scholarly journals LB3. Daptomycin Plus Fosfomycin vs. Daptomycin Monotherapy for Methicillin-Resistant Staphylococcus aureus Bacteremia: A Multicenter, Randomized, Clinical Trial

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S760-S760 ◽  
Author(s):  
Miquel Pujol ◽  
Jose-Maria Miro ◽  
Evelyn Shaw ◽  
Jose Maria Aguado ◽  
Rafael San-Juan Garrido ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Staphylococcus Aureus ◽  
Combination Therapy ◽  
Confidence Interval ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Treatment Success ◽  
Successful Outcome ◽  
Absolute Difference ◽  
Staphylococcus Aureus Bacteremia ◽  
To Receive

Abstract Background Daptomycin plus fosfomycin combination has demonstrated synergistic and bactericidal effect in animal models of methicillin-resistant Staphylococcus aureus bacteremia (MRSAB), but there is lack of data in humans. Method A randomized (1:1), open-label, clinical trial involving adults with MRSAB was conducted at 18 medical centers in Spain. Patients were assigned to receive daptomycin, 10 mg/kg IV daily plus fosfomycin, 2 g IV/6 hour (combination therapy) or to receive daptomycin 10 mg/kg/24 h IV (monotherapy) during 10 up to 14 days for uncomplicated bacteremia and 28 up to 42 days for complicated bacteremia. The primary efficacy endpoints were: (a) treatment success at Test-of-Cure visit (ToC: 6 weeks after end of therapy) and (b) treatment success at 7 days (defined as alive at day 7 and clearance of bacteremia without relapse from 8 to 90 days after randomization), according with the proposed primary endpoints for use in clinical trials in bloodstream infections in adults. Result Between December 2013 and November 2017, 674 patients with MRSAB were evaluated and 155 patients were randomized: 74 received combination therapy and 81 monotherapy. In intention-to-treat analysis, (a) at ToC visit successful outcome was achieved in 40 of 74 patients (54,1%) who received combination therapy as compared with 34 of 81 patients (42%) who were given monotherapy (54.1% vs. 42.0%; absolute difference, 12.1%; 95% confidence interval, 0%-27.0%); (b) at 7 days after starting the therapy: a successful outcome was achieved in 69 of 74 patients who received combination therapy as compared with 62 out of 81 patients who received monotherapy (93.2% vs. 76.5%; absolute difference, 16.7%; 95% confidence interval, 5.4%–27.7%). Combination therapy was associated with lower rates of microbiologic failure than monotherapy at ToC visit (0 vs. 9 patients, P = 0.009). Combination therapy, as compared with daptomycin monotherapy, was associated with a nonsignificantly higher rate of adverse events due to study medication leading to treatment failure and discontinuation of therapy: 6/74 (8.1%) vs. 3/81 (3.7%) (P = 0.31). Conclusion The combination of daptomycin plus fosfomycin was more effective than daptomycin alone for treating MRSAB (NCT01898338). Disclosures All authors: No reported disclosures.

scholarly journals Daptomycin Plus Fosfomycin Versus Daptomycin Alone for Methicillin-resistant Staphylococcus aureus Bacteremia and Endocarditis: A Randomized Clinical Trial

2020 ◽  
Author(s):  
Miquel Pujol ◽  
José-María Miró ◽  
Evelyn Shaw ◽  
Jose-María Aguado ◽  
Rafael San-Juan ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Staphylococcus Aureus ◽  
Adverse Events ◽  
Primary Endpoint ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Statistical Significance ◽  
Treatment Success ◽  
Open Label ◽  
Methicillin Resistant ◽  
Staphylococcus Aureus Bacteremia

