Ribotype 027 Clostridium difficile infections with measurable stool toxin have increased lactoferrin and are associated with a higher mortality

We evaluated clinical and diagnostic indicators of severe C. difficile infection (CDI) and their association with poor clinical outcome. A total of 210 patients positive according to PCR (toxin B: tcdB) were included, with patients having a median age of 62 years and a Charlson co-morbidity index (CI) score of 5. Ninety-one percent (n?=?191) were positive by toxigenic culture and 61 % (n?=?129) had stool toxin. Toxin-positive patients had significantly higher fecal lactoferrin (mean 316 μg/g versus 106 μg/g stool; p?<?0.0001). Forty percent of patients (n?=?85) were infected with ribotype 027 and significantly more of these patients had measurable stool toxin (79 % vs. 50 %; p?<?0.0001). The mean fecal lactoferrin was significantly higher for toxin-positive 027 CDI compared with the 027 toxin-negative group (317 vs 60 μg/g; p?=?0.0014). Ribotype 027 CDI with stool toxin showed a higher all-cause, 100-day mortality compared with non-027 with stool toxin (36 % vs 18 %; p?=?0.017). Logistic regression univariate analysis for odds ratio (OR) and p values revealed that age (OR?=?1.1), intensive care unit treatment (OR?=?2.7), CI (OR?=?1.2), 027 CDI (OR?=?2.1), white blood cell count (OR?=?1.0), albumin level (OR?=?0.1), and stool toxin-positive 027 CDI (OR?=?2.5) were significantly associated with 100-day mortality (p?<?0.05). In conclusion, CDI PCR-positive patients with 027 infection and stool toxin have increased lactoferrin and are at an increased risk of death.     

An outbreak of <Emphasis Type="Italic">Clostridium difficile</Emphasis> PCR ribotype 027 in Spain: risk factors for recurrence and a novel treatment strategy

An outbreak of Clostridium difficile infection (CDI) caused by ribotype 027 (B1/NAP1) began in our hospital in November 2014, and produced 141 episodes in the following months. The aim of this study is to describe this outbreak, assess risk factors for recurrence of CDI-027 and to analyze the implementation of a novel treatment strategy. This is a prospective study of all patients with CDI-027, from November 2014 to November 2015. The epidemiological data were collected daily for each patient. We compared clinical characteristics and treatment between patients with and without recurrence of CDI-027. Interestingly, liver cirrhosis was present in 22% of the patients, and most of them received prophylaxis for hepatic encephalopathy with rifaximin. Patients were also taking antimicrobial drugs (93.6%) and proton pump inhibitors (80.1%). Overall, 27 (23.5%) patients had a first recurrence of CDI-027. Liver cirrhosis increased the risk of recurrence (44.4% vs 14.8%). Patients treated with a prolonged oral vancomycin regimen vs the conventional regimen (oral metronidazole or 10 days of vancomycin) had fewer recurrences (8.6 versus 44.7% [p ≤ 0.01]; OR, 0.91; 95% CI, 0.028–0.294) and less attributable mortality (0% versus 7.1%; p = 0.058). We report an outbreak of CDI-027, mainly in patients with liver cirrhosis. Recurrence of CDI-027 was more common in those patients. A novel approach involving high-dose prolonged vancomycin taper as a first-line treatment, together with a bundle of outbreak measures, seemed to reduce the number of cases of CDI-027, recurrences, and attributable mortality. Nevertheless, this approach warrants further investigation.     

