Prevalence, genetic diversity of and factors associated with ESBL-producing Enterobacterales carriage in residents of French nursing homes.

OBJECTIVE: To determine the prevalence and genotypic characteristics of extended-spectrum ß-lactamase-producing Enterobacterales (ESBLE) and carbapenemase-producing Enterobacterales (CPE) in nursing homes (NHs) in a French region. Risk factors associated with their carriage were also investigated. METHODS: A point-prevalence survey was proposed from November 2017 to June 2018 to NHs in the study region. Volunteer residents were screened for ESBLE and CPE carriage. Escherichia coli and Klebsiella pneumoniae isolates were genotyped using multi-locus sequence typing, pulsed-field gel electrophoresis (PFGE) and phylogrouping (for E. coli alone). Collective and individual data were analysed by random-effects logistic regression. RESULTS: The study was conducted in 18 NHs and included 262 patients. Fifty-two patients (19.8%) carried at least one ESBLE, corresponding to 56 isolates (42 E. coli, 11 K. pneumoniae and three others), while no CPE was detected. The majority (27/42) of ESBL E. coli belonged to phylogroup B2, and ST131 was over-represented in this subset (21/27). PFGE analysis revealed ST131 cross-transmission within NHs. Regarding ESBL K. pneumoniae, nine of 11 isolates belonged to ST663, and PFGE suggested diffusion of the clone in six NHs. Significant individual risk factors for colonization by ESBLE were: use of a shared bathroom, previous antibiotic use and recent history of hospitalization. Significant collective protective factors were proper compliance with glove use and support of the NH by a healthcare facility. CONCLUSION: This study shows that NHs in the study region are an important reservoir of ESBLE, whereas no residents were CPE carriers. The control of ESBLE in NHs should focus on antibiotic stewardship and excreta management policies.

Current practice of French health professionals regarding Japanese encephalitis vaccination.

OBJECTIVE: Japanese encephalitis (JE) is a rare but severe disease. It is a potential threat for people traveling to endemic areas. The risk of developing JE is low (<1%), but the associated case fatality is high (30%). There is no specific treatment for JE, but a vaccine is available. We performed an observational survey to assess practices of French health professionals regarding JE vaccination. METHODS: Standardized questionnaires were sent by email to a sample of French health professionals practicing in vaccination centers. Participation was on a voluntary and anonymous basis. The questionnaires requested socio-demographic details, and included multiple choice questions. RESULTS: The response rate was 38.5%. Most participating health professionals had been working for more than three years in a vaccination center and declared not to be reluctant to perform JE vaccination. Reluctance was mostly based on the vaccine cost and on the difficulty to properly assess the risk for patients. The rapid protocol was largely preferred except in the overseas regions (P<0.05, Fisher's exact test). Traveling to South Asia and backpacking were considered at-risk conditions. Participants proposed the vaccination all year round. Most participants would not have proposed the JE vaccination for the concrete case outlined in the questionnaire. CONCLUSIONS: French health professionals are globally favorable to JE vaccination. However, assessing the risk of exposure is difficult in routine practice.

Clonal complex 398 methicillin-susceptible Staphylococcus aureus bloodstream infections are associated with high mortality.

Within the last decade, methicillin-resistant Staphylococcus aureus belonging to clonal complex 398 (CC398) has become a worldwide threat associated with livestock. More recently, methicillin-susceptible S. aureus (MSSA) belonging to CC398 have been increasingly reported as a cause of invasive infections in patients without livestock contact. We investigated risk factors associated with CC398 bloodstream infections (BSIs) compared with non-CC398 BSIs with a case-control study in a French university Hospital. From January 2010 to December 2014, nonduplicate Staphylococcus aureus (SA) isolates responsible for BSIs in adult patient were typed to identify those belonging to CC398. Each adult patient with a CC398 SA BSI (cases) was matched with 2 non-CC398 SA BSI controls randomly selected on the basis of the time at risk, the unit of hospitalization and susceptibility to methicillin. We retrospectively extracted the clinical information from electronic medical records and used conditional logistic regression for univariate and multivariate analyses. We identified 67 CC398 isolates among the 770 SA responsible for BSI in adult patients. All CC398 isolates were susceptible to methicillin. The proportion of CC398 among MSSA increased steadily from 4.6% in 2010 to 15.1% in 2013 and then stabilized at 13.8% in 2014. Factors significantly associated with CC398 MSSA BSIs were healthcare-associated infection (odds ratio (OR) 3.02, 95% confidence interval (CI) 1.19-7.63), history of neurologic disease (OR 2.51, 95% CI 1.13-5.65) and 30-day mortality (OR 2.44, 95% CI 1.23-4.85).

