Time to intestinal clearance of carbapenemase-producing Enterobacterales in hospital patients: a longitudinal retrospective observational cohort study.

BACKGROUND: Intestinal clearance of carbapenemase-producing Enterobacterales (CPE-IC) is a cornerstone to discontinue isolation precautions for CPE patients in hospitals. This study aimed to evaluate the time to spontaneous CPE-IC and identify its potential associated risk factors. METHODS: This retrospective cohort study was carried out between January 2018 and September 2020 on all patients in a 3200-bed teaching referral hospital with confirmed CPE intestinal carriage. CPE-IC was defined as at least three consecutive CPE-negative rectal swab cultures without a subsequent positive result. A survival analysis was performed to determine the median time to CPE-IC. A multivariate Cox model was implemented to explore the factors associated with CPE-IC. RESULTS: A total of 110 patients were positives for CPE, of whom 27 (24.5%) achieved CPE-IC. Median time to CPE-IC was 698 days. Univariate analysis showed that female sex (P=0.046), multiple CPE-species in index cultures (P=0.005), Escherichia coli or Klebsiella spp. (P=0.001 and P=0.028, respectively) were significantly associated with the time to CPE-IC. Multivariate analysis highlighted that identification of E. coli carbapenemase-producing or CPEs harbouring ESBL genes in index culture extended the median time to CPE-IC, respectively (adjusted hazard ratio (aHR) = 0.13 (95% confidence interval: 0.04-0.45]; P=0.001 and aHR = 0.34 (95% confidence interval: 0.12-0.90); P=0.031). CONCLUSION: Intestinal decolonization of CPE can take several months to years to occur. Carbapenemase-producing E. coli are likely to play a key role in delaying intestinal decolonization, probably through horizontal gene transfer between species. Therefore, discontinuation of isolation precautions in CPE-patients should be considered with caution.

Spread of viruses, which measures are the most apt to control COVID-19?

The persistent debate about the modes of transmission of SARS-CoV2 and preventive measures has illustrated the limits of our knowledge regarding the measures to be implemented in the face of viral risk. Past and present (pandemic-related) scientific data underline the complexity of the phenomenon and its variability over time. Several factors contribute to the risk of transmission, starting with incidence in the general population (i.e., colonization pressure) and herd immunity. Other major factors include intensity of symptoms, interactions with the reservoir (proximity and duration of contact), the specific characteristics of the virus(es) involved, and a number of unpredictable elements (humidity, temperature, ventilation…). In this review, we will emphasize the difficulty of "standardizing" the situations that might explain the discrepancies found in the literature. We will show that the airborne route remains the main mode of transmission. Regarding preventive measures of prevention, while vaccination remains the cornerstone of the fight against viral outbreaks, we will remind the reader that wearing a mask is the main barrier measure and that the choice of type of mask depends on the risk situations. Finally, we believe that the recent pandemic should induce us in the future to modify our recommendations by adapting our measures in hospitals, not to the pathogen concerned, which is currently the case, but rather to the type of at-risk situation.

Prevalence and risk factors for carriage of extended-spectrum ß-lactamase-producing enterobacteriaceae in rehabilitation wards in France.

