Use of the Mucorales qPCR on blood to screen high-risk hematology patients is associated with better survival.

Our objective was to determine whether the twice-weekly screening of high-risk hematology patients by Mucorales qPCR on serum affects the prognosis of mucormycosis. Results from all serum Mucorales qPCR tests performed on patients from the hematology unit from January 2017 to December 2022 were analyzed. Patients with positive results were classified as having proven, probable or 'PCR-only' mucormycosis. One-month mortality for the local cohort was compared with that of a national cohort of cases of mucormycosis collected by the French surveillance network for invasive fungal disease ('Réseau de surveillances des infections fongiques invasives en France' (RESSIF)) from 2012 to 2018. From 2017 to 2022, 7825 serum Mucorales qPCR tests were performed for patients from the hematology unit; 107 patients with at least one positive Mucorales qPCR (164 positive samples) were identified. Sixty patients (70 positive samples, median Cq = 40) had no radiological criteria for mucormycosis and were considered not to have invasive fungal disease (70/7825, 0.9% false positives). It was not possible to classify disease status for six patients (12 positive samples, median Cq = 38). Forty-one patients (82 positive samples, median Cq = 35) had a final diagnosis of mucormycosis. In comparison with the RESSIF cohort, the local cohort was independently associated with a 48% lower one-month all-cause mortality rate (age-, sex-, and primary disease-adjusted hazard ratio = 0.52; 95% confidence interval: 0.29-0.94; P 0.03). Proactive screening for invasive mold diseases in high-risk hematology patients, including twice-weekly Mucorales qPCR on serum, was associated with mucormycosis higher survival.

Emerging Corynebacterium diphtheriae Species Complex Infections, Réunion Island, France, 2015-2020.

Clinical, epidemiologic, and microbiologic analyses revealed emergence of 26 cases of Corynebacterium diphtheriae species complex infections on Réunion Island, France, during 2015-2020. Isolates were genetically diverse, indicating circulation and local transmission of several diphtheria sublineages. Clinicians should remain aware of the risk for diphtheria and improve diagnostic methods and patient management.

Evaluation of Serum Mucorales Polymerase Chain Reaction (PCR) for the Diagnosis of Mucormycoses: The MODIMUCOR Prospective Trial.

BACKGROUND: Early diagnosis and prompt initiation of specific antifungal treatment are essential for improving the prognosis of mucormycosis. We aimed to assess the performance of serum Mucorales quantitative polymerase chain reaction (qPCR) for the early diagnosis and follow-up of mucormycosis. METHODS: We prospectively enrolled 232 patients with suspicion of invasive mold disease, evaluated using standard imaging and mycological procedures. Thirteen additional patients with proven or probable mucormycosis were included to analyze DNA load kinetics. Serum samples were collected twice-a-week for Mucorales qPCR tests targeting the Mucorales genera Lichtheimia, Rhizomucor, and Mucor/Rhizopus. RESULTS: The sensitivity was 85.2%, specificity 89.8%, and positive and negative likelihood ratios 8.3 and 0.17, respectively in this prospective study. The first Mucorales qPCR-positive serum was observed a median of 4 days (interquartile range [IQR], 0-9) before sampling of the first mycological or histological positive specimen and a median of one day (IQR, -2 to 6) before the first imaging was performed. Negativity of Mucorales qPCR within seven days after liposomal-amphotericin B initiation was associated with an 85% lower 30-day mortality rate (adjusted hazard ratio = 0·15, 95% confidence interval [.03-.73], P = .02). CONCLUSIONS: Our study argues for the inclusion of qPCR for the detection of circulating Mucorales DNA for mucormycosis diagnosis and follow-up after treatment initiation. Positive results should be added to the criteria for the consensual definitions from the European Organization for the Research and Treatment of Cancer/Mycoses Study Group Education and Research Consortium (EORTC/MSGERC), as already done for Aspergillus PCR.

