Evaluation of the HANDOC score and the 2023 ISCVID and ESC Duke clinical criteria for the diagnosis of infective endocarditis among patients with streptococcal bacteremia.

BACKGROUND: Streptococci are a common cause of infective endocarditis (IE). We aimed to evaluate the performance of the HANDOC score to identify patients at high-risk for IE and the Duke clinical criteria of the European Society of Cardiology (ESC; 2015 and 2023 versions) and the 2023 version from the International Society of Cardiovascular Infectious Diseases (ISCVID) in diagnosing IE among patients with streptococcal bacteremia. METHODS: This retrospective study included adult patients with streptococcal bacteremia hospitalized at Lausanne University Hospital. Episodes were classified as IE by the Endocarditis Team. A HANDOC score >2 classified patients as high-risk for IE. RESULTS: Among 851 episodes with streptococcal bacteremia, IE was diagnosed in 171 episodes (20%). Among 607 episodes with non-beta-hemolytic streptococci, 213 (35%) had HANDOC scores >2 points; 132 (22%) had IE. The sensitivity of the HANDOC score to identify episodes at high-risk for IE was 95% (90-98%), the specificity 82% (78-85%), and the NPV 98% (96-99%). 2015 Duke-ESC, 2023 Duke-ISCVID, and 2023 Duke-ESC clinical criteria classified 114 (13%), 145 (17%), and 126 (15%) episodes as definite IE, respectively. Sensitivity for the 2015 Duke-ESC, 2023 Duke-ISCVID, and 2023 Duke-ESC clinical criteria was calculated at 65% (57-72%), 81% (74-86%), and 73% (65-79%), respectively, with specificity at 100% (98-100%), 99% (98-100%), and 99% (98-100%), respectively. CONCLUSIONS: The HANDOC score showed an excellent NPV to identify episodes at high-risk for IE. Among the different versions of the Duke criteria, the 2023 Duke-ISCVID version fared better for the diagnosis of IE among streptococcal bacteremia.

Association of persistent positive blood cultures and infective endocarditis: A cohort study among patients with suspected infective endocarditis.

OBJECTIVES: To ascertain whether infective endocarditis (IE) was associated with persistent bacteraemia/candidaemia among patients with suspected IE. METHODS: This study included bacteraemic/candidaemic adult patients with echocardiography and follow-up blood cultures. Persistent bacteraemia/candidaemia was defined as continued positive blood cultures with the same microorganism for 48 h or more after antibiotic treatment initiation. Each case was classified for IE by the Endocarditis Team. RESULTS: Among 1962 episodes of suspected IE, IE (605; 31%) was the most prevalent infection type. Persistent bacteraemia/candidaemia was observed in 426 (22%) episodes. Persistent bacteraemia was more common among episodes with Staphylococcus aureus bacteraemia compared to episodes with positive blood cultures for other pathogens (32%, 298/933 vs 12%, 128/1029; P < 0.001). Multivariable analysis demonstrated that cardiac predisposing factors (aOR 1.84, 95% CI 1.31-2.60), community or non-nosocomial healthcare-associated (2.85, 2.10-3.88), bacteraemia by high-risk bacteria, such as S. aureus, streptococci, enterococci or HACEK (1.84, 1.31-2.60), two or more positive sets of index blood cultures (6.99, 4.60-10.63), persistent bacteraemia/candidaemia for 48 h from antimicrobial treatment initiation (1.43, 1.05-1.93), embolic events within 48h from antimicrobial treatment initiation (12.81, 9.43-17.41), and immunological phenomena (3.87, 1.09-1.78) were associated with infective endocarditis. CONCLUSIONS: IE was associated with persistent bacteraemia/candidaemia, along with other commonly associated factors.

Predictors of Mortality of Streptococcal Bacteremia and the Role of Infectious Diseases Consultation: A Retrospective Cohort Study.