Abstract Background We aimed to determine whether daptomycin plus fosfomycin provides higher treatment success than daptomycin alone for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and endocarditis. Methods A randomized (1:1) phase 3 superiority, open-label, and parallel group clinical trial of adult inpatients with MRSA bacteremia was conducted at 18 Spanish hospitals. Patients were randomly assigned to receive either 10 mg/kg of daptomycin intravenously daily plus 2 g of fosfomycin intravenously every 6 hours, or 10 mg/kg of daptomycin intravenously daily. Primary endpoint was treatment success 6 weeks after the end of therapy. Results Of 167 patients randomized, 155 completed the trial and were assessed for the primary endpoint. Treatment success at 6 weeks after the end of therapy was achieved in 40 of 74 patients who received daptomycin plus fosfomycin and in 34 of 81 patients who were given daptomycin alone (54.1% vs 42.0%; relative risk, 1.29 [95% confidence interval, .93–1.8]; P = .135). At 6 weeks, daptomycin plus fosfomycin was associated with lower microbiologic failure (0 vs 9 patients; P = .003) and lower complicated bacteremia (16.2% vs 32.1%; P = .022). Adverse events leading to treatment discontinuation occurred in 13 of 74 patients (17.6%) receiving daptomycin plus fosfomycin, and in 4 of 81 patients (4.9%) receiving daptomycin alone (P = .018). Conclusions Daptomycin plus fosfomycin provided 12% higher rate of treatment success than daptomycin alone, but this difference did not reach statistical significance. This antibiotic combination prevented microbiological failure and complicated bacteremia, but it was more often associated with adverse events. Clinical Trials Registration NCT01898338.

scholarly journals Adjunctive ceftaroline in combination with daptomycin or vancomycin for complicated methicillin-resistant Staphylococcus aureus bacteremia after monotherapy failure

2019 ◽  
Vol 6 ◽  
pp. 204993611988650 ◽  
Author(s):  
Joseph Patrik Hornak ◽  
Seher Anjum ◽  
David Reynoso
Keyword(s):  
Staphylococcus Aureus ◽  
Combination Therapy ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Treatment Options ◽  
Source Control ◽  
Optimal Timing ◽  
Methicillin Resistant ◽  
Staphylococcus Aureus Bacteremia ◽  
Persistent Bacteremia

Background: Methicillin-resistant Staphylococcus aureus bacteremia (MRSA-B) may fail to improve with standard monotherapy, particularly in patients with multifocal infection, incomplete source control, or persistent bacteremia. Synergy observed in vitro between ceftaroline (CPT) and daptomycin (DAP) or vancomycin (VAN) may translate into clinical benefit. Here, we describe our experience with DAP/CPT and VAN/CPT for complicated MRSA-B after monotherapy failure. Methods: Single-center, retrospective review of consecutive patients treated with DAP/CPT or VAN/CPT for MRSA-B after monotherapy failure from 1 January 2016 to 30 November 2018. Results: We identified 11 instances of combination therapy in 10 patients (DAP/CPT = 6, VAN/CPT = 5) with 1 patient receiving VAN/CPT followed by DAP/CPT. Rates of multifocal infection, incomplete source control, persistent bacteremia, and infective endocarditis were high (100%, 80%, 60%, and 60%, respectively). Combination therapy was initiated most commonly for persistent bacteremia (60%). When patients were persistently bacteremic, median preceding duration was 13 days and median time to clearance was 3 days. Total microbiologic cure rate was 100%. There were zero instances of bacteremia relapse at 30 days (30D) or 60 days (60D). All-cause 30D and 60D mortality rates were 11.1% and 33.3%, respectively. Conclusions: Combination therapy demonstrated success in diverse cases of refractory MRSA-B, including instances of persistent bacteremia paired with incomplete source control. Optimal timing and therapeutic cadence for combination therapy remain unclear. Our findings suggest that DAP/CPT and VAN/CPT can be considered for complicated MRSA bacteremia when other treatment options fail or are unavailable. We propose persistent bacteremia with incomplete source control to be a clinical niche particularly worthy of further investigation.

scholarly journals Ceftaroline in Combination With Trimethoprim-Sulfamethoxazole for Salvage Therapy of Methicillin-Resistant Staphylococcus aureus Bacteremia and Endocarditis

2014 ◽  
Vol 1 (2) ◽  
Author(s):  
Valeria Fabre ◽  
Marcela Ferrada ◽  
Whitney R. Buckel ◽  
Edina Avdic ◽  
Sara E. Cosgrove
Keyword(s):  
Staphylococcus Aureus ◽  
Clinical Trials ◽  
Salvage Therapy ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Treatment Success ◽  
Ceftaroline Fosamil ◽  
Methicillin Resistant ◽  
Staphylococcus Aureus Bacteremia ◽  
Report Data

