Epidemiology, Resistance Profiles, and Outcomes of Bloodstream Infections in Community-Onset Sepsis in the United States.

OBJECTIVES: To describe frequency of positive blood cultures, patterns of pathogens' characteristics and their resistance profile in patients with blood cultures drawn due to a presumed diagnosis of community-onset sepsis, and to examine the association between blood culture-positive pathogens and hospital mortality. DESIGN: Retrospective cohort study. SETTING: Two hundred one U.S. hospitals from 2016 to 2020 using the Premier Healthcare Database. SUBJECTS: Adult patients presenting with community-onset sepsis who had blood cultures collected within 2 days of hospital admission. We defined sepsis using the U.S. Centers for Disease Control Adult Sepsis Event Surveillance criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified 147,061 patients with community-onset sepsis. The number of blood culture-positive sepsis episodes was 21,167 (14%) and the number of nonblood culture-positive sepsis episodes was 20,326 (14%). Among patients with blood culture-positive sepsis, Gram-negative rods were isolated in 55% of patients, Gram-positive cocci were isolated in 47%. Of those, methicillin-resistant Staphylococcus aureus (MRSA) was 11%, ceftriaxone-resistant Enterobacterales /extended-spectrum ß-lactamase was 7%, and carbapenem-resistant Enterobacterales was 1.3%. The crude in-hospital mortality was 17% for culture-negative sepsis, 13% for nonblood culture-positive sepsis, and 17% for blood culture-positive sepsis. In multilevel logistic regression models, compared with culture-negative sepsis, blood culture-positive sepsis (adjusted odds ratio [aOR], 0.89; 95% CI, 0.85-0.94) and nonblood culture-positive sepsis (aOR, 0.82; 95% CI, 0.78-0.87) were associated with lower odds of in-hospital mortality. Acinetobacter species, Pseudomonas aeruginosa , methicillin-sensitive Staphylococcus aureus , and MRSA were associated with higher in-hospital mortality, whereas Escherichia coli , Klebsiella species, Proteus species, and Streptococcus species were associated with lower in-hospital mortality. CONCLUSIONS: In patients hospitalized with community-onset sepsis, the prevalence of blood culture-positive sepsis was 14%. Among positive blood culture sepsis resistant organisms were infrequent. Compared with culture-negative sepsis, blood culture-positive sepsis and nonblood culture-positive sepsis were associated with lower in-hospital mortality.

Antibiotic stewardship program (ASP) in palliative care: antibiotics, to give or not to give.

Antimicrobial therapy in terminally ill patients remains controversial as goals of care tend to be focused on optimizing comfort. International guidelines recommend for antibiotic stewardship program (ASP) involvement in antibiotic decisions in palliative patients. The primary objective was to evaluate the clinical impact of ASP interventions made to stop broad-spectrum intravenous antibiotics in terminally ill patients. This was a retrospective chart review of 459 terminally ill patients in Singapore General Hospital audited by ASP between December 2010 and December 2018. Antibiotic duration, time-to-terminal discharge for end-of-life care, time-to-mortality, and mortality rates of patients with antibiotics ceased or continued upon ASP recommendations were compared. A total of 283 and 176 antibiotic courses were ceased and continued post-intervention, respectively. The intervention acceptance rate was 61.7%. The 7-day mortality rate (47.3% vs 61.9%, p = 0.003) was lower in the ceased group, while 30-day mortality rate (76.0% vs 81.2%, p = 0.203) and time-to-mortality post-intervention (3 [0-24] vs 2 [0-27] days, p = 0.066) did not differ between the ceased and continued groups. After excluding the 57 patients who had antibiotics continued until death within 48 h of intervention, only time-to-mortality post-intervention was statistically significantly shorter in the ceased group (3 [0-24] vs 4 [0-27], p < 0.001). Of the 131 terminally discharged patients, antibiotic duration (4 [0-17] vs 6.5 [1-14] days, p = 0.001) and time-to-terminal discharge post-intervention (6 [0-74] vs 10.5 [3-63] days, p = 0.001) were shorter in the ceased group. Antibiotic cessation in terminally ill patients was safe, and was associated with a significantly shorter time-to-terminal discharge.

