Correction to: Early Stepdown From Echinocandin to Fluconazole Treatment in Candidemia: A Post Hoc Analysis of Three Cohort Studies.

[This corrects the article DOI: 10.1093/ofid/ofab250.].

Early Stepdown From Echinocandin to Fluconazole Treatment in Candidemia: A Post Hoc Analysis of Three Cohort Studies.

BACKGROUND: There are no clear criteria for antifungal de-escalation after initial empirical treatments. We hypothesized that early de-escalation (ED) (within 5 days) to fluconazole is safe in fluconazole-susceptible candidemia with controlled source of infection. METHODS: This is a multicenter post hoc study that included consecutive patients from 3 prospective candidemia cohorts (2007-2016). The impact of ED and factors associated with mortality were assessed. RESULTS: Of 1023 candidemia episodes, 235 met inclusion criteria. Of these, 54 (23%) were classified as the ED group and 181 (77%) were classified as the non-ED group. ED was more common in catheter-related candidemia (51.9% vs 31.5%; P = .006) and episodes caused by Candida parapsilosis, yet it was less frequent in patients in the intensive care unit (24.1% vs 39.2%; P = .043), infections caused by Nakaseomyces glabrata (0% vs 9.9%; P = .016), and candidemia from an unknown source (24.1% vs 47%; P = .003). In the ED and non-ED groups, 30-day mortality was 11.1% and 29.8% (P = .006), respectively. Chronic obstructive pulmonary disease (odds ratio [OR], 3.97; 95% confidence interval [CI], 1.48-10.61), Pitt score > 2 (OR, 4.39; 95% CI, 1.94-9.20), unknown source of candidemia (OR, 2.59; 95% CI, 1.14-5.86), candidemia caused by Candida albicans (OR, 3.92; 95% CI, 1.48-10.61), and prior surgery (OR, 0.29; 95% CI, 0.08-0.97) were independent predictors of mortality. Similar results were found when a propensity score for receiving ED was incorporated into the model. ED had no significant impact on mortality (OR, 0.50; 95% CI, 0.16-1.53). CONCLUSIONS: Early de-escalation is a safe strategy in patients with candidemia caused by fluconazole-susceptible strains with controlled source of bloodstream infection and hemodynamic stability. These results are important to apply antifungal stewardship strategies.

Experience with the use of siltuximab in patients with SARS-CoV-2 infection.

OBJECTIVE: The study aims to describe characteristics and clinical outcome of patients with SARS-CoV-2 infection that received siltuximab according to a protocol that aimed to early block the activity of IL-6 to avoid the progression of the inflammatory flare. METHODS: Retrospective review of the first 31 patients with SARS-CoV-2 treated with siltuximab, in Hospital Clinic of Barcelona or Hospital Universitario Salamanca, from March to April 2020 with positive polymerase-chain reaction (PCR) from a nasopharyngeal swab. RESULTS: The cohort included 31 cases that received siltuximab with a median (IQR) age of 62 (56-71) and 71% were males. The most frequent comorbidity was hypertension (48%). The median dose of siltuximab was 800 mg ranging between 785 and 900 mg. 7 patients received siltuximab as a salvage therapy after one dose of tocilizumab. At the end of the study, a total of 26 (83.9) patients had been discharged alive and the mortality rate was 16.1% but only 1 out of 24 that received siltuximab as a first line option (4%). CONCLUSIONS: Siltuximab is a well-tolerated alternative to tocilizumab when administered as a first line option in patients with COVID-19 pneumonia within the first 10 days from symptoms onset and high C-reactive protein.

Tocilizumab reduces the risk of ICU admission and mortality in patients with SARS-CoV-2 infection.

