The association of infectious diseases consultation and 30-day mortality rates among veterans with enterococcal bacteraemia: a propensity score-matched retrospective cohort study.

OBJECTIVES: Infectious disease consultation (IDC) has been associated with improved outcomes in several infections, but the benefit of IDC among patients with enterococcal bacteraemia has not been fully evaluated. METHODS: We performed a 1:1 propensity score-matched retrospective cohort study evaluating all patients with enterococcal bacteraemia at 121 Veterans Health Administration acute-care hospitals from 2011 to 2020. The primary outcome was 30-day mortality. We performed conditional logistic regression to calculate the OR to determine the independent association of IDC and 30-day mortality adjusted for vancomycin susceptibility and the primary source of bacteraemia. RESULTS: A total of 12,666 patients with enterococcal bacteraemia were included; 8400 (63.3%) had IDC, and 4266 (36.7%) did not have IDC. Two thousand nine hundred seventy-two patients in each group were included after propensity score matching. Conditional logistic regression revealed that IDC was associated with a significantly lower 30-day mortality rate compared with patients without IDC (OR = 0.56; 95% CI, 0.50-0.64). The association of IDC was observed irrespective of vancomycin susceptibility, and when the primary source of bacteraemia was a urinary tract infection, or from an unknown primary source. IDC was also associated with higher appropriate antibiotic use, blood culture clearance documentation, and the use of echocardiography. DISCUSSION: Our study suggests that IDC was associated with improved care processes and 30-day mortality rates among patients with enterococcal bacteraemia. IDC should be considered for patients with enterococcal bacteraemia.

Infección urinaria por enterococos: Factores de riesgo y mortalidad. Estudio observacional / Urinary tract infection caused by Enterococcus spp.: risk factors and mortality. An observational study

Antecedentes y objetivo Los enterococos son una causa frecuente de infecciones del tracto urinario (ITU). Este trabajo pretende definir los factores de riesgo asociados con las ITU causadas por enterococos y determinar su mortalidad global y los factores de riesgo predictivos. Materiales y métodos Se llevó a cabo un estudio retrospectivo sobre las ITU bacteriémicas por enterococos en pacientes hospitalizados. Se compararon 106 sujetos hospitalizados por ITU bacteriémicas por enterococos con una muestra aleatoria de 100 pacientes hospitalizados por ITU bacteriémicas por otras enterobacterias. Resultados Se analizó un total de 106 sujetos hospitalizados por ITU por enterococos, 51 de ellos con hemocultivos positivos concomitantes. La distribución por especies fue: 83% por Enterococcus faecalis (E. faecalis) y 17% por Enterococcus faecium (E. faecium). La puntuación media en el índice de comorbilidad de Charlson fue de 5,9 ± 2,9. Al comparar las ITU bacteriémicas por enterococos con las causadas por otras enterobacterias se identificaron los siguientes factores predictivos independientes de ITU bacteriémicas por enterococos: sexo masculino, uropatía obstructiva, infección nosocomial, cánceres de vías urinarias y tratamiento antibiótico previo. En conjunto, la mortalidad hospitalaria fue del 16,5% y se asoció con una mayor puntuación de la escala para la evaluación del daño orgánico secuencial (SOFA) (> 4), a enfermedades concomitantes graves, como inmunodepresión, hemopatía maligna y nefrostomía, y a la especie E. faecium y su patrón de resistencia a la ampicilina o la vancomicina (p < 0,05). Un tratamiento antibiótico empírico adecuado no se relacionó con un mejor pronóstico (p > 0,05). Conclusiones Los enterococos son una causa frecuente de ITU complicadas en pacientes con factores de riesgo. La elevada mortalidad vinculada con la severidad de la infección y el grado de comorbilidad podrían justificar un tratamiento empírico en pacientes de riesgo (AU)