Risk factors for the emergence of multidrug-resistant organisms in liver cirrhosis.

BACKGROUND: Multidrug-resistant organisms (MDROs) are a reality that can alter the paradigm of treatment and prevention of infection in patients with liver cirrhosis (LC). OBJECTIVE: Identify risk factors for the occurrence of MDROs in patients with LC. PATIENTS AND METHODS: Prospective study from October 2017 to March 2018 in consecutively hospitalized patients with decompensated LC with infection. Blood, urine and ascitic fluid cultures were analyzed. A p-value ≤0.05 was considered statistically significant. RESULTS: MDROs isolated in 18 of 52 episodes of infection. MDROs were associated with the use of proton pump inhibitors (PPIs) (p=0.0312), antibiotic therapy in the last 90 days (p=0.0033) and discharge within preceding 30 days or current hospitalization above 48h (p=0.0082). There was higher 90-day mortality in patients with MDROs infection (71.4% versus 35.7%, p=0.0316). CONCLUSION: MDROs infections were prevalent in this cohort and associated with 90-day mortality. Use of PPIs and antibiotics increased the risk of MDROs infections, suggesting that its prescription should be restricted to formal indication. Hospitalization was associated with the onset of MDROs, so LC patients should stay at the hospital the least possible. It is relevant to investigate other factors predisposing to the emergence of these microorganisms, in order to prevent it.

Single Dose of Oral Azithromycin With or Without Amoxicillin to Prevent Peripartum Infection in Laboring, High-Risk Women in Cameroon: A Randomized Controlled Trial.

OBJECTIVE: To compare the effectiveness of single-dose azithromycin, with or without amoxicillin, with placebo to prevent peripartum infection in laboring women. METHODS: We conducted a multicenter, three-group, double-blind randomized controlled trial of women with viable term nonanomalous pregnancies with either prolonged labor of 18 hours or longer or rupture of membranes for 8 hours or longer in Cameroon. Women with chorioamnionitis before randomization, study drug contraindications, or planned cesarean births were excluded. Women were randomized to oral azithromycin 1 g-placebo (group 1), oral azithromycin 1 g-oral amoxicillin 2 g (group 2), or placebo-placebo (group 3). All groups received usual care, including antibiotics given at the health care professional's discretion. The primary outcome was a composite of maternal peripartum infection or death from any cause up to 6 weeks postpartum. Two primary comparisons (group 1 vs group 3 and group 2 vs group 3) were planned. We estimated that 241 women per group (planning for 750 total) would provide 80% power at two-sided α=0.05 (0.025 per comparison) to detect a 50% effect size assuming 20% baseline composite infection rate. RESULTS: From January 6, 2018, to May 15, 2020, 6,531 women were screened, and 756 (253 in group 1, 253 in group 2, and 250 in group 3) were randomized. Baseline characteristics (including body mass index, duration of rupture of membranes or labor, and parity) were balanced across groups, except for maternal age. More than 60% of women in each group received usual-care antibiotics: more than 90% penicillin and approximately 50% for prolonged rupture of membranes across all study groups. Composite outcome incidences were similar in antibiotic groups 1 (6%) and 2 (7%) compared with placebo group 3 (10%) (RR 0.6, 95% CI 0.3-1.2; 0.7, 95% CI 0.4-1.3, respectively). Chorioamnionitis and wound infection were significantly lower in group 2 (3.2% vs 0.4% and 4% vs 0.8% respectively, both P=.02) compared with group 3. There were no differences in other maternal or neonatal outcomes including neonatal infection. CONCLUSION: A single dose of oral azithromycin with or without amoxicillin for prolonged labor or rupture of membranes at term did not reduce maternal peripartum or neonatal infection. Observed lower than expected infection rates and frequent usual-care antibiotic use may have contributed to these findings. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03248297. FUNDING SOURCE: Merck for Mothers Investigator Studies Program grant.

Probiotic-mediated p38 MAPK immune signaling prolongs the survival of Caenorhabditis elegans exposed to pathogenic bacteria.