Elevated lactoferrin is associated with moderate to severe Clostridium difficile disease, stool toxin, and 027 infection

We evaluated blood and fecal biomarkers as indicators of severity in symptomatic patients with confirmed Clostridium difficile infection (CDI). Recruitment included patients with CDI based on clinical symptoms and supporting laboratory findings. Disease severity was defined by physician’s assessment and blood and fecal biomarkers were measured. Toxigenic culture done using spore enrichment and toxin B detected by tissue culture were done as confirmatory tests. Polymerase chain reaction (PCR) ribotyping was performed on each isolate. There were 98 patients recruited, with 85 (87 %) confirmed cases of toxigenic CDI (21 severe, 57 moderate, and seven mild), of which 68 (80 %) were also stool toxin-positive. Elevated lactoferrin (p?=?0.01), increased white blood cell (WBC) count (p?=?0.08), and low serum albumin (p?=?0.03) were all associated with the more severe cases of CDI. Ribotype 027 infection accounted for 71 % of severe cases (p?<?0.01) and patients with stool toxin had significantly higher lactoferrin levels and WBC counts (p?<?0.05). Our findings show that elevated fecal lactoferrin, along with increased WBC count and low serum albumin, were associated with more severe CDI. In addition, patients infected with ribotype 027 and those with stool toxin had significantly higher fecal lactoferrin and WBC counts.     

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.     

Use of highly discriminatory fingerprinting to analyze clusters of Clostridium difficile infection cases due to epidemic ribotype 027 strains

We compared multilocus variable-number tandem-repeat analysis (MLVA) and macrorestriction endonuclease analysis using pulsed-field gel electrophoresis (PFGE) to determine their utility to identify clusters of Clostridium difficile infection (CDI) among 91 isolates of PCR ribotype 027 (NAP1, for North American pulsed-field type 1) from nine hospitals (and 10 general practitioners associated with one institution) in England. We also examined whether mortality in CDI cases was associated with specific MLVA subtypes. PFGE discriminated between ribotype 027 strains at >98% similarity, identifying five pulsovars (I to V) of 1 to 53 isolates. MLVA was markedly more discriminatory, identifying 23 types of 1 to 15 isolates (>71% similarity). PFGE pulsovars I and IV contained 14 and 8 MLVA types, respectively. Twenty-one of twenty-three (91%) of MLVA types were specific to individual PFGE pulsovars. Four CDI clusters were identified in institution A by conventional epidemiological analysis. MLVA typing identified two enlarged and two additional clusters. Thirty of forty-four (68%) patients in institution A with CDI caused by ribotype 027 strains were assigned to seven distinct clusters by a combination of MLVA typing and epidemiological records. Of 33 patients, comprising 14 different MLVA types, nine (27%) died by day 30 (early deaths). Eight of nine (89%) were associated with PFGE type IV C. difficile ribotype 027. Five of nine early deaths were associated with MLVA type 16, which was the dominant type in this cohort (10/33 cases); 4 other distinct MLVA types accounted for the other early deaths. MLVA was far superior to PFGE for analyzing clusters of CDI both within and between institutions. Further study is needed to examine whether subtypes of C. difficile ribotype 027 affect outcome.     

Clostridium difficile isolates with increased sporulation: emergence of PCR ribotype 002 in Hong Kong

We identified a predominant clone of Clostridium difficile PCR ribotype 002, which was associated with an increased sporulation frequency. In 2009, 3,528 stool samples from 2,440 patients were tested for toxigenic C. difficile in a healthcare region in Hong Kong. A total of 345 toxigenic strains from 307 (13.3%) patients were found. Ribotype 002 was the predominant ribotype, which constituted 35 samples from 29 (9.4%) patients. The mean sporulation frequency of ribotype 002 was 20.2%, which was significantly higher than that of the 56 randomly selected ribotypes other than 002 as concurrent controls (3.7%, p?<?0.001). Patients carrying toxigenic ribotype 002 were more frequently admitted from an elderly home (p?=?0.01) and received more ??-lactam antibiotics in the preceding 3 months compared with the controls (p?=?0.04) . The identification of toxigenic ribotype 002 in 2009 was temporally related to a significant increase in both the incidence of toxigenic C. difficile from 0.53 to 0.95 per 1,000 admissions (p?<?0.001) and the rate of positive detection from 4.17% to 6.28% (p?<?0.001) between period 1 (2004?C2008) and period 2 (2009). This finding should alert both the physician and the infection control team to the establishment of and possible outbreaks by ribotype 002 in our hospitals, as in the case of ribotype 027.     

