colon after the gut microbiota has been altered by antibiotic therapy. Consequently, it produces toxins A and B that directly cause disease. Despite the enormous public health problem posed by this pathogen, the molecular mechanisms that regulate production of the toxins, which are directly responsible for disease, remained largely unknown until now. Here, we show that C. difficile toxin synthesis is regulated by an accessory gene regulator quorum-signaling system, which is mediated through a small (<1,000-Da) thiolactone that can be detected directly in stools of CDI patients. These findings provide direct evidence of the mechanism of regulation of C. difficile toxin synthesis and offer exciting new avenues both for rapid detection of C. difficile infection and development of quorum-signaling-based non-antibiotic therapies to combat this life-threatening emerging pathogen.

Clostridium difficile infection: a Serbian single-center experience.

Clostridium difficile infection (CDI) is the most common cause of hospital-acquired diarrhea. Severity of CDI is associated with advanced age and co-morbidities. The clinical spectrum varies from mild watery diarrhea to severe fulminant pseudomembranous colitis with complications. This study conducted over a six-year period (2008 to 2013) included 510 patients treated at the University Hospital for Infectious and Tropical Diseases in Belgrade, Serbia. In patients with a history of previous hospitalization and/or treatment with antimicrobial agents who developed diarrhea, the diagnosis was established with rapid tests for C. difficile toxin A and B and by stool culture for C. difficile (454 patients) or by endoscopic examination and histological analyses of the biopsy samples taken from the colonic mucosa (56 patients). The mean age of patients was 67.71±13.34 years. A total of 67.8% patients were older than 65 years. Over half (58.7%) of the patients were female. 93% had been previously hospitalized and/or had surgical interventions, during which they had been treated with antibiotics. In the clinical presentation spectrum, pseudomembranous colitis occurred in 51.0%. The mean duration of illness after the introduction of specific antibiotic therapy was 7.10 ± 4.88 days. Complications developed in 14 patients. The disease relapsed in 43 (8.4%). Thirty-two (6.3%) patients died, mostly due to co-morbidities. CDI is the most important cause of hospital-acquired diarrhea in Serbia. The disease mainly affects elderly patients with co-morbidities. The incidence of complications is low and prognosis is age dependent and related to pre-existing diseases.

Outcomes and Risk Factors Associated with Clostridium difficile Diarrhea in Hospitalized Adult Patients.

Background. The epidemiology of Clostridium difficile infection has changed over time. Therefore, it is essential to monitor the characteristics of patients at risk of infection and factors associated with poor prognosis. Objective. To evaluate factors associated with C. difficile infection and with poor prognosis in those with documented C. difficile colitis. Methods. A retrospective case-control study of 75 patients with documented C. difficile colitis and 75 controls with hospital-acquired diarrhea of other causes. Stepwise multiple logistic regression was used to identify factors associated with C. difficile infection among patients with hospital-acquired diarrhea. Results. Previous antibiotic treatment (odds ratio (OR), 13.3; 95% confidence interval (CI), 1.40–126.90), abdominal distension (OR, 3.85; 95% CI, 1.35–10.98), and fecal leukocytes (OR, 8.79; 95% CI, 1.41–54.61) are considered as predictors of C. difficile colitis; anorexia was negatively associated with C. difficile infection (OR, 0.15; 95% CI, 0.03–0.66). Enteral tube feeding was independently associated with a composite outcome that included in-hospital mortality, intensive care unit admission, and treatment failure (OR, 3.75; 95%CI, 1.24–11.29). Conclusions. Previous antibiotic use and presence of fecal leukocytes in patients with hospital-acquired diarrhea are associated with C. difficile colitis and enteral tube support with complications associated with C. difficile colitis.

Use of mCherry Red fluorescent protein for studies of protein localization and gene expression in Clostridium difficile.

