159 Persistent MRSA bacteremia 8 This paper reviews the basic science and clinical literature behind persistent MRSAB. We discuss the contribution from the host and the pathogen in the pathophysiology of SAB. Persistent MRSAB Persistent SAB is the strongest predictor of complicated SAB [11]. Multiple observational studies have identified the stark difference in mortality in patients with persistent SAB compared to those whose bacteremia promptly resolves [12– 14]. One recent cohort of 884 patients with SAB (approximately one-third with MRSAB) determined that increasing duration of positive S. aureus blood cultures was associated with increased rates of metastatic complications, length of stay, and 30day mortality [12]. The investigators concluded that each additional day of bacteremia was associated with a relative risk of death of 1.16 [12]. Another multinational cohort of 1588 patients with SAB found that 90-day mortality almost doubled (22 to 39%) when the duration of bacteremia increased from 1 day to 2–4 days [14]. Both studies underlined the severe consequences of persistent SAB. The consequences relating to treatment and further diagnostic evaluation are discussed later in this review. Both the definition and the frequency of persistent SAB have evolved over the past two decades [15]. In the early 2000s, Fowler et al. defined persistent bacteremia as ≥7 days of positive blood cultures [16] on the basis of the median duration bacteremia in patients with MRSA [17,18]. The reliable therapeutic options for MRSAB during that era were limited to vancomycin only. As a result, the designation of persistent MRSAB had little therapeutic consequence, as in most clinical cases, the vancomycin was simply continued. Since then, however, several new antibiotics with effectiveness against MRSA have been approved by the Food and Drug Administration (FDA). One antibiotic, daptomycin [19], has been approved specifically for MRSAB. In addition, other antibiotics such as the fifth-generation cephalosporin ceftaroline [20] are frequently used off-label for MRSAB. Given the ability to use alternate antibiotics and some data supporting combination antibiotic therapy for MRSAB (discussed in Section 4.2), more recent reports have suggested modifying the definition of persistent MRSAB to include patients with positive blood cultures for as few as 2 days [14].This shorter duration allows for a “check point” to consider alternate therapy and broader diagnostic evaluation [21].
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