Background and objective Urinary tract infections (UTIs) are frequently caused by Enterococcus spp. This work aims to define the risk factors associated with UTIs caused by Enterococci and to determine its overall mortality and predictive risk factors. Materials and methods A retrospective study was conducted on bacteremic UTIs caused by Enterococcus spp. among inpatients. We compared 106 inpatients with bacteremic UTIs caused by Enterococcus spp. vs. a random sample of 100 inpatients with bacteremic UTIs caused by other enterobacteria. Results A total of 106 inpatients with UTIs caused by Enterococcus spp. were analyzed, 51 of whom had concomitant positive blood cultures. Distribution by species was 83% E. faecalis and 17% E. faecium. The mean Charlson Comorbidity Index score was 5.9 ± 2.9. Upon comparing bacteremic UTIs caused by Enterococcus spp. vs. bacteremic UTIs caused by others enterobacteria, we found the following independent predictors of bacteremic UTI by Enterococcus: male sex, obstructive uropathy, nosocomial infection, cancers of the urinary system, and previous antimicrobial treatment. Overall, inpatient mortality was 16.5% and was associated with a higher Sequential Organ Failure Assessment (SOFA) score (>4); severe comorbidities such as immunosuppression, malignant hemopathy, and nephrostomy; and Enterococcus faecium species and its pattern of resistance to ampicillin or vancomycin (p< 0.05). Appropriate empiric antibiotic therapy was not associated with a better prognosis (p >0.05). Conclusions Enterococcus spp. is a frequent cause of complicated UTI in patients with risk factors. High mortality secondary to a severe clinical condition and high comorbidity may be sufficient for justifying the implementation of empiric treatment of at-risk patients (AU)

Time to positivity as a prognostic factor in bloodstream infections with Enterococcus spp.

Time to positivity (TTP) is the delay of time from incubation to blood culture positivity. Short TTP can predict mortality and source of infection. The aim of this study was to investigate the value of TTP of patients with bloodstream infections with enterococci (E-BSI).In a single centre retrospective cohort study in Germany, the data of 244 patients with monomicrobial E-BSI were analyzed with hospital mortality as the primary outcome of interest from January 1 2014 to December 31 2016. Mortality rate of patients with bloodstream infections (BSI) with E. faecalis was 16.7%, Vancomycin sensitive E. faecium (VSEfm) 26.7% and Vancomycin resistant E. faecium (VREfm) 38.2%. Cut-offs showed a significantly higher mortality rate when compared to longer TTP (E. faecalis: P=0.047; VSEfm: P=0.02), but were not risk factors in survival analysis (E.faecalis: HR (hazard ratio): 2.73; P=0.17; VSEfm: HR: 1.63; P=0.15; VREfm: HR: 1.24; P=0.63). TTP≤10.5 hours with E. faecalis BSI was a discriminator for cardiovascular source of infection (AUC: 0.75). A short TTP could predict mortality rates and source of infection but was not an independent parameter for risk of death in survival analysis.

Systematic review and meta-analysis to explore optimal therapeutic range of vancomycin trough level for infected paediatric patients with Gram-positive pathogens to reduce mortality and nephrotoxicity risk.

The aim of this study was to investigate the association between vancomycin trough level and clinical outcomes (mortality and nephrotoxicity) among infected paediatric patients with Gram-positive pathogens. We systematically searched the Scopus, EMBASE, Cochrane Central Register of Controlled Trials, PubMed and CINAHL databases up to March 2020. A total of seven retrospective cohort or case-control studies were included to compare clinical effects and safety: three studies set the threshold of vancomycin trough level at 10 mg/L and the others set it at 15 mg/L. Our analysis showed that vancomycin trough level of 10-15 mg/L was associated with significantly lower mortality [<10 mg/L vs. ≥10 mg/L, odds ratio (OR) = 3.21, 95% confidence interval (CI) 1.74-5.91; and <15 mg/L vs. ≥15 mg/L, OR = 0.31, 95% CI 0.10-0.95). The high vancomycin trough group (≥10 mg/L or ≥15 mg/L) showed a higher incidence of nephrotoxicity (<10 mg/L vs. ≥10 mg/L, OR = 0.06, 95% CI 0.03-0.12; and <15 mg/L vs. ≥15 mg/L, OR = 0.28, 95% CI 0.12-0.65). This is the first meta-analysis to reveal the optimal therapeutic range of vancomycin trough level in children. Our findings strongly suggest a superior benefit of vancomycin trough of 10-15 mg/L for paediatric patients.

Surgical treatment of infective endocarditis in intravenous drug abusers.

