Faecium Bacteremia Research Articles

Trends in Enterococcus faecium Bacteremia: Exploring Risk Factors with Emphasis on Prior Antibiotic Exposure

Enterococcal bacteremia (EB) is on the rise both in Sweden and globally. While Enterococcus faecalis (E. faecalis) is susceptible to ampicillin and piperacillin/tazobactam (pip/taz), Enterococcus faecium (E. faecium) is not. Historically, most enterococcal infections have been caused by E. faecalis, but the epidemiology is changing with increasing recognition of enterococci as nosocomial pathogens and the emergence of resistance to commonly used antimicrobial agents. The use of pip/taz has increased dramatically in Sweden, but it is unknown if this has affected the relative incidence of E. faecalis/E. faecium bacteremia. Here, we investigate whether the number and proportion of E. faecium bacteremia (EfmB) cases have increased. Additionally, risk factors associated with EfmB with a focus on prior antibiotic exposure are analyzed. Medical journals of 360 patients with EB admitted to Sahlgrenska University Hospital are reviewed. The proportion of EfmB cases increased from 41% in 2015 to 51% in 2021. Hospital-acquired infection, previous exposure to pip/taz, and carbapenems are identified as independent risk factors for EfmB. There are considerable patient-related differences between the EfmB and EfsB groups, but there is no difference in mortality rates. In conclusion, the increasing proportion of EfmB cases is concerning and is seen parallel to the expanding use of pip/taz, one possible contributing factor. Our findings suggest that a cautious approach to antibiotic use is essential to prevent the spread of antibiotic-resistant bacteria.

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...

Characteristics and Prevalence of Vancomycin-variable Enterococcus faecium bacteremia in southern Taiwan

BackgroundVancomycin-variable enterococci (VVE) are vanA-carrying Enterococcus faecium that are phenotypically susceptible to vancomycin and can only be detected using molecular methods, leading to the possibility of treatment failure and posing threats to infection control. This study aimed to determine the prevalence of VVE and its associated clinical risk factors. MethodsThis retrospective study was conducted in two hospitals in southern Taiwan. Patients with phenotypically vancomycin-susceptible E. faecium bacteremia were enrolled between 2017 and 2021. VVEs were defined as isolates harboring the vanA gene that were phenotypically susceptible to vancomycin. Vancomycin-susceptible E. faecium (VSE) isolates were phenotypically susceptible to vancomycin and lacked vanA or vanB genes. ResultsOf the 142 enrolled patients, 121 (85.2%) had VSE and 21 (14.8%) had VVE. Resistance rates to penicillin, tetracycline, and fosfomycin were higher in VVE isolates. Malignancy (adjusted odds ratio [aOR] = 4.87; 95% confidence interval [CI] 1.54–15.41, p = 0.007) and central venous catheter usage (aOR = 4.69; 95% CI 1.49–14.78, p = 0.008) were the independent risk factors associated with VVE bacteremia. Being male (aOR = 0.12, CI 0.03–0.44, p = 0.002) was less likely to be associated with VVE bacteremia. Although VVE was not associated with 30-day mortality (38.1% [VVE] vs. 35.5% [VSE], p = 0.822), one case of subsequent vancomycin-resistant enterococci infection in the VVE group with vancomycin treatment (4.8%, 1/21) was identified, which led to subsequent mortality. ConclusionsThe prevalence of VVE was high among E. faecium isolates with vancomycin-susceptible phenotypes in southern Taiwan. Although the current study revealed that VVE bacteremia was not associated with poor clinical outcome, further multicenter surveillance survey is recommended to evaluate the possible impact of VVE on public health in Taiwan.

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.

Risk Factors for 30-Day Mortality in Nosocomial Enterococcal Bloodstream Infections.

Enterococci commonly cause nosocomial bloodstream infections (BSIs), and the global incidence of vancomycin-resistant enterococci (VRE) BSIs is rising. This study aimed to assess the risk factors for enterococcal BSIs and 30-day mortality, stratified by Enterococcus species, vancomycin resistance, and treatment appropriateness. We conducted a retrospective cohort study (2014-2021) including all hospitalized adult patients with at least one blood culture positive for Enterococcus faecalis or Enterococcus faecium. We included 584 patients with enterococcal BSI: 93 were attributed to vancomycin-resistant E. faecium. The overall 30-day mortality was 27.5%; higher in cases of BSI due to vancomycin-resistant E. faecium (36.6%) and vancomycin-sensitive E. faecium (31.8%) compared to E. faecalis BSIs (23.2%) (p = 0.016). This result was confirmed by multivariable Cox analysis. Independent predictors of increased mortality included the PITT score, complicated bacteremia, and age (HR = 1.269, p < 0.001; HR = 1.818, p < 0.001; HR = 1.022, p = 0.005, respectively). Conversely, male gender, consultation with infectious disease (ID) specialists, and appropriate treatment were associated with reduced mortality (HR = 0.666, p = 0.014; HR = 0.504, p < 0.001; HR = 0.682, p = 0.026, respectively). In conclusion, vancomycin-resistant E. faecium bacteremia is independently associated with a higher risk of 30-day mortality.

