Enterococcus Faecium Bacteremia Research Articles

The role of time to positive blood cultures in enhancing the predictive capability of DENOVA score for diagnosing infective endocarditis in patients with Enterococcus faecalis bacteremia.

DENOVA-score is useful to stratify the risk of infective endocarditis (IE) in Enterococcus faecalis bacteremia. Recently, time to positive (TTP) of blood cultures has also been related with a higher risk of IE. The objective was to evaluate DENOVA- score with TTP to improve its specificity. We performed a retrospective, case-control study in adult patients with E. faecalis bacteremia. Thirty-nine patients with definite E. faecalis IE and 82 with E. faecalis bacteremia were included. The addition of a TTP ≤ 8 h to DENOVA-score did not improve the diagnostic accuracy of this score.

Lower specificity of the ESC2023 diagnostic criteria for infective endocarditis when spondylodiscitis is regarded as a vascular phenomenon.

The ESC diagnostic criteria for infective endocarditis (IE) added spondylodiscitis as minor diagnostic criterion. Of patients with Staphylococcus aureus, streptococcal or Enterococcus faecalis bacteremia, 11 of 1807 episodes were reclassified to definite IE of which nine were not treated as IE. Spondylodiscitis as a minor criterion decreases specificity of the criteria.

Bacteriophage and antibiotic combination therapy for recurrent Enterococcus faecium bacteremia.

Phage therapy is an emerging therapeutic approach for treating bacterial infections that do not respond to traditional antibiotics. The addition of phage therapy to systemic antibiotics to treat a patient with recurrent E. faecium infections that were non-responsive to antibiotics alone resulted in fewer hospitalizations and improved the patient's quality of life. Combination phage and antibiotic therapy reduced E. faecium and VRE abundance in the patient's stool. Eventually, an anti-phage antibody response emerged that was able to neutralize phage activity, which may have limited clinical efficacy. This study demonstrates the potential of phages as an additional option in the antimicrobial toolbox for treating invasive enterococcal infections and highlights the need for further investigation to ensure phage therapy can be deployed for maximum clinical benefit.

Antibacterial activity evaluation of cambuí extract against multi-resistant Enterococcus faecium

Bacterial resistance is a global public health issue. Among these pathogens, Enterococcus faecium nosocomial has been highlighted due to its potential to cause bacteremia infections. The incidence of resistant Enterococcus faecium bacteremia has enhanced over time, thereby, it has caused high rates of mortality. Hence, it led to the interest in natural drugs. Plant extracts from the Myrtaceae family have a broad-spectrum antimicrobial action. Among the plants of this family, we can highlight cambuí, due to its wide variety of bioactive compounds such as phenolic compounds. Polyphenols are bioactive molecules that can inhibit the growth of resistant bacteria such as Enterococcus faecium. For this, the present study aimed to obtain bioactive extracts from cambuí using pressurized hot water to grow inhibition of multi-resistant Enterococcus faecium nosocomial. In the present study, antibacterial compounds were obtained after extraction kinetics over 120 minutes at a temperature of 50º C, a flow rate of 1 mL/min-1, and a constant pressure of 200 bar using water as the extraction solvent. Flavonoids and other phenolic compounds from cambuí extracts were quantified by spectrophotometric methods. The TSA using the well-diffusion method was used to verify the sensitivity of the bacterium Enterococcus faecium against cambuí aqueous extract. The results showed that the best extraction time was 60 minutes using 60 mL of water. The cambuí aqueous extract showed a relevant amount of flavonoids and other phenolic compounds, hence, this extract was able to inhibit the growth of the bacterium Enterococcus faecium resistant to Ampicillin, Imipenem, Vancomycin, and Teicoplanin.

Assessing Clinical Outcomes of Vancomycin Treatment in Adult Patients with Vancomycin-Susceptible Enterococcus faecium Bacteremia.

