Clostridioides difficile infection: an update.

Clostridioides difficile (C. difficile) is a Gram-positive, spore-forming anaerobic bacterium emerged as a leading cause of diarrhea globally. CDI's (Clostridioides difficile infection) impact on healthcare systems is concerning due to high treatment cost and increased hospitalisation time. The incidence of CDI has been influenced by hypervirulent strains such as the 027 ribotype, responsible for significant outbreaks in North America and Europe. CDI's epidemiology has evolved, showing increased community-acquired cases alongside traditional hospital-acquired infections. Mortality rates remain high, with recurrent infections further elevating the risk. Transmission of C. difficile primarily occurs via spores, which survive in healthcare settings and play a pivotal role in transmission. Not only health workers, but also the food chain could have a significant impact on the transmission of infection, although no confirmed foodborne cases have been documented. Pathogenicity of C. difficile involves spore germination and toxin production. Toxins A and B can cause cellular damage and inflammatory responses in the host, leading to colitis. Clinical picture can range from mild diarrhea to fulminant colitis with toxic megacolon, and bowel perforation. Risk factors for CDI include antibiotic exposure, advanced age, hospitalization, and use of proton pump inhibitors. Patients who experience abdominal surgery or patients with inflammatory bowel disease (IBD) are particularly susceptible due to their compromised gut microbiota. Management of CDI has evolved, with fidaxomicin emerging as a superior treatment option over vancomycin for initial and recurrent infections due to its reduction of recurrence rate. Faecal microbiota transplantation (FMT) is effective for recurrent CDI, restoring gut eubiosis. Bezlotoxumab, a monoclonal antibody against C. difficile toxin B, has shown promise in reducing recurrence rates. Severe cases of CDI may require surgical intervention, particularly in instances of toxic megacolon or bowel perforation. In conclusion, CDI remains a significant clinical entity. Further research are needed to improve patients' outcome and reduce the burden on healthcare systems.

Association of piperacillin/tazobactam MIC and mortality in a cohort of ceftriaxone-resistant Escherichia coli bloodstream infections treated with piperacillin/tazobactam and carbapenems: a multicentric propensity score-weighted observational cohort study.

OBJECTIVES: To assess the impact of piperacillin/tazobactam MICs on in-hospital 30 day mortality in patients with third-generation cephalosporin-resistant Escherichia coli bloodstream infection treated with piperacillin/tazobactam, compared with those treated with carbapenems. METHODS: A multicentre retrospective cohort study was conducted in three large academic hospitals in Italy between 2018 and 2022. The study population comprised patients with monomicrobial third-generation cephalosporin-resistant E. coli bloodstream infection, who received either piperacillin/tazobactam or carbapenem therapy within 48 h of blood culture collection. The primary outcome was in-hospital 30 day all-cause mortality. A propensity score was used to estimate the likelihood of receiving empirical piperacillin/tazobactam treatment. Cox regression models were performed to ascertain risk factors independently associated with in-hospital 30 day mortality. RESULTS: Of the 412 consecutive patients included in the study, 51% received empirical therapy with piperacillin/tazobactam, while 49% received carbapenem therapy. In the propensity-adjusted multiple Cox model, the Pitt bacteraemia score [HR 1.38 (95% CI, 0.85-2.16)] and piperacillin/tazobactam MICs of 8 mg/L [HR 2.35 (95% CI, 1.35-3.95)] and ≥16 mg/L [HR 3.69 (95% CI, 1.86-6.91)] were significantly associated with increased in-hospital 30 day mortality, while the empirical use of piperacillin/tazobactam was not found to predict in-hospital 30 day mortality [HR 1.38 (95% CI, 0.85-2.16)]. CONCLUSIONS: Piperacillin/tazobactam use might not be associated with increased mortality in treating third-generation cephalosporin-resistant E. coli bloodstream infections when the MIC is <8 mg/L.

Anakinra in hospitalized COVID-19 patients guided by baseline soluble urokinase plasminogen receptor plasma levels: A real world, retrospective cohort study.

BACKGROUND: In patients with COVID-19 and baseline soluble urokinase plasminogen receptor plasma (suPAR) levels ≥ 6ng/mL, early administration of anakinra, a recombinant interleukin-1 receptor antagonist, may prevent disease progression and death. In case of suPAR testing unavailability, the Severe COvid Prediction Estimate (SCOPE) score may be used as an alternative in guiding treatment decisions. METHODS: We conducted a monocenter, retrospective cohort study, including patients with SARS-CoV2 infection and respiratory failure. Patients treated with anakinra (anakinra group, AG) were compared to two control groups of patients who did not receive anakinra, respectively with ≥ 6 ng/mL (CG1) and < 6 ng/mL (CG2) baseline suPAR levels. Controls were manually paired by age, sex, date of admission and vaccination status and, for patients with high baseline suPAR, propensity score weighting for receiving anakinra was applied. Primary endpoint of the study was disease progression at day 14 from admission, as defined by patient distribution on a simplified version of the 11-point World Health Organization Clinical Progression Scale (WHO-CPS). RESULTS: Between July, 2021 and January, 2022, 153 patients were included, among which 56 were treated with off-label anakinra, 49 retrospectively fulfilled prescriptive criteria for anakinra and were assigned to CG1, and 48 presented with suPAR levels < 6ng/mL and were assigned to CG2. At day 14, when comparing to CG1, patients who received anakinra had significantly reduced odds of progressing towards worse clinical outcome both in ordinal regression analysis (OR 0.25, 95% CI 0.11-0.54, p<0.001) and in propensity-adjusted multiple logistic regression analysis (OR 0.32, 95% CI 0.12-0.82, p = 0.021) thus controlling for a wide number of covariates. Sensitivities of baseline suPAR and SCOPE score in predicting progression towards severe disease or death at day 14 were similar (83% vs 100%, p = 0.59). CONCLUSION: This real-word, retrospective cohort study confirmed the safety and the efficacy of suPAR-guided, early use of anakinra in hospitalized COVID-19 patients with respiratory failure.

Impact of SARS-CoV-2 Epidemic on Antimicrobial Resistance: A Literature Review.

Antimicrobial resistance is an urgent threat to public health and global development; in this scenario, the SARS-CoV2 pandemic has caused a major disruption of healthcare systems and practices. A narrative review was conducted on articles focusing on the impact of COVID-19 on multidrug-resistant gram-negative, gram-positive bacteria, and fungi. We found that, worldwide, multiple studies reported an unexpected high incidence of infections due to methicillin-resistant S. aureus, carbapenem-resistant A. baumannii, carbapenem-resistant Enterobacteriaceae, and C. auris among COVID-19 patients admitted to the intensive care unit. In this setting, inappropriate antimicrobial exposure, environmental contamination, and discontinuation of infection control measures may have driven selection and diffusion of drug-resistant pathogens.

Adjunctive corticosteroid treatment for organizing pneumonia in COVID-19 patients with persistent respiratory failure.

Since the beginning of COVID-19 pandemic, clinical, radiological and histopathological features consistent with viral-induced organizing pneumonia (OP) have been reported as hallmark characteristics of the disease. Here, we describe the case of ten patients with severe COVID-19 pneumonia treated with methylprednisolone 1mg/kg for showing clinical and radiological features suggestive of OP at least 20 days after symptom onset and despite standard treatment for COVID-19.