Emergence of Clostridium difficile toxinotype III, PCR-ribotype 027-associated disease, France, 2006.
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Publications and source records attributed to F Barbut.
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The aim of this study was to evaluate the number of deaths associated with nosocomial infections (NI) and the contribution of these NI to death. A multicentre descriptive study was conducted in 16 tertiary-care hospitals (14 222 beds) in Northern France. Medical records of consecutive patients who died at least 48 h after admission were reviewed for cause of death, NI and disease severity, before admission and before NI onset. The contribution of NI to death was assessed by agreement between two physicians according to a three-category scale of probability. Among the 1945 patients who died during the study, 26.6% had an NI. According to the agreed diagnosis, NI contributed to the deaths of 284 (14.6%) patients(certainly for 6.6% and possibly for 8%), thereby ranking NI as the fourth most frequent cause of death. Considering the deaths that had not been anticipated independently of NI two weeks before they occurred, NI definitely contributed to 2.8% of them. Lower respiratory tract, bloodstream and surgical wound infections were responsible for 39, 20 and 14%, respectively,of all NI in these patients. The impact of NI on in-hospital mortality seems to be lower than had previously been estimated in France based on US data from the 1970s and 1980s. To improve healthcare quality, further studies are needed to elucidate the processes that may contribute to fatal severe NI.
UNLABELLED: Totally implantable venous access ports (TIVAP) are valuable medical devices for long-term intravenous treatment such as parenteral nutrition, cancer chemotherapy or antiviral therapy. Implantation and use of these devices are each associated with infectious or mechanical complications. AIMS OF THE STUDY: To determine the frequency of complications and to analyze bacterial contamination of different parts of TIVAP (tip, septum, internal lumen of the port). MATERIAL AND METHODS: Clinical charts of patients, which TIVAP was removed between April 20th to December 31st 2003, were retrospectively reviewed. Infectious complications (local and septicemic) and non-infectious complications (i.e. obstruction, thrombosis, drug extravasation...) were defined using clinical and/or microbiological criteria. Quantitative culture from different parts of the TIVAP was performed. RESULTS: One hundred and ten patients (age 57 +/- 14-years-old, 94.3% cancers) were included, corresponding to 57,018 catheter-days: 39.1% had one or more non-infectious complications (density incidence: 0.86 for 1000 catheter-days). Among the 49 complications, obstruction, thrombosis, extravasations and malposition accounted for 30.6%, 30.6% 4.1% and 6% of cases. Twenty-one patients (19.1%) had an infectious complication: 11 were local and 14 were systemic (density incidence 0.43 for 1000 catheter-days). Bacteria responsible for TIVAP-associated bacteraemia were coagulase negative staphylococci (N = 2), Staphylococcus aureus susceptible to methicilline (N = 3), micrococci (N = 1), corynebacteria (N = 1) or Gram-negative bacilli (N = 8). Comparison of quantitative culture of the different parts of TIVAP with a threshold at 10(3) CFU/ml showed that culture of tip, septum and port has a sensitivity of 47.6% 57.1% and 61.9 %, respectively and a specificity of 100% 92.1% and 92.1%, respectively for the diagnosis of TIVAP infection. CONCLUSION: Complications associated to TIVAP are frequent but incidence that we have reported is comparable with previous studies. Analysis of internal lumen of the port is the most sensitive method for the diagnosis of TIVAP-associated infections.