Enterococcal bacteremia is associated with high mortality and long-term hospitalization. Here, we aimed to investigate the clinical outcomes and evaluate the risk factors for mortality in adult patients treated with vancomycin (VCM) for vancomycin-susceptible Enterococcus faecium (E. faecium) bacteremia. This is a retrospective, record-based study. The data were collected from inpatients at a single university hospital between January 2009 and December 2020. The area under the curve (AUC) of VCM was calculated using the Bayesian approach. The primary outcome was a 30-day in-hospital mortality. A univariate analysis showed significant differences in the concomitant use of vasopressors, history of the use of no clinically relevant activity antimicrobial agents against E. faecium, VCM plasma trough concentration, and renal dysfunction during VCM administration between the 30-day in-hospital mortality and survival groups. However, the groups' AUC/minimum inhibitory concentration (MIC) were not significantly different. A multivariate analysis suggested that concomitant vasopressors may be an independent risk factor for 30-day in-hospital mortality (odds ratio, 7.81; 95% confidence interval, 1.16-52.9; p = 0.035). The VCM plasma trough concentrations and the AUC/MIC in the mortality group were higher than those in the surviving group. No association between the AUC/MIC and the treatment effect in E. faecium bacteremia was assumed, because the known, target AUC/MIC were sufficiently achieved in the mortality group. There may be no association between the AUC/MIC and the treatment effect in E. faecium bacteremia. When an immunocompromised host develops E. faecium bacteremia with septic shock, especially when a vasopressor is used in a patient with unstable hemodynamics, it may be difficult to treat it, despite efforts to ensure the appropriate AUC/MIC and therapeutic vancomycin concentration levels.

Bartonella henselae mitral valve endocarditis associated with multi‐resistant Enterococcus faecalis bacteraemia in a cat

AbstractFeline infective endocarditis is a difficult condition to detect and diagnose early, with a poor long‐term prognosis. This case report describes the clinical, laboratory, instrumental and histological findings in a 12‐year‐old cat with Bartonella henselae endocarditis associated with multi‐resistant Enterococcus faecalis bacteraemia. The latter pathogen recently emerged as deadly nosocomial bacteria in humans and is considered a common cause of infective endocarditis. The prolonged corticosteroid therapy administered in the cat probably played a role in the onset of B. henselae endocarditis and E. faecalis intestinal translocation and bacteraemia. Echocardiography remains the tool of choice to suspect infective endocarditis, as it can detect vegetative lesions consistent with this condition. Feline infective endocarditis should always be considered as a differential diagnosis in cats, especially when there are signs of systemic disease, a history of prolonged corticosteroid treatment or concomitant infections.

Association between ratio of area under the concentration–time curve to minimum inhibitory concentration of vancomycin and clinical outcomes in Enterococcus faecium bacteremia

The purpose of this study was to evaluate the relationship between the treatment resolution of Enterococcus faecium bacteremia and the pharmacodynamic targets of vancomycin. This is a retrospective single-center cohort study involving patients with E. faecium bacteremia on vancomycin therapy hospitalized between January 2010 and December 2021. The average vancomycin area under the concentration–time curve (AUC)0 –24 was computed using the Bayesian approach. The minimum inhibitory concentration (MIC) was determined using the broth microdilution method, and The AUC24/MIC value over the initial 24–48 h of therapy was calculated. We assessed 30-day mortality, as the primary outcome. Classification and regression tree analysis (CART) was used to identify the vancomycin AUC24/MIC target associated with 30-day mortality. Eighty-seven patients with E. faecium bacteremia were included in this study, with 14 (16.1%) being non-survivors. In the CART analysis, vancomycin AUC/MIC ≥414.3 was associated with a higher treatment success. In multivariate analysis, an AUC/MIC ≥414.3 was a significant factor for treatment success (adjusted odds ratio = 17.5, 95% confidence interval, 3.7–83.9). Our findings suggest that a target vancomycin AUC/MIC ≥414.3 is a good prognostic indicator and could be useful for treatment monitoring of E. faecium bacteremia.

