scholarly journals Combination Therapy With Lysin CF-301 and Antibiotic Is Superior to Antibiotic Alone for Treating Methicillin-Resistant Staphylococcus aureus–Induced Murine Bacteremia

2013 ◽  
Vol 209 (9) ◽  
pp. 1469-1478 ◽  
Author(s):  
Raymond Schuch ◽  
Han M. Lee ◽  
Brent C. Schneider ◽  
Karen L. Sauve ◽  
Christina Law ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Combination Therapy ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistant

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 β-Lactamase Inhibitors Enhance the Synergy between β-Lactam Antibiotics and Daptomycin against Methicillin-Resistant Staphylococcus aureus

2016 ◽  
Vol 61 (1) ◽  
Author(s):  
Karl Evans R. Henson ◽  
Juwon Yim ◽  
Jordan R. Smith ◽  
George Sakoulas ◽  
Michael J. Rybak
Keyword(s):  
Staphylococcus Aureus ◽  
Combination Therapy ◽  
Synergistic Effect ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistant ◽  
Content Type ◽  
Time Kill ◽  
Lactamase Inhibitor

ABSTRACT The evidence for using combination therapy for the treatment of serious methicillin-resistant Staphylococcus aureus (MRSA) infections is growing. In this study, we investigated the synergistic effect of daptomycin (DAP) combined with piperacillin-tazobactam and ampicillin-sulbactam against MRSA in time-kill experiments. Six of eight strains demonstrated synergy between DAP and the β-lactam–β-lactamase inhibitor (BLI) combination. In 5/8 strains, the synergy occurred only in the presence of the BLI, highlighting a role for BLIs in peptide–β-lactam synergy.

scholarly journals 204. Clinical Outcomes with Ceftaroline Monotherapy versus Daptomycin-Ceftaroline Combination Therapy in the Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S209-S210
Author(s):  
Gabriela Andonie ◽  
Elizabeth O Hand ◽  
Kelly R Reveles ◽  
Kristi A Traugott
Keyword(s):  
Staphylococcus Aureus ◽  
Combination Therapy ◽  
Clinical Outcomes ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Controlled Trial ◽  
Primary Source ◽  
Retrospective Chart Review ◽  
Combination Group ◽  
Methicillin Resistant ◽  
Significant Difference

Abstract Background Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with poor outcomes and increased mortality. Daptomycin (DAP) and ceftaroline (CPT) in combination has been explored as a potential treatment option and showed improved outcomes compared to vancomycin/standard therapy. CPT monotherapy has been evaluated as salvage therapy for MRSA bacteremia but, to our knowledge, not as a comparator to DAP-CPT combination therapy. The purpose of this study is to compare the clinical outcomes of DAP and CPT combination therapy to CPT monotherapy in the setting of MRSA bacteremia. Methods A retrospective chart review of adult patients (≥ 18 years of age) admitted to University Health from January 2017 to December 2020 with a diagnosis of MRSA bacteremia was performed. Patients received either CPT monotherapy or DAP-CPT combination therapy for a minimum of 48 hours during their course of therapy. Results Thirty-two patients met inclusion criteria and were evaluated. Primary source of infection was pulmonary in the CPT monotherapy group (n=7/24; 29.2%) and osteomyelitis in the DAP-CPT combination group (n= 4/8; 50.0%). Median duration of bacteremia was 8 days and 9 days in the CPT monotherapy and DAP-CPT combination group, respectively. Microbiological cure was achieved in 95.8% (n=23/24) of patients in the CPT monotherapy and 100% (n=8/8) of patients in the DAP-CPT combination group. Bacteremia relapse (30 day, p=0.62; 60 day, p=0.63), readmission rates (30 day, p=0.62; 60 day, p=0.63), and mortality rates (30 day, p=0.70; 90 day, p=0.85) were similar in both groups. There was no statistically significant difference in safety parameters, including incidence of acute kidney injury (p=1.00) and creatine kinase elevations (p=1.00). Bone marrow suppression after at least 72 hours of therapy, including anemia, leukopenia, and thrombocytopenia, was also not statistically significant between groups. Conclusion This study was unable to find a statistically significant difference in clinical outcomes between patients receiving CPT monotherapy or DAP-CPT combination therapy. A large prospective, randomized controlled trial to assess CPT monotherapy and DAP-CPT combination therapy for the treatment of persistent MRSA bacteremia is warranted. Disclosures All Authors: No reported disclosures

scholarly journals 686. Comparing Treatments of Methicillin-Resistant Staphylococcus aureus Infective Endocarditis by People Who Inject Drugs

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S445-S446
Author(s):  
Nicholas Rebold ◽  
Sara Alosaimy ◽  
Abdalhamid M Lagnf ◽  
Dana Holger ◽  
Michael J Rybak
Keyword(s):  
Staphylococcus Aureus ◽  
Infective Endocarditis ◽  
Combination Therapy ◽  
People Who Inject Drugs ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Hospital Length ◽  
Hospital Length Of Stay ◽  
Source Control ◽  
Chi Square ◽  
Methicillin Resistant

Abstract Background People who inject drugs (PWID) are at high risk for infective endocarditis (IE) with high-mortality pathogens such as methicillin-resistant Staphylococcus aureus (MRSA). Stigma against PWID may cause differences in treatment and outcomes between these patients infected with MRSA IE. Methods Single center retrospective cohort study from August 2006 to February 2021 that includes adult patients diagnosed with IE. Primary outcomes included 90-day all-cause mortality, 60-day MRSA recurrence, 60-day readmission, and hospital length of stay (LOS). Statistical analysis was performed by chi-square, t-test, and Mann-Whitney-U as appropriate. Results A total of 214 patients were diagnosed with MRSA IE; 89 PWID and 125 non-PWID. The mean (SD) age was 47.4±12.4 years (PWID) vs 59.3 ±16.0 years (non-PWID) (p< 0.001). Patients were primarily male (56%), but differed in terms of race 34% African-American (AA) (PWID) vs 66% AA (non-PWID) (p< 0001). Mean APACHE II scores differed between groups: 16(±9.9) (PWID) vs 19(±8.1) (non-PWID) (p< 0.008). Among patients who cleared bacteremia, mean (SD) duration was 5.7(±3.9) days and was not significant between groups (p< 0.64). Valve-type was 93% native and 7% prosthetic and not different between groups (p< 0.16). Infectious Diseases consult did not differ at 96% overall (p< 0.31), but pursuit of source control nearly reached significance at 27% for PWID vs 41% non-PWID (p< 0.06). Similarly, use of combination therapy daptomycin and ceftaroline was nearly significant: 21% (PWID) vs 12% (non-PWID) (p< 0.09). Odds ratio of PWID and combination therapy remained non-significant after regression: 0.39(0.14-1.1,p< 0.07). Primary 90-day mortality was lower in PWID vs non-PWID (15% vs 30%) respectively (p< 0.01), but did not differ in 60-day MRSA recurrence (p< 1.0) at 9%, 60-day readmission (p< 1.0) at 33%, or median LOS (IQR) (p< 0.46) at 15 (10-24) days overall. Conclusion While PWID are significantly younger, less critically ill, and have lower mortality compared to non-PWID, they have similar LOS, MRSA recurrence, and readmission rates. Analyses suggest a potential difference in the pursuit of source control and combination therapy among PWID, however more studies may be needed to achieve significance. Disclosures Michael J. Rybak, PharmD, MPH, PhD, Paratek Pharmaceuticals (Research Grant or Support)

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