scholarly journals In Vitro Antimicrobial Activity of Fosfomycin, Rifampin, Vancomycin, Daptomycin Alone and in Combination Against Vancomycin-Resistant Enterococci

2021 ◽  
Author(s):  
Wei Yu ◽  
Yiheng Jiang ◽  
Hao Xu ◽  
Li Zhang ◽  
Xuehang Jin ◽  
...  
Keyword(s):  
Virulence Genes ◽  
Therapeutic Option ◽  
Bactericidal Effect ◽  
Resistance Determinant ◽  
Vancomycin Resistant Enterococci ◽  
Vancomycin Resistant ◽  
High Level ◽  
Time Kill ◽  
Level Resistance

Abstract OBJECTIVESThe emergence of vancomycin resistant enterococci (VRE) is shortening the choices for clinical anti-infective therapy. The aim of this study was to investigate the mechanism of vancomycin resistance and evaluate the effect of fosfomycin (FM), rifampin (RIF), vancomycin (VAN), linezolid (LNZ), daptomycin (DAP) alone or in combination against VRE.METHODSEight VRE isolates were collected. A total of 18 antibiotics susceptibility tests were further done for VRE. Whole genome sequencing and bioinformatics analysis were performed. The effect of FM, RIF, VNA, LNZ, DAP alone or in combination was determined using anti-biofilm testing and the time-kill assay.RESULTSAll isolates were susceptible to LNZ and DPA. The high-level resistance determinant of VAN in these strains was due to VanA-type cassette. MLST revealed two different STs for vancomycin-resistant Enterococcus faecium (VREm) and four different STs for vancomycin-resistant E. faecalis (VREs). Virulence genes in VREs were more than VREm, especially for 4942 isolated from blood. Gene acm and uppS were only identified in VREm, while virulence genes related to cytolysin were only found in E. faecalis. Further in vitro anti-biofilm testing and time-kill assay found FM (83 mg/L) combined with DAP (20.6 mg/L) and DAP monotherapy (47.1 mg/L) showed bactericidal effect against 8 tested VRE strains at 24h. CONCLUSIONSThe high-level resistance determinant of VAN in these strains was due to VanA-type cassette. FM combined with DAP might be greater potential therapeutic option against VRE.

scholarly journals Analysis of genetic diversity and antibiotic options for clinical Listeria monocytogenes infections in China

2021 ◽  
Author(s):  
Wei Yu ◽  
Yicheng Huang ◽  
Chaoqun Ying ◽  
Yanzi Zhou ◽  
Li Zhang ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Biofilm Formation ◽  
Virulence Genes ◽  
Genomic Island ◽  
Therapeutic Option ◽  
Treatment Options ◽  
Bactericidal Effect ◽  
Time Kill ◽  
Sequence Types

Abstract Background The aim of this study was to investigate the mechanism of Listeria monocytogenes (Lm) pathogenicity and resistance. In addition, the effect of existing treatment options against Lm were systematically evaluated. Methods Six Lm isolates were collected and antimicrobial susceptibility testing of 15 antibiotics were done. Subsequently, whole genome sequencing and bioinformatics analysis were performed. Biofilm formation was evaluated by crystal violet staining. Furthermore, the effect of meropenem, linezolid, penicillin, vancomycin, trimethoprim/sulfamethoxazole were determined using the time-kill assay. Results Four sequence types (STs) were identified (ST1, ST3, ST87, ST451). Multi-virulence-locus sequence typing (MVLST) results classified ST87 isolates into cluster. All isolates were resistant to fosfomycin and daptomycin with fosX and mprF. In addition, a total of 80 virulence genes were detected and 72 genes were found in all six isolates. Seven genes associated with haemolysin were found in 26530 and 115423. However, due to lack of one genomic island including virulence genes related to flagellar synthesis, isolate 115423 produced less biofilm than five other isolates. Even all isolates were susceptible to vancomycin, the in vitro time-kill assay showed vancomycin monotherapy resulted in less than 2 log10 CFU/mL compared with the initial count. Trimethoprim/sulfamethoxazole at serum or cerebrospinal fluid concentrations had bactericidal effect against tested Lm strains at 24 h. Conclusions ST87 clone was a typical prevalent ST in clinical Lm isolates in China. Trimethoprim/sulfamethoxazole might be greater potential therapeutic option against Lm infections.

