Clinical impact of multidrug-resistant bacteria in older hospitalized patients with community-acquired urinary tract infection.

INTRODUCTION: Previous studies have described some risk factors for multidrug-resistant (MDR) bacteria in urinary tract infection (UTI). However, the clinical impact of MDR bacteria on older hospitalized patients with community-acquired UTI has not been broadly analyzed. We conducted a study in older adults with community-acquired UTI in order to identify risk factors for MDR bacteria and to know their clinical impact. METHODS: Cohort prospective observational study of patients of 65 years or older, consecutively admitted to a university hospital, diagnosed with community-acquired UTI. We compared epidemiological and clinical variables and outcomes, from UTI due to MDR and non-MDR bacteria. Independent risk factors for MDR bacteria were analyzed using logistic regression. RESULTS: 348 patients were included, 41.4% of them with UTI due to MDR bacteria. Median age was 81 years. Hospital mortality was 8.6%, with no difference between the MDR and non-MDR bacteria groups. Median length of stay was 5 [4-8] days, with a longer stay in the MDR group (6 [4-8] vs. 5 [4-7] days, p = 0.029). Inadequate empirical antimicrobial therapy (IEAT) was 23.3%, with statistically significant differences between groups (33.3% vs. 16.2%, p < 0.001). Healthcare-associated UTI variables, in particular previous antimicrobial therapy and residence in a nursing home, were found to be independent risk factors for MDR bacteria. CONCLUSIONS: The clinical impact of MDR bacteria was moderate. MDR bacteria cases had higher IEAT and longer hospital stay, although mortality was not higher. Previous antimicrobial therapy and residence in a nursing home were independent risk factors for MDR bacteria.

Prognostic accuracy of Quick SOFA in older adults hospitalised with community acquired urinary tract infection.

INTRODUCTION: Quick [Sepsis-related] Sequential Organ Failure Assessment (qSOFA) is a prognostic score based on sepsis-3 definition, easy to carry out, whose application has been studied in older adults with sepsis from different sources and respiratory sepsis. However, to date no study has analysed its prognostic accuracy in older adults admitted to hospital with community urinary tract infection. METHODS: In a prospective study of 282 older adults admitted to hospital with community acquired urinary tract infection, the application of qSOFA to predict hospital mortality was analysed. The predictive capacity of qSOFA for in-hospital mortality was compared with Systemic Inflammatory Response Syndrome score (SIRS) and Sequential Organ Failure Assessment (SOFA), which require laboratory test in order to be calculated. RESULTS: In a population with a median age of 81 years, where 51.8% were males and 10.6% had septic shock, qSOFA showed sensibility and specificity of 88.46 and 75.78% and area under the receiver operating characteristic curves (AUROC) of 0.810. AUROC for qSOFA was significantly higher than that of SIRS (AUROC 0.597, P = .005) and with no statistical differences with SOFA (AUROC 0.841, P = .635). CONCLUSION: qSOFA showed a better predictive prognostic accuracy than SIRS and similar to SOFA in older adults admitted to hospital with community acquired urinary tract infection, having the advantage of not requiring laboratory tests.

Features of Cytomegalovirus DNAemia Blips in Allogeneic Hematopoietic Stem Cell Transplant Recipients: Implications for Optimization of Preemptive Antiviral Therapy Strategies.

