Effect of biannual azithromycin distribution on antibody responses to malaria, bacterial, and protozoan pathogens in Niger.

The MORDOR trial in Niger, Malawi, and Tanzania found that biannual mass distribution of azithromycin to children younger than 5 years led to a 13.5% reduction in all-cause mortality (NCT02048007). To help elucidate the mechanism for mortality reduction, we report IgG responses to 11 malaria, bacterial, and protozoan pathogens using a multiplex bead assay in pre-specified substudy of 30 communities in the rural Niger placebo-controlled trial over a three-year period (n = 5642 blood specimens, n = 3814 children ages 1-59 months). Mass azithromycin reduces Campylobacter spp. force of infection by 29% (hazard ratio = 0.71, 95% CI: 0.56, 0.89; P = 0.004) but serological measures show no significant differences between groups for other pathogens against a backdrop of high transmission. Results align with a recent microbiome study in the communities. Given significant sequelae of Campylobacter infection among preschool aged children, our results support an important mechanism through which biannual mass distribution of azithromycin likely reduces mortality in Niger.

Outbreak of NDM-1-Producing Escherichia coli in a Coronavirus Disease 2019 Intensive Care Unit in a Mexican Tertiary Care Center.

Emergency department areas were repurposed as intensive care units (ICUs) for patients with acute respiratory distress syndrome during the initial months of the coronavirus disease 2019 (COVID-19) pandemic. We describe an outbreak of New Delhi metallo-ß-lactamase 1 (NDM-1)-producing Escherichia coli infections in critically ill COVID-19 patients admitted to one of the repurposed units. Seven patients developed infections (6 ventilator-associated pneumonia [VAP] and 1 urinary tract infection [UTI]) due to carbapenem-resistant E. coli, and only two survived. Five of the affected patients and four additional patients had rectal carriage of carbapenem-resistant E. coli. The E. coli strain from the affected patients corresponded to a single sequence type. Rectal screening identified isolates of two other sequence types bearing blaNDM-1. Isolates of all three sequence types harbored an IncFII plasmid. The plasmid was confirmed to carry blaNDM-1 through conjugation. An outbreak of clonal NDM-1-producing E. coli isolates and subsequent dissemination of NDM-1 through mobile elements to other E. coli strains occurred after hospital conversion during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. This emphasizes the need for infection control practices in surge scenarios. IMPORTANCE The SARS-CoV-2 pandemic has resulted in a surge of critically ill patients. Hospitals have had to adapt to the demand by repurposing areas as intensive care units. This has resulted in high workload and disruption of usual hospital workflows. Surge capacity guidelines and pandemic response plans do not contemplate how to limit collateral damage from issues like hospital-acquired infections. It is vital to ensure quality of care in surge scenarios.

Escherichia coli bloodstream infections in the western interior of British Columbia, Canada: a population-based cohort study.

Our population-based study objectives were to describe characteristics and outcomes of Escherichia coli bloodstream infections (BSIs), and to evaluate factors associated with outcomes. We included incident E. coli BSIs from western interior residents (British Columbia, Canada; 04/2010-03/2020). We obtained data including patient demographics, location of onset, infection focus, Charlson comorbidity index (CCI), antimicrobial resistance, 30-day all-cause mortality and length of hospital stay (LOS). Using multivariable logistic regression models fitted with generalised estimating equations, we estimated factors associated with 30-day mortality and long post-infection LOS (>75th percentile). We identified 1080 incident E. coli BSIs in 1009 patients. The crude incidence and 30-day mortality rates were 59.1 BSIs and 6.8 deaths/100 000 person-years, respectively. The 30-day case fatality risk was 11.5%. Compared to community-acquired E. coli BSIs, either healthcare-associated or nosocomial cases had higher odds of 30-day mortality. Older cases, non-urogenital BSI foci and CCI ⩾ 3 had higher odds of 30-day mortality compared to younger cases, urogenital foci and CCI < 3. In patients that survived to discharge, those with extended-spectrum ß-lactamase (ESBL)-producing E. coli BSIs, nosocomial BSIs, and CCI ⩾ 3 had higher odds of long post-infection LOS compared to those with non-ESBL-producing, community-acquired and healthcare-associated, and CCI < 3. There is a substantial disease burden from E. coli BSIs.

The Galleria mellonella-Enteropathogenic Escherichia coli Model System: Characterization of Pathogen Virulence and Insect Immune Responses.

