Impact of malignancy on <Emphasis Type="Italic">Clostridium difficile</Emphasis> infection

Purpose

The purpose of this study was to investigate the impact of malignancy and chemotherapy on the clinical and microbiological characteristics of Clostridium difficile infections (CDI).

Methods

CDI patients with a history of malignancy within 5 years were defined as the cancer group. The characteristics of the patients were compared according to the presence of malignancy.

Results

Of 580 patients with CDI, 159 (27.4 %) belonged to the cancer group and 421 (72.6 %) to the non-cancer group. More of the patients in the cancer group than those in the non-cancer group had been hospitalized within the prior 2 months (P?<?0.001). Leukocytosis was more common in the non-cancer group (P?=?0.034), while infection by PCR ribotype 017 strains was more common in the cancer group, with marginal significance (P?=?0.07). Recurrence was more frequent in the cancer group (20.4 % vs. 9.5 %, P =0.005) and cancer was an independent risk factor for recurrence of CDI (OR?=?2.66, 95 % CI 1.34-5.29, P =0.005). Age also contributed to the recurrence of CDI (OR?=?1.03, 95 % CI 1.00-1.06, P =0.026).

Conclusions

Malignancy and age are independent risk factors for recurrence of CDI. Cancer patients require careful observation for recurrence after treatment of CDI.

     

Community-acquired <Emphasis Type="Italic">Clostridium difficile</Emphasis> infection in Serbian pediatric population

Carriage of Clostridium (C.) difficile in the intestinum of children, as well as its role in the disease (diarrhea) onset, is still controversial. The aim of this study is to investigate the community-acquired Clostridium difficile infection (CA-CDI) in Serbian pediatric population and to describe the basic clinical characteristics and risk factors for CA-CDI occurrence in Serbian pediatric population. The data obtained from 63 Serbian pediatric patients with CA-CDI and from control group of 126 children with community-acquired diarrhea, whose stool specimens were negative for C. difficile and toxins A/B, were mutually compared. In the current work, we found that children with CA-CDI display a significantly less severe disease clinical presentation than children with diarrheas of other origin. Lethal outcome was noted in two cases, but in children with severe underlying diseases (Crohn’s disease and leukemia). By using the multivariate statistical regression model, the following statistically significant risk factors for community-acquired C. difficile-associated diarrhea development were determined: previous application of laxatives (OR?=?0.199, CI 0.55–0.79, p?=?0.015), general antibiotic use during the previous 2 months (OR?=?0.05, CI 0.02–0.17, p?<?0.001), and specifically the use of penicillins (OR?=?0.112, CI 0.04–0.31, p?<?0.0001) and cephalosporins (OR?=?0.16, CI 40.06–0.44, p?<?0.0001). Antibiotics from the groups of cephalosporins and penicillins were found to be the most important independent risk factors. Laxative application plays a significant role in the community-acquired Clostridium difficile infections in children, with mechanisms that are not completely understood.     

Outcomes of <Emphasis Type="Italic">Clostridium difficile</Emphasis>-suspected diarrhea in a French university hospital

Clostridium difficile infection (CDI) produces a variety of clinical presentations ranging from mild diarrhea to severe infection with fulminant colitis, septic shock, and death. CDI puts a heavy burden on healthcare systems due to increased morbidity and mortality, and higher costs. We evaluated the clinical impact of CDI in terms of complications and mortality in a French university hospital compared with patients with diarrhea unrelated to CDI. A 3-year prospective, observational, cohort study was conducted in a French university hospital. Inpatients aged 18 years or older with CDI-suspected diarrhea were eligible to participate in the study and were followed for up to 60 days after CDI testing. Among the 945 patients with diarrhea included, 233 had confirmed CDI. Overall, 106 patients (11.2%) developed at least one of the following complications: colectomy, colitis, ileitis/rectitis, ileus, intestinal perforation, megacolon, multiorgan failure, pancolitis, peritonitis, pseudomembranous colitis, renal failure, and sepsis/septic shock. The complication rate was significantly higher in patients with diarrhea related to C. difficile than in non-CDI patients (26.6% vs 6.2%, P?<?0.001). At day 60, 137 (14.5%) patients had died, with 37 deaths among the CDI group (15.9%). Death was attributable to CDI in 15 patients (6.4%). Complications are more frequent among CDI cases than in patients with diarrhea not related to C. difficile. Assessment of CDI is necessary to ensure allocation of sufficient resources to CDI prevention.     