The host-microbiota cross-talk represents an important factor contributing to innate immune response and host resistance during infection. It has been shown that probiotic lactobacilli exhibit the ability to modulate innate immunity and enhance pathogen elimination. Here we showed that heat-inactivated probiotic strain Lactobacillus curvatus BGMK2-41 stimulates immune response and resistance of the Caenorhabditis elegans against Staphylococcus aureus and Pseudomonas aeruginosa. By employing qRT-PCR and western blot analysis we showed that heat-inactivated BGMK2-41 activated PMK-1/p38 MAPK immunity pathway which prolongs the survival of C. elegans exposed to pathogenic bacteria in nematode killing assays. The C. elegans pmk-1 mutant was used to demonstrate a mechanistic basis for the antimicrobial potential of BGMK2-41, showing that BGMK2-41 upregulated PMK-1/p38 MAPK dependent transcription of C-type lectins, lysozymes and tight junction protein CLC-1. Overall, this study suggests that PMK-1/p38 MAPK-dependent immune regulation by BGMK2-41 is essential for probiotic-mediated C. elegans protection against gram-positive and gram-negative bacteria and could be further explored for development of probiotics with the potential to increase resistance of the host towards pathogens.

Identifying early indicators of secondary peritonitis in critically ill patients with cirrhosis.

Ascitic fluid infection (AFI) is a life-threatening complication of cirrhosis. We aimed to identify early indicators of secondary peritonitis (SP), which requires emergency surgery, and to describe the outcomes of SP and spontaneous bacterial/fungal peritonitis (SBFP). Adults with cirrhosis and AFI admitted to 16 university or university-affiliated ICUs in France between 2002 and 2017 were studied retrospectively. Cases were identified by searching the hospital databases for relevant ICD-10 codes and hospital charts for AFI. Logistic multivariate regression was performed to identify factors associated with SP. Secondary outcomes were short- and long-term mortality and survivors' functional outcomes. Of 178 included patients (137 men and 41 women; mean age, 58 ± 11 years), 21 (11.8%) had SP, confirmed by surgery in 16 cases and by abdominal computed tomography in 5 cases. Time to diagnosis exceeded 24 h in 7/21 patients with SP. By multivariate analysis, factors independently associated with SP were ascitic leukocyte count > 10,000/mm3 (OR 3.70; 95%CI 1.38-9.85; P = 0.009) and absence of laboratory signs of decompensated cirrhosis (OR 4.53; 95%CI 1.30-15.68; P = 0.017). The 1-year mortality rates in patients with SBFP and SP were 81.0% and 77.5%, respectively (Log-rank test, P = 0.92). Patients with SP vs. SBFP had no differences in 1-year functional outcomes. This multicenter retrospective study identified two indicators of SP as opposed to SBFP in patients with cirrhosis. Using these indicators may help to provide early surgical treatment.

Identifying Risk Factors for Secondary Infection Post-SARS-CoV-2 Infection in Patients With Severe and Critical COVID-19.

Emerging evidence has unveiled the secondary infection as one of the mortal causes of post-SARS-CoV-2 infection, but the factors related to secondary bacterial or fungi infection remains largely unexplored. We here systematically investigated the factors that might contribute to secondary infection. By clinical examination index analysis of patients, combined with the integrative analysis with RNA-seq analysis in the peripheral blood mononuclear cell isolated shortly from initial infection, this study showed that the antibiotic catabolic process and myeloid cell homeostasis were activated while the T-cell response were relatively repressed in those with the risk of secondary infection. Further monitoring analysis of immune cell and liver injury analysis showed that the risk of secondary infection was accompanied by severe lymphocytopenia at the intermediate and late stages and liver injury at the early stages of SARS-CoV-2. Moreover, the metagenomics analysis of bronchoalveolar lavage fluid and the microbial culture analysis, to some extent, showed that the severe pneumonia-related bacteria have already existed in the initial infection.

Mitigating multiple stresses in Pangasianodon hypophthalmus with a novel dietary mixture of selenium nanoparticles and Omega-3-fatty acid.

