Clinical Outcomes of Daptomycin for Vancomycin-resistant Enterococcus Bacteremia
Abstract Purpose In light of recent evidence suggesting enhancement of daptomycin activity against vancomycin-resistant Enterococcus (VRE) by ampicillin and other β-lactam antibiotics, we evaluated the safety profile and clinical efficacy of daptomycin with and without concomitant β-lactam antimicro...
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Published in | Clinical therapeutics Vol. 37; no. 7; pp. 1443 - 1453.e2 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
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United States
Elsevier Inc
01.07.2015
Elsevier Limited |
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Abstract | Abstract Purpose In light of recent evidence suggesting enhancement of daptomycin activity against vancomycin-resistant Enterococcus (VRE) by ampicillin and other β-lactam antibiotics, we evaluated the safety profile and clinical efficacy of daptomycin with and without concomitant β-lactam antimicrobials in the treatment of VRE ( faecium or faecalis ) bacteremia from multiple centers across the United States. Methods Data were collected retrospectively as part of a larger multicenter registry (The Cubicin Outcomes Registry and Experience). Efficacy and clinical outcomes in patients with VRE bacteremia who received at least 3 days of daptomycin with or without concomitant β-lactams were analyzed. Although all the cases involved daptomycin-susceptible VRE, additional analysis was performed to examine whether the adjunctive β-lactam would play a more pivotal role in cases where the daptomycin MIC was in the upper limit of the susceptibility range, indicating that daptomycin monotherapy efficacy may be relatively compromised compared with cases with lower daptomycin MICs. Findings Two hundred sixty-two patients from 33 hospitals were evaluated. Most patients had at least one significant comorbidity, such as solid-organ or bone marrow transplantation (16%), neutropenia (36%), dialysis dependency (20%), or critical illness (36%) requiring care in an intensive care unit. Overall treatment success was 86% (n = 225/262), and treatment success for patients taking concomitant β-lactams was 86% (n = 105/122). Logistic regression identified treatment failure to be associated with sepsis (odds ratio = 3.42; P = 0.009) and an elevated daptomycin MIC (3–4 µg/mL) (odds ratio = 3.23, P = 0.013). No significant increase in clinical failure was seen among patients with elevated daptomycin MIC who received concomitant β-lactam therapy (clinical success, 88% vs 79% for MIC ≤2 vs 3–4 µg/mL, respectively; P = 0.417). Of 262 patients, 33 (13%) experienced ≥1 adverse event possibly related to daptomycin (increased creatine kinase in 8 patients). Implications Overall, daptomycin was effective and well tolerated for VRE bacteremia, with lower effectiveness noted with daptomycin MIC of 3 to 4 µg/mL. Concomitant β-lactam therapy with daptomycin may improve clinical outcomes in this setting. Further studies are needed to characterize the potential benefit of concomitant β-lactams with daptomycin. |
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AbstractList | In light of recent evidence suggesting enhancement of daptomycin activity against vancomycin-resistant Enterococcus (VRE) by ampicillin and other β-lactam antibiotics, we evaluated the safety profile and clinical efficacy of daptomycin with and without concomitant β-lactam antimicrobials in the treatment of VRE (faecium or faecalis) bacteremia from multiple centers across the United States.
Data were collected retrospectively as part of a larger multicenter registry (The Cubicin Outcomes Registry and Experience). Efficacy and clinical outcomes in patients with VRE bacteremia who received at least 3 days of daptomycin with or without concomitant β-lactams were analyzed. Although all the cases involved daptomycin-susceptible VRE, additional analysis was performed to examine whether the adjunctive β-lactam would play a more pivotal role in cases where the daptomycin MIC was in the upper limit of the susceptibility range, indicating that daptomycin monotherapy efficacy may be relatively compromised compared with cases with lower daptomycin MICs.