The ClosER study: results from a three-year pan-European longitudinal surveillance of antibiotic resistance among prevalent Clostridium difficile ribotypes, 2011–2014

ObjectivesUntil the introduction of fidaxomicin, antimicrobial treatment for Clostridium difficile infection (CDI) was limited to metronidazole and vancomycin. The changing epidemiology of CDI and the emergence of epidemic C. difficile PCR ribotype 027 necessitate continued surveillance to identify shifts in antibiotic susceptibility. ClosER, currently the largest pan-European epidemiological study of C. difficile ribotype distribution and antibiotic susceptibility, aimed to undertake antimicrobial resistance surveillance pre- and post-introduction of fidaxomicin.MethodsBetween July 2011 and July 2014, 39 sites across 22 European countries submitted 2830 C. difficile isolates for ribotyping, toxin testing and susceptibility testing to metronidazole, vancomycin, fidaxomicin, rifampicin, moxifloxacin, clindamycin, imipenem, chloramphenicol and tigecycline.ResultsRibotypes 027, 014, 001, 078, 020, 002, 126, 015 and 005 were most frequently isolated, and emergent ribotypes 198 and 356 were identified in Hungary and Italy, respectively. All isolates were susceptible to fidaxomicin, with scarce resistance to metronidazole (0.2%, 6/2694), vancomycin (0.1%, 2/2694) and tigecycline (0%). Rifampicin, moxifloxacin and clindamycin resistance was evident in multiple ribotypes. Lack of ribotype diversity correlated with greater antimicrobial resistance. Epidemic ribotypes (027/001) were associated with multiple antimicrobial resistance, and ribotypes 017, 018 and 356 with high-level resistance. Additional factors may also influence local ribotype prevalence.ConclusionsFidaxomicin susceptibility was retained post-introduction, and resistance to metronidazole and vancomycin was rare. Continued surveillance is needed, with more accurate classification and clarification of ribotype subtypes to further understand their role in the spread of resistance. Other factors may also influence changes in prevalence of C. difficile ribotypes with reduced antibiotic susceptibility.     

Host factors are more important in predicting recurrent Clostridium difficile infection than ribotype and use of antibiotics

ObjectiveA frequent complication of Clostridium difficile infection (CDI) is recurrent disease. The aim of this study was to determine whether early recurrence risk was higher after infection with ribotype 027 (outbreak strain) compared with infection with endemic strain types of C. difficile.MethodsConsecutive patients diagnosed with CDI between May 2013 and March 2014 were included (outbreak strain, and non-outbreak strains). Patients who developed recurrent CDI within 30 days after completion of CDI treatment, were compared with patients without a recurrence. Medical charts were reviewed for demographic and clinical characteristics. General practitioners were contacted to complete data about the occurrence of recurrent CDI, and the use of medication after hospital discharge.ResultsIn total, 135 patients were at risk for the development of recurrent CDI; 74 patients were infected by ribotype 027, and 61 patients by other ribotypes. Thirty-nine patients (29%) developed recurrent CDI within 30 days after completion of CDI treatment. In multivariable analysis, age ≥70 years (HR 3.05, 95% CI 1.54–6.03), and a duration of CDI treatment ≥11 days (HR 1.92, 95% CI 1.00–3.69) were clearly associated with recurrence; infection with ribotype 027 showed a HR of 1.72 (95% CI 0.88–3.33).ConclusionDuring this outbreak of C. difficile in a tertiary care centre, age and a prolonged duration of CDI therapy (which is most likely a marker of underlying disease severity) were the main risk factors for recurrent CDI. This points to host factors as more important predictors for recurrent CDI than strain type or antibiotic use.     

Risk factors for recurrence in patients with Clostridium difficile infection due to 027 and non-027 ribotypes

Objectives

Our objective was to evaluate factors associated with recurrence in patients with 027+ and 027– Clostridium difficile infection (CDI).

The undiagnosed cases of Clostridium difficile infection in a whole nation: where is the problem?

