On the use of intravenous metronidazole for severe and complicated Clostridioides difficile infection: a review and meta-analysis.

The European Society of Clinical Microbiology and Infectious Disease (ESCMID) has advised against the use of metronidazole for fulminant Clostridioides difficile (C. difficile) infection (CDI) in their latest guidelines. They suggest using oral vancomycin alone instead. This recommendation is based on a few retrospective studies, which have multiple biases. We evaluated the three studies that led ESCMID to advise against intravenous metronidazole for fulminant CDI and performed a meta-analysis. The meta-analysis revealed a mild (2.7%), not statistically significant (p=0.8) difference in mortality between the two groups. The high heterogeneity (I2= 89%) should also be noted. The decision to add or remove metronidazole should be discussed in the near future. In the meantime, combination therapy could be a cautious treatment for fulminant CDI.

Clostridioides difficile infection: history, epidemiology, risk factors, prevention, clinical manifestations, treatment, and future options.

SUMMARYClostridioides difficile infection (CDI) is one of the major issues in nosocomial infections. This bacterium is constantly evolving and poses complex challenges for clinicians, often encountered in real-life scenarios. In the face of CDI, we are increasingly equipped with new therapeutic strategies, such as monoclonal antibodies and live biotherapeutic products, which need to be thoroughly understood to fully harness their benefits. Moreover, interesting options are currently under study for the future, including bacteriophages, vaccines, and antibiotic inhibitors. Surveillance and prevention strategies continue to play a pivotal role in limiting the spread of the infection. In this review, we aim to provide the reader with a comprehensive overview of epidemiological aspects, predisposing factors, clinical manifestations, diagnostic tools, and current and future prophylactic and therapeutic options for C. difficile infection.

Understanding the effect of heating rate on hydrothermal liquefaction: A comprehensive investigation from model compounds to a real food waste.

Hydrothermal liquefaction (HTL) emerges as an efficient technology for converting food waste into biocrude. Among HTL parameters, the impact of heating rate is understudied. This study systematically explores its variation (5-115 K/min) on HTL performance using actual food waste and model compounds representing its constituents. Results revealed that an increase in heating rates significantly impacts HTL performances (+63 % biocrude and -34 % solid with food waste) with short residence times, as slower heating rates imply a longer overall time and a higher kinetic advancement of the reaction. Conversely, with longer residence times, the influence of heating rates becomes negligible, as kinetics during heating times are overshadowed by those at operating temperatures. A subtle effect of heating variation at extended residence time was observed only with carbohydrates. This research emphasizes the utility of a kinetic severity factor (KSF) as a valuable tool for simultaneously considering heating rates, operating times, and temperatures.

Intravenous Fosfomycin for Systemic Multidrug-Resistant Pseudomonas aeruginosa Infections.

Human Pseudomonas infections have high morbidity and mortality rates. Pseudomonas bacteria can cause sepsis or septic shock; they produce biofilm and commonly exhibit a multidrug-resistant phenotype. The choice of antimicrobial therapy in many cases is challenging, and deep knowledge of clinical, microbiological, and pharmacological issues is required. Intravenous fosfomycin is being repurposed in a combination given its favorable pharmacokinetic/pharmacodynamic properties (a small molecule with favorable kinetic both in bloodstream infection and in deep-seated infections), antibiofilm activity, and its interesting synergistic effects with other antimicrobials. Recent literature on epidemiological, microbiological, pharmacological, and clinical data on intravenous fosfomycin therapy against Pseudomonas is herein reviewed and discussed.

A pediatric case of Chlamydia psittaci caused severe Acute Respiratory Distress Syndrome (ARDS) in Italy.

