Comparative Effectiveness and Safety of Standard-, Medium-, and High-Dose Daptomycin Strategies for the Treatment of Vancomycin-Resistant Enterococcal Bacteremia Among Veterans Affairs Patients

Britt, Nicholas S.; Potter, Emily M.; Patel, Nimish; Steed, Molly E.

doi:10.1093/cid/ciw815

Cited by 46 publications

(95 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, ID specialist consultation has previously been associated with improved clinical outcomes in other Gram-positive BSIs, perhaps due to more diligent and aggressive source identification and control (24,25). In a recent analysis of hospitalized VA patients with VRE-BSI treated with daptomycin, ID specialist consultation was also independently associated with improved survival (26). We believe future analyses of VREF-BSI should consider the potential influence of ID consultation on clinical outcomes.…”

Section: Discussionmentioning

confidence: 92%

Effect of Continuous and Sequential Therapy among Veterans Receiving Daptomycin or Linezolid for Vancomycin-Resistant Enterococcus faecium Bacteremia

Britt

Potter

Patel

et al. 2017

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

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 ϭ 1,348], DAP [n ϭ 1,055], LZD-to-DAP [n ϭ 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 ϭ 0.042). After PS matching, this relationship persisted (RR, 1.13; 95% CI, 1.02 to 1.26; P ϭ 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 ϭ 0.021), suggesting a benefit may still be derived with sequential therapy. LZD-treated patients experienced more adverse events, including a Ն50% reduction in platelets (RR, 1.07; 95% CI, 1.03 to 1.11; P ϭ 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 ϭ 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.KEYWORDS Enterococcus, antimicrobial resistance, bloodstream infection, daptomycin, linezolid, transplant infectious diseases, vancomycin resistance V ancomycin-resistant Enterococcus faecium bloodstream infections (VREF-BSI) represent a significant health care-associated complication (1-4). The clinical impact of VREF-BSI is increasing, and most E. faecium strains are now vancomycin resistant (1, 2). As mortality associated with VREF-BSI is high, optimal treatment balancing effectiveness and safety is critical (1, 5).Many small retrospective studies have compared daptomycin (DAP) and linezolid (LZD) for treatment of VREF-BSI (6-10). Two recent meta-analyses of these investigations found an apparent survival benefit associated with LZD treatment, despite the fact that none of the individual studies included found a statistically significant differ-

show abstract

Section: Discussionmentioning

confidence: 92%

Effect of Continuous and Sequential Therapy among Veterans Receiving Daptomycin or Linezolid for Vancomycin-Resistant Enterococcus faecium Bacteremia

Britt

Potter

Patel

et al. 2017

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

show abstract

“…It is also reported that daptomycin has an adverse effect concerning creatinine phosphokinase (CPK) elevation . To date, the safety of daptomycin treatment has been widely investigated in relation to various types of infections and pathogens . Although a few reports describe the higher risk of CPK elevation in high‐dose treatment, almost all other previous reports demonstrated the safety of daptomycin treatment with a low or no significant incidence of CPK elevation or other adverse effects, even with high‐dose treatment .…”

Section: What Is Known and Objectivementioning

confidence: 99%

Observational retrospective single‐centre study in Japan to assess the clinical significance of serum daptomycin levels in creatinine phosphokinase elevation

et al. 2019

View full text Add to dashboard Cite

What is known and objective Daptomycin‐induced creatinine phosphokinase (CPK) elevation is reported to be associated with its trough level (Ctrough; breakpoint of 24.3 μg/mL). However, even with high‐dose treatment (ie, > 8 mg/kg), the safety of daptomycin treatment is widely demonstrated with low or no significant incidence of CPK elevation or other adverse effects, despite the possibility of Ctrough above 24.3 μg/mL. Therefore, we questioned the clinical significance of Ctrough levels of 24.3 μg/mL. In this study, we retrospectively evaluated the significance of Ctrough in the clinical setting, in addition to completing a retrospective safety assessment of daptomycin utilizing electronic health records. Methods Patients who had received daptomycin treatment for > 4 days from July 2011 to June 2015 were enrolled. Serum daptomycin levels, including Ctrough and peak (Cpeak), were measured by high‐performance liquid chromatography equipped with a photodiode array. To evaluate the safety, patients’ characteristics and relevant laboratory test values were reviewed retrospectively using an electronic medical record system. Results and discussion A total of 52 therapeutic cases for 46 patients were identified; of these, Ctrough and Cpeak levels were measured in 27 and 28 cases, respectively, and 6 patients received multiple courses of daptomycin treatment. The median age of the 52 patients was 68 years (range: 19‐88 years), and 14 patients initially had an estimated creatinine clearance of less than 30 mL/min. Seven cases indicated a Ctrough of above 24.3 μg/mL; however, none of these presented CPK elevation, which meets with the study definition for abnormality. Furthermore, of the two patients with abnormal CPK elevations, only one patient had a measured Ctrough (of 10.9 μg/mL). Their CPK abnormalities were temporal and did not result in treatment discontinuation. The other four patients discontinued daptomycin treatment due to suspicions of adverse effects. Of the discontinued patients, two had measured Ctrough levels; these were 8.6 and 8.1 μg/mL. All patients with abnormal CPK elevation or treatment discontinuation exhibited Ctrough levels lower than 24.3 μg/mL. In this study, two patients receiving high‐dose daptomycin (ie, 9.4 and 10.0 mg/kg) had observed Ctrough levels similar to patients who received doses of daptomycin < 9 mg/kg. What is new and conclusions The safety of daptomycin treatment was suggested in this study. Ctrough level of 24.3 μg/mL was not suggested as a significant clinical index for the incidence of CPK elevation, adverse effects or treatment discontinuation. Thus, acceptable tolerability towards higher Ctrough levels than 24.3 μg/mL was also suggested, though further studies are required. On the other hand, low levels of daptomycin in blood were unexpectedly observed in two cases, despite the high‐dose treatments. Accordingly, the monitoring of serum daptomycin levels may also be useful to assess cases in which subtherapeutic levels were achieved.