Fecal calprotectin concentrations in cancer patients with <Emphasis Type="Italic">Clostridium difficile</Emphasis> infection

Fecal calprotectin (fCPT) has been used as a surrogate marker for assessment of intestinal inflammation. We explore the utility of fCPT values as a diagnostic aid in cancer patients with suspected Clostridium difficile infection (CDI). A total of 232 stool specimens submitted for GeneXpert C. difficile PCR testing were included in the study. All specimens were tested for fCPT and toxin/GDH antigens. Clinical severity of CDI cases was determined by the IDSA/SHEA criteria. Significant differences of median fCPT values between CDI (n?=?117, Median 183.6 μg/g) and non-CDI (n?=?115, 145.6 μg/g, p?=?0.006) patients were seen. In CDI patents, significantly lower fCPT values were found in patients with mild to moderate (n?=?95, 182.1 μg/g) than those with severe and severe to complicated (n?=?22, 218.5 μg/g, p?=?0.014) scores, and among those that were toxin positive (n?=?24, 200.2 μg/g) vs. toxin negative (n?=?86, 182.8 μg/g, p?=?0.044). Despite this overall trend, wide variations in fCPT values were found in all categories examined. A logistic regression analysis revealed that the fCPT values correlated independently with the severity of clinical manifestations (OR?=?2.021, 95%CI?=?1.132–3.608); however, it did not correlate with other clinical outcomes. Our study findings show that high fecal calprotectin levels correlate with toxin-positive and clinically severe CDI; however, wide variations in individual measurements preclude establishment of reliable cut-offs for routine diagnostic use in cancer patients.     

Molecular-based diagnosis of <Emphasis Type="Italic">Clostridium difficile</Emphasis> infection is associated with reduced mortality

Polymerase chain reaction (PCR) for the diagnosis of Clostridium difficile infection (CDI) might result in overdiagnosis. The clinical outcomes of symptomatic CDI patients diagnosed by PCR remain uncertain. We aimed to determine whether patients whose diagnosis of CDI was based on PCR had different characteristics and clinical outcomes than those diagnosed by toxin immunoassay. Consecutive CDI patients, hospitalized at Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel, between January 2013 and January 2016, were identified retrospectively and included in the study. Diagnosis of CDI was based on PCR or diagnosis by immunoassay for C. difficile toxin. The main outcome was 30- and 90-day all-cause mortality. The PCR group included 165 patients and the immunoassay group included 157 patients. In comparison to the immunoassay group, patients in the PCR group were more likely to be younger, to be independent, to undergo previous abdominal surgery, and to use laxatives. The 30-day mortality rate in the PCR group was significantly lower than that in the immunoassay group, 29/165 (18%) vs 49/157 (31%), respectively; p?=?0.028. On multivariate analysis, PCR diagnosis was associated with reduced mortality, OR 0.48 (95% CI 0.26–0.88). PCR-based diagnosis of CDI is associated with reduced all-cause mortality rates. Further studies are needed to determine the management of patients with discrepant immunoassay and PCR diagnosis of CDI.     