Underdiagnosis of Clostridium difficile infection (CDI) because of lack of clinical suspicion or the use of non-sensitive diagnostic techniques is a known problem whose real magnitude has not yet been quantified. In order to estimate the extent of this underdiagnosis, we performed C. difficile cultures on all unformed stool specimens sent—irrespective of the type of request—to a series of laboratories in Spain on a single day. The specimens were cultured, and isolates were characterized at a central reference laboratory. A total of 807 specimens from 730 patients aged ≥2 years were selected from 118 laboratories covering 75.4% of the Spanish population. The estimated rate of hospital-acquired CDI was 2.4 episodes per 1000 admissions or 3.8 episodes per 10 000 patient-days. Only half of the episodes occurred in patients hospitalized for >2 days. Two of every three episodes went undiagnosed or were misdiagnosed, owing to non-sensitive diagnostic tests (19.0%) or lack of clinical suspicion and request (47.6%; mostly young people or non-hospitalized patients). The main ribotypes were 014/020 (20.5%), 001 (18.2%), and 126/078 (18.2%). No ribotype 027 strains were detected. Strains were fully susceptible to metronidazole and vancomycin. CDI was underdiagnosed in diarrhoeic stools in a high proportion of episodes, owing to the use of non-sensitive techniques or lack of clinical suspicion, particularly in people aged <65 years or patients with community-acquired diarrhoea. C. difficile toxins should be routinely sought in unformed stools of any origin sent for microbiological diagnosis. The ribotype 027 clone has not yet disseminated in Spain.     

Oral teicoplanin versus oral vancomycin for the treatment of severe <Emphasis Type="Italic">Clostridium difficile</Emphasis> infection: a prospective observational study

The aim of this study was to compare clinical cure rate, recurrence rate and time to resolution of diarrhea in patients with severe and severe-complicated Clostridium difficile infection (CDI) treated with teicoplanin or vancomycin. This two-year prospective observational study included patients with first episode or first recurrence of CDI who had severe or severe-complicated CDI and were treated with teicoplanin or vancomycin. Primary outcomes of interest were clinical cure rate at discharge and recurrence rate after eight weeks follow up, and secondary outcomes were all-cause mortality and time to resolution of diarrhea. Among 287 study patients, 107 were treated with teicoplanin and 180 with vancomycin. The mean age of patients was 73.5?±?10.6 years. One hundred eighty six patients (64.8%) had prior CDI episode. Severe complicated disease was detected in 23/107 (21.5%) and 42/180 (23.3%) patients treated with teicoplanin and vancomycin, respectively. There was no statistically significant difference in time to resolution of diarrhea between two treatment arms (6.0?±?3.4 vs 6.2?±?3.1 days, p?=?0.672). Treatment with teicoplanin resulted in significantly higher clinical cure rate compared to vancomycin [90.7% vs 79.4%, p?=?0.013, odds ratio (OR) (95% confidence interval (CI)) 2.51 (1.19–5.28)]. Recurrence rates were significantly lower in patients treated with teicoplanin [9/97 (9.3%) vs 49/143 (34.3%), p?<?0.001, OR (95%CI) 0.20 (0.09–0.42)]. There was no statistically significant difference in overall mortality rate. Teicoplanin might be a good treatment option for patients with severe CDI. Patients treated with teicoplanin experienced remarkably lower recurrence rates compared to vancomycin-treated patients.     

Clostridium difficile as a cause of healthcare-associated diarrhoea among children in Auckland,New Zealand: clinical and molecular epidemiology

