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0031 - Oral unknown, whether mutations that alterate cell wall composition and lead to colistin resistance would also lead to changes in biofilm Antimicrobial Resistence - Diagnostic, Epidemiology and formation and virulence. Evolution towards colistin resistance in P. Measures (FG PR) aeruginosa might furthermore be enhanced by a combination therapy with metronidazole, a drug presumably increasing the The importance of adjusting for Enterococcus species when mutation frequency. The aim of the study was to explore the link assessing the burden of vancomycin resistance. A cohort study between antibiotic exposure and biofilm formation and virulence. including over 1,000 cases of enterococcal bloodstream Methods: As a continouse culture device, a morbidostat was used infection. to expose several clinical strains to three antibiotic conditions - T. Kramer*1, C. Remschmidt1, S. Werner2, M. Behnke1, F. Swab1, colistin, colistin & metronidazole, and metronidazole - and to G. Werner3, P. Gastmeier1, R. Leistner1 create samples with various colistin resistance levels. Biofilm 1Charité- Universitätsmedizin Berlin , Institute for hygiene and assays were performed using the peg-lid method to detect the environmental medicine, Berlin, Germany amount of viable cells. 2Charité- Universitätmedizin Berlin, Department of Medical and To quantify the virulence, the Galleria mellonella infection model Financial Controlling, Berlin, Germany was used. 3Robert Koch Institute (FG13) , National Reference Centre for Results: Three clinical P. aeruginosa isolates were incubated in the Staphylococci and Enterococci, Wernigerode, Germany morbidostat. Over a three week timeframe, we collected samples from the morbidostat cultures. This provided us with a total of 81 Question P. aeruginosa strains with different colistin resistance levels. These Infections caused by vancomycin-resistant enterococci (VRE) are evolved strains were further investigated and compared to their on the rise worldwide. Few studies have tried to estimate the baseline strains that were not cultured in the morbidostat. mortality burden as well as the financial burden of those infections The biofilm experiments showed that the number of viable cells in and found that VRE are associated with increased mortality and the biofilm measured using the peg-lid method increased heavily higher hospital costs. However, it is unclear whether these worse under colistin exposure in the highly colistin resistant samples outcomes are attributable to vancomycin resistance only or whether (MIC ≥16µg/ml). There was much less or no increase in the the enterococcal species (Enterococcus faecium or Enterococcus metronidazole only conditions, and no increase in the medium run faecalis) play an important role. We therefore aimed to determine samples. the burden of enterococci infections attributable to vancomycin In terms of virulence, the medium run as well as the metronidazole resistance and pathogen species (E. faecium and E. faecalis) in only condition samples showed a trend of attenuation in the cases of bloodstream infection (BSI). Galleria mellonella infection model. On the other hand, 9 out of 22 Methods highly colistin resistant strains showed a significant reduction We conducted a retrospective cohort study on patients with BSI (p<0,05) of up to 91,5% in death rates compared to the medium run caused by Enterococcus faecium or Enterococcus faecalis between samples. 2008 and 2015 in three tertiary care hospitals. We used univariate Conclusion: The morbidostat allowed us to create colistin-resistant and multivariable regression analyses to compare risk factors for P. aeruginosa strains with a wide range of MICs. Congruent to in-hospital mortality and length of stay. We calculated total colistin resistance, the strains produced more biofilm containing hospital costs more viable cells and were less virulent. Thus, these strains carry a Results higher risk of bacteremia for patients with clinical devices coated Overall, we identified 1,160 consecutive cases of BSI caused by with biofilm but might be less pathogenic. enterococci: 596 (51.4%) cases of E. faecium BSI and 564 (48.6%) cases of E. faecalis BSI. 103 cases of E. faecium BSI (17.3%) and 0039 - Oral 1 case of E. faecalis BSI (0.2%) were infected by vancomycin- resistant isolates. Multivariable analyses revealed (i) that in Antimicrobial Resistence - Diagnostic, Epidemiology and addition to different underlying diseases E. faecium was an Measures (FG PR) independent risk factor for in-hospital mortality and prolonged hospital stay and (ii) that vancomycin-resistance did not further Comparison of Vitek 2, three different gradient strip tests and increase the risk for the described outcomes among E. faecium- classical broth microdilution in detecting vanB-positive isolates. However, the overall hospital costs were significantly Enterococcus faecium isolates with low vancomycin MICs higher in vancomycin resistant Enterococcus faecium-BSI cases as I. Klare1, J. Bender1, C. Fleige1, A. Hamprecht1, S. Gatermann1, G. compared to vancomycin susceptible Enterococcus faecium- and Werner*1 Enterococcus faecalis-BSI cases 1Robert Koch Institute, Infectious Diseases, Wernigerode, Conclusions Germany Our data indicates that in-hospital mortality and infection- attributed hospital stay in enterococci BSI might rather be Introduction. German hospital patients are challenged by an influenced by Enterococcus species and underlying diseases than increasing number of vancomycin-resistant enterococci (VRE) by