BACKGROUND: This case of psittacosis in children, is the first described in literature, in Italy. This respiratory infection can be transmitted to humans from the inhalation of respiratory secretions, feces and plumage aerosol of infected birds (and other animals). Usually it can have an asymptomatic or paucisymptomatic course, and the onset is often flu-like, but in this case the child risked his life for a severe respiratory failure. This report is unique because in children psittacosis is rare, and always misdiagnosed, or could cause a delayed diagnosis because of lack of awareness among the paediatricians and physicians. Furthermore, psittacosis enters a differential diagnosis with SARS-COV2 infection because both diseases may determine dyspnea and atypical pneumonia, up to acute respiratory failure. CASE PRESENTATION: This clinical case talks about a three-and-a-half-year-old male child affected by psittacosis (or ornithosis), with severe dyspnea and systemic symptoms who required oro-tracheal intubation for acute respiratory failure. The child had slept in a room at home, with some recently bought parrots affected by psittacosis. Initially the child was treated with empiric antibiotic therapy (i.v.ceftriaxone and teicoplanin), but after having isolated the DNA of the germ "Chlamydia psittaci" in both serological and through bronchoalveolar lavage (BAL), he was treated with targeted antibiotic therapy: tetracyclines (doxicillin). CONCLUSIONS: Psittacosis is an extremely contagious disease, caused by an intracellular germ, called "Chlamydia psittaci", a Gram-negative bacterium, transmitted to humans in particular by infected birds, responsible for atypical pneumonia, with acute and chronic respiratory symptoms, sometimes with multi-organ failure and disseminated intravascular coagulation. Even if it is a rare respiratory disease among children, a good doctor must think about psittacosis as cause of respiratory symptoms (and not only flu or SARS-COV2), above all through a correct medical history, in order to provide a targeted antibiotic therapy. An interesting case of psittacosis in a child is being reported here, which has been treated successfully with doxycillin.

Antibiotics Use in COVID-19 Patients: A Systematic Literature Review.

The issue of bacterial infections in COVID-19 patients has received increasing attention among scientists. Antibiotics were widely prescribed during the early phase of the pandemic. We performed a literature review to assess the reasons, evidence and practices on the use of antibiotics in COVID-19 in- and outpatients. Published articles providing data on antibiotics use in COVID-19 patients were identified through computerized literature searches on the MEDLINE and SCOPUS databases. Searching the MEDLINE database, the following search terms were adopted: ((antibiotic) AND (COVID-19)). Searching the SCOPUS database, the following search terms were used: ((antibiotic treatment) AND (COVID-19)). The risk of bias in the included studies was not assessed. Both quantitative and qualitative information were summarized by means of textual descriptions. Five-hundred-ninety-three studies were identified, published from January 2020 to 30 October 2022. Thirty-six studies were included in this systematic review. Of the 36 included studies, 32 studies were on the use of antibiotics in COVID-19 inpatients and 4 on antibiotic use in COVID-19 outpatients. Apart from the studies identified and included in the review, the main recommendations on antibiotic treatment from 5 guidelines for the clinical management of COVID-19 were also summarized in a separate paragraph. Antibiotics should not be prescribed during COVID-19 unless there is a strong clinical suspicion of bacterial coinfection or superinfection.

Bezlotoxumab in Patients with a Primary Clostridioides difficile Infection: A Literature Review.

BACKGROUND: Nowadays, one of the main issues in the management of Clostridioides difficile infection (CDI) is the high rate of recurrences (rCDI), causing increased mortality and higher health care costs. OBJECTIVES: To assess the available evidence on the use of bezlotoxumab for the prevention of rCDI during a first CDI episode. METHODS: Published articles on bezlotoxumab during a primary CDI episode were identified through computerized literature searches with the search terms [(bezlotoxumab) AND (CDI) OR (Clostridioides difficile infection)] using PubMed and by reviewing the references of retrieved articles. PubMed was searched until 31 August 2022. RESULTS: Eighty-eight studies were identified as published from December 2014 to June 2022. Five studies were included in this study, one was a phase III clinical trial and four were sub-analyses or extensions of the previous phase III clinical trial. In the phase III clinical trial, the subgroup analysis on the included primary CDI patients showed that 13.5% of patients receiving bezlotoxumab had an rCDI, whilst 20.9% of patients in the placebo group had an rCDI at the twelve weeks follow-up (absolute difference: -7.4). CONCLUSIONS: Bezlotoxumab administration during the standard of care antibiotic therapy is effective and safe in reducing the rate of rCDI. Despite its high cost, evidence suggests considering bezlotoxumab in patients with a primary CDI episode. Further studies are needed to assess the benefit in specific subgroups of primary CDI patients and to define the risk factors to guide bezlotoxumab use.

Alveolar-Arterial Gradient Is an Early Marker to Predict Severe Pneumonia in COVID-19 Patients.