Effects of a novel dietary mixture of selenium nanoparticles (Se-NPs) and omega-3-fatty acids i.e., Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on mitigating arsenic pollution, high-temperature stress and bacterial infection were investigated in Pangasianodon hypophthalmus. To aim this, four isocaloric and iso-nitrogenous diets were prepared: control feed (no supplementation), Se-NPs at 0.2 mg kg-1 diet with EPA + DHA at 0.2, 0.4 and 0.6% as supplemented diets. Fish were reared under normal condition or concurrent exposure to arsenic (2.65 mg L-1), and temperature (34 °C) (As + T) stress for 105 days. The experiment was conducted with eight treatments in triplicates. Response to various stresses i.e., primary (cortisol), secondary (oxidative stress, immunity, and stress biomarkers) and tertiary stress response (growth performance, bioaccumulation and mortality due to bacterial infection) were determined. Supplementation of dietary Se-NPs at 0.2 mg kg-1 diet and EPA + DHA at 0.2 and 0.4% reduced the primary stress level. Exposure to arsenic and temperature (As + T) and fed with control diet and EPA + DHA at 0.6% aggravated the cortisol level. Anti-oxidative enzymes (Catalase, superoxide dismutase, glutathione peroxidase and glutathione-s-transferase) and immunity (Nitroblue tetrazolium, total protein, albumin, globulin, A:G ratio, total immunoglobulin and myeloperoxidase) of the fish were augmented by supplementation of Se-NPs and EPA + DHA at 0.2 and 0.4%. Neurotransmitter enzyme, HSP 70, Vitamin C were significantly enhanced (p < 0.01) with supplementation of Se-NPs at 0.2 mg kg-1 and EPA + DHA at 0.2 and 0.4%. Whereas total lipid, cholesterol, phospholipid, triglyceride and very low-density lipoprotein (VLDL) were reduced (p < 0.01) with the supplementation of Se-NPs at 0.2 mg kg-1 diet and EPA + DHA at 0.2 and 0.4%. Tertiary stress response viz. growth performance was also significantly enhanced with supplementation of Se-NPs at 0.2 mg kg-1 and EPA + DHA at 0.2 and 0.4% reared under As + T. Whereas arsenic bioaccumulation in fish tissues was significantly reduced with dietary supplementation of Se-NPs and EPA + DHA. Cumulative mortality and relative percentage survival were reduced with Se-NPs at 0.2 mg kg-1 and EPA + DHA at 0.2 and 0.4%. The investigation revealed that a novel combination of Se-NPs at 0.2 mg kg-1 and EPA + DHA at 0.4% followed by 0.2% has the potential to alleviate temperature stress, bacterial infection and arsenic pollution. Whereas diet containing Se-NPs at 0.2 mg kg-1 diet and EPA + DHA at 0.6% was noticeably enhanced the stress in P. hypophthalmus.

Hepatic FGF21 preserves thermoregulation and cardiovascular function during bacterial inflammation.

Sickness behaviors, including anorexia, are evolutionarily conserved responses to acute infections. Inflammation-induced anorexia causes dramatic metabolic changes, of which components critical to survival are unique depending on the type of inflammation. Glucose supplementation during the anorectic period induced by bacterial inflammation suppresses adaptive fasting metabolic pathways, including fibroblast growth factor 21 (FGF21), and decreases survival. Consistent with this observation, FGF21-deficient mice are more susceptible to mortality from endotoxemia and polybacterial peritonitis. Here, we report that increased circulating FGF21 during bacterial inflammation is hepatic derived and required for survival through the maintenance of thermogenesis, energy expenditure, and cardiac function. FGF21 signaling downstream of its obligate coreceptor, ß-Klotho (KLB), is required in bacterial sepsis. However, FGF21 modulates thermogenesis and chronotropy independent of the adipose, forebrain, and hypothalamus, which are operative in cold adaptation, suggesting that in bacterial inflammation, either FGF21 signals through a novel, undescribed target tissue or concurrent signaling of multiple KLB-expressing tissues is required.

Role of Bacterial Infection in the Development of Acute Liver Failure in Patients with Decompensated Alcoholic Liver Cirrhosis.

