In a retrospective study conducted in an Italian tertiary care hospital, the incidence of nosocomial candidemia was evaluated together with causative pathogens, treatment, and risk factors for death. Over a 6-year period (1992-1997), a total of 189 episodes of candidemia occurred in 189 patients (mean age 58+/-19 years), accounting for an average incidence of 1.14 episodes per 10,000 patient-days per year. The most common reasons for hospitalization were solid neoplasia (21%), trauma (17%), abdominal diseases requiring surgery (13%), and cardiovascular diseases (13%). No patient was neutropenic within 3 weeks prior to the onset of candidemia. One hundred thirty patients were hospitalized in intensive care units, 47 patients in surgical wards, and 12 patients in medical wards. Candida albicans was the most frequently isolated pathogen, accounting for 54% of fungal isolates, followed by Candida parapsilosis (23%), Candida glabrata (7%), Candida tropicalis (5%), Candida pelliculosa (4%), Candida lusitaniae (1%), Candida humicula (1%), and other non-albicans Candida spp. (5%). Seventy-six (41%) patients received adequate antifungal therapy. Seventy-one (58%) of the 123 evaluable patients with central venous catheters underwent line removal; 51 of them had catheter-related candidemia. The 30-day crude mortality rate was 45%. Older age, hospitalization in an intensive care unit, a longer duration of candidemia, retention of central lines, and inadequate antifungal therapy were significantly associated with poor outcome. In the present study, nosocomial candidemia was a frequent and relatively underestimated illness. Adequate antifungal therapy and central line removal independently reduced the high mortality of the disease.

Background Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. Methods A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. Results In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6–24.0, P = 0.52) and 22.4% (97.5% CI: 17.2–28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. Conclusions Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).

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Seven patients with staphylococcal neurosurgical shunt infections were treated with intraventricular teicoplanin. Two infants received 5 mg/d, three patients received 20 mg/d, and two patients received 20 mg every other day. Six of these patients also received intravenous antibiotics. Three patients had infections caused by methicillin-susceptible Staphylococcus epidermidis, and one patient had an infection caused by methicillin-resistant S. epidermidis. Three patients were infected with Staphylococcus aureus (one with a methicillin-resistant strain and two with methicillin-susceptible strains). The mean duration of intraventricular therapy was 16 days. Sterilization of cerebrospinal fluid (CSF) was obtained after an average of 4.4 days. All patients were cured both clinically and microbiologically. No significant adverse effects were observed in any patients. Penetration of teicoplanin into the CSF after intravenous administration was poor. However, after intraventricular administration, high and prolonged peak and trough levels of teicoplanin were detected in the CSF. Bactericidal activity of the CSF was remarkable, exceeding the 1:8 dilution in the majority of the cases. The alternate-day schedule of intraventricular administration of teicoplanin was as effective as the once-daily regimen.