What are the options for salvage therapy in patients with persistent Methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia?

From the Guidelines

For persistent methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia requiring salvage therapy, I recommend combination therapy with a beta-lactam antibiotic plus either daptomycin or an aminoglycoside, as this approach has been supported by recent guidelines and studies 1. The most effective combination would be cefazolin (2g IV every 8 hours) or an anti-staphylococcal penicillin (ASP) such as nafcillin or oxacillin (2g IV every 4 hours), combined with daptomycin (8-10 mg/kg IV daily) or gentamicin (1 mg/kg IV every 8 hours). Key considerations in the management of persistent MSSA bacteremia include:

• Early source control, which is essential for clearing the infection 1
• Using a treatment duration of 4–6 weeks for bacteremia with high-risk features, as recommended by evidence-based and guideline-supported practices 1
• Regular monitoring of renal function, complete blood counts, and drug levels (for aminoglycosides) to minimize the risk of adverse effects
• Infectious disease consultation to guide management and ensure optimal outcomes
• Consideration of additional imaging and intervention if persistent bacteremia is suspected to be due to complications like endocarditis, septic thrombophlebitis, or undrained abscesses 1. It is also crucial to note that vancomycin or daptomycin may be used for methicillin-resistant S. aureus (MRSA), but for MSSA, cefazolin or ASP is the preferred choice 1. The choice of antibiotic regimen should be guided by the patient's clinical response, blood culture clearance, and the presence of any complications or high-risk features.

From the FDA Drug Label

1. 9 Persisting or Relapsing S. aureus Bacteremia/Endocarditis Patients with persisting or relapsing S. aureus bacteremia/endocarditis or poor clinical response should have repeat blood cultures. If a blood culture is positive for S aureus, minimum inhibitory concentration (MIC) susceptibility testing of the isolate should be performed using a standardized procedure, and diagnostic evaluation of the patient should be performed to rule out sequestered foci of infection. Appropriate surgical intervention (e.g., debridement, removal of prosthetic devices, valve replacement surgery) and/or consideration of a change in antibacterial regimen may be required. Failure of treatment due to persisting or relapsing S. aureus bacteremia/endocarditis may be due to reduced daptomycin susceptibility (as evidenced by increasing MIC of the S. aureus isolate) [see Clinical Studies (14.2)] .

For salvage therapy in patients with persistent MSSA bacteremia, the following steps should be taken:

• Repeat blood cultures
• Perform MIC susceptibility testing of the isolate
• Diagnostic evaluation to rule out sequestered foci of infection
• Consider change in antibacterial regimen or surgical intervention 2

From the Research

Salvage Therapy for Persistent MSSA Bacteremia

• The study 3 found that cefazolin and ertapenem combination therapy was used successfully to salvage 11 cases of persistent methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia, including immediate clearance (≤24 hours) in 8 cases.
• The combination of cefazolin and ertapenem provides potent in vivo activity against MSSA beyond what is predicted in vitro and warrants further clinical study in the treatment of refractory MSSA bacteremia and endocarditis 3.

Salvage Therapy for Persistent MRSA Bacteremia

• The study 4 found that persistent MRSA bacteremia can be difficult to successfully eliminate, especially when source control is not possible due to an irremovable focus or the bacteremia still persists despite surgical intervention.
• The employment of novel strategies is required to effectively treat patients with persistent MRSA bacteremia, and these may frequently involve combination drug therapy 4.
• The study 5 found that daptomycin plus ceftaroline may be an option to hasten clearance of refractory staphylococcal bacteremia, with ceftaroline offering dual benefit via synergy with both daptomycin and sensitization to innate host defense peptide cathelicidin LL37.
• The study 6 found that linezolid could be a potential first-line drug against MRSA bacteremia as well as vancomycin or daptomycin, with comparable effectiveness and safety outcomes.
• The study 7 found that ceftaroline is an effective agent for the salvage treatment of MRSA bacteremia, with off-label doses up to 600 mg every 8 hours often used to achieve optimal pharmacokinetic/pharmacodynamic parameters.

Treatment Options

• Combination antibiotic therapy, such as vancomycin combined with a β-lactam, daptomycin-based therapy, ceftaroline-based therapy, linezolid-based therapy, quinupristin/dalfopristin, telavancin, trimethoprim/sulfamethoxazole-based therapy, and fosfomycin-based therapy, may be considered for use in MRSA salvage treatment 4.
• Cefazolin and ertapenem combination therapy may be considered for use in MSSA salvage treatment 3.
• Ceftaroline monotherapy may be considered for use in MRSA salvage treatment, especially in cases where patients have failed or progressed on other therapies 7.