Cytomegalovirus (CMV) DNAemia occurs frequently in allogeneic hematopoietic stem cell transplant recipients (allo-HSCT). There is limited information about the incidence, features, and clinical impact of CMV DNAemia blips (episodes defined by an isolated positive PCR result) in this setting. In this retrospective study, 225 consecutive adult patients undergoing any modality of allo-HSCT at our center between May 2012 and July 2019 were included. Plasma CMV DNA load was monitored using a highly sensitive real-time PCR assay. In all, 187 of 225 patients had CMV DNAemia through day 365 after allo-HSCT (total number of episodes, n = 379). Eighty-three of the 187 patients had 1 or more blips (n = 104). Blips occurred as a first episode of CMV DNAemia as opposed to prolonged CMV DNAemia (≥2 consecutive positive PCR results) in 47 patients; in 20 of these patients, blips represented the only documented episode throughout the study period, and in 27 patients, blips preceded a prolonged CMV DNAemia episode. In the remaining 36 patients, blips developed as recurrences. Blips presenting as initial episodes occurred more frequently (P < .001) in patients receiving an allograft from a CMV-seropositive donor. The cumulative incidence of recurrent CMV DNAemia following initial blips, self-resolving prolonged CMV DNAemia episodes, or CMV DNAemia episodes treated preemptively with antivirals was not significantly different (P = .34). Receiver operating characteristic curve analysis indicated that a CMV DNA load cutoff of 48 IU/mL yielded the highest combined sensitivity (66%) and specificity (70.2%) for predicting a prolonged CMV DNAemia episode. The practical implications of our data in the optimization of preemptive antiviral therapy strategies are discussed.

Missing Cases of Herpes Simplex Virus (HSV) Infection of the Central Nervous System When the Reller Criteria Are Applied for HSV PCR Testing: a Multicenter Study.

Previous studies suggested that herpes simplex virus (HSV) PCR testing can be safely deferred in patients with normal cerebrospinal fluid (CSF) white blood cell (WBC) counts and protein levels as long as they are older than 2 years of age and are not immunocompromised, the so-called Reller criteria. In this multicenter study, we retrospectively assessed the validity of these screening criteria in our setting. A total of 4,404 CSF specimens submitted for HSV PCR testing to the respective microbiology laboratories at the participating hospitals between 2012 and 2018 were included. Six commercially available HSV PCR assays were used across the participating centers. Ninety-one of the 4,404 CSF specimens (2.1%) tested were positive for HSV DNA (75 samples for HSV-1 and 16 for HSV-2). Nine patients failed to meet the Reller criteria, of whom seven were deemed to truly have HSV encephalitis. Overall, no significant correlation between HSV PCR cycle threshold (CT ) values and WBC counts or total protein levels was found. In addition, median HSV PCR CT s were comparable between patients who met the Reller criteria and those who did not (P = 0.531). In summary, we show that HSV DNA may be detected in CSF specimens with normal WBC and protein levels collected from immunocompetent individuals older than 2 years with HSV encephalitis. Nevertheless, the data also indicate that the number of cases detected could be lowered at least by half if CSF specimens with borderline WBC counts (4 cells/mm3) as well as children of any age are systematically tested.

Community-onset Pseudomonas aeruginosa urinary sepsis in elderly people: Predictive factors, adequacy of empirical therapy and outcomes.

Purpose To know the predictive factors for Pseudomonas aeruginosa (PA) urinary sepsis in hospitalised elderly patients coming from community, the adequacy of empirical antibiotic therapy and its outcomes. Methods Retrospective case-control study conducted between 2007 and 2017. Patients aged 65 years or older with PA urinary sepsis were included as cases. Three age-matched controls, with urinary sepsis caused by other microorganisms, were selected for each case. Predictors for PA urinary sepsis were determined by logistic regression analysis. Adequacy of empirical antibiotic therapy and outcomes were compared between both groups. Results A total of 332 patients, from which 83 were cases, were included. Predictive factors for PA urinary sepsis were as follows: male sex (OR 3.16, 95% CI 1.61-6.10; P < .001), urinary catheter (OR 3.25, 95% CI 1.73-6.11; P < .001) and healthcare-associated infection (OR 5.52, 95% CI 1.76 -17.29; P = .003). Inadequate empirical antimicrobial therapy (IEAT) and length of hospital stay were higher in PA group (42% vs 24%, P = .002; 7.45 ± 4.36 days vs 6.43 ± 3.82 days, P = .045, respectively), but mortality was not different (7.2% vs 8.8%, P = .648). Conclusions Pseudomonas aeruginosa urinary sepsis in elderly people was associated with male sex, urinary catheter and healthcare-associated infection. These infections had a higher rate of IEAT and a longer hospital stay than urinary sepsis caused by other microorganisms.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) proteomic profiling of cerebrospinal fluid in the diagnosis of enteroviral meningitis: a proof-of-principle study.

