Vancomycin-Resistant<i>Enterococcus faecium</i>(VRE) Bacteremia in Infective Endocarditis Successfully Treated with Combination Daptomycin and Tigecycline

Polidori, Marina; Nuccorini, A.; Tascini, Carlo; Gemignani, G; Iapoce, Riccardo; Leonildi, Alessandro; Tagliaferri, Enrico; Menichetti, Francesco

doi:10.1179/joc.2011.23.4.240

Cited by 34 publications

(20 citation statements)

References 8 publications

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“…Several reports have demonstrated effective use of daptomycin plus tigecycline for the treatment of endocarditis caused by E. faecium (44)(45)(46). In our hands, this combination was frequently antagonistic, but again, in vivo data are required to confirm this finding.…”

Section: Discussionsupporting

confidence: 47%

In Vitro Activity of Daptomycin in Combination with β-Lactams, Gentamicin, Rifampin, and Tigecycline against Daptomycin-Nonsusceptible Enterococci

Wong-Beringer

Charlton

Miller

et al. 2015

Antimicrob Agents Chemother

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f Enterococci that are nonsusceptible (NS; MIC > 4 g/ml) to daptomycin are an emerging clinical concern. The synergistic combination of daptomycin plus beta-lactams has been shown to be effective against vancomycin-resistant Enterococcus (VRE) species in vitro. This study systematically evaluated by in vitro time-kill studies the effect of daptomycin in combination with ampicillin, cefazolin, ceftriaxone, ceftaroline, ertapenem, gentamicin, tigecycline, and rifampin, for a collection of 9 daptomycin-NS enterococci that exhibited a broad range of MICs and different resistance-conferring mutations. We found that ampicillin plus daptomycin yielded the most consistent synergy but did so only for isolates with mutations to the liaFSR system. Daptomycin binding was found to be enhanced by ampicillin in a representative isolate with such mutations but not for an isolate with mutation to the yycFGHIJ system. In contrast, ampicillin enhanced the killing of the LL-37 human antimicrobial peptide against daptomycin-NS E. faecium with either the liaFSR or yycFGHIJ mutation. Antagonism was noted only for rifampin and tigecycline and only for 2 or 3 isolates. These data add support to the growing body of evidence indicating that therapy combining daptomycin and ampicillin may be helpful in eradicating refractory VRE infections. Daptomycin is a cyclic lipopeptide antimicrobial agent with bactericidal activity against Gram-positive bacteria, including Enterococcus spp. Daptomycin is not approved by the U.S. Food and Drug Administration (FDA) for the treatment of infections caused by vancomycin-resistant Enterococcus (VRE) strains (e.g., vancomycin-resistant Enterococcus faecalis) or by vancomycin-susceptible or -resistant E. faecium strains. However, due to a limited number of available therapeutic options, daptomycin is frequently used in clinical practice for treatment of serious infections caused by these bacteria. No daptomycin resistance breakpoint has been established for the enterococci by the Clinical and Laboratory Standards Institute or the U.S. FDA. Isolates with MICs above the susceptible breakpoint of 4 g/ml are therefore referred to as daptomycin-nonsusceptible (DNS) isolates (1). The prevalence of DNS Enterococcus strains in the United States remains low, ranging from 0.02% for E. faecalis to 0.18% for E. faecium (2). Nonetheless, we and others have isolated DNS Enterococcus strains from both patients treated with and patients naive to daptomycin therapy (3-8) and much higher rates of DNS E. faecium have been reported in Europe (9).The recent description of daptomycin-susceptible Enterococcus strains for which daptomycin exhibits only bacteriostatic activity (10, 11) brings further into question the role of daptomycin for the treatment of enterococcal infections. These isolates have decreased susceptibility to daptomycin (DSD), with daptomycin MICs ranging from 3 to 4 g/ml, which is higher than the wildtype modal daptomycin MICs of 0.5 g/ml for E. faecalis and 2.0 g/ml for E. faecium (12). These isolates harbor po...

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Section: Discussionsupporting

confidence: 47%

In Vitro Activity of Daptomycin in Combination with β-Lactams, Gentamicin, Rifampin, and Tigecycline against Daptomycin-Nonsusceptible Enterococci

Wong-Beringer

Charlton

Miller

et al. 2015

Antimicrob Agents Chemother

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“…In a recent ICAAC, Ceron et al presented a 5-year study on daptomycin efficacy for enterococcal IE, with promising results [184]. Some successfully treated cases of multidrugresistant E. faecium endocarditis with daptomycin plus tigecycline combination have been reported [130,[134][135][136]. The conclusion of a very recent study reviewing all reported daptomycinnonsusceptible strains was that resistance to daptomycin among enterococci (defined as MICs >4 μg/ml) is rare [185].…”