Outcomes of patients who received CAR T cell therapy and developed IEC-HS treated with cytokine directed therapy.

7516 Background: Immune effector cell hemophagocytic lymphohistiocytosis IEC-HS is a complication of CAR T cell therapy (CART). This study aims to look at the outcomes of CART patients who develop IEC-HS. Methods: Patients who developed IEC-HS after receiving CART and patients who developed IEC-HS without (nonCART) between December 2020 and March 2022 were included. Results: The 20 CART patients were older than the 25 nonCART patients. Peak ferritin, fibrinogen, CRP, serum creatinine and transaminases were similar between the 2 group. CART patients had lower white blood cell count and platelets and bilirubin than the nonCART patients. CART patients were more like to have markedly elevated IL-6 levels (&gt; 315 mg/ml), higher IL-18, higher MCP-1, and suppressed IL-1β and GMCSF than nonCART patients (Table). Treatment of IEC-HS included tocilizumab (n = 19), anakinra (n = 18) siltuximab (n = 4) and basiliximab (n = 4), dexamethasone (n = 18) methylprednisolone (n = 6), etoposide (n = 1) and ruxolitinib (n = 1). A significant response defined by a 90% reduction or normalization of the cytokine was observed with IL-10 and IFN-ϒ in 92.3% and 84.6% of the CART patients respectively. An intermediate response was noted with TNF, IL-6, MCP-1 and MIP-1 in 38.4%, 30.8% and 61.6% and 38.5% of the patients respectively. No patient had a significant response in IL-2Rα or IL-1β and only 7.7% had a significant response in IL-18. Of the 5 patients who had a MIP-1 response, 4 were on basiliximab +/- high flow continuous venovenous hemofiltration and the only patient that had an IL-18 response was on both modalities. The 100-day mortality after IEC-HS in the CART patients was 40% and was associated with higher peak and lower best ferritin but not the percentage reduction (Table). Higher TNF (90.3 pg/ml vs 37.2 pg/ml, p = 0.05), markedly elevated levels of IL-6 (92% vs 50%, p = 0.03) and IL-10 (33% vs 0%) and an IL-6 response (44.4% vs 0%) were associated with survival at day 100. IL-6 responders had lower peak ferritin vs IL-6 nonresponders (14066 mcg/L vs 45051 mcg/L, p = 0.08). Enterococcus faecium bacteremia developed in 75% of the nonsurvivors vs 16.6% of the 100-day survivors (p = 0.009). Survivors cleared the enterococcus bacteremia within days while nonsurvivors had protracted bacteremia. Conclusions: IEC-HS is devastating complication of CART. Anti-cytokine therapy can reduce some cytokines and ferritin but overimmunosuppression may lead infectious complication, in particular with E. faecium. Better biomarkers are needed to finetune immunosuppressive therapy in order to avoid over-immunosuppression. [Table: see text]

Hospital-acquired bloodstream infections in critically ill cirrhotic patients: a post-hoc analysis of the EUROBACT-2 international cohort study

BackgroundHospital-acquired bloodstream infections are common in the intensive care unit (ICU) and have a high mortality rate. Patients with cirrhosis are especially susceptible to infections, yet there is a knowledge gap in the epidemiological distinctions in hospital-acquired bloodstream infections between cirrhotic and non-cirrhotic patients in the ICU. It has been suggested that cirrhotic patients, present a trend towards more gram-positive infections, and especially enterococcal infections. This study aims to describe epidemiological differences in hospital-acquired bloodstream infections between cirrhotic and non-cirrhotic patients hospitalized in the ICU regarding infection sources, microorganisms and mortality.MethodsUsing prospective Eurobact-2 international cohort study data, we compared hospital-acquired bloodstream infections sources and microorganisms in cirrhotic and non-cirrhotic patients. The association between Enterococcus faecium and cirrhosis was studied using a multivariable mixed logistic regression. The association between cirrhosis and mortality was assessed by a multivariable frailty Cox model.ResultsAmong the 1059 hospital-acquired bloodstream infections patients included from 101 centers, 160 had cirrhosis. Hospital-acquired bloodstream infection source in cirrhotic patients was primarily abdominal (35.6%), while it was pulmonary (18.9%) for non-cirrhotic (p < 0.01). Gram-positive hospital-acquired bloodstream infections accounted for 42.3% in cirrhotic patients compared to 33.2% in non-cirrhotic patients (p = 0.02). Hospital-acquired bloodstream infections in cirrhotic patients were most frequently caused by Klebsiella spp (16.5%), coagulase-negative Staphylococci (13.7%) and E. faecium (11.5%). E. faecium bacteremia was more frequent in cirrhotic patients (11.5% versus 4.5%, p < 0.01). After adjusting for possible confounding factors, cirrhosis was associated with higher E. faecium hospital-acquired bloodstream infections risk (Odds ratio 2.5, 95% CI 1.3–4.5, p < 0.01). Cirrhotic patients had increased mortality compared to non-cirrhotic patients (Hazard Ratio 1.3, 95% CI 1.01–1.7, p = 0.045).ConclusionsCritically ill cirrhotic patients with hospital-acquired bloodstream infections exhibit distinct epidemiology, with more Gram-positive infections and particularly Enterococcus faecium.

