We describe a large series of patients with chronic obstructive pulmonary disease (COPD) and probable invasive pulmonary aspergillosis (IPA), and the risk factors and incidence of the disease in patients with isolation of Aspergillus from lower respiratory tract samples. From 2000 to 2007, we retrospectively studied all patients admitted with COPD and isolation of Aspergillus (239; 16.3/1000 admissions). Multivariate logistic regression and survival curves were used. Fifty-three patients had probable IPA (3.6 cases of IPA per 1000 COPD admissions). IPA affects at least 22.1% of patients with COPD and isolation of Aspergillus in culture. In 33 of the 53 patients with probable IPA, serum galactomannan was determined; in 14 (42.4%) of these, the result was positive. Five variables were independent predictors of IPA with statistical significance: admission to the intensive-care unit, chronic heart failure, antibiotic treatment received in the 3 months prior to admission, the accumulated dosage of corticosteroids equivalent to >700 mg prednisone received in the 3 months prior to admission, and the similar accumulated dosage of corticosteroids received from admission to the first clinical isolation of Aspergillus. Multivariate analysis gave an area under the curve of 0.925 (95% CI 0.888-0.962; p <0.001). The overall mean survival of the cohort was 64.1% (28.3% for IPA patients and 75.2% for non-IPA patients). The median number of days of survival was 48 (95% CI 33.07-62.92). However, we found statistically significant differences between patients with IPA (29 days; 95% CI 20.59-37.40) and patients without IPA (86 days; 95% CI 61.13-110.86) (log rank, p <0.001).

ESBLEC is an important cause of COBSI due to E. coli. Clinicians should consider adequate empirical therapy with coverage of these pathogens for patients with risk factors.

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.

Extended-spectrum-␤-lactamase (ESBL)-producing Escherichia coli (ESBLEC) is an increasing cause of community and nosocomial infections worldwide. However, there is scarce clinical information about nosocomial bloodstream infections (BSIs)caused by these pathogens. We performed a study to investigate the risk factors for and prognosis of nosocomial BSIs due to ESBLEC in 13 Spanish hospitals. Risk factors were assessed by using a case-control-control study; 96 cases (2 to 16% of all nosocomial BSIs due to E. coli in the participating centers) were included; the most frequent ESBL was CTX-M-14 (48% of the isolates). We found CTX-M-15 in 10% of the isolates, which means that this enzyme is emerging as a cause of invasive infections in Spain. By repetitive extragenic palindromic sequence-PCR, most isolates were found to be clonally unrelated. By multivariate analysis, the risk factors for nosocomial BSIs due to ESBLEC were found to be organ transplant (odds ratio [OR] ‫؍‬ 4.8; 95% confidence interval [CI] ‫؍‬ 1.4 to 15.7), the previous use of oxyimino-␤-lactams (OR ‫؍‬ 6.0; 95% CI ‫؍‬ 3.0 to 11.8), and unknown BSI source (protective; OR ‫؍‬ 0.4; 95% CI ‫؍‬ 0.2 to 0.9), and duration of hospital stay (OR ‫؍‬ 1.02; 95% CI ‫؍‬ 1.00 to 1.03). The variables independently associated with mortality were a Pitt score of >1 (OR ‫؍‬ 3.9; 95% CI ‫؍‬ 1.2 to 12.9), a high-risk source (OR ‫؍‬ 5.5; 95% CI ‫؍‬ 1.4 to 21.9), and resistance to more than three antibiotics, apart from penicillins and cephalosporins (OR ‫؍‬ 6.5; 95% CI ‫؍‬ 1.4 to 30.0). Inappropriate empirical therapy was not associated with mortality. We conclude that ESBLEC is an important cause of nosocomial BSIs. The previous use of oxyimino-␤-lactams was the only modifiable risk factor found. Resistance to drugs other than penicillins and cephalosporins was associated with increased mortality.Gram-negative organisms are an important cause of nosocomial bloodstream infections (BSIs) (33), particularly when the source of the BSI is the urinary, respiratory, or gastrointestinal tract. Recently, the reemergence of Gram-negative organisms as a cause of primary BSIs has also been reported (1). In the United States, Escherichia coli is the fifth most common cause of nosocomial BSIs and is the first most common cause among Gram-negative organisms, and BSIs caused by E. coli are reported to be associated with a crude mortality rate of 22% (34); in Spain, it is the second most common cause of nosocomial BSIs (23).In recent years, extended-spectrum ß-lactamases (ESBLs), particularly those of the CTX-M family, have spread worldwide among E. coli strains inside and outside hospitals (20,26); consequently, the prevalence of BSIs caused by ESBL-producing E. coli has significantly increased (24, 28). ESBLs confer resistance to penicillins and cephalosporins and are frequently associated with resistance to fluoroquinolones, aminoglycosides, and trimethoprim-sulfamethoxazole (18); thus, ESBLproducing microorganisms are frequently truly multidrug resistant. Both antibiotic resistance a...

Antifungal stewardship (AFS) programmes are needed in tertiary-care hospitals. Our aim is to describe a bedside non-restrictive AFS programme, and to evaluate its economic impact. During the first year of the AFS a bundle of non-interventional measures were implemented. During the second year an infectious diseases specialist visited 453 patients receiving candins, liposomal amphotericin B, voriconazole or posaconazole. Monthly costs were studied with an interrupted time series (ITS) analysis. The main prescribing departments were haematology (35%), medical departments (23%), and intensive care units (20%). Reasons to start antifungal therapy were: targeted therapy (36%), prophylaxis (32%), empirical therapy (20%) and pre-emptive therapy (12%). At the initial visit, diagnostic advice was provided in 40% of cases. The most common therapeutic recommendations were to de-escalate the antifungal drug (17%) or to suspend it (7%). Annual total antifungal expenditure was reduced from US$3.8 million to US$2.9 million over the first 2 years, generating net savings of US$407,663 and US$824,458 per year after considering the cost of additional staff required. The ITS analyses showed a significant economic impact after the first 12 months of the intervention (p 0.042 at month 13), which was enhanced in the following 24 months (p 0.006 at month 35). The number of defined daily doses decreased from 66.4 to 54.8 per 1000 patient-days. Incidence of candidaemia was reduced from 1.49 to 1.14 (p 0.08) and related mortality was reduced from 28% to 16% (p 0.1). A collaborative and non-compulsory AFS program based on bedside intervention is an efficacious and cost-effective approach that optimizes the use of AF drugs.