The use of Galleria mellonella (Linnaeus) (Lepidoptera: Pyralidae), an economical insect model, for the study of enteropathogenic Escherichia coli (Migula) (EPEC), a diarrheagenic human pathogen, has been demonstrated previously but remains poorly understood. The present study characterizes the Galleria-EPEC system extensively for future studies using this system. We found that EPEC causes disease in G. mellonella larvae when injected intrahemocoelically but not orally. Disease manifests as increased mortality, decreased survival time, delayed pupation, decreased pupal mass, increased pupal duration, and hemocytopenia. Disease symptoms are dose-dependent and can be used as metrics for measuring EPEC virulence in future studies. The type III secretion system was only partially responsible for EPEC virulence in G. mellonella while the majority of the virulence remains unknown in origin. EPEC elicits insect anti-bacterial immune responses including melanization, hemolymph coagulation, nodulation, and phagocytosis. The immune responses were unable to control EPEC replication in the early stage of infection (≤3 h post-injection). EPEC clearance from the hemocoel does not guarantee insect survival. Overall, this study provided insights into EPEC virulence and pathogenesis in G. mellonella and identified areas of future research using this system.

Mortality in Escherichia coli bloodstream infections: a multinational population-based cohort study.

BACKGROUND: Escherichia coli is the most common cause of bloodstream infections (BSIs) and mortality is an important aspect of burden of disease. Using a multinational population-based cohort of E. coli BSIs, our objectives were to evaluate 30-day case fatality risk and mortality rate, and determine factors associated with each. METHODS: During 2014-2018, we identified 30-day deaths from all incident E. coli BSIs from surveillance nationally in Finland, and regionally in Sweden (Skaraborg) and Canada (Calgary, Sherbrooke, western interior). We used a multivariable logistic regression model to estimate factors associated with 30-day case fatality risk. The explanatory variables considered for inclusion were year (2014-2018), region (five areas), age (< 70-years-old, ≥70-years-old), sex (female, male), third-generation cephalosporin (3GC) resistance (susceptible, resistant), and location of onset (community-onset, hospital-onset). The European Union 28-country 2018 population was used to directly age and sex standardize mortality rates. We used a multivariable Poisson model to estimate factors associated with mortality rate, and year, region, age and sex were considered for inclusion. RESULTS: From 38.7 million person-years of surveillance, we identified 2961 30-day deaths in 30,923 incident E. coli BSIs. The overall 30-day case fatality risk was 9.6% (2961/30923). Calgary, Skaraborg, and western interior had significantly increased odds of 30-day mortality compared to Finland. Hospital-onset and 3GC-resistant E. coli BSIs had significantly increased odds of mortality compared to community-onset and 3GC-susceptible. The significant association between age and odds of mortality varied with sex, and contrasts were used to interpret this interaction relationship. The overall standardized 30-day mortality rate was 8.5 deaths/100,000 person-years. Sherbrooke had a significantly lower 30-day mortality rate compared to Finland. Patients that were either ≥70-years-old or male both experienced significantly higher mortality rates than those < 70-years-old or female. CONCLUSIONS: In our study populations, region, age, and sex were significantly associated with both 30-day case fatality risk and mortality rate. Additionally, 3GC resistance and location of onset were significantly associated with 30-day case fatality risk. Escherichia coli BSIs caused a considerable burden of disease from 30-day mortality. When analyzing population-based mortality data, it is important to explore mortality through two lenses, mortality rate and case fatality risk.

Potential interventions for an antimicrobial stewardship bundle for Escherichia coli bacteraemia.

INTRODUCTION: Escherichia coli is the most commonly identified bacteraemia, and causes a broad spectrum of diseases. The range of clinical conditions associated with E. coli bacteraemia mean that antimicrobial therapy is highly variable. This study aimed to determine the workload, efficiency and potential impact of an antimicrobial stewardship (AMS) bundle approach to E. coli bacteraemia. METHODS: An observational cohort study of patients with E. coli bacteraemia was performed, and a review of each case's entire medical record was undertaken. A number of AMS interventions were modelled on this cohort to assess their impact on overall days of antimicrobial therapy and time to optimized antimicrobial therapy. RESULTS: In total, 566 episodes of E. coli bacteraemia were identified. A number of AMS interventions were modelled to assess their impact. The strict implementation of guideline-based therapy was found to increase the number of patients receiving ineffective empirical therapy to 38/266 (14.3%) compared with 27/266 (10.2%) patients when w hen non-guideline-adherent therapy was allowed. A scheduled review by an AMS team on day 3 of empirical therapy could lead to a narrower-spectrum intravenous antibiotic in 237/515 (46%) cases, and 386 cases (68.2% of cohort) could have their duration of therapy reduced by a median of 7 days. CONCLUSION: This study provides detailed description of a large cohort of patients with E. coli bacteraemia. There remains significant variability in empirical treatment, choice of step-down therapy and antimicrobial duration. A significant opportunity exists for AMS programmes to impact the management of E. coli bacteraemia through a bundled approach.