Acquisition of carbapenem-resistant Gram-negative bacilli in intensive care unit: predictors and molecular epidemiology.

OBJECTIVES: We had for aim to determine the risk factors for acquiring carbapenem-intermediate or -resistant Gram-negative bacilli (CR-GNB) in an intensive care unit (ICU) and to identify the resistance mechanisms involved. PATIENTS AND METHODS: We conducted an observational prospective cohort study during 6 months in medical and surgical ICUs of the Besançon Teaching Hospital. Patients with acquired CR-GNB were patients whose cultures (screening or diagnosis) became positive more than 48h after admission to the ICU. The risk factors for ICU-acquired CR-GNB were determined by multivariate logistic regression. CR-GNB isolates were typed by pulsed-field gel electrophoresis (PFGE) and screened for resistance mechanisms with phenotypic and genotypic tests. RESULTS: Twenty-three of the 347 included patients had acquired a CR-GNB. The multivariate analysis revealed significant associations between this acquisition and the duration of previous treatments with piperacillin-tazobactam (adjusted odds ratio [aOR], 1.13, P=0.02) and aminoglycosides (aOR, 1.62; P=0.005), but not with carbapenems. The CR-GNB strains were identified as Pseudomonas aeruginosa (n=10), Stenotrophomonas maltophilia (n=7), and Enterobacter cloacae (n=6). No acquired carbapenemase-producing strain was identified. PFGE typing identified 1 multiple clone among P. aeruginosa isolates (4 patients), whereas for the other bacteria, all the strains were different. CONCLUSION: Our study results suggest that the strategy to prevent the emergence and spread of CR-GNB should not be limited to the sole restriction of carbapenem use in ICU settings.

A 10-year survey of fungal aerocontamination in hospital corridors: a reliable sentinel to predict fungal exposure risk?

BACKGROUND: Invasive mould infections represent a threat for high-risk patients hospitalized in haematology units. French guidelines recommend that fungal aerocontamination monitoring should be performed quarterly. Since 2002, Besançon University Hospital has expanded to include several new buildings. Consequently, environmental surveys have been re-inforced and are now performed on a weekly basis. AIM: To retrospectively assess the contribution of fungal aerocontamination measurement in haematology corridors and main hospital corridors as a sentinel to assess fungal exposure and risk of invasive mould infections. METHODS: Over a 10-year period, 2706 air samples were taken by impaction every week in the same locations in haematology corridors and main hospital corridors. All fungal species were identified. The Haematology and Hospital Hygiene Departments were alerted systematically whenever a peak of opportunistic species was detected and corrective action was planned. Since 2007, each case of invasive aspergillosis has been reported to the French health authorities. Cuzick's test, Mann-Kendall's trend test, autocorrelation and Spearman's correlation rank test were used for statistical analysis. FINDINGS: Over 10 years of surveillance, 12 peaks of Aspergillus fumigatus (>40 colony-forming units/m(3)) were observed in the main hospital corridors, and A. fumigatus contamination was detected up to six times per year in the haematology corridors. In order to limit fungal exposure, the decision was made to perform additional checks on ventilation systems and heating, increase biocleaning and develop clear instructions. CONCLUSION: No significant link was observed between A. fumigatus detection and invasive aspergillosis. Weekly surveys have helped to improve the vigilance of the medical teams. Nevertheless, 58 cases of invasive aspergillosis have been identified since 2007.

Hospital cross-transmission of extended-spectrum ß-lactamase producing Escherichia coli and Klebsiella pneumoniae.

