Clinical experience with daptomycin in Europe: the first 2.5 years

Gonzalez-Ruiz, Armando; Beiras-Fernández, Andrés; Lehmkuhl, H.; Seaton, R.A.; Loeffler, Juergen; Chaves, Ricardo L.

doi:10.1093/jac/dkq528

Cited by 73 publications

(72 citation statements)

References 27 publications

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“…Future studies will have to determine the rate of IE recurrences with such a treatment, but it must be considered that, in complicated cases or those affected by aggressive agents such as S aureus, which are very difficult to eradicate despite adequate antibiotherapy (4 of 5 patients with methicillin-resistant microorganisms treated with daptomycin died), surgery remains the only effective therapy. [27][28][29] IE is a life-threatening condition, with a risk of in-hospital mortality of 15% (10%-22%), which increases up to 40% (23%-40%) in cases of prosthetic valve IE. 3,24,[30][31][32] The cumulative mortality rate at the 1-year follow-up is ≈30% overall and 45% for prosthetic valve IE.…”

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confidence: 99%

Infective Endocarditis After Transcatheter Aortic Valve Implantation

et al. 2015

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Background-We aimed to determine the incidence, predictors, clinical characteristics, management, and outcomes of infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI). Methods and Results-This multicenter registry included 53 patients (mean age, 79±8 years; men, 57%) who suffered IE after TAVI of 7944 patients after a mean follow-up of 1.1±1.2 years (incidence, 0.67%, 0.50% within the first year after TAVI). Mean time from TAVI was 6 months (interquartile range, 1-14 months). Orotracheal intubation (hazard ratio, 3.87; 95% confidence interval, 1.55-9.64; P=0.004) and the self-expandable CoreValve system (hazard ratio, 3.12; 95% confidence interval, 1.37-7.14; P=0.007) were associated with IE (multivariate analysis including 3067 patients with individual data).The most frequent causal microorganisms were coagulase-negative staphylococci (24%), followed by Staphylococcus aureus (21%) and enterococci (21%). Vegetations were present in 77% of patients (transcatheter valve leaflets, 39%; stent frame, 17%; mitral valve, 21%). At least 1 complication of IE occurred in 87% of patients (heart failure in 68%). However, only 11% of patients underwent valve intervention (valve explantation and valve-in-valve procedure in 4 and 2 patients, respectively). The mortality rate in hospital was 47.2% and increased to 66% at the 1-year follow-up. IE complications such as heart failure (P=0.037) and septic shock (P=0.002) were associated with increased in-hospital mortality. Conclusions-The incidence of IE at 1 year after TAVI was 0.50%, and the risk increased with the use of orotracheal intubation and a self-expandable valve system. Staphylococci and enterococci were the most common agents. Although most patients presented at least 1 complication of IE, valve intervention was performed in a minority of patients, and nearly half of the patients died during the hospitalization period. Clinical Perspective on p 1574Transcatheter aortic valve implantation (TAVI) represents a paradigm shift in the treatment of aortic stenosis in patients considered at high or prohibitive surgical risk. 5 The reported rates of early IE after TAVI have varied from 0.1% to 3.03%, [6][7][8] with no differences compared with surgical aortic valve replacement, as shown in the prospective randomized Placement of Aortic Transcatheter Valves (PARTNER) trial. 6 However, data on the clinical characteristics, causes, treatment, and clinical outcomes of IE after TAVI are scarce and limited to case reports and small series, which indeed may suffer from publication bias.9 Such information is crucial to improve both the diagnosis and management of this entity in the context of TAVI. The particular features of TAVI candidates and the specific design of transcatheter valve prostheses, including a much higher amount of metal (stent frame) around the valve leaflets compared with surgical valves, may indeed alter the outcome and management of IE. The objectives of this multicenter registry were thus to evaluate the incidence, predictors, and cl...

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Infective Endocarditis After Transcatheter Aortic Valve Implantation

et al. 2015

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“…is rare (8)(9)(10)(11)(12). Daptomycin-nonsusceptible enterococci, however, are emerging as a cause of health careassociated infection (4,6) and may be fairly common; they comprised 3.9% of 2,029 Enterococcus faecium isolates from U.S. hospitals over the period 2007 to 2010 (13) and 15.2% among VRE blood isolates at a New York cancer center (14).…”

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Identification of a Novel Clone, ST736, among Enterococcus faecium Clinical Isolates and Its Association with Daptomycin Nonsusceptibility

