Clinical impact of time to results from the microbiology laboratory in bloodstream infections caused by carbapenemase-producing Enterobacterales (TIME-CPE STUDY).

OBJECTIVES: To evaluate the impact of time to results (TTR) on the outcome of patients with carbapenemase-producing Enterobacterales bloodstream infections (CPE-BSI). METHODS: Times-series study conducted from January 2014 to December 2021, selecting patients with first CPE-BSI episodes. Periods of intervention were defined according to implementation of diagnostic bundle tests in the microbiology laboratory: pre-intervention (January 2014-December 2017) and post-intervention (January 2018-December 2021). TTR was defined as time elapsed from positivity time of the blood culture bottles to physicians' notification of CPE-BSI episodes, and was evaluated in patients who received inappropriate empirical and switched to appropriate targeted treatment (switch group). Analysis of a composite unfavourable outcome (mortality at Day 30 and/or persistent and/or recurrent bacteraemia) was performed for the total episodes and in the switch group. RESULTS: One hundred and nine episodes were analysed: 66 pre-intervention and 43 post-intervention. Compared with pre-intervention, patients in the post-intervention period were younger (68 versus 63 years, P = 0.04), had INCREMENT score > 7 (31.8% versus 53.5%, P = 0.02) and unfavourable outcome (37.9% versus 20.9%, P = 0.04). Proportion of TTR > 30 h was more frequent pre-intervention than post-intervention (61.7% versus 35.5%, P = 0.02). In multivariate analysis of the 109 episodes, source other than urinary or biliary (OR 2.76, 95% CI 1.11-6.86) was associated with unfavourable outcome, while targeted appropriate treatment trended to being protective (OR 0.17, 95% CI 0.03-1.00). Considering the switch group (n = 78), source other than urinary or biliary (OR 14.9, 95% CI 3.25-69.05) and TTR > 30 h (OR 4.72, 95% CI 1.29-17.22) were associated with unfavourable outcome. CONCLUSIONS: Decreased TTR in the post-intervention period was associated with the outcome in patients with CPE-BSI episodes.

COVID-19 associated infections in the ICU setting: A retrospective analysis in a tertiary-care hospital.

Introduction: Our work describes the frequency of superinfections in COVID-19 ICU patients and identifies risk factors for its appearance. Second, we evaluated ICU length of stay, in-hospital mortality and analyzed a subgroup of multidrug-resistant microorganisms (MDROs) infections. Methods: Retrospective study conducted between March and June 2020. Superinfections were defined as appeared ≥48 h. Bacterial and fungal infections were included, and sources were ventilator-associated lower respiratory tract infection (VA-LRTI), primary bloodstream infection (BSI), secondary BSI, and urinary tract infection (UTI). We performed a univariate analysis and a multivariate analysis of the risk factors. Results: Two-hundred thirteen patients were included. We documented 174 episodes in 95 (44.6%) patients: 78 VA-LRTI, 66 primary BSI, 9 secondary BSI and 21 UTI. MDROs caused 29.3% of the episodes. The median time from admission to the first episode was 18 days and was longer in MDROs than in non-MDROs (28 vs. 16 days, p < 0.01). In multivariate analysis use of corticosteroids (OR 4.9, 95% CI 1.4-16.9, p 0.01), tocilizumab (OR 2.4, 95% CI 1.1-5.9, p 0.03) and broad-spectrum antibiotics within first 7 days of admission (OR 2.5, 95% CI 1.2-5.1, p < 0.01) were associated with superinfections. Patients with superinfections presented respect to controls prolonged ICU stay (35 vs. 12 days, p < 0.01) but not higher in-hospital mortality (45.3% vs. 39.7%, p 0.13). Conclusions: Superinfections in ICU patients are frequent in late course of admission. Corticosteroids, tocilizumab, and previous broad-spectrum antibiotics are identified as risk factors for its development.

