Ventilator-Associated Lower Respiratory Tract Bacterial Infections in COVID-19 Compared With Non-COVID-19 Patients.

OBJECTIVES: Ventilator-associated lower respiratory tract infections (VA-LRTIs) are associated with prolonged length of stay and increased mortality. We aimed to investigate the occurrence of bacterial VA-LRTI among mechanically ventilated COVID-19 patients and compare these findings to non-COVID-19 cohorts throughout the first and second wave of the pandemic. DESIGN: Retrospective cohort study. SETTING: Karolinska University Hospital, Stockholm, Sweden. PATIENTS: All patients greater than or equal to 18 years treated with mechanical ventilation between January 1, 2011, and December 31, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The cohort consisted of 20,223 ICU episodes (479 COVID-19), with a VA-LRTI incidence proportion of 30% (129/426) in COVID-19 and 18% (1,081/5,907) in non-COVID-19 among patients ventilated greater than or equal to 48 hours. The median length of ventilator treatment for COVID-19 patients was 10 days (interquartile range, 5-18 d), which was significantly longer than for all other investigated specific diagnoses. The VA-LRTI incidence rate per 1,000 ventilator days at risk was 31 (95% CI, 26-37) for COVID-19 and 34 (95% CI, 32-36) for non-COVID-19. With COVID-19 as reference, adjusted subdistribution hazard ratios for VA-LRTI was 0.29-0.50 (95% CI, < 1) for influenza, bacterial pneumonia, acute respiratory distress syndrome, and severe sepsis, but 1.38 (95% CI, 1.15-1.65) for specific noninfectious diagnoses. Compared with COVID-19 in the first wave of the pandemic, COVID-19 in the second wave had adjusted subdistribution hazard ratio of 1.85 (95% CI, 1.14-2.99). In early VA-LRTI Staphylococcus aureus was more common and Streptococcus pneumoniae, Haemophilus influenzae, and Escherichia coli less common in COVID-19 patients, while Serratia species was more often identified in late VA-LRTI. CONCLUSIONS: COVID-19 is associated with exceptionally long durations of mechanical ventilation treatment and high VA-LRTI occurrence proportions. The incidence rate of VA-LRTI was compared with the pooled non-COVID-19 cohort, however, not increased in COVID-19. Significant differences in the incidence of VA-LRTI occurred between the first and second wave of the COVID-19 pandemic.

Bacterial co-infections in community-acquired pneumonia caused by SARS-CoV-2, influenza virus and respiratory syncytial virus.

BACKGROUND: A mismatch between a widespread use of broad-spectrum antibiotic agents and a low prevalence of reported bacterial co-infections in patients with SARS-CoV-2 infections has been observed. Herein, we sought to characterize and compare bacterial co-infections at admission in hospitalized patients with SARS-CoV-2, influenza or respiratory syncytial virus (RSV) positive community-acquired pneumonia (CAP). METHODS: A retrospective cohort study of bacterial co-infections at admission in SARS-CoV-2, influenza or RSV-positive adult patients with CAP admitted to Karolinska University Hospital in Stockholm, Sweden, from year 2011 to 2020. The prevalence of bacterial co-infections was investigated and compared between the three virus groups. In each virus group, length of stay, ICU-admission and 30-day mortality was compared in patients with and without bacterial co-infection, adjusting for age, sex and co-morbidities. In the SARS-CoV-2 group, risk factors for bacterial co-infection, were assessed using logistic regression models and creation of two scoring systems based on disease severity, age, co-morbidities and inflammatory markers with assessment of concordance statistics. RESULTS: Compared to influenza and RSV, the bacterial co-infection testing frequency in SARS-CoV-2 was lower for all included test modalities. Four percent [46/1243 (95% CI 3-5)] of all SARS-CoV-2 patients had a bacterial co-infection at admission, whereas the proportion was 27% [209/775 (95% CI 24-30)] and 29% [69/242 (95% CI 23-35)] in influenza and RSV, respectively. S. pneumoniae and S. aureus constituted the most common bacterial findings for all three virus groups. Comparing SARS-CoV-2 positive patients with and without bacterial co-infection at admission, a relevant association could not be demonstrated nor excluded with regards to risk of ICU-admission (aHR 1.53, 95% CI 0.87-2.69) or 30-day mortality (aHR 1.28, 95% CI 0.66-2.46) in adjusted analyses. Bacterial co-infection was associated with increased inflammatory markers, but the diagnostic accuracy was not substantially different in a scoring system based on disease severity, age, co-morbidities and inflammatory parameters [C statistic 0.66 (95% CI 0.59-0.74)], compared to using disease severity, age and co-morbidities only [C statistic 0.63 (95% CI 0.56-0.70)]. CONCLUSIONS: The prevalence of bacterial co-infections was significantly lower in patients with community-acquired SARS-CoV-2 positive pneumonia as compared to influenza and RSV positive pneumonia.