AIMS: To determine the incidence of surgical site infections and to identify risk factors for infections. METHOD: A prospective study of surgical site infections (SSI) after cesarean section was carried out from September 1997 to September 1998 (pilot study) and from January 2000 to August 2003, using the methodology of the American National Nosocomial Infection Surveillance System. Follow up of women was performed by midwives until discharge and during the post-natal visit. Suspected surgical site infections were confirmed by surgeons and infection control practitioners. The microbiological file of each patient was edited 30 days after cesarean section. Risk factors were analyzed using a logistic regression model. RESULTS: During the pilot study, infection rate was estimated at 3.2%. At multivariate analysis, factors independently associated with an increased risk of SSI were ASA score > 1, performance of cesarean section in a room not dedicated to this activity, and use of an open urine drainage system. During the following years (2000-2003), infection rates progressively decreased to reach 1.9% in 2003. Infections included superficial wound infections (involving skin and subcutaneous tissue) (47%), deep wound infections (involving deep and soft tissue (fascia and muscle) (20%) and organ/space infections (i.e. endometritis, pelvic abscess) (33%). Infections occurred after patient discharge in 47.5% of cases and diagnosis was based only on clinical findings in 30% of cases. Infected patients were hospitalized longer (median: 6 days) than non infected patients. CONCLUSION: Prospective surveillance of SSI led to better awareness of infectious problems among health care workers, to identification of risk factors and evaluation of health procedures. Surveillance contributed to a decrease in nosocomial infections.
BACKGROUND: Clostridium difficile is the main cause of nosocomial infectious diarrhoea and the causative agent of antibiotic-associated colitis. The involvement of C. difficile infection in antibiotic-associated diarrhoea in the community is poorly documented. METHODS: We studied prospectively 266 adult out-patients in the Paris (France) area who were prescribed a 5-10-day course of antimicrobial chemotherapy. Stools were screened for C. difficile before and 14 days after the start of treatment by standard culture, toxigenic culture and testing for the cytopathic effect of toxin B. Patients were requested to note daily stool frequency and consistency. Diarrhoea was defined as the passage of at least three loose stools per day. RESULTS: Forty-six (17.5%) of the 262 assessable patients had diarrhoea during the study period. Diarrhoea was mild and self-limited in all patients, and lasted for only 1 day in 65.6% of cases. C. difficile was isolated before and after treatment from one patient, who did not develop diarrhoea. C. difficile was detected only on day 14 in 10 patients (3.8%). The isolate was toxin producing in seven patients. Four of these seven patients had mild self-limited diarrhoea. Toxin-producing C. difficile was isolated significantly more frequently from patients who had diarrhoea than from those who were diarrhoea free (8.7% vs. 1.4%, P = 0.02). CONCLUSION: The acquisition of toxin-producing C. difficile appears to be frequent during antimicrobial chemotherapy in the community [estimated rate of 2700 (1150-5400) cases per 100 000 exposures to antibiotics]. However, C. difficile is not the main agent of mild antibiotic-associated diarrhoea in out-patients.
OBJECTIVE: Peripheral venous catheter (PVC)-associated complications were prospectively evaluated in a 2 month-study performed in 3 different wards. METHODS: For each inserted PVC, the following complications were observed daily by an external investigator: tenderness, erythema, swelling or induration, palpable cord and purulence. PVC that were removed were systematically sent to the Microbiology department and analysed according to the semi-quantitative method described by Brun-Buisson et al. RESULTS: A total of 525 PVC (corresponding to 1,036 catheterisation-days) were included. Main clinical complications were erythema (22.1%), tenderness (21.9%), swelling or induration (20.9%), palpable cord (2.7%) and purulence (0.2%). Phlebitis, defined by 2 or more of the following signs: tenderness, erythema, swelling or induration and palpable cord, was observed in 22%. Catheter colonization (> or = 103 CFU/ml) occurred in 13%. Bacteria isolated from colonized catheters were coagulase-negative staphylococci (88.1%), Staphylococcus aureus (7.1%) and Candida sp. (4.8%). Multivariate risk factor analysis showed that age > or = 55 y. (OR = 3.16, p = 0.003), insertion on articulation site (OR = 2.94, p = 0.01) or in jugular vein (OR = 8.18, p = 0.01) and > 72 hour-catheterisation (OR = 4.74, p = 0.0003) were significantly associated with PVC colonization. Risk factors for phlebitis were skin lesions (OR = 1.88, p < 0.016), active infection unrelated to PVC (OR = 2.8, p = 0.001), "poor quality" peripheral vein (OR = 2.46, p < 0.02) and > 72 hour-catherisation (OR = 2.38, p = 0.009). CONCLUSION: Complications associated with peripheral venous catheters are frequent but remain benign. They could probably be reduced by a systematic change every 72-96 hours as recommended by different guidelines.