Introducción: Nuestro trabajo describe la frecuencia de sobreinfecciones en pacientes con COVID-19 en UCI e identifica factores de riesgo asociados con su aparición. Secundariamente, evaluamos la estancia en UCI, mortalidad intrahospitalaria y analizamos un subgrupo de infecciones causadas por microorganismos multirresistentes (MDR). Métodos: Estudio realizado entre marzo y junio de 2020. Definimos como sobreinfección a aquellas que aparecieron ≥48 h del ingreso. Incluimos las causadas por bacterias y hongos y evaluamos la infección respiratoria asociada a la ventilación mecánica (IRAVM), bacteriemia primaria, bacteriemia secundaria e infección del tracto urinario. Se realizó un análisis multivariante de los factores de riesgo. Resultados: Incluimos 213 pacientes, documentándose 174 episodios de sobreinfección en 95 casos (44,6%): IRAVM 78 episodios, bacteriemia primaria 66, bacteriemia secundaria 9 e ITU 21. Los MDR causaron el 29,3% de los episodios. La mediana de tiempo hasta el primer episodio fue de 18 días, siendo mayor en las causadas por MDR vs. no MDR (28 vs. 16, p < 0,01). El análisis multivariante identificó la administración de corticoides (OR 4,9 IC 95% 1,4-16,9), tocilizumab (OR 2,4 IC 95% 1,1-5,9) y antibióticos de amplio espectro (OR 2,5 IC 95% 1,2-5,1) como factores de riesgo asociados. Los pacientes con sobreinfección presentaron una estancia en UCI más prolongada (35 vs. 12 días, p < 0,01) pero no mayor mortalidad intrahospitalaria (45,3% vs. 39,7%, p 0,13). Conclusiones: Las sobreinfecciones en los pacientes con COVID-19 aparecen tardíamente. La administración de corticoides, tocilizumab y antibióticos de amplio espectro se asocia con su aparición.

COVID-19-Associated Pulmonary Aspergillosis, March-August 2020.

Pneumonia caused by severe acute respiratory syndrome coronavirus 2 emerged in China at the end of 2019. Because of the severe immunomodulation and lymphocyte depletion caused by this virus and the subsequent administration of drugs directed at the immune system, we anticipated that patients might experience fungal superinfection. We collected data from 186 patients who had coronavirus disease-associated pulmonary aspergillosis (CAPA) worldwide during March-August 2020. Overall, 182 patients were admitted to the intensive care unit (ICU), including 180 with acute respiratory distress syndrome and 175 who received mechanical ventilation. CAPA was diagnosed a median of 10 days after coronavirus disease diagnosis. Aspergillus fumigatus was identified in 80.3% of patient cultures, 4 of which were azole-resistant. Most (52.7%) patients received voriconazole. In total, 52.2% of patients died; of the deaths, 33.0% were attributed to CAPA. We found that the cumulative incidence of CAPA in the ICU ranged from 1.0% to 39.1%.

Invasive pulmonary aspergillosis in the COVID-19 era: An expected new entity.

OBJECTIVES: Information on the recently COVID-19-associated pulmonary aspergillosis (CAPA) entity is scarce. We describe eight CAPA patients, compare them to colonised ICU patients with coronavirus disease 2019 (COVID-19), and review the published literature from Western countries. METHODS: Prospective study (March to May, 2020) that included all COVID-19 patients admitted to a tertiary hospital. Modified AspICU and European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria were used. RESULTS: COVID-19-associated pulmonary aspergillosis was diagnosed in eight patients (3.3% of 239 ICU patients), mostly affected non-immunocompromised patients (75%) with severe acute respiratory distress syndrome (ARDS) receiving corticosteroids. Diagnosis was established after a median of 15 days under mechanical ventilation. Bronchoalveolar lavage was performed in two patients with positive Aspergillus fumigatus cultures and galactomannan (GM) index. Serum GM was positive in 4/8 (50%). Thoracic CT scan findings fulfilled EORTC/MSG criteria in one case. Isavuconazole was used in 4/8 cases. CAPA-related mortality was 100% (8/8). Compared with colonised patients, CAPA subjects were administered tocilizumab more often (100% vs. 40%, p = .04), underwent longer courses of antibacterial therapy (13 vs. 5 days, p = .008), and had a higher all-cause mortality (100% vs. 40%, p = .04). We reviewed 96 similar cases from recent publications: 59 probable CAPA (also putative according modified AspICU), 56 putative cases and 13 colonisations according AspICU algorithm; according EORTC/MSG six proven and two probable. Overall, mortality in the reviewed series was 56.3%. CONCLUSIONS: COVID-19-associated pulmonary aspergillosis must be considered a serious and potentially life-threatening complication in patients with severe COVID-19 receiving immunosuppressive treatment.

Effectiveness of short treatment duration for carbapenemase-producing Enterobacterales in bloodstream-infections: A retrospective cohort study.