Background: One of the main challenges in the management of COVID-19 patients is to early assess and stratify them according to their risk of developing severe pneumonia. The alveolar−arterial oxygen gradient (D(A-a)O2) is defined as the difference between the alveolar and arteriolar concentration of oxygen, an accurate index of the ventilatory function. The aim of this study is to evaluate D(A-a)O2 as a marker for predicting severe pneumonia in COVID-19 patients, in comparison to the PaO2/FiO2. Methods: This retrospective, multicentric cohort study included COVID-19 patients admitted to two Italian hospitals between April and July 2020. Clinical and laboratory data were retrospectively collected at the time of hospital admission and during hospitalization. The presence of severe COVID-19 pneumonia was evaluated, as defined by the Infectious Diseases Society of America (IDSA) criteria for community-acquired pneumonia (CAP). Patients were divided in severe and non-severe groups. Results: Overall, 53 COVID-19 patients were included in the study: male were 30/53 (57%), and 10/53 (19%) had severe pneumonia. Patients with severe pneumonia reported dyspnea more often than non-severe patients (90% vs. 39.5%; p = 0.031). A history of chronic obstructive pulmonary disease (COPD) was recalled by 5/10 (50%) patients with severe pneumonia, and only in 6/43 (1.4%) of non-severe cases (p = 0.023). A ROC curve, for D(A-a)O2 >60 mmHg in detecting severe pneumonia, showed an area under the curve (AUC) of 0.877 (95% CI: 0.675−1), while the AUC of PaO2/FiO2 < 263 mmHg resulted 0.802 (95% CI: 0.544−1). D(A-a)O2 in comparison to PaO2/FiO2 had a higher sensibility (77.8% vs. 66.7%), positive predictive value (75% vs. 71.4%), negative predictive value (94% vs. 91%), and similar specificity (94.4% vs. 95.5%). Conclusions: Our study suggests that the D(A-a)O2 is more appropriate than PaO2/FiO2 to identify COVID-19 patients at risk of developing severe pneumonia early.

Vaccine-Induced Subacute Thyroiditis (De Quervain's) after mRNA Vaccine against SARS-CoV-2: A Case Report and Systematic Review.

De Quervain's thyroiditis, sometimes referred to as subacute thyroiditis (SAT), is the most common granulomatous disease of the thyroid, typically found after a viral infection in middle-aged women. The mRNA encoding for the angiotensin-converting enzyme-2 (ACE-2) receptor is expressed in follicular thyroid cells, making them a potential target for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Besides infection, SARS-CoV-2 vaccines have also been implicated in SAT pathogenesis. We present a case of a woman developing SAT following vaccination with Comirnaty by Pfizer Inc. (New-York, USA). We performed a systematic review of similar cases available in the literature to provide a better understanding of the topic. We searched the databases PubMed and Embase and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Patient records were then sorted according to the type of administered vaccine and a statistical analysis of the extracted data was performed. No statistically significant difference between mRNA vaccines and other vaccines in inducing SAT was found, nor was any found in terms of patient demographics, symptoms at presentation, initial, or follow-up blood tests. In our case report, we described the possible association between SARS-CoV-2 mRNA-based vaccine Comirnaty and SAT.

Invasive cryptococcal disease in COVID-19: systematic review of the literature and analysis.

During the Coronavirus Disease 2019 (COVID-19) pandemic, an increasing number of fungal infections associated with SARS-CoV-2 infection have been reported. Among them, cryptococcosis could be a life-threatening disease. We performed a Systematic Review (PRISMA Statement) of cryptococcosis and COVID-19 co-infection, case report/series were included: a total of 34 cases were found, then we added our case report. We collected patients' data and performed a statistical analysis comparing two groups of patients sorted by outcome: "dead" and "alive". Three cases were excluded for lack of information. To compare categorical data, we used a Fisher-exact test (α=0.05). To compare quantitative variables a U Mann-Whitney test was used (α=0.05), with a 95% Confidence Interval. A total of 32 co-infected patients were included in the statistical analysis. Mortality rate was 17/32 (53.1%): these patients were included in "dead" group, and 15/32 (46.9%) patients survived and were included in "alive" group. Overall, males were 25/32 (78.1%), the median age was 60 years (IQR 53-70) with non-statistically significant difference between groups (p=0.149 and p=0.911, respectively). Three variables were associated with mortality: ARDS, ICU admission and inadequate treatment. Overall, 21 out of 24 (87.5%) patients were in ARDS with a statistically significant difference among two groups (p=0.028). ICU admission for COVID-19 was observed in 18/26 (69.2%), more frequently among dead group (p=0.034). Finally, 15/32 (46.9%) patients had adequate treatment (amphotericin B + flucytosine for invasive cryptococcosis) mostly among alive patients (p=0.039). In conclusion, mortality due to cryptococcal infection among COVID-19 patients remains high but an early diagnosis and appropriate treatment could reduce mortality.

