Bruno Coignard

Recommendations for Surveillance of Clostridium difficile-Associated Disease

BACKGROUND The epidemiology of Clostridium difficile-associated disease (CDAD) is changing, with evidence of increased incidence and severity. However, the understanding of the magnitude of and reasons for this change is currently hampered by the lack of standardized surveillance methods. OBJECTIVE AND METHODS An ad hoc C. difficile surveillance working group was formed to develop interim surveillance definitions and recommendations based on existing literature and expert opinion that can help to improve CDAD surveillance and prevention efforts. DEFINITIONS AND RECOMMENDATIONS A CDAD case patient was defined as a patient with symptoms of diarrhea or toxic megacolon combined with a positive result of a laboratory assay and/or endoscopic or histopathologic evidence of pseudomembranous colitis. Recurrent CDAD was defined as repeated episodes within 8 weeks of each other. Severe CDAD was defined by CDAD-associated admission to an intensive care unit, colectomy, or death within 30 days after onset. Case patients were categorized by the setting in which C. difficile was likely acquired, to account for recent evidence that suggests that healthcare facility-associated CDAD may have its onset in the community up to 4 weeks after discharge. Tracking of healthcare facility-onset, healthcare facility-associated CDAD is the minimum surveillance required for healthcare settings; tracking of community-onset, healthcare facility-associated CDAD should be performed only in conjunction with tracking of healthcare facility-onset, healthcare facility-associated CDAD. Community-associated CDAD was defined by symptom onset more than 12 weeks after the last discharge from a healthcare facility. Rates of both healthcare facility-onset, healthcare facility-associated CDAD and community-onset, healthcare facility-associated CDAD should be expressed as case patients per 10,000 patient-days; rates of community-associated CDAD should be expressed as case patients per 100,000 person-years.

Infection control measures to limit the spread of Clostridium difficile

Clostridium difficile-associated diarrhoea (CDAD) presents mainly as a nosocomial infection, usually after antimicrobial therapy. Many outbreaks have been attributed to C. difficile, some due to a new hyper-virulent strain that may cause more severe disease and a worse patient outcome. As a result of CDAD, large numbers of C. difficile spores may be excreted by affected patients. Spores then survive for months in the environment; they cannot be destroyed by standard alcohol-based hand disinfection, and persist despite usual environmental cleaning agents. All these factors increase the risk of C. difficile transmission. Once CDAD is diagnosed in a patient, immediate implementation of appropriate infection control measures is mandatory in order to prevent further spread within the hospital. The quality and quantity of antibiotic prescribing should be reviewed to minimise the selective pressure for CDAD. This article provides a review of the literature that can be used for evidence-based guidelines to limit the spread of C. difficile. These include early diagnosis of CDAD, surveillance of CDAD cases, education of staff, appropriate use of isolation precautions, hand hygiene, protective clothing, environmental cleaning and cleaning of medical equipment, good antibiotic stewardship, and specific measures during outbreaks. Existing local protocols and practices for the control of C. difficile should be carefully reviewed and modified if necessary.

Epidemiological trends in invasive aspergillosis in France: the SAIF network (2005–2007)

A prospective (2005-2007) hospital-based multicentre surveillance of EORTC/MSG-proven or probable invasive aspergillosis (IA) cases whatever the underlying diseases was implemented in 12 French academic hospitals. Admissions per hospital and transplantation procedures were obtained. Cox regression models were used to determine risk factors associated with the 12-week overall mortality. With 424 case-patients included, the median incidence/hospital was 0.271/10(3) admissions (range 0.072-0.910) without significant alteration of incidence and seasonality over time. Among the 393 adults (62% men, 56 years (16-84 years)), 15% had proven IA, 78% haematological conditions, and 92.9% had lung involvement. Acute leukaemia (34.6%) and allogeneic stem cell transplantation (21.4%) were major host factors, together with chronic lymphoproliferative disorders (21.6%), which emerged as a new high-risk group. The other risk host factors consisted of solid organ transplantation (8.7%), solid tumours (4.3%), systemic inflammatory diseases (4.6%) and chronic respiratory diseases (2.3%). Serum galactomannan tests were more often positive (≥69%) for acute leukaemia and allogeneic stem cell transplantation than for the others (<42%; p <10(-3)). When positive (n = 245), cultures mainly yielded Aspergillus fumigatus (79.7%). First-line antifungal therapy consisted of voriconazole, caspofungin, lipid formulations of amphotericin, or any combination therapy (52%, 14%, 8% and 19.9%, respectively). Twelve-week overall mortality was 44.8% (95% CI, 39.8-50.0); it was 41% when first-line therapy included voriconazole and 60% otherwise (p <0.001). Independent factors for 12-week mortality were older age, positivity for both culture and galactomannan and central nervous system or pleural involvement, while any strategy containing voriconazole was protective.

