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.

Factors associated with hospital admission and adverse outcome for COVID-19: Role of social factors and medical care.

BACKGROUND: Beyond sex, age, and various comorbidities, geographical origin and socioeconomic deprivation are associated with Coronavirus Disease (COVID-19) morbidity and mortality in the general population. We aimed to assess factors associated with severe forms of COVID-19 after a hospital emergency department visit, focusing on socioeconomic factors. METHODS: Patients with laboratory-confirmed COVID-19 attending the emergency department of Béclère Hospital (France) in March-April 2020 were included. Postal addresses were used to obtain two geographical deprivation indices at the neighborhood level. Factors associated with hospitalization and factors associated with adverse outcomes, i.e. mechanical ventilation or death, were studied using logistic and Cox analyses, respectively. RESULTS: Among 399 included patients, 321 were hospitalized. Neither geographical origin nor socioeconomic deprivation was associated with any of the outcomes. Being male, older, overweight or obese, diabetic, or having a neuropsychiatric disorder were independent risk factors for hospitalization. Among 296 patients hospitalized at Béclère Hospital, 91 experienced an adverse outcome. Older age, being overweight or obese, desaturation and extent of chest CT scan lesions>25% at admission (aHR: 2.2 [95% CI: 1.3-3.5]) and higher peak CRP levels and acute kidney failure (aHR: 2.0 [1.2-3.3]) during follow-up were independently associated with adverse outcomes, whereas treatment with hydrocortisone reduced the risk of mechanical ventilation or death by half (aHR: 0.5 [0.3-0.8]). CONCLUSION: No association between geographical origin or socioeconomic deprivation and the occurrence of a severe form of COVID-19 was observed in our population after arrival to the emergency department. Empirical corticosteroid use with hydrocortisone had a strong protective impact.

Evaluation of an 'all-in-one' seven-day whole-genome sequencing solution in the investigation of a Staphylococcus aureus outbreak in a neonatal intensive care unit.

BACKGROUND: Meticillin-susceptible and -resistant Staphylococcus aureus (MSSA and MRSA) are responsible for outbreaks in intensive care units. MSSA infections have the same morbidity and mortality rate as MRSA infections but are studied less often. Whole-genome sequencing (WGS) is used increasingly for outbreak monitoring, but still requires specific installation and trained personnel to obtain and analyse the data. AIM: To evaluate the workflow and benefits of EpiSeq solution (bioMérieux, Marcy l'Etoile, France) in exploring the increased incidence of S. aureus bloodstream infections in a neonatal intensive care unit (NICU). METHODS: Four S. aureus bacteraemia isolates and 27 colonization isolates obtained between January and July 2016 were submitted to the 'all in one solution' EpiSeq [WGS, quality data assessment, multi-locus sequence typing (MLST), spa typing, virulome and resistome characterization, and phylogenetic tree construction]. More in-depth analyses were performed (whole-genome MLST and whole-genome single nucleotide polymorphism (wgSNP)] with BioNumerics software (Applied Maths, Sint-Martens-Latem, Belgium). FINDINGS: Nine different sequence types and 13 different spa types were found among the 31 isolates studied. Among those isolates, 11 (seven patients) were ST146 spa type t002, five (four patients) were ST30 and four (four patients) were ST398. The 11 ST146 isolates had a maximum of seven pairwise SNP differences. CONCLUSION: Use of EpiSeq solution allowed fast demonstration of the polyclonal profile of the MSSA population in neonates, and enabled the suspicion of a global outbreak to be ruled out. However, wgSNP analysis showed the transmission and persistence of one sequence type for over six months in the NICU, and enabled the infection control team to adapt its response.

Carriage of ESBL-producing Enterobacteriaceae in French hospitals: the PORTABLSE study.

BACKGROUND: Currently, contact precautions are recommended for patients colonized or infected with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE). Recent studies have challenged this strategy. This study aimed to assess the rate of ESBL-PE faecal carriage among hospitalized patients according to type of hospital ward, and to identify risk factors associated with carriage. METHODS: A point prevalence study was conducted in five different types of hospital ward [medical, surgical, intensive care unit (ICU), after care and rehabilitation, and geriatric] in eight French hospitals. All patients included in the study provided a fresh stool sample. RESULTS: In total, 554 patients were included in the study, with a median age of 73 years (range 60-82 years). The overall faecal carriage rate of ESBL-PE was 17.7%. The most frequently encountered species among ESBL-PE was Escherichia coli (71.4%), followed by Klebsiella pneumoniae (14.3%). Risk factors associated with ESBL-PE faecal carriage on univariate analysis were: living in the Paris region (P<0.01) and hospitalization on a geriatric ward (P<0.01). Interestingly, the cumulative duration of hospital stay before screening was not associated with a significantly higher prevalence of ESBL-PE carriage, regardless of ward type. The ESBL-PE colonization rate was much higher for patients hospitalized on geriatric wards (28.1%) and ICUs (21.7%) compared with those for patients hospitalized on surgical wards (14.8%), medical wards (12.8%) or aftercare and rehabilitation (11.2%). CONCLUSION: The overall prevalence of ESBL-PE faecal carriage was 17.7%, with only 21% of patients identified previously as carriers. The delay between admission and screening was not associated with an increase in ESBL-PE faecal carriage.