BACKGROUND: Despite current progress in antibiotic therapy and medical management, infective endocarditis remains a serious condition presenting with high mortality rates. It also is a life-threatening complication in patients with a history of chronic intravenous drug abuse. In this study, we analyzed our institutional experience on the surgical therapy of infective endocarditis in patients with active intravenous drug abuse. The aim of the study is to identify the predictive factors of mortality and morbidity in this subgroup of patients. METHODS: Between 2007 and 2020, a total of 24 patients (7 female, mean age 38.5 ± 8.7) presenting with active intravenous drug abuse underwent a surgical treatment for the infective endocarditis at out center. The primary endpoint was survival at 30th day after the surgery. The secondary composite endpoint included freedom from death, recurrent endocarditis, re-do surgery, and postoperative stroke during the follow-up period. Mean follow-up was 4.2 ± 4.3 years. RESULTS: Staphylococcus species was the most common pathogen detected in the preoperative blood cultures. Infection caused by Enterococcus species as well as liver function impairment were identified as mortality predictor factors. Logistic EuroSCORE and EusoSCORE-II were also predictive factors for mortality in univariate analysis. Survival at 1 and 3 years was 78 and 72% respectively. Thirty-day survival was 88%. 30-day freedom from combined endpoint was 83% and after 1 and 3 years, 69 and 58% of the patients respectively were free from combined endpoint. Five patients (20.8%) were readmitted with recurrent infective endocarditis. CONCLUSION: In patients presenting with active intravenous drug abuse, treatment of infective endocarditis should be performed as aggressively as possible and should be followed by antibiotic therapy to avoid high mortality rates and recurrent endocarditis. Early intervention is advisable in patients with an infective endocarditis and enterococcus species in the preoperative blood cultures, liver function deterioration as well as cardiac function impairment. Attention should be also payed to addiction treatment, due to the elevated relapse rate in patients who actively inject drugs. However, larger prospective studies are necessary to support our results. As septic shock is the most frequent cause of death, new treatment options, e.g. blood purification should be evaluated.

Evaluation of the Neonatal Sequential Organ Failure Assessment and Mortality Risk in Preterm Infants With Late-Onset Infection.

Importance: Infection in neonates remains a substantial problem. Advances for this population are hindered by the absence of a consensus definition for sepsis. In adults, the Sequential Organ Failure Assessment (SOFA) operationalizes mortality risk with infection and defines sepsis. The generalizability of the neonatal SOFA (nSOFA) for neonatal late-onset infection-related mortality remains unknown. Objective: To determine the generalizability of the nSOFA for neonatal late-onset infection-related mortality across multiple sites. Design, Setting, and Participants: A multicenter retrospective cohort study was conducted at 7 academic neonatal intensive care units between January 1, 2010, and December 31, 2019. Participants included 653 preterm (<33 weeks) very low-birth-weight infants. Exposures: Late-onset (>72 hours of life) infection including bacteremia, fungemia, or surgical peritonitis. Main Outcomes and Measures: The primary outcome was late-onset infection episode mortality. The nSOFA scores from survivors and nonsurvivors with confirmed late-onset infection were compared at 9 time points (T) preceding and following event onset. Results: In the 653 infants who met inclusion criteria, median gestational age was 25.5 weeks (interquartile range, 24-27 weeks) and median birth weight was 780 g (interquartile range, 638-960 g). A total of 366 infants (56%) were male. Late-onset infection episode mortality occurred in 97 infants (15%). Area under the receiver operating characteristic curves for mortality in the total cohort ranged across study centers from 0.71 to 0.95 (T0 hours), 0.77 to 0.96 (T6 hours), and 0.78 to 0.96 (T12 hours), with utility noted at all centers and in aggregate. Using the maximum nSOFA score at T0 or T6, the area under the receiver operating characteristic curve for mortality was 0.88 (95% CI, 0.84-0.91). Analyses stratified by sex or Gram-stain identification of pathogen class or restricted to infants born at less than 25 weeks' completed gestation did not reduce the association of the nSOFA score with infection-related mortality. Conclusions and Relevance: The nSOFA score was associated with late-onset infection mortality in preterm infants at the time of evaluation both in aggregate and in each center. These findings suggest that the nSOFA may serve as the foundation for a consensus definition of sepsis in this population.

Bacillus cereus Induces Severe Infections in Preterm Neonates: Implication at the Hospital and Human Milk Bank Level.