Vancomycin-sensitive Enterococcus faecium bacteraemia - hospital transmission and mortality in a Danish University Hospital.

Introduction. The emergence of vancomycin-resistant Enterococcus faecium (VREfm) has left the vancomycin-sensitive E. faecium (VSEfm) strains almost unnoticed.Hypothesis. Molecular characteristics, hospital transmission patterns and clinical impact of VSEfm have changed, and VSEfm is a predictor of VREfm introduction.Aim. We wanted to do a molecular characterization of VSEfm to identify hospital transmissions and links between VSEfm and VREfm, and to investigate the demographics, treatment and impact on mortality of VSEfm bacteraemia.Methodology. VSEfm and VREfm blood culture isolates from Odense University Hospital, Denmark, from 2015 to 2019 were characterized using whole-genome sequencing and core-genome multilocus sequence typing (cgMLST). Clonal shifts and diversity of the VREfm isolates were compared to the VSEfm isolates. Hospital records were used for clinical data and transmission investigation of VSEfm cases.Results. Six-hundred and thirty VSEfm isolates from 599 patients belonged to 42 sequence types (STs) and 131 complex types (CTs) in several clusters. Multiple types were involved in putative transmission, occurring over the entire period. Twenty-seven VREfm bacteraemia cases were included. No correlation between the VSEfm and VREfm clones was identified. The 30 day mortality was 40 %, but only in 6.3 % of the cases, VSEfm bacteraemia was the likely cause of death.Conclusion. The molecular types of VSEfm bacteraemia isolates are changing and diverse. No direct correlation between VSEfm and the introduction of VREfm was found, but widespread hospital transmission indicates a presence of risk factors that could facilitate transmission of other micro-organisms as well. VSEfm bacteraemia is rarely the cause of death, indicating that 30 day mortality does not reflect the cause of death.

Impact of a prospective audit and feedback antimicrobial stewardship programme on carbapenem consumption: a quasi-experimental study (IPANEMA study).

To test the hypothesis that a prospective audit and feedback (PAF) intervention combined with electronic tools will reduce carbapenem use without negatively affecting patient outcomes. A quasi-experimental, pre-intervention and intervention study was performed conducted in the urology department of a university hospital. The intervention involved implementing a PAF within an antimicrobial stewardship programme with the aid of an electronic tool. The primary outcome was carbapenem use, assessed by DDD/100 patient-days (PD). Secondary outcomes included evaluating the effect of the intervention on overall antibiotic use measured by DDD/100 PD and days of therapy (DOT)/100 PD, as well as patient safety. The chi-squared test or t-test was used, and the Poisson model was employed to assess the association between the intervention and outcomes. A 9% decrease in carbapenem DDD/100 PD was observed during the intervention period (IR = 0.91; 95% CI = 0.85-0.97, P = 0.007). The proportion of patients who received carbapenem treatment dropped from 17.8% to 16.5% [incidence ratio (IR) = 0.95; 95% CI = 0.86-2.05, P = 0.31]. Carbapenem DOT/100 PD decreased from 12.4 to 11.0 (IR = 0.89; 95% CI = 0.83-0.94, P < 0.001). Overall antibiotic DDD/100 PD decreased by 3% (IR = 0.97; 95% CI = 0.94-0.99, P = 0.001) and DOT/100 PD by 7% (IR = 0.93; 95% CI = 0.91-0.95, P < 0.001). The incidence of infections caused by carbapenemase-producing microorganisms, Enterococcus faecium bacteraemia and Clostridioides difficile-associated diarrhoea episodes was similar in the pre-intervention and intervention periods. ESBL incidence rate decreased, but the differences were not statistically significant (3.94/1000 PD versus 2.88/1000 PD, P = 0.111). Length of hospital stay, in-hospital all-cause mortality, and 30 day readmission incidence remained unchanged. The implementation of PAF combined with an electronic tool was an effective and safe intervention for reducing carbapenem use.