Two hundred sixty-two patients from 33 hospitals were evaluated. Most patients had at least one significant comorbidity, such as solid-organ or bone marrow transplantation (16%), neutropenia (36%), dialysis dependency (20%), or critical illness (36%) requiring care in an intensive care unit. Overall treatment success was 86% (n = 225/262), and treatment success for patients taking concomitant β-lactams was 86% (n = 105/122). Logistic regression identified treatment failure to be associated with sepsis (odds ratio = 3.42; P = 0.009) and an elevated daptomycin MIC (3–4 µg/mL) (odds ratio = 3.23, P = 0.013). No significant increase in clinical failure was seen among patients with elevated daptomycin MIC who received concomitant β-lactam therapy (clinical success, 88% vs 79% for MIC ≤2 vs 3–4 µg/mL, respectively; P = 0.417). Of 262 patients, 33 (13%) experienced ≥1 adverse event possibly related to daptomycin (increased creatine kinase in 8 patients).
Overall, daptomycin was effective and well tolerated for VRE bacteremia, with lower effectiveness noted with daptomycin MIC of 3 to 4 µg/mL. Concomitant β-lactam therapy with daptomycin may improve clinical outcomes in this setting. Further studies are needed to characterize the potential benefit of concomitant β-lactams with daptomycin. PURPOSEIn light of recent evidence suggesting enhancement of daptomycin activity against vancomycin-resistant Enterococcus (VRE) by ampicillin and other β-lactam antibiotics, we evaluated the safety profile and clinical efficacy of daptomycin with and without concomitant β-lactam antimicrobials in the treatment of VRE (faecium or faecalis) bacteremia from multiple centers across the United States.METHODSData were collected retrospectively as part of a larger multicenter registry (The Cubicin Outcomes Registry and Experience). Efficacy and clinical outcomes in patients with VRE bacteremia who received at least 3 days of daptomycin with or without concomitant β-lactams were analyzed. Although all the cases involved daptomycin-susceptible VRE, additional analysis was performed to examine whether the adjunctive β-lactam would play a more pivotal role in cases where the daptomycin MIC was in the upper limit of the susceptibility range, indicating that daptomycin monotherapy efficacy may be relatively compromised compared with cases with lower daptomycin MICs.FINDINGSTwo hundred sixty-two patients from 33 hospitals were evaluated. Most patients had at least one significant comorbidity, such as solid-organ or bone marrow transplantation (16%), neutropenia (36%), dialysis dependency (20%), or critical illness (36%) requiring care in an intensive care unit. Overall treatment success was 86% (n = 225/262), and treatment success for patients taking concomitant β-lactams was 86% (n = 105/122). Logistic regression identified treatment failure to be associated with sepsis (odds ratio = 3.42; P = 0.009) and an elevated daptomycin MIC (3-4 µg/mL) (odds ratio = 3.23, P = 0.013). No significant increase in clinical failure was seen among patients with elevated daptomycin MIC who received concomitant β-lactam therapy (clinical success, 88% vs 79% for MIC ≤2 vs 3-4 µg/mL, respectively; P = 0.417). Of 262 patients, 33 (13%) experienced ≥1 adverse event possibly related to daptomycin (increased creatine kinase in 8 patients).IMPLICATIONSOverall, daptomycin was effective and well tolerated for VRE bacteremia, with lower effectiveness noted with daptomycin MIC of 3 to 4 µg/mL. Concomitant β-lactam therapy with daptomycin may improve clinical outcomes in this setting. Further studies are needed to characterize the potential benefit of concomitant β-lactams with daptomycin. Purpose In light of recent evidence suggesting enhancement of daptomycin activity against vancomycin-resistant Enterococcus (VRE) by ampicillin and other beta -lactam antibiotics, we evaluated the safety profile and clinical efficacy of daptomycin with and without concomitant beta -lactam antimicrobials in the treatment of VRE (faecium or faecalis) bacteremia from multiple centers across the United States. Methods Data were collected retrospectively as part of a larger multicenter registry (The Cubicin Outcomes Registry and Experience). Efficacy and clinical outcomes in patients with VRE bacteremia who received