Editorial Commentary: Linezolid vs Daptomycin for Vancomycin-Resistant Enterococci: The Evidence Gap Between Trials and Clinical Experience.
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SUBMITTER: McKinnell JA
PROVIDER: S-EPMC4551011 | biostudies-literature | 2015 Sep
REPOSITORIES: biostudies-literature
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Editorial Commentary: Linezolid vs Daptomycin for Vancomycin-Resistant Enterococci: The Evidence Gap Between Trials and Clinical Experience.
McKinnell James A JA Arias Cesar A CA
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20150610 6
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Project description:Infections with multidrug resistant (MDR) Enterococcus faecium (Efm) are a growing problem. Vancomycin resistance in enterococci has long challenged treatment, necessitating the use of linezolid or daptomycin. Subsequently, daptomycin-, linezolid-, vancomycin-resistant Efm (DLVRE) infections have emerged. Case reports and guidelines for treating DLVRE infections are limited. Here, we describe the clinical and laboratory management of an MDR Efm protracted intraabdominal (IA) infection and breakthrough DLVRE bacteremia. Serial Efm resistance was evaluated using whole genome sequencing (WGS), susceptibility testing, and synergy analysis. Prior to in vitro synergy testing, combination antimicrobial therapy with daptomycin (DAP) and ceftaroline (CPT) was employed to treat the patient's central line-associated DLVRE bloodstream infection. In vitro antimicrobial testing revealed no synergy between daptomycin and ceftaroline; however, the patient's bacteremia cleared following initiation of both in conjunction with catheter removal. Sequencing of the DLVRE isolates revealed multiple genomic mutations which explained both linezolid and daptomycin resistance phenotypes and confirmed the presence of a plasmid containing the vanA operon. Sequential WGS of two additional bacterial isolates from the same patient revealed protracted colonization with a single DLVRE clone and suggested the development of bacterial subpopulations. Pairing clinical isolate susceptibilities with WGS and synergy testing should be encouraged in clinical practice to better inform antimicrobial management in cases of multidrug resistance.
| S-EPMC9372734 | biostudies-literature
Project description:IntroductionVancomycin-resistant Enterococci (VRE) infections cause significant morbidity and mortality in liver transplant (LT) recipients. Management is challenging, especially in the setting of daptomycin resistance (DR).MethodsSingle-center retrospective review of patients who underwent LT between January 1, 2020, and December 31, 2022, and developed VRE infections. Descriptive statistics were used and Kaplan-Meier curves estimated freedom from treatment failure and survival.ResultsForty-two patients (median age 58; 64% female; 67% white) were included. Alcohol-related cirrhosis (48%) and metabolic dysfunction-associated steatohepatitis (31%) were the most common indications for LT, and most were from deceased donors (86%). VRE infection occurred at a median of 21 days after LT, and 16% had known prior VRE colonization. Common infection sites were blood (45%, n = 19), intraabdominal (36%, n = 15), and urine (36%, n = 15). Most were initially treated with daptomycin alone (64%) or in combination with other agents (21%); 7% received linezolid alone. Twelve (29%) developed breakthrough infections during treatment and 11 (26%) had recurrent infections after discontinuation of treatment. All-cause mortality was 36% (n = 15) at a median of 90 days after VRE infection diagnosis and was nearly twice as high in patients with DR (63%).ConclusionVRE infection in LT recipients relapsed or recurred in over 25%. Mortality was high, especially in cases with DR. More data is needed to establish an optimal treatment approach, particularly for relapse and DR.
| S-EPMC11666863 | biostudies-literature
Project description:BackgroundVancomycin-resistant enterococci (VRE) are a major cause of morbidity and mortality in immunocompromised patients. Tracking the dissemination of VRE strains is crucial to understand the dynamics of emergence and spread of VRE in the hospital setting.MethodsWhole genome sequencing (WGS) and phylogenetic analyses were performed to identify dominant VRE strains and potential transmission networks between 35 patients with VRE-positive rectal swabs and their rooms (main rooms and bathrooms) on the leukemia (LKM) and the hematopoietic cell transplant (HCT) floors. Sequence types (STs), drug resistance genes, and patients' outcomes were also determined.ResultsA total of 89 VRE strains grouped into 10 different STs, of which newly described STs were isolated from both floors (ST736, ST494, ST772, and ST1516). We observed highly genetically related strains transmitted between rooms, floors, and time periods in an average period of 39 days (ranging from 3 to 90 days). Of 5 VRE bacteremia events, 3 strains were lacking the pili operon fms14-17-13 (ST203) and the remaining 2 were resistant to daptomycin (DAP; ST736, ST664). Of 10 patients harboring DAP-resistant strains, only 2 were exposed to DAP within 4 months before strain recovery.ConclusionsOur comparisons of VRE strains derived from the environment and immunocompromised patients confirmed horizontal transfer of highly related genetic lineages of multidrug-resistant (particularly to DAP) VRE strains between HCT and LKM patients and their room environment. Implementing WGS can be useful in distinguishing VRE reservoirs where interventions can be targeted to prevent and control the spread of highly resistant organisms.