Bacteria in Extracorporeal Membrane Oxygenation Circuit Clots of a Patient With Persistent Bacteremia: A Case Report.

A neonate with pulmonary hypertension was supported with extracorporeal membrane oxygenation (ECMO). During ECMO support, the patient developed Enterococcus faecalis bacteremia, treated with targeted antibiotics. Despite the maximum dose of antibiotics, routine blood cultures remained positive throughout the ECMO treatment. A circuit change was performed due to buildup of thrombotic material and disseminated intravascular coagulation (DIC) inside the circuit. Thrombus formation was more extensive in the first than the second circuit. Gram-positive diplococci were present in all initial circuit clots and gram-positive masses surrounded by fibrin were found inside thrombi of the second circuit. Scanning electron microscopy (SEM) revealed a dense fibrin network with embedded red blood cells and bacteria in the first circuit. In the second circuit, SEM analysis revealed scattered micro thrombi. Polymerase chain reaction for identification of bacteria in the thrombus of the first circuit showed the same bacteria as found in blood cultures and did not achieve a sufficient signal in the second circuit. This case report shows that bacteria can nestle in thrombi of an ECMO circuit and that there is a rationale for a circuit change in a patient with persistent positive blood cultures and DIC.

Teicoplanin and vancomycin as treatment for glycopeptide-susceptible Enterococcus faecium bacteraemia: a propensity score-adjusted non-inferior comparative study.

Limited evidence is available regarding alternative therapeutic agents to vancomycin in treating glycopeptide-susceptible Enterococcus faecium (GSEF) bacteraemia. This study assessed the effectiveness and safety of teicoplanin compared with vancomycin for treating GSEF bacteraemia. This was a retrospective, non-inferiority cohort study. Patients aged ≥18 years who developed GSEF bacteraemia and received either teicoplanin or vancomycin were included. The primary effectiveness outcome was the clinical success at the end of treatment, with a generalized linear model using the propensity score for selecting the agent as a covariate. We used an absolute difference of 20% in clinical success as the non-inferiority margin. Using multivariable logistic regression, the primary safety outcome was the incidence of acute kidney injury (AKI). In total, 164 patients (74 and 90 in the teicoplanin and vancomycin groups, respectively) were included. Overall, 64.9% (48/74) and 48.9% (44/90) of patients in the teicoplanin and vancomycin groups, respectively, achieved the primary effectiveness outcome. A generalized linear analysis showed an adjusted effectiveness difference of 9.9% (95% CI, -0.9% to 20.0%; P = 0.07), indicating non-inferiority of teicoplanin versus vancomycin. The incidence of AKI was 8.1% (6/74) and 24.4% (22/90) in the teicoplanin and vancomycin groups, respectively, with an adjusted OR of 0.242 (95% CI, 0.068 to 0.864; P = 0.029), indicating significantly lower AKI risk in the teicoplanin than in the vancomycin group. Teicoplanin is a safe and useful alternative therapeutic agent for treating GSEF bacteraemia.

Pharmacokinetic/pharmacodynamic analysis of vancomycin in patients with Enterococcus faecium bacteraemia: a retrospective cohort study

ObjectivesThe trough concentration of vancomycin and the area under the concentration–time curve (AUC)/minimum inhibitory concentration (MIC) ratio are crucial in determining vancomycin efficacy against methicillin-resistant Staphylococcus aureus. However, the use...

Effect of the Minimum Inhibitory Concentration of Vancomycin on the Clinical Outcome of Enterococcus faecium Bacteremia.