The emergence of linezolid resistance among Enterococci in intestinal microbiota of treated patients is unrelated to individual pharmacokinetic characteristics.

Linezolid is an antimicrobial agent for the treatment of multiresistant Gram-positive infections. We assessed the impact of linezolid on the microbiota and the emergence of resistance and investigated its relationship with plasma pharmacokinetics of the antibiotic. Twenty-eight patients were treated for the first time with linezolid administered orally (n = 17) or parenterally (n = 11) at 600 mg twice a day. Linezolid plasma pharmacokinetic analysis was performed on day 7. Colonization by fecal enterococci, pharyngeal streptococci, and nasal staphylococci were assessed using selective media with or without supplemental linezolid. The resistance to linezolid was characterized. The treatment led to a decrease of enterococci, staphylococci, and streptococci in the fecal (P = 0.03), nasal, and pharyngeal (P < 0.01) microbiotas. The appearance of resistant strains was observed only in enterococci from the fecal microbiota between the 7th and 21st days of treatment in four patients (14.3%). The resistance was mainly due for the first time to the mutation G2447T in the 23S rRNA gene. No pharmacokinetic parameters were significantly different between the patients, regardless of the appearance of resistance. The emergence of linezolid resistance during treatment was observed only in the intestinal microbiota and unrelated to pharmacokinetic parameters. However, colonization by Gram-positive bacteria was reduced as a result of treatment in all microbiotas.

A retrospective study of daptomycin use in a Paris teaching-hospital.

OBJECTIVE: We retrospectively studied daptomycin use during 2010 at the Bichat-Claude-Bernard teaching-hospital (Paris) to observe the evolution of daptomycin prescriptions. PATIENTS AND METHODS: Twenty-one patients were included and several parameters were documented: site of infection, bacterial species involved, reason for daptomycin use, dose and clinical outcome. RESULTS: Ninety-five percent of daptomycin prescritions were off-label and most did not comply with local guidelines. Fifteen of the 21 patients were cured (71%), including 9 patients of the 12 with off-label and off-local recommendation prescriptions (75%). Osteitis and Enterococcus spp endocarditis were the new indications. Daptomycin was increasingly used at higher doses: 52% of our patients were given doses above 6mg/kg. Staphylococcus spp. was the most frequent pathogen responsible for infection is our patients, followed by Enterococcus spp. CONCLUSION: Daptomycin use is likely to evolve because of its effectiveness in the treatment of osteitis, left-sided and Enterococcus spp. infective endocarditis. It is generally used at higher doses, which are well tolerated. However, therapeutic monitoring needs to be developed. The antibiotic commission of our hospital gave new recommendations for daptomycin use in 2011.

[Linezolid: antibacterial activity, clinical efficacy and resistance]. / Le linézolide: activité antibactérienne, intérêts cliniques et résistance.

Linezolid is a synthetic antibiotic, the first available agent in a new class of antibiotic called the oxazolidinones, whose particular mechanism of action consists in inhibiting the initiation of protein synthesis. Its spectrum of in vitro and in vivo activity includes staphylococci, streptococci, enterococci, corynebacteria and some anaerobic bacteria (Peptostreptococcus, Clostridium, and Fusobacterium). The first therapeutic results were very encouraging, leading to the marketing of the product in France in 2002. Linezolid is indicated in the treatment of pneumonia and the complicated infections of the skin. Pharmacocinetics studies have shown that linezolid has an excellent bioavailability allowing a fast relay per os. However, failures of treatment under linezolid were reported and resistant strains of staphylococci and enterococci were obtained in vitro and in vivo after therapeutic use of this antibiotic. Changes in the domain V of 23S rRNA were found in the site of fixation, the most frequent was (G out of U) in position 2576 (numbering E. coli). In a context where resistance to traditional treatments in enterococci, pneumococci and S. aureus do not cease to increase, linezolid can be regarded as a therapeutic alternative to treat the infections with Gram-positive cocci.