Tuberculosis among Migrant Populations in Sicily: A Field Report.

BACKGROUND: In the EU, tuberculosis (TB) mainly affects vulnerable people, including migrants. From 2014 to 2017, we have estimated the frequency of both tuberculosis and latent tuberculosis infection (LTBI) among the migrant population hosted in 41 reception centers in western Sicily (ITaCA network). MATERIALS AND METHODS: All migrants were consecutively recruited for the screening of TB infection with physical examination and TST in 1,020 migrants and with IGRA in the others 2,690. The screening was carried out 4-8 weeks after landing in Sicily. For all migrants with a positive screening test, chest X-ray and smear examination were performed. LTBI was defined by positivity of TST or IGRA with negative X-ray chest, clinical, and smear examination. Active TB was defined by radiological and/or clinical and/or sputum positivity in a patient with a TST or IGRA positivity. RESULTS: We evaluated a total of 3,710 migrants, of which 89% came from Sub-Saharan countries; 2,811 were males, 899 were females, with a median age of 22 years (IQR: 18-25). TB infection was diagnosed in 501 persons (13.5%) of which 440 (11.8%) had LTBI and 61 had active TB (1.6%): 1 had lymph node TB, 1 had intestinal TB, and 59 had pulmonary TB (38 sputum smear positive TB; no drug-resistant TB were observed). CONCLUSIONS: TB screening is critical to early diagnosis and treatment.

Influence of the Catalyst Particle Size on the Aqueous Phase Reforming of n-Butanol Over Rh/ZrO2.

Butanol is a by-product obtained from biomass that can be valorized through aqueous phase reforming. Rh/ZrO2 catalysts were prepared and characterized, varying the size of the support particles. The results showed a relatively mild effect of internal mass transport on butanol conversion. However, the influence of internal transport limitations on the product distribution was much stronger, promoting consecutive reactions, i.e., dehydrogenation, hydrogenolysis, and reforming of propane and ethane. Hydrogen consuming reactions, i.e., hydrogenolysis, were more strongly enhanced than hydrogen producing reactions due to internal concentration gradients. Large support particles deactivated faster, attributed to high concentrations of butyraldehyde inside the catalyst particles, enhancing deposit formation via aldol condensation reactions. Consequently, also the local butyric acid concentration was high, decreasing the local pH, enhancing Rh leaching. The influence of internal transfer limitation on product distribution and stability is discussed based on a reaction scheme with three main stages, i.e., (1) formation of liquid intermediates via dehydrogenation, (2) formation of gas via decarbonylation/decarboxylation reactions, and (3) hydrocarbon hydrogenolysis/reforming/dehydrogenation.

Robust Mesoporous CoMo/γ-Al2O3 Catalysts from Cyclodextrin-Based Supramolecular Assemblies for Hydrothermal Processing of Microalgae: Effect of the Preparation Method.

Hydrothermal liquefaction (HTL) is a promising technology for the production of biocrude oil from microalgae. Although this catalyst-free technology is efficient under high-temperature and high-pressure conditions, the biocrude yield and quality can be further improved by using heterogeneous catalysts. The design of robust catalysts that preserve their performance under hydrothermal conditions will be therefore very important in the development of biorefinery technologies. In this work, we describe two different synthetic routes (i.e., impregnation and cyclodextrin-assisted one-pot colloidal approach), for the preparation in aqueous phase of six high surface area CoMo/γ-Al2O3 catalysts. Catalytic tests performed on the HTL of Nannochloropsis gaditana microalga indicate that solids prepared by the one-pot colloidal approach show higher hydrothermal stability and enhanced biocrude yield with respect to the catalyst-free test. The positive effect of the substitution of the block copolymer Tetronic T90R4 for Pluronic F127 in the preparation procedure was evidenced by diffuse reflectance UV-visible spectroscopy, X-ray diffraction, N2-adsorption-desorption, and H2-temperature-programmed reduction measurements and confirmed by the higher quality of the obtained biocrude, which exhibited lower oxygen content and higher-energy recovery equal to 62.5% of the initial biomass.