Lower Specificity of the European Society of Cardiology 2023 Diagnostic Criteria for Infective Endocarditis When Spondylodiscitis Is Regarded as a Vascular Phenomenon.

The ESC diagnostic criteria for infective endocarditis (IE) added spondylodiscitis as a minor criterion. This resulted in that 11 of 1807 patients with Staphylococcus aureus, streptococcal, or Enterococcus faecalis bacteremia, were reclassified from possible to definite IE, of whom only two were treated as IE.

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.

The population structure of vancomycin-resistant and -susceptible Enterococcus faecium in a low-prevalence antimicrobial resistance setting is highly influenced by circulating global hospital-associated clones.

Between 2010 and 2015 the incidence of vancomycin-resistant Enterococcus faecium (VREfm) in Norway increased dramatically. Hence, we selected (1) a random subset of vancomycin-resistant enterococci (VRE) from the Norwegian Surveillance System for Communicable Diseases (2010-15; n=239) and (2) Norwegian vancomycin-susceptible E. faecium (VSEfm) bacteraemia isolates from the national surveillance system for antimicrobial resistance in microbes (2008 and 2014; n=261) for further analysis. Whole-genome sequences were collected for population structure, van gene cluster, mobile genetic element and virulome analysis, as well as antimicrobial susceptibility testing. Comparative genomic and phylogeographical analyses were performed with complete genomes of global E. faecium strains from the National Center for Biotechnology Information (NCBI) (1946-2022; n=272). All Norwegian VREfm and most of the VSEfm clustered with global hospital-associated sequence types (STs) in the phylogenetic subclade A1. The vanB2 subtype carried by chromosomal Tn1549 integrative conjugative elements was the dominant van type. The major Norwegian VREfm cluster types (CTs) were in accordance with concurrent European CTs. The dominant vanB-type VREfm CTs, ST192-CT3/26 and ST117-CT24, were mostly linked to a single hospital in Norway where the clones spread after independent chromosomal acquisition of Tn1549. The less prevalent vanA VRE were associated with more diverse CTs and vanA carrying Inc18 or RepA_N plasmids with toxin-antitoxin systems. Only 5 % of the Norwegian VRE were Enterococcus faecalis, all of which contained vanB. The Norwegian VREfm and VSEfm isolates harboured CT-specific virulence factor (VF) profiles supporting biofilm formation and colonization. The dominant VREfm CTs in general hosted more virulence determinants than VSEfm. The phylogenetic clade B VSEfm isolates (n=21), recently classified as Enterococcus lactis, harboured fewer VFs than E. faecium in general, and particularly subclade A1 isolates. In conclusion, the population structure of Norwegian E. faecium isolates mirrors the globally prevalent clones and particularly concurrent European VREfm/VSEfm CTs. Novel chromosomal acquisition of vanB2 on Tn1549 from the gut microbiota, however, formed a single major hospital VREfm outbreak. Dominant VREfm CTs contained more VFs than VSEfm.

