173 Persistent MRSA bacteremia 8 No randomized controlled trials to date have addressed this specific question, leaving an unmet need for medical practice. However, until high-quality evidence is available, the available literature provides suggestions for best practice regarding the treatment of persistent MRSAB. The management of MRSAB consists of three important pillars: source control, antibiotic treatment, and follow-up blood cultures. For evaluation of metastatic infection sites as targets for source control, the transesophageal echocardiogram is the most evidence based [123,124]. For positron emission tomography/computed tomography (PET-CT), there is evidence for impacting management and for reducing mortality in patients with SAB [125,126], although this latter finding may have been confounded by the introduction of immortal time bias related to including patients dying before undergoing PET-CT. Thorough clinical assessment by a trained infectious diseases consultant has been proven to be beneficial in the management of MRSAB [127]. In the case of positive follow-up blood cultures and thus persistent bacteremia despite adequate treatment, potential targets for source control must be reevaluated, and subsequently also the antibiotic therapy. This is particularly true now, as the specific antibiotic treatment options have evolved over time. The past For decades, vancomycin monotherapy was the only recommended antibiotic treatment for MRSAB. This was primarily due to the lack of other options for monotherapy. There has been a multiplicity of attempts to craft an effective combination antibiotic therapy for SAB. Adjunctive gentamicin appeared to be an attractive option according to in vitro data, but was associated with increased nephrotoxicity without any clinical benefit [128]. Alternatives for vancomycin, such as trimethoprim-sulfamethoxazole, did not achieve non-inferiority for the treatment of MRSAB [18,129]. For many years, the addition of rifampin was thought to improve outcomes, but the ARREST trial has ruled out that hypothesis: outcomes in both MSSA and MRSAB did not improve with adjunctive rifampin [130]. Historically, there were few options for treatment of persistent MRSAB. When confronted with persistent MRSAB > 7 days after vancomycin initiation and a MIC of 2 µg/mL, almost three-quarters of surveyed American ID consultants in 2005 would continue vancomycin and add another drug, usually rifampin or gentamicin. Less than 20% would switch to another agent [131]. Rather than clinical inertia, this approach was likely a consequence of the paucity of agents with proven efficacy for SAB. This changed in 2006, when daptomycin was proven to be non-inferior to vancomycin in the treatment of MRSAB [19].
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