scholarly journals Oritavancin Activity Tested against Molecularly Characterized Staphylococci and Enterococci Displaying Elevated Linezolid MIC Results

2016 ◽  
Vol 60 (6) ◽  
pp. 3817-3820
Author(s):  
Rodrigo E. Mendes ◽  
David J. Farrell ◽  
Helio S. Sader ◽  
Robert K. Flamm ◽  
Ronald N. Jones
Keyword(s):  
Enterococcus Faecalis ◽  
Enterococcus Faecium ◽  
Cross Resistance ◽  
Content Type

Oritavancin (MIC50/90, 0.03/0.06 to 0.12 μg/ml) had potent activity against linezolid-resistant staphylococci, as well asEnterococcus faecalisandEnterococcus faecium(oritavancin MIC50/90, 0.015/0.12 μg/ml against both species). All linezolid-resistant isolates were inhibited by oritavancin at ≤0.12 μg/ml. These results confirmed the absence of cross-resistance between linezolid and oritavancin in staphylococci and enterococci.

scholarly journals Surotomycin Demonstrates LowIn VitroFrequency of Resistance and Rapid Bactericidal Activity in Clostridium difficile, Enterococcus faecalis, and Enterococcus faecium

2014 ◽  
Vol 58 (7) ◽  
pp. 3976-3982 ◽  
Author(s):  
Carmela T. M. Mascio ◽  
Laurent Chesnel ◽  
Grace Thorne ◽  
Jared A. Silverman
Keyword(s):  
Clostridium Difficile ◽  
Enterococcus Faecalis ◽  
Bactericidal Activity ◽  
Enterococcus Faecium ◽  
Limit Of Detection ◽  
Serial Passage ◽  
Cross Resistance ◽  
Content Type ◽  
Naive Control ◽  
Emergence Of Resistance

ABSTRACTSurotomycin (CB-183,315) is an orally administered, minimally absorbed, selective bactericidal cyclic lipopeptide in phase 3 development for the treatment ofClostridium difficile-associated diarrhea. The aim of this study was to evaluate the emergence of resistance inC. difficile(ATCC 700057 and three recent clinical isolates from the restriction endonuclease analysis groups BI, BK, and K), vancomycin-susceptible (VS)Enterococcus faecalis(ATCC 49452), vancomycin-resistant (VR)E. faecalis(ATCC 700802), VSEnterococcus faecium(ATCC 6569), and VRE. faecium(ATCC 51559) under anaerobic conditions. The rate of spontaneous resistance was below the limit of detection (<10−8to <10−9) for surotomycin at 16 and 32× the MIC for all isolates tested. Under selective pressure by serial passage,C. difficilegrew in a maximum of 4 μg/ml surotomycin (final MICs of 2 to 8 μg/ml [4- to 16-fold higher than those of the naive control]) at day 15, with the exception of theC. difficileBK strain, which grew in 16 to 32 μg/ml (final MICs of 8 to 32 μg/ml [16- to 64-fold higher than those of the naive control]). Enterococci remained relatively unchanged over 15 days, growing in a maximum of 8 μg/ml surotomycin (final MICs of 2 to 16 μg/ml [8- to 64-fold higher than those of the naive control]). Of the isolates tested, no cross-resistance to vancomycin, rifampin, ampicillin, metronidazole, or moxifloxacin was observed. Surotomycin at 20× MIC demonstrated equally rapid bactericidal activity (≥3-log-unit reduction in CFU/ml in ≤8 h) against naive and reduced-susceptibility isolates ofC. difficile, VSEnterococcus(VSE), and VREnterococcus(VRE), except forC. difficileBK (2.6-log-unit reductions for both). These results suggest that emergence of resistance to surotomycin againstC. difficile,E. faecalis, andE. faeciumis likely to be rare.

scholarly journals Pharmacodynamics of Daptomycin against Enterococcus faecium and Enterococcus faecalis in the Murine Thigh Infection Model

