Clinical Data on Daptomycin plus Ceftaroline versus Standard of Care Monotherapy in the Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia

Geriak, Matthew; Haddad, Fadi; Rizvi, Khulood; Rose, Warren E.; Kullar, Ravina; LaPlante, Kerry L.; Yu, Marie; Vasina, Logan; Ouellette, Krista; Zervos, Marcus J.; Nizet, Victor; Sakoulas, George

doi:10.1128/aac.02483-18

Cited by 138 publications

(126 citation statements)

References 33 publications

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“…In this study, the prognostic values of IL‐17A, IL‐10, sE‐selectin and IL‐8 identified in a discovery cohort enriched for microbiological failure and mortality were validated in an unselected cohort of serially enrolled patients with SAB, with very similar AUROC between the two studies. Importantly, high IL‐17A, IL‐10 and sE‐selectin were superior to clinical metrics in risk‐stratifying patients for persistent bacteraemia when using the threshold of 5 days of positive blood cultures, a time frame supported by recent studies . These three biomarkers were correlated with each other, providing a possible explanation for why inclusion of additional biomarkers did not significantly improve the linear model or lasso model.…”

Section: Discussionmentioning

confidence: 65%

“…a time frame supported by recent studies. 13,14 These three biomarkers were correlated with each other, providing a possible explanation for why inclusion of additional biomarkers did not significantly improve the linear model or lasso model. They were also more strongly associated with IE/endovascular infections when compared to clinical risk factors, routinely available laboratory measures and the other five biomarkers.…”

Section: Discussionmentioning

confidence: 99%

“…Higher‐risk patients could be treated more aggressively with better antibiotic regimens. A proof‐of‐concept study of this approach demonstrated significant mortality reduction in patients treated with daptomycin plus ceftaroline compared with vancomycin alone in the subgroup of patients with elevated IL‐10 …”

Section: Discussionmentioning

confidence: 99%

“…Infection‐related mortality was assessed by retrospective chart review by two Board‐certified infectious disease physicians using the following criteria: culture positive and/or persistent infection focus and/or systemic signs and symptoms at the time of death or attending physician considered death to be attributable to SAB. Persistent bacteraemia was defined as any positive blood culture on or after 5 days during the initial hospitalisation, regardless of whether there was a preceding negative blood culture . Seven patients classified as persistent bacteraemia had positive blood cultures following negative cultures.…”

Section: Methodsmentioning

confidence: 99%

“…A proof-of-concept study of this approach demonstrated significant mortality reduction in patients treated with daptomycin plus ceftaroline compared with vancomycin alone in the subgroup of patients with elevated IL-10. 14 IL-17A and IL-10 have potential clinical utility for ruling out the need for more invasive and higher sensitivity TEE diagnostic imaging in favor of TTE imaging for low-risk biomarker-negative patients. 17 Delays in diagnosing IE by imaging (TTE or TEE) can range from days to weeks and is a predictor of valve destruction and requirement for surgery, and significantly, more embolic events were observed with delays of ≥ 4 days.…”

Section: Clinical Endocarditismentioning

confidence: 99%

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Risk stratification biomarkers for Staphylococcus aureus bacteraemia

Cao¹,

Guimaraes²,

Peck³

et al. 2020

Clin & Trans Imm

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Objectives To identify risk stratification biomarkers to enrich for the subset of Staphylococcus aureus bacteraemia patients who develop deep‐seated tissue infections with high morbidity and mortality to guide clinical trial enrolment and clinical management. Methods We evaluated the prognostic value of eight biomarkers for persistent bacteraemia, mortality and endovascular infection foci in a validation cohort of 160 patients with S. aureus bacteraemia enrolled consecutively over 3 years. Results High levels of IL‐17A, IL‐10 or soluble E‐selectin at bacteraemia diagnosis correlated with the duration of positive blood cultures. When thresholds defined in an independent cohort were applied, these biomarkers were robust predictors of persistent bacteraemia or endovascular infection. High serum levels of IL‐17A and IL‐10 often preceded the radiographic diagnosis of infective endocarditis, suggesting potential utility for prioritising diagnostic radiographic imaging. High IL‐8 was prognostic for all‐cause mortality, while IL‐17A and IL‐10 were superior to clinical metrics in discriminating between attributable mortality and non‐attributable mortality. High IL‐17A and IL‐10 identified more patients who developed microbiological failure or mortality than were identified by infective endocarditis diagnosis. Conclusion These biomarkers offer potential utility to identify patients at risk of persistent bacteraemia to guide diagnostic imaging and clinical management. Low biomarker levels could be used to rule out the need for more invasive TEE imaging in patients at lower risk of infective endocarditis. These biomarkers could enable clinical trials by enriching for patients with the greatest need for novel therapies.