OBJECTIVE: To conduct a survey of the methods used in clinical microbiology laboratories in Europe to diagnose infection with Clostridium difficile. METHODS: A questionnaire was devised and sent to a co-ordinating member of the Study Group in each of eight European countries. This co-ordinator was in charge of forwarding the questionnaire to hospital laboratories arbitrarily selected. The number of laboratories in each country was determined on the basis of one laboratory for 10,000 beds of hospitalization. This questionnaire covered different aspects pertaining to Clostridium difficile associated to diarrhea (CDAD) diagnosis such as circumstances of request, criteria used for undertaking C. difficile investigations, methods used for the diagnosis, etc. RESULTS: A total of 212 questionnaires were completed and submitted for analysis: 87.7% of laboratories reported routinely performing C. difficile diagnostic tests. Methods used included toxin detection (93%), culture (55%), and glutamate dehydrogenase (GDH) detection (5.9%). Among the laboratories detecting toxins, different enzyme immunoassays (EIA) and cytotoxicity assays were used in 79% and 17.3% of cases, respectively. Among the different strategies reported, 4.8% were considered suboptimal for the diagnosis of C. difficile infections, but marked discrepancies could be observed between countries. The overall incidence (median) of CDAD was estimated at 1.1 for 1,000 patient admissions. CONCLUSION: The results of this study suggest marked discrepancies between laboratories and also between countries regarding the criteria by which C. difficile is investigated for, and the methods and the strategies that are used for the diagnosis of C. difficile. These discrepancies could be explained by the lack of clear guidelines for C. difficile diagnosis in each country, and by the importance that physicians attach to C. difficile. Precise guidelines for C. difficile diagnosis would be the first step to make possible accurate comparison of the incidence and the epidemiology of CDAD from one hospital to another or from one country to another.
A prospective cohort study with retrospective validation was initiated in order to assess whether a monthly bacteriological report improves the accuracy in detecting hospital-acquired infections (HAI). The setting was a 14-bed medical intensive care unit (ICU) in a 821 bed French university affiliated hospital. One thousand, six hundred and two patients were admitted during the two-year study period, the mean age was 58+/-19 years, the mean Simplified Acute Physiology Score 2 (SAPS 2) was 34+/-21, and ICU mortality was 14%. The microbiology laboratory sent monthly bacteriological reports of urine samples and central venous catheter (CVC) tips back to the intensive-care unit physician in charge of the HAI surveillance programme. This enabled a comparison to be made between prospectively and retrospectively diagnosed hospital-acquired urinary tract infections (HAUTI) and CVC-related infections (HACVCI), HAUTI were prospectively identified in 51 cases (incidence density=10.03/1,000 days) and 23 more cases were found after receiving the monthly bacteriological report (final HAUTI incidence density=14.6/1,000 days, P<0.05). HACVCI were prospectively recognized in 13 cases (incidence density=4/1,000 days) and eight more cases were discovered (final HACVCI incidence density=6.52/1,000 days,P >0.1). All retrospectively diagnosed HAI occurred during the last 48 h of the patients' ICU stay. We conclude that the routine HAI surveillance programme is reliable, except for the last 48 h in the ICU. The monthly bacteriological report improved the accuracy of the HAI reporting rate.
We describe the risk factors and microbiological findings of an outbreak of Clostridium difficile (CD)-related diarrhoea in the Medical Oncology Department of the Curie Institute. Screening for CD in stools was performed on 59 patients with diarrhoea and 146 patients without diarrhoea. Toxin secretion, serotyping (enzyme-linked immunosorbant assay) and genotyping (AP-polymerase chain reaction) were performed on 39 CD strains from 32 patients. The risk factors for toxigenic CD-positive diarrhoea were also investigated. Twenty-seven (46%) patients with diarrhoea and 12 (8%) patients without diarrhoea were CD-positive (P<0.001). Patients with diarrhoea were older (P=0.03). Chemotherapy was a risk factor for toxigenic CD-related diarrhoea (P=0.02) and antibiotic treatment was a risk factor only in those patients who were also receiving chemotherapy. Serotyping and genotyping showed that several strains were involved in this outbreak, with only two instances of patient-to-patient transmission, involving four and two patients.