Population-Based Analysis of Invasive Fungal Infections, France, 2001–2010

These infections are underrecognized as a cause of death in the general population and high-risk groups.

High Rate of Acquisition but Short Duration of Carriage of Multidrug-Resistant Enterobacteriaceae After Travel to the Tropics

BACKGROUND Multidrug-resistant Enterobacteriaceae (MRE) are widespread in the community, especially in tropical regions. Travelers are at risk of acquiring MRE in these regions, but the precise extent of the problem is not known. METHODS From February 2012 to April 2013, travelers attending 6 international vaccination centers in the Paris area prior to traveling to tropical regions were asked to provide a fecal sample before and after their trip. Those found to have acquired MRE were asked to send fecal samples 1, 2, 3, 6, and 12 months after their return, or until MRE was no longer detected. The fecal relative abundance of MRE among all Enterobacteriaceae was determined in each carrier. RESULTS Among 824 participating travelers, 574 provided fecal samples before and after travel and were not MRE carriers before departure. Of these, 292 (50.9%) acquired an average of 1.8 MRE. Three travelers (0.5%) acquired carbapenemase-producing Enterobacteriaceae. The acquisition rate was higher in Asia (142/196 [72.4%]) than in sub-Saharan Africa (93/195 [47.7%]) or Latin America (57/183 [31.1%]). MRE acquisition was associated with the type of travel, diarrhea, and exposure to β-lactams during the travel. Three months after return, 4.7% of the travelers carried MRE. Carriage lasted longer in travelers returning from Asia and in travelers with a high relative abundance of MRE at return. CONCLUSIONS MRE acquisition is very frequent among travelers to tropical regions. Travel to these regions should be considered a risk factor of MRE carriage during the first 3 months after return, but not beyond. CLINICAL TRIALS REGISTRATION NCT01526187.

VEB-1 Extended-spectrum beta-lactamase-producing Acinetobacter baumannii, France.

VEB-1 extended-spectrum β-lactamase–producing Acinetobacter baumannii was responsible for an outbreak in hospitals in France. A national alert was triggered in September 2003 when 4 hospitals reported clusters of A. baumannii infection with similar susceptibility profiles. Case definitions and laboratory guidelines were disseminated, and prospective surveillance was implemented; strains were sent to a single laboratory for characterization and typing. From April 2003 through June 2004, 53 hospitals reported 290 cases of A. baumannii infection or colonization; 275 isolates were blaVEB-1-positive and clonally related. Cases were first reported in 5 districts of northern France, then in 10 other districts in 4 regions. Within a region, interhospital spread was associated with patient transfer. In northern France, investigation and control measures led to a reduction of reported cases after January 2004. The national alert enabled early control of new clusters, demonstrating the usefulness of early warning about antimicrobial drug resistance.

French national program for prevention of healthcare-associated infections and antimicrobial resistance, 1992-2008: positive trends, but perseverance needed.

OBJECTIVE To describe the French program for the prevention of healthcare-associated infections and antibiotic resistance and provide results for some of the indicators available to evaluate the program. In addition to structures and process indicators, the 2 outcome indicators selected were the rate of surgical site infection and the proportion of methicillin-resistant Staphylococcus aureus (MRSA) isolates among the S. aureus isolates recovered. DESIGN Descriptive study of the evolution of the national structures for control of healthcare-associated infections since 1992. Through national surveillance networks, process indicators were available from 1993 to 2006, surgical site infection rates were available from 1999 to 2005, and prevalence rates for MRSA infection were available from 2001 to 2007. RESULTS A comprehensive national program has gradually been set up in France during the period from 1993 to 2004, which included strengthening of organized infection control activities at the local, regional, and national levels and developing large networks for surveillance of specific infections and antibiotic resistance. These achievements were complemented by instituting mandatory notification for unusual nosocomial events, especially outbreaks. The second phase of the program involved the implementation of 5 national quality indicators with public reporting. Surgical site infection rates decreased by 25% over a 6-year period. In France, the median proportion of MRSA among S. aureus isolates recovered from patients with bacteremia decreased from 33.4% to 25.7% during the period from 2001 to 2007, whereas this proportion increased in many other European countries. CONCLUSIONS Very few national programs have been evaluated since the Study on the Efficacy of Nosocomial Infection Control. Although continuing efforts are required, the French program appears to have been effective at reducing infection rates.

