Studies on bloodstream infections and infective endocarditis

Diagnosis and treatment of bloodstream infections (BSIs) and infective endocarditis (IE) remain a challenge to treating physicians. Determining the microorganisms responsible is of major importance. New microbiological methods have emerged in the diagnosis of these entities with blood cultures remaining as a cornerstone. Changing epidemiology of IE and its risk groups pose a challenge to their treatment. BSIs and IE both contribute to a major morbidity and mortality. Hence, optimal treatment of these entities is imperative. Study I evaluated the impact of new microbiological method, short incubation matrix assisted laser desorption/ionization time-of-flight mass spectrometry (si-MALDI-TOF), on the antimicrobial treatment of BSIs caused by Pseudomonas aeruginosa, Enterococcus spp. and AmpC-producing Enterobacteriaceae when introduced into a routine clinical setting. Patients were treated at Helsinki University Hospital (HUS) between February 2014 and March 2015. A total of 124 BSI episodes were included. In 69 episodes si-MALDI-TOF identified the causative agent and in 55 episodes conventional identification methods were used. Identification by si-MALDI-TOF lead to 12.8% increase in episodes in which patients received appropriate antimicrobial treatment within 48 hours after the blood culture draw, which was the primary endpoint. In BSIs caused by Enterococcus spp. (n=62) the observed increase in appropriate antimicrobial treatment was 22.4% (87.9% vs 65.5%, P=0.038). In a subgroup of patients with immunosuppression si-MALDI-TOF method was observed to offer a significant benefit. Implementation of si-MALDI-TOF into a routine clinical setting was associated with an increased proportion of patients with appropriate antibiotic treatment within 48 hours after blood culture draw, especially in case of enterococcal BSIs. Study II explored bacteremia in patients with complicated skin and skin structure infections (cSSSI) in a population-based study including 460 patients with cSSSI from Helsinki, Finland and Gothenburg, Sweden. Blood cultures were positive in nearly one-fourth of those 258 patients from whom they were obtained. Diabetes, symptom duration less than two days and higher CRP level were associated with more frequent blood culture sampling, whereas surgical wound infection and peripheral artery disease were associated with less frequent blood culture sampling. None of the factors associated with blood culture drawing were found to be associated with blood culture positivity. Alcohol abuse was the only distinct patient characteristic associated with blood culture positivity. Patients with bacteremia had antibiotic treatment streamlined more often compared to non-bacteremic patients, which demonstrates a clear benefit of the information acquired from positive blood cultures. Given the high percentage of bacteremia amongst those from whom blood was cultured, difficulties in predicting patients with bacteremia and benefit of the information acquired from positive blood cultures, clinicians should order blood cultures from patients with cSSSI with low threshold. Study III evaluated the impact of pre-operative antimicrobial treatment duration on the yield of valve cultures and bacterial 16S PCR obtained during surgery for IE and the diagnostic value of PCR. The study cohort included 87 surgically treated IE patients from HUS between years 2011-2016 and from whom valve culture and PCR sample from resected endocardial material were obtained. None of the patients with preoperative antimicrobial treatment duration longer than two weeks had positive valve cultures. PCR positivity was 91% in those patients with antimicrobial treatment duration less than two weeks and 53% in those with more than two weeks. In PCR positive cases preoperative antimicrobial treatment duration was significantly shorter than in PCR negative cases. PCR sampling had a diagnostic impact in one-sixth of the cases. Pre-operative treatment duration was shown to have a negative effect on the yield of both valve cultures and PCR. PCR sampling had added diagnostic value, especially in blood culture negative cases. Study IV was a population-based study including all adult patients diagnosed with IE in Helsinki University Hospital Area between 2013 and 2017. The objective of this study was to describe the epidemiology, the spectrum of the microorganisms responsible for IE, clinical picture and the treatment and outcome of IE in the study region. Another objective was to determine the proportions of IE episodes according to the source of infection (i.e., mode of acquisition) and to define the characteristics of these groups and compare their differences. In all, 313 episodes of IE originating from 291 patients were included in the study cohort. Staphylococcus aureus was the leading cause accounting for one-third of the cases, followed by viridans group streptococci and Enterococcus spp. Equal proportions of community-acquired IE, health care-associated IE and drug use-related IE were observed, each accounting about for one-third of the cases. Distinct features of these entities were described and also different outcomes. Health care-associated IE was associated with more underlying diseases, prosthetic valve involvement, enterococcal etiology and higher mortality than community-acquired IE. Intravenous drug use-related IE was associated with more frequent right-sided and bilateral involvement, Staphylococcus aureus as etiology but no difference in mortality compared to community-acquired IE. High proportion of health care-associated IE and intravenous drug use-related IE pose a challenge for treatment, but also an opportunity for selected preventive strategies. In areas with common drug use, concomitant IE may account for a substantial proportion of all IE episodes, equal to that of health care-associated IE.