| S-EPMC8677550 | biostudies-literature
Project description:PurposeThe 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 studies indicated FM (83 mg/L) combined with DAP (20.6 mg/L) and DAP monotherapy (47.1 mg/L) had bactericidal effect against VRE isolates at 24h.ConclusionHigh-level resistance determinant of VAN in tested isolates was due to VanA-type cassette. FM combined with DAP is a potential therapeutic option for VRE infections.
| S-EPMC8285921 | biostudies-literature
Project description:BackgroundLinezolid, which has bacteriostatic activity, is approved for the treatment of vancomycin-resistant enterococci (VRE) infections. Meanwhile, daptomycin exerts bactericidal activity against VRE, but is not approved for the treatment of VRE bacteremia. Only a few studies with small sample sizes have compared the effectiveness of these drugs for treatment of VRE bacteremia.MethodsPubMed, EMBASE, and the Cochrane Library were searched for studies of VRE bacteremia treatment published before January 1, 2014. All studies reporting daptomycin and linezolid treatment outcomes simultaneously were included. The endpoints were mortality and microbiological cure. The adjusted odds ratios (aORs) of mortality in daptomycin- and linezolid-treated patients were extracted if available. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for all outcomes using a random-effects model.ResultsThirteen studies (532 patients receiving daptomycin, 656 patients receiving linezolid) met the selection criteria. All studies had retrospective cohort designs and relatively small sample sizes. Eight studies compared the aORs of mortality in daptomycin- and linezolid-treated patients. Four studies were published as conference papers and there was significant heterogeneity among these studies (I2 = 63%, p = 0.04). Daptomycin use was not associated with better microbiological cure (daptomycin vs. linezolid, OR: 0.67, 95% CI: 0.42-1.06, p = 0.09). However, mortality was higher in patients receiving daptomycin (OR: 1.43, 95% CI: 1.09-1.86, p = 0.009). Subgroup analysis of studies that reported aORs indicated that daptomycin was associated with higher mortality (OR: 1.59, 95% CI: 1.02-2.50, p = 0.04). There was no evidence of publication bias, but all enrolled studies were retrospective, had small sample sizes, and had substantial limitations.ConclusionsAlthough limited data is available, the current meta-analysis shows that linezolid treatment for VRE bacteremia was associated with a lower mortality than daptomycin treatment. However, the results should be interpreted cautiously because of limitations inherent to retrospective studies and the high heterogeneity among studies. A large randomized trial is needed to confirm the present results.
| S-EPMC4269951 | biostudies-literature
Project description:Limited therapeutic options exist for the treatment of vancomycin-resistant Enterococcus (VRE) bacteremia; the most commonly used are daptomycin and linezolid. We attempted a systematic review and meta-analysis of the comparative efficacy of those two agents. Studies comparing daptomycin to linezolid treatment for VRE bacteremia, published until August 2012, were identified from the MEDLINE, EMBASE, CENTRAL, ISI Web of Science, and SCOPUS databases. All comparative studies on patients older than 18 years of age that provided mortality data were considered eligible for this systematic review and meta-analysis. ?he primary outcome of the meta-analysis was 30-day all-cause mortality. Ten retrospective studies including 967 patients were identified. Patients treated with daptomycin had significantly higher 30-day all-cause mortality (odds ratio [OR], 1.61; 95% confidence interval [CI], 1.08 to 2.40) and infection-related mortality (OR, 3.61; 95% CI, 1.42 to 9.20) rates than patients treated with linezolid. When data from all 10 studies were combined, overall mortality was also significantly increased among patients treated with daptomycin (OR, 1.41; 95% CI, 1.06 to 1.89). These findings were confirmed when odds ratios adjusted for potential confounders were pooled. Relapse rates among patients treated with daptomycin were also higher (OR, 2.51; 95% CI, 0.94 to 6.72), although this difference did not reach statistical significance. Adverse event rates were not significantly different between the two groups. Notwithstanding the absence of randomized prospective data, available evidence suggests that mortality rates may be higher with daptomycin than with linezolid among patients treated for VRE bacteremia.
| S-EPMC3910884 | biostudies-other
Project description:Whole-genome sequencing was used to examine a persistent Enterococcus faecium bacteremia that acquired heteroresistance to three antibiotics in response to prolonged multidrug therapy. A comparison of the complete genomes before and after each change revealed the emergence of known resistance determinants for vancomycin and linezolid and suggested that a novel mutation in fabF, encoding a fatty acid synthase, was responsible for daptomycin nonsusceptibility. Plasmid recombination contributed to the progressive loss of vancomycin resistance after withdrawal of the drug.