High efficiency biosynthesis of O-polysaccharide-based vaccines against extraintestinal pathogenic Escherichia coli.

Extraintestinal pathogenic Escherichia coli (ExPEC) has presented a major clinical infection emerged in the past decades. O-polysaccharide (OPS)-based glycoconjugate vaccines produced using the bacterial glycosylation machinery can be utilized to confer protection against such infection. However, constructing a low-cost microbial cell factory for high-efficient production of OPS-based glycoconjugate vaccines remains challenging. Here, we engineered a glyco-optimized chassis strain by reprogramming metabolic network. The yield was enhanced to 38.6 mg L-1, the highest level reported so far. MS analysis showed that designed glycosylation sequon was modified by target polysaccharide with high glycosylation efficiency of 90.7 % and 76.7 % for CTB-O5 and CTB-O7, respectively. The glycoconjugate vaccines purified from this biosystem elicited a marked increase in protection against ExPEC infection in mouse model, compared to a non-optimized system. The glyco-optimized platform established here is broadly suitable for polysaccharide-based conjugate production against ExPEC and other surface-polysaccharide-producing pathogens.

Predicting Adverse Outcomes for Shiga Toxin-Producing Escherichia coli Infections in Emergency Departments.

OBJECTIVE: To assess the performance of a hemolytic uremic syndrome (HUS) severity score among children with Shiga toxin-producing Escherichia coli (STEC) infections and HUS by stratifying them according to their risk of adverse events. The score has not been previously evaluated in a North American acute care setting. STUDY DESIGN: We reviewed medical records of children <18 years old infected with STEC and treated in 1 of 38 participating emergency departments in North America between 2011 and 2015. The HUS severity score (hemoglobin [g/dL] plus 2-times serum creatinine [mg/dL]) was calculated using first available laboratory results. Children with scores >13 were designated as high-risk. We assessed score performance to predict severe adverse events (ie, dialysis, neurologic complication, respiratory failure, and death) using discrimination and net benefit (ie, threshold probability), with subgroup analyses by age and day-of-illness. RESULTS: A total of 167 children had HUS, of whom 92.8% (155/167) had relevant data to calculate the score; 60.6% (94/155) experienced a severe adverse event. Discrimination was acceptable overall (area under the curve 0.71, 95% CI 0.63-0.79) and better among children <5 years old (area under the curve 0.77, 95% CI 0.68-0.87). For children <5 years, greatest net benefit was achieved for a threshold probability >26%. CONCLUSIONS: The HUS severity score was able to discriminate between high- and low-risk children <5 years old with STEC-associated HUS at a statistically acceptable level; however, it did not appear to provide clinical benefit at a meaningful risk threshold.

Efficacy of loading dose colistin versus carbapenems for treatment of extended spectrum beta lactamase producing Enterobacteriaceae.