We examined 74 patients with acute decompensation of alcoholic liver cirrhosis: 34 (45.9%) with bacterial infection (group 1) and 40 (54.1%) without bacterial infection (group 2). The degree and index of acute-on-chronic liver failure (ACLF) were determined using an on-line CLIF-C ACLF Calculator and the levels of cytokeratin-18 fragments, TNFα, IL-1ß, IL-4, IL-6, and IL-8. In group 1, AST, cytokeratin-18, TNFα, IL-1ß, IL-6, degree and score of ACLF were significantly higher than in group 2. ACLF developed in 18 (52.9%) patients in group 1 and in 11 (27.5%) (p<0.05) patients in group 2. Within 1 month, 10 (29.4%) patients of group 1 and 2 (5%) patients of group 2 died (p<0.05). Patients with bacterial infection showed a more severe course of alcoholic liver cirrhosis and ACLF than those without bacterial infection.

Association between perioperative allogeneic red blood cell transfusion and infection after clean-contaminated surgery: a retrospective cohort study.

BACKGROUND: Allogeneic red blood cell (RBC) transfusion can induce immunosuppression, which can then increase the susceptibility to postoperative infection. However, studies in different types of surgery show conflicting results regarding this effect. METHODS: In this retrospective cohort study conducted in a tertiary referral centre, we included adult patients undergoing clean-contaminated surgery from 2014 to 2018. Patients who received allogeneic RBC transfusion from preoperative Day 30 to postoperative Day 30 were included into the transfusion group. The control group was matched for the type of surgery in a 1:1 ratio. The primary outcome was infection within 30 days after surgery, which was defined by healthcare-associated infection, and identified mainly based on antibiotic regimens, microbiology tests, and medical notes. RESULTS: Among the 8098 included patients, 1525 (18.8%) developed 1904 episodes of postoperative infection. Perioperative RBC transfusion was associated with an increased risk of postoperative infection after controlling for 27 confounders by multivariable regression analysis (odds ratio [OR]: 1.60; 95% confidence interval [CI]: 1.39-1.84; P<0.001) and propensity score weighing (OR: 1.64; 95% CI: 1.45-1.85; P<0.001) and matching (OR: 1.70; 95% CI: 1.43-2.01; P<0.001), and a dose-response relationship was observed. The transfusion group also showed higher risks of surgical site infection, pneumonia, bloodstream infection, multiple infections, intensive care admission, unplanned reoperation, prolonged postoperative length of hospital stay, and all-cause death. CONCLUSIONS: Perioperative allogeneic RBC transfusion is associated with an increased risk of infection after clean-contaminated surgery in a dose-response manner. Close monitoring of infections and enhanced prophylactic strategies should be considered after transfusion.

Influenza co-infection associated with severity and mortality in COVID-19 patients.

BACKGROUND: In COVID-19 patients, undetected co-infections may have severe clinical implications associated with increased hospitalization, varied treatment approaches and mortality. Therefore, we investigated the implications of viral and bacterial co-infection in COVID-19 clinical outcomes. METHODS: Nasopharyngeal samples were obtained from 48 COVID-19 patients (29% ICU and 71% non-ICU) and screened for the presence of 24 respiratory pathogens using six multiplex PCR panels. RESULTS: We found evidence of co-infection in 34 COVID-19 patients (71%). Influenza A H1N1 (n = 17), Chlamydia pneumoniae (n = 13) and human adenovirus (n = 10) were the most commonly detected pathogens. Viral co-infection was associated with increased ICU admission (r = 0.1) and higher mortality (OR 1.78, CI = 0.38-8.28) compared to bacterial co-infections (OR 0.44, CI = 0.08-2.45). Two thirds of COVID-19 critically ill patients who died, had a co-infection; and Influenza A H1N1 was the only pathogen for which a direct relationship with mortality was seen (r = 0.2). CONCLUSIONS: Our study highlights the importance of screening for co-infecting viruses in COVID-19 patients, that could be the leading cause of disease severity and death. Given the high prevalence of Influenza co-infection in our study, increased coverage of flu vaccination is encouraged to mitigate the transmission of influenza virus during the on-going COVID-19 pandemic and reduce the risk of severe outcome and mortality.

Topical emollient for preventing infection in preterm infants.