Human breast milk (HBM) is a source of essential nutrients for infants and is particularly recommended for preterm neonates when their own mother's milk is not available. It provides protection against infections and decreases necrotizing enterocolitis and cardiovascular diseases. Nevertheless, HBM spoilage can occur due to contamination by pathogens, and the risk of a shortage of HBM is very often present. B. cereus is the most frequent ubiquitous bacteria responsible for HBM being discarded. It can contaminate HBM at all stages, from its collect point to the storage and delivery. B. cereus can induce severe infection in newborns with very low birth weight, with sometimes fatal outcomes. Although the source of contamination is rarely identified, in some cases, HBM was suspected as a potential source. Even if the risk is low, as infection due to B. cereus in preterm infants should not be overlooked, human milk banks follow strict procedures to avoid contamination, to accurately identify remaining bacteria following pasteurization and to discard non-compliant milk samples. In this review, we present a literature overview of B. cereus infections reported in neonates and the suspected sources of contamination. We highlight the procedures followed by the human milk banks from the collection of the milk to its microbiological characterization in Europe. We also present improved detection and decontamination methods that might help to decrease the risk and to preserve the public's confidence in this vital biological product for infants whose mothers cannot breastfeed.

Resection and replacement of thoracic aortic graft infections.

OBJECTIVES: Thoracic aortic graft infection (TAGI) presents a formidable challenge with high mortality. We evaluated our 22-year experience managing TAGI with extensive debridement, graft replacement, vascularized tissue coverage, and aggressive antibiotics. METHODS: We reviewed all consecutive patients with TAGI from 1991 to 2013. We also compared infected cases versus noninfected reoperative controls using a case-control design. Standard statistical methods were used for descriptive analysis, and Kaplan-Meier for survival analysis. RESULTS: We treated 32 TAGI patients, involving 19 ascending/arch (A/A) and 13 descending/thoracoabdominal (D/TAA) grafts, including 4 endografts. In total, 19 (59.4%) presented with pseudoaneurysm and 11 (34.4%) with aortic fistula. Vascularized tissue (omentum or muscle) coverage was possible in 22 (71.0%) patients. Thirty-day mortality occurred in 3 (9.4%) patients, with no 30-day mortality among those receiving vascularized graft coverage (P = .018). During follow-up, reinfection occurred in 8 patients (25% [4 A/A and 4 D/TAA]). Five-year overall (A/A 45.4% vs D/TAA 28.9%, P = .434) and reinfection-free (A/A 19.2%, D/TAA 27%, P = .409) survival was similar between groups. Long-term mortality was greater after endograft infection (100% vs 25% at 2.5 months, P = .0007) or aortobronchial fistulization (100% vs 37.9% at 6 months, P = .026). Time to reintervention was shorter in infected versus non-infected reoperative cases (31 vs 83 months, P < .0001), but there were no significant differences in long-term mortality after reoperation. CONCLUSIONS: TAGI continues to represent a highly morbid surgical challenge. Prompt antimicrobial coverage, debridement, graft replacement, and vascularized graft coverage, yielded best long-term results. Endograft infection and aortobronchial fistula had very poor prognoses.

Analysis of blood stream infections, antibiograms and clinical outcomes in haematological patients with febrile neutropenia: data from a tertiary care haematology institute in India.

Timely administration of appropriate empirical antibiotics in febrile neutropenia is crucial for favourable patient outcomes. There are guidelines in place recommending such antibiotics. However, regional variations and local epidemiological data must be evaluated to tailor the antibiotics for best possible and rational use. In this study, we audited the clinical and microbiological data of febrile neutropenic episodes occurring at a tertiary care haematology institution. Three hundred and ninety-three febrile neutropenic episodes occurring in 123 patients over a 1-year period were analysed for microbial profile, sensitivity and resistance patterns, and finally clinical outcomes. Gram-negative bacilli (GNB) blood stream infections (46.9%) were more prevalent as compared to gram-positive infections (41.9%). Overall mortality due to complicated neutropenic sepsis was 19.5% (24/123 patients). Increased resistance to carbapenems, beta-lactam beta-lactamase inhibitor combinations, aminoglycosides, fluoroquinolones, and cephalosporins were observed. Cefepime and tigecycline resistance were seen in 20% and 15% GNB isolates, respectively. Chest was the most frequent focus of infection, and acute myeloid leukaemia (AML) was the most common underlying disorder which correlated with the likelihood of death (p < 0.01). Multidrug-resistant GNB (esp. Klebsiella sp.) are still most worrisome isolates in neutropenic patients. Single-agent cefepime or piperacillin-tazobactam/tigecycline combination may be considered empirical agents. Chest infections and AML were independent predictors of poor clinical outcome in neutropenic patients. Regular audit of infections and antibiotic susceptibility data is needed to improve clinical outcomes in patients with febrile neutropenia.