BACKGROUND: Streptococcal bacteremia is associated with high mortality. Thia study aims to identify predictors of mortality among patients with streptococcal bacteremia. METHODS: This retrospective study was conducted at the Lausanne University Hospital, Switzerland, and included episodes of streptococcal bacteremia among adult patients from 2015 to 2023. RESULTS: During the study period, 861 episodes of streptococcal bacteremia were included. The majority of episodes were categorized in the Mitis group (348 episodes; 40%), followed by the Pyogenic group (215; 25%). Endocarditis was the most common source of bacteremia (164; 19%). The overall 14-day mortality rate was 8% (65 episodes). The results from the Cox multivariable regression model showed that a Charlson comorbidity index >4 (P .001; hazard ratio [HR], 2.87; confidence interval [CI]: 1.58-5.22), Streptococcus pyogenes (P = .011; HR, 2.54;CI: 1.24-5.21), sepsis (P < .001; HR, 7.48; CI: 3.86-14.47), lower respiratory tract infection (P = .002; HR, 2.62; CI: 1.42-4.81), and absence of source control interventions within 48 hours despite being warranted (P = .002; HR, 2.62; CI: 1.43-4.80) were associated with 14-day mortality. Conversely, interventions performed within 48 hours of bacteremia onset, such as infectious diseases consultation (P < .001; HR, 0.29; CI: .17-.48) and appropriate antimicrobial treatment (P < .001; HR, .28; CI: .14-.57), were associated with improved outcome. CONCLUSIONS: Our findings underscore the pivotal role of infectious diseases consultation in guiding antimicrobial treatment and recommending source control interventions for patients with streptococcal bacteremia.

Evaluation of the 2023 Duke-International Society of Cardiovascular Infectious Diseases Criteria in a Multicenter Cohort of Patients With Suspected Infective Endocarditis.

BACKGROUND: Since publication of Duke criteria for infective endocarditis (IE) diagnosis, several modifications have been proposed. We aimed to evaluate the diagnostic performance of the Duke-ISCVID (International Society of Cardiovascular Infectious Diseases) 2023 criteria compared to prior versions from 2000 (Duke-Li 2000) and 2015 (Duke-ESC [European Society for Cardiology] 2015). METHODS: This study was conducted at 2 university hospitals between 2014 and 2022 among patients with suspected IE. A case was classified as IE (final IE diagnosis) by the Endocarditis Team. Sensitivity for each version of the Duke criteria was calculated among patients with confirmed IE based on pathological, surgical, and microbiological data. Specificity for each version of the Duke criteria was calculated among patients with suspected IE for whom IE diagnosis was ruled out. RESULTS: In total, 2132 episodes with suspected IE were included, of which 1101 (52%) had final IE diagnosis. Definite IE by pathologic criteria was found in 285 (13%), 285 (13%), and 345 (16%) patients using the Duke-Li 2000, Duke-ESC 2015, or the Duke-ISCVID 2023 criteria, respectively. IE was excluded by histopathology in 25 (1%) patients. The Duke-ISCVID 2023 clinical criteria showed a higher sensitivity (84%) compared to previous versions (70%). However, specificity of the new clinical criteria was lower (60%) compared to previous versions (74%). CONCLUSIONS: The Duke-ISCVID 2023 criteria led to an increase in sensitivity compared to previous versions. Further studies are needed to evaluate items that could increase sensitivity by reducing the number of IE patients misclassified as possible, but without having detrimental effect on specificity of Duke criteria.

Myeloid-Derived Suppressor-like Cells as a Prognostic Marker in Critically Ill Patients: Insights from Experimental Endotoxemia and Intensive Care Patients.