BACKGROUND: Breakdown of the developmentally immature epidermal barrier may permit entry for micro-organisms leading to invasive infection in preterm infants. Topical emollients may improve skin integrity and barrier function and thereby prevent invasive infection, a major cause of mortality and morbidity in preterm infants. OBJECTIVES: To assess the effect of topical application of emollients (ointments, creams, or oils) on the risk of invasive infection and mortality in preterm infants. SEARCH METHODS: We searched CENTRAL via Cochrane Register of Studies (CRS) Web and MEDLINE via Ovid (updated 08 January 2021) and the reference lists of retrieved articles. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that assessed the effect of prophylactic application of topical emollient on the risk of invasive infection, mortality, other morbidity, and growth and development in preterm infants. DATA COLLECTION AND ANALYSIS: We used the standard methods of Cochrane Neonatal. Two review authors separately evaluated trial quality, extracted data, and synthesised effect estimates using risk ratio (RR), risk difference (RD), and mean difference. We used the GRADE approach to assess the certainty of evidence for effects on mortality and invasive infection. MAIN RESULTS: We included 22 trials with a total of 5578 infant participants. The main potential sources of bias were lack of clarity on the methods used to generate random sequences and conceal allocation in half of the trials, and lack of masking of parents, caregivers, clinicians, and investigators in all of the trials. Eight trials (2086 infants) examined the effect of topical ointments or creams. Most participants were very preterm infants cared for in healthcare facilities in high-income countries. Meta-analyses suggested that topical ointments or creams may have little or no effect on invasive infection (RR 1.13, 95% confidence interval (CI) 0.97 to 1.31; low certainty evidence) or mortality (RR 0.94, 95% CI 0.82 to 1.08; low certainty evidence). Fifteen trials (3492 infants) assessed the effect of topical plant or vegetable oils. Most of these trials were undertaken in low- or middle-income countries and were based in healthcare facilities. One large (2249 infants) community-based trial occurred in a rural field practice in India. Meta-analyses suggested that topical oils may reduce invasive infection (RR 0.71, 95% CI 0.52 to 0.96; I² = 52%; low certainty evidence) but have little or no effect on mortality (RR 0.94, 95% CI 0.82 to 1.08, I² = 3%; low certainty evidence). One trial (316 infants) that compared petroleum-based ointment versus sunflower seed oil in very preterm infants in Bangladesh showed little or no effect on invasive infection (RR 0.91, 95% CI 0.57 to 1.46; low certainty evidence), but suggested that ointment may lower mortality slightly (RR 0.82, 95% CI 0.68 to 0.98; RD -0.12, 95% CI -0.23 to -0.01; number needed to treat for an additional beneficial outcome 8, 95% CI 4 to 100; low certainty evidence). One trial (64 infants) that assessed the effect of coconut oil versus mineral oil in preterm infants with birth weight 1500 g to 2000 g in India reported no episodes of invasive infection or death in either group (very low certainty evidence). AUTHORS' CONCLUSIONS: The level of certainty about the effects of emollient therapy on invasive infection or death in preterm infants is low. Since these interventions are mostly inexpensive, readily accessible, and generally acceptable, further good-quality randomised controlled trials in healthcare facilities, and in community settings in low- or middle-income countries, may be justified.

Prevalence and outcomes of co-infection and superinfection with SARS-CoV-2 and other pathogens: A systematic review and meta-analysis.

