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We investigated the impact of a multimodal intervention to improve the compliance of BC collections as a composite outcome, taking into account both blood volume collected and absence of solitary BC. We performed a quasi-experimental study using a before-after design (5 months for pre- and post-intervention evaluation) in an adult emergency department at a tertiary care hospital that showed that a multimodal intervention was associated with a dramatic increase in the proportion of blood cultures that were collected as recommended per national guidelines, from 17.3% (328/1896) to 68.9% (744/1080), P < 0.0001. The implementation of such intervention in other settings could improve the diagnosis of bloodstream infections and reduce irrelevant costs. [ABSTRACT FROM AUTHOR]

Besides phenotypic antimicrobial susceptibility testing (AST), whole genome sequencing (WGS) is a promising alternative approach for detection of resistance phenotypes. The aim of this study was to investigate the concordance between WGS-based resistance prediction and phenotypic AST results for enterococcal clinical isolates using a user-friendly online tools and databases. A total of 172 clinical isolates (34 E. faecalis, 138 E. faecium) received at the French National Reference Center for enterococci from 2017 to 2020 were included. AST was performed by disc diffusion or MIC determination for 14 antibiotics according to CA-SFM/EUCAST guidelines. The genome of all strains was sequenced using the Illumina technology (MiSeq) with bioinformatic analysis from raw reads using online tools ResFinder 4.1 and LRE-finder 1.0. For both E. faecalis and E. faecium, performances of WGS-based genotype to predict resistant phenotypes were excellent (concordance > 90%), particularly for antibiotics commonly used for treatment of enterococcal infections such as ampicillin, gentamicin, vancomycin, teicoplanin, and linezolid. Note that 100% very major errors were found for quinupristin-dalfopristin, tigecycline, and rifampicin for which resistance mutations are not included in databases. Also, it was not possible to predict phenotype from genotype for daptomycin for the same reason. WGS combined with online tools could be easily used by non-expert clinical microbiologists as a rapid and reliable tool for prediction of phenotypic resistance to first-line antibiotics among enterococci. Nonetheless, some improvements should be made such as the implementation of resistance mutations in the database for some antibiotics. [ABSTRACT FROM AUTHOR]

The role of intestinal bacterial microbiota has been described as key in the pathophysiology of Crohn's disease (CD). CD is characterized by frequent relapses after periods of remission which are not entirely understood. In this paper, we investigate whether the heterogeneity in microbiota profiles in CD patients could be a suitable predictor for these relapses. This prospective observational study involved 259 CD patients, in which 41 provided an additional total of 62 consecutive fecal samples, with an average interval of 25 weeks in between each of these samples. Fecal microbiota was analyzed by massive genomic sequencing through 16 S rRNA amplicon sampling. We found that our 259 CD patients could be split into three distinct subgroups of microbiota (G1, G2, G3). From G1 to G3, we noticed a progressive decrease in alpha diversity (p ≤ 0.0001) but no change in the fecal calprotectin (FC) level. Focusing on the 103 consecutive samples from 41 CD patients, we showed that the patients microbiota profiles were remarkably stable over time and associated with increasing symptom severity. Investigating further this microbiota/severity association revealed that the first signs of aggravation are (1) a loss of the main anti-inflammatory Short-Chain Fatty Acids (SCFAs) Roseburia, Eubacterium, Subdoligranumum, Ruminococcus (P < 0.05), (2) an increase in pro-inflammatory pathogens Proteus, Finegoldia (P < 0.05) while (3) an increase of other minor SCFA producers such as Ezakiella, Anaerococcus, Megasphaera, Anaeroglobus, Fenollaria (P < 0.05). Further aggravation of clinical signs is significantly linked to the subsequent loss of these minor SCFAs species and to an increase in other proinflammatory Proteobacteria such as Klebsiella, Pseudomonas, Salmonella, Acinetobacter, Hafnia and proinflammatory Firmicutes such as Staphylococcus, Enterococcus, Streptococcus. (P < 0.05). To our knowledge, this is the first study (1) specifically identifying subgroups of microbiota profiles in CD patients, (2) relating these groups to the evolution of symptoms over time and (3) showing a two-step process in CD symptoms' worsening. This paves the way towards a better understanding of patient-to-patient heterogeneity, as well as providing early warning signals of future aggravation of the symptoms and eventually adapting empirically treatments. [ABSTRACT FROM AUTHOR]