Colistin provides in vitro activity against numerous ESBL-producing and carbapenem-resistant bacteria. However, clinical information with respect to its utilization in infection caused by ESBL producers is limited. The aim of this study was a comparison of mortality rates of loading dose (LD) colistin and carbapenems as definitive therapies in a cohort of patients with infections caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae. A retrospective cohort study in 396 patients with ESBL-producing E.coli and K.pneumoniae infection at a university-affiliated hospital was conducted between 1 January 2005 and 30 June 2015 to compare outcomes of infected patients who received LD colistin (95 patients) with carbapenems (301 patients). The three primary outcomes were 30-day mortality, clinical response and microbiological response. The most common infection types were urinary tract infection (49.49%), followed by pneumonia (40.66%), bacteremia (13.64%), skin and soft tissue infections (4.80%) and intra-abdominal infection (3.03%). LD colistin group provided higher 30-day mortality when compared with carbapenems group (HR 7.97; 95% CI 3.68 to 17.25; P = 0.001). LD colistin was also independently associated with clinical failure (HR 4.30; 95% CI 1.93 to 9.57; P = 0.001) and bacteriological failure (HR 9.49; 95% CI 3.76 to 23.96; P = 0.001) when compared with those who received carbapenems. LD colistin treatment was associated with poorer outcomes, i.e. mortality rate, clinical response and microbiological response. Moreover, when adjusted confounding factors, LD colistin was still less effective than carbapenems. It should be noted that, however, the use of Vitek-2 to assess colistin susceptibility could provide inaccurate results. Also, the difference in baseline characteristics could still remain in retrospective study although compensation by hazard ratio adjustment was performed. Therefore, clinical utilization of LD colistin should be recommended as an alternative for treatment ESBL-producing Enterobacteriaceae only in the circumstances where carbapenems cannot be utilized, but this recommendation must be considered carefully.

Epidemiology, Risk Factors, and Clinical Outcomes of Bloodstream Infection due to Extended-Spectrum Beta-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae in Hematologic Malignancy: A Retrospective Study from Central South China.

Objective: To determine the epidemiology, risk factors, and prognosis of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae bloodstream infections (BSIs) among hematology malignancy (HM) patients in China. Method: From January 2010 to June 2018, we retrospectively collected and analyzed the 449 HM patients with E. coli or K. pneumoniae BSIs from three leading hospitals in Hunan Province, China. Results: Two hundred four (45.4%) patients harbored ESBL-producing bacteremia. The proportion of ESBL-producing bacteremia increased significantly with the growth of the year, with a ratio of 34.47% in 2010-2014 to 54.7% in 2015-2018. Comparing with non-ESBL groups in HM patients, central venous catheter (odds ratio [OR] 1.717, p = 0.009), previous antibiotic exposure (OR 1.559, p = 0.035), and E. coli (OR 2.561, p ≤ 0.001) among ESBL groups were independent risk factors. No significant differences in 30-day mortality were tested in patients with BSI caused by ESBL-producing or non-ESBL-producing E. coli and K. pneumoniae (17.1% vs. 16.7%; p = 0. 893). The proportion of carbapenem used within 72 hours after the onset of bacteremia in two groups was high, which was routinely used as "last-resort drugs" in Gram-negative bacterial infections. Risk factors associated with 30-day mortality in HM patients with E. coli or K. pneumoniae bacteremia were myelodysplastic syndrome, incomplete remission of the disease, Multinational Association of Supportive Care in Cancer score <21, Pitt bacteremia score ≥4, Charlson comorbidity score >3, catheter insertion, use of vasopressors, and inappropriate antibiotics within 72 hours of BSI onset. Conclusions: The results of this study may provide some references for the whole process management of HM patients with BSIs.

Prognosis of Patients with Sepsis and Non-Hepatic Hyperammonemia: A Cohort Study.

BACKGROUND Hyperammonemia has been reported in some critically ill patients with sepsis who do not have hepatic failure. A significant proportion of patients with non-hepatic hyperammonemia have underlying sepsis, but the association between non-hepatic hyperammonemia and prognosis is unclear. MATERIAL AND METHODS Information about patients with sepsis and non-hepatic hyperammonemia was retrieved from the Medical Information Mart for Intensive Care-III database. Survival rates were analyzed using the Kaplan-Meier method. Multivariate logistic regression models were employed to identify prognostic factors. Receiver operating characteristic (ROC) curve analysis was used to measure the predictive ability of ammonia in terms of patient mortality. RESULTS A total of 265 patients with sepsis were enrolled in this study. Compared with the non-hyperammonemia group, the patients with hyperammonemia had significantly higher rates of hospital (59.8% vs. 43.0%, P=0.007), 30-day (47.7% vs. 34.8%, P=0.036), 90-day (61.7% vs. 43.7%, P=0.004), and 1-year mortality (67.3% vs. 49.4%, P=0.004). In the survival analysis, hyperammonemia was associated with these outcomes. Serum ammonia level was an independent predictor of hospital mortality. The area under the ROC curve for the ammonia levels had poor discriminative capacity. The hyperammonemia group also had significantly lower Glasgow Coma Scale scores (P=0.020) and higher incidences of delirium (15.9% vs. 8.2%, P=0.034) and encephalopathy (37.4% vs. 19.6%, P=0.001). Intestinal infection and urinary tract infection with organisms such as Escherichia coli may be risk factors for hyperammonemia in patients who have sepsis. CONCLUSIONS Higher ammonia levels are associated with poorer prognosis in patients with sepsis. Ammonia also may be associated with sepsis-associated encephalopathy. Therefore, we recommend that serum ammonia levels be measured in patients who are suspected of having sepsis.