184. Implications of Enterococcus faecalis penicillin susceptibility in patients with bacteremia

Abstract Background Enterococcus faecalis isolates with an elevated penicillin minimum inhibitory concentration (MIC) ≥ 4 mg/L have decreased in vitro ampicillin plus ceftriaxone bactericidal and synergistic activity, despite ampicillin susceptibility. This phenotype’s implication on patient outcomes and prevalence in the US is unknown due to limited penicillin susceptibility reporting. Methods This was a retrospective cohort study of adult patients with E. faecalis bacteremia between August 20, 2018 and May 13, 2021 from the Mount Sinai Health System in New York City. Patients were excluded if they were discharged or deceased within 48 hours of index blood culture, did not receive active definitive therapy, or the blood culture was determined to be contamination. The primary outcome was differences in 30-day and 90-day mortality based on the penicillin MIC and the secondary outcome was microbiological relapse. Multivariable logistic regression was used to identify risk factors for 90-day mortality. Corresponding blood isolates were tested for penicillin susceptibility by broth microdilution in accordance with CLSI. Results A total of 124 patients were included, with 27% having an elevated penicillin MIC ≥ 4 mg/L. Differences in baseline characteristics (Table 1) as well as source of infection and treatments received (Table 2) were similar between groups. Endocarditis infected 18.5% of patients and was less common in cases with an elevated penicillin MIC. Thirty-day and 90-day mortality, and microbiological relapse were higher in cases with an elevated penicillin MIC (14.4% vs. 20.6%, p=0.58; 20% vs. 26.5%, p=0.59; and 4.4% vs. 8.8%, p=0.39, respectively). Pitt bacteremia score and prior ceftriaxone usage had a higher odds of 90-day mortality (OR 1.2 [95% CI 1.03-1.4], p=0.02; OR 2.8 [95% CI 1.02-7.9], p=0.04, respectively), whereas definitive treatment with an aminopenicillin compared to piperacillin/tazobactam was protective of 90-day mortality (OR 0.21 [95% CI 0.05-0.93], p=0.04). Conclusion E. faecalis with an elevated penicillin MIC ≥ 4 mg/L is present in over a quarter of patients across New York City. Larger studies are warranted to determine the impact on patient outcomes. E. faecalis bacteremia treatment with piperacillin/tazobactam may be associated higher mortality. Disclosures Jaclyn A. Cusumano, PharmD, BCIDP, Shionogi: Advisor/Consultant

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.

Blalock-Taussig Shunt Blockage Caused by Small Colony Variants of Enterococcus faecalis.

To the Editors: Small colony variants (SCVs) constitute a subpopulation of nutrient-demanding bacteria that grow slower than the wild type. Selection pressure exerted by environmental factors, such as antimicrobial agents.1,2 SCVs of Enterococcus sp. are less frequent. We report the first case of Blalock–Taussig shunt (BTS) blockage caused by SCVs of Enterococcus faecalis. A 1-year-old boy diagnosed with tetralogy of Fallot underwent left BTS surgery and closure of patent ductus arteriosus 10 months before presentation. On postoperative day 11, a catheter-related bloodstream infection (CRBSI) was caused by E. faecalis. The peripherally inserted central catheter was removed. Echocardiography revealed the absence of verrucae, and the modified Duke criteria were not definite. Ampicillin was administered for 2 weeks; 4 months postcompletion of this therapy, the left BTS was occluded, and a right BTS surgery was performed with the left BTS remaining in place. Although he underwent this surgery for endocardial repair, the left BTS was only removed during the operation, as pus was found in the occluded left BTS during the intraoperative manipulation. No bacteria were detected in the pus using Gram staining, but vancomycin was administered for suspected shunt infection. After 2 days of culture, colonies of approximately 0.2–1 mm and 2–3 mm diameters were observed on the blood agar medium maintained in an aerobic environment and the Brucella HK agar (Kyokuto, Inc. Tokyo, Japan) medium maintained in an anaerobic environment, respectively (Fig. 1). Although biochemical analysis indicated Enterococcus spp., identification and drug sensitivity test performed using Micro Scan Walkaway 40 plus (Beckman Coulter, Inc. CA) indicated poor growth after 24 hours of incubation. Matrix-assisted laser desorption/ionization–time-of-flight analysis indicated the presence of E. faecalis; hence, the antimicrobial was changed to ampicillin, which was administered for 4 weeks to control the mediastinitis. He was discharged without sequelae and had no recurrence of bacteremia for over a year.FIGURE 1.: Bacterial colonies cultured using blood agar and Brucella HK agar media.SCVs originated due to stresses, such as perioperative exposure to antimicrobials used to treat E. faecalis bacteremia. In addition, the short duration of antimicrobial therapy used to treat CRBSI may be another reason. Enterococcus spp. bacteremia is considerably associated with the occurrence of infectious endocarditis (IE) caused by a prosthetic valve; hence, echocardiography is recommended.3 In this case, antimicrobials were administered for 2 weeks. However, 4–6 weeks of antimicrobial therapy may be appropriate for treating IE. SCVs, with a typical phenotype of low virulence and long-term persistence, adapt to the intracellular environment more efficiently than the wild type. We have listed previously reported cases of SCVs of Enterococcus spp. (Table Supplemental Digital Content 1, https://links.lww.com/INF/E930,); half of which were IE, including two cases of IE related to prosthetic valves, which may be attributed to the fact that SCVs tend to form biofilms, leading to infection in prostheses.4 Moreover, Enterococcus spp. have higher probability of forming biofilms than other bacteria. E. faecalis is particularly more prone to biofilm formation than E. faecium.5 This case indicates that SCVs of E. faecalis may survive for a long period, especially in case of artifact infection.