One Health compartmental analysis of ESBL-producing Escherichia coli on Reunion Island reveals partitioning between humans and livestock.

BACKGROUND: Extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-Ec) is a major cause of infections worldwide. An understanding of the reservoirs and modes of transmission of these pathogens is essential, to tackle their increasing frequency. OBJECTIVES: We investigated the contributions of various compartments (humans, animals, environment), to human colonization or infection with ESBL-Ec over a 3 year period, on an island. METHODS: The study was performed on Reunion Island (Southwest Indian Ocean). We collected ESBL-Ec isolates prospectively from humans, wastewater and livestock between April 2015 and December 2018. Human specimens were recovered from a regional surveillance system representative of the island's health facilities. These isolates were compared with those from livestock and urban/rural wastewater, by whole-genome sequencing. RESULTS: We collected 410 ESBL-Ec isolates: 161 from humans, 161 from wastewater and 88 from animals. Phylogenomic analysis demonstrated high diversity (100 STs), with different STs predominating among isolates from humans (ST131, ST38, ST10) and animals (ST57, ST156). The large majority (90%) of the STs, including ST131, were principally associated with a single compartment. The CTX-M-15, CTX-M-27 and CTX-M-14 enzymes were most common in humans/human wastewater, whereas CTX-M-1 predominated in animals. Isolates of human and animal origin had different plasmids carrying blaCTX-M genes, with the exception of a conserved IncI1-ST3 blaCTX-M-1 plasmid. CONCLUSIONS: These molecular data suggest that, despite their high level of contamination, animals are not a major source of the ESBL-Ec found in humans living on this densely populated high-income island. Public health policies should therefore focus primarily on human-to-human transmission, to prevent human infections with ESBL-Ec.

Do Contact Precautions Reduce the Incidence of Intensive Care Unit-Acquired Pseudomonas aeruginosa Infections? The DPCPYO (Detection and Contact Precautions for Patients With P. aeruginosa) Cluster-Randomized Crossover Trial.

BACKGROUND: The issue of contact precautions as contributory factors for reducing Pseudomonas aeruginosa (Pa) infections in intensive care units (ICUs) remains questioned. We evaluated the impact of the addition of contact precautions to standard precautions for Pa-positive patients on incidence of ICU-acquired Pa infections. METHODS: In this multicenter, cluster-randomized crossover trial, 10 French ICUs were randomly assigned (1:1) to sequence 0-1 (6-month control period [CP]/3-month washout period/6-month intervention period [IP]) or sequence 1-0 (6-month IP/3-month washout period/6-month CP). A surveillance screening program for Pa was implemented. Competing-risks regression models were built with death and discharge without the occurrence of ICU-acquired Pa infection (the primary outcome) as competing events. Models were adjusted for within-ICU correlation and patient- and ICU-level covariates. The Simpson diversity index (SDI) and transmission index (TI) of Pa isolates were derived from pulsed-field gel electrophoresis typing. RESULTS: Within recruited ICUs, the cumulative incidence and incidence rate of ICU-acquired Pa infections were 3.38% (55/1625) versus 3.44% (57/1658) and 3.31 versus 3.52 per 1000 patient-days at risk during the CP and IP, respectively. Multivariable models indicated that the intervention did not significantly change the cumulative incidence (subdistribution hazard ratio, .91; 95% confidence interval [CI], .49-1.67; P = .76) or rate (cause-specific hazard ratio, 1.36; 95% CI, .71-2.63; P = .36) of the primary outcome. SDI and TI did not significantly differ between CP and IP. CONCLUSIONS: The addition of contact precautions to standard precautions for Pa-positive patients with a surveillance screening program does not significantly reduce ICU-acquired Pa infections in non-outbreak situations. Clinical Trials Registration. ISRCTN92710225.

Investigating new serological and tissue markers for the follow-up of patients operated for alveolar echinococcosis.