Cerebrospinal fluid cell count variability is a major confounding factor in external ventricular drain-associated infection surveillance diagnostics: a prospective observational study.

BACKGROUND: External ventricular drain (EVD)-related infections (EVDIs) are feared complications that are difficult to rapidly and correctly diagnose, which can lead to unnecessary treatment with broad-spectrum antibiotics. No readily available diagnostic parameters have been identified to reliably predict or identify EVDIs. Moreover, intraventricular hemorrhage is common and affect cerebrospinal fluid (CSF) cellularity. The relationship between leukocytes and erythrocytes is often used to identify suspected infection and triggers the use of antibiotics pending results of cultures, which may take days. Cell count based surveillance diagnostics assumes a homogeneous distribution of cells in the CSF. Given the intraventricular sedimentation of erythrocytes on computed tomography scans this assumption may be erroneous and could affect diagnostics. AIMS: To evaluate the consistency of cell counts in serially sampled CSF from EVDs, with and without patient repositioning, to assess the effect on infection diagnostics. METHODS: We performed a prospective single-center study where routine CSF sampling was followed by a second sample after 10 min, allocated around a standard patient repositioning, or not. Changes in absolute and pairwise cell counts and ratios were analyzed, including mixed regression models. RESULTS: Data from 51 patients and 162 paired samples were analyzed. We observed substantial changes in CSF cellularity as the result of both resampling and repositioning, with repositioning found to be an independent predictor of bidirectional cellular change. Glucose and lactate levels were affected, however clinically non-significant. No positive CSF cultures were seen during the study. Thirty percent (30%) of patients changed suspected EVDI status, as defined by the cell component of local and national guidelines, when resampling after repositioning. CONCLUSIONS: CSF cell counts are not consistent and are affected by patient movement suggesting a heterogeneity in the intraventricular space. The relationship between leukocytes and erythrocytes was less affected than absolute changes. Importantly, cell changes are found to increase with increased cellularity, often leading to changes in suspected EVDI status. Faster and more precise diagnostics are needed, and methods such as emerging next generation sequencing techniques my provide tools to more timely and accurately guide antibiotic treatment. Trial Registration NCT04736407, Clinicaltrials.gov, retrospectively registered 2nd February 2021.

The bacteriology in adult patients with pneumonia and parapneumonic effusions: increased yield with DNA sequencing method.