We acknowledge that AI and automatization could change the daily activity of microbiologists by freeing up more time for interpretation, which is increasingly needed for up-to-date techniques such as NGS. As authors, we agree that some of the mentioned innovations such as artificial intelligence (AI) or the advent of next-generation sequencing (NGS) applications will change the daily life of microbiologists. [Extracted from the article]

The aim of the study was to characterize the antimicrobial activity of clinically-relevant biocides (chlorhexidine digluconate, benzalkonium chloride, PVP-iodine and triclosan) and to determine the sRNA expression profiles under biocide exposure in two major bacterial opportunistic pathogens, Enterococcus faecium and Staphylococcus aureus. In vitro activities were evaluated against S. aureus HG003 and E. faecium Aus0004. We determined MIC, MBC, sub-inhibitory concentrations (SIC) and growth curves under SIC conditions. sRNA expression study under SIC exposure of biocides was performed by RT-qPCR on 3 sRNAs expressed in S. aureus (RNAIII, SprD and SprX) and the first 9 sRNAs identified as expressed in E. faecium. MICs were higher against E. faecium than for S. aureus. Growth curves under increasing biocide concentrations highlighted two types of bactericidal activity: "on/off" effect for chlorhexidine, benzalkonium chloride, PVP-iodine and a "concentration-dependent" activity for triclosan. Exposure to biocide SICs led to an alteration of several sRNA expression profiles, mostly repressed. The distinct biocide activity profiles must be evaluated with other compounds and bacterial species to enrich the prediction of resistance risks associated with biocide usage. Biocide exposure induces various sRNA-mediated responses in both S. aureus and E. faecium, and further investigations are needed to decipher sRNA-driven regulatory networks. [ABSTRACT FROM AUTHOR]

Objectives: Prosthetic vascular graft infection (PVGI) is a very severe disease. We aimed to determine the factors associated with treatment failure. Methods: Patients admitted to two University Hospitals with PVGI were included in this retrospective study. PVGI was classified as possible, probable or proven according to an original set of diagnostic criteria. We defined treatment failure if one of the following events occurred within the first year after PVGI diagnosis: death and infection recurrence due to the same or another pathogen. Results: One hundred and twelve patients were diagnosed with possible (n = 26), probable (n = 22) and proven (n = 64) PVGI. Bacterial documentation was obtained for 81% of patients. The most frequently identified pathogen was Staphylococcus aureus (n = 39). Surgery was performed in 96 patients (86%). Antibiotics were administered for more than 6 weeks in 41% of patients. Treatment failure occurred in 30 patients (27.5%). The factors associated with a lower probability of treatment failure were total removal of the infected graft (OR = 0.2, 95% CI [0.1–0.6]), rifampicin administration (OR = 0.3 [0.1–0.9]) and possible PVGI according to the GRIP criteria (OR = 0.3 [0.1–0.9]). Conclusions: Treatment failure occurred in 27.5% of patients with PVGI. Total removal of the infected graft and rifampicin administration were associated with better outcomes. [ABSTRACT FROM AUTHOR]

Antibiotic stewardship programmes (ASP) are essential to tackle antibiotic resistance. Clinical microbiologists (CMs) play a key role in these programmes; however, few studies describe their actual involvement. Our objective was to explore CMs' involvement in French hospital ASP. In 2018, we conducted a survey among CMs working in large public French hospitals (600 acute care beds or more). The questionnaire focused on the following topics: microbiology department's characteristics, hospital ASP, and CMs' involvement in this programme, including their use of rapid diagnostic tests (RDT). Fifty/74 CMs answered (response rate 68%), with 68% working in a teaching hospital. CMs were leading the ASP in 6% of cases, and 57% of hospitals had a multidisciplinary antibiotic stewardship team. Most microbiology departments (92%) were using specific PCR, processed 24/7 in 74% of hospitals. More than half (58%) were using syndromic panel-based testing, 94% mass spectrometry, and 96% immunochromatographic/colorimetric RDT. Blood cultures were processed 24/7 in 44% of hospitals. CMs were involved in this. Finally, 42% of CMs wished to be more involved in their hospital's ASP, the most frequently reported barrier being lack of time (36%). CMs should be more involved in ASP. RDT are widely used, but not implemented in an optimal way. [ABSTRACT FROM AUTHOR]