Binary toxin and its clinical importance in <Emphasis Type="Italic">Clostridium difficile</Emphasis> infection,Belgium

Binary toxin-producing Clostridium difficile strains such as ribotypes 027 and 078 have been associated with increased Clostridium difficile infection (CDI) severity. Our objective was to investigate the association between presence of the binary toxin gene and CDI severity and recurrence. We performed a laboratory-based retrospective study including patients between January 2013 and March 2015 whose fecal samples were analyzed by polymerase chain reaction (PCR) for the presence of the genes for toxin B and binary toxin and a deletion in the tcdC gene, specific for ribotype 027. Clinical and epidemiological characteristics were compared between 33 binary toxin-positive CDI patients and 33 binary toxin-negative CDI patients. Subsequently, the characteristics of 66 CDI patients were compared to those of 66 diarrhea patients who were carriers of non-toxigenic C. difficile strains. Fifty-nine of 1034 (5.7 %) fecal samples analyzed by PCR were binary toxin-positive, belonging to 33 different patients. No samples were positive for ribotype 027. Binary toxin-positive CDI patients did not differ from binary toxin-negative CDI patients in terms of disease recurrence, morbidity, or mortality, except for a higher peripheral leukocytosis in the binary toxin-positive group (16.30?×?10⁹/L vs. 11.65?×?10⁹/L; p?=?0.02). The second part of our study showed that CDI patients had more severe disease, but not a higher 30-day mortality rate than diarrhea patients with a non-toxicogenic C. difficile strain. In our setting with a low prevalence of ribotype 027, the presence of the binary toxin gene is not associated with poor outcome.     

First recurrence of <Emphasis Type="Italic">Clostridium difficile</Emphasis> infection: clinical relevance,risk factors,and prognosis

Therapy for recurrent Clostridium difficile-associated diarrhea (CDAD) is challenging. We evaluated the frequency, associated risk factors, and prognosis of first CDAD recurrences. Prospective cohort study of all consecutive cases of primary CDAD diagnosed in a university hospital from January 2006 to June 2013. Recurrent infection was defined as reappearance of symptoms within 8 weeks of the primary diagnosis, provided that CDAD symptoms had previously resolved and a new toxin test was positive. Predictors of a first episode of recurrent CDAD were determined by logistic regression analysis. In total, 502 patients (51.6 % men) with a mean age of 62.3 years (SD 18.5) had CDAD; 379 (76 %) were cured, 61 (12 %) had a first recurrence, 52 (10 %) died within 30 days of the CDAD diagnosis, nine (2 %) required colectomy, and one was lost to follow-up. Among the 61 patients with a first recurrence, 36 (59.3 %) were cured, 15 (23.7 %) had a second recurrence, nine (15.3 %) died, and one (1.7 %) required colectomy. On multivariate analysis, age older than 65 years (OR 2.04; 95 % CI, 1.14-3.68; P?<?0.02) and enteral nutrition (OR, 3.62; 95%CI, 1.66-7.87; P?<?0.01) were predictors of a first recurrence. A risk score was developed for first CDAD recurrence using the predictive factors and selected biological variables. In our CDAD cohort, 12 % of patients had a first recurrence of this disease, in which the prognosis was less favorable than that of the primary episode, as it heralded a higher risk of additional recurrences. Patient age and enteral nutrition were predictors of a first recurrence.     

<Emphasis Type="Italic">Clostridium difficile</Emphasis>-Associated Diarrhoea After Internal Fixation of Intertrochanteric Femoral Fractures

The aim of the study presented here was to record the incidence and outcome of Clostridium difficile-associated diarrhoea in patients undergoing surgery for intertrochanteric femoral fractures. Between January 2000 and June 2001, a total of 239 patients who underwent surgery after sustaining an intertrochanteric femoral fracture were included in the study. Seventeen patients developed Clostridium difficile-associated diarrhoea (incidence risk, 7.1%), and six patients died after developing the condition (case fatality rate, 35%). Thus, Clostridium difficile-associated diarrhoea was found to cause significant morbidity and mortality after surgery for intertrochanteric femoral fractures, and antibiotics should be used judiciously in this group of patients.     