scholarly journals Efficacy of Ampicillin plus Ceftriaxone in Treatment of Experimental Endocarditis Due to Enterococcus faecalis Strains Highly Resistant to Aminoglycosides

1999 ◽  
Vol 43 (3) ◽  
pp. 639-646 ◽  
Author(s):  
Joan Gavaldà ◽  
Carmen Torres ◽  
Carmen Tenorio ◽  
Pedro López ◽  
Myriam Zaragoza ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Enterococcus Faecalis ◽  
Pharmacokinetic Parameters ◽  
Initial Inoculum ◽  
High Level ◽  
Time Kill ◽  
Disk Method ◽  
Level Resistance

The purpose of this work was to evaluate the in vitro possibilities of ampicillin-ceftriaxone combinations for 10 Enterococcus faecalis strains with high-level resistance to aminoglycosides (HLRAg) and to assess the efficacy of ampicillin plus ceftriaxone, both administered with humanlike pharmacokinetics, for the treatment of experimental endocarditis due to HLRAg E. faecalis. A reduction of 1 to 4 dilutions in MICs of ampicillin was obtained when ampicillin was combined with a fixed subinhibitory ceftriaxone concentration of 4 μg/ml. This potentiating effect was also observed by the double disk method with all 10 strains. Time-kill studies performed with 1 and 2 μg of ampicillin alone per ml or in combination with 5, 10, 20, 40, and 60 μg of ceftriaxone per ml showed a ≥2 log10 reduction in CFU per milliliter with respect to ampicillin alone and to the initial inoculum for all 10E. faecalis strains studied. This effect was obtained for seven strains with the combination of 2 μg of ampicillin per ml plus 10 μg of ceftriaxone per ml and for six strains with 5 μg of ceftriaxone per ml. Animals with catheter-induced endocarditis were infected intravenously with 108 CFU of E. faecalis V48 or 105 CFU of E. faecalisV45 and were treated for 3 days with humanlike pharmacokinetics of 2 g of ampicillin every 4 h, alone or combined with 2 g of ceftriaxone every 12 h. The levels in serum and the pharmacokinetic parameters of the humanlike pharmacokinetics of ampicillin or ceftriaxone in rabbits were similar to those found in humans treated with 2 g of ampicillin or ceftriaxone intravenously. Results of the therapy for experimental endocarditis caused by E. faecalis V48 or V45 showed that the residual bacterial titers in aortic valve vegetations were significantly lower in the animals treated with the combinations of ampicillin plus ceftriaxone than in those treated with ampicillin alone (P < 0.001). The combination of ampicillin and ceftriaxone showed in vitro and in vivo synergism against HLRAgE. faecalis.

scholarly journals High-level vancomycin-resistant enterococci causing hospital infections

1989 ◽  
Vol 103 (1) ◽  
pp. 173-181 ◽  
Author(s):  
A. H. C. Uttley ◽  
R. C. George ◽  
J. Naidoo ◽  
N. Woodford ◽  
A. P. Johnson ◽  
...  
Keyword(s):  
Plasmid Dna ◽  
Vancomycin Resistance ◽  
Recipient Strain ◽  
Hospital Infections ◽  
Minimal Inhibitory Concentrations ◽  
Vancomycin Resistant Enterococci ◽  
Vancomycin Resistant ◽  
Many Sources ◽  
High Level ◽  
Level Resistance

SUMMARYNosocomial infection or colonization due to enterococci with high-level resistance to vancomycin (minimal inhibitory concentrations [MICs] between 64 and > 2000 mg/L) has occurred in 41 patients with renal disease. These vancomycin-resistant enterococci were cultured from many sources including blood. All but one strain contained one or more plasmids ranging in molecular weight from 1·0 to 40 Megadaltons (MDa). Vancomycin resistance was transferable by conjugation to a susceptible recipient strain ofEnterococcus faecalisbut this was not always associated with plasmid DNA. The emergence of transferable high-level vancomycin resistance in enterococci causing significant clinical infections is of particular importance since vancomycin is widely regarded as a reserve drug for the management of infections with multi-resistant Gram-positive organisms.

scholarly journals Is there any association between antibiotic resistance and virulence genes in Enterococcus isolates?

