Early antibiotic therapy and clinical outcomes of left-sided enterococcus faecalis endocarditis

Background Antibiotic treatment of Enterococcus faecalis endocarditis is based on limited evidence and relapse- and mortality rates are high. Treatment is further complicated by the increasingly aging population, which increases the risk of medical side effects. Purpose To examine antibiotic treatment of Enterococcus faecalis endocarditis. Methods We used the nationwide registry NIDUS (NatIonal Danish endocarditis stUdieS) to identify all patients with first-time Enterococcus faecalis endocarditis between 2016-2021. Antibiotic treatment was characterized for the early critical phase (first 10 days). Patients were compared in mono- and combination therapy. We compared relapse, recurrence and mortality rates in unadjusted and adjusted analyses using logistic regression and multiple cox regression. Results In total, we included 392 patients (80.6% male) with Enterococcus faecalis endocarditis of which 59 (15.1%) patients received monotherapy and 333 (84.9%) patients received combination therapy. Patients in monotherapy were older (79.3 years versus 76.0 years) and more comorbid with higher rates of cancer (16.9% versus 8.5%). Prosthetic valve endocarditis was equally common in the two groups (37.3% versus 35.4%, p=0.8). Patients in monotherapy were less likely to have a definite endocarditis diagnosis (69.5% versus 86.5%). The most frequent antimicrobial regimens were ampicillin + gentamicin (65.4%), ampicillin + linezolid (6.6%) and ampicillin + ceftriaxone (5.1%) for combination therapy and ampicillin (74.6%), vancomycin (16.9%), and penicillin (6.8%) for monotherapy. Both groups had low surgical rates (10.2% versus 11.7% within 10 days, p=0.7). 6-month relapse rates (8.5% versus 5.4%, p=0.6) and recurrence rates (6.8% versus 5.1%, p=0.6) in the two groups. No statistically significant difference was found in 6-month mortality rate in unadjusted (22.3% 95% CI 12.6-33.7 versus 24.5% 95% CI 20.0-29.3) and adjusted analysis (HR: 1.24 (0.67-2.28) between patient in monotherapy and combination therapy. Conclusion The majority of patients with Enterococcus Faecalis endocarditis are treated with combination therapy as suggested by guidelines. Patients in monotherapy and combination therapy were fundamentally different in characteristics and presentation, however equally treated with surgical therapy. No statistical significant difference was found in relapse, recurrence and 6-month mortality rate. Studies on efficacy of treatment are needed, preferably clinical trials.