2018 ◽  
Vol 62 (10) ◽  
Author(s):  
James M. Kidd ◽  
Kamilia Abdelraouf ◽  
Tomefa E. Asempa ◽  
Romney M. Humphries ◽  
David P. Nicolau
Keyword(s):  
Enterococcus Faecalis ◽  
Enterococcus Faecium ◽  
Hill Equation ◽  
Infection Model ◽  
Free Drug Concentration ◽  
Time Curve ◽  
Content Type ◽  
Concentration Time ◽  
The Hill ◽  
Susceptibility Breakpoint

ABSTRACT The Clinical and Laboratory Standards Institute (CLSI) daptomycin MIC susceptibility breakpoint for the treatment of enterococcal infections is ≤4 μg/ml. However, patients receiving daptomycin for the treatment of infections caused by enterococci with MICs of ≤4 μg/ml may experience treatment failures. We assessed the pharmacodynamics of daptomycin against enterococci in a neutropenic murine thigh infection model and determined the exposures necessary for bacteriostasis and a 1-log10-CFU reduction of Enterococcus faecalis and Enterococcus faecium. We further characterized daptomycin efficacy at clinically achievable exposures. Six E. faecium and 6 E. faecalis isolates (daptomycin MICs, 0.5 to 32 μg/ml) were studied. Daptomycin was administered at various doses over 24 h to achieve area under the free drug concentration-time curve-to-MIC ratios (fAUC0–24/MIC) ranging from 1 to 148. Daptomycin regimens that simulate mean human exposures following doses of 6, 8, and 10 mg/kg of body weight/day were also studied. Efficacy was assessed by the differences in the number of log10 CFU per thigh at 24 h. The Hill equation was used to estimate the fAUC0–24/MIC required to achieve bacteriostasis and a 1-log10-CFU reduction. For E. faecium, a 1-log10-CFU reduction required an fAUC0–24/MIC of 12.9 (R2 = 0.71). For E. faecalis, a 1-log10-CFU reduction was not achieved, while the fAUC0–24/MIC required for stasis was 7.2 (R2 = 0.8). With a human-simulated regimen of 6 mg/kg/day, a 1-log10-CFU reduction was observed in 3/3 E. faecium isolates with MICs of <4 μg/ml and 0/3 E. faecium isolates with MICs of ≥4 μg/ml; however, a 1-log10-CFU reduction was not achieved for any of the 6 E. faecalis isolates. These results, alongside clinical data, prompt a reevaluation of the current breakpoint.

scholarly journals β-Lactams Enhance Daptomycin Activity against Vancomycin-Resistant Enterococcus faecalis and Enterococcus faecium inIn VitroPharmacokinetic/Pharmacodynamic Models

2015 ◽  
Vol 59 (5) ◽  
pp. 2842-2848 ◽  
Author(s):  
Jordan R. Smith ◽  
Katie E. Barber ◽  
Animesh Raut ◽  
Michael J. Rybak
Keyword(s):  
Body Weight ◽  
Combination Therapy ◽  
Enterococcus Faecalis ◽  
Enterococcus Faecium ◽  
Single Agent ◽  
Vancomycin Resistant Enterococcus ◽  
Content Type ◽  
Vancomycin Resistant ◽  
Combination Regimens