OBJECTIVE: We analyse the effectiveness of short courses of adequate treatment in patients with episodes of carbapenemase-producing Enterobacterales bloodstream-infections (CPE-BSI). METHODS: Patients with first monomicrobial CPE-BSI episodes who received ≥72 h of appropriate treatment from 2014-2022 were selected. Detection of CPE was established on the basis of phenotypic antibiogram and confirmation by PCR and/or immunochromatographic methods. Patients were classified in short treatment group (STG) those who received 3-10 days of appropriate treatment, and long treatment (LTG) those receiving >10 days. Unfavourable outcome consisted in a composite of global 30-day mortality and/or persistent bacteremia and/or recurrent bacteremia. Inverse probability of treatment weighting (IPTW) analysis was performed to compare the outcome between the two study groups. RESULTS: We included 105 CPE-BSI episodes: 99 were caused by OXA-48-like, 4 VIM and 2 KPC carbapenemases. Thirty-nine patients (37.1%) were included in the STG and 66 (62.9%) in LTG. The STG group presented frequent treatment with ceftazidime-avibactam (43.6% vs. 24.2%, P = 0.03) and lower in-hospital stay (21 days vs. 32 days, P = 0.02). Overall, 28 patients (26.7%) presented unfavourable outcome: IPTW analysis showed no differences in the outcome between STG to LTG groups (24.2% vs. 30.8%, weighted-risk difference 6.6%, P = 0.44). Patients with unfavourable outcome presented more frequently source other than urinary-biliary (46.4% vs. 23.4%, P = 0.02), received less frequently ceftazidime-avibactam (14.3% vs. 37.7%, P = 0.02) and presented frequently with absence of source control when indicated (28.6% vs. 13.0%, P = 0.06). CONCLUSIONS: Short treatment durations for CPE-BSI episodes may be effective, as long as they are appropriate and source control is performed.

Real-world Use of Bezlotoxumab and Fecal Microbiota Transplantation for the Treatment of Clostridioides difficile Infection.

Background: We aimed to describe the frequency of use and effectiveness of bezlotoxumab (BZX) and fecal microbiota transplantation (FMT) in patients with Clostridioides difficile infection (CDI) in real-world practice. Methods: This was a retrospective study conducted in a university hospital in which adult patients treated with BZX or FMT from January 2018 to April 2021 were included. The primary objective was to evaluate the effectiveness of BZX and FMT in preventing early (within 8 weeks) and late (within 1 year) CDI recurrences (rCDI). A multivariate analysis of risk factors for early recurrence was performed. Results: Of 1377 consecutive CDI episodes, 117 (8.5%) received BZX or FMT, with full information available for 100 of the episodes: 51 received BZX, and 49 received FMT. BZX was used mostly in immunosuppressed patients (66.7%) and in first episodes or first recurrences in 70.6% of the cases. FMT was prescribed only in CDI recurrences. Despite the different conditions of the patients, there were no significant differences between BZX and FMT in preventing early rCDI (19.6% vs 24.5%; P = .55) or late rCDI (9.8% vs 18.4%; P = .31). In the multivariate analysis, risk factors for recurrence were presence of ≥2 previous rCDI episodes (odds ratio [OR], 2.90; 95% CI, 1.03-8.63) and use of non-CDI antibiotics (OR, 3.45; 95% CI, 1.24-9.57). Conclusions: BZX and FMT were infrequently used in real-world practice. Both treatments had similar effectiveness in preventing CDI recurrence despite their application to different populations.

Cost analysis of disease including treatment with dalbavancin in a Spanish hospital: ECODAL ANALYSIS.

INTRODUCTION AND AIM: Dalbavancin is an antibiotic with activity against gram-positive bacteria that allows early discharge of patients requiring intravenous therapy. Outpatient treatment helps offset hospitalisation costs associated with standard intravenous treatment. Our objective was to assess the cost of disease management, including treatment with dalbavancin, in a Spanish hospital for 1 year, and the hypothetical costs associated with treatment with other therapeutic alternatives to dalbavancin. METHODS: A single-centre, observational, retrospective post-hoc analysis was conducted based on electronic medical records analysing all patients who received dalbavancin treatment throughout 1 year; cost analysis was performed for the whole process. In addition, three scenarios designed on the basis of real clinical practice by clinical experts were hypothesised: (i) individual therapeutic alternative to dalbavancin, (ii) all patients treated with daptomycin, and (iii) all days of dalbavancin as outpatient treatment transformed into hospital stay. Costs were obtained from the hospital. RESULTS: Thirty-four patients were treated with dalbavancin; their mean age was 57.9 years, and 70.6% were men. The main reasons for dalbavancin use were outpatient management (61.7%, n = 21) and ensuring treatment adherence (26.5%, n = 9). The main indications were: osteoarticular infection (32.4%) and infective endocarditis (29.4%). One-half (50%) of the infections were due to Staphylococcus aureus (23.5% were methicillin resistant). All patients achieved clinical resolution, and no costs associated with dalbavancin-associated adverse events or re-admissions were reported. The mean total cost of treatment was 22,738€ per patient, with the greatest expenditures in interventions (8,413€) and hospital stay (6,885€). The mean cost of dalbavancin treatment was 3,936€; without dalbavancin, this cost could have been increased to 3,324-11,038€ depending on the scenario, mainly due to hospital stays. MAIN LIMITATION: Limited sample size obtained from a single centre. CONCLUSION: The economic impact of the management of these infections is high. The cost of dalbavancin is offset by the decreased length of stay.