The use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) for diagnosing viral infections by directly testing clinical specimens has not previously been explored. In this proof-of-principle study, we tested the hypothesis that proteomic profiling of cerebrospinal fluid (CSF) by mass spectrometry may be useful in the diagnosis of enteroviral (EV) meningitis. A total of 114 cryopreserved CSF samples were analyzed, of which 47 were positive for EV and 67 were negative. Total CSF proteins were precipitated and subjected to MALDI-TOF-MS analysis in a low (2-20 kDa) molecular weight range using a MicroFlex LT mass spectrometer. The whole data set was randomly split into a training set (n = 76 specimens) and a validation set (n = 38 samples). Backward/forward stepwise logistic regression analyses identified 30 peaks that were differentially present in EV-positive and EV-negative specimens. These were used to build a model which displayed an overall classification accuracy of 93%. The discriminative ability of the model was confirmed by using a validation sample set (overall accuracy 83%). In fact, the model was able to correctly classify 61 out of 67 EV-negative samples and 42 out of 47 EV-positive specimens. EV meningitis is associated with a distinctive protein profile that may be directly detectable in CSF specimens by MALDI-TOF-MS.

Assessing the risk of cytomegalovirus DNAaemia in allogeneic stem cell transplant recipients by monitoring oxidative-stress markers in plasma.

The level of antioxidants, such as thiol-containing tripeptide glutathione (GSH), in cytomegalovirus (CMV)-infected cells is notably increased. We previously showed that GSH levels in plasma, as measured by untargeted 1H nuclear magnetic resonance, are higher in allogeneic stem cell transplant (allo-SCT) recipients who subsequently develop CMV viraemia. We hypothesized that the net level of oxidative-stress markers present in plasma may be reduced in patients who develop CMV DNAaemia compared to those who do not. We serially monitored the levels of malondialdehyde (MDA) and carbonylated proteins (CPs) early after allo-SCT and assessed whether they could predict the occurrence of CMV DNAaemia. MDA levels were measured in 43 patients (28 had CMV DNAaemia) and CPs were quantified in 53 patients (38 patients developed CMV DNAaemia). The area under the curve (AUC) value for MDA, but not for CPs, was significantly lower in patients who subsequently developed CMV DNAaemia compared to those who remained DNAaemia-free (P=0.043). A trend toward lower MDA AUC values was observed in episodes of CMV DNAaemia with faster CMV replicative kinetics and in those who reached higher peak CMV DNA levels. Moreover, receiver operating characteristic curve analyses indicated that the MDA biomarker had the predictive ability to discriminate between patients with or without subsequent CMV DNAaemia (AUC=0.69, 95 % confidence interval 0.51-0.85, P=0.05). In summary, serial quantitation of MDA may be useful for individualizing antiviral prophylaxis therapies (targeted prophylaxis) in the upcoming era of new antiviral drugs with improved safety profiles.

Prospective cohort study of risk factors for extended-spectrum ß-lactamase-producing Escherichia coli urinary tract infections in elderly patients admitted to hospital.