OBJECTIVES: We had for objective to measure the incidence and the clonal diversity of Escherichia coli and Klebsiella pneumoniae producing extended-spectrum ß-lactamases (ESBL) in order to assess the role of patient stay in amplification of the phenomenon, in our teaching hospital. MATERIAL AND METHODS: We measured the quarterly incidence rates of E. coli and K. pneumoniae producing or not producing ESBL in clinical samples between 1999 and 2010. The incidence of ESBL-producing isolates was season-adjusted. We determined the pulsotype of and identified the ESBL in all non-redundant strains isolated between 2009 and 2010. RESULTS: The incidence for 1000 hospitalization days increased from 0.00 to 0.44 for ESBL-producing E. coli, from 0.012 to 0.24 for ESBL-producing K. pneumoniae, from 1999 to 2010. Fifty-three different clones of E. coli were identified among the 61 genotyped isolates. The 28 K. pneumoniae isolates genotyped clustered into 11 different clones, among which one major epidemic clone that included 18 isolates. Respectively 66 and 75% of E. coli and K. pneumoniae isolates produced a CTX-M group 1 ESBL. CONCLUSION: The hospital seems to play a different role in the amplification of ESBL according to the producing species (K. pneumoniae or E. coli). ESBL-producing E. coli seem to have a limited cross-transmission within the hospital and seem to be added to non-producers. Conversely, ESBL-producing K. pneumoniae seem to be cross-transmitted within the hospital and to replace non-producers.

Antibiotic prescription in nursing homes for dependent elderly people: a cross-sectional study in Franche-Comté.

OBJECTIVES: We had for objective to determine the rate of patients treated with antibiotics and the determinants of antibiotic stewardship in nursing homes for dependent elderly people (French acronym EHPAD), of a French region (Franche-Comté). PATIENTS AND METHODS: A representative sample of EHPAD, in Franche-Comté, was included in a cross-sectional study made between April and June 2012. An external auditor and the EHPAD head physician collected data on the facility and on residents receiving antibiotics on the study day. An infectious diseases specialist and an infection control practitioner analyzed each prescription, a posteriori, to assess criteria of antimicrobial stewardship including re-assessment of the prescription between 48 and 72h after initiation of antibiotic treatment. RESULTS: Sixty-one (2.76%) of the 2210 residents in 18 nursing homes were under antibiotic treatment. This rate ranged from 0% to 7.5% among nursing homes. Sixty-two percent of prescriptions complied with recommendations regarding the choice of the drug, and 41.5% could not be improved by choosing an agent with a weaker ecological impact. Globally, 17.8% of prescriptions met all stewardship criteria including re-assessment of the prescription between 48 and 72h after initiation of antibiotic treatment. CONCLUSIONS: The study results differed. The rate of antibiotic prescription was low in Franche-Comté EHPAD compared to available European data, but antibiotic therapy could be greatly improved. This stresses the need to better train EHPAD physicians for antibiotic stewardship.

Relationship between prevalence of device-associated infections and alcohol-based hand-rub consumption: a multi-level approach.

Using a multi-level logistic regression model, we determined whether there was any relationship between alcohol-based hand-rub consumption and prevalence of device-associated infections (DAIs) in French healthcare facilities (HCFs). Two national databases were used: the 2006 French prevalence survey of nosocomial infections, and the 2006 French infection control indicator database which includes alcohol-based hand-rub consumption as an indicator (ICSHA: indicateur de consommation de solution hydro-alcoolique). Only patients with at least one medical device (urinary catheter, vascular catheter or tracheal tube) who were present in an HCF for at least two days were included in the analysis. A multi-level statistical analysis was performed to assess the joint effect of patient-level and hospital-level variables. In all, 814 HCFs, each with a minimum of 15 study patients, were included, giving a total of 53,459 patients. The overall prevalence of DAI was 6.7% (95% confidence interval: 6.4-6.9). The median value of ICSHA was 37.2%. There was no association between DAI prevalence and ICSHA, but all patient-level variables were associated with DAI prevalence. Patient-level variables explain 25% of the hospital-level variation in DAI prevalence, although 60% of this variation remains unexplained when both patient and hospital variables are included in the model. To further assess any association between DAI prevalence and hand hygiene, additional studies on hand hygiene practices specifically associated with invasive medical device manipulation are required.