AIMS: Alveolar echinococcosis (AE) is characterized by a chronically progressing hepatic injury caused by Echinococcus multilocularis. Surgery presently remains the best curative option. Currently, biological predictive features derived from the resected specimens are not suitable to assess surgery efficacy. The present study was designed to investigate whether a selection of markers measured on the resected specimens exhibits predictive features related to parasite viability, or to a total elimination of the parasite, in addition to serological markers. METHODS AND RESULTS: In a collaboration between two centres, one in France (Besançon), and one in Switzerland (Bern), samples from 40 AE patients were analysed by microarray and serology techniques, individually. Paired serum samples before and after surgery were obtained for 26 patients. In the sera, a significant decrease in PD-L1 levels was observed after surgery, in addition to anti-Em18 levels. In the liver tissue, low levels of Cluster of Differentiation (CD)-3 were correlated with the absence of serum anti-Em18 after surgery. CONCLUSION: This study showed PD-L1 is promising as a potential serological marker and further confirmed the performance of anti-Em18 serology. Further studies on a larger cohort are needed to confirm the utility of performing systematically microarray on resected liver tissue.

Echinococcus multilocularis vesicular fluid inhibits activation and proliferation of natural killer cells.

Alveolar echinococcosis is a severe chronic helminthic disease that mimics slow-growing liver cancer. The immune evasion strategy of Echinococcus multilocularis Leuckart, 1863 remains poorly understood. The aim of this study was to investigate in vitro the impact of E. multilocularis vesicular fluid (Em-VF) on peripheral blood mononuclear cells (PBMC) and on natural killer (NK) cells. PBMC and NK cells were exposed to Em-VF (1 µg/ml) during six days. The effect of Em-VF was assessed on CD69, viability and proliferation, and on and transforming growth factor ß (TGF-ß), interferon γ (IFN-γ), interleukin 17 (IL-17) and interleukin 10, using flow cytometry and ELISA, respectively. Exposure to Em-VF had no bearing on PBMC's viability, proliferation and expression of CD69. In contrast, higher levels of IL-17 at day three and of TGF-ß at day six were observed in PBMC supernatant after exposure to Em-VF (p < 0.05, Wilcoxon signed-rank test). Exposure to Em-VF induced a significant decrease of CD69 expression of NK cells at day three and a significant decrease of proliferation of NK cells at day six (p < 0.05, Wilcoxon signed-rank test). In contrast, NK cells viability and levels of cytokines did not vary significantly over Em-VF stimulation. Exposure to Em-VF had a significant bearing on activation and proliferation of NK cells. NK cells may play an important role in the immune response of the host against E. multilocularis.

The health and economic burden of bloodstream infections caused by antimicrobial-susceptible and non-susceptible Enterobacteriaceae and Staphylococcus aureus in European hospitals, 2010 and 2011: a multicentre retrospective cohort study.

We performed a multicentre retrospective cohort study including 606,649 acute inpatient episodes at 10 European hospitals in 2010 and 2011 to estimate the impact of antimicrobial resistance on hospital mortality, excess length of stay (LOS) and cost. Bloodstream infections (BSI) caused by third-generation cephalosporin-resistant Enterobacteriaceae (3GCRE), meticillin-susceptible (MSSA) and -resistant Staphylococcus aureus (MRSA) increased the daily risk of hospital death (adjusted hazard ratio (HR) = 1.80; 95% confidence interval (CI): 1.34-2.42, HR = 1.81; 95% CI: 1.49-2.20 and HR = 2.42; 95% CI: 1.66-3.51, respectively) and prolonged LOS (9.3 days; 95% CI: 9.2-9.4, 11.5 days; 95% CI: 11.5-11.6 and 13.3 days; 95% CI: 13.2-13.4, respectively). BSI with third-generation cephalosporin-susceptible Enterobacteriaceae (3GCSE) significantly increased LOS (5.9 days; 95% CI: 5.8-5.9) but not hazard of death (1.16; 95% CI: 0.98-1.36). 3GCRE significantly increased the hazard of death (1.63; 95% CI: 1.13-2.35), excess LOS (4.9 days; 95% CI: 1.1-8.7) and cost compared with susceptible strains, whereas meticillin resistance did not. The annual cost of 3GCRE BSI was higher than of MRSA BSI. While BSI with S. aureus had greater impact on mortality, excess LOS and cost than Enterobacteriaceae per infection, the impact of antimicrobial resistance was greater for Enterobacteriaceae.