| S-EPMC5913925 | biostudies-literature
Project description:BackgroundAntimicrobial drug resistance, including vancomycin-resistant enterococci (VRE), has long been an inescapable clinical problem. If vancomycin loose its therapeutic relevance, a regimen of linezolid combined with fosfomycin may provide an alternative option.MethodsIn this study, the in vitro antimicrobial effect of linezolid combined with fosfomycin on several different types of VRE was investigated using a checkerboard method and time-kill assays. Based on the results of the 24 h time-kill assays, a 22 factorial design was then adopted. Finally, the post-antibiotic effect (PAE), post-antibiotic sub-minimum inhibitory concentration effect (PASME), and single sub-minimum inhibitory concentration effect (SME) of a combination of the two drugs on three selected strains was examined.ResultsThe checkerboard method and factorial design analysis showed that linezolid combined with fosfomycin not only had synergistic and additive effects but also had an interactive effect on VREs. The time-kill assays showed that 1× minimum inhibitory concentration (MIC) of linezolid combined with 1× MIC or 1/4× MIC of fosfomycin had no statistically significant difference in the bactericidal effect against VRE at 24 h (P>0.05). The combination of the two drugs did not significantly extend the PAE or the SME; however, in relation to 1/4× MIC, the combination of the two drugs significantly prolonged the duration of the PASME compared to that of a single drug on VREs (P<0.05; with values of 1.97±0.01, 4.32±0.18, and 1.74±0.13 h, respectively).ConclusionsOur results showed that when linezolid is selected for the treatment of VRE infections, sub-inhibitory concentrations of fosfomycin can be administered at multiple intervals to improve the therapeutic effect.
| S-EPMC8904999 | biostudies-literature
Project description:Vancomycin-resistant Enterococcus faecium bloodstream infections (VREF-BSI) cause significant mortality, highlighting the need to optimize their treatment. We compared the effectiveness and safety of daptomycin (DAP) and linezolid (LZD) as continuous or sequential therapy for VREF-BSI in a national, retrospective, propensity score (PS)-matched cohort study of hospitalized Veterans Affairs patients (2004 to 2014). We compared clinical outcomes and adverse events among patients treated with continuous LZD, continuous DAP, or sequential LZD followed by DAP (LZD-to-DAP). Secondarily, we analyzed the impact of infectious diseases (ID) consultation and source of VREF-BSI. A total of 2,630 patients were included in the effectiveness analysis (LZD [n = 1,348], DAP [n = 1,055], LZD-to-DAP [n = 227]). LZD was associated with increased 30-day mortality versus DAP (risk ratio [RR], 1.11; 95% confidence interval [CI], 1.01 to 1.22; P = 0.042). After PS matching, this relationship persisted (RR, 1.13; 95% CI, 1.02 to 1.26; P = 0.015). LZD-to-DAP switchers had lower mortality than those remaining on LZD (RR, 1.29; 95% CI, 1.03 to 1.63; P = 0.021), suggesting a benefit may still be derived with sequential therapy. LZD-treated patients experienced more adverse events, including a ≥50% reduction in platelets (RR, 1.07; 95% CI, 1.03 to 1.11; P = 0.001). DAP was associated with lower mortality than was LZD in patients with endocarditis (RR, 1.20; 95% CI, 1.02 to 1.41; P = 0.024); however, there was no statistically significant association between treatment group and mortality with regard to other sources of infection. Therefore, source of infection appears to be important in selection of patients most likely to benefit from DAP over LZD.
| S-EPMC5404546 | biostudies-literature
Project description:IntroductionEnterococcus faecalis is a significant cause of nosocomial infections and is difficult to treat because of intrinsic and acquired resistance to many antibiotics. In addition, the emergence of linezolid-resistant E. faecalis (LZR-Efa) is reducing the choices available for anti-infective therapy. The aim of this study was to examine the in vitro antibacterial effects of fosfomycin (FM), vancomycin (VAN) and daptomycin (DAP), alone and in combination, against LZR-Efa.MethodsFive LZR-Efa strains and E. faecalis ATCC 29212 were studied. The antibacterial effects of FM, and of FM, VAN and DAP, were assessed using the time-kill assay. Biofilm formation and elimination were evaluated by crystal violet staining.ResultsWhen used at concentrations greater than 0.5 × MIC, FM did not produce dose-dependent effects against LZR-Efa isolates. The use of DAP (47.1 mg/L) alone, and FM (83 mg/L) combined with DAP (20.6 mg/L), produced a persistent inhibitory effect against both planktonic LZR-Efa isolates and those forming biofilms. In addition, FM and VAN combined with glucose-6-phosphate produced visible eradication effects against biofilms grown for 24 h, while DAP alone or combined with FM resulted in the best eradication activity against biofilms grown for 72 h prior to exposure.ConclusionThe use of FM combined with DAP provided the best potential therapeutic option for treating LZR-Efa infections out of those tested. In addition, the optimum treatment for biofilm elimination depended on the stage of biofilm formation.
| S-EPMC7680468 | biostudies-literature