BACKGROUND: Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli are currently common in community-onset infections, limiting therapeutic options. In this work we aim to identify the prevalence of and risk factors for ESBL-producing E. coli in elderly patients with urinary tract infections (UTI) admitted to hospital. METHODS: Prospective cohort study on elderly patients with E. coli UTI admitted to a university hospital in Spain, from January 2013 to December 2015. Clinical features, microbiology and outcomes were recorded from the electronic medical records and reviewed by two researchers. Cases were segregated according to ESBL-producing E. coli. Risk factors for ESBL-producing E. coli were analysed by multivariate analysis. RESULTS: The prevalence of ESBL-producing E. coli was 27.4% (85/310). Healthcare-associated UTI was the only risk factor for ESBL-producing E. coli (OR 6.79; 95% CI 3.22-14.31, P < .001) by multivariate analysis. ESBL-producing E. coli was 43.9% in the healthcare-associated UTI group and 8.9% in the community-acquired UTI group (P < .001). Inadequate empirical antibiotic therapy and length of stay in hospital were higher in the ESBL-producing E. coli group than in the non-ESBL-producing E. coli group (62.3% vs 5.3% and 6.60 ± 3.69 days vs 5.61 ± 3.16 days, respectively). Mortality was not significantly different between groups (13% in ESBL-producing E. coli group vs 7.5% in non-ESBL-producing E. coli group, P = .140). SUMMARY: Healthcare-associated UTI was a risk factor for ESBL-producing E. coli in elderly patients with UTI admitted to hospital. Our results might help clinicians in choosing empirical antibiotics in an overall high rate setting of ESBL-producing E. coli.

Performance evaluation of the Alinity m system for quantifying cytomegalovirus DNA in samples of the respiratory, gastrointestinal, and urinary tract.

Quantitation of cytomegalovirus (CMV) DNA load in specimens other than blood such as bronchoalveolar lavages, intestinal biopsies, or urine has become a common practice as an ancillary tool for the diagnosis of CMV pneumonitis, intestinal disease, or congenital infection, respectively. Nevertheless, most commercially available CMV PCR platforms have not been validated for CMV DNA detection in these specimen types. In this study, a laboratory-developed test based on Alinity m CMV ("Alinity LDT") was evaluated. Reproducibility assessment using spiked bronchial aspirate (BAS) or urine samples showed low standard deviations of 0.08 and 0.27 Log IU/mL, respectively. Evaluating the clinical performance of Alinity LDT in comparison to a laboratory-developed test based on RealTime CMV ("RealTime LDT") showed good concordance across 200 clinical specimens including respiratory specimens, intestinal biopsies, urine, and stool. A high Pearson's correlation coefficient of r = 0.92, a low mean bias of -0.12 Log IU/mL, a good qualitative agreement of 90%, and a Cohen's kappa value of 0.76 (substantial agreement) were observed. In separate analyses of the sample types BAS, tracheal aspirates, bronchoalveolar lavage, biopsies, and urine, the assay results correlated well between the two platforms with r values between 0.88 and 0.99 and a bias <0.5 Log IU/mL. Overall, the fully automated, continuous, random access Alinity LDT yielded good reproducibility, high concordance, and good correlation to RealTime LDT in respiratory, gastrointestinal, and urine samples and may enhance patient management with rapid result reporting.IMPORTANCEIn transplant recipients, a major cause for morbidity and mortality is end-organ disease by primary or secondary CMV infection of the respiratory or gastrointestinal tract. In addition, sensorineural hearing loss and neurodevelopmental abnormalities are frequent sequelae of congenital CMV infections in newborns. Standard of care for highly sensitive detection and quantitation of the CMV DNA load in plasma and whole blood specimens is real-time PCR testing. Beyond that, there is a need for quantitative determination of CMV DNA levels in respiratory, gastrointestinal, and urinary tract specimens using a highly automated, random access CMV PCR assay with a short turnaround time to enable early diagnosis and treatment. In the present study, clinical performance of the fully automated Alinity m analyzer in comparison to the current RealTime LDT assay was evaluated in eight different off-label sample types.

[Post-mortem microbiology analysis]. / Análisis microbiológico post mórtem.

Post-mortem microbiology is useful in both clinical and forensic autopsies, and allows a suspected infection to be confirmed. Indeed, it is routinely applied to donor studies in the clinical setting, as well as in sudden and unexpected death in the forensic field. Implementation of specific sampling techniques in autopsy can minimize the possibility of contamination, making interpretation of the results easier. Specific interpretation criteria for post-mortem cultures, the use of molecular diagnosis, and its fusion with molecular biology and histopathology have led to post-mortem microbiology playing a major role in autopsy. Multidisciplinary work involving microbiologists, pathologists, and forensic physicians will help to improve the achievements of post-mortem microbiology, prevent infectious diseases, and contribute to a healthier population.