Cercarial shedding from <Emphasis Type="Italic">Galba</Emphasis><Emphasis Type="Italic">truncatula</Emphasis> infected with <Emphasis Type="Italic">Fasciola</Emphasis><Emphasis Type="Italic">gigantica</Emphasis> of distinct geographic origins

Galba truncatula snails were experimentally infected with either of two different isolates of Fasciola gigantica, originating from Egypt or China, to determine the influence of these isolates on the characteristics of snail infections. The survival rates of G. truncatula on day 30 post-exposure were 90.0% and 60.2% in the Egyptian and Chinese groups, respectively. The frequency of cercaria-shedding snails within the Egyptian group was 79.8%, whereas in the Chinese group it was 22.4%. The parasite origin had a significant effect on the durations of the prepatent and patent periods. The mean number of cercariae shed from the Egyptian group was significantly greater than that shed from the Chinese group (a mean of 275.5 per cercaria-shedding snail compared with 29.0). These results could be explained by the fact that G. truncatula might be a natural intermediate host for F. gigantica in Egypt, and the greater adaptability of the Egyptian miracidia of F. gigantica to unusual snail hosts. These results demonstrate the influence of the geographic origin of the parasite on the success of trematodes infecting snails.     

Cysteine proteinases from promastigotes of <Emphasis Type="Italic">Leishmania</Emphasis> (<Emphasis Type="Italic">Viannia</Emphasis>) <Emphasis Type="Italic">braziliensis</Emphasis>

Leishmania (Viannia) braziliensis is the major causative agent of American tegumentary leishmaniasis, a disease that has a wide geographical distribution and is a severe public health problem. The cysteine proteinase B (CPB) from Leishmania spp. represents an important virulence factor. In this study, we characterized and localized cysteine proteinases in L. (V.) braziliensis promastigotes. By a combination of triton X-114 extraction, concanavalin A-affinity, and ion exchange chromatographies, we obtained an enriched fraction of hydrophobic proteins rich in mannose residues. This fraction contained two proteinases of 63 and 43 kDa, which were recognized by a CPB antiserum, and were partially sensitive to E-64 in enzymatic assays with the peptide Glu-Phe-Leu. In confocal microscopy, the CPB homologues localized in the peripheral region of the parasite. This data together with direct agglutination and flow cytometry assays suggest a surface localization of the CPB homologues. The incubation of intact promastigotes with phospholipase C reduced the number of CPB-positive cells, while anti-cross-reacting determinant and anti-CPB antisera recognized two polypeptides (63 and 43 kDa) derived from phospholipase C treatment, suggesting that some CPB isoforms may be glycosylphosphatidylinositol-anchored. Collectively, our results suggest the presence of CPB homologues in L. braziliensis surface and highlight the need for further studies on L. braziliensis cysteine proteinases, which require enrichment methods for enzymatic detection.     

Prognosis of <Emphasis Type="Italic">Clostridium difficile</Emphasis> infection in adult oncohaematological patients: experience from a large prospective observational study

The aim of the study is to evaluate demographics, epidemiology, clinical characteristics, treatment and outcomes of Clostridium difficile infection (CDI) in patients with and without concurrent cancer. This is a prospective cohort study of consecutive primary CDI episodes in adults (January 2006–December 2016). CDI was diagnosed on the presence of diarrhoea and positive stool testing for toxigenic C. difficile. Univariate analysis assessed differences between cancer and non-cancer patients. Risk factors of all-cause 30-day mortality were determinate using the logistic multivariable procedure. In total, 787 CDI episodes were recorded, 191 in cancer patients (median age 64, IQR 50–73). Of these, 120 (63%) had solid and 71 (37%) haematological malignancies (24 received a stem cell transplant). At the CDI diagnosis, 158 (82.7%) cancer patients had prior antibiotics and 150 (78.5%) were receiving proton pump inhibitors. Fifty-seven (80.3%) patients with haematological and 52 (43.3%) with solid malignancies were under chemotherapy at diagnosis; 25 (35.2%) with haematological and 11 (9.2%) with solid malignancies had an absolute neutrophil count <?1000/mm³. Overall, 30-day mortality was higher in cancer patients than in those without (19.2 vs. 8.6% respectively, p?<?0.001); recurrence rates did not vary significantly (11.1 vs. 11%, p?=?0.936). By type of neoplasm, 30-day mortality was higher in patients with haematological malignancies and solid tumours than in patients without cancer (respectively, 25.4 vs. 8.6%; p?<?0.001 and 15 vs. 8.6%; p?<?0.001). Our results suggest that the prognosis of CDI (30-day mortality) is poorer in patients with cancer than in those without although percentages of recurrent infection are similar in these two patient populations.     

