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

Abstract

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.

Outer-membrane-acting peptides and lipid II-targeting antibiotics cooperatively kill Gram-negative pathogens

“…Additionally, engineering of the best hits provided a variant, L-11, with great potential to extend vancomycin’s spectrum against (MDR) Gram-negative pathogens. Synergies of vancomycin with other antimicrobials are well documented when targeting Gram-positive bacteria 30 – 32 , as well as its synergy in combination with outer-membrane perturbing (or not 33 ) antibiotics as colistins 34 , 35 . However, these combinations are still under study because of the relatively high toxicity observed 36 .…”

Ceftaroline-Associated Encephalopathy: A Rare Adverse Effect

“…Despite its only labeled indications being for aBSSSIs and CAP, ceftaroline has been used off-label for other MRSA infections, including infective endocarditis (IE). Ceftaroline has been linked to improved sterilization of blood when used with daptomycin in patients with MRSA IE versus daptomycin or vancomycin monotherapy [10]. Doses used in these case series are often higher than those studied in CANVAS/FOCUS trials, however, with sparse data on the safety and tolerability of increased dosing.…”

New-Generation Antibiotics for Treatment of Gram-Positive Infections: A Review with Focus on Endocarditis and Osteomyelitis

“…Daptomycin is a cyclic lipopeptide antibiotic with bactericidal activity against staphylococci, streptococci, and enterococci including VRE and MRSA [33]. It has different mechanisms of action including disruption of cell membrane function and inhibition of protein, DNA, and RNA synthesis.…”

“…Therefore, at least once-weekly CPK monitoring is required. Clearance of daptomycin is predominantly renal, and dosage adjustment is required when creatinine clearance is <30 mL/min [33,36].…”