Patients admitted to the intensive care unit (ICU) often experience endotoxemia, nosocomial infections and sepsis. Polymorphonuclear and monocytic myeloid-derived suppressor cells (PMN-MDSCs and M-MDSCs) can have an important impact on the development of infectious diseases, but little is known about their potential predictive value in critically ill patients. Here, we used unsupervised flow cytometry analyses to quantify MDSC-like cells in healthy subjects challenged with endotoxin and in critically ill patients admitted to intensive care units and at risk of developing infections. Cells phenotypically similar to PMN-MDSCs and M-MDSCs increased after endotoxin challenge. Similar cells were elevated in patients at ICU admission and normalized at ICU discharge. A subpopulation of M-MDSC-like cells expressing intermediate levels of CD15 (CD15int M-MDSCs) was associated with overall mortality (p = 0.02). Interestingly, the high abundance of PMN-MDSCs and CD15int M-MDSCs was a good predictor of mortality (p = 0.0046 and 0.014), with area under the ROC curve for mortality of 0.70 (95% CI = 0.4-1.0) and 0.86 (0.62-1.0), respectively. Overall, our observations support the idea that MDSCs represent biomarkers for sepsis and that flow cytometry monitoring of MDSCs may be used to risk-stratify ICU patients for targeted therapy.

Heterogeneity in practices to reduce the risk of transmission of Clostridioides difficile in healthcare settings: a survey of ESCMID Study Group for Clostridioides difficile (ESGCD) members.

Clostridioides difficile is a leading cause of healthcare-associated infections. The main objective was to assess the current landscape of CDI infection prevention and control (IPC) practices. An anonymous survey of IPC practices for CDI was conducted between July 25 and October 31, 2022. Precautions for symptomatic patients were applicable for 75.9% and were discontinued 48 h minimum after the resolution of diarrhea for 40.7% of respondents. Daily cleaning of CDI patients' rooms was reported by 23 (42.6%). There was unexpected heterogeneity in IPC practices regarding the hospital management of CDI.

Prevalence of Infective Endocarditis among Patients with Staphylococcus aureus Bacteraemia and Bone and Joint Infections.

We aimed to evaluate the occurrence of infective endocarditis (IE) among patients with bone and joint infections (BJIs) and Staphylococcus aureus bacteraemia. This observational study was conducted at Lausanne University Hospital, Switzerland, from 2014 to 2023, and included episodes involving BJI, S. aureus bacteraemia, and cardiac imaging studies. The endocarditis team defined IE. Among the 384 included episodes, 289 (75%) involved native BJI (NBJI; 118 septic arthritis, 105 acute vertebral or non-vertebral osteomyelitis, 101 chronic osteitis), and 112 (29%) involved orthopedic implant-associated infection (OIAI; 78 prosthetic joint infection and 35 osteosynthesis/spondylodesis infection). Fifty-one episodes involved two or more types of BJI, with 17 episodes exhibiting both NBJI and OIAI. IE was diagnosed in 102 (27%) episodes. IE prevalence was 31% among patients with NBJI and 13% among patients with OIAI (p < 0.001). The study revealed a high prevalence of IE among S. aureus bacteraemic patients with NBJI, with notably lower prevalence among those with OIAI.

Eyes Wide Shut: A Cohort Study Questioning the Role of Fundoscopy in Infective Endocarditis Diagnosis.

In this retrospective/prospective study, we assessed the role of fundoscopy in 711 episodes with suspected infective endocarditis (IE); 238 (33%) had IE. Ocular embolic events (retinal emboli or chorioretinitis/endophthalmitis) and Roth spots were found in 37 (5%) and 34 (5%) episodes, respectively, but had no impact on IE diagnosis.

Evaluation of the 2023 Duke-ISCVID and 2023 Duke-ESC Clinical Criteria for the Diagnosis of Infective Endocarditis in a Multicenter Cohort of Patients With Staphylococcus aureus Bacteremia.

