Importance It is suggested that patients with Cutibacterium acnes endocarditis often present without fever or abnormal inflammatory markers. However, no study has yet confirmed this statement.Obje...Show moreImportance It is suggested that patients with Cutibacterium acnes endocarditis often present without fever or abnormal inflammatory markers. However, no study has yet confirmed this statement.Objective To assess the clinical characteristics and outcomes of patients with C acnes endocarditis.Design, Setting, and Participants A case series of 105 patients presenting to 7 hospitals in the Netherlands and France (4 university hospitals and 3 teaching hospitals) with definite endocarditis according to the modified Duke criteria between January 1, 2010, and December 31, 2020, was performed. Clinical characteristics and outcomes were retrieved from medical records. Cases were identified by blood or valve and prosthesis cultures positive for C acnes, retrieved from the medical microbiology databases. Infected pacemaker or internal cardioverter defibrillator lead cases were excluded. Statistical analysis was performed in November 2022.Main Outcomes and Measures Main outcomes included symptoms at presentation, presence of prosthetic valve endocarditis, laboratory test results at presentation, time to positive results of blood cultures, 30-day and 1-year mortality rates, type of treatment (conservative or surgical), and endocarditis relapse rates.Results A total of 105 patients (mean [SD] age, 61.1 [13.9] years; 96 men [91.4%]; 93 patients [88.6%] with prosthetic valve endocarditis) were identified and included. Seventy patients (66.7%) did not experience fever prior to hospital admission, nor was it present at hospitalization. The median C-reactive protein level was 3.6 mg/dL (IQR, 1.2-7.5 mg/dL), and the median leukocyte count was 10.0 × 103/µL (IQR, 8.2-12.2 × 103/µL). The median time to positive blood culture results was 7 days (IQR, 6-9 days). Surgery or reoperation was indicated for 88 patients and performed for 80 patients. Not performing the indicated surgical procedure was associated with high mortality rates. Seventeen patients were treated conservatively, in accordance with the European Society of Cardiology guideline; these patients showed relatively high rates of endocarditis recurrence (5 of 17 [29.4%]).Conclusions and Relevance This case series suggests that C acnes endocarditis was seen predominantly among male patients with prosthetic heart valves. Diagnosing C acnes endocarditis is difficult due to its atypical presentation, with frequent absence of fever and inflammatory markers. The prolonged time to positivity of blood culture results further delays the diagnostic process. Not performing a surgical procedure when indicated seems to be associated with higher mortality rates. For prosthetic valve endocarditis with small vegetations, there should be a low threshold for surgery because this group seems prone to endocarditis recurrence. Show less
Metoprolol is among the most frequently prescribed beta-blockers for the treatment of various cardiovascular diseases. Genetic polymorphism within CYP2D6 has been shown to affect the rate of... Show moreMetoprolol is among the most frequently prescribed beta-blockers for the treatment of various cardiovascular diseases. Genetic polymorphism within CYP2D6 has been shown to affect the rate of metabolism of metoprolol. Whether metoprolol dose adjustments are indicated in CYP2D6 poor metabolizers (PMs) has thus far not well been studied. The aim of this study was to determine the effect of the CYP2D6 genotype on the metoprolol maintenance dose in a chronic Dutch patient population. Patients were included if they were treated with metoprolol and in whom CYP2D6 genotype status was known. Patient and treatment characteristics were obtained retrospectively from the electronic healthcare records. Metoprolol maintenance dose was the primary endpoint and was defined as the last known dose that the patients had been treated with. Genotype data were categorized into four phenotypes, that is, PMs, intermediate metabolizers, extensive metabolizers, and ultra-rapid metabolizers (UMs). The endpoints were analyzed as PM versus non-PM. A total of 105 patients were included. The mean +/- SD maintenance dose in PMs (n = 12) was significantly lower compared with non-PMs (n = 93), that is, 48 +/- 20 versus 84 +/- 53 mg, respectively (P = 0.019). No association of the CYP2D6 genotype with the incidence of side effects was observed, although there was a trend for increased risk of drowsiness (P = 0.053). The results of this study show that the CYP2D6 genotype is associated with the maintenance dose of metoprolol. Patients with the CYP2D6 PM phenotype may benefit from a lower metoprolol starting dose, followed by further dose titration to provide patient-tailored therapy and thereby increase the effectiveness of treatment. Show less
Saporito, S.; Houthuizen, P.; Aben, J.P.M.M.; Westenberg, J.J.M.; Bosch, H.C.M. van den; Assen, H.C. van; Mischi, M. 2018