show abstract

“…As a bactericidal agent, it has a potential advantage as a treatment option for deep‐seated infections such as infective endocarditis. Daptomycin dosing for enterococcal infections is variable, and recent data suggest that higher doses may be beneficial for invasive VRE infections . Due to variability in dosing, frequently used regimens for daptomycin, along with other antimicrobial agents commonly used to treat enterococcal infections, are summarized in Table .…”

Section: Currently Available Anti‐vre Antibiotics and Resistancementioning

confidence: 99%

“…Several in vitro studies and limited clinical data have demonstrated that reduced daptomycin susceptibility is attributable to suboptimal dosing and potential mutations in isolates with daptomycin MICs in the 3–4 μg/ml range . In vitro pharmacokinetic/pharmacodynamic (PK/PD) dose response experiments have demonstrated that daptomycin at a minimum of 8 mg/kg/day is required for sufficient bactericidal kill, and 10 mg/kg/day maybe needed to prevent the emergence of resistance in high‐inoculum infections caused by VRE faecalis and faecium . Recently, a multicenter retrospective cohort study that included 62 E. faecium bloodstream infections showed that initial isolates with elevated daptomycin MICs at 3–4 μg/ml were predictive of microbiologic treatment failure with daptomycin and suggested that the current CLSI susceptibility breakpoint for enterococci should be reevaluated …”

Section: Currently Available Anti‐vre Antibiotics and Resistancementioning

confidence: 99%

“…This is especially true in the treatment of VRE faecium that fails to respond to traditional therapeutic options. Recently, two studies corroborated that daptomycin may be a more appropriate choice than linezolid for the treatment of VRE bacteremia and that high‐dose daptomycin, up to 10 mg/kg/day, is likely a better choice than lower doses . In these studies, the role of daptomycin combination therapy with β‐lactams is not as easily defined.…”

Section: Conclusion and Opinionmentioning

confidence: 99%

See 1 more Smart Citation

Role of Combination Antimicrobial Therapy for Vancomycin‐Resistant Enterococcus faecium Infections: Review of the Current Evidence

2017

View full text Add to dashboard Cite

Enterococcus species are the second most common cause of nosocomial infections in the United States and are particularly concerning in critically ill patients with preexisting comorbid conditions. Rising resistance to antimicrobials that were historically used as front-line agents for treatment of enterococcal infections, such as ampicillin, vancomycin, and aminoglycosides, further complicates the treatment of these infections. Of particular concern are Enterococcus faecium strains that are associated with the highest rate of vancomycin resistance. The introduction of antimicrobial agents with specific activity against vancomycin-resistant Enterococcus (VRE) faecium including daptomycin, linezolid, quinupristin-dalfopristin, and tigecycline did not completely resolve this clinical dilemma. In this review, the mechanisms of action and resistance to currently available anti-VRE antimicrobial agents including newer agents such as oritavancin and dalbavancin will be presented. In addition, novel combination therapies including b-lactams and fosfomycin, and the promising results from in vitro, animal studies, and clinical experience in the treatment of VRE faecium will be discussed.

show abstract

Comparative Effectiveness and Safety of Standard-, Medium-, and High-Dose Daptomycin Strategies for the Treatment of Vancomycin-Resistant Enterococcal Bacteremia Among Veterans Affairs Patients

Abstract: High-dose daptomycin was associated with improved survival and microbiological clearance in VRE-BSI.

Cited by 46 publications

References 42 publications

Effect of Continuous and Sequential Therapy among Veterans Receiving Daptomycin or Linezolid for Vancomycin-Resistant Enterococcus faecium Bacteremia

Effect of Continuous and Sequential Therapy among Veterans Receiving Daptomycin or Linezolid for Vancomycin-Resistant Enterococcus faecium Bacteremia

Observational retrospective single‐centre study in Japan to assess the clinical significance of serum daptomycin levels in creatinine phosphokinase elevation

Role of Combination Antimicrobial Therapy for Vancomycin‐Resistant Enterococcus faecium Infections: Review of the Current Evidence

Contact Info

Product

Resources

About