OBJECTIVES: Extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-PE) are a major public health concern worldwide. Little is known about the prevalence of ESBL-PE colonization in rehabilitation wards in France. Our aim was to determine the prevalence of ESBL-PE colonization in rehabilitation wards in the Parisian area and to identify potential risk factors for ESBL-PE carriage. PATIENTS AND METHODS: This one-day prospective study was performed in three rehabilitation wards in Paris, France, between September 1, 2016, and June 26, 2017. Rectal samples were collected for microbial analysis from patients who were present at 8am and all isolates recovered were identified by mass spectrometry. The presence of ESBL-PE was confirmed using a double-disk synergy test according to EUCAST recommendations. Risk factors for colonization were determined by univariate and multivariate analyses. RESULTS: A total of 136 patients were analyzed (50.7% of female patients; median age 71 years). Twenty-eight patients (20.6%) were colonized with ESBL-PE on the day of sampling. Escherichia coli was identified in 15 (50%) cases and Klebsiella pneumoniae in six (20%). None of the variables studied was significantly associated with a higher risk of ESBL-PE colonization. However, there was a tendency for a higher risk of ESBL-PE colonization with dementia (OR = 6.116 [95%CI: 0.92-40.57]; p = 0.06) and diabetes with complications (OR = 2.853 [95%CI: 1-8.16]; p = 0.05). CONCLUSIONS: Patients in rehabilitation wards showed a high rate of ESBL-PE colonization (21%). Continuous monitoring of antibiotic resistance among potentially pathogenic bacteria, including ESBL-PE, is crucial as colonized patients represent an important reservoir for transmission after discharge outside the hospital setting.

One-day prevalence of asymptomatic carriage of toxigenic and non-toxigenic Clostridioides difficile in 10 French hospitals.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Environmental SARS-CoV-2 contamination in hospital rooms of patients with acute COVID-19.

OBJECTIVE: Data on the transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) remain conflicting. Airborne transmission is still debated. However, hospital risk control requires better understanding of the different modes of transmission. This study aimed to evaluate the frequency of, and factors associated with, environmental air and surface contamination in the rooms of patients with coronavirus disease 2019 in the acute phase of the disease. METHODS: Sixty-five consecutive patients were included in this study. For each patient, seven room surfaces, air 1 m and 3 m from the patient's head, the inner surface of the patient's mask, and the outer surface of healthcare workers' (HCW) masks were sampled. Environmental contamination was assessed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) for SARS-CoV-2 RNA on surfaces, air and masks. A viral isolation test was performed on Vero cells for samples with an RT-qPCR cycle threshold (Ct) ≤37. RESULTS: SARS-CoV-2 RNA was detected by RT-qPCR in 34%, 12%, 50% and 10% of surface, air, patient mask and HCW mask samples, respectively. Infectious virus was isolated in culture from two samples among the 85 positive samples with Ct ≤37. On multi-variate analysis, only a positive result for SARS-CoV-2 RT-qPCR for patients' face masks was found to be significantly associated with surface contamination (odds ratio 5.79, 95% confidence interval 1.31-25.67; P=0.025). CONCLUSION: This study found that surface contamination by SARS-CoV-2 was more common than air and mask contamination. However, viable virus was rare. The inner surface of a patient's mask could be used as a marker to identify those at higher risk of contamination.

Adverse events associated with patient isolation: a systematic literature review and meta-analysis.

BACKGROUND: Patient isolation is widely recommended and used in healthcare institutions to prevent transmission of multidrug-resistant organisms (MDROs). However, its risk: benefit ratio is debated. AIM: To assess, based on newly published studies, whether or not there are physical and psychological adverse events associated with patient isolation. METHODS: Systematic literature review and meta-analysis were performed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Studies were systematically searched from PubMed, from May 1st, 2009 to January 31st, 2020. The concepts of the research questions were defined as: 'Adverse events', 'patient isolation or cohorting', and 'multi-drug resistant organisms colonized or infection patients'. Three reviewers independently screened studies and extracted data. All statistical analysis was performed with Stata Software and R. FINDINGS: After screening titles of 15,921 articles and abstracts of 196, and reviewing full texts of 50 studies, 19 studies were included. Studies were divided into three groups: four qualitative studies, seven observational studies suitable for meta-analysis, and eight other observational studies. Meta-analysis shows no adverse events related to clinical care or patients' experience associated with patient isolation. CONCLUSION: More studies with correct methodology, including a control group and standardized inclusion criteria, must be conducted to confirm our results.

Epidemiology and clinical characteristics of Klebsiella spp. meningitis in France.

