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

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.

Author(s):  
Miquel Pujol ◽  
José-María Miró ◽  
Evelyn Shaw ◽  
Jose-María Aguado ◽  
Rafael San-Juan ◽  
...  

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.


Antibiotics ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 30 ◽  
Author(s):  
Nicole Lounsbury ◽  
Mary Reeber ◽  
Georges Mina ◽  
Christiane Chbib

Objective: The objective of this review is to describe the outcomes of patients treated with ceftaroline in the non-Food and Drug Administration (FDA) approved indication of methicillin-resistant Staphylococcus aureus (MRSA) infections in both pediatric and adult populations. Data sources: A systematic overview was conducted by searching PubMed, Medline, and The Cochrane Library up to January 2019. Study selection and data extraction: All English-language clinical trials and case reports related to the efficacy of ceftaroline in new, not-yet-approved FDA indications in MRSA infections in pediatric or adult populations. Data synthesis: In the case of MRSA bacteremia (MRSAB) infections, three different randomized studies in pediatric patients showed effectiveness of ceftaroline. When used in the case of adult populations with MRSA bacteremia, a small trial of 16 patients showed 50% clinical success in patients with acute bacterial skin and skin structure infections versus 63% clinical success in patients with community-acquired bacterial pneumonia. Another case series of six refractory case reports showed 50% clinical success of ceftaroline in patients with MRSA. Conclusions: Although there are few case reports and limited data to date, ceftaroline fosamil should continue to be studied as an alternative therapy in MRSA infections in both pediatric and adult populations. Clinical success rates of ceftaroline were, in most cases, considered high when treating patients with MRSA infection. More clinical trials need to be studied. In the specific case of MRSA bacteremia, the treatment options remain few and ceftaroline should be extensively studied for the salvage treatment of MRSAB.


2019 ◽  
Vol 24 (4) ◽  
pp. 312-319 ◽  
Author(s):  
Rebecca B. Regen ◽  
Sarah S. Schuman ◽  
Rebecca F. Chhim ◽  
Sandra R. Arnold ◽  
Kelley R. Lee

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.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S804-S805
Author(s):  
Andrei Zidaru ◽  
Hannah Ryan Russo ◽  
Kady Phe

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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