Fluorescent proteins are powerful reporters in biology, but most require O2 for chromophore maturation, making them inherently difficult to use in anaerobic bacteria. Clostridium difficile, a strict anaerobe with a genomic GC content of only 29%, is the leading cause of hospital-acquired diarrhea in developed countries, and new methods for studying this pathogen are sorely needed. We recently demonstrated that a cyan fluorescent protein called CFPopt that has been codon optimized for production in low-GC bacteria can be used to study protein localization in C. difficile provided the cells are fixed prior to exposure to air. We describe here a codon-optimized variant of mCherry (mCherryOpt) that exhibits faster acquisition of fluorescence and a better signal-to-noise ratio than CFPopt. We utilized mCherryOpt to construct plasmids for studying protein localization (pRAN473) and gene expression (pDSW1728) in C. difficile. Plasmid pRAN473 is an mCherryOpt fusion vector with a tetracycline-inducible promoter. To document its biological utility, we demonstrated septal localization of two cell division proteins, MldA and ZapA. Plasmid pDSW1728 is designed for cloning a promoter of interest upstream of mCherryOpt. As proof of principle, we studied the expression of the pdaV operon, which is required for lysozyme resistance. In confirmation and extension of previous reports, we found that expression of the pdaV operon requires the alternative sigma factor σ(v) and that induction by lysozyme is dose dependent and uniform across the population of lysozyme-treated cells.

Incidence and Risk Factors Associated with Clostridium Difficile Infection in Cord Blood Transplant

▪Background:Clostridium difficile infection (CDI) is the leading cause of hospital-acquired diarrhea. The incidence of CDI in patients hospitalized for stem cell transplant (SCT) is much higher than in other inpatients, reaching between 12.5-30%. Antibiotic exposure, duration of hospitalization, and acute graft-versus-host disease (aGVHD) can contribute to the increased incidence of CDI. The incidence of CDI and risk factors associated with its development after cord blood transplant (CBT) have not been well-studied.Methods: Ninety-five patients who received CBT at Vanderbilt University Medical Center from 2002 to 2013 were retrospectively reviewed. CDI was diagnosed using a stool toxin assay prior to 2011; DNA testing was used after 2011. CBT patients with CDI were compared to patients without CDI.Results: Of 95 CBT patients, 34 (37.8%) developed CDI. Thirty day cumulative incidence of CDI was 37%. Comparative data on CDI incidence at our institution for general adult inpatients is being collected. Pre-transplant characteristics of patients are shown in Table 1 and transplant characteristics are shown in Table 2. There was no significant difference in incidence of aGVHD in patients with CDI (76.5%) and without CDI (59%). CDI was diagnosed in 41.6% (25/56) of patients with aGVHD who received systemic steroids and only in 23% (9/39) of patients with aGVHD who did not receive systemic steroids (P<0.05). Time (mean) to CDI (with death due to other causes as a competing risk) was shorter in patients receiving systemic steroids (80 days vs. 90 days, P<0.05). Among patients who received systemic steroids, CDI-infected patients had received higher dosages (mean 1.68 mg/kg vs. 1.28 mg/kg, P<0.05). There was no difference in incidence of CDI based on antibiotic exposure, type of antibiotic use, number of episodes of bacteremia, GI aGVHD, and recurrence of aGVHD (data not shown). Diagnostic modality (toxin assay vs. DNA testing) did not impact the CDI incidence rate. Using Cox-proportional hazards model, peak dose of steroids was an independent predictor of CDI (HR=2.42, 95% CI 1.02-4.01, p<0.05).Conclusions: Our study shows that CDI is an important infectious complication of CBT with an incidence of 37%. CDI patients were more likely to have received systemic steroids for aGVHD, and at higher dosages. The connections between CDI, steroids, and aGVHD need to be explored further. Strategies to prevent CDI in this high-risk group need to be developed.Table 1:Pre-transplant characteristics of patients with and without Clostridium difficile infection (CDI)CDI (N=34)No CDI (N=61)Age, y, mean (range)21 (3 mo-57 y)28 (6 mo-65 y)Gender, n (%)Female19 (55.9)29 (47.5)Male15 (44.1)32 (52.5)Race, n (%)African American9 (26.5)15 (24.6)Caucasian20 (58.0)37 (60.7)Hispanic3 (8.8)5 (8.2)Other2 (5.9)4 (6.5)Diagnosis, n (%)Acute leukemia23 (67.6)28 (45.8)Other leukemia0 (0)3 (4.9)Lymphoma5 (14.7)5 (8.2)Myeloid disorders3 (8.8)17 (27.9)Other3 (8.8)8 (13.1)Risk status, n (%)Low7 (20.6)19 (31.1)Intermediate12 (35.3)11 (18.0)High12 (35.3)27 (44.3)Table 2:Transplant characteristics of patients with and without Clostridium difficile infection (CDI)CDI (N=34)No CDI (N=61)Type of transplant, n (%)Single unit19 (55.9)29 (47.5)Double unit15 (44.1)32 (52.5)Cell dose, mean, range6.3 (0.7-27.3)5.7 (1.7-16.1)Recipient CMV seropositive, n (%)19 (55.9)28 (45.9)Total body irradiation, n (%)29 (85.3)51 (83.6)Conditioning intensity, n (%)Ablative24 (70.6)40 (65.6)Non- ablative10 (29.4)21 (34.4)Use of ATG, n (%)16 (47.1)24 (39.3)GVHD prophylaxis, n (%)Mycophenolate mofetil29 (85.3)55 (90.2)Calcineurin inhibitors34 (100)61 (100)Duration of neutropenia, days, mean (range)21.6 (7-37)23 (9-49)Acute GVHD, n (%)26 (76.5)36 (59.0)Type of acute GVHD, n (%)Skin13 (38.2)24 (39.3)GI19 (55.9)23 (37.7)Liver0 (0)3 (4.9)Systemic steroids received for acute GVHD*, n (%)25 (73.5)31 (50.8)Steroid dose received for acute GVHD*, mean in mg/kg1.681.28Survival, n (%)Alive16 (47.0)34 (55.8)DeceasedDisease6 (17.6)12 (19.7)Infection9 (26.5)11 (18.0)GVHD2 (5.9)1 (1.6)Other1 (2.9)3 (4.9)*indicates statistical significance with p<0.05 DisclosuresNo relevant conflicts of interest to declare.