Epidemiological data suggest that ceftriaxone may promote the emergence of commensal AmpC-overproducing Enterobacteriaceae because of a high biliary excretion. We tested this hypothesis in hospitalized patients either treated by ceftriaxone alone or receiving no antibiotics. Hospitalized patients with no previous antibiotics or hospitalization in the last 3 months, treated only with ceftriaxone, were prospectively included. For each ceftriaxone-treated patient, a control patient receiving no antibiotics was included. Clinical data and stools were collected at T0 (before antibiotics) and T1 (at the end of ceftriaxone treatment or at discharge) and T2 (3–6 months after T1) for the ceftriaxone-treated patients and at T0 and T1 for control patients. Third-generation cephalosporin-resistant Enterobacteriaceae were detected, identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF), and characterized genetically. Clonal relatedness was evaluated by random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR). Fifteen ceftriaxone and 22 control patients were included. Patients’ characteristics did not differ. At T0, 2/15 ceftriaxone-treated versus 1/22 control patients carried third-generation cephalosporin-resistant Enterobacteriaceae (p = 0.6). At T1, 4/15 (27%) ceftriaxone-treated patients carried AmpC producers versus 0/22 control patients (p = 0.02). Additionally, two and three subjects carried extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae in the ceftriaxone and control groups, respectively (p = 1). At T2, three ceftriaxone-treated patients still carried AmpC-producing Enterobacteriaceae with the same RAPD profile as at T1. In hospitalized subjects with no other selective pressure, treatment by ceftriaxone alone promotes the gut colonization by AmpC-overproducing Enterobacteriaceae in over a quarter of patients, with a persistent carriage after the end of antibiotic exposure. The ecological impact of ceftriaxone should not be underestimated. [ABSTRACT FROM AUTHOR]

Background: Treatment of Gram-positive pathogens remains a major health issue due to the presence of methicillin-resistant Staphylococcus aureus (MRSA) and Vancomycin-Resistant Enterococcus spp. Daptomycin offers an alternative after therapeutic failure using glycopeptides. Yet its use requires strict control given its financial impact and environmental risks. Since 2014, the use of daptomycin within our hospital has intensified, occasionally outside the scope of its approved indications.Objectives: The aim of this study is to analyze the appropriateness of daptomycin prescriptions.Setting: This work was conducted in a 1500-bed University Hospital.Method: A descriptive retrospective study was conducted from November 2013 to July 2014. All patients having received at least 2 days of treatment were included. Analysis of the appropriateness of daptomycin prescriptions was conducted by a multidisciplinary team comprised of infectious diseases specialists, pharmacists and a microbiologist. The appropriateness of daptomycin prescriptions was established based on Infectious Diseases Society of America recommendations published in 2011.Main Outcome Measures: The indicators chosen to determine appropriateness of prescription were: treatment indication, prescribed dose and other antibiotics associated with the daptomycin prescription.Results: 19 patients (14 men/5 women) were included. Observed indications were: bone and joint infection (n = 6; 32 %), infectious endocarditis (n = 5; 26 %), bacteremia (n = 5; 26 %) and complicated skin and soft tissue infection (n = 3; 16 %). Identified pathogens were: MRSA (n = 14; 74 %), methicillin-resistant coagulase-negative Staphylococcus (n = 4; 21 %) and Streptococcus mitis (n = 1; 5 %). Daptomycin was prescribed as first-line treatment in 32 % of cases (n = 6). The mean dosage was 9 mg/kg/day (5-11 mg/kg/day) for a mean duration of 11 days (2; 55 days). Clinical success was observed in 42 % of cases (n = 8). Appropriateness for daptomycin use was only established for 15 % of prescriptions (n = 3).Conclusion: Faced with a lack of recent recommendations on the subject, our multidisciplinary team issued a local consensus, defining the indications and dosage modalities for this reserve antibiotic. This multidisciplinary approach enables improved use of recent anti-MRSA drugs. [ABSTRACT FROM AUTHOR]