BACKGROUND: The Duke criteria for infective endocarditis (IE) diagnosis underwent revisions in 2023 by the European Society of Cardiology (ESC) and the International Society for Cardiovascular Infectious Diseases (ISCVID). This study aims to assess the diagnostic accuracy of these criteria, focusing on patients with Staphylococcus aureus bacteremia (SAB). METHODS: This Swiss multicenter study conducted between 2014 and 2023 pooled data from three cohorts. It evaluated the performance of each iteration of the Duke criteria by assessing the degree of concordance between definite S. aureus IE (SAIE) and the diagnoses made by the Endocarditis Team (2018-23) or IE expert clinicians (2014-17). RESULTS: Among 1344 SAB episodes analyzed, 486 (36%) were identified as cases of SAIE. The 2023 Duke-ISCVID and 2023 Duke-ESC criteria demonstrated improved sensitivity for SAIE diagnosis (81% and 82%, respectively) compared to the 2015 Duke-ESC criteria (75%). However, the new criteria exhibited reduced specificity for SAIE (96% for both) compared to the 2015 criteria (99%). Spondylodiscitis was more prevalent among patients with SAIE compared to those with SAB alone (10% vs 7%, P = .026). However, when patients meeting the minor 2015 Duke-ESC vascular criterion were excluded, the incidence of spondylodiscitis was similar between SAIE and SAB patients (6% vs 5%, P = .461). CONCLUSIONS: The 2023 Duke-ISCVID and 2023 Duke-ESC clinical criteria show improved sensitivity for SAIE diagnosis compared to 2015 Duke-ESC criteria. However, this increase in sensitivity comes at the expense of reduced specificity. Future research should aim at evaluating the impact of each component introduced within these criteria.

Risk of embolic events before and after antibiotic treatment initiation among patients with left-side infective endocarditis.

PURPOSE: Embolic events (EEs) are a common complication of left-side infective endocarditis (IE). The aim of the present study was to identify risk factors for the occurrence of EEs before or after antibiotic treatment instauration among patients with definite or possible IE. METHODS: This retro-prospective study was conducted at the Lausanne University Hospital, Lausanne, Switzerland, from January 2014 to June 2022. EEs and IE were defined according to modified Duke criteria. RESULTS: A total of 441 left-side IE episodes were included (334: 76% were definite and 107; 24% possible IE). EE were diagnosed in 260 (59%) episodes; in 190 (43%) before antibiotic treatment initiation and 148 (34%) after. Central nervous system (184; 42%) was the most common site of EE. Multivariable analysis identified S. aureus (P 0.022), immunological phenomena (P < 0.001), sepsis (P 0.027), vegetation size ≥ 10 mm (P 0.003) and intracardiac abscess (P 0.022) as predictors of EEs before antibiotic treatment initiation. For EEs after antibiotic treatment initiation, multivariable analysis revealed vegetation size ≥ 10 mm (P < 0.001), intracardiac abscess (P 0.035) and prior EE (P 0.042), as independent predictors of EEs, while valve surgery (P < 0.001) was associated with lower risk for EEs. CONCLUSIONS: We reported a high percentage of EEs among patients with left-side IE; vegetation size, intracardiac abscess, S. aureus and sepsis were independently associated with the occurrence of EEs. In addition to antibiotic treatment, early surgery led to further decrease in EEs incidence.

Update on microbiota-derived therapies for recurrent Clostridioides difficile infections.

BACKGROUND: Faecal microbiota transplantation (FMT) is the standard treatment for patients with multiple recurrent Clostridioides difficile infection (rCDI). Recently, new commercially developed human microbiota-derived medicinal products have been evaluated and Food and Drug Administration-approved with considerable differences in terms of composition, administration, and targeted populations. OBJECTIVES: To review available data on the different microbiota-derived treatments at the stage of advanced clinical evaluation and research in rCDI in comparison with FMT. SOURCES: Phase II or III trials evaluating a microbiota-derived medicinal product to prevent rCDI. CONTENT: Two commercial microbiota-derived medicinal products are approved by the Food and Drug Administration: Rebyota (RBX2660 Ferring Pharmaceuticals, marketed in the United States) and VOWST (SER-109 -Seres Therapeutics, marketed in the United States), whereas VE303 (Vedanta Biosciences Inc) will be studied in phase III trial. RBX2660 and SER-109 are based on the processing of stools from healthy donors, whereas VE303 consists of a defined bacterial consortium originating from human stools and produced from clonal cell banks. All have proven efficacy to prevent rCDI compared with placebo in patients considered at high risk of recurrence. However, the heterogeneity of the inclusion criteria, and the time between each episode and CDI diagnostics makes direct comparison between trials difficult. The differences regarding the risk of recurrence between the treatment and placebo arms were lower than previously described for FMT (FMT: Δ = 50.5%; RBX2660-phase III: Δ = 13.1%; SER-109-phase III: Δ = 28%; high-dose VE303-phase-II: Δ = 31.7%). All treatments presented a good overall safety profile with mainly mild gastrointestinal symptoms. IMPLICATIONS: Stool-derived products and bacterial consortia need to be clearly distinguished in terms of product characterization and their associated risks with specific long-term post-marketing evaluation similar to registries used for FMT. Their place in the therapeutic strategy for patients with rCDI requires further studies to determine the most appropriate patient population and administration route to prevent rCDI.