2019 ◽  
Vol 6 (12) ◽  
pp. 310-315
Author(s):  
Nergis Aşgın ◽  
Emre Taşkın
Keyword(s):  
Antibiotic Resistance ◽  
Virulence Genes ◽  
Multidrug Resistant ◽  
Automated System ◽  
High Frequencies ◽  
Resistant Strains ◽  
Vancomycin Resistant ◽  
High Level

Objective: In this study, we aim to determine the frequency of antibiotic resistance and five virulence genes in Enterococcus species and the relationship between antibiotic resistance and virulence genes. Material and Methods: A total of 86 Enterococcus strains isolated from inpatients between 2015 and 2016 were included. Identification and antibiotic susceptibilities of strains were determined using a BD Phoenix fully automated system. The presence of virulence-associated genes (esp, gel E, asa1, hyl, and cyl) were investigated by using PCR method. Results: Of the 86 Enterococcus strains, 53 (61.6%) and 33 (38.4%) were Enterococcus faecium and Enterococcus faecalis, respectively. Vancomycin and high-level gentamicin resistance (HLGR) in E. faecalis strains were 0.6% and 60.6%, respectively. Furthermore, 52 of the 53 E. faecium strains were both vancomycin-resistant and HLGR. The frequency of esp, gel E, asa1, cyl, and hyl was 91.9%, 60.5%, 54.7%, 43%, and 26.7%, respectively.  The asa 1, cyl, and gel E genes were detected at high frequencies in vancomycin-susceptible and non-HLGR strains, whereas hyl gene was detected at high frequencies in vancomycin-resistant and HLGR strains. Conclusion: Virulence genes were more frequent in vancomycin-susceptible and non-HLGR Enterococcus strains than in the resistant strains. Although infections caused by multidrug-resistant strains are difficult to treat, it should be considered that susceptible strains have more virulence genes. This may reduce the in vivo efficacy of drugs and lead to treatment failures. Therefore, in addition to the in vitro susceptibilities of drugs, clinical efficacy should be monitored.

scholarly journals Efficacy of vancomycin and teicoplanin alone and in combination with streptomycin in experimental, low-level vancomycin-resistant, VanB-type Enterococcus faecalis endocarditis.

1996 ◽  
Vol 40 (1) ◽  
pp. 55-60 ◽  
Author(s):  
D P Nicolau ◽  
M N Marangos ◽  
C H Nightingale ◽  
K B Patel ◽  
B W Cooper ◽  
...  
Keyword(s):  
Enterococcus Faecalis ◽  
Resistant Strain ◽  
Low Level ◽  
Vancomycin Resistant ◽  
Low Levels ◽  
High Level ◽  
Isogenic Strains ◽  
Level Resistance

The efficacy of vancomycin (VM) and teicoplanin (TE), alone and in combination with streptomycin (SM), against enterococci that express low-level VanB-type VM resistance was investigated in experimental endocarditis using isogenic strains of Enterococcus faecalis susceptible to glycopeptides and aminoglycosides or inducibly resistant to low levels of VM (MIC = 16 micrograms/ml). VM was significantly less active against the resistant strain than against the susceptible strain, establishing that low-level VanB-type VM resistance can influence therapeutic efficacy. By contrast, TE had equally good activity against both strains. VM or TE combined with SM was synergistic and bactericidal against the resistant strain in vitro. While both combinations were efficient in reducing bacterial density in vivo, TE plus SM was significantly superior to VM plus SM if valve sterilization was considered. These data suggest that despite the presence of low-level VanB-type resistance, combination therapy with a glycopeptide and SM (and presumably other aminoglycosides to which there is not high-level resistance) will nevertheless provide effective bactericidal activity.

scholarly journals A Comparison of High-Level Aminoglycoside Resistance in Vancomycin-Sensitive and Vancomycin-Resistant Enterococcus Species

2002 ◽  
Vol 30 (5) ◽  
pp. 529-534 ◽  
Author(s):  
H Yazgi ◽  
M Ertek ◽  
S Erol ◽  
A Ayyildiz
Keyword(s):  
Brain Heart Infusion ◽  
Bactericidal Effect ◽  
Vancomycin Resistance ◽  
Glycopeptide Antibiotics ◽  
Aminoglycoside Resistance ◽  
Significant Difference ◽  
Vancomycin Resistant ◽  
High Level ◽  
Infusion Agar ◽  
Level Resistance