Redescription of <Emphasis Type="Italic">Lemuricola</Emphasis> (<Emphasis Type="Italic">Madoxyuris</Emphasis>) <Emphasis Type="Italic">bauchoti</Emphasis> (Nematoda,Oxyuridae) from <Emphasis Type="Italic">Lemur catta</Emphasis> in Madagascar

Lemuricola (Madoxyuris) bauchoti Chabaud, Brygoo et Petter, 1965 is redescribed from material collected from the ring-tailed lemur, Lemur catta, from the Beza Mahafaly Special Reserve in Madagascar using the scanning electron microscope. This is a new host record and the first oxyurid reported from the ring-tailed lemur. Previously, records of each species of the subgenus Madoxyuris have been restricted to a single host species, but the close relationship between these nematodes and their Strepsirrhini hosts will only be proven when additional records fill in the gaps in their distribution.     

<Emphasis Type="Italic">P</Emphasis>. <Emphasis Type="Italic">aeruginosa</Emphasis> Biofilms in CF Infection

Pseudomonas aeruginosa is an opportunistic pathogen of immunocompromised hosts. In cystic fibrosis (CF), P. aeruginosa causes acute and chronic lung infections that result in significant morbidity and mortality. P. aeruginosa possesses several traits that contribute to its ability to colonize and persist in acute and chronic infections. These include high resistance to antimicrobials, ability to form biofilms, plethora of virulence products, and metabolic versatility. In P. aeruginosa, a cell-to-cell communication process termed quorum sensing (QS) regulates many of these factors that contribute to its pathogenesis. Recent evidence suggests that the CF lung environment presents a specialized niche for P. aeruginosa. The relationship of P. aeruginosa QS, biofilm formation, and the CF lung environment is discussed.     

Functional polymorphisms in <Emphasis Type="Italic">XRCC</Emphasis>-<Emphasis Type="Italic">1</Emphasis> and <Emphasis Type="Italic">APE</Emphasis>-<Emphasis Type="Italic">1</Emphasis> contribute to increased apoptosis and risk of ulcerative colitis

Objective  

The present study was designed to investigate the role of X-ray cross-complementing group 1 (XRCC1) and apurinic/apyrimidinic endonuclease 1 (APE1) polymorphisms in apoptosis and the risk of ulcerative colitis (UC).     

Antimicrobial effects of Manuka honey on in vitro biofilm formation by <Emphasis Type="Italic">Clostridium difficile</Emphasis>

Clostridium difficile is the cause of the nosocomial C. difficile infection (CDI). The conventional antibiotics used in CDI therapy are often unsuccessful, and recurrent infections may occur. Biofilm formation by C. difficile is associated with chronic or recurrent infections; biofilms may contribute to virulence and impaired antimicrobial efficacy. Manuka honey, derived from the Manuka tree (Leptospermum scoparium), is known to exhibit antimicrobial properties that are associated with its significant content of methylglyoxal, a natural antibiotic. The aim of the present study was to determine the antimicrobial effect of Manuka honey on clinical C. difficile strains belonging to four prominent polymerase chain reaction (PCR) ribotypes (RTs) (RT017, RT023, RT027 and RT046) and on their biofilm formation in vitro. Minimal inhibitory and bactericidal concentrations (MICs and MBCs, respectively) were determined using the broth dilution method. The biomass of the biofilm and the clearance of C. difficile biofilms by Manuka honey were determined using the crystal violet staining method. The MIC and MBC of Manuka honey for C. difficile strains were equal at 6.25% (v/v). PCR RT027 strains produced more biofilm in vitro than the other examined strains. Manuka honey effectively inhibited biofilm formation by C. difficile strains of different PCR RTs.