Microbial epidemiology and clinical risk factors of carbapenemase-producing Enterobacterales amongst Irish patients from first detection in 2009 until 2020.

Background: Carbapenemase producing Enterobacterales (CPE) are major public health threats. Aim: To review microbial epidemiology of CPE, as well as clinical risk factors and infections, amongst CPE positive patients over 12 years in an Irish tertiary hospital. Methods: Retrospective observational study of data extracted from a laboratory CPE database, electronic healthcare records and manual review of patient charts. Common risk factors, treatment regimens for all CPE related infections, and clinical outcomes were ascertained. Findings: Among CPE strains isolated from 460 patients, Klebsiella pneumoniae carbapenemase (KPC) was the carbapenemase most frequently detected, accounting for 87.4% (459) of all CPE enzymes. Citrobacter species 177 (33.7%) were the most common species harbouring this enzyme. 428 CPE positive patients (93%) were identified in the acute hospital setting; the most common risk factor for CPE acquisition was history of hospitalisation, observed in 305 (66%) cases. Thirty patients (6.5%) had confirmed infections post-acquisition, of which four were bloodstream infections. There were 19 subsequent episodes of non CPE-related bacteraemia in this cohort. All causal mortality at 30 days was 41 patients (8.9%). However, clinical review determined that CPE was an indirect associative factor in 8 patient deaths. Conclusions: In this tertiary hospital setting, microbial epidemiology is changing; with both OXA-48 enzymes and KPC-producing Citrobacter species becoming more prevalent. Whilst the burden of CPE related infections, especially bacteraemia, was low over the study period, it remains critical that basic infection prevention and control practices are adhered to lest the observed changes in epidemiology result in an increase in clinical manifestations.

Association between tocilizumab treatment of hyperinflammatory patients with COVID-19 in a critical care setting and elevated incidence of hospital-acquired bacterial and invasive fungal infections.

BACKGROUND: Tocilizumab is an interleukin-6 inhibitor that reduces mortality and the need for invasive mechanical ventilation, while increasing the possibility of successful hospital discharge for hyperinflammatory patients with severe coronavirus disease 2019 (COVID-19). No increase in adverse events or serious infections has been reported previously. AIM: To describe the characteristics and outcomes of patients with severe COVID-19 in critical care who received tocilizumab, and to compare mortality and length of hospital stay for patients who received tocilizumab (N=41) with those who did not (N=33). METHODS: Retrospective review of data related to patients with COVID-19 who received tocilizumab in a critical care setting from 1st January to 31st December 2021. FINDINGS: Amongst COVID-19 survivors, those who had received tocilizumab had longer intensive care unit (ICU) stays (median length 21 vs 9 days) and hospital stays (45 vs 34 days) compared with those who had not received tocilizumab. Thirty-day mortality (29% vs 36%; P=0.5196) and 60-day mortality (37% and 42%; P=0.6138) were not significantly lower in patients who received tocilizumab. Serious bacterial and fungal infections occurred at higher frequency amongst patients who received tocilizumab [odds ratio (OR) 2.67, 95% confidence interval (CI) 1.04-6.86; P=0.042], and at significantly higher frequency than in non-COVID-19 ICU admissions (OR 5.26, 95% CI 3.08-9.00; P<0.0001). CONCLUSIONS: In this single-centre study, patients in critical care with severe COVID-19 who received tocilizumab had a greater number of serious bacterial and fungal infections, but this may not have been a direct effect of tocilizumab treatment.