The aim of this study was to use a 16S rDNA sequencing method in combination with conventional culture in patients with parapneumonic effusions (PPE) to evaluate the methods, study the microbiological spectrum, and examine the presence of bacteria within the different stages of PPE. Adults with community-acquired pneumonia (CAP) and PPE (n = 197) admitted to the Departments of Infectious Diseases at four hospitals in Stockholm County during 2011-2014 were prospectively studied. All patients underwent thoracentesis. Twenty-seven non-infectious pleural effusions were used as controls. The pleural samples were analyzed with culture, 16S rDNA sequencing, pH, glucose, and lactate dehydrogenase. Microbiological etiology was found in 99/197 (50%) of the patients with mixed infections in 20 cases. The most common pathogens were viridans streptococci (n = 37) and anaerobic bacteria (n = 40). Among the 152 patients with both methods performed, 26/152 (17%) and 94/152 (62%) had bacteria identified with culture and 16S rDNA sequencing respectively (p < 0.001). In 24/26 (92%) culture-positive cases, the same organism was identified by 16S rDNA. All controls were negative in both methods. Among the patients with complicated PPE and complete sampling, bacteria were found in 69/74 patients (93%), all detected with 16S rDNA sequencing, compared to 23/74 (31%) culture-positive samples (p < 0.001). Compared with culture, 16S rDNA sequencing substantially improved the microbiological yield, a microbiological diagnosis was achieved in almost all patients with complicated PPE, and the specificity seemed to be high. 16S rDNA sequencing should be used together with culture in patients with PPE to guide antibiotic therapy.

Facile Preparation of Hydrophobic Colloidal MFI and CHA Crystals and Oriented Ultrathin Films.

We report novel routes for synthesis of defect-free, hydrophobic and monodispersed 10 nm (5 unit cells) thick MFI crystals and 100 nm CHA crystals. The crystals are obtained in high yield and display very high 1-butanol adsorption from aqueous solution. These crystals are assembled in monolayers for the growth of ultrathin and uniformly oriented films with thicknesses of 36 nm and 330 nm, respectively, using a synthesis gel in the form of a powder. This method is very simple and may open up for industrial preparation of materials with improved performances.

Adsorption of Butanol and Water Vapors in Silicalite-1 Films with a Low Defect Density.

Pure silica zeolites are potentially hydrophobic and have therefore been considered to be interesting candidates for separating alcohols, e.g., 1-butanol, from water. Zeolites are traditionally synthesized at high pH, leading to the formation of intracrystalline defects in the form of silanol defects in the framework. These silanol groups introduce polar adsorption sites into the framework, potentially reducing the adsorption selectivity toward alcohols in alcohol/water mixtures. In contrast, zeolites prepared at neutral pH using the fluoride route contain significantly fewer defects. Such crystals should show a much higher butanol/water selectivity than crystals prepared in traditional hydroxide (OH-) media. Moreover, silanol groups are present at the external surface of the zeolite crystals; therefore, minimizing the external surface of the studied adsorbent is important. In this work, we determine adsorption isotherms of 1-butanol and water in silicalite-1 films prepared in a fluoride (F-) medium using in situ attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy. This film was composed of well intergrown, plate-shaped b-oriented crystals, resulting in a low external area. Single-component adsorption isotherms of 1-butanol and water were determined in the temperature range of 35-80 °C. The 1-butanol isotherms were typical for an adsorbate showing a high affinity for a microporous material and a large increase in the amount adsorbed at low partial pressures of 1-butanol. The Langmuir-Freundlich model was successfully fitted to the 1-butanol isotherms, and the heat of adsorption was determined. Water showed a very low affinity for the adsorbent, and the amounts adsorbed were very similar to previous reports for large silicalite-1 crystals prepared in a fluoride medium. The sample also adsorbed much less water than did a reference silicalite-1(OH-) film containing a high density of internal defects.The results show that silicalite-1 films prepared in a F- medium with a low density of defects and external area are very promising for the selective recovery of 1-butanol from aqueous solutions.

Colloidal Defect-Free Silicalite-1 Single Crystals: Preparation, Structure Characterization, Adsorption, and Separation Properties for Alcohol/Water Mixtures.