Validation of an automated blood culture system for sterility testing of cell therapy products.

BACKGROUND AIMS: Automated blood culture systems are widely used for the detection of microorganisms in cell therapy products. However, they are not validated by the manufacturers for this purpose. The aim of this study was to assess the ability of the Bactec system (Becton-Dickinson, Le Pont-De-Claix, France) to detect the microorganisms that could contaminate cell therapy products. METHODS: Three types of vials and conditions were tested: Plus Aerobic/F and Anaerobic/F media incubated at 35°C and Mycosis IC/F medium incubated at 30°C. All vials were incubated 10 days. We tested 18 microorganisms, including slow growers and some with fastidious nutritional requirements (10 bacteria, four yeasts, four filamentous fungi), each with four inocula (10-10(4) colony-forming units) performed in quintuplicate. RESULTS: The combination of Plus Aerobic/F and Plus Anaerobic/F vials detected all the tested pathogenic bacteria, all the tested Gram-positive skin commensal or environmental bacteria, all the tested yeasts, and three of four tested filamentous fungi. The addition of the Mycosis IC/F vial extended the range of detected microorganisms to one fungal environmental contaminant. Two bacterial environmental contaminants were not detected by our method. Low inocula of the skin contaminant Propionibacterium acnes were detected only after 7 days of incubation. CONCLUSIONS: These data suggest that (i) the prolongation of the incubation time of Plus Aerobic/F and Plus Anaerobic/F vials from 7 to 10 days and (ii) the use of Mycosis IC/F medium make minor contributions in the sterility testing of cell therapy products. We have validated the Bactec method using aerobic and anaerobic vials incubated 7 days at 35°C.

The effects of switching from ceftriaxone to cefotaxime on the occurrence of third-generation cephalosporin-resistant Enterobacterales: A stepped-wedge cluster randomized trial.

OBJECTIVES: To evaluate the effects of the replacement of ceftriaxone by cefotaxime on the incidence of third-generation cephalosporin-resistant Enterobacterales (3GC-RE). PATIENTS AND METHODS: We conducted a 24-month monocentric prospective, stepped-wedge cluster randomized controlled trial. During the control phase of the study, clinicians prescribed either ceftriaxone or cefotaxime. During the intervention phase, they systematically prescribed cefotaxime. RESULTS: The cefotaxime/ceftriaxone ratio was inversely correlated with the incidence of 3GC-RE. All in all, 3GC-RE incidence was 1.05 (27/25,692) acquired cases/1000 hospitalization days during the control phase and 0.54 (11/20,419) acquired cases/1000 hospitalization days during the intervention phase (incidence rate ratio [IRR] = 0.51 [0.22-1.07], p = 0.06). In multivariable analysis, intervention phase (versus control phase) (p = 0.007), cefotaxime/ceftriaxone ratio (p = 0.003) and imported 3GC-RE (p = 0.005) were associated with the incidence of acquired cases of 3GC-RE. CONCLUSIONS: We found that replacing ceftriaxone with cefotaxime reduced the occurrence of 3GC-RE isolates. More studies are needed to confirm these results.

Antibiotics involved in the occurrence of antibiotic-resistant bacteria: a nationwide multilevel study suggests differences within antibiotic classes.