Fluoroquinolones Are Useful as Directed Treatment for Complicated UTI in a Setting with a High Prevalence of Quinolone-Resistant Microorganisms.

Fluoroquinolones (FQs) have been widely used for treating urinary tract infections (UTIs); however, the increasing emergence of resistant strains has compromised their use. We aimed to know the usefulness of FQs for the treatment of community-acquired UTI in a setting with a high prevalence of fluoroquinolone-resistant microorganisms. A prospective observational study of patients diagnosed with community-acquired UTI was conducted, in which their outcomes according to whether they had FQs or not in their empirical and directed treatments were compared. A multivariate analysis was performed to identify risk factors for UTIs due to ciprofloxacin-resistant microorganisms. A total of 419 patients were included; 162 (38.7%) patients were treated with FQs, as empirical treatment in 27 (6.4%), and as directed treatment in 135 (32.2%). In-hospital mortality (2.2% vs. 6.6%, p 0.044) and 30-day mortality (4.4 vs. 11%, p 0.028) were both lower in the group of patients directly treated with FQ, while there were no differences when FQs were used as empirical treatment. A total of 37.2% of the cases were resistant to ciprofloxacin, which was associated with healthcare-associated UTI (OR 2.7, 95% CI 2-3.7) and prior exposure to FQs (OR 2.7, 95 % CI 1.9-3.7). In conclusion, our findings show that in a setting with a high prevalence of community-acquired UTI caused by quinolone-resistant microorganisms, FQs as directed treatment for community-acquired UTI were associated with better outcomes than other antibiotics, but their use as empirical treatment is not indicated, even in those cases without risk factors for quinolones resistance.

Influence of Sepsis on the Middle-Term Outcomes for Urinary Tract Infections in Elderly People.

Urinary tract infection (UTI) is a common condition that predominantly affects elderly people, who are particularly susceptible to developing sepsis. Previous studies have indicated a detrimental effect of sepsis on short-term outcomes in elderly patients with UTI, but there is a lack of data about the middle-term prognosis. The aim of this study was to investigate the influence of sepsis on the middle-term prognosis of patients aged 65 years or older with complicated community-acquired UTIs. A prospective observational study of patients admitted to a hospital with UTI. We conducted a comparison of epidemiological and clinical variables between septic and nonseptic patients with UTI, as well as their 6-month case-fatality rate. A total of 412 cases were included, 47.8% of them with sepsis. Septic patients were older (83 vs. 80 years, p < 0.001), but did not have more comorbidities. The short-term case-fatality rate was higher in septic patients and this difference persisted at 6 months (34% vs. 18.6%, p = 0.003). Furthermore, age older than 75 years, Barthel index <40 and healthcare-associated UTI were also associated with the middle-term case-fatality rate. In conclusion, the detrimental impact of sepsis is maintained on the middle-term prognosis of elderly patients with UTI. Age, functional status and healthcare-associated UTIs also play significant roles in shaping patient outcomes.

Risk Factors and the Impact of Multidrug-Resistant Bacteria on Community-Acquired Urinary Sepsis.

Risk factors for multidrug-resistant bacteria (MDRB) in nosocomial urinary tract infection (UTI) have been widely studied. However, these risk factors have not been analyzed in community-acquired urinary sepsis (US), nor have its outcomes been studied. The aim of our study is to determine risk factors for MDRB in community-acquired US and its influence on outcomes. Prospective observational study of patients with community-acquired US admitted to a university hospital. We compared epidemiological and clinical variables and outcomes of US due to MDRB and non-MDRB. Independent risk factors for MDRB were analyzed using logistic regression. A total of 193 patients were included, 33.7% of them with US due to MDRB. The median age of patients was 82 years. Hospital mortality was 17.6%, with no difference between the MDRB and non-MDRB groups. The length of hospital stay was 5 (4-8) days, with a non-significant tendency to longer hospital stays in the MDRB group (6 (4-10) vs. 5 (4-8) days, p = 0.051). Healthcare-associated US was found to be an independent risk factor for MDR bacteria by multivariate analysis. In conclusion, the impact of MDR bacteria on the outcomes of community-acquired urinary sepsis was mild. Healthcare-associated US was an independent risk factor for MDR bacteria.