Vancomycin (VCM) is an antibiotic widely used in the treatment of resistant bacteria. In patients with methicillin-resistant Staphylococcus aureus (MRSA) infection, the clinical outcome differs according to the VCM minimum inhibitory concentration (MIC) of isolates. However, the effect of VCM MIC on the clinical outcome is unclear for bacterial species other than MRSA. This study evaluated the relationship between the VCM MIC and clinical outcomes in patients with Enterococcus faecium bacteremia. This study included patients who had E. faecium detected in at least one set of blood cultures between April 2011 and March 2022. The study assessed the outcome according to the VCM MIC. The primary outcome was the 30-day mortality rate. Measures of interest included the initial serum concentration of VCM, MIC, the area under the curve (AUC), and the AUC over 24-48 hours (AUC24-48 h). A total of 26 patients were included in the study, of whom 5 died and 21 survived. The 30-day mortality was higher in patients with higher MICs and lower serum albumin levels. Patients with a serum albumin level <2.0 mg/dl and a MIC ≥1 μg/ml had significantly shorter survival than those who did not (p=0.013, log-rank test). The 30-day mortality rate of patients with E. faecium bacteremia is associated with the VCM MIC of E. faecium isolates and the patient's nutritional status. Patients with albumin <2 mg/dl and MIC ≥1 μg/ml may have a poor outcome and require careful clinical monitoring.

A case of cat bite associated Pasteurella multocida prosthetic joint infection

Cases of Pasteurella multocida related joint infections are often late in onset, but with the increase in prosthetic joints should be considered, especially in knee infections. Often thought of in relation to animal bites, these infections are further transmitted by nasal secretions, scratches, and licking behavior. We present a case of Pasteurella multocida joint infection in a patient who presented with a classic inciting factor of a cat bite, but presented initially with Enterococcus faecalis bacteremia, which obscured the clinical picture. This patient provides a good reminder of why all patients with cat bites and prosthesis should receive antibiotic prophylaxis post bite, as well as a good reminder to clinicians to keep P. multocida on their differential.

Plasma Microbial Cell-Free DNA to Characterize Infection Vs Cytokine Release Syndrome in Pediatric Patients with B ALL after CAR T Cell Therapy