INTRODUCTION: The recovery of other pathogens in patients with SARS-CoV-2 infection has been reported, either at the time of a SARS-CoV-2 infection diagnosis (co-infection) or subsequently (superinfection). However, data on the prevalence, microbiology, and outcomes of co-infection and superinfection are limited. The purpose of this study was to examine the occurrence of co-infections and superinfections and their outcomes among patients with SARS-CoV-2 infection. PATIENTS AND METHODS: We searched literature databases for studies published from October 1, 2019, through February 8, 2021. We included studies that reported clinical features and outcomes of co-infection or superinfection of SARS-CoV-2 and other pathogens in hospitalized and non-hospitalized patients. We followed PRISMA guidelines, and we registered the protocol with PROSPERO as: CRD42020189763. RESULTS: Of 6639 articles screened, 118 were included in the random effects meta-analysis. The pooled prevalence of co-infection was 19% (95% confidence interval [CI]: 14%-25%, I2 = 98%) and that of superinfection was 24% (95% CI: 19%-30%). Pooled prevalence of pathogen type stratified by co- or superinfection were: viral co-infections, 10% (95% CI: 6%-14%); viral superinfections, 4% (95% CI: 0%-10%); bacterial co-infections, 8% (95% CI: 5%-11%); bacterial superinfections, 20% (95% CI: 13%-28%); fungal co-infections, 4% (95% CI: 2%-7%); and fungal superinfections, 8% (95% CI: 4%-13%). Patients with a co-infection or superinfection had higher odds of dying than those who only had SARS-CoV-2 infection (odds ratio = 3.31, 95% CI: 1.82-5.99). Compared to those with co-infections, patients with superinfections had a higher prevalence of mechanical ventilation (45% [95% CI: 33%-58%] vs. 10% [95% CI: 5%-16%]), but patients with co-infections had a greater average length of hospital stay than those with superinfections (mean = 29.0 days, standard deviation [SD] = 6.7 vs. mean = 16 days, SD = 6.2, respectively). CONCLUSIONS: Our study showed that as many as 19% of patients with COVID-19 have co-infections and 24% have superinfections. The presence of either co-infection or superinfection was associated with poor outcomes, including increased mortality. Our findings support the need for diagnostic testing to identify and treat co-occurring respiratory infections among patients with SARS-CoV-2 infection.

Impact of obesity on outcome of severe bacterial infections.

INTRODUCTION: Obesity is a rapidly growing global health concern with considerable negative impact on life-time expectancy. It has yet not been clarified if and how obesity impacts outcomes of severe bacterial infections. The aim of this study was to determine how body mass index impacts outcome of severe bacterial infections in a well-defined population-based cohort. METHODS: This study is based on a cohort of 2196 patients included in a Swedish prospective, population-based, consecutive observational study of the incidence of community-onset severe sepsis and septic shock in adults. All patients with weight and height documented in the medical records on admission were included. RESULTS: The case fatality rate (CFR) was negatively correlating with increasing BMI. Outcomes included 28-day CFR (p-value = 0.002), hospital CFR (p-value = 0.039) and 1-year CFR (p-value<0.001). When BMI was applied as continuous variable in a multiple logistic regression together with other possible covariates, we still could discern that BMI was associated with decreasing 28-day CFR (OR = 0.93, 95% CI 0.88-0.98, p-value = 0.009) and 1-year CFR (OR = 0.94, 95% CI 0.91-0.97, p-value<0.001). CONCLUSION: The hypothesis and paradox of obesity being associated with higher survival rates in severe bacterial infections was confirmed in this prospective, population-based observational study.

Infections in hematopoietic stem cell transplant patients admitted to Hematology intensive care unit: a single-center study.

OBJECTIVE: The aim of this study was to investigate the data of HSCT patients who were admitted to our Hematology ICU due to infections or infectious complications. MATERIALS AND METHODS: HSCT patients who were admitted to our Hematology ICU between 01 January 2014 and 01 September 2017 were analyzed retrospectively. RESULTS: 62 HSCT patients were included in this study. The median age was 55.5 years and 58% of the patients were allogeneic HSCT patients. Major underlying hematologic disorders were multiple myeloma (29%) and lymphoma (27.4%). The most common reasons for ICU admission were sepsis/septic shock (61.3%) and acute respiratory failure (54.8%). Overall ICU mortality rate was 45.2%. However, a lot of factors were related with ICU mortality of HSCT patients in univariate analysis, only APACHE II score was found to be an independent risk factor for ICU mortality. While there was infection in 58 patients at ICU admission, new infections developed in 38 patients during ICU stay. The most common new infection was pneumonia/VAP, while the most frequently isolated bacteria were Acinetobacter baumannii. Length of ICU stay, sepsis/septic shock as a reason for ICU admission and the presence of urinary catheter at ICU admission were determined factors for ICU-acquired infections. There was no difference between autologous and allogeneic stem cell transplant patients in terms of ICU morbidities and mortality. However, pneumonia/VAP developed in the ICU was higher in autologous HSCT patients, while bloodstream/catheter-related bloodstream infection was higher in allogeneic HSCT patients. CONCLUSION: It was concluded that early or late post-HSCT infections and related complications (sepsis, organ failure, etc.) constituted a major part of the reasons for ICU admission, ICU mortality and ICU morbidities.