COVID-19 associated infections in the ICU setting: A retrospective analysis in a tertiary-care hospital.

INTRODUCTION: Our work describes the frequency of superinfections in COVID-19 ICU patients and identifies risk factors for its appearance. Second, we evaluated ICU length of stay, in-hospital mortality and analyzed a subgroup of multidrug-resistant microorganisms (MDROs) infections. METHODS: Retrospective study conducted between March and June 2020. Superinfections were defined as appeared ≥48h. Bacterial and fungal infections were included, and sources were ventilator-associated lower respiratory tract infection (VA-LRTI), primary bloodstream infection (BSI), secondary BSI, and urinary tract infection (UTI). We performed a univariate analysis and a multivariate analysis of the risk factors. RESULTS: Two-hundred thirteen patients were included. We documented 174 episodes in 95 (44.6%) patients: 78 VA-LRTI, 66 primary BSI, 9 secondary BSI and 21 UTI. MDROs caused 29.3% of the episodes. The median time from admission to the first episode was 18 days and was longer in MDROs than in non-MDROs (28 vs. 16 days, p<0.01). In multivariate analysis use of corticosteroids (OR 4.9, 95% CI 1.4-16.9, p 0.01), tocilizumab (OR 2.4, 95% CI 1.1-5.9, p 0.03) and broad-spectrum antibiotics within first 7 days of admission (OR 2.5, 95% CI 1.2-5.1, p<0.01) were associated with superinfections. Patients with superinfections presented respect to controls prolonged ICU stay (35 vs. 12 days, p<0.01) but not higher in-hospital mortality (45.3% vs. 39.7%, p 0.13). CONCLUSIONS: Superinfections in ICU patients are frequent in late course of admission. Corticosteroids, tocilizumab, and previous broad-spectrum antibiotics are identified as risk factors for its development.

Infective Endocarditis in Diabetic Patients: A Different Profile with Prognostic Consequences.

Background. Infective Endocarditis (IE) is a severe condition. Diabetes mellitus (DM) has been associated with a poor prognosis in other settings. Our aim was to describe the profile and prognosis of IE with and without DM and to analyze the prognostic relevance of DM-related organ damage. Methods. Retrospective analysis of the Spanish IE Registry (2008−2020). Results. The cohort comprises 5590 IE patients with a mean age of 65.0 ± 15.5 years; 3764 (67.3%) were male. DM was found in 1625 patients (29.1%) and 515 presented DM-related organ damage. DM prevalence during the first half of the study period was 27.6% vs. 30.6% in the last half, p = 0.015. Patients with DM presented higher in-hospital mortality than those without DM (521 [32.1%] vs. 924 [23.3%], p < 0.001) and higher one-year mortality (640 [39.4%] vs. 1131 [28.5%], p < 0.001). Among DM patients, organ damage was associated with higher in-hospital (200 [38.8%] vs. 321 [28.9%], p < 0.001) and one-year mortality (247 [48.0%] vs. 393 [35.4%], p < 0.001). Multivariate analyses showed an independent association of DM with in-hospital (odds ratio [OR] = 1.34, 95% confidence interval [CI]: 1.16−1.55, p < 0.001) and one-year mortality (OR = 1.38, 95% CI: 1.21−1.59, p < 0.001). Among DM patients, organ damage was independently associated with higher in-hospital (OR = 1.37, 95% CI: 1.06−1.76, p = 0.015) and one-year mortality (OR = 1.59, 95% CI = 1.26−2.01, p < 0.001) Conclusions. The prevalence of DM among patients with IE is increasing and is already above 30%. DM is independently associated with a poor prognosis, particularly in the case of DM with organ damage.