Evaluation of the health and healthcare system burden due to antimicrobial-resistant Escherichia coli infections in humans: a systematic review and meta-analysis.

BACKGROUND: Assessment of the burden of disease due to antimicrobial-resistant Escherichia coli infections facilitates understanding the scale of the problem and potential impacts, and comparison to other diseases, which allows prioritization of research, surveillance, and funding. Using systematic review and meta-analysis methodology, the objectives were to evaluate whether humans with antimicrobial-resistant E. coli infections experience increases in measures of health or healthcare system burden when compared to susceptible E. coli infections. METHODS: Comprehensive literature searches were performed in four primary and seven grey literature databases. Analytic observational studies of human E. coli infections that assessed the impact of resistance to third/fourth/fifth-generation cephalosporins, resistance to quinolones, and/or multidrug resistance on mortality, treatment failure, length of hospital stay and/or healthcare costs were included. Two researchers independently performed screening, data extraction, and risk of bias assessment. When possible, random effect meta-analyses followed by assessment of the confidence in the cumulative evidence were performed for mortality and length of hospital stay outcomes, and narrative syntheses were performed for treatment failure and healthcare costs. RESULTS: Literature searches identified 14,759 de-duplicated records and 76 articles were included. Based on 30-day and all-cause mortality meta-analyses, regardless of the type of resistance, there was a significant increase in the odds of dying with resistant E. coli infections compared to susceptible infections. A summary mean difference was not presented for total length of hospital stay meta-analyses due to substantial to considerable heterogeneity. Since small numbers of studies contributed to meta-analyses for bacterium-attributable mortality and post-infection length of hospital stay, the summary results should be considered with caution. Studies contributing results for treatment failure and healthcare costs had considerable variability in definitions and reporting. CONCLUSIONS: Overall, resistant E. coli infections were associated with significant 30-day and all-cause mortality burden. More research and/or improved reporting are necessary to facilitate quantitative syntheses of bacterium-attributable mortality, length of hospital stay, and hospital costs. Protocol Registration PROSPERO CRD42018111197.

Factors associated with typical enteropathogenic Escherichia coli infection among children <5 years old with moderate-to-severe diarrhoea in rural western Kenya, 2008-2012.

Typical enteropathogenic Escherichia coli (tEPEC) infection is a major cause of diarrhoea and contributor to mortality in children <5 years old in developing countries. Data were analysed from the Global Enteric Multicenter Study examining children <5 years old seeking care for moderate-to-severe diarrhoea (MSD) in Kenya. Stool specimens were tested for enteric pathogens, including by multiplex polymerase chain reaction for gene targets of tEPEC. Demographic, clinical and anthropometric data were collected at enrolment and ~60-days later; multivariable logistic regressions were constructed. Of 1778 MSD cases enrolled from 2008 to 2012, 135 (7.6%) children tested positive for tEPEC. In a case-to-case comparison among MSD cases, tEPEC was independently associated with presentation at enrolment with a loss of skin turgor (adjusted odds ratio (aOR) 2.08, 95% confidence interval (CI) 1.37-3.17), and convulsions (aOR 2.83, 95% CI 1.12-7.14). At follow-up, infants with tEPEC compared to those without were associated with being underweight (OR 2.2, 95% CI 1.3-3.6) and wasted (OR 2.5, 95% CI 1.3-4.6). Among MSD cases, tEPEC was associated with mortality (aOR 2.85, 95% CI 1.47-5.55). This study suggests that tEPEC contributes to morbidity and mortality in children. Interventions aimed at defining and reducing the burden of tEPEC and its sequelae should be urgently investigated, prioritised and implemented.

Clinical and Microbiological Analysis of Risk Factors for Mortality in Patients with Carbapenem-Resistant Enterobacteriaceae Bacteremia.