at least 3 days of daptomycin with or without concomitant beta -lactams were analyzed. Although all the cases involved daptomycin-susceptible VRE, additional analysis was performed to examine whether the adjunctive beta -lactam would play a more pivotal role in cases where the daptomycin MIC was in the upper limit of the susceptibility range, indicating that daptomycin monotherapy efficacy may be relatively compromised compared with cases with lower daptomycin MICs. Findings Two hundred sixty-two patients from 33 hospitals were evaluated. Most patients had at least one significant comorbidity, such as solid-organ or bone marrow transplantation (16%), neutropenia (36%), dialysis dependency (20%), or critical illness (36%) requiring care in an intensive care unit. Overall treatment success was 86% (n = 225/262), and treatment success for patients taking concomitant beta -lactams was 86% (n = 105/122). Logistic regression identified treatment failure to be associated with sepsis (odds ratio = 3.42; P = 0.009) and an elevated daptomycin MIC (3-4 mu g/mL) (odds ratio = 3.23, P = 0.013). No significant increase in clinical failure was seen among patients with elevated daptomycin MIC who received concomitant beta -lactam therapy (clinical success, 88% vs 79% for MIC less than or equal to 2 vs 3-4 mu g/mL, respectively; P = 0.417). Of 262 patients, 33 (13%) experienced greater than or equal to 1 adverse event possibly related to daptomycin (increased creatine kinase in 8 patients). Implications Overall, daptomycin was effective and well tolerated for VRE bacteremia, with lower effectiveness noted with daptomycin MIC of 3 to 4 mu g/mL. Concomitant beta -lactam therapy with daptomycin may improve clinical outcomes in this setting. Further studies are needed to characterize the potential benefit of concomitant beta -lactams with daptomycin. Purpose In light of recent evidence suggesting enhancement of daptomycin activity against vancomycin-resistantEnterococcus(VRE) by ampicillin and other β-lactam antibiotics, we evaluated the safety profile and clinical efficacy of daptomycin with and without concomitant β-lactam antimicrobials in the treatment of VRE (faeciumorfaecalis) bacteremia from multiple centers across the United States. Methods Data were collected retrospectively as part of a larger multicenter registry (The Cubicin Outcomes Registry and Experience). Efficacy and clinical outcomes in patients with VRE bacteremia who received at least 3 days of daptomycin with or without concomitant β-lactams were analyzed. Although all the cases involved daptomycin-susceptible VRE, additional analysis was performed to examine whether the adjunctive β-lactam would play a more pivotal role in cases where the daptomycin MIC was in the upper limit of the susceptibility range, indicating that daptomycin monotherapy efficacy may be relatively compromised compared with cases with lower daptomycin MICs. Findings Two hundred sixty-two patients from 33 hospitals were evaluated. Most patients had at least one significant comorbidity, such as solid-organ or bone marrow transplantation (16%), neutropenia (36%), dialysis dependency (20%), or critical illness (36%) requiring care in an intensive care unit. Overall treatment success was 86% (n = 225/262), and treatment success for patients taking concomitant β-lactams was 86% (n = 105/122). Logistic regression identified treatment failure to be associated with sepsis (odds ratio = 3.42;P= 0.009) and an elevated daptomycin MIC (3-4 µg/mL) (odds ratio = 3.23,P= 0.013). No significant increase in clinical failure was seen among patients with elevated daptomycin MIC who received concomitant β-lactam therapy (clinical success, 88% vs 79% for MIC <=2 vs 3-4 µg/mL, respectively;P= 0.417). Of 262 patients, 33 (13%) experienced >=1 adverse event possibly related to daptomycin (increased creatine kinase in 8 patients). Implications Overall, daptomycin was effective and well tolerated for VRE bacteremia, with lower effectiveness noted with daptomycin MIC of 3 to 4 µg/mL. Concomitant β-lactam therapy with daptomycin may improve clinical outcomes in this setting. Further studies are needed to characterize the potential benefit of concomitant β-lactams with daptomycin. Abstract Purpose In light of recent evidence suggesting