Determination of a Tentative Epidemiological Cut-Off Value (ECOFF) for Dalbavancin and Enterococcus faecium

Dalbavancin is a lipoglycopeptide antibiotic that shows potent activity against Gram-positive bacteria. It circumvents vanB-type glycopeptide resistance mechanisms; however, data on the in vitro activity of dalbavancin for Enterococcus faecium (E. faecium) are scarce, and thus, no breakpoints are provided. In recent years, there has been a continuing shift from vanA-type to vanB-type vancomycin-resistance in enterococci in Central Europe. Therefore, we aimed to investigate the in vitro activity of dalbavancin against different van-genotypes, with particular focus on vanB-type E. faecium. Dalbavancin susceptibility was determined for 25 van-negative, 50 vanA-positive, and 101 vanB-positive clinical E. faecium isolates (typed by cgMLST). Epidemiological Cut-Off Values (ECOFFs) were determined using ECOFFinder. For vanB-type E. faecium isolates, dalbavancin MICs were similar to those of vancomycin-susceptible isolates reaching values no higher than 0.125 mg/L. ECOFFs for van-negative and vanB-positive isolates were 0.5 mg/l and 0.25 mg/L respectively. In contrast, E. faecium possessing vanA predominantly showed dalbavancin MICs >8 mg/L, therefore preventing the determination of an ECOFF. We demonstrated the potent in vitro activity of dalbavancin against vancomycin-susceptible and vanB-type E. faecium. On the basis of the observed wildtype distribution, a dalbavancin MIC of 0.25 mg/L can be suggested as a tentative ECOFF for E. faecium.Dalbavancin is a lipoglycopeptide antibiotic that shows potent activity against Gram-positive bacteria. It circumvents vanB-type glycopeptide resistance mechanisms; however, data on the in vitro activity of dalbavancin for Enterococcus faecium (E. faecium) are scarce, and thus, no breakpoints are provided. In recent years, there has been a continuing shift from vanA-type to vanB-type vancomycin-resistance in enterococci in Central Europe. Therefore, we aimed to investigate the in vitro activity of dalbavancin against different van-genotypes, with particular focus on vanB-type E. faecium. Dalbavancin susceptibility was determined for 25 van-negative, 50 vanA-positive, and 101 vanB-positive clinical E. faecium isolates (typed by cgMLST). Epidemiological Cut-Off Values (ECOFFs) were determined using ECOFFinder. For vanB-type E. faecium isolates, dalbavancin MICs were similar to those of vancomycin-susceptible isolates reaching values no higher than 0.125 mg/L. ECOFFs for van-negative and vanB-positive isolates were 0.5 mg/l and 0.25 mg/L respectively. In contrast, E. faecium possessing vanA predominantly showed dalbavancin MICs >8 mg/L, therefore preventing the determination of an ECOFF. We demonstrated the potent in vitro activity of dalbavancin against vancomycin-susceptible and vanB-type E. faecium. On the basis of the observed wildtype distribution, a dalbavancin MIC of 0.25 mg/L can be suggested as a tentative ECOFF for E. faecium.Peer Reviewe

Glycopeptide resistance in Enterococcus spp. and coagulase-negative staphylococci from hospitalised patients in Germany: occurrence, characteristics and dalbavancin susceptibility

Objectives: The aim of this study was to evaluate the occurrence of glycopeptide resistance in enterococci and coagulase-negative staphylococci (CoNS) and to determine the susceptibilities of the identified glycopeptide-resistant isolates to dalbavancin. Methods: Twenty-two medical laboratories participated in the study conducted in 2016/17 by the Paul-Ehrlich-Society for Chemotherapy. Each laboratory was asked to collect 30 Enterococcus spp. (limited to Enterococcus faecalis and Enterococcus faecium) and 30 CoNS isolates consecutively from hospitalised patients with a proven or suspected infection. Results: A total of 1285 isolates were collected, comprising 364 E. faecalis, 291 E. faecium and 630 CoNS. No E. faecalis isolates (0%) but 76 E. faecium isolates (26.1%) were vancomycin-resistant, of which 21 showed the VanA type and 55 the VanB type. The proportion of vancomycin-resistant strains among E. faecium isolates from patients in intensive care units (21.6%) was significantly lower than that from patients on regular wards (30.5%). Among the CoNS, 67 isolates (10.6%) were teicoplanin-resistant but none were vancomycin-resistant, with resistance only detected in Staphylococcus epidermidis (12.2%), Staphylococcus haemolyticus (17.9%) and Staphylococcus hominis (13.2%). Dalbavancin at ≤0.25 mg/L inhibited all VanB-type enterococci and 95.5% of teicoplanin-resistant CoNS. Conclusion: The level of glycopeptide resistance in E. faecalis remains very low in Germany but achieved 26% in E. faecium and was >10% in CoNS. Dalbavancin appears to be a feasible option for treating infections caused by VanB-type vancomycin-resistant E. faecium and teicoplanin-resistant CoNS.Peer Reviewe