The aim of this study was to investigate whether there was a significant difference in high-level aminoglycoside resistance (HLAR) between vancomycin-sensitive enterococci (VSE) and vancomycin-resistant enterococci (VRE). Vancomycin resistance was determined in 116 Enterococcus isolates using brain-heart infusion agar containing 6 μg/ml vancomycin. HLAR was determined by both standard agar screening and disk diffusion methods. Streptomycin and gentamicin were used as predictors of HLAR. Vancomycin resistance and HLAR were found in 17 (14.7%) and 41 (35.3%) of the Enterococcus strains, respectively. HLAR was found in 11 of 17 VRE and 30 of 98 VSE strains. HLAR in VRE strains was significantly higher than in VSE. More enterococcal strains were found to be resistant to both gentamicin and streptomycin (29) than to gentamicin (one) or streptomycin (11) alone. The HLAR rate in VRE was two-fold higher than in VSE. The synergistic bactericidal effect of aminoglycosides and β-lactam or glycopeptide antibiotics is lost if there is high-level resistance to aminoglycosides.

scholarly journals High diversity of vancomycin-resistant Enterococcus faecium isolated in Southern Brazil

2019 ◽  
Author(s):  
Renata O Soares ◽  
Gabriela R Cunha ◽  
Vinicius P Perez ◽  
Jussara L Siqueira ◽  
Gustavo E Sambrano ◽  
...  
Keyword(s):  
Profile Analysis ◽  
Southern Brazil ◽  
Porto Alegre ◽  
Vancomycin Resistant Enterococci ◽  
Antimicrobial Susceptibility Profile ◽  
Vancomycin Resistant ◽  
Clonal Spread ◽  
High Level ◽  
Relationship Of ◽  
Level Resistance

Background. Vancomycin-resistant enterococci (VRE) are common in some hospital settings and their clonal spread has been described in different regions of the world. We determined the antimicrobial susceptibility profile and the clonal relationship of VRE isolates recovered from inpatients at three general hospitals of Porto Alegre, Brazil. Results. Ninety-four VRE were characterized as Enterococcus faecium and exhibited resistance to teicoplanin, ampicillin, ciprofloxacin, and susceptibility to linezolid, quinupristin-dalfopristin and daptomycin. High level resistance to gentamicin was detected in 13.8% of them. All VREfm harbored vanA gene, while 85.1% and 94.7% harbored respectively esp and acm virulence genes. PFGE profile analysis revealed 23 clonal types including 79 isolates, while 15 isolates exhibited unique pattern type, showing a polyclonal distribution of VREfm in Southern Brazil. Conclusion. These findings contribute to the local understanding regarding the characteristics of the circulating VREs in the region.

Development of high level daptomycin resistance (HLDR) in Abiotrophia and Granulicatella spp isolates from patients with infective endocarditis (IE).

2021 ◽  
Author(s):  
María A. Cañas ◽  
Adrian Téllez ◽  
Cristina García de la Mària ◽  
Anders Dahl ◽  
Javier García-González ◽  
...  
Keyword(s):  
Infective Endocarditis ◽  
Combination Therapy ◽  
Minimal Inhibitory Concentration ◽  
Inhibitory Concentration ◽  
Therapeutic Option ◽  
Combination Therapies ◽  
Viridans Streptococci ◽  
High Level ◽  
Time Kill

Abiotrophia and Granulicatella species are fastidious organisms, representing around 1%–3% of infective endocarditis (IE). Little is known about the optimal antibiotic treatment of these species, and daptomycin has been suggested as a therapeutic option. We describe the antimicrobial profile in Abiotrophia and Granulicatella IE isolates, investigate high-level daptomycin resistance (HLDR) development and evaluate daptomycin activity in combination therapy. In vitro studies with 16 IE strains (6 A. defectiva , 9 G. adiacens and 1 G. elegans ) were performed using microdilution to determine minimal inhibitory concentration (MIC) and time-kill methodology to evaluate combination therapy. Daptomycin non-susceptibility (DNS; MIC≥ 2 mg/L) and HLDR (MIC≥256 mg/L) were based on existing Clinical and Laboratory Standards (CLSI) breakpoints for viridans streptococci. All isolates were susceptible to vancomycin: G. adiacens was more susceptible to penicillin and ampicillin than A. defectiva (22% vs. 0%, and 67% vs. 33%) but less susceptible to ceftriaxone and daptomycin (56% vs. 83%, and 11% vs. 50%). HLDR developed in both A. defectiva (33%) and G. adiacens (78%) after 24h exposure to daptomycin. Combination therapy did not prevent the development of daptomycin resistance with ampicillin (2/3 strains), gentamicin (2/3 strains), ceftriaxone (2/3 strains) or ceftaroline (2/3 strains). Once developed, HLDR was stable for a prolonged time (>3 weeks) in G. adiacens , whereas in A. defectiva the HLDR it reversed to baseline MIC at day 10. This study is first to demonstrate rapid HLDR development in Abiotrophia and Granulicatella species in vitro . Resistance was stable, and most combination therapies did not prevent it.