OBJECTIVES: To identify the antibiotics potentially the most involved in the occurrence of antibiotic-resistant bacteria from an ecological perspective in French healthcare facilities (HCFs). METHODS: This study was based on data from the French antimicrobial surveillance network (ATB-RAISIN, 2007-09). Antibiotics were expressed in defined daily doses per 1000 patient-days. Antibiotic-resistant bacteria were considered as count data adjusted for patient-days. These were third-generation cephalosporin (3GC)- and ciprofloxacin-resistant Escherichia coli, cefotaxime-resistant Enterobacter cloacae, methicillin-resistant Staphylococcus aureus and ceftazidime-, imipenem- and ciprofloxacin-resistant Pseudomonas aeruginosa. Three-level negative binomial regression models were built to take into account the hierarchical structure of data: level 1, repeated measures each year (count outcome, time, antibiotics); level 2, HCFs (type and size); and level 3, regions (geographical area). RESULTS: A total of 701 HCFs from 20 French regions and up to 1339 HCF-years were analysed. The use of ceftriaxone, but not of cefotaxime, was positively correlated with incidence rates of 3GC- and ciprofloxacin-resistant E. coli. In contrast, both 3GCs were positively correlated with the incidence rate of cefotaxime-resistant E. cloacae. Higher levels of use of ciprofloxacin and/or ofloxacin, but not of levofloxacin, were associated with higher incidence rates of 3GC- and ciprofloxacin-resistant E. coli, cefotaxime-resistant E. cloacae, methicillin-resistant S. aureus and ceftazidime- and ciprofloxacin-resistant P. aeruginosa. CONCLUSIONS: Our study suggests differences within antibiotic classes in promoting antibiotic resistance. We identified ceftriaxone, ciprofloxacin and ofloxacin as priority targets in public health strategies designed to reduce antibiotic use and antibiotic-resistant bacteria in French HCFs.

Population structure of community-acquired extended-spectrum beta-lactamase producing Escherichia coli and methicillin resistant Staphylococcus aureus in a French region showed no difference between urban and rural areas.

Antimicrobial resistance is a global health issue and extended-spectrum ß-lactamase producing Escherichia coli (ESBL-Ec) and methicillin-resistant Staphylococcus aureus (MRSA) are of particular concern. Whole genome sequencing analysis of isolates from the community is essential to understand the circulation of those multidrug-resistant bacteria. Our main objective was to determine the population structure of clinical ESBL-Ec and MRSA isolated in the community setting of a French region. For this purpose, isolates were collected from 23 sites belonging to 6 private medical biology laboratories in the Bourgogne-Franche-Comté region. One hundred ninety ESBL-Ec and 67 MRSA were sequenced using the Illumina technology. Genomic analyses were performed to determine the bacterial typing, presence of antibiotic resistance genes, metal resistance genes as well as virulence genes. Analysis showed that ST131 was the major ESBL-Ec clone circulating in the region, representing 42.1% of the ESBL-Ec isolates. The blaCTX-M genes represented 98% of blaESBL with the majority being blaCTX-M-15 (53.9%). MRSA population consisted of mainly of CC8 (50.7%) and CC5 (38.8%) clonal complexes. Interestingly, we found a prevalence of 40% of the zinc resistance gene czrC in our MRSA population. We observed no differences in our ESBL-Ec or MRSA populations between urban and rural areas in our French region, suggesting no impact of population density or rural environment.

Epidemiology and risk factors for febrile ureteral stent-associated urinary tract infections: A prospective observational cohort study.