OBJECTIVES: The aims of this study were to identify whether the site of acquisition or the underlying carbapenem-resistant Enterobacteriaceae (CRE) resistance mechanism was associated with clinical outcomes, and to evaluate risk factors for 14-day mortality in patients with CRE bacteremia. MATERIALS AND METHODS: A retrospective cohort study was conducted at a 2700-bed tertiary center. All adult patients with monomicrobial carbapenem-resistant Escherichia coli or Klebsiella pneumoniae bacteremia from 2011 to 2018 were included. All blood isolates collected were tested with a modified carbapenem inactivation method for phenotypic detection of carbapenemase. RESULTS: Of 133 patients with monomicrobial CRE bacteremia, 63 (47.4%) were infected with carbapenemase-producing CRE (CP-CRE), and 70 (52.6%) with non-CP-CRE. Patients with community-onset infection (COI) were more likely to present with biliary or urinary tract infections, less likely to have ineradicable or non-eradicated foci and to receive appropriate empirical therapy, and marginally more likely to have CP-CRE compared with those with hospital-acquired infection (HAI). However, 14-day mortality was significantly lower in COI than HAI (7% vs 29%, P = 0.01). Patients who died were more likely to have had a higher APACHE II score, ineradicable or non-eradicated foci, and a lower chance of having received appropriate antibiotic treatment. Multivariate analysis revealed that HAI, high APACHE II score, and inappropriate antibiotic treatment were independent risk factors for mortality. Carbapenemase production did not affect mortality. CONCLUSIONS: The results of this study indicate that timely, appropriate treatment is essential for managing CRE bacteremia, regardless of carbapenemase production, particularly in critically ill patients with hospital-acquired bacteremia.

Does inappropriate initial antibiotic therapy affect in-hospital mortality of patients in the emergency department with Escherichia coli and Klebsiella pneumoniae bloodstream infections?

Extended-spectrum ß-lactamase (ESBL)-positive bloodstream infection (BSI) is on the rise worldwide. The purpose of this study is to evaluate the impact of inappropriate initial antibiotic therapy (IIAT) on in-hospital mortality of patients in the emergency department (ED) with Escherichia coli and Klebsiella pneumoniae BSIs. This retrospective single-center cohort study included all adult patients with E. coli and K. pneumoniae BSIs between January 2007 and December 2013, who had undergone a blood culture test and initiation of antibiotics within 6 h of ED registration time. Multiple logistic regression was used to adjust for bacterial species, IIAT, time to antibiotics, age, sex, quick Sepsis Related Organ Failure Assessment (qSOFA) score ⩾ 2, and comorbidities. A total of 3533 patients were enrolled (2967 alive and 566 deceased, in-hospital mortality rate 16%). The patients with K. pneumoniae ESBL-positive BSI had the highest mortality rate. Non-survivors had qSOFA scores ⩾ 2 (33.6% vs 9.5%, P < 0.001), more IIAT (15.0% vs 10.7%, P = 0.004), but shorter mean time to antibiotics (1.70 vs 1.84 h, P < 0.001). A qSOFA score ⩾ 2 is the most significant predictor for in-hospital mortality; however, IIAT and time to antibiotics were not significant predictors in multiple logistic regression analysis. In subgroup analysis divided by qSOFA scores, IIAT was still not a significant predictor. Severity of the disease (qSOFA score ⩾ 2) is the key factor influencing in-hospital mortality of patients with E. coli and K. pneumoniae BSIs. The time to antibiotics and IIAT were not significant predictors because they in turn were affected by disease severity.

Weissella confusa DD_A7 pre-treatment to zebrafish larvae ameliorates the inflammation response against Escherichia coli O157:H7.

