Multiplex microarray PCR Unyvero BCU system to accelerate relevant antimicrobial treatment in polymicrobial bloodstream infection.

PURPOSE: To evaluate the performance of a rapid multiplex microarray-based method (Unyvero BCU system, BCU) to identify microorganisms and detect antimicrobial resistance directly from positive blood culture (BC) bottles with polymicrobial growth, and to assess relevance of information provided for timely guidance of polymicrobial bloodstream infection treatment. METHODS: Accuracy, time-to-actionable results and potential impact of BCU on antimicrobial treatment were compared with those of standard of care during a prospective study for the sample analysis (November 2017-November 2018) and a retrospective study for the clinical data analysis and the time-to-result analysis. The study was complemented with an experimental study, based on spiked blood cultures to assess the ability of the method to detect antimicrobial resistance genes. RESULTS: Sixty-five clinical polymicrobial BC samples (163 total microorganisms) and 30 simulated polymicrobial BC samples (60 strains) were included. BCU reported 84.6% samples as polymicrobial, correctly identified all the bacteria of the mix for 72.3% samples (47/65) and detected bacteria that were missed by the conventional culture for 13.8% samples. All identifications and antimicrobial resistances were accurately detected for 61.5% (40/65) samples. Limitations concerned the detection of anaerobes, enterococci and enterobacterial susceptibility to third generation cephalosporins. BCU results would have guided antimicrobial treatment for 50.8% of the cases (33/65) in a timely and relevant manner, had no impact for 27.7% (18/65) and been misleading for 18.5% (12/65). CONCLUSIONS: Despite some limitations, the Unyvero BCU system is a rapid and reliable method for polymicrobial BC sample analysis.

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.

Fosfomycin, from susceptibility to resistance: Impact of the new guidelines on breakpoints.

The fosfomycin breakpoint using the disc diffusion method (DDM) changed in the 2019 CA-SFM/EUCAST guidelines v2 (24mm versus 19mm). We assessed its impact on categorization of Enterobacterales recovered from urine samples in emergency departments. A total of 7749 and 2348 strains were tested using the DDM and the broth microdilution method (BMD), respectively. The DDM with the 19-mm breakpoint was in accordance with the BMD. Using the 24-mm breakpoint, the overall rate of fosfomycin resistance in Enterobacterales increased by three-fold (5.6% vs 18.1%, P<0.01) and reached 2.8% and 86.5% in E. coli and K. pneumoniae, respectively. French guidelines for the management of community-acquired UTI remain appropriate. The accuracy of the methods for routine fosfomycin susceptibility testing should be assessed. The role of fosfomycin in the treatment of documented CA-UTI due to Enterobacterales other than E. coli should be evaluated considering its rate of resistance and recent data reporting low accuracy.

Implementation of antibiotic stewardship programmes in French ICUs in 2018: a nationwide cross-sectional survey.

BACKGROUND: Antibiotic stewardship programmes have a pivotal role in ICUs, but the level of implementation of these programmes at the regional or national level is not well known. OBJECTIVES: The aim of our study was to assess the level of implementation of antibiotic stewardship programmes in French ICUs. METHODS: We conducted a nationwide cross-sectional survey from January to March 2018 using an online questionnaire sent as an E-mail link to ICU specialists (one questionnaire per ICU). RESULTS: Overall, 113 out of 206 (55%) ICUs participated. Access to local epidemiology regarding bacterial resistance and antibiotic consumption data was reported in 84% and 65% of ICUs, respectively. Local guidelines for antibiotic use were available in 54% of ICUs. The duration of empirical antibiotic therapy was limited in 46% of cases, following the recommendation of an external expert in 33%. An antibiotic stewardship programme leader was reported at the hospital level by 94% of respondents, being an infectious disease physician in 80%. His/her role in the ICU was mostly to discuss specific cases (50%) and to provide advice on antibiotic prescriptions (26%). Regarding microbiological diagnosis, blood cultures were not processed at night or during weekends in 57%. Molecular biology and MS techniques were available in 62% and 59% of cases, respectively. Therapeutic drug monitoring of ß-lactams was available in 46% of cases. Forty-three percent of respondents knew the expression 'antimicrobial/antibiotic stewardship'. CONCLUSIONS: Antibiotic stewardship programmes are not optimally implemented in French ICUs. Improvement efforts and regular monitoring of the level of implementation are needed.

Inventory of Extended-Spectrum-ß-Lactamase-Producing Enterobacteriaceae in France as Assessed by a Multicenter Study.