scholarly journals Impact of Human Serum Albumin on Oritavancin In Vitro Activity against Enterococci

2009 ◽  
Vol 53 (6) ◽  
pp. 2687-2689 ◽  
Author(s):  
Geoffrey A. McKay ◽  
Sylvain Beaulieu ◽  
Ingrid Sarmiento ◽  
Francis F. Arhin ◽  
Thomas R. Parr ◽  
...  
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Vancomycin Resistant Enterococci ◽  
Vancomycin Resistant ◽  
Time Kill ◽  
The Impact

ABSTRACT Oritavancin is a lipoglycopeptide with activity against gram-positive pathogens including vancomycin-resistant enterococci. The impact of human serum albumin (HSA) on oritavancin activity against enterococci was compared to those of vancomycin, daptomycin, teicoplanin, and linezolid in vitro using MIC and time-kill methods. Oritavancin MICs increased between 0- and 8-fold in the presence of HSA. In time-kill assays with HSA, oritavancin retained activity, killing or inhibiting enterococci more rapidly than did comparators when peak concentrations were simulated.

scholarly journals Oritavancin Combinations with β-Lactams against Multidrug-Resistant Staphylococcus aureus and Vancomycin-Resistant Enterococci

2016 ◽  
Vol 60 (4) ◽  
pp. 2352-2358 ◽  
Author(s):  
Jordan R. Smith ◽  
Juwon Yim ◽  
Animesh Raut ◽  
Michael J. Rybak
Keyword(s):  
Staphylococcus Aureus ◽  
Single Agent ◽  
Multidrug Resistant ◽  
Content Type ◽  
Vancomycin Resistant Enterococci ◽  
Complex Models ◽  
Vancomycin Resistant ◽  
Mrsa Strains ◽  
Time Kill

ABSTRACTOritavancin possesses activity against vancomycin-resistant enterococci (VRE) and methicillin-resistantStaphylococcus aureus(MRSA).In vitrodata suggest synergy between beta-lactams (BLs) and vancomycin or daptomycin, agents similar to oritavancin. We evaluated the activities of BLs combined with oritavancin against MRSA and VRE. Oritavancin MICs were determined for 30 strains, 5 each of MRSA, daptomycin-nonsusceptible (DNS) MRSA, vancomycin-intermediate MRSA (VISA), heteroresistant VISA (hVISA), vancomycin-resistantEnterococcus faecalis, and vancomycin-resistantEnterococcus faecium. Oritavancin MICs were determined in the presence of subinhibitory concentrations of BLs. Oritavancin combined with ceftaroline, cefazolin, or nafcillin was evaluated for lethal synergy against MRSA, and oritavancin combined with ceftaroline, ampicillin, or ertapenem was evaluated for lethal synergy against VRE in 24-h time-kill assays. Oritavancin at 0.5× the MIC was combined with BLs at 0.5× the MIC or the biological free peak concentration, whichever one was lower. Synergy was defined as a ≥2-log10-CFU/ml difference between the killing achieved with the combination and that achieved with the most active single agent at 24 h. Oritavancin MICs were ≤0.125 μg/ml for all MRSA isolates except three VISA isolates with MICs of 0.25 μg/ml. Oritavancin MICs for VRE ranged from 0.03 to 0.125 μg/ml. Oritavancin in combination with ceftaroline was synergistic against all MRSA phenotypes and statistically superior to all other combinations against DNS MRSA, hVISA, and MRSA isolates (P< 0.02). Oritavancin in combination with cefazolin and oritavancin in combination with nafcillin were also synergistic against all MRSA strains. Synergy between oritavancin and all BLs was revealed against VRE strain 8019, while synergy between oritavancin and ampicillin or ertapenem but not ceftaroline was demonstrated against VRE strain R7164. The data support the potential use of oritavancin in combination with BLs, especially oritavancin in combination with ceftaroline, for the treatment of infections caused by MRSA. The data from the present study are not as strong for oritavancin in combination with BLs for VRE. Further study of both MRSA and VRE in more complex models is warranted.

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