The phylogenetic landscape and nosocomial spread of the multidrug-resistant opportunist Stenotrophomonas maltophilia

Recent studies portend a rising global spread and adaptation of human- or healthcare-associated pathogens. Here, we analyse an international collection of the emerging, multidrug-resistant, opportunistic pathogen Stenotrophomonas maltophilia from 22 countries to infer population structure and clonality at a global level. We show that the S. maltophilia complex is divided into 23 monophyletic lineages, most of which harbour strains of all degrees of human virulence. Lineage Sm6 comprises the highest rate of human-associated strains, linked to key virulence and resistance genes. Transmission analysis identifies potential outbreak events of genetically closely related strains isolated within days or weeks in the same hospitals

Temporal changes in clinical and radiographic variables in dogs with preclinical myxomatous mitral valve disease: The EPIC study

The Evaluation of pimobendan in dogs with cardiomegaly caused by preclinical myxomatous mitral valve disease (EPIC) study monitored dogs with myxomatous mitral valve disease (MMVD) as they developed congestive heart failure (CHF)

In-vitro activity of ceftolozane/tazobactam against Pseudomonas aeruginosa and Enterobacteriaceae isolates recovered from hospitalized patients in Germany

To evaluate the activity of ceftolozane/tazobactam compared with other broad-spectrum antimicrobials against Pseudomonas aeruginosa and Enterobacteriaceae, 497 non-duplicate P. aeruginosa and 802 Enterobacteriaceae clinical isolates were consecutively collected during the period from September 2014 to April 2015 from patients in Germany with bloodstream, lower respiratory tract, intra-abdominal or urinary tract infections. Antimicrobial susceptibility testing was performed by broth microdilution. Results were interpreted according to EUCAST criteria. Ceftolozane/tazobactam showed good activity against Escherichia coli and Klebsiella pneumoniae isolates with MIC50/90 values of 0.25/0.5 mg/L and 0.25/1 mg/L, respectively. Comparatively, piperacillin/tazobactam, ceftazidime and meropenem MIC50/90 values were 2/8 mg/L, 0.25/8 mg/L and <= 0.03/<= 0.03 mg/L, respectively, for E. coli, and 2/16 mg/L, 0.12/8 mg/L, and <= 0.03/<= 0.03 mg/L, respectively, for K. pneumoniae isolates. The activity of ceftolozane/tazobactam against P. aeruginosa was superior to that of other antipseudomonal antimicrobials. Based on MIC50/90 values, ceftolozane/tazobactam (0.5/2 mg/L) was more active than piperacillin/tazobactam (8/64 mg/L), ceftazidime (2/16 mg/L), cefepime (2/16 mg/L) or meropenem (0.5/8 mg/L). In conclusion, ceftolozane/tazobactam exhibited the best in vitro potency of the antibiotics tested against P. aeruginosa, including isolates that were resistant to piperacillin/tazobactam, cefepime, ceftazidime, doripenem, meropenem, ciprofloxacin, levofloxacin, amikacin, and tobramycin. Ceftolozane/tazobactam has the potential to become a useful addition to the limited armamentarium of drugs that can be used to treat this problem pathogen. (c) 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved

Thirty years of VRE in Germany – “expect the unexpected”: The view from the National Reference Centre for Staphylococci and Enterococci

Enterococci are commensals of the intestinal tract of many animals and humans. Of the various known and still unnamed new enterococcal species, only isolates of Enterococcus faecium and Enterococcus faecalis have received increased medical and public health attention. According to textbook knowledge, the majority of infections are caused by E. faecalis. In recent decades, the number of enterococcal infections has increased, with the increase being exclusively associated with a rising number of nosocomial E. faecium infections. This increase has been accompanied by the dissemination of certain hospital-acquired strain variants and an alarming progress in the development of antibiotic resistance namely vancomycin resistance. With this review we focus on a description of the specific situation of vancomycin resistance among clinical E. faecium isolates in Germany over the past 30 years. The present review describes three VRE episodes in Germany, each of which is framed by the beginning and end of the respective decade. The first episode is specified by the first appearance of VRE in 1990 and a country-wide spread of specific vanA-type VRE strains (ST117/CT24) until the late 1990s. The second decade was initially marked by regional clusters and VRE outbreaks in hospitals in South-Western Germany in 2004 and 2005, mainly caused by vanA-type VRE of ST203. Against the background of a certain “basic level” of VRE prevalence throughout Germany, an early shift from the vanA genotype to the vanB genotype in clinical isolates already occurred at the end of the 2000s without much notice. With the beginning of the third decade in 2010, VRE rates in Germany have permanently increased, first in some federal states and soon after country-wide. Besides an increase in VRE prevalence, this decade was marked by a sharp increase in vanB-type resistance and a dominance of a few, novel strain variants like ST192 and later on ST117 (CT71, CT469) and ST80 (CT1065). The largest VRE outbreak, which involved about 2,900 patients and lasted over three years, was caused by a novel and until that time, unknown strain type of ST80/CT1013 (vanB). Across all periods, VRE outbreaks were mainly oligoclonal and strain types varied over space (hospital wards) and time. The spread of VRE strains obviously respects political borders; for instance, both vancomycin-variable enterococci which were highly prevalent in Denmark and ST796 VRE which successfully disseminated in Australia and Switzerland, were still completely absent among German hospital patients, until to date