Changing trends in vancomycin-resistant enterococci in French hospitals, 2001–08

OBJECTIVES Unprecedented outbreaks of vancomycin-resistant enterococci (VRE) have occurred in French hospitals since 2004. The aim of this study was to provide a picture of the spread and control of VRE in France and to characterize the isolates. METHODS Notification of VRE cases to Institut de Veille Sanitaire has been mandatory since 2001. Isolates of VRE were sent to the National Reference Centre for species and vancomycin-resistance gene identification. Isolates were tested for antimicrobial susceptibility and typed by PFGE and multilocus sequence typing. RESULTS Five hundred and four VRE notifications from 195 hospitals were recorded, corresponding to 2475 cases of infection (n=243) or colonization (n=2232) and 74 episodes of clustered cases. Outbreaks were controlled by implementation of infection control measures, although the number of new hospitals reporting isolation of VRE was increasing. The majority of 902 VRE isolated from 2006 to 2008 were Enterococcus faecium (94.8%) with the vanA or vanB gene. No isolate was resistant to linezolid, tigecycline or fusidic acid. PFGE analysis showed 161 different patterns. Generally a few predominant clones and several minor clones spread in a single hospital. In a subset of 46 representatives of PFGE clones, 13 different sequence types were characterized, all belonging to clonal complex CC17, while the esp and hyl genes were inconsistently detected. CONCLUSIONS The national mandatory notification of unusual nosocomial events allowed rapid identification of VRE outbreaks and early implementation of control measures that have proved effective. However, VRE continue to emerge in a growing number of hospitals.

National multidrug-resistant bacteria (MDRB) surveillance in France through the RAISIN network: a 9 year experience

BACKGROUND In the mid-1990s, the prevalence rate of multidrug-resistant bacteria (MDRB) in French hospitals was high and control of MDRB spread then became a major priority in the national infection control programme (ICP). METHODS To evaluate the impact of the ICP, a national coordination of MDRB surveillance was set up in 2002. Data were collected 3 months a year in healthcare facilities (HCFs) on a voluntary basis. All clinical specimens of methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBLE) were prospectively included. Incidences per 1000 patient days (PDs) were calculated and trends in incidence from 2003 to 2010 were assessed. RESULTS Participation in the surveillance increased from 478 HCFs in 2002 to 933 in 2010. In 2010, MRSA incidence was 0.40/1000 PDs: 1.14 in intensive care units (ICUs), 0.48 in acute care facilities (ACFs) and 0.27 in rehabilitation and long-term care facilities (RLTCFs). ESBLE incidence was 0.39/1000 PDs: 1.63 in ICUs, 0.46 in ACFs and 0.23 in RLTCFs. MRSA incidence significantly decreased from 0.72/1000 PDs in 2003 to 0.41/1000 PDs in 2010 (P<10(-3)); in contrast, ESBLE incidence significantly increased from 0.17/1000 PDs to 0.48/1000 PDs (P<10(-3)). The most prevalent ESBLE were Enterobacter aerogenes (34%) and Escherichia coli (25%) in 2003 and E. coli (60%) and Klebsiella pneumoniae (18%) in 2010. CONCLUSION These results demonstrate the positive impact of the national ICP on MRSA rates. In contrast, ESBLE incidence, especially ESBL-producing E. coli, is increasing dramatically and represents a serious threat for hospitals and for the community that deserves specific control actions.

Clinical and microbiological features of Clostridium difficile infections in France: The ICD-RAISIN 2009 national survey☆☆☆

INTRODUCTION The surveillance of Clostridium difficile infections (CDI) in France was reinforced after the emergence of the PCR-ribotype 027 epidemic clone in 2006; notification of case clusters or severe cases by healthcare facilities (HCF) became mandatory. The French Public Health Surveillance Institute (InVS) and the C. difficile National Reference Center (NRC) launched a national, prospective, multicentric survey to complete available data, in 2009. The survey had for objectives to assess CDI incidence and to characterize the strains responsible for CDI. PATIENTS AND METHODS Every month from March to August 2009, HCF notified the total number of new CDI cases, admissions, and patient-days (PD) to the InVS. A subset of participating HCF sent strains, isolated in March 2009 from CDI patients, to the NRC. RESULTS One hundred and five HCF with acute care wards and 95 with rehabilitation/long-term care (RLTC) wards participated in the 6-month epidemiological study. The incidence of CDI was 2.28 or 1.15 cases per 10,000 PD in acute care (n=1316 cases) or RLTC (n=295 cases), respectively. Seventy-eight HCF participated in the microbiological study. Two hundred and twenty-four (94.9%) of the 236 strains received by the NRC were toxigenic. The five major PCR-ribotypes were 014/020/077 (18.7%), 078/126 (12.1%), 015 (8.5%), 002 (8%), and 005 (4.9%). CONCLUSION The incidence of CDI in 2009 in France remained lower than in other European countries, suggesting a successful impact of the 2006 recommendations for CDI control.