Core genome multilocus sequence typing of Clostridioides difficile to investigate transmission in the hospital setting.

PURPOSE: Traditional epidemiological investigations of healthcare-associated Clostridioides difficile infection (HA-CDI) are often insufficient. This study aimed to evaluate a procedure that includes secondary isolation and genomic typing of single toxigenic colonies using core genome multilocus sequence typing (cgMLST) for the investigation of C. difficile transmission. METHODS: We analyzed retrospectively all toxigenic C. difficile-positive stool samples stored at the Lausanne University Hospital over 6 consecutive months. All isolates were initially typed and classified using a modified double-locus sequence typing (DLST) method. Genome comparison of isolates with the same DLST and clustering were subsequently performed using cgMLST. The electronic administrative records of patients with CDI were investigated for spatiotemporal epidemiological links supporting hospital transmission. A comparative descriptive analysis between genomic and epidemiological data was then performed. RESULTS: From January to June 2021, 86 C. difficile isolates were recovered from thawed samples of 71 patients. Thirteen different DLST types were shared by > 1 patient, and 13 were observed in single patients. A genomic cluster was defined as a set of isolates from different patients with ≤ 3 locus differences, determined by cgMLST. Seven genomic clusters were identified, among which plausible epidemiological links were identified in only 4/7 clusters. CONCLUSION: Among clusters determined by cgMLST analysis, roughly 40% included unexplained HA-CDI acquisitions, which may be explained by unidentified epidemiological links, asymptomatic colonization, and/or shared common community reservoirs. The use of DLST, followed by whole genome sequencing analysis, is a promising and cost-effective stepwise approach for the investigation of CDI transmission in the hospital setting.

Temporal changes in fecal microbiota of patients infected with COVID-19: a longitudinal cohort.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a multifaceted disease potentially responsible for various clinical manifestations including gastro-intestinal symptoms. Several evidences suggest that the intestine is a critical site of immune cell development, gut microbiota could therefore play a key role in lung immune response. We designed a monocentric longitudinal observational study to describe the gut microbiota profile in COVID-19 patients and compare it to a pre-existing cohort of ventilated non-COVID-19 patients. METHODS: From March to December 2020, we included patients admitted for COVID-19 in medicine (43 not ventilated) or intensive care unit (ICU) (14 ventilated) with a positive SARS-CoV-2 RT-PCR assay in a respiratory tract sample. 16S metagenomics was performed on rectal swabs from these 57 COVID-19 patients, 35 with one and 22 with multiple stool collections. Nineteen non-COVID-19 ICU controls were also enrolled, among which 14 developed ventilator-associated pneumonia (pneumonia group) and five remained without infection (control group). SARS-CoV-2 viral loads in fecal samples were measured by qPCR. RESULTS: Although similar at inclusion, Shannon alpha diversity appeared significantly lower in COVID-19 and pneumonia groups than in the control group at day 7. Furthermore, the microbiota composition became distinct between COVID-19 and non-COVID-19 groups. The fecal microbiota of COVID-19 patients was characterized by increased Bacteroides and the pneumonia group by Prevotella. In a distance-based redundancy analysis, only COVID-19 presented significant effects on the microbiota composition. Moreover, patients in ICU harbored increased Campylobacter and decreased butyrate-producing bacteria, such as Lachnospiraceae, Roseburia and Faecalibacterium as compared to patients in medicine. Both the stay in ICU and patient were significant factors affecting the microbiota composition. SARS-CoV-2 viral loads were higher in ICU than in non-ICU patients. CONCLUSIONS: Overall, we identified distinct characteristics of the gut microbiota in COVID-19 patients compared to control groups. COVID-19 patients were primarily characterized by increased Bacteroides and decreased Prevotella. Moreover, disease severity showed a negative correlation with butyrate-producing bacteria. These features could offer valuable insights into potential targets for modulating the host response through the microbiota and contribute to a better understanding of the disease's pathophysiology. TRIAL REGISTRATION: CER-VD 2020-00755 (05.05.2020) & 2017-01820 (08.06.2018).