Introduction Chimeric antigen receptor (CAR) T cell therapy is a promising treatment for pediatric patients with relapsed or refractory B cell acute lymphoblastic leukemia (R/R B ALL). Cytokine release syndrome (CRS) is a common toxicity characterized by fever and hemodynamic instability due to pro-inflammatory cytokines. Patients receiving CAR-T cell therapy are also at high risk of infection. Because both infection and CRS present with fever and signs of inflammation, they can be difficult to distinguish. Karius Inc has developed and validated a novel method for detecting and quantifying microbial cell free DNA (mcfDNA) in plasma for over 1000 species. McfDNA of organisms observed above background at statistically significant levels are reported in molecules per microliter (MPM). This retrospective cohort study sought to describe bacterial Karius Test®(KT) results, concordance with blood culture results, and association with signs of CRS in pediatric patients in the first 2 months after CAR-T cell infusion for R/R B ALL. Methods We identified 27 patients who had received CAR-T cell therapy at Lucile Packard Children's Hospital between November 2017 and March 2021 with banked plasma samples available for KT. Patients received CARs targeting CD19, CD22, or CD19-CD22 bispecific. We performed KT prior to CAR-T infusion, week 1, week 2, week 3 and week 4 or later. KT results were classified as likely pathogenic if MPM was >300 or if the same organism was detected on 2 consecutive tests. Results KT results are summarized in Table 1. Five patients had a least 1 positive blood culture in the 2 months post CAR-T infusion. Two of these patients had concurrent KT results that detected the same organism. Patient 3 experienced coagulase negativeStaphylococcus (CONS) bacteremia on days 0-2 post CAR-T. He was febrile a few hours after CAR-T infusion with no signs of CRS. KT was positive for Staphylococcus epidermidis on day -6 and day +3 after CAR-T infusion at MPM of 104,913 and 17,957, respectively. Patient 20 had grade 3 CRS by day 9 which improved after tocilizumab and steroids. She had recurrence of fevers at Day 24 and was treated with broad spectrum antimicrobials as well as immunosuppressive therapy for CRS. Blood cultures were persistently positive for CONS. She developed severe hyperammonemia at Day 56 with no evidence of hepatic dysfunction and subsequently progressed to cerebral edema and died on day 60 post CAR-T. Mycoplasma hominis was detected by bacterial sequencing on autopsy. KT detected M. hominis at a very low level (MPM 104) on day 21 post CAR-T. Subsequent measurements found increasing MPM for M. hominis at 89,071 on day 52 and then 201,096 on day 57 (Figure 1). Case reports have described M. hominis as a cause of severe hyperammonemia in immunocompromised patients. The 3 remaining patients (Patients 1, 2, and 30) did not have positive KT results for various reasons. Patient 1 experienced Enterococcus faecium bacteremia on day 23 but did not have a banked sample available for KT. This was in the setting of fevers and hypotension after progression of leukemia post CAR-T. Patient 2 had Streptococcus mitis bacteremia on day 11 post CAR-T and was started on cefepime. His KT was positive for Escherichia coli (but not s. mitis) at 11,559 MPM on day 14. He did not have blood cultures drawn that day so it is unclear if this KT result would have been detected on blood culture. Patient 30 had one blood culture positive for CONS. She was briefly treated with cefepime which was discontinued when subsequent cultures were negative. The CONS was thought to be a contaminant. KT was negative. Patients 2 and 30 had blood cultures sent in the setting of persistent fevers with rising inflammatory markers and Grade 1 CRS. Analysis across the cohort suggests KT positivity may correlate with periods of increased inflammation after CAR-T infusion. The relationship between KT positivity, inflammatory laboratory values, elevated temperature, and CRS score will be presented. Conclusions KT results may be helpful in identifying organisms in febrile patients following CAR-T when other diagnostic measures are unrevealing. This is especially true for fastidious organisms that may not grow in blood culture. Increased KT positivity during times of inflammation after CAR-T may reflect low level translocation rather than environmental contaminants. More work is needed to determine how best to use KT clinically in this patient population. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A RARE CASE OF ENTEROCOCCUS FAECALIS BIOPROSTHETIC AORTIC VALVE ABSCESS

A RARE CASE OF ENTEROCOCCUS FAECALIS BIOPROSTHETIC AORTIC VALVE ABSCESS

S2010 Colonic Carcinoma With Neuroendocrine Features Diagnosed in the Setting of Enterococcus faecalis Bacteremia, Endocarditis and Embolic Phenomenon

