Abstract The disease spectrum caused by Clostridium difficile infection ranges from antibiotic-associated diarrhoea to life-threatening clinical manifestations such as pseudomembranous colitis. C. ...difficile infection is precipitated by antimicrobial therapy that causes a disruption of the normal colonic microbiota, predisposing to C. difficile intestinal colonisation. The pathogenicity of C. difficile is mediated by two exotoxins, TcdA and TcdB, both of which damage the human colonic mucosa and are potent cytotoxic enzymes. C. difficile must first be implanted in the gut and attach to epithelial cells, which are protected by a layer of dense mucus. Confirmed and putative accessory virulence factors that could play a role in adherence and intestinal colonisation have been identified and include proteolytic enzymes and adhesins. Recently, the epidemiology of C. difficile infection has radically changed and an increased incidence is associated with outbreaks in North America and Europe. Several reports suggest that disease severity is increasing to include sepsis syndrome and toxin megacolon. Elderly, debilitated patients in hospitals and nursing homes are particularly vulnerable. A hypervirulent, epidemic strain has been associated with the changing epidemiology and severity of disease. Here, we review the characteristics of the epidemic NAP1, PCR ribotype 027 C. difficile strain that could explain its hypervirulence and epidemic spread.
Currently, contact precautions are recommended for patients colonized or infected with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE). Recent studies have challenged this ...strategy. This study aimed to assess the rate of ESBL-PE faecal carriage among hospitalized patients according to type of hospital ward, and to identify risk factors associated with carriage.
A point prevalence study was conducted in five different types of hospital ward medical, surgical, intensive care unit (ICU), after care and rehabilitation, and geriatric in eight French hospitals. All patients included in the study provided a fresh stool sample.
In total, 554 patients were included in the study, with a median age of 73 years (range 60–82 years). The overall faecal carriage rate of ESBL-PE was 17.7%. The most frequently encountered species among ESBL-PE was Escherichia coli (71.4%), followed by Klebsiella pneumoniae (14.3%). Risk factors associated with ESBL-PE faecal carriage on univariate analysis were: living in the Paris region (P<0.01) and hospitalization on a geriatric ward (P<0.01). Interestingly, the cumulative duration of hospital stay before screening was not associated with a significantly higher prevalence of ESBL-PE carriage, regardless of ward type. The ESBL-PE colonization rate was much higher for patients hospitalized on geriatric wards (28.1%) and ICUs (21.7%) compared with those for patients hospitalized on surgical wards (14.8%), medical wards (12.8%) or aftercare and rehabilitation (11.2%).
The overall prevalence of ESBL-PE faecal carriage was 17.7%, with only 21% of patients identified previously as carriers. The delay between admission and screening was not associated with an increase in ESBL-PE faecal carriage.
Purpose
To analyze trends in incidence and mortality of candidemia in intensive care units (ICUs) vs. non-ICU hospitalized patients and to determine risk factors for infection by specific species and ...for death.
Methods
Active hospital-based surveillance program of incident episodes of candidemia due to common species in 24 tertiary care hospitals in the Paris area, France between October 2002 and September 2010.
Results
Among 2,507 adult cases included, 2,571
Candida
isolates were collected and species were
C. albicans
(56 %),
C. glabrata
(18.6 %),
C. parapsilosis
(11.5 %),
C. tropicalis
(9.3 %),
C. krusei
(2.9 %), and
C. kefyr
(1.8 %). Candidemia occurred in ICU in 1,206 patients (48.1 %). When comparing ICU vs. non-ICU patients, the former had significantly more frequent surgery during the past 30 days, were more often preexposed to fluconazole and treated with echinocandin, and were less frequently infected with
C. parapsilosis
. Risk factors and age remained unchanged during the study period. A significant increased incidence in the overall population and ICU was found. The odds of being infected with a given species in ICU was influenced by risk factors and preexposure to fluconazole and caspofungin. Echinocandins initial therapy increased over time in ICU (4.6 % first year of study, to 48.5 % last year of study,
p
< 0.0001). ICU patients had a higher day-30 death rate than non-ICU patients (odds ratio OR 2.12; 95 % confidence interval CI 1.66–2.72;
p
< 0.0001). The day-30 and early (<day 8) death rates increased over time in ICU (from 41.5 % the first to 56.9 % the last year of study (
p
= 0.001) and 28.7–38.8 % (
p
= 0.0292), respectively). Independent risk factors for day-30 death in ICU were age, arterial catheter,
Candida
species, preexposure to caspofungin, and lack of antifungal therapy at the time of blood cultures results (
p
< 0.05).
Conclusions
The availability of new antifungals and the publication of numerous guidelines did not prevent an increase of candidemia and death in ICU patients in the Paris area.
Since echinocandins are recommended as first line therapy for invasive candidiasis, detection of resistance, mainly due to alteration in FKS protein, is of main interest. EUCAST AFST recommends ...testing both MIC of anidulafungin and micafungin, and breakpoints (BPs) have been proposed to detect echinocandin-resistant isolates. We analyzed MIC distribution for all three available echinocandins of 2,787 clinical yeast isolates corresponding to 5 common and 16 rare yeast species, using the standardized EUCAST method for anidulafungin and modified for caspofungin and micafungin (AM3-MIC). In our database, 64 isolates of common pathogenic species were resistant to anidulafungin, according to the EUCAST BP, and/or to caspofungin, using our previously published threshold (AM3-MIC ≥ 0.5 mg/L). Among these 64 isolates, 50 exhibited 21 different FKS mutations. We analyzed the capacity of caspofungin AM3-MIC and anidulafungin MIC determination in detecting isolates with FKS mutation. They were always identified using caspofungin AM3-MIC and the local threshold while some isolates were misclassified using anidulafungin MIC and EUCAST threshold. However, both methods misclassified four wild-type C. glabrata as resistant. Based on a large data set from a single center, the use of AM3-MIC testing for caspofungin looks promising in identifying non-wild-type C. albicans, C. tropicalis and P. kudiravzevii isolates, but additional multicenter comparison is mandatory to conclude on the possible superiority of AM3-MIC testing compared to the EUCAST method.