We aimed to determine the incidence of Clostridium difficile infection (CDI), the molecular epidemiology of circulating C. difficile strains and risk factors for CDI among hospitalised children in the Auckland region. A cross-sectional study was undertaken of hospitalised children <15 years of age in two hospitals investigated for healthcare-associated diarrhoea between November 2011 and June 2012. Stool specimens were analysed for the presence of C. difficile using a two-step testing algorithm including polymerase chain reaction (PCR). C. difficile was cultured and PCR ribotyping performed. Demographic data, illness characteristics and risk factors were compared between children with and without CDI. Non-duplicate stool specimens were collected from 320 children with a median age of 1.2 years (range 3 days to 15 years). Forty-six patients (14 %) tested met the definition for CDI. The overall incidence of CDI was 2.0 per 10,000 bed days. The percentage of positive tests among neonates was only 2.6 %. PCR ribotyping showed a range of strains, with ribotype 014 being the most common. Significant risk factors for CDI were treatment with proton pump inhibitors [risk ratio (RR) 1.74, 95 % confidence interval (CI) 1.09–5.59; p?=?0.002], presence of underlying malignancy (RR 2.71, 95 % CI 1.65–4.62; p?=?0.001), receiving chemotherapy (RR 2.70, 95 % CI 1.41–4.83; p?=?0.003) and exposure to antibiotics (RR 1.17, 95 % CI 0.99–1.17; p?=?0.03). C. difficile is an important cause of healthcare-associated diarrhoea in this paediatric population. The notion that neonatal populations will always have high rates of colonisation with C. difficile may not be correct. Several risk factors associated with CDI among adults were also found to be significant.     

Successful combat of an outbreak due to Clostridium difficile PCR ribotype 027 and recognition of specific risk factors

In the period April–September 2005, an outbreak of Clostridium difficile infection (CDI) due to PCR ribotype  027 occurred among 50 patients in a 341-bed community hospital in Harderwijk, The Netherlands. A retrospective case–control study was performed to identify risk factors specific for CDI, using a group of patients with CDI ( n  = 45), a group of randomly selected control patients without diarrhoea ( n  = 90), and a group of patients with non-infectious diarrhoea ( n  = 109). Risk factors for CDI and for non-CDI diarrhoea were identified using multiple logistic regression analysis. Independent risk factors for CDI were: age above 65 years (OR 2.6; 95% CI  1.0–5.7), duration of hospitalization (OR 1.04 per additional day; 95% CI  1.0–1.1), and antibiotic use (OR 12.5; 95% CI  3.2–48.1). Of the antibiotics used, cephalosporins and fluoroquinolones were identified as the major risk factors for development of CDI. The risk of developing CDI was particularly high in people receiving a combination of a cephalosporin and a fluoroquinolone (OR 57.5; 95% CI  6.8–483.6). The main factors affecting the risk of non-CDI diarrhoea were proton-pump inhibitors, immunosuppressive drugs, underlying digestive system disease, previous surgery, and gastric tube feeding. The outbreak ended only after implementation of restricted use of cephalosporins and a complete ban on fluoroquinolones, in addition to general hygienic measures, cohorting of patients in a separate ward, education of staff, and intensified environmental cleaning. The results of this study support the importance of appropriate antimicrobial stewardship in the control of hospital outbreaks with C. difficile PCR ribotype  027.     

Comparison of resistance against erythromycin and moxifloxacin, presence of binary toxin gene and PCR ribotypes in Clostridium difficile isolates from 1990 and 2008

Worldwide increasing rates of Clostridium difficile infections (CDI) with severe courses and outbreaks have been reported. This change in CDI epidemiology has on one hand been related to the spread of specific PCR ribotypes (e.g. 027) and on the other hand to increased prevalence of resistant C. difficile strains. This single-centre retrospective analysis characterized resistance against erythromycin and moxifloxacin, presence of binary toxin gene and ribotypes in 73 C. difficile isolates from 2008 in comparison with 23 isolates from 1990. In 1990, five different PCR ribotypes including 027 were identified. Resistance against erythromycin was detected in 3 of 23 (13%), while 20 of 23 (87%) from all isolates were susceptible to both erythromycin and moxifloxacin. In contrast, in 2008 a significantly increased prevalence of resistant C. difficile strains was observed, with 40 of 73 (54.8%) isolates being resistant against both antibiotics. Resistant C. difficile strains were mainly assigned to PCR ribotype 001. No isolates belonging to PCR ribotype 027 were identified. Our data provide evidence that the increase of resistant C. difficile strains belonging to PCR ribotype 001 rather than the spread of C. difficile PCR ribotype 027 contribute to the changing epidemiology of CDI.     