enhancement of daptomycin activity against vancomycin-resistant Enterococcus (VRE) by ampicillin and other β-lactam antibiotics, we evaluated the safety profile and clinical efficacy of daptomycin with and without concomitant β-lactam antimicrobials in the treatment of VRE ( faecium or faecalis ) bacteremia from multiple centers across the United States. Methods Data were collected retrospectively as part of a larger multicenter registry (The Cubicin Outcomes Registry and Experience). Efficacy and clinical outcomes in patients with VRE bacteremia who received at least 3 days of daptomycin with or without concomitant β-lactams were analyzed. Although all the cases involved daptomycin-susceptible VRE, additional analysis was performed to examine whether the adjunctive β-lactam would play a more pivotal role in cases where the daptomycin MIC was in the upper limit of the susceptibility range, indicating that daptomycin monotherapy efficacy may be relatively compromised compared with cases with lower daptomycin MICs. Findings Two hundred sixty-two patients from 33 hospitals were evaluated. Most patients had at least one significant comorbidity, such as solid-organ or bone marrow transplantation (16%), neutropenia (36%), dialysis dependency (20%), or critical illness (36%) requiring care in an intensive care unit. Overall treatment success was 86% (n = 225/262), and treatment success for patients taking concomitant β-lactams was 86% (n = 105/122). Logistic regression identified treatment failure to be associated with sepsis (odds ratio = 3.42; P = 0.009) and an elevated daptomycin MIC (3–4 µg/mL) (odds ratio = 3.23, P = 0.013). No significant increase in clinical failure was seen among patients with elevated daptomycin MIC who received concomitant β-lactam therapy (clinical success, 88% vs 79% for MIC ≤2 vs 3–4 µg/mL, respectively; P = 0.417). Of 262 patients, 33 (13%) experienced ≥1 adverse event possibly related to daptomycin (increased creatine kinase in 8 patients). Implications Overall, daptomycin was effective and well tolerated for VRE bacteremia, with lower effectiveness noted with daptomycin MIC of 3 to 4 µg/mL. Concomitant β-lactam therapy with daptomycin may improve clinical outcomes in this setting. Further studies are needed to characterize the potential benefit of concomitant β-lactams with daptomycin. |
Author | Lamp, Kenneth C., PharmD Yoon, Min J., MPH Moise, Pamela A., PharmD Reyes, Katherine, MD McKinnell, James A., MD DePestel, Daryl D., PharmD Sakoulas, George, MD Zervos, Marcus J., MD |
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BackLink | https://www.ncbi.nlm.nih.gov/pubmed/25982687$$D View this record in MEDLINE/PubMed |
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Keywords | daptomycin MIC, enterococci β-lactam VRE bacteremia enterococcus |
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Snippet | Abstract Purpose In light of recent evidence suggesting enhancement of daptomycin activity against vancomycin-resistant Enterococcus (VRE) by ampicillin and... In light of recent evidence suggesting enhancement of daptomycin activity against vancomycin-resistant Enterococcus (VRE) by ampicillin and other β-lactam... Purpose In light of recent evidence suggesting enhancement of daptomycin activity against vancomycin-resistantEnterococcus(VRE) by ampicillin and other... PURPOSEIn light of recent evidence suggesting enhancement of daptomycin activity against vancomycin-resistant Enterococcus (VRE) by ampicillin and other... Purpose In light of recent evidence suggesting enhancement of daptomycin activity against vancomycin-resistant Enterococcus (VRE) by ampicillin and other beta... |
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SubjectTerms | Adult Aged Anti-Bacterial Agents - therapeutic use Antibiotics Bacteremia - drug therapy Clinical outcomes daptomycin Daptomycin - therapeutic use Drug dosages Enterococcus Female Humans Intensive care Internal Medicine Laboratories Male Medical Education Medical records MIC, enterococci Microbial Sensitivity Tests Middle Aged Mortality Multivariate analysis Retreatment Retrospective Studies Sepsis Success United States Vancomycin - therapeutic use Vancomycin Resistance VRE bacteremia Young Adult β-lactam |
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