Vagococcus sp. a porcine pathogen: molecular and phenotypic characterization of strains isolated from diseased pigs in Brazil.

INTRODUCTION: Vagococcus spp. is known for its importance as a systemic and zoonotic bacterial pathogen even though it is not often reported in pigs. This is related to the pathogen misidentification due to the lack of usage of more discriminatory diagnostic techniques. Here we present the first report of Vagococcus lutrae in swine and the characterization of Vagococcus fluvialis and Vagococcus lutrae isolated from diseased animals. METHODOLOGY: Between 2012 and 2017, 11 strains with morphological characteristics similar to Streptococcus spp. were isolated from pigs presenting different clinical signs. Bacterial identification was performed by matrix assisted laser desorption ionization time of flight (MALDI-TOF) mass spectrometry and confirmed by 16S rRNA sequencing and biochemical profile. Strains were further genotyped by single-enzyme amplified fragment length polymorphism (SE-AFLP). Broth microdilution was used to determine the minimal inhibitory concentration of the antimicrobials of veterinary interest. RESULTS: Ten strains were identified as V. fluvialis and one was identified as V. lutrae. The SE-AFLP analysis enabled the species differentiation with specific clustering of all V. fluvialis separately from the V. lutrae strain. Most strains presented growth in the maximum antibiotic concentration values tested for eight of the 10 analyzed antimicrobial classes. CONCLUSIONS: The observed resistance pattern can represent a problem for veterinary and producers in the treatment of diseases associated Vagococcus spp. in swine production. Vagococcus species may also be a risk for pig industry workers. The data described here will be of great value in further understanding the behavior of this pathogen in animal production.

Vancomycin-resistant enterococci infection and predisposing factors for infection and mortality in patients with acute leukaemia and febrile neutropenia.

BACKGROUND: Vancomycin-resistant enterococcus (VRE) is an infectious agent that can increase morbidity and mortality, especially in patients with neutropenia in haematology departments. We analysed VRE infections and mortality rates among VRE colonized patients with acute leukaemia, defined predisposing risk factors for infection and mortality, and investigated the influence of daptomycin or linezolid treatment on mortality. PATIENTS-METHODS: We included 200 VRE colonized adult acute leukaemia patients with febrile neutropenia between January 2010 and January 2016. Data were collected from electronic files. RESULTS: There were 179 patients in the colonized group, and 21 patients in the infected group. Enterococcus faecium (van A) was isolated from all patients. The infection rate was 10.5 %, and the types of infections noted were as follows: bloodstream (n = 14; 66.7 %), skin and soft tissue (n = 3; 14.3 %), urinary (n = 2; 9.5 %), and others (9.5 %). In the multivariate logistic regression analysis, exposure to invasive procedures, coinfection status, and >15 days of VRE positivity were independent risk factors for VRE infections. In hospital mortality rates were 57.1 % in the infected group, and 9.5 % in the colonized group (p < 0.001). Older age, female gender, absolute neutropenia, and coinfection status were statistically significant predictor of survival. CONCLUSION: Vancomycin-resistant enterococcus infections are associated with high morbidity and mortality in haematology patients with neutropenia. Clinicians should be aware of predisposing risk factors for VRE infection to avoid unfavourable outcomes. We believe that larger studies are necessary regarding the influence of treatment with daptomycin and linezolid.

Circular RNA PRKCI and microRNA-545 relate to sepsis risk, disease severity and 28-day mortality.

