Real-World Treatment of Enterococcal Infections with Daptomycin: Insights from a Large European Registry (EU-CORE)

Lübbert, Christoph; Rodloff, Arne C.; Hamed, Kamal

doi:10.1007/s40121-015-0072-z

Cited by 11 publications

(7 citation statements)

References 35 publications

(30 reference statements)

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“…However, in certain settings daptomycin resistance may be considerably more frequent, as illustrated by a study including 4,274 E. faecium and 7,007 E. faecalis isolates from 19 US hospitals, which found daptomycin resistance among 3.9 and 0.2% of E. faecium and E. faecalis isolates, respectively ( Edelsberg et al, 2014 ). Similar levels of daptomycin resistance in E. faecium were recently reported for a German hospital ( Lübbert et al, 2015 ).…”

Section: Emergence Of Antibiotic Resistance In Enterococcisupporting

confidence: 85%

Global Emergence and Dissemination of Enterococci as Nosocomial Pathogens: Attack of the Clones?

et al. 2016

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Enterococci are Gram-positive bacteria that are found in plants, soil and as commensals of the gastrointestinal tract of humans, mammals, and insects. Despite their commensal nature, they have also become globally important nosocomial pathogens. Within the genus Enterococcus, Enterococcus faecium, and Enterococcus faecalis are clinically most relevant. In this review, we will discuss how E. faecium and E. faecalis have evolved to become a globally disseminated nosocomial pathogen. E. faecium has a defined sub-population that is associated with hospitalized patients and is rarely encountered in community settings. These hospital-associated clones are characterized by the acquisition of adaptive genetic elements, including genes involved in metabolism, biofilm formation, and antibiotic resistance. In contrast to E. faecium, clones of E. faecalis isolated from hospitalized patients, including strains causing clinical infections, are not exclusively found in hospitals but are also present in healthy individuals and animals. This observation suggests that the division between commensals and hospital-adapted lineages is less clear for E. faecalis than for E. faecium. In addition, genes that are reported to be associated with virulence of E. faecalis are often not unique to clinical isolates, but are also found in strains that originate from commensal niches. As a reflection of more ancient association of E. faecalis with different hosts, these determinants Thus, they may not represent genuine virulence genes but may act as host-adaptive functions that are useful in a variety of intestinal environments. The scope of the review is to summarize recent trends in the emergence of antibiotic resistance and explore recent developments in the molecular epidemiology, population structure and mechanisms of adaptation of E. faecium and E. faecalis.

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Section: Emergence Of Antibiotic Resistance In Enterococcisupporting

confidence: 85%

Global Emergence and Dissemination of Enterococci as Nosocomial Pathogens: Attack of the Clones?

et al. 2016

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“…However, taking into account the azole resistance rate of 32.9%, significant failure rates of fluconazole-based empirical antifungal therapies for Candida infections have to be considered. It is well known that numerous interventional ERC procedures accompanied by antibiotic therapy predispose for increased antimicrobial resistance in patients with acute cholangitis [ 25 , 27 ], and enterococcal species are often involved in this process [ 42 , 43 ]. Therefore, adequate microbiological diagnosis is essential and should include analysis of the extracted stents.…”

Section: Discussionmentioning

confidence: 99%

Epidemiology and Resistance Patterns of Bacterial and Fungal Colonization of Biliary Plastic Stents: A Prospective Cohort Study