OBJECTIVES: To describe the epidemiology of Klebsiella spp. meningitis in France with respect to clinical and bacteriological data. METHODS: We performed a four-year multicenter, retrospective, observational study. The primary objective was to provide a clinical description of patients with Klebsiella spp. meningitis. Secondary objectives were to compare community-acquired meningitis and healthcare-associated meningitis and to analyze factors associated with mortality. RESULTS: We enrolled 131 patients with Klebsiella spp. meningitis. Eighty-two (62.6%) infections were reported following neurosurgery. Twenty-eight strains (21.4%) were resistant to third-generation cephalosporins (3GC). The median [IQR] cellularity was 980/mm3 [116-5550], the median protein level was 5.67 [1.62-9] g/L and the median CSF glucose level was 2.5 [0-3.4] mmol/L. The in-hospital mortality rate was 23.6%. Community-acquired meningitis isolates were more frequently susceptible to 3GC than isolates from healthcare-associated meningitis (89.2% versus 72%; P=0.04). Comorbidities reported for patients with community-acquired meningitis were mainly diabetes mellitus and liver cirrhosis. In multivariate analysis, focal neurological disorder at the time of diagnosis was the only factor associated with in-hospital mortality (P=0.01). CONCLUSIONS: Purulent meningitis caused by Klebsiella spp. needs to be considered in patients with community-acquired meningitis and preexisting conditions, as well as in case of meningitis following neurosurgical procedures.

FUrTIHF: French urinary tract infections in healthcare facilities - five-year historic cohort (2014-2018).

BACKGROUND: Urinary tract infections (UTIs) are common and diverse. Even when not severe, UTIs regularly lead to hospitalization, but their hospital burden remains unknown. This study aimed to estimate the national incidence of hospitalized UTIs in France. METHODS: A historic five-year cohort of adult patients hospitalized with UTIs in France was extracted from the medico-administrative databases using an ICD-10 code algorithm built by a multidisciplinary team. The performance parameters were estimated blindly, by reviewing 1122 cases, using medical reports as the gold standard, giving a global predictive positive value of 70.4% (95% confidence interval 66.6-74.1). The national incidence of UTIs was then estimated. RESULTS: A total of 2,083,973 patients with UTIs were hospitalized over the period, giving an adjusted incidence rate of ∼900 cases/100,000 inhabitants, stable over the period, higher in females and increasing with age; 1.2% were device-associated UTIs. Unspecific acute cystitis represented almost two-thirds of cases (63.5%); followed by pyelonephritis (23.6%) and prostatitis (12.4%). More than three-quarters of patients had at least one comorbid condition (76.8%). CONCLUSIONS: This national cohort study is the first to date to estimate the incidence of UTI-related hospitalizations in France. UTIs represent a substantial burden of care. Further analysis will provide data for more informed goal-of-care discussions targeting each type of UTI, their management and outcomes.

Relative faecal abundance of extended-spectrum ß-lactamase-producing Enterobacterales and its impact on infections among intensive care unit patients: a pilot study.

This pilot prospective study assessed the association between the faecal relative abundance of extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PE) and the occurrence of ESBL-PE related infections. Twenty-four patients were included. The median ESBL relative abundance was 32.4%. The mean ESBL-PE relative abundance (ESBL-PE-RA) was more than five-fold higher in patients exposed during the last three months to antibiotics (P = 0.002). Furthermore, the mean ESBL relative abundance was more than two-fold higher in patients colonized with non-E. coli strains (P = 0.044). The mean ESBL-PE-RA was more than 10-fold higher for the concordant patients than for the discordant patients (59.1% vs 4.9%; P < 0.001).

Risk factors for the environmental spread of different multidrug-resistant organisms: a prospective cohort study.