This study aimed to explore the clinical values of circular RNA protein kinase C iota (circ-PRKCI) and its target microRNA-545 (miR-545) in sepsis patients. Plasma samples of 121 sepsis patients and 60 healthy controls (HCs) were collected, then circ-PRKCI and miR-545 expressions were detected using RT-qPCR. Sepsis patients' demographics, biochemical indexes, medical histories, infection information were recorded. Besides, comprehensive disease scores (APACHE II score and SOFA score) were assessed within 24 h after admission. According to the survival status, 28-day mortality was calculated. Decreased circ-PRKCI expression and increased miR-545 expression were observed in sepsis patients compared to HCs, both of which had close correlations with sepsis risk. Besides, circ-PRKCI was negatively correlated with miR-545 in sepsis patients and HCs, respectively. Circ-PRKCI was negatively correlated with serum creatinine, white blood cell, C-reactive protein, APACHE II score, SOFA score, but positively correlated with albumin, which also related to blood stream infection (as primary infection site) and anaerobes infection in sepsis patients. Whereas the miR-545 showed a roughly opposite tendency. Decreased circ-PRKCI and increased miR-545 expressions were discovered in deaths compared to survivors, and both of them had values for predicting 28-day mortality risk in sepsis patients, which were slightly lower than the predictive values of APACHE II score and SOFA score for predicting 28-day mortality risk. Multivariate logistic analyses displayed circ-PRKCI as an independent factor predicting decreased 28-day mortality risk. In conclusion, circ-PRCKI insufficiency and miR-545 sufficiency were related to sepsis risk, clinical disease severity and 28-day mortality risk.

A retrospective observational study on enterococcal bacteraemia and endocarditis at a regional hospital in New South Wales, Australia.

BACKGROUND: Enterococcal infection poses a major clinical problem due to increasing antibiotic resistance and rising numbers of health care related infections. It is also associated with high morbidity and mortality. The aim of this study is to examine demographic characteristics, co-morbidities and clinical outcomes of the patients as well as susceptibility spectrum of all Enterococcal bacteraemia and endocarditis. METHODS: A retrospective observational study was performed on cases of Enterococcal bacteraemia and endocarditis at Port Macquarie Base Hospital, New South Wales, Australia from 1st January 2012 till 31st December 2018. RESULTS: Out of 75 patients with Enterococcal bacteraemia, about 70% were male. E.faecalis was responsible for about two-thirds of bacteraemia. E.faecalis most commonly presented as infective endocarditis whereas intraabdominal infection was the most common presentation for E.faecium. 90-day all-cause mortality for all Enterococcal bacteraemia was 29.3% (22 out of 75) with a higher mortality rate with E.faecium bacteraemia in comparison to E.faecalis bacteraemia (47.8% Vs 20.8%). Vancomycin resistance was noted only in 17.4% of E.faecium species. There were 18 patients with infective endocarditis over 7 years period with a yearly prevalence rate of 2.6%. Readmission was 78% and mortality was 16.7% within 90 days of admission. Regarding the use of echocardiogram, about 41.3% of Enterococcal bacteraemia did not have echocardiograms. CONCLUSION: Enterococcal bacteraemia was associated with high morbidity and mortality, particularly secondary to E.faecium bacteraemia. Enterococcal IE was associated with high rates of complications, readmissions, and prolonged inpatient stay.

Microbiology and risk factors for gram-positive Cocci bacteremia in biliary infections.

BACKGROUND: The rapid antibiotics treatment targeted to a specific pathogen can improve clinical outcomes of septicemia. We aimed to evaluate the clinical characteristics and outcomes of biliary septicemia caused by cholangitis or cholecystitis according to causative organisms. METHODS: We performed a retrospective cohort study in 151 patients diagnosed with cholangitis or cholecystitis with bacterial septicemia from January 2013 to December 2015. All patients showed clinical evidence of biliary tract infection and had blood isolates that demonstrated septicemia. RESULTS: Gram-negative, gram-positive, and both types of bacteria caused 84.1% (127/151), 13.2% (20/151), and 2.6% (4/151) episodes of septicemia, respectively. The most common infecting organisms were Escherichia coli among gram-negative bacteria and Enterococcus species (Enterococcus casseliflavus and Enterococcus faecalis) among gram-positive bacteria. There were no differences in mortality, re-admission rate, and need for emergency decompression procedures between the gram-positive and gram-negative septicemia groups. In univariate analysis, previous gastrectomy history was associated with gram-positive bacteremia. Multivariate analysis also showed that previous gastrectomy history was strongly associated with gram-positive septicemia (Odds ratio = 5.47, 95% CI: 1.19-25.23; P = 0.029). CONCLUSIONS: Previous gastrectomy history was related to biliary septicemia induced by gram-positive organisms. This information would aid the choice of empirical antibiotics.