Introduction: A 77-year-old man with a history of hypertension, hyperlipidemia, prior ischemic stroke, and chronic back pain presented with fever and confusion 3 days after undergoing a lumbar epidural steroid injection. Case Description/Methods: A 77-year-old man with a history of hypertension, hyperlipidemia, prior ischemic stroke, and chronic back pain presented with fever and confusion 3 days after undergoing a lumbar epidural steroid injection. Multiple sets of blood cultures grew Enterococcus faecalis. His CRP was elevated at 86. An MRI scan of the spine was negative for epidural abscess. Brain MRI revealed multiple acute embolic infarcts. Transthoracic echocardiography revealed a mobile 8mm vegetation, and transesophageal echocardiography confirmed mitral valve endocarditis. CT of the abdomen and pelvis revealed colonic wall thickening at the hepatic flexure with coexistent fat stranding and lymphadenopathy. Subsequent colonoscopy revealed a 1 cm solitary cratered ulcer with heaped up borders at the hepatic flexure (Figure A). Histopathology demonstrated a high-grade carcinoma immunophenotypically positive for colonic (CDX2+, SATB2+, CK20+, CK7-) and neuroendocrine differentiation (chromogranin+, synaptophysin+) (Figure C, D). The favored diagnosis was colonic high-grade neuroendocrine carcinoma, large cell type. PET/CT Dotatate scan was negative for uptake at the hepatic flexure reflecting poor differentiation of the carcinoma and lack of somatostatin receptors expression. Subsequent PET/CT FDG scan was positive reflecting high FDG avidity in the identified hepatic flexure hypermetabolic lesion, surrounding lymph nodes, and numerous hepatic lesions (Figure B). The patient was treated with antibiotics for endocarditis and started on carboplatin and etoposide. Discussion: Classically, Streptococcus bovis bacteremia and endocarditis are associated with colorectal cancer. Evidence is accumulating for a link between Enterococcus faecalis, a component of gut flora, and colorectal adenocarcinoma. The biopsies of the ulcerated mass at the hepatic flexure, in our patient with Enterococcus faecalis bacteremia and endocarditis, suggested a primary colonic neuroendocrine carcinoma, large cell type. Neuroendocrine tumors of the colon arise from enterochromaffin cells in the crypts of Lieberkuhn. Colon carcinoid tumors are rare, with an annual incidence of approximately 0.2 per 100,000. Most neuroendocrine tumors are asymptomatic at the time of diagnosis and often present with metastatic disease.Figure 1.: A: Colonoscopy revealing a 1 cm solitary cratered ulcer at the hepatic flexure. B: PET/CT FDG scan showing high FDG avidity at hepatic flexure. C: Histopathology H&E stain showing poorly differentiated carcinoma. D: Histopathology chromogranin stain positivity confirming neuroendocrine differentiation.

Short versus extended treatment with a carbapenem in patients with high-risk fever of unknown origin during neutropenia: a non-inferiority, open-label, multicentre, randomised trial

Early antibiotic discontinuation has been advocated in haematology patients with fever of unknown origin during chemotherapy-induced neutropenia, but its safety is unknown. We aimed to assess if short treatment with carbapenems is non-inferior to extended treatment. This non-inferiority, open-label, multicentre, randomised trial was done in six hospitals in the Netherlands. Adult patients (≥18 years) who were treated with intensive chemotherapy or haematopoietic stem-cell transplantation (HSCT) for a haematological malignancy, and had fever of unknown origin during high-risk neutropenia (<0·5 × 109/L expected for ≥7 days) were eligible. After onset of fever, patients received either 500 mg intravenous imipenem-cilastatin four times a day or 1000 mg intravenous meropenem three times a day. Between 48 h and 72 h of treatment, participants were randomly assigned (1:1) by a computer-generated sequence to receive a short-term (72 h [60-84]; short treatment group) or extended (≥9 days until being afebrile for 5 days or neutrophil recovery; extended treatment group) carbapenem regimen. The composite primary endpoint was treatment failure, defined as recurrent fever or a carbapenem-sensitive infection between day 4 and day 9 and septic shock or respiratory failure or death from day 4 until neutrophil recovery. The study was designed to assess the non-inferiority of the short treatment compared with the extended treatment regimen, with a non-inferiority margin of 10%. The primary outcome was adjudicated by an independent outcome committee, who were masked to treatment allocation, and was analysed in the intention-to-treat and per-protocol populations. The trial is completed and registered with ClinicalTrials.gov, NCT02149329. Between Dec 1, 2014, and July 1, 2019, 281 patients were included in the intention-to-treat analysis: 144 (51%) patients were assigned to the short treatment group and 137 (49%) to the extended treatment group. Median age was 59 years (IQR 52-65); 109 (39%) patients were women and 172 (61%) were men; 205 (73%) patients received HSCT. In the intention-to-treat analysis, 28 (19%) of 144 patients in the short treatment group versus 21 (15%) of 137 patients in the extended treatment group had treatment failure (adjusted risk difference [ARD] 4·0% [90% CI -1·7% to 9·7%]; p=0·25). In the per-protocol analysis (n=225), 24 (23%) of 104 patients in the short treatment group and 19 (16%) of 121 patients in the extended treatment group had treatment failure (ARD 7·3% [0·3% to 14·9%]; p=0·11). The most common grade 3-5 infection-related adverse events were mucositis (23 [20%] of 114 adverse events in the short treatment group vs 28 [29%] of 98 adverse events in the extended treatment group), fever of unknown origin (20 [18%] vs 16 [16%] events), and bacteraemia (15 [13%] vs 13 [13%] events). The number of serious adverse events were higher in the short treatment group (23 [16%] of 144 patients) than in the extended treatment group (14 [10%] of 137 patients), due to an increased rate of readmission (17 [12%] patients in the short treatment group vs ten [7%] in the extended treatment group). Death before 30 days after neutrophil recovery occurred in five (3%) participants in the short treatment group: two due to progressive leukaemia, two due to candidaemia, and one due to Enterococcus faecium bacteraemia and drug-induced pneumonitis. One (1%) patient died in the extended treatment group due to candidaemia. None of the deaths were related to carbapenem-sensitive infections. Early discontinuation of carbapenem treatment in patients with febrile neutropenia of unknown origin does not result in increased treatment failure. Our study supports short treatment if patients are afebrile after 3 days of carbapenem treatment. However, because secondary analyses suggested that serious adverse events and all-cause mortality occurred more often in patients who are persistantly febrile the short treatment group, we recommend vigilance for non-susceptible pathogens and early resumption of empirical therapy in patients who are deteriorating. The Netherlands Organisation for Health Research and Development and Fonds NutsOhra.