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Section: Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Clinical Endocarditismentioning

confidence: 99%

See 3 more Smart Citations

Risk stratification biomarkers for Staphylococcus aureus bacteraemia

Cao¹,

Guimaraes²,

Peck³

et al. 2020

Clin & Trans Imm

View full text Add to dashboard Cite

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Combination Therapy for Methicillin-Resistant Staphylococcus aureus Bacteremia

Gandhi

Malani

2020

JAMA

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Effect of Vancomycin or Daptomycin With vs Without an Antistaphylococcal β-Lactam on Mortality, Bacteremia, Relapse, or Treatment Failure in Patients With MRSA Bacteremia

Tong

Lye

Yahav

et al. 2020

JAMA

191

152

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IMPORTANCE Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with mortality of more than 20%. Combining standard therapy with a β-lactam antibiotic has been associated with reduced mortality, although adequately powered randomized clinical trials of this intervention have not been conducted. OBJECTIVE To determine whether combining an antistaphylococcal β-lactam with standard therapy is more effective than standard therapy alone in patients with MRSA bacteremia. DESIGN, SETTING, AND PARTICIPANTS Open-label, randomized clinical trial conducted at 27 hospital sites in 4 countries from August 2015 to July 2018 among 352 hospitalized adults with MRSA bacteremia. Follow-up was complete on October 23, 2018.INTERVENTIONS Participants were randomized to standard therapy (intravenous vancomycin or daptomycin) plus an antistaphylococcal β-lactam (intravenous flucloxacillin, cloxacillin, or cefazolin) (n = 174) or standard therapy alone (n = 178). Total duration of therapy was determined by treating clinicians and the β-lactam was administered for 7 days. MAIN OUTCOMES AND MEASURESThe primary end point was a 90-day composite of mortality, persistent bacteremia at day 5, microbiological relapse, and microbiological treatment failure. Secondary outcomes included mortality at days 14, 42, and 90; persistent bacteremia at days 2 and 5; acute kidney injury (AKI); microbiological relapse; microbiological treatment failure; and duration of intravenous antibiotics. RESULTSThe data and safety monitoring board recommended early termination of the study prior to enrollment of 440 patients because of safety. Among 352 patients randomized (mean age, 62.2 [SD, 17.7] years; 121 women [34.4%]), 345 (98%) completed the trial. The primary end point was met by 59 (35%) with combination therapy and 68 (39%) with standard therapy (absolute difference, −4.2%; 95% CI, −14.3% to 6.0%). Seven of 9 prespecified secondary end points showed no significant difference. For the combination therapy vs standard therapy groups, all-cause 90-day mortality occurred in 35 (21%) vs 28 (16%) (difference, 4.5%; 95% CI, −3.7% to 12.7%); persistent bacteremia at day 5 was observed in 19 of 166 (11%) vs 35 of 172 (20%) (difference, −8.9%; 95% CI, −16.6% to −1.2%); and, excluding patients receiving dialysis at baseline, AKI occurred in 34 of 145 (23%) vs 9 of 145 (6%) (difference, 17.2%; 95% CI, 9.3%-25.2%).CONCLUSIONS AND RELEVANCE Among patients with MRSA bacteremia, addition of an antistaphylococcal β-lactam to standard antibiotic therapy with vancomycin or daptomycin did not result in significant improvement in the primary composite end point of mortality, persistent bacteremia, relapse, or treatment failure. Early trial termination for safety concerns and the possibility that the study was underpowered to detect clinically important differences in favor of the intervention should be considered when interpreting the findings.

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Clinical Data on Daptomycin plus Ceftaroline versus Standard of Care Monotherapy in the Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia

Cited by 138 publications

References 33 publications

Risk stratification biomarkers for Staphylococcus aureus bacteraemia

Risk stratification biomarkers for Staphylococcus aureus bacteraemia

Combination Therapy for Methicillin-Resistant Staphylococcus aureus Bacteremia

Effect of Vancomycin or Daptomycin With vs Without an Antistaphylococcal β-Lactam on Mortality, Bacteremia, Relapse, or Treatment Failure in Patients With MRSA Bacteremia

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