The objective of this study was to perform an inventory of the extended-spectrum-ß-lactamase (ESBL)-producing Enterobacteriaceae isolates responsible for infections in French hospitals and to assess the mechanisms associated with ESBL diffusion. A total of 200 nonredundant ESBL-producing Enterobacteriaceae strains isolated from clinical samples were collected during a multicenter study performed in 18 representative French hospitals. Antibiotic resistance genes were identified by PCR and sequencing experiments. The clonal relatedness between isolates was investigated by the use of the DiversiLab system. ESBL-encoding plasmids were compared by PCR-based replicon typing and plasmid multilocus sequence typing. CTX-M-15, CTX-M-1, CTX-M-14, and SHV-12 were the most prevalent ESBLs (8% to 46.5%). The three CTX-M-type EBSLs were significantly observed in Escherichia coli (37.1%, 24.2%, and 21.8%, respectively), and CTX-M-15 was the predominant ESBL in Klebsiella pneumoniae (81.1%). SHV-12 was associated with ESBL-encoding Enterobacter cloacae strains (37.9%). qnrB, aac(6')-Ib-cr, and aac(3)-II genes were the main plasmid-mediated resistance genes, with prevalences ranging between 19.5% and 45% according to the ESBL results. Molecular typing did not identify wide clonal diffusion. Plasmid analysis suggested the diffusion of low numbers of ESBL-encoding plasmids, especially in K. pneumoniae and E. cloacae However, the ESBL-encoding genes were observed in different plasmid replicons according to the bacterial species. The prevalences of ESBL subtypes differ according to the Enterobacteriaceae species. Plasmid spread is a key determinant of this epidemiology, and the link observed between the ESBL-encoding plasmids and the bacterial host explains the differences observed in the Enterobacteriaceae species.

Bacteraemic urinary tract infections may mimic respiratory infections: a nested case-control study.

Daily practice suggests that respiratory signs may be observed in bacteraemic urinary infections (BUI). Our objective was to search for an association between the presence of respiratory symptoms and the bacteraemic nature of urinary tract infections (UTI). A nested case-control study was carried out based on our computerised dashboard from January 2011 to June 2015. Cases were defined as patients with a BUI due to Enterobacteriaceae species, identified in blood and urine cultures. Controls had fever and a positive urinary sample but sterile blood cultures (NBUI) and a final diagnosis of urinary infection. Patients from the BUI group were 1:1 matched to the NBUI group according to four parameters: age, gender, cardiovascular and pulmonary comorbid conditions. Subjects with cognitive impairment limiting clinical accuracy and those with healthcare-associated infections were excluded. We compared systematically recorded respiratory and urinary symptoms between groups: signs on auscultation, dyspnoea, chest pain, cough and sputum, dysuria with burning, pollakiuria, flank or costovertebral angle tenderness and ischuria. One hundred BUI were compared to 100 NBUI, both groups exhibiting a similar rate for all considered comorbid conditions. In the BUI group, 58 % showed at least one respiratory sign vs. 20 % in the NBUI group, p < 0.001, while urinary signs were less frequent: 54 % vs. 71 %, p = 0.013. In the multivariate analysis, BUI was associated with the presence of abnormal pulmonary auscultation [adjusted odds ratio (AOR), 5.91; p < 0.001] and a trend towards less urinary symptoms (AOR, 1.58; p = 0.058). Patients with BUI presented with significantly more respiratory signs, which overshadowed urinary symptoms, compared to those with non-bacteraemic UTI. Such observations impact clinical decision-making.

Selective reporting of antibiotic susceptibility data improves the appropriateness of intended antibiotic prescriptions in urinary tract infections: a case-vignette randomised study.

The purpose of this investigation was to assess the impact of selective reporting of antibiotic susceptibility data on the appropriateness of intended documented antibiotic prescriptions in urinary tract infections (UTIs) among residents training in general practice. We conducted a randomised-controlled case-vignette study in three French universities using a questionnaire with four UTI vignettes. In each university, residents were randomly allocated to two groups: a control group with usual full-length reporting of antibiotic susceptibility data (25 antibiotics) and an intervention group with selective reporting of antibiotic susceptibility data (2 to 4 antibiotics only). 326/611 residents (53 %) participated in the survey, 157/305 (52 %) in the intervention group and 169/306 (55 %) in the control group. For all four UTI scenarios, selective reporting of antibiotic susceptibility data significantly improved the appropriateness of antibiotic prescriptions (absolute increase ranging from 7 to 41 %, depending on the vignette). The variety of antibiotic prescriptions was reduced in the intervention group, and cephalosporins and fluoroquinolones were less often prescribed. Among 325 respondents, 124 (38 %) declared being either not really or not at all at ease with antibiotic susceptibility data, whereas 112/157 (71 %) of the residents in the intervention group declared that selective reporting of antibiotic susceptibility data made their antibiotic choice easier. Selective reporting of antibiotic susceptibility data could be a promising strategy to improve antibiotic use in UTIs, as part of a multi-faceted antibiotic stewardship programme. Microbiology laboratories should be aware that they can have a significant influence on antibiotic use.