OBJECTIVE: In some patients the immune response triggered by SARS-CoV-2 is unbalanced, presenting an acute respiratory distress syndrome which in many cases requires intensive care unit (ICU) admission. The limitation of ICU beds has been one of the major burdens in the management around the world; therefore, clinical strategies to avoid ICU admission are needed. We aimed to describe the influence of tocilizumab on the need of transfer to ICU or death in non-critically ill patients. METHODS: A retrospective study of 171 patients with SARS-CoV-2 infection that did not qualify as requiring transfer to ICU during the first 24h after admission to a conventional ward, were included. The criteria to receive tocilizumab was radiological impairment, oxygen demand or an increasing of inflammatory parameters, however, the ultimate decision was left to the attending physician judgement. The primary outcome was the need of ICU admission or death whichever came first. RESULTS: A total of 77 patients received tocilizumab and 94 did not. The tocilizumab group had less ICU admissions (10.3% vs. 27.6%, P=0.005) and need of invasive ventilation (0 vs 13.8%, P=0.001). In the multivariable analysis, tocilizumab remained as a protective variable (OR: 0.03, CI 95%: 0.007-0.1, P=0.0001) of ICU admission or death. CONCLUSIONS: Tocilizumab in early stages of the inflammatory flare could reduce an important number of ICU admissions and mechanical ventilation. The mortality rate of 10.3% among patients receiving tocilizumab appears to be lower than other reports. This is a non-randomized study and the results should be interpreted with caution.

Predictors of multidrug-resistant Pseudomonas aeruginosa in neutropenic patients with bloodstream infection.

OBJECTIVES: To assess risk factors for multidrug-resistant Pseudomonas aeruginosa (MDR-PA) infection in neutropenic patients. METHODS: Single-centre retrospective analysis of consecutive bloodstream infection (BSI) episodes (2004-2017, Barcelona). Two multivariate regression models were used at BSI diagnosis and P. aeruginosa detection. Significant predictors were used to establish rules for stratifying patients according to MDR-PA BSI risk. RESULTS: Of 661 Gram-negative BSI episodes, 190 (28.7%) were caused by P. aeruginosa (70 MDR-PA). Independent factors associated with MDR-PA among Gram-negative organisms were haematological malignancy (OR 3.30; 95% CI 1.15-9.50), pulmonary source of infection (OR 7.85; 95% CI 3.32-18.56), nosocomial-acquired BSI (OR 3.52; 95% CI 1.74-7.09), previous antipseudomonal cephalosporin (OR 13.66; 95% CI 6.64-28.10) and piperacillin/tazobactam (OR 2.42; 95% CI 1.04-5.63), and BSI occurring during ceftriaxone (OR 4.27; 95% CI 1.15-15.83). Once P. aeruginosa was identified as the BSI aetiological pathogen, nosocomial acquisition (OR 7.13; 95% CI 2.87-17.67), haematological malignancy (OR 3.44; 95% CI 1.07-10.98), previous antipseudomonal cephalosporin (OR 3.82; 95% CI 1.42-10.22) and quinolones (OR 3.97; 95% CI 1.37-11.48), corticosteroids (OR 2.92; 95% CI 1.15-7.40), and BSI occurring during quinolone (OR 4.88; 95% CI 1.58-15.05) and ß-lactam other than ertapenem (OR 4.51; 95% CI 1.45-14.04) were independently associated with MDR-PA. Per regression coefficients, 1 point was assigned to each parameter, except for nosocomial-acquired BSI (3 points). In the second analysis, a score >3 points identified 60 (86.3%) out of 70 individuals with MDR-PA BSI and discarded 100 (84.2%) out of 120 with non-MDR-PA BSI. CONCLUSIONS: A simple score based on demographic and clinical factors allows stratification of individuals with bacteraemia according to their risk of MDR-PA BSI, and may help facilitate the use of rapid MDR-detection tools and improve early antibiotic appropriateness.

Prophylaxis of mould infections.

Invasive fungal infection continues to be an important cause of morbidity and mortality in haematological patients. Antifungal prophylaxis in these patients has remarkably increased survival since its introduction. In recent years, new antifungals have been on the rise, being more effective and having less toxicity than previous ones. Nonetheless, the number of patients at risk of fungal infection has also been increasing due to the continuous appearance of new immunosuppressive treatments. As a result of such, we face a changing situation that requires constant updating.

Optimizing antimicrobial prescribing: a practical decalogue.

Increasing antibiotic resistance is one of the leading problems in the Public Agenda worldwide. In the last 20 years, the pace of antimicrobial drug development has markedly slowed leading to a dramatic world situation. Infections with antibiotic-resistant microorganisms have been associated with increased length of stay, mortality and costs. Improving antimicrobial prescribing is one of the tools in our hands to optimize the outcomes of patients with moderate to severe infections and control the emerging of resistance. Several clues to improve antimicrobial prescribing are provided as a key-messages decalogue.