BACKGROUND: Substantial scientific evidence shows that contamination of environmental surfaces in hospitals plays an important role in the transmission of multidrug-resistant organisms (MDROs). To date, studies have failed to identify the risk factors associated with environmental contamination. AIM: To evaluate, compare, and identify factors associated with environmental contamination around carriers of different MDROs. METHODS: This was a prospective cohort study from May 2018 to February 2020. A total of 125 patients were included, having been admitted to Avicenne Hospital and Hotel Dieu de France de Beyrouth Hospital who were faecal carriers of MDROs (extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PE), carbapenemase-producing Enterobacterales (CPE), vancomycin-resistant enterococci (VRE)). For each patient, quantification of MDRO in stool was undertaken, plus a qualitative evaluation of the presence of MDRO in six different environmental sites; and clinical data were collected. FINDINGS: MDROs comprised ESBL-PE (34%), CPE (45%), and VRE (21%). The most frequent MDRO species was Escherichia coli. Contamination of at least one environmental site was observed for 22 (18%) patients. Only carriage of VanA was associated with a significantly higher risk of dissemination. Having a urinary catheter, carriage of OXA48 and E. coli were protective factors against environmental contamination. There were no significant differences in environmental contamination between E. coli and other Enterobacterales or between ESBL-PE and CPE. CONCLUSIONS: Hospital environmental contamination rates are substantially higher for patients with VRE, compared to the low environment dissemination rates around ESBL-PE and CPE. Further studies on a larger scale are needed to confirm the validity of our findings.

[Short recommendations from the CIAFU: Interest of the urine bacterial culture performed before endo-rectal prostate biopsy]. / Recommandations courtes du CIAFU : intérêt de l'ECBU avant biopsie de la prostate réalisée par voie endo-rectale.

Prostate biopsy is sometimes complicated by infection which can lead to death. The risk factors remain controversial, notably the urine bacterial culture carried out before a prostate biopsy. The increase in resistance induces an increase in the number of complications and the need to define new antibiotic prophylaxis strategies. The urine bacterial culture remains widely discussed in cases with post-prostate biopsy infections and urologists or experts await clear recommendations on this subject. The Infectiology Committee of the French Association of Urology has therefore set up a literature analysis work in order to reach a consensus within the committee. METHOD: A literature search was performed on Pubmed and Medline. We selected randomized studies or meta-analyzes using the keywords "prostate biopsy" and "infection" or "infectious complications". All abstracts and articles have been analyzed. The summary of the analysis was reviewed by all the members of the committee proposing the most consensual recommendation possible. RESULTS: The literature on the subject remains poor, but no evidence of a link between prebiopsy bacteriuria and post-biopsy infection has been demonstrated. CONCLUSIONS: Apart from a clinical situation which could evoke a male urinary tract infection, and moreover having to prefer the postponement of biopsies, it is not recommended to perform a routine urine culture before endo-rectal prostate biopsies (expert opinion).

SARS-CoV-2 was already spreading in France in late December 2019.

The COVID-19 epidemic is believed to have started in late January 2020 in France. Here we report a case of a patient hospitalised in December 2019 in an intensive care unit in a hospital in the north of Paris for haemoptysis with no aetiological diagnosis. RT-PCR was performed retrospectively on the stored respiratory sample and confirmed the diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Based on this result, it appears that the COVID-19 epidemic started much earlier in France.

Can environmental contamination be explained by particular traits associated with patients?

BACKGROUND: Little is known about patient risk factors associated with environmental contamination. AIM: To evaluate the rate of environmental contamination and to investigate individual risk factors. METHODS: A prospective cohort study was conducted. Each day, five rooms occupied by patients were selected. Five critical surfaces were systematically swabbed twice a day before and after cleaning. Clinical characteristics of all patients were collected. Logisitic regression was performed to evaluate the association between environmental contamination and patients' characteristics. FINDINGS: A total of 107 consecutive patients were included and 1052 environmental samples were performed. Nineteen (18%) patients were known previously colonized/infected with a multidrug-resistant organism (MDRO). Respectively, 723 (69%) and 112 (11%) samples grew with ≥1 and >2.5 cfu/cm2 bacteria, resulting in 62 (58%) contaminated rooms. Considering positive samples with at least one pathogenic bacterium, 16 (15%) rooms were contaminated. By univariate and multivariate analysis, no variables analysed were associated with the environmental contamination. Considering contaminated rooms with >2.5 cfu/cm2, three factors were protective for environmental contamination: known MDRO carriers/infected patients (odds ratio: 0.25; 95% confidence interval: 0.09-0.72; P = 0.01), patients with urinary catheter (0.19; 0.04-0.89; P = 0.03) and hospitalization in single room (0.3; 0.15-0.6; P < 0.001). CONCLUSION: This study was conducted in a non-outbreak situation and showed a low rate of environmental contamination with pathogenic bacteria. Only 11% of environmental samples grew with >2.5 cfu/cm2, and they were related to non-pathogenic bacteria. No risk factors associated with environmental contamination were identified.