Impact of an intervention to control Clostridium difficile infection on hospital- and community-onset disease; an interrupted time series analysis

Strategies to reduce rates of Clostridium difficile infection (CDI) generally recommend isolation or cohorting of active cases and the reduced use of cephalosporin and quinolone antibiotics. Data supporting these recommendations come predominantly from the setting of epidemic disease caused by ribotype 027 strains. We introduced an initiative involving a restrictive antibiotic policy and a CDI-cohort ward at an acute, 820-bed teaching hospital where ribotype 027 strains account for only one quarter of all CDI cases. Antibiotic use and monthly CDI cases in the 12 months before and the 15 months after the initiative were compared using an interrupted time series analysis and segmented regression analysis. The initiative resulted in a reduced level of cephalosporin and quinolone use (22.0% and 38.7%, respectively, both p <0.001) and changes in the trends of antibiotic use such that cephalosporin use decreased by an additional 62.1 defined daily doses (DDD) per month (p <0.001) and antipseudomonal penicillin use increased by 20.7 DDD per month (p = 0.011). There were no significant changes in doxycycline or carbapenem use. Although the number of CDI cases each month was falling before the intervention, there was a significant increase in the rate of reduction after the intervention from 3% to 8% per month (0.92, 95% CI 0.86–0.99, p = 0.03). During the study period, there was no change in the proportion of cases having their onset in the community, nor in the proportion of ribotype 027 cases. CDI cohorting and restriction of cephalosporin and quinolone use are effective in reducing CDI cases in a setting where ribotype 027 is endemic.     

Clinical characteristics of Clostridium difficile infection in hospitalized patients with antibiotic-associated diarrhea in a university hospital in China

The purpose of this study was to identify clinical characteristics of Clostridium difficile infection (CDI) in patients with antibiotic-associated diarrhea (AAD). A prospective study was conducted among patients hospitalized in Fudan University Hospital Huashan from August 1, 2012 to July 31, 2013. Toxigenic C. difficile isolates were characterized by PCR ribotyping and multilocus sequence typing. AAD developed in 1.0 % (206/20437) of the antibiotic-treated hospitalized patients and toxigenic C. difficile was isolated from 30.6 % (63/206) of patients with AAD. The frequency of AAD was highest in the intensive care unit (10.7 %); however the proportion of CDI in AAD was highest in the Geriatric Unit (38 %). AAD ranged in severity from mild to moderate. One case with pseudomembranous colitis was identified. Use of carbapenems was found to significantly increase the risk of CDI (OR, 2.31; 95 % CI, 1.22–4.38; p?=?0.011). Patient demographics, presumed risk factors, clinical manifestations and laboratory findings revealed no significant difference between patients with CDI and non-C. difficile AAD. Over 90 % of the patients with CDI or non-C. difficile AAD were cured. Two patients had CDI recurrence. Ribotype H was the dominant (18.8 %) genotype, followed by ribotype 012 and ribotype 017. C. difficile plays a significant role in AAD in our setting in China. Because the severity of diarrhea ranges from mild to moderate, it is difficult for Chinese clinicians to identify CDI from AAD patients, therefore CDI should be included in the routine differential diagnoses for hospitalized patients presenting with AAD.     

Clostridium Difficile Infection after Allogeneic Hematopoietic Stem Cell Transplant: Strain Diversity and Outcomes Associated with NAP1/027