Wang

Kamalakaran

Dhand

et al. 2014

Antimicrob Agents Chemother

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Resistance to daptomycin in enterococcal clinical isolates remains rare but is being increasingly reported in the United States and worldwide. There are limited data on the genetic relatedness and microbiological and clinical characteristics of daptomycinnonsusceptible enterococcal clinical isolates. In this study, we assessed the population genetics of daptomycin-nonsusceptible Enterococcus faecium (DNSE) clinical isolates by multilocus sequence typing (MLST) and whole-genome sequencing analysis. Forty-two nonduplicate DNSE isolates and 43 randomly selected daptomycin-susceptible E. faecium isolates were included in the analysis. All E. faecium isolates were recovered from patients at a tertiary care medical center in suburban New York City from May 2009 through December 2013. The daptomycin MICs of the DNSE isolates ranged from 6 to >256 g/ml. Three major clones of E. faecium (ST18, ST412, and ST736) were identified among these clinical isolates by MLST and whole-genome sequence-based analysis. A newly recognized clone, ST736, was seen in 32 of 42 (76.2%) DNSE isolates and in only 14 of 43 (32.6%) daptomycin-susceptible E. faecium isolates (P < 0.0001). This report provides evidence of the association between E. faecium clone ST736 and daptomycin nonsusceptibility. The identification and potential spread of this novel E. faecium clone and its association with daptomycin nonsusceptibility constitute a challenge for patient management and infection control at our medical center.

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“…Although DAP has not been approved for the treatment of enterococcal bacteremia or vancomycin-resistant enterococcus (VRE) infections, it is frequently used off-label for these purposes (8,19). Interestingly, the DAP breakpoint is 4 g/ml, which is four times higher than its breakpoint for staphylococci (12).…”

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Correlation between Mutations in liaFSR of Enterococcus faecium and MIC of Daptomycin: Revisiting Daptomycin Breakpoints

Munita

Panesso

Diaz

et al. 2012

Antimicrob Agents Chemother

105

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h Mutations in liaFSR, a three-component regulatory system controlling cell-envelope stress response, were recently linked with the emergence of daptomycin (DAP) resistance in enterococci. Our previous work showed that a liaF mutation increased the DAP MIC of a vancomycin-resistant Enterococcus faecalis strain from 1 to 3 g/ml (the DAP breakpoint is 4 g/ml), suggesting that mutations in the liaFSR system could be a pivotal initial event in the development of DAP resistance. With the hypothesis that clinical enterococcal isolates with DAP MICs between 3 and 4 g/ml might harbor mutations in liaFSR, we studied 38 Enterococcus faecium bloodstream isolates, of which 8 had DAP MICs between 3 and 4 g/ml by Etest in Mueller-Hinton agar. Interestingly, 6 of these 8 isolates had predicted amino acid changes in the LiaFSR system. Moreover, we previously showed that among 6 DAP-resistant E. faecium isolates (MICs of >4 g/ml), 5 had mutations in liaFSR. In contrast, none of 16 E. faecium isolates with a DAP MIC of <2 g/ml harbored mutations in this system (P < 0.0001). All but one isolate with liaFSR changes exhibited DAP MICs of >16 g/ml by Etest using brain heart infusion agar (BHIA), a medium that better supports enterococcal growth. Our findings provide a strong association between DAP MICs within the upper susceptibility range and mutations in the liaFSR system. Concomitant susceptibility testing on BHIA may be useful for identifying these E. faecium first-step mutants. Our results also suggest that the current DAP breakpoint for E. faecium may need to be reevaluated. Enterococci are leading causes of nosocomial infections in the United States, and multidrug-resistant (MDR) isolates have become an important clinical problem throughout the world. Enterococcus faecalis and Enterococcus faecium account for most of the clinically relevant enterococcal isolates recovered from infections in humans (20). The treatment of enterococcal infections is particularly challenging due to the emergence of MDR isolates and the paucity of newer therapeutic alternatives. Moreover, the dissemination of a hospital-associated clade of ampicillin-and vancomycin-resistant E. faecium (17) has dramatically reduced the options for the treatment of severe enterococcal infections (1).Daptomycin (DAP) is a cyclic lipopeptide antibiotic that exhibits in vitro bactericidal activity against MDR enterococci and is one of the few therapeutic options available for these organisms. Although DAP has not been approved for the treatment of enterococcal bacteremia or vancomycin-resistant enterococcus (VRE) infections, it is frequently used off-label for these purposes (8,19). Interestingly, the DAP breakpoint is 4 g/ml, which is four times higher than its breakpoint for staphylococci (12). However, clinical and microbiological failures have been described in subjects with E. faecium bacteremia and MICs close to the breakpoint (3 to 4 g/ml) (4, 35). Moreover, animal models of S. aureus endocarditis have shown decreased efficacy of DAP when treating susceptible m...

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Clinical experience with daptomycin in Europe: the first 2.5 years

Cited by 73 publications

References 27 publications

Infective Endocarditis After Transcatheter Aortic Valve Implantation

Infective Endocarditis After Transcatheter Aortic Valve Implantation

Identification of a Novel Clone, ST736, among Enterococcus faecium Clinical Isolates and Its Association with Daptomycin Nonsusceptibility

Correlation between Mutations in liaFSR of Enterococcus faecium and MIC of Daptomycin: Revisiting Daptomycin Breakpoints

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