OBJECTIVES: We aimed to determine the incidence and risk factors of febrile ureteral stent-associated urinary tract infections (FUSAUTI). METHODS: Hospitalized adult patients with ureteral stent (US) placement or exchange were prospectively enrolled. Patients with kidney transplantation of less than one year were excluded. Patients were followed until US removal/exchange or six months after inclusion. RESULTS: Out of 663 patients included in the study, 48 had at least one FUSAUTI (cumulative incidence 7.24%; 95% confidence interval [CI] 5.39-9.48). The incidence rate of FUSAUTI was 9.04 (95% CI 6.67-12.2) per 10,000 US-days. Ten patients (20.8%) experienced sepsis or septic shock. The most frequently isolated microorganisms were Escherichia coli (38%), Enterococcus spp. (14.5%), Candida spp. (9%) and Pseudomonas aeruginosa (9%). In multivariable logistic regression analysis, female gender, an age adjusted Charlson comorbidity index score> 3, an urethral stent placement concomitant with US placement, and a history of urinary tract infection within three months were significantly associated with a higher risk of FUSAUTI. CONCLUSION: After US placement, 7.24% of patients developed at least one FUSAUTI and, in a quarter of cases, a serious infection. Urethral stent placement was the only modifiable risk factor identified. Future interventional studies are needed to reduce FUSAUTI in these patients.

Persistent contamination of a hospital hot water network by Legionellapneumophila.

OBJECTIVES: We assessed the contamination with Legionella pneumophila (Lp) of the hot water network (HWN) of a hospital, mapped the risk of contamination, and evaluated the relatedness of isolates. We further validated phenotypically the biological features that could account for the contamination of the network. METHODS: We collected 360 water samples from October 2017 to September 2018 in 36 sampling points of a HWN of a building from a hospital in France. Lp were quantified and identified with culture-based methods and serotyping. Lp concentrations were correlated with water temperature, date and location of isolation. Lp isolates were genotyped by pulsed-field gel electrophoresis and compared to a collection of isolates retrieved in the same HWN two years later, or in other HWN from the same hospital. RESULTS: 207/360 (57.5%) samples were positive with Lp. In the hot water production system, Lp concentration was negatively associated with water temperature. In the distribution system, the risk of recovering Lp decreased when temperature was >55 °C (p < 10-3), the proportion of samples with Lp increased with distance from the production network (p < 10-3), and the risk of finding high loads of Lp increased 7.96 times in summer (p = 0.001). All Lp isolates (n = 135) were of serotype 3, and 134 (99.3%) shared the same pulsotype which is found two years later (Lp G). In vitro competition experiments showed that a 3-day culture of Lp G on agar inhibited the growth of a different pulsotype of Lp (Lp O) contaminating another HWN of the same hospital (p = 0.050). We also found that only Lp G survived to a 24h-incubation in water at 55 °C (p = 0.014). CONCLUSION: We report here a persistent contamination with Lp of a hospital HWN. Lp concentrations were correlated with water temperature, season, and distance from the production system. Such persistent contamination could be due to biotic parameters such as intra-Legionella inhibition and tolerance to high temperature, but also to the non-optimal configuration of the HWN that prevented the maintenance of high temperature and optimal water circulation.

Epidemiology and risk factors of nasal carriage of Staphylococcus aureus CC398 in two distinct cohorts in France.

Background: We aimed to determine the prevalence and factors associated with nasal carriage of Staphylococcus aureus CC398 in the community and among hospitalized patients. Methods: We conducted a prospective cohort study in a French university hospital and a cross-sectional study in the surrounding region. Results: From June 2019 to July 2020, 591 healthy blood donors (HBDs) and 647 hospitalized patients (HPs) were included. S. aureus CC398 was more prevalent in HBDs than in HPs (7.3% [5.3-9.7] vs. 3.8% [2.4-5.5], p = 0.006). Among S. aureus nasal carriers, the prevalence of CC398 isolates was 24.6% in HBDs and 18.3% in HPs (p = 0.19). No MRSA belonged to CC398. In multivariate analysis, prior antibiotic intake in the past year (OR 3.11 [1.37-7.06]) and active smoking (OR 3.01 [1.00-9.05]) were associated with S. aureus CC398 nasal carriage in the HBD cohort. A history of neurological disease was associated with nasal carriage (OR = 5.43 [1.21-24.2]), whereas an age between 82 and 90 years (OR 0.11 [0.02-0.54]) and diabetes (OR 0.18 [0.04-0.85]) were protective factors in the HP cohort. Contact with livestock was not a risk factor in either cohort. Conclusion: The prevalence of MSSA CC398 was higher in the community than hospitalized patients. Factors associated with nasal carriage of MSSA CC398 were primarily related to general preconditions. No environmental sources of exposure were identified.