Impact of thoracoabdominal imaging on diagnosis and management in patients with suspected infective endocarditis.

BACKGROUND: Embolic events (EEs) are a common complication of infective endocarditis (IE) and their presence can impact diagnosis and modify the therapeutic plan. The present study aimed to describe the role of thoracoabdominal imaging, either thoracoabdominal-pelvic Computed Tomography or 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography, on diagnosis and management of patients with suspected IE. METHODS: This study was conducted at a university hospital, from January 2014 to June 2022. EEs and IE were defined according to modified Duke criteria. RESULTS: Among 966 episodes with suspected IE and thoracoabdominal imaging, 528 (55%) patients were asymptomatic. At least one EE was found in 205 (21%) episodes. Based on thoracoabdominal imaging findings, the diagnosis was reclassified from rejected to possible or from possible to definite IE in 6 (1%) and 10 (1%) episodes, respectively. Among the 413 patients with IE, at least one EE was found on thoracoabdominal imaging in 143 (35%) episodes. Together with the presence of left-side valvular vegetation >10 mm, the results of thoracoabdominal imaging established a surgical indication (prevention of embolism) in 15 (4%) episodes, 7 of which were asymptomatic. CONCLUSIONS: Thoracoabdominal imaging performed in asymptomatic patients with suspected IE improved the diagnosis in only a small proportion of patients. Thoracoabdominal imaging led to a new surgical indication (in association with left-side valvular vegetation >10 mm) in only a small percentage of patients.

The role of early defervescence in ruling out infective endocarditis: a cohort study.

OBJECTIVES: To evaluate the role of defervescence within 4 days from antibiotic treatment initiation in ruling out infective endocarditis (IE) among patients suspected of such diagnosis. METHODS: This study was conducted at the Lausanne University Hospital, Switzerland (January 2014 to May 2022). All patients with suspected IE being febrile upon presentation were included. IE was classified according to the modified Duke criteria proposed by the 2015 European Society of Cardiology guidelines, before or after applying the criterion 'resolution of symptoms suggesting IE within 4 days of the introduction of antibiotic therapy' based solely on early defervescence. RESULTS: Among 1022 episodes with suspected IE, 332 (37%) had IE according to Endocarditis-Team evaluation; 248 were classified by clinical Duke criteria as definite and 84 as possible IE. The rate of defervescence within 4 days from antibiotic treatment initiation was similar (p 0.547) among episodes without (606/690; 88%) and those with IE (287/332; 86%); among episodes classified as definite and possible IE by clinical Duke criteria, 211 of 248 (85%) and 76 of 84 (90%), respectively, defervesced within 4 days from antibiotic treatment initiation. By using early defervescence as a rejection criterion, the 76 episodes with final IE diagnosis classified as possible by clinical criteria could be reclassified as rejected. DISCUSSION: The majority of IE episodes defervesced within 4 days from antibiotic treatment initiation; thus, early defervescence should not be used to rule out the diagnosis of IE.