Abstract No clinical trials have investigated the use of ceftaroline fosamil for salvage therapy of methicillin-resistant Staphylococcus aureus bacteremia and endocarditis. We report data on 29 patients who received ceftaroline ± another antimicrobial for this indication. Ninety percent of patients had microbiologic cure and 31% had treatment success with a median follow-up of 6 months.

scholarly journals Vancomycin Treatment Failure in Children With Methicillin-Resistant Staphylococcus aureus Bacteremia

2019 ◽  
Vol 24 (4) ◽  
pp. 312-319 ◽  
Author(s):  
Rebecca B. Regen ◽  
Sarah S. Schuman ◽  
Rebecca F. Chhim ◽  
Sandra R. Arnold ◽  
Kelley R. Lee
Keyword(s):  
Staphylococcus Aureus ◽  
Treatment Failure ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Treatment Success ◽  
Area Under The Curve ◽  
Failure Criteria ◽  
Methicillin Resistant ◽  
Staphylococcus Aureus Bacteremia ◽  
Persistent Bacteremia ◽  
Vancomycin Treatment

OBJECTIVES Limited data exist regarding clinical outcomes of invasive methicillin-resistant Staphylococcus aureus (MRSA) infections in children treated with vancomycin. Treatment success in adults correlates best with an area under the curve/minimum inhibitory concentration (AUC24/MIC) ratio ≥400. It is unknown if this relationship is useful in children. METHODS Charts of children who received vancomycin ≥5 days for MRSA bacteremia with a steady state trough were reviewed. AUC24/MIC ratios were estimated using 2 different vancomycin clearance equations. Vancomycin treatment failure was defined as persistent bacteremia ≥7 days, recurrent bacteremia within 30 days, or 30-day mortality. RESULTS There were 67 bacteremia episodes in 65 patients. Nine (13.4%) met failure criteria: persistent bacteremia (n = 6), recurrent bacteremia (n = 2), 30-day mortality (n = 1). There were no differences between patients receiving <60 mg/kg/day and ≥60 mg/kg/day of vancomycin in median trough (11.9 versus 12.3 mg/L, p = 0.1). Troughs did not correlate well with AUC24/MIC ratios (R2 = 0.32 and 0.22). Patients receiving ≥60 mg/kg/day had greater probability of achieving ratios ≥400. There were no significant differences in median dose (p = 0.8), trough (p = 0.24), or AUC24/MIC ratios (p = 0.07 and p = 0.6) between patients with treatment success and failure. CONCLUSIONS Treatment failure was lower than previously reported in children. AUC24/MIC ratios ≥400 were frequently achieved but were not associated with treatment success, dose, or troughs. Prospective studies using standard definitions of vancomycin treatment failure are needed to understand treatment failure in children with MRSA bacteremia.

scholarly journals 276. Comparison of Ceftaroline in Combination with Either Vancomycin or Daptomycin for the Treatment of Methicillin-resistant Staphylococcus aureus Bacteremia

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S138-S139
Author(s):  
Stephanie N Welch ◽  
Jacqueline Meredith ◽  
Danya Roshdy ◽  
Leigh A Medaris ◽  
Lewis McCurdy
Keyword(s):  
Staphylococcus Aureus ◽  
Combination Therapy ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Clinical Success ◽  
Unit Length ◽  
Culture Collection ◽  
Methicillin Resistant ◽  
Staphylococcus Aureus Bacteremia ◽  
Therapy Initiation ◽  
Secondary Endpoints