Evaluation of polymerase chain reaction assays for direct screening of carbapenemase-producing Enterobacteriaceae from rectal swabs: a diagnostic meta-analysis.

Recently, molecular assays have been demonstrated to be reliable for rapid detection of carbapenemase-producing Enterobacteriaceae (CPE) directly from positive blood cultures, reducing significantly the time for identification. Few studies have tested their performance on rectal swabs and no comprehensive conclusions have been reached regarding their utility for infection control management. Our aim was to review and assess the overall diagnostic test accuracy of polymerase chain reaction for the detection of CPE in rectal swabs. The electronic database PubMed was searched, up to October 1st, 2019, without language restriction or publication date restrictions. First, the concepts of the research questions were defined: 'carbapenemase-producing Enterobacteriaceae', 'molecular testing', 'test detection', and 'rectal screening'. Two reviewers independently screened studies, extracted data, and assessed quality using the QUADAS-2 instrument. Statistical analyses were carried out in Stata software using the bivariate model. In all, 143 articles were screened and 16 studies were included. Five (31%) of the studies were conducted in the context of a CPE outbreak; one study (6%) included patients pre-identified with CPE in clinical samples (blood or tracheal secretions), whereas the rest (63%) collected rectal swabs from patients considered at high risk of colonization. The molecular assays evaluated had a relatively good sensitivity of 0.95 (95% confidence interval (CI): 0.902-0.989), and an excellent specificity of 0.994 (95% CI: 0.965-1). Molecular techniques seem to be a useful, accurate diagnostic tool in screening for carriage of CPE in contact patients around a fortuitous discovery of a non-isolated hospitalized carrier patient.

Infections caused by naturally AmpC-producing Enterobacteriaceae: Can we use third-generation cephalosporins? A narrative review.

The burden of antibiotic-resistant infections among Gram-negative bacteria is increasing. Resistance to third-generation cephalosporins (3GCs) in Enterobacteriaceae is mainly conferred by the acquisition of ß-lactamases or by deregulation of natural genetically-encoded ß-lactamase enzymes. Enterobacteriaceae such as Enterobacter spp., Serratia marcescens, Citrobacter freundii, Providencia spp. and Morganella morganii (ESCPM group) possess chromosomally-encoded inducible AmpC ß-lactamases. AmpC can be overproduced as a response to ß-lactam antibiotic exposure or by constitutive dysfunction of the AmpC regulation system. This overproduction can lead to the inactivation of 3GCs. Based on small clinical studies, international guidelines and expert recommendations suggest that 3GCs should be avoided as definitive therapy for infections caused by ESCPM group organisms. In this narrative review, we discuss the published literature and evaluate the risk related to 3GC use in the case of documented ESCPM infection.

Awareness among French healthcare workers of the transmission of multidrug resistant organisms: a large cross-sectional survey.