Section: Vancomycin-resistant Strainsmentioning

confidence: 90%

Enterococcal Endocarditis Revisited

et al. 2015

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The Enterococcus species is the third main cause of infective endocarditis (IE) worldwide, and it is gaining relevance, especially among healthcare-associated cases. Patients with enterococcal IE are older and have more comorbidities than other types of IE. Classical treatment options are limited due to the emergence of high-level aminoglycosides resistance (HLAR), vancomycin resistance and multidrug resistance in some cases. Besides, few new antimicrobial alternatives have shown real efficacy, despite some of them being recommended by major guidelines (including linezolid and daptomycin). Ampicillin plus ceftriaxone 2 g iv./12 h is a good option for Enterococcus faecalis IE caused by HLAR strains, but randomized clinical trials are essential to demonstrate its efficacy for non-HLAR EFIE and to compare it with ampicillin plus short-course gentamicin. The main mechanisms of resistance and treatment options are also reviewed for other enterococcal species.

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“…24,25,[27][28][29][30][31] Treatment of severe sepsis by Gram-positive bacteria in the fragile patient should be evaluated based on the patient's additional risk factors and comorbidities and on the ecosystem of the hospital where they are being treated in relation to the percentage of methicillinresistant Staphylococcus aureus that is present.…”

Section: The Treatment Of Sepsis In the Fragile Patientmentioning

confidence: 99%

“…If microbiological findings reveal a methicillinsensitive S. aureus, then the choice could fall on: oxacillin 2 g iv every 6 h. [30][31][32][33][34] We have divided the therapeutic proposals for the treatment of sepsis regardless of whether etiology is Gram-positive or Gram-negative. Nonetheless, empirical approach therapy still remains valid when the causative agent is uncertain; in this case the recommendation is to associate: piperacillin-tazobactam 4.5 g ¥ 3 iv (or continuous infusion) or meropenem 1 g ¥ 3 iv + amikacin 15-20 mg/kg/day iv administered once + glycopeptide or daptomycin.…”

Section: The Treatment Of Sepsis In the Fragile Patientmentioning

confidence: 99%

Sepsis in frail patient

2016

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Frailty is defined as a clinical syndrome in which three or more of the following criteria are present: unintentional weight loss, self-reported exhaustion, weakness (grip strength), slow walking speed and low physical activity. Sepsis is defined as an inflammatory response to infection, with severe sepsis and septic shock being the most severe forms. The incidence of severe sepsis increases with older age and several studies have shown that there are many risk factors that predispose the elderly to a higher incidence of sepsis. Pre-existing co-morbidities such as cancer, diabetes, obesity, human immunodeficiency virus, and renal or pulmonary disease can cause sepsis, but other factors including poor lifestyle habits (i.e., smoking, drug or alcohol abuse), malnutrition, and endocrine deficiencies, which are frequent in the elderly, may also predispose to severe infections. Other risk factors for sepsis include recurrent hospitalization, especially in the Intensive Care Unit, and nursing home residence, where interventions such as urinary catheterization or multiple drug use are quite frequent and many studies reported that people above 65 years of age are three times more likely to be admitted to hospital than those aged 16-64 years, and have a higher risk of prolonged hospital stays, institutionalization and death. Clinical evaluation of the frail patient with sepsis poses some challenges. The immune response becomes progressively less efficient with increasing age thereby causing an altered response to infection and it is important to know that the clinical evaluation of the so-called fragile patient with severe infection should take into account the sometimes unusual signs and symptoms that, if identified, can lead to early diagnosis. Laboratory diagnostics can also be of great help in this setting. The treatment of sepsis in the fragile patient can be empirical or based on microbiological culture. Moreover, frail patient population presents many clinical problems with numerous comorbidities, therefore anti-infective treatment is difficult, so the physician’s armamentarium must include many antibiotic drugs, of which there are far more available for the treatment of sepsis caused by Gram-positive bacteria than for sepsis caused by Gram-negative ones or fungi.

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Vancomycin-ResistantEnterococcus faecium(VRE) Bacteremia in Infective Endocarditis Successfully Treated with Combination Daptomycin and Tigecycline

Cited by 34 publications

References 8 publications

In Vitro Activity of Daptomycin in Combination with β-Lactams, Gentamicin, Rifampin, and Tigecycline against Daptomycin-Nonsusceptible Enterococci

In Vitro Activity of Daptomycin in Combination with β-Lactams, Gentamicin, Rifampin, and Tigecycline against Daptomycin-Nonsusceptible Enterococci

Enterococcal Endocarditis Revisited

Sepsis in frail patient

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