Ribosomal and mitochondrial DNA target for real-time PCR diagnosis of invasive aspergillosis.

The aim of the present study was to assess the diagnostic efficacy of a combination of two quantitative Aspergillus PCR assays, targeting a mitochondrial and a ribosomal target, in patients with risk factors for invasive aspergillosis (IA) and positive galactomannan (GM) antigen. Forty-four patients with hematological malignancies and risk factors for IA according to revised European Organization for Research on Treatment of Cancer and the Mycoses Study Group criteria (EORTC/MSG) criteria and presenting at least two sequential GM-positive sera were included in the study. Mitochondrial PCR was carried out prospectively on all GM-positive serum samples. Ribosomal PCR was carried out retrospectively on frozen stored sera. The sensitivities of mitochondrial and ribosomal PCRs were 58% and 50%, respectively. The diagnostic test performance was improved by using a combination of both PCR assays and by considering a patient PCR positive when at least two positive results were obtained. The sensitivity, specificity, and positive and negative likelihood ratios were 65%, 94%, and 11.8 and 0.37, respectively. A significant association between fatal outcome at 90 days and positive results of ribosomal PCR assays was observed (adjusted hazard ratio = 8.2; 95% confidence interval [CI] = 1.0 to 65.8; P = 0.048). Our results showed that the combination of two PCR assays targeting mitochondrial and ribosomal Aspergillus DNA improves the sensitivity of PCR in the diagnosis of IA in hematological patients with risk factors and positive GM results. This study also confirms that a positive PCR result is associated with a poor prognosis in these patients and should lead to specific antifungal therapy being introduced immediately.

Multilevel modelling of the prevalence of hospitalized patients infected with Pseudomonas aeruginosa.

Pseudomonas aeruginosa is one of the leading nosocomial pathogens. The question of the respective contribution of endogenous and exogenous sources remains controversial. In this study, we shed new light on this issue by means of a multilevel logistic regression analysis which allowed a simultaneous investigation of factors associated with prevalence of patients infected with P. aeruginosa at two levels: patient and healthcare facility (HCF) in the eastern regions of France. A total of 25 533 in-patients from 51 HCFs were included in the analysis. The overall prevalence was 0·37% (range 0-1·65%). Multilevel modelling estimated that <14% of total variability of the outcome variable was explained by differences between HCFs and that after adjusting for patient-level variables, which explained 52% of HCF-level variance, the latter became non-significantly different from zero. A compositional effect (patient factors), rather than a contextual effect (ecological factors), explains heterogeneity of the prevalence of patients infected with P. aeruginosa in the eastern HCFs of France.

Molecular epidemiology of multidrug-resistant Pseudomonas aeruginosa in a French university hospital.

The aim of this study was to assess the incidence and molecular epidemiology of multidrug-resistant (MDR) Pseudomonas aeruginosa in our university hospital. Analysis included antimicrobial susceptibility profiling, bla gene identification and pulsed-field gel electrophoresis (PFGE). During the one-year study, 654 patients had at least one sample that tested positive for P. aeruginosa, of whom 38 (5.8%) were colonised or infected with an MDR isolate, giving an incidence of 0.1 patient per 1000 patient-days. The 38 non-duplicate isolates yielded 12 different PFGE patterns, three of which included isolates from four patients and one of which included isolates from 15 patients. Two isolates produced acquired extended-spectrum ß-lactamase (one OXA-14 and one OXA-28). Genotyping showed that cross-transmission was responsible for about 70% of MDR P. aeruginosa cases although spatio-temporal analysis failed to demonstrate when this might have occurred for most cases. The major epidemic and the three main micro-epidemic clones were already present in our hospital with a more susceptible phenotype. It is likely that some P. aeruginosa clones are endemic in our hospital and that, within these clones, MDR isolates emerge under antibiotic pressure. Our results indicate that cross-transmission plays a major role in the spread of MDR P. aeruginosa and suggest that priority should be given to the improvement of standard hygienic precautions.

Molecular epidemiology of Enterobacter cloacae in a neonatal department: a 2-year surveillance study.