ABSTRACTEnterococcus faecalisandEnterococcus faeciumare frequently resistant to vancomycin and β-lactams. In enterococcal infections with reduced glycopeptide susceptibility, combination therapy is often administered. Our objective was to conduct pharmacokinetic/pharmacodynamic (PK/PD) models to evaluate β-lactam synergy with daptomycin (DAP) against resistant enterococci. OneE. faecalisstrain (R6981) and twoE. faeciumstrains (R6370 and 8019) were evaluated. DAP MICs were obtained. All strains were evaluated for response to LL37, an antimicrobial peptide, in the presence and absence of ceftaroline (CPT), ertapenem (ERT), and ampicillin (AMP). After 96 h,in vitromodels were run simulating 10 mg DAP/kg body weight/day, 600 mg CPT every 8 h (q8h), 2 g AMP q4h, and 1 g ERT q24h, both alone and in combination against all strains. DAP MICs were 2, 4, and 4 μg/ml for strains R6981, R6370, and 8019, respectively. PK/PD models demonstrated bactericidal activity with DAP-CPT, DAP-AMP, and DAP-ERT combinations against strain 8019 (P< 0.001 and log10CFU/ml reduction of >2 compared to any single agent). Against strains R6981 and R6370, the DAP-AMP combination demonstrated enhancement against R6370 but not R6981, while the combinations of DAP-CPT and DAP-ERT were bactericidal, demonstrated enhancement, and were statistically superior to all other regimens at 96 h (P< 0.001) against both strains. CPT, ERT, and AMP similarly augmented LL37 killing against strain 8019. In strains R6981 and R6370, CPT and ERT aided LL37 more than AMP (P< 0.001). Compared to DAP alone, combination regimens provide better killing and prevent resistance. Clinical research involving DAP combinations is warranted.

scholarly journals Mutation Landscape of Acquired Cross-Resistance to Glycopeptide and β-Lactam Antibiotics in Enterococcus faecium

2015 ◽  
Vol 59 (9) ◽  
pp. 5306-5315 ◽  
Author(s):  
Emmanuelle Sacco ◽  
Mélanie Cortes ◽  
Nathalie Josseaume ◽  
Christiane Bouchier ◽  
Vincent Dubée ◽  
...  
Keyword(s):  
Enterococcus Faecium ◽  
Selection Procedure ◽  
Sugar Metabolism ◽  
Cross Resistance ◽  
Mismatch Repair Gene ◽  
Repair Gene ◽  
Content Type ◽  
Regulatory Systems ◽  
Regulatory Circuits ◽  
Neutral Mutations

ABSTRACTBypass of thed,d-transpeptidase activity of penicillin-binding proteins by anl,d-transpeptidase (Ldtfm) results in resistance to ampicillin and glycopeptides inEnterococcus faeciumM9, a mutant obtained by nine consecutive selection steps. Resistance requires activation of a cryptic locus for production of the essential tetrapeptide-containing substrate of Ldtfmand impaired activity of protein phosphatase StpA. Here, whole-genome sequencing revealed a high mutation rate for the entire selection procedure (79 mutations in 900 generations). Acquisition of a mutation in the mismatch repair genemutLhad little impact on the frequency of rifampin-resistant mutants although the mutation spectrum of M9 was typical of impaired MutL with high transversion to transition (40/11) and substitution to deletion (51/28) ratios. M9 did not mainly accumulate neutral mutations since base substitutions occurred more frequently in coding sequences than expected (χ2= 5.0;P< 0.05) and silent mutations were underrepresented (χ2= 5.72;P< 0.02). None of the mutations directly affected recognition of the tetrapeptide substrate of Ldtfmby peptidoglycan synthesis enzymes. Instead, mutations appear to remodel regulatory circuits involving two-component regulatory systems and sugar metabolism. The high number of mutations required for activation of thel,d-transpeptidase pathway may strongly limit emergence of cross-resistance to ampicillin and glycopeptides by this mechanism.

scholarly journals Tedizolid as Step-Down Therapy following Daptomycin versus Continuation of Daptomycin against Enterococci and Methicillin- and Vancomycin-Resistant Staphylococcus aureus in a Rat Endocarditis Model

2020 ◽  
Vol 64 (5) ◽  
Author(s):  
Kavindra V. Singh ◽  
Cesar A. Arias ◽  
Barbara E. Murray
Keyword(s):  
Staphylococcus Aureus ◽  
Enterococcus Faecalis ◽  
Enterococcus Faecium ◽  
Content Type ◽  
Vancomycin Resistant ◽  
Step Down