vancomycin resistance. Future studies should consider adjusting from colonizations and infections. This trend is mainly driven by for Enterococcus species in addition to vancomycin resistance in an increase in vanB-positive VRE (1). Further, there is a growing order to provide a conservative estimate for the burden of VRE recognition of vanB-VRE with low level vancomycin MICs just infections. below the breakpoint of R >4 mg/L. Uncertain diagnostic results may rely on confirmation by alternative tests such as gradient strip 0034 - Oral assays (e.g., Etest®). Importantly, in July 2018 EUCAST issued a warning regarding less reliable strip assay results for determining Antimicrobial Resistence - Diagnostic, Epidemiology and and confirming vancomycin resistance in enterococci (2). Measures (FG PR) Objectives. We established a strain collection of vanB-positive E. faecium isolates from all over Germany (n= 80) showing low level The impact of antibiotic pressure on the phenotypic evolution vancomycin MICs in previous standard diagnostic assays. We of clinical antibiotic resistant - Pseudomonas aeruginosa in a aimed at comparing performance of various diagnostic standard Morbidostat device and confirmatory tests to identify and determine vanB-type B. Jentzsch*1, M. Javed1, M. Willmann1 vancomycin resistance. 1Institute of Medical Microbiology and Hygiene, Tübingen, Methods. We compared the performance in determining Germany vancomycin MICs of bioMerieux"s Vitek II (card AST P611), of classical broth microdilution ("in house" procedure and plates) and Question: Colistin is a last-resort antibiotic against Pseudomonas of gradient strip assay from three providers (Oxoid, Liofilchem, aeruginosa interacting with the bacterial cell wall. It is still bioMerieux). For the latter we compared the standard procedure vs. the "macromethod"; the latter includes a richer medium (BHI likely the initial source of ESBL-E however, rats might function as instead of MH), a higher inoculum (McFarland 2 instead of infection source and transmission hub, accelerated by frequent McFarland 0.5) and a longer incubation time of up to 48h. E. interactions at a human-wildlife interface. faecalis ATCC20912, E. faecium ATCC19434 and E. gallinarum BM4174 (vanC1) and E. casseliflavus ATCC25788 (vanC2) 0056 - Oral reference isolates were used as controls. Results. Presence of vanB in all study isolates was confirmed. The Antimicrobial Resistence - Diagnostic, Epidemiology and collection was especially enriched with isolates demonstrating Measures (FG PR) vancomycin MICs of 2 - 4 mg/L (S) and 8 mg/L (R) in classical broth microdilution. We excluded vanB strains with vancomycin Thinking Outside the Box: Potential Association of MICs of 1 mg/L and/or below since these strains may possess Carbapenem Resistance with Nurse Density in Europe – A 30 defects in vanB resistance regulation. Preliminary results already Country Observational Study document various MIC results in relation to the method used. H. Kaba*1, E. Kuhlmann2, M. Kaase1, S. Scheithauer1 Automated MIC determination in Vitek II revealed the highest 1University Medical Center Göttingen (UMG), Institute of Infection number of isolates with an MIC of ≤4 mg/L ("S"). Generally, the Control and Infectious Diseases, Göttingen, Germany "macromethod" was more sensitive than the standard gradient strip 2Hannover Medical School (MHH), Institute of Epidemiology, protocol. Strips of the three producers performed differently. (study Social Medicine and Health System Research, Hannover, Germany will be completed and results evaluated by December 2018). 1) Klare et al. Epid Bull 2017;46:519 – 527 Background: Antimicrobial resistance (AMR) is one of the biggest 2) http://www.eucast.org/ast_of_bacteria/warnings/ contemporary public health threats. Estimations reveal a worldwide increase in resistance, which will cause higher rates of therapy 0043 - Oral failure, mortality and growing healthcare expenditure. Objectives: The aim was to investigate potential associations
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  • ( 12 ) United States Patent

    ( 12 ) United States Patent

    US009956282B2 (12 ) United States Patent ( 10 ) Patent No. : US 9 ,956 , 282 B2 Cook et al. (45 ) Date of Patent: May 1 , 2018 ( 54 ) BACTERIAL COMPOSITIONS AND (58 ) Field of Classification Search METHODS OF USE THEREOF FOR None TREATMENT OF IMMUNE SYSTEM See application file for complete search history . DISORDERS ( 56 ) References Cited (71 ) Applicant : Seres Therapeutics , Inc. , Cambridge , U . S . PATENT DOCUMENTS MA (US ) 3 ,009 , 864 A 11 / 1961 Gordon - Aldterton et al . 3 , 228 , 838 A 1 / 1966 Rinfret (72 ) Inventors : David N . Cook , Brooklyn , NY (US ) ; 3 ,608 ,030 A 11/ 1971 Grant David Arthur Berry , Brookline, MA 4 ,077 , 227 A 3 / 1978 Larson 4 ,205 , 132 A 5 / 1980 Sandine (US ) ; Geoffrey von Maltzahn , Boston , 4 ,655 , 047 A 4 / 1987 Temple MA (US ) ; Matthew R . Henn , 4 ,689 ,226 A 8 / 1987 Nurmi Somerville , MA (US ) ; Han Zhang , 4 ,839 , 281 A 6 / 1989 Gorbach et al. Oakton , VA (US ); Brian Goodman , 5 , 196 , 205 A 3 / 1993 Borody 5 , 425 , 951 A 6 / 1995 Goodrich Boston , MA (US ) 5 ,436 , 002 A 7 / 1995 Payne 5 ,443 , 826 A 8 / 1995 Borody ( 73 ) Assignee : Seres Therapeutics , Inc. , Cambridge , 5 ,599 ,795 A 2 / 1997 McCann 5 . 648 , 206 A 7 / 1997 Goodrich MA (US ) 5 , 951 , 977 A 9 / 1999 Nisbet et al. 5 , 965 , 128 A 10 / 1999 Doyle et al. ( * ) Notice : Subject to any disclaimer , the term of this 6 ,589 , 771 B1 7 /2003 Marshall patent is extended or adjusted under 35 6 , 645 , 530 B1 . 11 /2003 Borody U .