Prevalence, Etiology, and Outcome of Sepsis among Critically Ill Patients in Malawi.

There are scarce data describing the etiology and clinical sequelae of sepsis in low- and middle-income countries (LMICs). This study describes the prevalence and etiology of sepsis among critically ill patients at a referral hospital in Malawi. We conducted an observational prospective cohort study of adults admitted to the intensive care unit or high-dependency unit (HDU) from January 29, 2018 to March 15, 2018. We stratified the cohort based on the prevalence of sepsis as defined in the following three ways: quick sequential organ failure assessment (qSOFA) score ≥ 2, clinical suspicion of systemic infection, and qSOFA score ≥ 2 plus suspected systemic infection. We measured clinical characteristics and blood and urine cultures for all patients; antimicrobial sensitivities were assessed for positive cultures. During the study period, 103 patients were admitted and 76 patients were analyzed. The cohort comprised 39% male, and the median age was 30 (interquartile range: 23-40) years. Eighteen (24%), 50 (66%), and 12 patients (16%) had sepsis based on the three definitions, respectively. Four blood cultures (5%) were positive, two from patients with sepsis by all three definitions and two from patients with clinically suspected infection only. All blood bacterial isolates were multidrug resistant. Of five patients with urinary tract infection, three had sepsis secondary to multidrug-resistant bacteria. Hospital mortality for patients with sepsis based on the three definitions ranged from 42% to 75% versus 12% to 26% for non-septic patients. In summary, mortality associated with sepsis at this Malawi hospital is high. Bacteremia was infrequently detected, but isolated pathogens were multidrug resistant.

Daptomycin perioperative prophylaxis for the prevention of vancomycin-resistant Enterococcus infection in colonized liver transplant recipients.

BACKGROUND: Vancomycin-resistant Enterococcus (VRE)-colonized liver transplantation (LT) recipients have increased post-LT morbidity, mortality, and higher rates of VRE infections compared with their non-colonized counterparts. Pre-LT screening for VRE colonization and inclusion of daptomycin in the perioperative antibiotic prophylaxis regimen may mitigate this risk. METHODS: We performed a retrospective chart review of liver transplant recipients aged ≥ 18 years between 2013 and August 2019 to identify pre-LT VRE-colonized recipients and whether they received daptomycin perioperative prophylaxis (DPP). Demographic and clinical characteristics, including risk factors for VRE infection, were collected. Outcomes measured were VRE-related infection and all-cause mortality within 90 days of LT. RESULTS: Of the 27 VRE-colonized liver transplant recipients within the study period, 25 received DPP. All recipients were admitted to the intensive care unit postoperatively, six (24%) required reoperation, fifteen (60%) required renal replacement therapy, and eight (32%) experienced postoperative hemorrhage within 90 days post-transplant. Two recipients (8%) experienced acute cellular rejection, but no primary graft failure was seen within 90 days. Among those who received DPP, no infections related to VRE or death was seen within 90 days of LT. The two VRE-colonized recipients who did not receive DPP both developed VRE bacteremia in the early post-LT period. CONCLUSION: Despite having multiple risk factors for post-LT VRE infection, VRE-colonized recipients who received DPP did not develop VRE-related infections in the first 90 days post-LT. Our experience demonstrates that pre-LT VRE screening and DPP may be associated with a reduction in VRE infection in the early post-LT period, but this strategy warrants further evaluation in prospective studies.

Epidemiology, treatment and outcomes of bloodstream infection due to vancomycin-resistant enterococci in cancer patients in a vanB endemic setting.