Risk Factors for Bacteremia and Its Clinical Impact on Complicated Community-Acquired Urinary Tract Infection.

Bacteremia has been associated with severity in some infections; however, its impact on the prognosis of urinary tract infections (UTIs) is still disputed. Our goal is to determine the risk factors for bacteremia and its clinical impact on hospitalized patients with complicated community-acquired urinary tract infections. We conducted a prospective observational study of patients admitted to the hospital with complicated community-acquired UTIs. Clinical variables and outcomes of patients with and without bacteremia were compared, and multivariate analysis was performed to identify risk factors for bacteremia and mortality. Of 279 patients with complicated community-acquired UTIs, 37.6% had positive blood cultures. Risk factors for bacteremia by multivariate analysis were temperature ≥ 38 °C (p = 0.006, OR 1.3 (95% CI 1.1-1.7)) and procalcitonin ≥ 0.5 ng/mL (p = 0.005, OR 8.5 (95% CI 2.2-39.4)). In-hospital and 30-day mortality were 9% and 13.6%, respectively. Quick SOFA (p = 0.030, OR 5.4 (95% CI 1.2-24.9)) and Barthel Index <40% (p = 0.020, OR 4.8 (95% CI 1.3-18.2)) were associated with 30-day mortality by multivariate analysis. However, bacteremia was not associated with 30-day mortality (p = 0.154, OR 2.7 (95% CI 0.7-10.3)). Our study found that febrile community-acquired UTIs and elevated procalcitonin were risk factors for bacteremia. The outcomes in patients with bacteremia were slightly worse, but without significant differences in mortality.

Lactate/albumin ratio prognostic value for mortality in patients older than 65 years with complicated urinary tract infection.

BACKGROUND: Lactate to albumin ratio (LAR) is an emerging sepsis biomarker that has been tested for mortality in patients with sepsis of different focus. Our goal is to evaluate the prognostic value of LAR in patients admitted to the hospital due to complicated urinary tract infections. METHODS: Prospective observational study of patients older than 65 years diagnosed with UTI. Area under the ROC curve, sensibility, and specificity to predict 30-day mortality were calculated for LAR, qSOFA and SOFA. RESULTS: 341 UTI cases were analyzed. 30-day mortality (20.2% vs. 6.7%, p < 0.001) and longer hospital stay (5 [4-8] vs. 4 [3-7], p 0.018) were associated with LAR ≥ 0.708. LAR has no statistically significant differences compared to qSOFA and SOFA for predicting 30-day mortality (AUROC 0.737 vs. 0.832 and 0.777 respectively, p 0.119 and p 0.496). The sensitivity of LAR was similar to the sensitivity of qSOFA and SOFA (60.8% vs. 84.4% and 82.2, respectively, p 0.746 and 0.837). However, its specificity was lower than the specificity of qSOFA (60.8% vs. 75%, p 0.003), but similar to the specificity of SOFA (60.8% vs. 57.8%, p 0.787). CONCLUSION: LAR has no significant differences with other well-stablished scores in sepsis, such as qSOFA and SOFA, to predict 30-day mortality in patients with complicated UTI.

Comparison of quick Pitt to quick sofa and sofa scores for scoring of severity for patients with urinary tract infection.