Enterococcus faecalis bacteremia, cardiac implantable electronic device, extraction, and the risk of recurrence

PurposeIn all patients with cardiac implantable electronic devices (CIED) and Enterococcus faecalis bacteremia (EfsB), endocarditis (IE) and CIED infection should be suspected. Guidelines recommend extraction of the CIED when CIED infection or IE is diagnosed. Whether extraction of the CIED should be done in other situations with EfsB is not known. We aimed to describe the management and outcome of patients with CIED and monomicrobial EfsB, in relation to extraction and recurrent EfsB.MethodsA population-based cohort of patients with monomicrobial EfsB from January 2014 to November 2020 was identified through microbiology registers in the Region Skåne, Sweden. Data on CIED and other clinical features were collected from medical records.ResultsAmong 1087 episodes of EfsB, 72 patients with CIED and monomicrobial EfsB were identified. Five of these patients were diagnosed with IE (7%), three of whom had echocardiographic changes on the CIED. Four CIED were extracted (6%). Recurrences were found in seven of 68 patients (10%) not subjected to extraction and in none of the extracted. In the group of patients without extraction, community acquisition and predisposition for IE were significantly associated with recurrent infection in univariate analyses. No infections involving the CIED were diagnosed during the recurrences.ConclusionsIn patient with monomicrobial EfsB, it seems safe to omit extraction if no structural changes are found on the CIED.

Sign of the Times: Updating Infective Endocarditis Diagnostic Criteria to Recognize Enterococcus faecalis as a Typical Endocarditis Bacterium.

The modified Duke criteria requires that Enterococcus faecalis bacteremia must be both community-acquired and without known focus in order to be considered a microbiological "Major" diagnostic criterion in the diagnosis of infective endocarditis. We believe that the microbiological diagnostic criteria should be updated to regard E. faecalis as a "typical" endocarditis bacterium as is currently the case, for example, viridans group streptococci and Staphylococcus aureus. Using data from a prospective study of 344 patients with E. faecalis bacteremia evaluated with echocardiography, we demonstrate that designating E. faecalis as a "typical" endocarditis pathogen, regardless the place of acquisition or the portal of entry, improved the sensitivity to correctly identify definite endocarditis from 70% (modified Duke criteria) to 96% (enterococcal adjusted Duke criteria).