In vitro activity of ceftobiprole against key pathogens associated with pneumonia in hospitalized patients: results from the PEG surveillance study, 2010

Empirical treatment of hospital-acquired pneumonia (HAP) has increasingly been threatened by methicillin-resistant Staphylococcus aureus (MRSA) and multidrug resistant Gram-negative pathogens. In contrast, empirical treatment of community-acquired pneumonia (CAP) is primarily impeded by antimicrobial-resistant pneumococci. Ceftobiprole, recently approved for the treatment of HAP and CAP in Europe, is active against a broad-spectrum of Gram-positive and Gram-negative pathogens, including MRSA and Pseudomonas aeruginosa. The objective of this study was to evaluate the susceptibility of ceftobiprole among 1,246 S. aureus, Streptococcus pneumoniae, Enterobacteriaceae species and P. aeruginosa isolated from respiratory tract and blood. Isolates were collected in 25 laboratories across Germany, Switzerland and Austria. Minimum inhibitory concentrations (MICs) were determined using the microdilution method according to the standard ISO 20776-1:2006 and interpreted by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints. Two-thirds of the isolates were obtained from respiratory specimens and one third from blood. There were 544 intensive care unit (ICU) isolates and 702 non-ICU isolates. The share of MRSA in S. aureus was 16%. Among pneumococci, 18.5% showed reduced susceptibility to penicillin. An extended-spectrum β-lactamase (ESBL) phenotype was confirmed for 18.4% of the Escherichia coli and 16.7% of the Klebsiella pneumoniae isolates. Of the P. aeruginosa isolates, 20.7% were ceftazidime-resistant. MIC50/90 values of ceftobiprole for methicillin-susceptible S. aureus (MSSA) and MRSA were 0.5/0.5 mg/L and 2/2 mg/L, respectively. All pneumococci were inhibited at 1 mg/L ceftobiprole. The activity of ceftobiprole against E. coli and K. pneumoniae was similar to that of ceftriaxone, but ceftobiprole showed superior activity against Enterobacteriaceae species known to produce chromosomally encoded AmpC-β-lactamases. MIC50/90 values of ceftobiprole for ceftazidime-susceptible (4/16 mg/L) and ceftazidime-resistant P. aeruginosa (16/>32 mg/L) were comparable to those of cefepime (4/8 mg/L and 32/>32 mg/L, respectively). These findings suggest that ceftobiprole may represent a suitable option for the empirical treatment of HAP and CAP

High Prevalence of the ermB Gene among Erythromycin-Resistant Streptococcus pneumoniae Isolates in Germany during the Winter of 2000-2001 and In Vitro Activity of Telithromycin

Of 595 isolates of Streptococcus pneumoniae from outpatients with respiratory tract infections, collected from 17 microbiology laboratories, 14.1% were resistant to erythromycin. Eighty-three erythromycin-resistant isolates were genetically analyzed, 83.1% of which harbored the ermB gene. Only four isolates (4.8%) harbored the mefA gene. Telithromycin exhibited potent activity against all isolates

Evaluation of a Phenotypic Algorithm to Direct Carbapenemase Testing in Pseudomonas aeruginosa: Validation in a Multicenter German Cohort

Pseudomonas aeruginosa remains a prominent nosocomial pathogen. Detection of carbapenemase-producing P. aeruginosa is vital to dictate antimicrobial therapy and infection control measures. A pragmatic, minimum inhibitory concentration-based algorithm using imipenem AND meropenem-resistant plus ceftazidime-, cefepime-, and piperacillin/tazobactam-nonsusceptible criterion was derived to guide carbapenemase testing in P. aeruginosa. This study was an assessment of the algorithm's test performance in a cohort of 985 nonduplicate P. aeruginosa isolates collected from 20 German medical laboratories. Susceptibility data were assessed in the algorithm using both Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) interpretations. Sensitivity and specificity were calculated to evaluate algorithm test performance. The original algorithm criteria resulted in high specificity (95-97%) using both CLSI and EUCAST criteria; however, it failed to capture five carbapenemase-harboring isolates testing piperacillin/tazobactam susceptibility (CLSI/EUCAST). Two carbapenemase-producing isolates were also meropenem susceptible per EUCAST. A modified algorithm utilizing imipenem OR meropenem-resistant plus ceftazidime and cefepime nonsusceptible, improved the sensitivity of the criteria without significantly compromising specificity (CLSI sensitivity/specificity: 96%/94% and EUCAST sensitivity/specificity: 96%/95%). Application of the modified algorithm criteria resulted in high sensitivity and specificity using both CLSI and EUCAST interpretations in a large cohort of clinical P. aeruginosa. Utilization of this algorithm can improve the efficiency of carbapenemase testing in the clinical laboratory