Clostridium difficile infection: review with special interest in hematologic patients

Correspondence: Jarmo Oksi Department of Infectious Diseases, Division of Medicine, Turku University Hospital; Faculty of Medicine Turku University, Turku, Finland E-mail: jarmo.oksi@utu.fi SUMMARY Clostridium difficile infection (CDI) is a major cause of hospital-acquired diarrhea and is most commonly associated with changes in normal intestinal microbiota caused by administration of antibiotics. Immunocompromized patients are on greater risk for CDI and recurrence of it. In a few years considerable amount of information has been gathered in different studies among hematologic patients with CDI. In this review the changing epidemiology and risk factors of CDI as well as its recurrence are presented. The treatment of CDI has been changed while one new compound has been approved recently and fecal microbiota transplant has been proven the most efficacious treatment for relapsing CDI. More research is needed to study the observed relationship between CDI and graft-versus-host-disease. Clostridium difficile infection: review with special interest in hematologic patients

Missed diagnosis of Clostridium difficile infection; a prospective evaluation of unselected stool samples

Clostridium difficile infection (CDI) is the leading cause of hospital-acquired diarrhoea in developed countries, however a high proportion of CDI episodes go undiagnosed, either because physicians do not request identification of toxigenic C. difficile or microbiologists do not perform the appropriate tests. To investigate the clinical characteristics of patients with CDI within a non-selected population and to determine risk factors for clinical underdiagnosis. We conducted a prospective study in which systematic testing for toxigenic C. difficile on all diarrhoeic stool samples was performed regardless of the clinician's request. Patients aged >2 years positive for toxigenic C. difficile and diarrhoea were enrolled (Jan-June 2013) and monitored at least 2 months after their last episode. We identified 204 cases of CDI, of which three-quarters were healthcare-associated. Most cases were mild to moderate (83.8%), the recurrence rate was 16.2%, and CDI-related mortality was low (2.5%). A significant proportion (12.7%) of CDI cases would have been missed owing to lack of clinical suspicion. Community-acquired cases and young age were risk factors for clinical underdiagnosis. Our data support the introduction of a systematic search for toxigenic C. difficile in all diarrhoeic stools from inpatients and outpatients older than 2 years.