Quick Pitt (qPitt), which includes temperature, systolic blood pressure, respiratory rate, cardiac arrest, and mental status, is a new prognostic score derived from the Pitt Bacteremia score. The aim of our study is to compare qPitt with quick SOFA (qSOFA) and SOFA for scoring of severity in patients with urinary tract infection (UTI). Prospective observational study of patients diagnosed with UTI. Area under the ROC curve, sensibility, and specificity to predict 30-day mortality were calculated for qPitt, qSOFA and SOFA and compared. 382 UTI cases were analyzed. Thirty-day mortality (18.8% vs. 5.9%, p < 0.001) and longer hospital stay (6 [1-11] vs. 4 [1-7] days, p < 0.001) were associated with qPitt ≥ 2. However, qPitt had a worse performance to predict 30-day mortality compared to qSOFA and SOFA (AUROC 0.692 vs. 0.832 and 0.806, respectively, p = 0.010 and p = 0.041). The sensitivity of qPitt was lower than the sensitivity of qSOFA and SOFA (70.45 vs. 84.09 for both qSOFA and SOFA, p < 0.001), with a specificity lower than qSOFA and similar to SOFA (60.36 vs. 82.25 and 63.61, p < 0.001 and p = 0.742, respectively). Quick Pitt had moderate prognostic accuracy and performed worse than qSOFA and SOFA scores for predicting mortality in patients with UTI.

Sex differences in aged 80 and over hospitalized patients with community-acquired UTI: A prospective observational study.

Aim: This study aimed to evaluate clinically significant sex differences that could have an effect on the choice of treatment and outcomes of urinary tract infection (UTI) in aged 80 and over hospitalized patients with community-acquired UTI. Methods: This was a prospective study of 161 patients aged 80 and over admitted to hospital with community-acquired UTI. Epidemiological, clinical, laboratory and microbiologic variables were compared between both sexes. Multivariate analysis was performed using logistic regression to determine the variables independently associated with sex. Results: In a population of 91 (56.52%) women and 70 (43.48%) men, aged 80 and over, we found that women were more likely to have cognitive impairment (p = 0.035) and less likely to have chronic obstructive pulmonary disease (COPD) (p = 0.006) and indwelling urinary catheter (p < 0.001) than men. Levels of creatinine were higher in men than in women (p = 0.008). Septic shock at presentation was more frequent in the male group (p = 0.043). Men had a higher rate of polymicrobial infection (p = 0.035) and Pseudomonas aeruginosa infection (p = 0.003). Factors independently associated with sex by multivariate analysis were septic shock, cognitive impairment, COPD and indwelling urinary catheter. Conclusion: Men aged 80 and over with community-acquired UTI had more septic shock at admission to hospital and higher rates of indwelling urinary catheter, while women had more cognitive impairment. There were no differences in outcomes between sexes.

Combined kinetic analysis of SARS-CoV-2 RNAemia, N-antigenemia and virus-specific antibodies in critically ill adult COVID-19 patients.

Combined kinetic analysis of plasma SARS-CoV-2 RNAemia, Nucleocapsid (N)-antigenemia and virus-specific antibodies may help ascertain the role of antibodies in preventing virus dissemination in COVID-19 patients. We performed this analysis in a cohort of 71 consecutive critically ill COVID-19 patients (49 male; median age, 65 years) using RT-PCR assay, lateral flow immunochromatography method and receptor binding domain (RBD) and N-based immunoassays. A total of 338 plasma specimens collected at a median of 12 days after symptoms onset were available for analyses. SARS-CoV-2 RNAemia and N-antigenemia were detected in 37 and 43 specimens from 26 (36.5%) and 30 (42.2%) patients, respectively. Free RNA was the main biological form of SARS-CoV-2 found in plasma. The detection rate for both viral components was associated with viral load at the upper respiratory tract. Median time to SARS-CoV-2-RBD antibody detection was 14 days (range, 4-38) from onset of symptoms. Decreasing antibody levels were observed in parallel to increasing levels of both RNAemia and N-antigenemia, yet overall a fairly modest inverse correlation (Rho = -0.35; P < 0.001) was seen between virus RNAemia and SARS-CoV-2-RBD antibody levels. The data cast doubts on a major involvement of antibodies in virus clearance from the bloodstream within the timeframe examined.

SARS-CoV-2-reactive IFN-γ-producing CD4+ and CD8+ T cells in blood do not correlate with clinical severity in unvaccinated critically ill COVID-19 patients.