Increasing multidrug-resistant pathogenic bacterial contamination in the environment has become the leading cause of food poisoning, resulting in life-threatening conditions due to late detection and limited therapeutic options. Escherichia coli O157:H7 is one such pathogen which is severely affecting the environmental livestock and ultimately leads to human infection. In this context, probiotics could be a useful strategy to minimize the growth of pathogens, as they produce several antimicrobial compounds and shows an exclusive competitive behavior against the pathogens. Therefore, supplementation of probiotics is wieldy accepted in the field of agriculture for the maintenance of animal's health. Previously, we reported that W. confusa DD_A7 possesses anti-bacterial and immune-stimulatory activity in-vitro. Therefore, in the present study, we investigated the impact of oral-administration of DD_A7 powder against E. coli O157:H7. The 6 days post-fertilized zebrafish larvae were used to evaluate the pathogenicity of the microbe. 1 × 108 CFU/ml of E. coli O157:H7 effectively induced the inflammatory response in zebrafish larvae. Where 1 × 108 CFU/ml DD_A7 pre-treatment prolonged the survivability of zebrafish larvae and improved the immune response of zebrafish larvae against pathogenic infection. The antibacterial property of DD_A7 against the pathogen correlated with the significant reduction of oxidative stress and host inflammatory response, by inhibiting NF-κB and its downstream signaling pathway. The findings demonstrated the prophylactic activity of DD_A7 suggesting that its supplementation improved the host defense mechanism by reducing oxidative stress. The growth of pathogen was effectively suppressed in the DD_A7 pre-treated larvae and maintained a healthy gastrointestinal environment in the zebrafish model.

Necrotizing fasciitis in haematological patients: a different scenario.

To describe and compare the characteristics of necrotizing fasciitis (NF) in patients with and without haematological malignancy. All adult patients diagnosed with NF and treated at our hospital were included (January 2010-March 2019). Diagnosis was based on intraoperative findings or consistent clinical/radiological characteristics, and patients were classified as group A (with haematological malignancy) or group B (without haematological malignancy). Student's t (quantitative), Fisher's exact (qualitative), and Kaplan-Meyer tests were used for the statistical analysis. The study included 29 patients: 8 in group A and 21 in group B. All haematological patients had severe neutropenia (0.2 [0.02-0.5] ×109 cells/L; p < 0.001) and positive blood cultures (100% vs. 61.9%; p = 0.04) at diagnosis. Gram-negative bacilli NF was more common in group A (87.5% vs. 9.5%; p = 0.001), predominantly due to Escherichia coli (50% vs. 9.5%; p = 0.056). Surgical treatment was less common in haematological patients (5 [62.5%] vs. 21 [100%]; p = 0.015). Overall, 9 (31%) patients died: 4 (50%) in group A and 5 (23.8%) in group B (p = 0.17). The univariate analysis showed that mortality tended to be higher (OR 3.2; 95%CI 0.57-17.7; p = 0.17) and to occur earlier (2.2 ± 2.6 vs. 14.2 ± 19.9 days; p = 0.13) in haematological patients. The LRINEC index > 6 did not predict mortality in either group. In our study, NF in patients with haematological malignancies was mainly due to Gram-negative bacilli, associated to high and early mortality rates. In our experience, the LRINEC scale was not useful for predicting mortality.

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.

A retrospective study on Escherichia coli bacteremia in immunocompromised patients: Microbiological features, clinical characteristics, and risk factors for shock and death.

BACKGROUND: To evaluate clinical features, bacterial characteristics, and risk factors for shock and mortality of immunocompromised patients with Escherichia coli bacteremia. METHODS: A nearly 6-year retrospective study of E coli bacteremia in 188 immunocompromised patients at Xiangya Hospital was conducted. Demographic, clinical, and laboratory data were documented. Phylogenetic background and virulence factors of E coli isolates were detected by polymerase chain reaction. Risk factors for shock and mortality were also investigated. RESULTS: Of all 188 E coli isolates, most prevalent virulence factors were fimH (91.0%), followed by traT (68.6%) and iutA (67.0%), while papG allele I, gafD, and cdtB were not detected. Phylogenetic group D was dominant (42.0%) among all isolates, and group B2 accounted for 17.6%, while group A and B1 accounted for 28.2% and 12.2%, respectively. In univariate analysis, ibeA and cnf1 were associated with mortality, which were not found in multivariate regression analysis. 22.3% of patients suffered shock, and 30-day mortality rate was 21.3%. MDR (HR 2.956; 95% CI, 1.091-8.012) was the only risk factor for shock, while adult (HR 0.239; 95% CI, 0.108-0.527) was a protective factor. Multivariate analysis revealed that shock (HR 4.268; 95% CI, 2.208-8.248; P < .001) and Charlson index > 2 (HR 2.073; 95% CI, 1.087-3.952; P = .027) were associated with fatal outcome. CONCLUSIONS: Escherichia coli bacteremia was highly lethal in immunocompromised patients, and host-related factors played major roles in poor prognosis, while bacterial determinants had little effect on outcome. This study also provided additional information about the virulence and phylogenetic group characteristics of E coli bacteremia.