Background Since 2002, linezolid, the first representative of the oxazolidinone class, has been widely prescribed, sometimes outside of approved indications. However, several cases of clinical outbreaks due to linezolid-resistant organisms have been reported, and its relatively high cost represents an economic challenge for hospital settings. Objectives The aim of this study was to assess the impact of different actions conducted by an antimicrobial stewardship team (AST) to control over-prescription of linezolid with regard to the defined daily dose (DDD) per 1,000 inhabitants per day. Setting This work was conducted in a 1,495-bed hospital from 2009 to 2013. An AST, gathering the departments of pharmacy, microbiology, and infectious diseases, assessed the pertinence of linezolid use and associated effect on the prescriber. Method A retrospective study was conducted throughout 2009. Three different evaluations were prospectively carried out, each for 3 months, between 2011 and 2013. Main outcome measure The indicators chosen to monitor the consumption of linezolid were the DDD per 1,000 inhabitants per day, which enabled a comparison to be made between hospitals from 2004 to 2012, and of the pertinence of its prescription by different departments. Results From 2009 to 2013, 239 patients were evaluated through three 3-month stages. Prescriptions were for off-label use in 45 % of cases. Prescriptions were considered appropriate in 60 % of cases. Unsuitable treatment was either modified or discontinued (62 and 38 % of cases, respectively). Mean duration of linezolid treatment was 8 days, i.e. below the national mean duration reported in the literature. To highlight the impact of action taken by the team, a consensual strategy to treat ventilator-acquired pneumonia was elaborated with principal prescribers. Throughout the study, the mean DDD per 1,000 inhabitants per day increased very slowly and was lower than the eleven other French hospitals, which were secondarily included in this study. Conclusion The multidisciplinary approach that was adopted for therapeutic education and delivery control led to an improvement in the proper use of linezolid. Similar strategy should be extended to other antimicrobial agents, such as carbapenems, for which both cost and risk of resistance emergence are of major concern. [ABSTRACT FROM AUTHOR]

To assess the presence of microbial DNA in the blood by polymerase chain reaction (PCR) and its association with disease severity and markers of inflammation in severe sepsis and to compare the performance of PCR with blood culture (BC). Prospective multicentric controlled observational study. Three surgical intensive care units in university centers and large teaching hospitals. One hundred forty-two patients with severe sepsis and 63 surgical controls. Presence of microbial DNA was assessed by multiplex PCR upon enrollment, and each time a BC was obtained. Controls had both approximately 4% positive PCRs and BCs. In severe sepsis, 34.7% of PCRs were positive compared to 16.5% of BCs ( P < 0.001). Consistently, 70.3% of BCs had a corresponding PCR result, while only 21.4% of PCR results were confirmed by BC. Compared to patients with negative PCRs at enrollment, those testing positive had higher organ dysfunction scores [SOFA, median (25th–75th percentile) 12 (7–15) vs. 9 (7–11); P = 0.023] and a trend toward higher mortality (PCR negative 25.3%; PCR positive 39.1%; P = 0.115). In septic patients, concordance between BC and PCR is moderate. However, PCR-based pathogen detection correlated with disease severity even if the BC remained negative, suggesting that presence of microbial DNA in the bloodstream is a significant event. The clinical utility to facilitate treatment decisions warrants investigation. [ABSTRACT FROM AUTHOR]

The adherent-invasive Escherichia coli (AIEC), which colonize the ileal mucosa of Crohn's disease patients, adhere to intestinal epithelial cells, invade them and exacerbate intestinal inflammation. The high nutrient competition between the commensal microbiota and AIEC pathobiont requires the latter to occupy their own metabolic niches to survive and proliferate within the gut. In this study, a global RNA sequencing of AIEC strain LF82 has been used to observe the impact of bile salts on the expression of metabolic genes. The results showed a global up-regulation of genes involved in degradation and a down-regulation of those implicated in biosynthesis. The main up-regulated degradation pathways were ethanolamine, 1,2-propanediol and citrate utilization, as well as the methyl-citrate pathway. Our study reveals that ethanolamine utilization bestows a competitive advantage of AIEC strains that are metabolically capable of its degradation in the presence of bile salts. We observed that bile salts activated secondary metabolism pathways that communicate to provide an energy benefit to AIEC. Bile salts may be used by AIEC as an environmental signal to promote their colonization. [ABSTRACT FROM AUTHOR]