Current Paradigms of Combination Therapy in Methicillin-Resistant Staphylococcus aureus (MRSA) Bacteremia: Does it Work, Which Combination, and For Which Patients?

Abstract

The last several years have seen an emergence of literature documenting the utility of combination antimicrobial therapy, particularly in the salvage of refractory MRSA bacteremia. Recent clinical data are shaping conundrums of which regimens may be more beneficial, which can be potentially harmful, and which subset of patients stand to benefit from more aggressive treatment regimens than called for by current standards. In addition, the incorporation of combination therapy for MRSA bacteremia should be accompanied by the reminder that antimicrobial therapy does not need to be uniform for the entire duration, with an early intensive phase in high inoculum infections (e.g. with combination therapy), followed by a consolidation phase (i.e. monotherapy). This review and perspective consolidates the recent data on this subject and directs future goals in filling the knowledge gaps to methodically move forward towards improving patient outcomes.

Decursinol Angelate Mitigates Sepsis Induced by Methicillin-Resistant Staphylococcus aureus Infection by Modulating the Inflammatory Responses of Macrophages

“…Macrophages with the pro-inflammatory phenotype were also decreased by DA, as shown by the downregulation of CD38 + populations in the plasma and liver, by which MRSA is primarily sequestered from the portal vein, and then disseminated to other organs, such as the kidneys [18]. Vancomycin and daptomycin are currently used for the management of patients with MRSA infection, and combinations with alternative antibiotics have been tested [32]. Although antibiotics are the primary option for the treatment of sepsis, their excessive use has resulted in the increasing emergence of antibiotic-resistant strains worldwide [33].…”

The Effect of Combination Therapy on Mortality and Adverse Events in Patients with Staphylococcus aureus Bacteraemia: A Systematic Review and Meta-analysis of Randomized Controlled Trials

“…8 Forest plot of the risk ratio (RR) for nephrotoxicity in patients with S. aureus bacteraemia (SAB) Fig. 9 Funnel chart for all-cause mortality indicators by RevMan Furthermore, combination therapy may have survival benefits for patients with complicated and metastatic bacteraemia with higher mortality, and only some specific combination therapy with less toxicity and more synergistic sterilization can reduce mortality [16,45]. In contrast to other b-lactam antibacterial drugs, ceftaroline is active against MRSA by binding to PBP2A and inhibiting peptidoglycan transpeptidation.…”

Approaching 65 Years: Is It Time to Consider Retirement of Vancomycin for Treating Methicillin-Resistant Staphylococcus aureus Endovascular Infections?

“…Injection drug users often have dynamic organ function, including augmented vancomycin clearance making vancomycin serum level target attainment challenging, if not impossible [ 36 ]. Vancomycin alternatives historically shunned due to high cost, such as daptomycin, ceftaroline (although off-label), and various antibiotic combinations, have promising effectiveness requiring further study validation for MRSA bacteremia without the associated drug monitoring and renal hazards associated with vancomycin therapy [ 37 ]. In combination with source control, it is prudent to consider high-dose daptomycin (eg, 8–10 mg/kg) for patients with MRSA bacteremia secondary to injection drug use, and likely all patients with MRSA bacteremia [ 14 , 16 , 17 , 38–41 ].…”

“…In combination with source control, it is prudent to consider high-dose daptomycin (eg, 8–10 mg/kg) for patients with MRSA bacteremia secondary to injection drug use, and likely all patients with MRSA bacteremia [ 14 , 16 , 17 , 38–41 ]. A possible exception includes those with uncomplicated MRSA bacteremia (low inoculum, catheter-related MRSA bacteremia patients who defervesce quickly following source control without repeat positive blood cultures) [ 37 , 42 ]. When treating a 75-kg patient with preserved renal function for MRSA bacteremia today, the cost balance between vancomycin and daptomycin actually tips in favor of daptomycin ( Table 2 ).…”