High prevalence of Pseudomonas aeruginosa carriage in residents of French and German long-term care facilities.

OBJECTIVES: To determine prevalence, incidence, and factors associated with Pseudomonas aeruginosa (PA) intestinal carriage in residents of long-term care facilities (LTCFs) and to understand the population structure of this pathogen in LTCFs from two European countries. METHODS: We assessed the prevalence of PA intestinal carriage and the incidence of acquisition by collecting fecal samples from 403 residents of 20 LTCFs. We collected 289 environmental samples from sinks and drinking water. Factors associated with carriage and acquisition of intestinal PA were identified. All PA isolates had their antibiotic phenotypic resistance profile determined and their genome sequenced, from which we assessed the population structure of the collection and identified resistance determinants. RESULTS: We found a high proportion of residents with PA intestinal carriage (51.6%) over the entire study period. Over the follow-up period, 28.6% of the residents acquired intestinal PA. Older age (OR, 1.29; 95% CI, 1.09-1.52; p = 0.002), urinary incontinence (OR, 2.56; 95% CI, 1.37-4.88; p = 0.003), and male sex (OR, 2.55; 95% CI, 1.05-6.18; p = 0.039) were associated with higher probability of carriage. Wheelchair usage (OR, 4.56; 95% CI, 1.38-15.05; p = 0.013) and a body mass index >25 (OR, 3.71; 95% CI, 1.17-11.82; p = 0.026) were associated with higher risk of PA acquisition. Population structure of our isolates was mainly non-clonal with 112 different STs among the 241 isolates. Most represented STs were high risk clones ST253 (n = 26), ST17 (n = 11), ST244 (n = 11), ST309 (n = 10), and ST395 (n = 10). Most PA isolates (86.3%) were susceptible to antibiotics, with no acquired genes conferring resistance to antipseudomonal agents. DISCUSSION: We found an unexpected high prevalence of PA intestinal carriage in LTCF residents mainly associated with individual-level factors. Our study revealed a polyclonal PA population structure suggesting that individual acquisition is more frequent than resident-to-resident transmission.

ESBL-producing Klebsiella pneumoniae in a University hospital: Molecular features, diffusion of epidemic clones and evaluation of cross-transmission.

The worldwide spread of Klebsiella pneumoniae producing extended-spectrum ß-lactamase (ESBL-Kp) is a significant threat. Specifically, various pandemic clones of ESBL-Kp are involved in hospital outbreaks and caused serious infections. In that context, we assessed the phenotypic and molecular features of a collection of ESBL-Kp isolates in a French university hospital and evaluated the occurrence of potential cross-transmissions. Over a 2-year period (2017-2018), 204 non-duplicate isolates of ESBL-Kp were isolated from clinical (n = 118, 57.8%) or screening (n = 86, 42.2%) sample cultures. These isolates were predominantly resistant to cotrimoxazole (88.8%) and ofloxacin (82.8%) but remained susceptible to imipenem (99.3%) and amikacin (93.8%). CTX-M-15 was the most frequent ESBL identified (83.6%). Multilocus sequence typing and pulse-field gel electrophoresis analysis showed an important genetic variability with 41 sequence types (ST) and 50 pulsotypes identified, and the over representation of the international epidemic clones ST307 and ST405. An epidemiological link attesting probable cross-transmission has been identified for 16 patients clustered in 4 groups during the study period. In conclusion, we showed here the dissemination of pandemic clones of ESBL-Kp in our hospital on a background of clonal diversity.

Hospital-diagnosed infections with Escherichia coli clonal group ST131 are mostly acquired in the community.