In this work, colloidal silicalite-1 single crystals are for the first time synthesized using fluoride as mineralizing agent at near neutral pH. SEM, TEM, DLS, XRD, solid-state (29)Si MAS NMR, and adsorption/desorption experiments using nitrogen, water, n-butanol, and ethanol as adsorbates were used to characterize the crystals. The single crystals have a platelike habit with a length of less than 170 nm and an aspect ratio (length/width) of about 1.2, and the thickness of the crystals is less than 40 nm. Compared with silicalite-1 crystals grown using hydroxide as mineralizing agent, the amount of structural defects in the lattice is significantly reduced and the hydrophobicity is increased. Membrane separation and adsorption results show that the synthesized defect-free crystals present high selectivity to alcohols from alcohol/water mixtures. The n-butanol/water adsorption selectivities were ca. 165 and 14 for the defect-free crystals and a reference sample containing defects, respectively, illustrating the improvement in n-butanol/water selectivity by eliminating the polar silanol defects.

Adsorption of water and butanol in silicalite-1 film studied with in situ attenuated total reflectance-Fourier transform infrared spectroscopy.

Biobutanol produced by, e.g., acetone-butanol-ethanol (ABE) fermentation is a promising alternative to petroleum-based chemicals as, e.g., solvent and fuel. Recovery of butanol from dilute fermentation broths by hydrophobic membranes and adsorbents has been identified as a promising route. In this work, the adsorption of water and butanol vapor in a silicalite-1 film was studied using in situ attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy to better understand the adsorption properties of silicalite-1 membranes and adsorbents. Single-component adsorption isotherms were determined in the temperature range of 35-120 °C, and the Langmuir model was successfully fitted to the experimental data. The adsorption of butanol is very favorable compared to that of water. When the silicalite-1 film was exposed to a butanol/water vapor mixture with 15 mol % butanol (which is the vapor composition of an aqueous solution containing 2 wt % butanol, a typical concentration in an ABE fermentation broth, i.e., the composition of the gas obtained from gas stripping of an ABE broth) at 35 °C, the adsorption selectivity toward butanol was as high as 107. These results confirm that silicalite-1 quite selectively adsorbs hydrocarbons from vapor mixtures. To the best of our knowledge, this is the first comprehensive study on the adsorption of water and butanol in silicalite-1 from vapor phase.

Procalcitonin levels in community-acquired pneumonia - correlation with aetiology and severity.

We studied procalcitonin (PCT) levels at hospital admittance and their association with aetiology and severity in patients with community-acquired pneumonia (CAP). Median PCT concentrations were higher in bacteraemic patients than in those without bacteraemia (6.11 µg/L vs 0.34 µg/L, p = 0.0002), in patients with non-bacteraemic pneumococcal aetiology than in those infected with other classic bacteria (1.18 vs 0.18, p = 0.038), and in patients with pneumococcal as compared with viral aetiology (2.43 vs 0.24, p = 0.017). When aetiology, bacteraemia and severity according to the pneumonia severity index (PSI) were included in logistic regression analyses with PCT > 0.5 as a dependent variable, the odds ratio (OR) for non-bacteraemic pneumococcal aetiology was 5.7 (p = 0.008) and 3.0 ( p = 0.1) for PSI 4-5. A separate analysis for bacteraemia and PSI 4-5 showed an OR of 17.5 (p = 0.008) and 2.7 (p = 0.092), respectively. In CAP patients, high PCT seems to be a good marker for invasive disease and pneumococcal aetiology. As a predictor of severity it appears to be less important.

Microstructure of bentonite in iron ore green pellets.

Sodium-activated calcium bentonite is used as a binder in iron ore pellets and is known to increase strength of both wet and dry iron ore green pellets. In this article, the microstructure of bentonite in magnetite pellets is revealed for the first time using scanning electron microscopy. The microstructure of bentonite in wet and dry iron ore pellets, as well as in distilled water, was imaged by various imaging techniques (e.g., imaging at low voltage with monochromatic and decelerated beam or low loss backscattered electrons) and cryogenic methods (i.e., high pressure freezing and plunge freezing in liquid ethane). In wet iron ore green pellets, clay tactoids (stacks of parallel primary clay platelets) were very well dispersed and formed a voluminous network occupying the space available between mineral particles. When the pellet was dried, bentonite was drawn to the contact points between the particles and formed solid bridges, which impart strength to the solid compact.