Successful treatment with daptomycin and ceftaroline of MDR Staphylococcus aureus native valve endocarditis: a case report

Abstract

Objectives The best therapeutic approach for treating MRSA endocarditis remains unknown, particularly in cases of high vancomycin MICs. We report here a case of daptomycin-non-susceptible, ceftaroline-resistant and fosfomycin-resistant MRSA native left valve endocarditis that was successfully treated with valve repair and a combination of high-dose daptomycin and ceftaroline. Methods Antimicrobial testing of the clinical strain was performed using Etest and microdilution broth methods. Time–kill and chequerboard methodologies were used to test the activity of antibiotic combinations. Results By Etest, the MIC of vancomycin was 2 mg/L, the MIC of daptomycin was 2 mg/L, the MIC of fosfomycin was 1024 mg/L and the MIC of ceftaroline was 1.5 mg/L. At the standard inoculum (105 cfu/mL), the three combinations of daptomycin plus ceftaroline, cloxacillin or fosfomycin were synergistic and bactericidal. However, when these combinations were tested using a higher inoculum (108 cfu/mL), all combinations were synergistic, but only daptomycin plus ceftaroline had bactericidal activity. Conclusions These results confirmed a synergistic effect between daptomycin plus ceftaroline and increased bactericidal activity against MRSA, suggesting that this combination may be effective for the treatment of invasive MRSA infection. Our experience highlights the potential clinical use of synergy testing to guide difficult treatment decisions in patients with MDR MRSA infection.

Dosing Considerations for Combination Antistaphylococcal β-Lactam and Glyco/lipopeptide Salvage Therapy for Resistant Gram-Positive Infections: A Systematic Review

“…In a 2019 case report, the efficacy of combination salvage therapy was reviewed in a 90-year-old patient with multidrug-resistant MRSA community-acquired left-sided endocarditis. 24 After 9 days of failed treatment with 2 days of vancomycin 2 g IV every 24 hours, followed by 7 days of daptomycin 800 mg IV every 24 hours, and fosfomycin IV 2 g every 6 hours, combination salvage therapy consisting of daptomycin 800 mg IV every 24 hours and ceftaroline 600 mg IV every 8 hours was initiated. 24 Blood cultures were cleared within 24 hours of combination salvage therapy and valve repair.…”

“…24 After 9 days of failed treatment with 2 days of vancomycin 2 g IV every 24 hours, followed by 7 days of daptomycin 800 mg IV every 24 hours, and fosfomycin IV 2 g every 6 hours, combination salvage therapy consisting of daptomycin 800 mg IV every 24 hours and ceftaroline 600 mg IV every 8 hours was initiated. 24 Blood cultures were cleared within 24 hours of combination salvage therapy and valve repair. The patient remained on combination salvage therapy for 42 days.…”

“…8 Of the data compiled and reviewed in this report, the duration of failed initial or empirical glycopeptide or lipopeptide therapy before conversion to combination salvage therapy ranged from 1 day to 30 days. 16,20-26…”

“…20 Clearance of blood cultures ranged within 1 to 4 days of combination salvage therapy, with most studies reporting negative cultures within 24 hours. 16,20-26 The decision to discontinue combination salvage therapy remains a gray area in clinical practice: whereas current Infectious Diseases Society of America guidelines for treatment of MRSA bacteremia recommend a minimum 2-week duration of therapy for uncomplicated bacteremia and 6-week duration for complicated bacteremia, those recommendations do not account for combination salvage therapy. 4 It may be reasonable to continue the combination therapy indefinitely until the complete resolution of the infection based on the mechanisms of action and synergy.…”

“…Evidence from this evaluation documents the successful treatment of gram-positive–resistant infections with combination salvage therapy with daptomycin 6 to 12 mg/kg IV every 24 hours with ceftaroline 200 to 600 mg IV every 8 to 12 hours, or in combination with vancomycin with a target trough of 15 to 20 µg/mL and ceftaroline 200 to 600 mg every 8 to 12 hours. 16,20-26 In addition, the largest sample size within the primary literature showed strong success of vancomycin in combination with flucloxacillin 2 g IV every 6 hours, though it is important to note that this product is not available in the United States and that ampicillin may represent a reasonable alternative. 20,27 The consideration of ampicillin is extrapolated from pharmacological and biochemical information and has not specifically been vetted in practice.…”