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.

The Hidden Cost of COVID-19: Focus on Antimicrobial Resistance in Bloodstream Infections.

Antibiotic resistance is one of the greatest growing public health threats and a worldwide priority. According to the WHO, drug-resistant diseases may cause 10 million deaths a year by 2050 and have a substantial impact on the global economy, driving up to 24 million people into poverty. The ongoing COVID-19 pandemic has exposed the fallacies and vulnerability of healthcare systems worldwide, displacing resources from existing programs and reducing funding for antimicrobial resistance (AMR) fighting efforts. Moreover, as already seen for other respiratory viruses, such as flu, COVID-19 is often associated with superinfections, prolonged hospital stays, and increased ICU admissions, further aggravating healthcare disruption. These events are accompanied by widespread antibiotic use, misuse, and inappropriate compliance with standard procedures with a potential long-term impact on AMR. Still, COVID-19-related measures such as increasing personal and environmental hygiene, social distancing, and decreasing hospital admissions could theoretically help the AMR cause. However, several reports have shown increased antimicrobial resistance during the COVID-19 pandemic. This narrative review focuses on this "twindemic", assessing the current knowledge of antimicrobial resistance in the COVID-19 era with a focus on bloodstream infections and provides insights into the lessons learned in the COVID-19 field that could be applied to antimicrobial stewardship initiatives.

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.

Single-agent Bevacizumab in Recurrent Glioblastoma After Second-line Chemotherapy With Fotemustine: The Experience of the Italian Association of Neuro-Oncology.

OBJECTIVES: Bevacizumab is an anti-vascular endothelial growth factor antibody used in the treatment of recurrent glioblastoma (GBM). Despite the large number of studies carried out in patients with recurrent GBM, little is known about the administration of this angiogenesis inhibitor after the failure of the second-line chemotherapy. MATERIALS AND METHODS: In this retrospective multicenter study, on behalf of the Italian Association of Neuro-Oncology, we reported the results obtained in 51 patients with recurrent GBM treated with single-agent bevacizumab after the failure of second-line chemotherapy with fotemustine. RESULTS: In March 2016, at the time of data analysis, 3 patients (14.4%) were still alive with stable disease, whereas 48 died due to disease progression. Kaplan-Meier estimated median survival from the diagnosis of GBM was 28 months (95% confidence interval [CI], 22.1-33.9 mo). Median survival measured from the beginning of fotemustine and bevacizumab therapy were 11.3 (95% CI, 8.4-13.6 mo) and 6 months (95% CI, 3.8-8.1 mo), respectively. The 6- and 12-month progression free survival rates from the beginning of bevacizumab treatment were 18% and 13%, respectively. CONCLUSIONS: On the basis of our data, in patients with recurrent GBM, the failure of a second-line chemotherapy with cytotoxic agents might not exclude the administration of bevacizumab as third-line chemotherapy.