255 General discussion 11 In chapter 7, we focused on acute kidney injury in patients with S. aureus bacteremia. The main finding of the study was the high overall incidence of acute kidney injury. Furthermore, we observed an early development of kidney injury with a median time to peak creatinine of three days after first positive blood culture. Reversibility occurred in the majority of patients and was mostly seen in the first seven days. The early onset and swift recovery of renal insufficiency suggest that hemodynamic deterioration early in the disease plays an important role, and makes toxicity of antibiotic therapy as the primary cause of renal failure less likely. Insight in the pathogenesis of acute kidney injury in S. aureus bacteremia has important diagnostic and therapeutic consequences. Currently, kidney injury is often incorrectly ascribed to beta-lactaminduced tubulointerstitial nephritis, triggering an antimicrobial switch to a less potent agent. Prospective studies that focus on the different causal mechanisms of acute kidney injury in patients with S. aureus bacteremia are warranted to minimize unnecessary deviation from optimal therapy. Urine biomarkers potentially have additional value herein, and are a current subject of research. Different biomarker profiles may reflect prerenal or structural renal damage, and subsequently guide the clinician in the decision to change antibiotic treatment or focus on hemodynamic optimalization. As a result of the low MRSA carriage prevalence in the Netherlands, MRSA bacteremia is exceptional in our country. However, in endemic regions such as the United States, MRSA bacteremia is common. Consequently, persistence of MRSA bacteremia despite appropriate antimicrobial treatment is also more frequently encountered. Chapter 8 reviewed the literature on persistent MRSA bacteremia, addressing relevant host and pathogen factors. Clinical risk factors in persistent MRSA bacteremia include the retention of implanted devices and presence of metastatic infection. Potential host genetic variation and biomarkers indicative of MRSA bacteremia have recently been identified and show promise for future diagnostic options. Key genetic and phenotypic characteristics of S. aureus that have been associated with persistent SAB are accessory gene regulator dysfunction, variation in virulence factor production and phenotypes, antibiotic tolerance and reduced vancomycin susceptibility [1214]. Considering treatment, vancomycin was the only recommended therapy for MRSA bacteremia for decades. Due to unfavorable safety profiles, many combinations of antibiotics have not been able to replace vancomycin. Since 2011, daptomycin is included in the guideline for MRSA bacteremia in the United States, but not in Europe. Although high-quality data is lacking, high-dose daptomycin (with a second antibiotic agent to prevent treatment-induced resistance), and the addition of ceftaroline, are currently regarded as ‘best practice treatment’ in persistent MRSA bacteremia [15]. Future therapeutical options may include ceftobiprole, dalbavancin, or non-antibiotic therapies such as bacteriophages.
RkJQdWJsaXNoZXIy MTk4NDMw