A surveillance program was implemented to investigate the molecular epidemiology of Enterobacter cloacae in neonatal units. This program ran for 2 years and involved screening for E. cloacae intestinal colonization of all infants at admission and weekly thereafter. In addition, mothers whose children were admitted to neonatal units were also screened. Pulsed-field gel electrophoresis analysis was used to establish genetic relationships between strains and to identify mother-to-child transmission. During the survey period, 166 (22.6%) of the 735 included children had E. cloacae intestinal colonization, and 29 (3.9%) patients gave clinical samples positive for E. cloacae. Genotyping revealed 90 different pulsotypes in the 199 clinical and screening isolates from neonates, including three major epidemic clones. Mother-to-child transmission of E. cloacae was directly responsible for 8.8% of intestinal colonization of the neonates. This surveillance program reveals a major contribution of patient-to-patient transmission and the rarity of mother-to-child transmission in the spread of E. cloacae in neonates. This highlights the importance of good compliance with infection control procedures by health-care workers.

Are antibiotic-resistant Pseudomonas aeruginosa isolated from hospitalised patients recovered in the hospital effluents?

Previous reports have studied the presence of antibiotic-resistant Pseudomonas aeruginosa strains in hospital wastewater without determination of their clonal relationship with the clinical strains of this species. The objectives of this study were to quantify the presence of P. aeruginosa in wastewater of our hospital, to determine their antibiotic-resistance profile and to potentially trace clinical antibiotic-resistant strains from patients to wastewater. Specimens were taken at the end of the wastewater network of our hospital just before the reject in the collective network of the town. Two specimens were taken each Monday during 12 weeks. All P. aeruginosa isolates recovered from hospitalised patients during the study period were collected. Genotyping of both clinical and wastewater isolates was determined by using pulsed-field gel electrophoresis (PFGE). The antibiotic-resistance profile of wastewater isolates was different from that of clinical isolates. The mechanisms involved in antibiotic resistance were different according to the origin of the isolates (wastewater versus human isolates). There was no common PFGE pattern in antibiotic-resistant P. aeruginosa from humans and wastewater. This study suggests that the risk of spread of antibiotic resistance in hospital wastewater is limited.

Effect of cheese consumption on emergence of antimicrobial resistance in the intestinal microflora induced by a short course of amoxicillin-clavulanic acid.

AIM: To study in a sequential prospective trial, the effect of cheese consumption on the emergence of Escherichia coli and enterococci resistance to amoxicillin after amoxicillin-clavulanic acid (amoxiclav) treatment. METHODS AND RESULTS: The study comprised two phases separated by 1 year. Each phase lasted 75 days for each volunteer (from day -13 to day 61). During the first phase, 18 healthy volunteers were given a 1-g dose of amoxiclav orally twice a day for 5 days (from day 0 to day 4). The design of phase 2 was identical to that of phase 1, except that the volunteers consumed 100 g of hard-cooked cheese from day -6 to day 19. Faecal samples were collected 20 times throughout the trial and were quantitatively assayed for total and amoxicillin-resistant (Amox(R)) E. coli and enterococci. The consumption of experimental cheese was associated with a decrease of Amox(R) enterococci during the post-antibiotic period, with the maximum level of Amox(R) enterococci falling from 6.2% to 0.03%. This effect was not observed for E. coli, and the type of cheese (raw milk vs pasteurized milk) did not influence the results. CONCLUSIONS: Consumption of cheese during amoxiclav treatment reduces the emergence of Amox(R) enterococci in faeces. SIGNIFICANCE AND CLINICAL IMPACT OF THE STUDY: Our clinical pilot trial suggests that there are likely to be benefits from consuming probiotic-containing cheese during antibiotic treatment.

[Are isolation measures needed in the hospital management of Acinetobacter baumannii colonizations-infections?]. / L'isolement septique des patients colonisés-infectés par Acinetobacter baumannii est-il totalement superflu, utile ou indispensable?