Clostridium difficile is the most common agent of nosocomial bacterial diarrhoea in adults. In 2006, C. difficile outbreaks were described in France with the highly virulent strain PCR-ribotype 027, ...which is also resistant to moxifloxacin and erythromycin. The aim of this study is to perform a phenotypic and molecular characterization of C. difficile strains isolated in Jean-Verdier-René-Muret hospitals. Thirty three C. difficile toxigenic strains isolated in symptomatic patients from 2001 to 2007 were studied. Toxins A and B detection was performed with an immunoenzymatic method (ICTAB, Meridian). The agar diffusion method was performed for determination of antibiotic susceptibility for metronidazole, vancomycin, erythromycin and moxifloxacin. The E-test was performed for determination of metronidazole, vancomycin and tigecycline MIC. Binary toxin genes cdtA and cdtB were detected by PCR. PCR-ribotyping was performed according to Bidet et al. From 2001 to 2007, all the isolates studied were susceptible to metronidazole, vancomycin and tigecyclin. We observed a significant decrease of susceptibility to moxifloxacin (100% in 2001 versus 28.5% in 2007) and to erythromycin (60% in 2001 versus 14% in 2007). Toxins A/B were detected in all the isolates. Fifteen per cent of the isolates studied produced the binary toxin not correlated with a specific PCR-ribotype. Ribotype 18 was the most prevalent PCR-ribotype detected since 2006. The isolates displaying this PCR-ribotype were resistant to erythromycin and moxifloxacin and were principally isolated in the same ward, suggesting cross infection. This study showed that: (1) over a six-year period, the susceptibility to metronidazole and vancomycin remained stable; (2) different clones of C. difficile circulated during these six years. Recently an epidemic strain resistant to erythromycin and moxifloxacin of ribotype 18 has emerged in the gastroenterology unit where fluoroquinolones are frequently used demonstrating the role of antibiotic selection pressure. The emergence of these isolates could explain the significant decrease of susceptibility to moxifloxacin and erythromycin observed in 2007. However, today, no isolate with a PCR-ribotype 027 was detected.
Clostridium difficile is the most common agent of postantibiotic and nosocomial bacterial diarrhoea. Since the emergence of the highly virulent and epidemic strain NAP1/027 in Europe, it appears ...necessary to isolate C. difficile strains to realize an epidemiologic follow-up by molecular typing. The aim of this work was to compare three selective culture conditions for the isolation of C. difficile.
One hundred and thirty stools collected from patients hospitalized at Jean Verdier were swabbed on the commercial medium CLO (BioMérieux) and on a medium prepared at the laboratory (CCTa: Columbia, cefoxitine 8 mg/l, cycloserine 250 mg/l, horse blood 5 %, sodium taurocholate 0.1 %) with and without preliminary alcoholic shock (EtOH). C. difficile was isolated from 38 stools and colonies were counted on each medium.
The fluorescence intensity of C. difficile colonies is comparable on CLO and CCTa-EtOH media, however their aspect is more characteristic on CLO. This medium appears very selective contrary to the CCTa medium on which an associated flora obstructs the fluorescence reading and requires a new isolation of the suspect strains. On average 30 times more colonies of C. difficile are counted on CCTa+/-EtOH than on CLO, suggesting the presence of great proportions of spores in the stools.
The medium CLO is successful for the isolation of C. difficile despite of its selectivity. Nevertheless, it appears interesting to associate a medium enhancing spore germination as the CCTa medium inoculated after alcoholic shock to increase the sensitivity of detection while being freed from conservation and transport conditions.
Asymptomatic faecal carriage of Clostridioides difficile has been widely evaluated, but its prevalence across a wide range of clinical departments and related risk factors are not well described. The ...objectives of the PORTADIFF study were to evaluate the prevalence and identifying risk factors leading to asymptomatic carriage of both toxigenic and non-toxigenic C. difficile.
The PORTADIFF study was a 1-day prevalence study carried out in 10 different French hospitals. Adult patients, who agreed to participate, were included in this study and provided a fresh stool sample. C. difficile strains isolated from carriage were characterized by polymerase chain reaction (PCR) detection of tcdA, tcdB, cdtA and cdtB, and PCR ribotyping.
In total, 721 patients were included in this study. The median age was 73 years (range 18–101 years) and the male/female ratio was 1.06. C. difficile (either toxigenic or non-toxigenic strains) was isolated from 79 (11%) patients; 42 (5.8%) strains were toxigenic. The prevalence rates of asymptomatic carriage ranged from 5% on surgical wards to 19% on long-term care wards. The main risk factors associated with asymptomatic carriage were antibiotic treatment within the preceding 3 months (81.8% vs 53.7%; P<0.01), hospitalization within the preceding 2 months (55.8% vs 33%; P<0.01), cumulative duration of hospital stay before study inclusion (mean 50.1 vs 34.5 days; P<0.047), and hospitalization on a ward with high global incidence of C. difficile infection.
Eleven percent of hospitalized patients were asymptomatic carriers of toxigenic or non-toxigenic C. difficile, and may constitute a potential reservoir of C. difficile strains.
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