ABSTRACT Tedizolid (TZD) and daptomycin (DAP) were assessed in a rat endocarditis model against Enterococcus faecalis, Enterococcus faecium (resistant to vancomycin and ampicillin), and Staphylococcus aureus. As a monotherapy, TZD for 5 days was not effective in a comparison with no-treatment controls, while DAP for 5 days was significantly effective against these bacteria. Step-down therapy (DAP for 3 days followed by TZD for 2 days) was as effective as DAP for 5 days and was comparable to 3 days of DAP plus ceftriaxone against all bacteria and to 3 days of DAP plus gentamicin against E. faecalis OG1RF.

scholarly journals Efficacy of Tedizolid against Enterococci and Staphylococci, Including cfr+ Strains, in a Mouse Peritonitis Model

2019 ◽  
Vol 63 (4) ◽  
Author(s):  
Kavindra V. Singh ◽  
Cesar A. Arias ◽  
Barbara E. Murray
Keyword(s):  
Staphylococcus Aureus ◽  
Enterococcus Faecalis ◽  
Enterococcus Faecium ◽  
Methicillin Resistant ◽  
Content Type ◽  
Peritonitis Model

ABSTRACT In a mouse peritonitis model, tedizolid was comparable to linezolid and daptomycin against an Enterococcus faecium strain (VANr, AMPr), an Enterococcus faecalis strain, and a methicillin-resistant Staphylococcus aureus (MRSA) strain with and without cfr. Against a cfr(B)+ E. faecium, tedizolid was inferior in vivo to linezolid and daptomycin, despite an ∼4-fold lower MIC.

scholarly journals Comparative In Vitro Activities of Ceftaroline and Tedizolid against Clinical Strains of Staphylococcus aureus and Enterococcus: Results from the China Antimicrobial Surveillance Network (CHINET) in 2018

2020 ◽  
Vol 64 (11) ◽  
Author(s):  
Yan Guo ◽  
Yang Yang ◽  
Yonggui Zheng ◽  
Shi Wu ◽  
Dandan Yin ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Enterococcus Faecalis ◽  
Enterococcus Faecium ◽  
Clinical Usefulness ◽  
Clinical Isolates ◽  
Surveillance Network ◽  
Content Type ◽  
Highly Active ◽  
Antimicrobial Surveillance

ABSTRACT The in vitro activities of ceftaroline and tedizolid were compared against Staphylococcus aureus, Enterococcus faecalis, and Enterococcus faecium clinical isolates collected from the China Antimicrobial Surveillance Network. Ceftaroline demonstrated potent activity against S. aureus isolates (MIC50/90, ≤0.25/1 mg/liter). Tedizolid was also highly active against S. aureus (MIC50/90, 0.25/0.5 mg/liter) and Enterococcus (MIC50/90, 0.5/0.5 mg/liter) isolates. Our results support the clinical usefulness of ceftaroline and tedizolid in treating Gram-positive infections.

scholarly journals Draft Genome Sequences of 43 Enterococcus faecalis and Enterococcus faecium Isolates from a Commercial Beef Processing Plant and Retail Ground Beef

2019 ◽  
Vol 8 (42) ◽  
Author(s):  
Devin B. Holman ◽  
Katherine E. Gzyl ◽  
Rahat Zaheer ◽  
Tineke H. Jones ◽  
Tim A. McAllister
Keyword(s):  
Enterococcus Faecalis ◽  
Enterococcus Faecium ◽  
Draft Genome ◽  
Ground Beef ◽  
Processing Plant ◽  
Genome Sequences ◽  
Content Type ◽  
Beef Processing ◽  
Processing Facility ◽  
Conveyor Belts

Here, we report the draft genome sequences of 36 Enterococcus faecalis and 7 Enterococcus faecium isolates recovered from a beef processing facility and retail ground beef. The beef processing facility samples were collected from beef carcasses, conveyor belts, and ground product.

scholarly journals Nonclinical and Clinical Enterococcus faecium Strains, but Not Enterococcus faecalis Strains, Have Distinct Structural and Functional Genomic Features