et al. 2016

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BackgroundPlastic stents used for the treatment of biliary obstruction will become occluded over time due to microbial colonization and formation of biofilms. Treatment of stent-associated cholangitis is often not effective because of inappropriate use of antimicrobial agents or antimicrobial resistance. We aimed to assess the current bacterial and fungal etiology of stent-associated biofilms, with particular emphasis on antimicrobial resistance.MethodsPatients with biliary strictures requiring endoscopic stent placement were prospectively enrolled. After the retrieval of stents, biofilms were disrupted by sonication, microorganisms were cultured, and isolates were identified by matrix-associated laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry and/or biochemical typing. Finally, minimum inhibitory concentrations (MICs) were determined for various antimicrobial agents. Selected stents were further analyzed by fluorescence in situ hybridization (FISH).ResultsAmong 120 patients (62.5% males, median age 64 years) with biliary strictures (35% malignant, 65% benign), 113 double pigtail polyurethane and 100 straight polyethylene stents were analyzed after a median indwelling time of 63 days (range, 1–1274 days). The stent occlusion rate was 11.5% and 13%, respectively, being associated with a significantly increased risk of cholangitis (38.5% vs. 9.1%, P<0.001). Ninety-five different bacterial and 13 fungal species were detected; polymicrobial colonization predominated (95.8% vs. 4.2%, P<0.001). Enterococci (79.3%), Enterobacteriaceae (73.7%), and Candida spp. (55.9%) were the leading pathogens. Candida species were more frequent in patients previously receiving prolonged antibiotic therapy (63% vs. 46.7%, P = 0.023). Vancomycin-resistant enterococci accounted for 13.7%, extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae with co-resistance to ciprofloxacin accounted for 13.9%, and azole-resistant Candida spp. accounted for 32.9% of the respective isolates.ConclusionsEnterococci and Candida species play an important role in the microbial colonization of biliary stents. Therefore, empirical antimicrobial treatment of stent-associated cholangitis should be guided toward enterococci, Enterobacteriaceae, streptococci, anaerobes, and Candida. To determine causative pathogens, an accurate microbiological analysis of the extracted stent(s) may be helpful.

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“…In our study, most patients were treated with high daptomycin doses (mean 10.125 mg/kg/day). Probably the delayed response observed in previous studies on EIE could be explained by the lower doses used (average dose of 8.5 mg/kg/day) [12], since the use of increased dosage has reported higher and more sustained killing, including for E. faecium [14, 15, 18, 19].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, several in vitro studies and some case reports have demonstrated synergistic activity against enterococci with the combination of daptomycin and other antibiotics [10, 11]. Daptomycin at higher doses ranging from 8 to 14 mg/kg/day has been used in EIE with variable and conflicting results, including non-favorable microbiologic and clinical response [12–14].…”

Section: Introductionmentioning

confidence: 99%

Should High-dose Daptomycin be an Alternative Treatment Regimen for Enterococcal Endocarditis?

et al. 2019

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IntroductionPrevious series on the use of daptomycin in enterococcal infective endocarditis (EIE) have shown various outcomes, including higher mortality rates. We analyzed the effectiveness of high-dose daptomycin for the treatment of EIE.MethodsWe performed a prospective study from 2010 to 2018 in a referral center in patients with native (NVE) and prosthetic valve endocarditis (PVE) due to Enterococcus spp. The standard high-dose daptomycin at our institution is 10–12 mg/kg/day (CLCr > 30 ml/min). We compared the efficacy of a daptomycin-based regimen (DBR) versus daptomycin-sparing regimen (DSR) and daptomycin monotherapy versus combination therapy. Primary endpoints of the study were evaluation of risk factors associated with 30-day mortality and failure at end of therapy.ResultsWe collected 43 EIE cases; 29 were NVE (67.4%). Overall, 16 (37.2%) were treated with DBR, mainly with combination regimens (11, 68.7%), in the majority of cases in association with ß-lactam (7, 43.7%). The mean administered dose of daptomycin was 10.125 mg/kg/day (range 8–12 mg/kg/day). Overall, patients treated with DBR compared with patients treated with DSR had no higher mortality rates and/or failure at end of therapy (6.2% vs. 22. 2%; P 0.41 and MICs 0.25–2 mg/l, 6.2% vs. 3.7%; P 1.0). In the sub-group of patients with NVE and PVE treated with DBR and DSR, no difference was found regarding the primary endpoints on the single or combined use of daptomycin.ConclusionOur findings suggest that high-dose daptomycin might be used as an alternative treatment regimen in EIE.

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Real-World Treatment of Enterococcal Infections with Daptomycin: Insights from a Large European Registry (EU-CORE)

Cited by 11 publications

References 35 publications

Global Emergence and Dissemination of Enterococci as Nosocomial Pathogens: Attack of the Clones?

Global Emergence and Dissemination of Enterococci as Nosocomial Pathogens: Attack of the Clones?

Epidemiology and Resistance Patterns of Bacterial and Fungal Colonization of Biliary Plastic Stents: A Prospective Cohort Study

Should High-dose Daptomycin be an Alternative Treatment Regimen for Enterococcal Endocarditis?

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