Allogeneic hematopoietic stem cell transplantation (HSCT) recipients are at high risk for developing Clostridium difficile infection (CDI). We studied the incidence, risk factors, NAP1/027 prevalence, and clinical outcomes, including acute lower gastrointestinal graft-versus-host disease (GI GVHD), associated with early CDI in this population. A retrospective review was conducted of patients who underwent allogeneic HSCT at Memorial Sloan Kettering Cancer Center from January 1, 2005 to September 30, 2010. Early CDI was defined as infection occurring from day −10 to day +40 from stem cell infusion. Among 793 patients who received allogeneic HSCTs, early CDI occurred in 11.9%; 56% cases were between day −5 and day +5. Overall incidence was 25.2 cases/10,000 at-risk days. There was a high prevalence of NAP1/027 strains during peak incidence (61% in 2008). NAP1/027 was the most common strain in both adult and pediatric cases (24% and 23%, respectively). CDI was clinically mild, including those due to NAP1/027. Metronidazole was the primary treatment for 91 of 94 patients, 7 of 8 cases refractory to metronidazole had no response to vancomycin, and none was due to NAP1/027. Relapse of CDI was common (31%). The cumulative incidence of GI GVHD in patients with and without early CDI was 6.8% and 8%, respectively (P = .5). Most cases of CDI occurred during conditioning or immediately after transplant. Despite high prevalence of NAP1/027, we found only mild disease. Most patients were treated successfully with metronidazole, irrespective of NAP1/027 status. There was no significant association between early CDI and subsequent development of GI GVHD. This study demonstrates the high incidence of CDI early after allogeneic HSCT with wide diversity among infecting strains. Despite the high prevalence of NAP1/027, the disease is mild but relapses are common. No association was found between CDI and subsequent development of GI GVHD.     

Epidemiology of Clostridium difficile-associated disease at University Hospital Basel including molecular characterisation of the isolates 2006–2007

A prospective study was conducted during a one-year period between 2006 and 2007 to describe the epidemiology of Clostridium difficile-associated disease (CDAD) at University Hospital Basel, Switzerland (UHBS) and to determine phenotypic and genotypic features of C. difficile strains isolated at the Microbiology Laboratory UHBS including strains from regional non-university hospitals. We prospectively identified 78 CDAD cases at UHBS with an incidence of 2.65/1,000 hospitalised patients or 2.3/10,000 patient-days. Sixteen patients (20.5%) were infected with clindamycin-resistant strains of PCR-ribotype 027 during an outbreak at the geriatric hospital. Among 124 single-patient isolates, 28 (22.6%) were resistant to moxifloxacin and 34 (27.4%) were resistant to clindamycin, but all remained susceptible to metronidazole and vancomycin. Of 102 toxigenic isolates, 19 (18.7%) had an 18-bp deletion in the tcdC gene, eight (7.8%) a 39-bp deletion, and one (1.0%) a 54-bp deletion. Genes for binary toxin were present in 27 (21.8%). PCR-ribotype 027 was associated with older age (median age 83.5 vs. 65.5 years, p < 0.0001) and longer duration of hospitalisation before onset of disease (median 15.5 vs. 9 days, p = 0.014) with a trend towards higher crude mortality, more severe disease, and previous use of macrolides compared to ribotype non-027. Overall, severe disease correlated with use of a nasogastric tube and surprisingly shorter duration of hospitalisation before onset of disease. Today, laboratory-based and epidemiological surveillance systems are required to monitor CDAD cases and emergence of new epidemic strains.     

The First Case of Antibiotic-associated Colitis by Clostridium difficile PCR Ribotype 027 in Korea

Clostridium difficile (C. difficile) is a common causative agent of pseudomembranous colitis (PMC). C. difficile-associated diarrhea (CDAD) ranges from mild diarrhea to life threatening PMC. Recently, a highly virulent strain of C. difficile polymerase chain reaction ribotype 027 was found in North America, Europe, and Japan. A 52-yr-old woman with anti-tuberculosis medication and neurogenic bladder due to traffic accident experienced five episodes of C. difficile PMC after taking antibiotics for pneumonia along with septic shock and acute renal failure. She was readmitted to the intensive care unit and treated with oral vancomycin with refractory of oral metronidazole, inotropics and probiotics for over 60 days. C. difficile isolated both at the first and the last admission was identified as C. difficile ribotype 027 by ribotyping, toxinotyping, and tcdC gene sequencing, which turned out the same pathogen as the epidemic hypervirulent B1/NAP1 strain. This is the first case of C. difficile PCR ribotype 027 in Korea. After discharge, she was maintained on probiotics and rifaximin for 3 weeks. She had no relapse for 6 months.