2013 ◽  
Vol 80 (1) ◽  
pp. 154-165 ◽  
Author(s):  
Eun Bae Kim ◽  
Maria L. Marco
Keyword(s):  
Antibiotic Resistance ◽  
Enterococcus Faecalis ◽  
Virulence Factors ◽  
Enterococcus Faecium ◽  
Food Production ◽  
Animal Health ◽  
Functional Genomic ◽  
Genomic Features ◽  
Content Type ◽  
Proximity Analysis

ABSTRACTCertain strains ofEnterococcus faeciumandEnterococcus faecaliscontribute beneficially to animal health and food production, while others are associated with nosocomial infections. To determine whether there are structural and functional genomic features that are distinct between nonclinical (NC) and clinical (CL) strains of those species, we analyzed the genomes of 31E. faeciumand 38E. faecalisstrains. Hierarchical clustering of 7,017 orthologs found in theE. faeciumpangenome revealed that NC strains clustered into two clades and are distinct from CL strains. NCE. faeciumgenomes are significantly smaller than CL genomes, and this difference was partly explained by significantly fewer mobile genetic elements (ME), virulence factors (VF), and antibiotic resistance (AR) genes.E. faeciumortholog comparisons identified 68 and 153 genes that are enriched for NC and CL strains, respectively. Proximity analysis showed that CL-enriched loci, and not NC-enriched loci, are more frequently colocalized on the genome with ME. In CL genomes, AR genes are also colocalized with ME, and VF are more frequently associated with CL-enriched loci. Genes in 23 functional groups are also differentially enriched between NC and CLE. faeciumgenomes. In contrast, differences were not observed between NC and CLE. faecalisgenomes despite their having larger genomes thanE. faecium. Our findings show that unlikeE. faecalis, NC and CLE. faeciumstrains are equipped with distinct structural and functional genomic features indicative of adaptation to different environments.

scholarly journals Genetic Variability of Vancomycin-Resistant Enterococcus faecium and Enterococcus faecalis Isolates from Humans, Chickens, and Pigs in Malaysia

2013 ◽  
Vol 79 (15) ◽  
pp. 4528-4533 ◽  
Author(s):  
Yitbarek Getachew ◽  
Latiffah Hassan ◽  
Zunita Zakaria ◽  
Saleha Abdul Aziz
Keyword(s):  
Enterococcus Faecalis ◽  
Enterococcus Faecium ◽  
Clonal Complex ◽  
Housekeeping Genes ◽  
Vancomycin Resistant Enterococcus ◽  
Content Type ◽  
Vancomycin Resistant Enterococci ◽  
Vancomycin Resistant ◽  
Sequence Types ◽  
Representative Samples

ABSTRACTVancomycin-resistant enterococci (VRE) have been reported to be present in humans, chickens, and pigs in Malaysia. In the present study, representative samples of VRE isolated from these populations were examined for similarities and differences by using the multilocus sequence typing (MLST) method. Housekeeping genes ofEnterococcus faecium(n= 14) andEnterococcus faecalis(n= 11) isolates were sequenced and analyzed using the MLST databases eBURST and goeBURST. We found five sequence types (STs) ofE. faeciumand six STs ofE. faecalisexisting in Malaysia.Enterococcus faeciumisolates belonging to ST203, ST17, ST55, ST79, and ST29 were identified, andE. faeciumST203 was the most common among humans. The MLST profiles ofE. faeciumfrom humans in this study were similar to the globally reported nosocomial-related strain lineage belonging to clonal complex 17 (CC17). Isolates from chickens and pigs have few similarities to those from humans, except for one isolate from a chicken, which was identified as ST203.E. faecalisisolates were more diverse and were identified as ST4, ST6, ST87, ST108, ST274, and ST244, which were grouped as specific to the three hosts.E. faecalis, belonging to the high-risk CC2 and CC87, were detected among isolates from humans. In conclusion, even though one isolate from a chicken was found clonal to that of humans, the MLST analysis ofE. faeciumandE. faecalissupports the findings of others who suggest VRE to be predominantly host specific and that clinically important strains are found mainly among humans. The infrequent detection of a human VRE clone in a chicken may in fact suggest a reverse transmission of VRE from humans to animals.

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