UNLABELLED: Until 2001, the infection control department of the Besançon university hospital (France) recommended isolation precautions for all patients colonized-infected by Acinetobacter baumannii (Ab) whatever the antibiotic susceptibility of the strain. These systematic isolation procedures were given up at the beginning of 2002 since the number of colonized-infected patients remained stable from 1998 to 2001. OBJECTIVE: The aim of this study was to evaluate the impact of this decision on the risk of Ab infection. METHOD: Incidence rates of colonization-infections that were observed during years 2002 and 2003 were compared with expected incidence rate, based on data from 1998-2001 period. Infection control practices and antibiotics consumption were evaluated for each ward of hospitalisation. Genotyping made it possible to determine diversity of clones inside each unit and the whole hospital. RESULTS: The expected incidence per 1000 patients-days was 0.22 in comparison with observed data in 2002, 0.34 (CI(95%) [0.28-0.42]), and in 2003, 0.53 (CI(95%) [0.45-0.63]). The expected number of Ab bloodstream infections, about two per year compared with the observed numbers in 2002 and 2003 respectively seven and 17. The number of unit with more than three cases per year increased from seven in 1999 to 18 in 2003. Antibiotics consumption did not change significantly. CONCLUSION: Genotyping results show the importance of cross-transmission in these units. Finally, observed results suggest that some measures of isolation precautions in addition to standard precautions are needed to prevent outbreaks of Ab.

[Hospital deaths attributable to nosocomial infections: surveillance in a university hospital]. / Mortalité hospitalière imputable aux infections nosocomiales: mise en place d'un observatoire dans un centre hospitalier universitaire.

OBJECTIVE: A system for monitoring deaths was set up at the Besançon University Hospital, in the Franche-Comté region of France, in January 2002. This article describes the principal results after 1 year of activity. MATERIALS AND METHODS: The main outcome was the descriptive surveillance of deaths due to nosocomial infections (NI), by means of a two-step process, in the identification of cases. The first step was the declaration of information concerning the possible existence of an NI at the time of death and the assignment of a prognostic score to each patient upon admission. The second step involved comparison of opinions concerning cases "selected" on the basis of clinical records. This system was completed by a methodological analysis of deaths considered to be partially or totally due to NIs, with the aim to suggest preventive actions. RESULTS: The overall rate of mortality in our hospital was 2.44 per 100 patients admitted. The overall proportion of deaths linked to hospital-acquired infections was 15.3%. We analysed eight of the 20 deaths possibly due to NI (MacCabe score of 1 or 0) in detail. In three of these eight cases, we showed that the cause of death was not NI. Methodical analysis of patient records showed that corrective actions could have been taken in three of these five cases. CONCLUSION: Our study suggests that it is possible to monitor deaths due to nosocomial infections continuously in a university hospital and favours re-implementing death analysis committees acknowledging the "useful error" concept which is culturally difficult to accept.

Emergence of Enterobacter cloacae as a common pathogen in neonatal units: pulsed-field gel electrophoresis analysis.

In the first week of December 2002, three infants hospitalized in the neonatal department of our hospital had blood cultures positive with Enterobacter cloacae. Screening cultures and genotyping showed that 10 of 25 screened patients also carried E. cloacae and that nine isolates belonged to the same clone as that responsible for all three bacteraemias. This epidemic cluster was limited to one of the two units of the department. Surveillance of both units continued until the end of March 2003; 51 of 159 neonates screened were colonized with E. cloacae, 38 out of 80 (47.5%) in the premature unit (PU) and 13 out of 79 (16.4%) in the paediatric intensive care unit (PICU). Pulsed-field gel electrophoresis (PFGE) analysis of 130 available isolates revealed 30 different pulsotypes, including 24 unique pulsotypes from individual patients and six from multiple patients. Antibiotic (particularly beta-lactam) use did not significantly vary from 1999 to 2003. The consumption of alcohol-based hand rub (four-fold higher in the PICU than in the PU) and nurse-to-patient ratio (1:2 in the PICU and 1:4 in the PU) might explain the higher cross-transmission rate in the PU. Finally, despite an epidemiological survey, we failed to identify the causes of the emergence of E. cloacae in our neonatology units. However, improved hygiene practices combined with restriction of admission led to the progressive disappearance of the epidemic strain. The increasing importance of this type of unit and the dramatic consequences of infections emphasize the need for additional research on the constitution of the flora of newborns and the mode of acquisition Gram-negative multi-resistant bacteria.