Clostridium difficile is responsible for 15-25% of cases of antibiotic-associated diarrhea (AAD) and for virtually all cases of antibiotic-associated pseudomembranous colitis (PMC). This anaerobic bacterium has been identified as the leading cause of nosocomial infectious diarrhea in adults and can be responsible for large outbreaks. Nosocomial C. difficile infection results in an increased length of stay in hospital ranging from 8 to 21 days. Risk factors for C. difficile-associated diarrhea include antimicrobial therapy, older age (>65 years), antineoplastic chemotherapy and length of hospital stay. Other interventions with high risk associations are enemas, nasogastric tubes, gastrointestinal surgery and antiperistaltic drugs. Prospective studies have shown that nosocomial transmission of C. difficile is frequent but often remains asymptomatic. Patients can be contaminated from environmental surfaces, shared instrumentation, hospital personnel hands and infected roommates. Once an outbreak starts, C. difficile may be spread rapidly throughout the hospital environment where spores may persist for months. Measures that are effective in reducing incidence of C. difficile infections and cross-infection include: (i) an accurate and rapid diagnosis, (ii) appropriate treatment, (iii) implementation of enteric precautions for symptomatic patients, (iv) reinforcement of hand-washing, (v) daily environmental disinfection, and (vi) a restrictive antibiotic policy. C. difficile is a common cause of infectious diarrhea and should be therefore systematically investigated in patients with nosocomial diarrhea.
Between March 1997 and December 1997, acid-fast bacilli (AFB) were detected on sputum and/or gastric aspirates smears from five patients hospitalized in the chest medicine department. These specimens grew M. gordonae. Based on AFB-positive smear and clinical presentation, four out of five patients received antituberculous treatment until species identification was known. Epidemiological investigation revealed a heavy contamination of water collected from refrigerated fountains located on the same floor as the patient cases. Strains isolated from four patients and the refrigerated fountain exhibited the same pulsed gel electrophoresis pattern (using DraI and XbaI enzymes) suggesting that positive smears were related to drinking water from the refrigerated fountain. This cluster of pseudo-infections underlines the necessity for a proper maintenance of water supply equipment in order to avoid inappropriate decisions deleterious for patients.
The aim of this study was to evaluate an immunoassay (Triage; Biosite Diagnostics, BMD, France) for detecting both a specific antigen of Clostridium difficile (glutamate dehydrogenase [GDH]) and toxin A. Evaluation of the test was carried out in 304 fecal samples from patients suspected of having Clostridium difficile-associated diseases. The results with GDH and toxin A were compared with those of a culture and cytotoxicity assay (toxin B). The prevalence rates for toxin B-positive and culture-positive fecal samples were 11.2% and 25%, respectively. The sensitivity of the Triage immunoassay was 90.8% for GDH and 79.4% for toxin A. A negative result with both toxin A and GDH was very reliably able to eliminate a diagnosis of Clostridium difficile-associated disease (negative predictive value 99.6%). Triage is a very rapid (20 min) and easy-to-perform test. It could be useful for diagnostic purposes and also for detecting nontoxigenic strains in epidemiogical studies.