The worldwide spread of E. coli ST131 has significantly contributed to the dissemination of E. coli producing extended-spectrum ß-lactamases (ESBL). In a French University hospital, we assessed the molecular features of ESBL-producing E. coli and identified risk factors in patients for colonization or infection with E. coli ST131. Over a 2-year period (2015-2017), each patient with at least one clinical isolate or one screening isolate positive with ESBL-producing E. coli were included (n = 491). The ST131 clonal group accounted for 17.5% (n = 86) of all ESBL-producing E. coli and represented 57.3% isolates of phylogroup B2. FimH-based sub-typing showed that 79.1% (68/86) of ST131 isolates were fimH30, among which 67.6% (n = 46), 20.6% (n = 14) and 11.8% (n = 8) isolates harbored genes encoding the ESBL CTX-M-15, CTX-M-27, and CTX-M-14, respectively. The multivariate analysis identified two factors independently associated with ST131 ESBL-producing E. coli isolates: infection (Odds ratio [OR] = 1.887, 95% confidence interval [CI]: 1.143-3.115; p = 0.013) and community acquisition (OR = 2.220, 95% CI: 1.335-3.693; p = 0.002). In conclusion, our study confirmed the predominance of ST131 clonal group among ESBL-producing E. coli and the difficulty to identify common risk factors associated with carriage of this pandemic clonal group.

12/111phiA Prophage Domestication Is Associated with Autoaggregation and Increased Ability to Produce Biofilm in Streptococcus agalactiae.

CC17 Streptococcus agalactiae carrying group-A prophages is increasingly responsible for neonatal infections. To investigate the impact of the genetic features of a group-A prophage, we first conducted an in silico analysis of the genome of 12/111phiA, a group-A prophage carried by a strain responsible for a bloodstream infection in a parturient. This revealed a Restriction Modification system, suggesting a prophage maintenance strategy and five ORFs of interest for the host and encoding a type II toxin antitoxin system RelB/YafQ, an endonuclease, an S-adenosylmethionine synthetase MetK, and an StrP-like adhesin. Using the WT strain cured from 12/111phiA and constructing deleted mutants for the ORFs of interest, and their complemented mutants, we demonstrated an impact of prophage features on growth characteristics, cell morphology and biofilm formation. Our findings argue in favor of 12/111phiA domestication by the host and a role of prophage features in cell autoaggregation, glycocalyx and biofilm formation. We suggest that lysogeny may promote GBS adaptation to the acid environment of the vagina, consequently colonizing and infecting neonates.

Resistance to third-generation cephalosporins in Escherichia coli in the French community: The times they are a-changin'?

OBJECTIVES: Since the early 2000s, Escherichia coli resistance to third-generation cephalosporins (3GCs) has been increasing in all European countries, mainly due to the spread of extended spectrum ß-lactamases (ESBLs). Here we present a retrospective study that combines resistance of E. coli to 3GCs and quinolones with data on antibiotic use in the community in a region of Northeastern France. METHODS: Since 2012, an observational surveillance of antimicrobial resistance and antibiotic use in the community was conducted: data on antimicrobial resistance in E. coli isolates were collected from 11 private laboratories, and consumption data were collected from the three main healthcare insurances. RESULTS: A significant decrease in the prevalence of resistance to 3GCs (from 5.6% to 4.2%; P < 0.001), nalidixic acid (from 16.7% to 14.8%; P = 0.004) and ciprofloxacin (from 10.9% to 8.1%; P < 0.001) was reported between 2015 and 2017. Although total antibiotic consumption did not vary significantly between 2012 and 2017, a decrease in the consumption of 3GCs (-32.%; P < 0.001) and quinolones (-25.5%; P < 0.001) was observed. CONCLUSION: Here we report a decrease in the prevalence of E. coli isolates resistant to 3GCs and quinolones in outpatients in the context of significant decreasing consumption of these two antibiotic classes.