Is hand-rub consumption correlated with hand hygiene and rate of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE)-acquired infections?

A retrospective investigation was conducted to determine whether the consumption of alcohol-based hand rub (ABHR) used was correlated with the incidence of acquired nosocomial infection due to meticillin-resistant Staphylococcus aureus or to extended-spectrum beta lactamase (ESBL)-producing strains. Between 2005 and 2008, the use of ABHRs increased significantly by 8 L per 1000 patient-days of hospitalization per year. During the same period, adherence to hand hygiene increased significantly from 55.6% to 70.9% (P < 0.0001). Despite these improvements there was a steady increase in the incidence of ESBL-producing strains in the past three years and no correlation was found between ABHR consumption and either nosocomially acquired ESBL or adherence to hand hygiene.

[Epidemiology of patients harboring extended-spectrum beta-lactamase-producing enterobacteriaceae (ESBLE), on admission]. / Épidémiologie des patients porteurs d'entérobactéries sécrétrices de bêtalactamase à spectre élargi (EBLSE), à l'admission.

OBJECTIVE: The incidence of extended-spectrum beta-lactamase-producing enterobacteria (ESBLE) has regularly increased over the last few years. However, little is known about epidemiology of ESBLE carriers in France. The objective of this study was to determine the ESBLE carriers or infected patients profile, identified within 48 hours following hospital admission. DESIGN: This retrospective study included all patients admitted in 2006 and 2007 at the Necker-Enfants-Malades (NEM) teaching hospital, carrying or infected with ESBLE isolated within 48 hours following admission. The pediatric and adult populations were compared. RESULTS: There was no significant difference between pediatric and adult populations. Escherichia coli and Klebsiella pneumoniae were the two main species isolated, accounting respectively for 59.6 and 21.1 % of the 114 isolated strains. Among the 114 analyzed files, 24 patients (21 %) were known to be EBLSE carriers, 37 (32 %) were transferred from another hospital, including 16 from another country. Concerning the 54 (47 %) other patients, five (4 %) came from a country with high prevalence, and 44 (39 %) were treated for a chronic illness. Only five patients (4 %) carrying ESBLE did not have any usual risk factor for multidrug resistance (MDR) bacterial carriage. CONCLUSIONS: In our study, 4 % of patients carrying ESBLE admitted had no usual risk factor for MDR bacteria. Targeted screening of previous carriers, patients with chronic illness, transferred patients, or patients coming from country with high prevalence, would help to limit the spread of ESBLE.

Identification of clinical coagulase-negative staphylococci, isolated in microbiology laboratories, by matrix-assisted laser desorption/ionization-time of flight mass spectrometry and two automated systems.

A study was performed to compare matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS), linked to a recently engineered microbial identification database, and two rapid identification (ID) automated systems, BD Phoenix (Becton Dickinson Diagnostic Systems, France) and VITEK-2 (bioMérieux, Marcy L'Etoile, France), for the ID of coagulase-negative staphylococci (CoNS). Two hundred and thirty-four clinical isolates of CoNS representing 20 species were analyzed. All CoNS isolates were characterized by sodA gene sequencing, allowing interpretation of the ID results obtained using the respective database of each apparatus. Overall correct ID results were obtained in 93.2%, 75.6% and 75.2% of the cases with the MALDI-TOF-MS, Phoenix and VITEK-2 systems, respectively. Mis-ID and absence of results occurred in 1.7% and 5.1% of the cases with MALDI-TOF-MS, in 23.1% and 1.3% with the Phoenix, and in 13.7% and 0.9% with the VITEK-2 systems, respectively. In addition, with the latter automate, 10.3% of the IDs were proposed with remote possibility. When excluding the CoNS species not included in the databases of at least one of the three systems, the final percentage of correct results, Mis-ID and absence of ID were 97.4%, 1.3% and 1.3% with MALDI-TOF-MS, 79%, 21% and 0% with the Phoenix, and 78.6%, 10.3% and 0.9% with the VITEK-2 system, respectively. The present study demonstrates the robustness and high sensitivity of our microbial identification database used with MALDI-TOF-MS technology. This approach represents a powerful tool for the fast ID of clinical CoNS isolates.