Abstract Background Recent studies have suggested that combination therapy may be preferred to monotherapy for select patients with methicillin-resistant Staphylococcus aureus bacteremia (MRSA-B); however, direct comparison between various combination regimens is lacking. Methods This was a multicenter, retrospective cohort study evaluating adult patients with MRSA-B who received vancomycin/ceftaroline (VAN+CPT) or daptomycin/ceftaroline (DAP+CPT) for at least 48 hours between April 1, 2017 and June 30, 2019. Patients with primary respiratory or central nervous system infections were excluded. The primary endpoint was rate of clinical success, defined as survival at 90 days, sterilization of blood cultures within 96 hours of combination therapy initiation, no perceived clinical failure requiring a change in MRSA-active therapy, and absence of recurrence. Secondary endpoints included time to culture clearance from combination therapy initiation, 30-day and in-hospital mortality, adverse events prompting antibiotic discontinuation, and hospital and intensive care unit length of stay. Results A total of 54 patients were included in the VAN+CPT group and 25 patients in the DAP+CPT group. Baseline characteristics were generally similar between groups, except patients in the VAN+CPT group were younger and more likely to have endocarditis. Bone/joint sources were more common in the DAP+CPT group. Initiation of combination therapy occurred 104.9 hours vs 140.0 hours from index culture collection in the VAN+CPT and DAP+CPT groups, respectively. Rates of clinical success were similar between groups (63.0% vs 64.0%, p=0.93). Time to culture clearance from combination therapy initiation was 50.9 hours in the VAN+CPT group compared to 48.6 hours in DAP+CPT (p=0.83). Rates of nephrotoxicity were higher in those who received VAN+CPT (16.7% vs 0%, p=0.04). Other secondary endpoints were similar between groups. Conclusion Rates of clinical success were similar between groups, though there was a significantly higher rate of nephrotoxicity noted in the VAN+CPT group. Our study supports that clinical outcomes may be similar between VAN+CPT and DAP+CPT, with greater safety concerns associated with VAN+CPT. Disclosures All Authors: No reported disclosures

scholarly journals 1624. Real World Experience with Daptomycin (DAP) and Ceftaroline (CPT) Combination Therapy for Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S804-S805
Author(s):  
Andrei Zidaru ◽  
Hannah Ryan Russo ◽  
Kady Phe
Keyword(s):  
Staphylococcus Aureus ◽  
Combination Therapy ◽  
Median Time ◽  
Real World ◽  
Salvage Therapy ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Real World Data ◽  
Methicillin Resistant ◽  
Staphylococcus Aureus Bacteremia ◽  
Persistent Bacteremia

Abstract Background Methicillin-resistant Staphylococcus aureus bacteremia is associated with significant mortality rates up to 30%. Guideline-recommended first-line therapy includes monotherapy with either vancomycin or DAP. Alternative regimens are recommended for persistent MRSA bacteremia of ≥ 7 days or earlier if evident clinical deterioration. The combination of DAP plus CPT has been investigated as salvage therapy due to its synergistic mechanism potential, but real-world data with the combination therapy is limited. The aim of this study was to evaluate the efficacy of DAP plus CPT combination therapy for the treatment of MRSA bacteremia and identify independent predictors of 30-day mortality. Methods This was a single center retrospective study of patients receiving DAP-CPT at any point in therapy for the treatment of MRSA bacteremia. Univariable and multivariable analyses were performed to identify independent predictors of 30-day mortality. Results Sixty-five unique patients received DAP-CPT with a median time to combination therapy of 7 days. There were no significant independent predictors of 30-day mortality. The most common reason for combination therapy was persistent bacteremia (80%, 52/65). Bacteremia was cleared in 90.8% (59/65) of patients and the 30-day mortality rate was 15.4% (10/65). Median time to bacteremia clearance after combination switch was 3 days. Eleven patients received DAP-CPT within 72 hours of index culture. Median time to bacteremia clearance for patients switched to DAP-CPT within 72 hours versus after 72 hours did not differ (2 vs 3 days; P = 0.526), however the overall median duration of bacteremia was 4 and 11 days (P = 0.018). In a sub analysis, the median time of bacteremia clearance following combination therapy was significantly longer for patients receiving renal replacement therapy (5 vs 2 days; P = 0.04). Conclusion There were no independent predictors of 30-day mortality identified. DAP-CPT combination therapy resulted in clearance of persistent bacteremia and may serve as an effective salvage therapy. Disclosures All Authors: No reported disclosures

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