The efficacy of ornithine alpha-ketoglutarate (OKG) in preventing bacterial translocation and dissemination, metabolic disorders and changes in mucosal enzyme activities was assessed in a model of bacterial translocation in rats. Antibiotic decontamination was performed 4 d before intragastric inoculation with an Escherichia coli strain (10(10) bacteria/kg body). Two days later, the rats were given either a lipopolysaccharide (LPS) 0127:B8 or a saline injection and were deprived of food for 24 h. Enteral nutrition, [Osmolite, 880 kJ/(kg. d)] supplemented with either OKG (LPS + OKG) or glycine (Saline + Gly or LPS + Gly), was then given for 2 d. Urinary total nitrogen losses and 3-methylhistidine excretion were determined daily. On killing at d 3, bacterial translocation to the mesenteric lymph nodes (MLN) and dissemination to the spleen and liver were evaluated, jejunal mucosa enzyme activities were assayed and tissue free amino acids in muscles were measured. Endotoxin induced translocation from the gut lumen to the MLN in all groups, whereas dissemination occurred only in LPS-treated rats. OKG significantly reduced dissemination of the bacteria in the spleen. 3-Methylhistidine excretion was greater in the LPS + Gly group (+25%, P: < 0.05) than in either the LPS + OKG or Saline + Gly group. The group fed the OKG-enriched diet had higher muscular glutamine, ornithine and arginine concentrations than did the Gly-supplemented groups (P: < 0.05). Intestinal sucrase and aminopeptidase activities were higher in the LPS + OKG group than in the LPS + Gly group (-30%, P: < 0.05). OKG supplementation limits bacterial dissemination and metabolic changes after injury in rats and thus may be useful in the prevention of gut-derived sepsis in critically ill patients.
Approximately 15 to 35% of patients with a first episode of Clostridium difficile-associated diarrhea relapse within 2 months. Between 1994 and 1997, strains from 93 hospitalized patients with C. difficile recurrences were fingerprinted by using both serotyping and PCR-ribotyping. The results showed that 48.4% of clinical recurrences were, in fact, reinfections with a different strain of C. difficile. Rates of clinical recurrences could therefore be reduced by implementing strict isolation precautions.
Clostridium difficile is now recognized as the major agent responsible for nosocomial diarrhea in adults. Among the genotyping methods available, arbitrarily primed PCR (AP-PCR), PCR-ribotyping, and pulsed-field gel electrophoresis (PFGE) have been widely used for investigating outbreaks of C. difficile infections. However, the comparative typing ability, reproducibility, discriminatory power, and efficiency of these methods have not been fully investigated. We compared the results of three methods-AP-PCR with three different primers (AP3, AP4, and AP5), PCR-ribotyping, and PFGE (with SmaI endonuclease)-to differentiate 99 strains of C. difficile that had been previously serogrouped. Typing abilities were 100% for PCR-ribotyping and AP-PCR with AP3 and 90% for PFGE, due to early DNA degradation in strains from serogroup G. Reproducibilities were 100% for PCR-ribotyping and PFGE but only 88% for AP-PCR with AP3, 67% for AP-PCR with AP4, and 33% for AP-PCR with AP5. Discriminatory power for unrelated strains was >0.95 for all the methods but was lower for PCR-ribotyping among serogroups D and C. PCR-based methods were easier and quicker to perform, but their fingerprints were more difficult to interpret than those of PFGE. We conclude that PCR-ribotyping offers the best combination of advantages as an initial typing tool for C. difficile.
We investigated whether rubbing with an alcohol solution increases compliance with hand disinfection in a medical intensive care unit (MICU). During a first period (P1), hand disinfection was achieved only through conventional washing, whereas during a second period (P2), hand disinfection could be achieved either through conventional washing or rubbing with an alcohol solution. There were 621 opportunities for hand disinfection during P1 and 905 opportunities during P2. General compliance during P1 was 42.4%, and reached 60.9% during P2 (p < 0.001). This improvement was observed among nurses (45.3% versus 66.9%, p < 0.001), senior physicians (37. 2% versus 55.5%, p < 0.001), and residents (46.9% versus 59.1%, p = 0.03). Acceptability and tolerance were evaluated through the answers to an anonymous questionnaire distributed to all 53 health care workers in the MICU. Rubbing with alcohol solution was an easy procedure (100% of responses) and induced mild side effects in less than 10% of respondents. In a complementary study conducted 3 mo after the first one, compliance remained better than during P1 (51. 3% versus 42.4%, p = 0.007). These findings suggest that rubbing with alcohol solution increases compliance with hand disinfection, and that it could be proposed as an alternative to conventional handwashing in the MICU.