Background: Much effort has been made over the last two decades to educate and train healthcare professionals working on antimicrobial resistance in French hospitals. However, little has been done in France to assess perceptions, attitudes and knowledge regarding multidrug resistant organisms (MDROs) and, more globally, these have never been evaluated in a large-scale population of medical and non-medical healthcare workers (HCWs). Our aim was to explore awareness among HCWs by evaluating their knowledge of MDROs and the associated control measures, by comparing perceptions between professional categories and by studying the impact of training and health beliefs. Methods: A multicentre cross-sectional study was conducted in 58 randomly selected French healthcare facilities with questionnaires including professional and demographic characteristics, and knowledge and perception of MDRO transmission and control. A knowledge score was calculated and used in a logistic regression analysis to identify factors associated with higher knowledge of MDROs, and the association between knowledge and perception. Results: Between June 2014 and March 2016, 8716/11,753 (participation rate, 74%) questionnaires were completed. The mean knowledge score was 4.7/8 (SD: 1.3) and 3.6/8 (SD: 1.4) in medical and non-medical HCWs, respectively. Five variables were positively associated with higher knowledge: working in a university hospital (adjusted odds ratio, 1.41, 95% CI 1.16-1.70); age classes 26-35 years (1.43, 1.23-1.6) and 36-45 years (1.19, 1.01-1.40); medical professional status (3.7, 3.09-4.44), working in an intensive care unit (1.28, 1.06-1.55), and having been trained on control of antimicrobial resistance (1.31, 1.16-1.48). After adjustment for these variables, greater knowledge was significantly associated with four cognitive factors: perceived susceptibility, attitude toward hand hygiene, self-efficacy, and motivation. Conclusions: We found a low level of MDRO awareness and knowledge of associated control measures among French HCWs. Training on hand hygiene and measures to control MDRO spread may be helpful in shaping beliefs and perceptions on MDRO control among other possible associated factors. Messages should be tailored to professional status and their perception. Other approaches should be designed, with more effective methods of training and cognitive interventions. Trial registration: Clinical Trials.gov NCT02265471. Registered 16 October 2014 - Retrospectively registered.

Can real-time polymerase chain reaction allow a faster recovery of hospital activity in cases of an incidental discovery of carbapenemase-producing Enterobacteriaceae and vancomycin-resistant Enterococci carriers?

BACKGROUND: Detection of faecal carriers of carbapenemase-producing Enterobacteriaceae (CPE) and vancomycin-resistant Enterococci (VRE) has become a routine medical practice in many countries. In an outbreak setting, several public health organizations recommend three-weekly rectal screenings to rule-out acquisition in contact patients. This strategy, associated with bed closures and reduction of medical activity for a relatively long time, seems costly. AIM: The objective of this study was to test the positive and negative predictive values of reverse transcription polymerase chain reaction (RT-PCR; GeneXpert®) carried-out at Day 0, compared with conventional three-weekly culture-based rectal screenings, in identifying, among contact patients, those who acquired CPE/VRE. METHODS: A multicentre retrospective study was conducted from January2015 to October2018. All contact patients (CPs) were included identified from index patients (IPs) colonized or infected with CPE/VRE, incidentally discovered. Each CP was investigated at Day 0 by PCR (GeneXpert®), and by the recommended three-weekly screenings. FINDINGS: Twenty-two IPs and 159 CPs were included. An average of 0.77 secondary cases per patient was noted, with a mean duration of contact of 10 days (range 1-64). Among the 159 CPs, 16 (10%) had a CPE/VRE-positive culture during the monitoring period. Rectal screenings were positive at Day 0 (10 patients), Day 7 (two patients), Day 14 (four patients). Thirteen of 16 patients with positive culture had a positive PCR at Day 0. Overall, a concordance of 97.5% (155/159) was observed between the three-weekly screenings and Day 0 PCR results. When performed on CPs at Day 0 of the identification of an IP, PCR (GeneXpert®) allowed the reduction in turnaround time by five to 27 days, compared to three-weekly screenings. Positive predictive value and negative predictive value were 100% and 98%, respectively. CONCLUSIONS: The use of RT-PCR (GeneXpert®) can avoid the three-weekly rectal samplings needed to rule-out acquisition of CPE/VRE.