Fungal and bacterial coinfections increase mortality of severely ill COVID-19 patients.

BACKGROUND: SARS-CoV-2 predisposes patients to secondary infections; however, a better understanding of the impact of coinfections on the outcome of hospitalized COVID-19 patients is still necessary. AIM: To analyse death risk due to coinfections in COVID-19 patients. METHODS: The odds of death of 212 severely ill COVID-19 patients were evaluated, with detailed focus on the risks for each pathogen, site of infection, comorbidities and length of hospitalization. FINDINGS: The mortality rate was 50.47%. Fungal and/or bacterial isolation occurred in 89 patients, of whom 83.14% died. Coinfected patients stayed hospitalized longer and had an increased odds of dying (odds ratio (OR): 13.45; R2 = 0.31). The risk of death was increased by bacterial (OR: 11.28) and fungal (OR: 5.97) coinfections, with increased levels of creatinine, leucocytes, urea and C-reactive protein. Coinfections increased the risk of death if patients suffered from cardiovascular disease (OR: 11.53), diabetes (OR: 6.00) or obesity (OR: 5.60) in comparison with patients with these comorbidities but without pathogen isolation. The increased risk of death was detected for coagulase-negative Staphylococcus (OR: 25.39), Candida non-albicans (OR: 11.12), S. aureus (OR: 10.72), Acinetobacter spp. (OR: 6.88), Pseudomonas spp. (OR: 4.77), and C. albicans (OR: 3.97). The high-risk sites of infection were blood, tracheal aspirate, and urine. Patients with coinfection undergoing invasive mechanical ventilation were 3.8 times more likely to die than those without positive cultures. CONCLUSION: Severe COVID-19 patients with secondary coinfections required longer hospitalization and had higher risk of death. The early diagnosis of coinfections is essential to identify high-risk patients and to determine the right interventions to reduce mortality.

What about tocilizumab? A retrospective study from a NYC Hospital during the COVID-19 outbreak.

BACKGROUND: Tocilizumab, an interleukin-6 receptor blocker, has been used in the inflammatory phase of COVID-19, but its impact independent of corticosteroids remains unclear in patients with severe disease. METHODS: In this retrospective analysis of patients with COVID-19 admitted between March 2 and April 14, 2020 to a large academic medical center in New York City, we describe outcomes associated with tocilizumab 400 mg (without methylprednisolone) compared to a propensity-matched control. The primary endpoints were change in a 7-point ordinal scale of oxygenation and ventilator free survival, both at days 14 and 28. Secondary endpoints include incidence of bacterial superinfections and gastrointestinal perforation. Primary outcomes were evaluated using t-test. RESULTS: We identified 33 patients who received tocilizumab and matched 74 controls based on demographics and health measures upon admission. After adjusting for illness severity and baseline ordinal scale, we failed to find evidence of an improvement in hypoxemia based on an ordinal scale at hospital day 14 in the tocilizumab group (OR 2.2; 95% CI, 0.7-6.5; p = 0.157) or day 28 (OR 1.1; 95% CI, 0.4-3.6; p = 0.82). There also was no evidence of an improvement in ventilator-free survival at day 14 (OR 0.8; 95% CI, 0.18-3.5; p = 0.75) or day 28 (OR 1.1; 95% CI, 0.1-1.8; p = 0.23). There was no increase in secondary bacterial infection rates in the tocilizumab group compared to controls (OR 0.37; 95% CI, 0.09-1.53; p = 0.168). CONCLUSIONS: There was no evidence to support an improvement in hypoxemia or ventilator-free survival with use of tocilizumab 400 mg in the absence of corticosteroids. No increase in secondary bacterial infections was observed in the group receiving tocilizumab.