BACKGROUND: Vancomycin-resistant enterococcus (VRE) is an important cause of infection in immunocompromised populations. Few studies have described the characteristics of vanB VRE infection. We sought to describe the epidemiology, treatment and outcomes of VRE bloodstream infections (BSI) in a vanB predominant setting in malignant hematology and oncology patients. METHODS: A retrospective review was performed at two large Australian centres and spanning a 6-year period (2008-2014). Evaluable outcomes were intensive care admission (ICU) within 48 h of BSI, all-cause mortality (7 and 30 days) and length of admission. RESULTS: Overall, 106 BSI episodes were observed in 96 patients, predominantly Enterococcus faecium vanB (105/106, 99%). Antibiotics were administered for a median of 17 days prior to BSI, and 76/96 (79%) were neutropenic at BSI onset. Of patients screened before BSI onset, 49/72 (68%) were found to be colonised. Treatment included teicoplanin (59), linezolid (6), daptomycin (2) and sequential/multiple agents (21). Mortality at 30-days was 31%. On multivariable analysis, teicoplanin was not associated with mortality at 30 days. CONCLUSIONS: VRE BSI in a vanB endemic setting occurred in the context of substantive prior antibiotic use and was associated with high 30-day mortality. Targeted screening identified 68% to be colonised prior to BSI. Teicoplanin therapy was not associated with poorer outcomes and warrants further study for vanB VRE BSI in cancer populations.

Epidemiology and microbiology of late-onset sepsis among preterm infants in China, 2015-2018: A cohort study.

OBJECTIVE: To describe the incidence, case-fatality rate and pathogen distribution of late-onset sepsis (LOS) among preterm infants in China. To investigate risk factors and short-term outcomes associated with LOS caused by Gram-positive bacteria, Gram-negative bacteria and fungi. METHODS: This cohort study included all infants born at <34 weeks' gestation and admitted to 25 tertiary hospitals in 19 provinces in China from May, 2015 to April, 2018. Infants were excluded who died or were discharged within 3 days of being born. RESULTS: A total of 1199 episodes of culture-positive LOS were identified in 1133 infants, with an incidence of 4.4% (1133/25,725). Overall, 15.4% (175/1133) of infants with LOS died and 10.0% (113/1133) of infants died within 7 days of LOS onset. Among 1214 isolated pathogens, Gram-negative bacteria were the most common (51.8%, 629/1214) and fungi accounted for 17.1% (207/1214). Use of central lines, longer duration of antibiotics and previous carbapenem exposure were related to increased risk of fungal LOS compared with Gram-positive bacteria. Gram-negative bacteria LOS was independently associated with increased risk of death, periventricular leukomalacia, bronchopulmonary dysplasia, and necrotizing enterocolitis. Fungal LOS was independently associated with increased risk of periventricular leukomalacia, bronchopulmonary dysplasia and necrotizing enterocolitis. CONCLUSIONS: Late-onset sepsis was a significant cause of morbidity and mortality in Chinese neonatal intensive care units, with a distinct pathogen distribution from industrial countries. Clinical guidelines on the prevention and treatment of LOS should be developed and tailored to these LOS characteristics in Chinese neonatal intensive care units.

Treatment and outcomes of Enterococcus faecium bloodstream infections in solid organ transplant recipients.

Optimal antimicrobial therapy for Enterococcus faecium bloodstream infection (EFBSI) in the solid organ transplant (SOT) population is not well defined. The purpose of this study was to describe the pharmacotherapy and outcomes of EFBSI in SOT patients. This was a single-center retrospective cohort of SOT patients with EFBSI from 2013 to 2019. Susceptibility testing was performed with Vitek® 2 or Etest. Estimates of optimal DAP pharmacokinetic/pharmacodynamic exposures (dose <10 mg/kg, fAUC/MIC >27.4) were made from previously established literature and equations. Fifty-one unique cases were included in the analysis. The median age was 61 years and liver (64%), intestinal (19%), and kidney (12%) were the most common organs transplanted. Most patients had indwelling central lines (75%) at the time of bacteremia; intra-abdominal abscesses/fluid collections were present in 44% of patients and 8% had endocarditis. Nineteen (37%) patients had polymicrobial infections. The most common definitive antimicrobial regimens were as follows: DAP plus beta-lactam (46%), DAP monotherapy (18%), and LZD (25%). Of the 33 patients that received DAP, 21% of E faecium isolates developed DAP resistance. 30-day mortality was 25% overall but higher in patients who received an initial DAP dose <10 mg/kg (43% vs 13%). Vancomycin-resistance, severity of illness, neutropenia, and source control were also associated with mortality. Inadequate DAP dosing for EFBSI may be associated with mortality in the SOT population. Larger, controlled analyses are necessary to determine the impact of optimized pharmacodynamics in this population.