We examined the relationship between peripheral blood levels of SARS-CoV-2 S (Spike protein)1/M (Membrane protein)-reactive IFN-γ-producing CD4+ and CD8+ T cells, serum levels of biomarkers of clinical severity, and mortality in critically ill COVID-19 patients. The potential association between SARS-CoV-2-S-Receptor Binding Domain (RBD)-specific IgG levels in sera and mortality was also investigated. SARS-CoV-2 T cells and anti-RBD IgG levels were monitored in 71 non-consecutive patients (49 male and 22 female; median age, 65 years) by whole-blood flow cytometry and Enzyme-linked immunosorbent assay (ELISA), respectively (326 specimens). SARS-CoV-2 RNA loads in paired tracheal aspirates [TA] (n = 147) were available from 54 patients. Serum levels of interleukin-6, ferritin, D-Dimer, lactose dehydrogenase and C-reactive protein in paired sera were known. SARS-CoV-2 T cells (either CD4+, CD8+ or both) were detectable in 70 patients. SARS-CoV-2 IFN-γ CD4+ T-cell responses were documented more frequently than their CD8+ counterparts (62 vs. 56 patients) and were of greater magnitude overall. Detectable SARS-CoV-2 S1/M-reactive CD8+ and CD4+ T-cell responses were associated with higher SARS-CoV-2 RNA loads in TA. SARS-CoV-2 RNA load in TA decreased over time, irrespective of the dynamics of SARS-CoV-2-reactive CD8+ and CD4+ T cells. No correlation was found between SARS-CoV-2 IFN-γ T-cell counts, anti-RBD IgG concentrations and biomarker serum levels (Rho ≤ 0.3). The kinetics of both T cell subsets was comparable between those who died or survived, whereas anti-RBD IgG levels were higher across different time points in deceased patients than in survivors. Enumeration of peripheral blood levels of SARS-CoV-2-S1/M-reactive IFN-γ CD4+ and CD8+ T cells does not predict viral clearance from the lower respiratory tract or poor clinical outcomes in critically ill COVID-19 patients. In contrast, anti-RBD IgG levels were directly associated with increased mortality.

Infant gut microbiota modulation by human milk disaccharides in humanized microbiome mice.

Human milk glycans present a unique diversity of structures that suggest different mechanisms by which they may affect the infant microbiome development. A humanized mouse model generated by infant fecal transplantation was utilized here to evaluate the impact of fucosyl-α1,3-GlcNAc (3FN), fucosyl-α1,6-GlcNAc, lacto-N-biose (LNB) and galacto-N-biose on the fecal microbiota and host-microbiota interactions. 16S rRNA amplicon sequencing showed that certain bacterial genera significantly increased (Ruminococcus and Oscillospira) or decreased (Eubacterium and Clostridium) in all disaccharide-supplemented groups. Interestingly, cluster analysis differentiates the consumption of fucosyl-oligosaccharides from galactosyl-oligosaccharides, highlighting the disappearance of Akkermansia genus in both fucosyl-oligosaccharides. An increment of the relative abundance of Coprococcus genus was only observed with 3FN. As well, LNB significantly increased the relative abundance of Bifidobacterium, whereas the absolute levels of this genus, as measured by quantitative real-time PCR, did not significantly increase. OTUs corresponding to the species Bifidobacterium longum, Bifidobacterium adolescentis and Ruminococcus gnavus were not present in the control after the 3-week intervention, but were shared among the donor and specific disaccharide groups, indicating that their survival is dependent on disaccharide supplementation. The 3FN-feeding group showed increased levels of butyrate and acetate in the colon, and decreased levels of serum HDL-cholesterol. 3FN also down-regulated the pro-inflammatory cytokine TNF-α and up-regulated the anti-inflammatory cytokines IL-10 and IL-13, and the Toll-like receptor 2 in the large intestine tissue. The present study revealed that the four disaccharides show efficacy in producing beneficial compositional shifts of the gut microbiota and in addition, the 3FN demonstrated physiological and immunomodulatory roles.