Características clínicas, pronóstico y factores asociados de la bacteriemia por Staphylococcus aureus en la actualidad / Clinical characteristics and prognosis of Staphylococcus aureus bacteremia

Introducción. Describimos las características de los pacientes con bacteriemia por Staphylococcus aureus en un hospital de tercer nivel y analizamos sus complicaciones, la mortalidad y los factores asociados a las mismas. Métodos. Se analizaron de manera retrospectiva los datos de los pacientes ingresados con bacteriemia por S. aureus entre marzo de 2020 y febrero de 2021 en el hospital universitario Miguel Servet de Zaragoza. Resultados. La mortalidad a los 14 días fue del 24,2% y la mortalidad a los 30 días del 40%. La aparición de complicaciones [HR 3,1 (1,2-8,05)] y la edad >65 años [HR 3,1 (IC95% 1,4-6,6)] disminuyeron la supervivencia global de manera significativa. En la regresión logística se asociaron a mayor mortalidad a los 30 días la edad >65 años [OR 6,3 (IC95% 1,7-23,1)], la presencia de sepsis [OR 19,3 (IC95% 5,4-68,7)] y solo con cierta tendencia, el número de frascos de HC (+) ≥3 [OR 5,4 (IC95% 0,8-34,1)]. Se asoció a mayor mortalidad a los 14 días el haber presentado sepsis [OR 58,2 (IC95% 5,7-592,9)], el número frascos de HC (+) ≥3 [OR 14,1 (IC95% 1,1-173,7)] y una edad >65 años [OR 1,1 (IC95% 1,03-1,1) años]. Cuando analizamos juntos aquellos con un TP ≤12 horas y un número frascos de HC (+) ≥3, la sepsis fue más frecuente [30 pacientes (66,6%) vs 15 pacientes (33,3%); OR 3,4 (IC95% 1,5-8)]. Conclusiones. La mortalidad a los 14 y a los 30 días fue elevada, observándose una peor evolución en los pacientes con mayor edad, presencia de sepsis, un mayor número de frascos de hemocultivos positivos y un tiempo hasta hemocultivos positivos ≤12 h. (AU)

Introduction. Staphylococcus aureus bacteremia patients characteristics at a tertiary hospital are described, and complications, mortality and associated factors are analyzed. Methods. Data from patients with S. aureus bacteremia admitted between March 2020 and February2021 at Miguel Servet university hospital in Zaragoza were retrospectively analyzed. Results. Results showed a 14 days mortality of 24.2% and an 30 days mortality of 40%. Overall survival decreased with complications appearance [HR 3.1 (1.2-8.05)] and age over 65 years [HR 3.1 (1.4-6.6)]. The adjusted analysis showed correlation between a higher mortality at 14 and 30 days with age over 65 years [OR 6.3 (1.7-23.1)], sepsis presence [OR 19.3 (5.4-68.7)] and number of positive (+) blood cultures ≥3 [OR 5.4 (0.8-34.1)]. Mortality at 14 days was associated with sepsis presence [OR 58.2 (5.7-592.9)], number of positive (+) blood cultures ≥3 [OR 14.1 (1.1-173.7)] and an older age [OR 1.1 (1.03-1.1)]. Analyzing time to positive blood cultures ≤12 hours and number of positive blood cultures ≥ 3 at the same time, frequency of sepsis increased [30 patients (66.6%) vs 15 patients (33.3%); OR 3.4 (IC95% 1.5-8)]. Conclusions. High 14- and 30-days mortality were found, as well as a worse evolution in older age patients, with sepsis presence, and with greater number of positive blood cultures and times to positive blood cultures ≤12 h. (AU)

Impacto de la bacteriemia por Staphylococcus aureus en pacientes con COVID-19 / Impact of Staphylococcus aureus bacteremia in COVID-19 patients

Introducción. La enfermedad causada por SARS-CoV-2 (COVID-19) ha supuesto un desafío para los profesionales sanitarios desde su aparición. Staphylococcus aureus es uno de los principales patógenos causantes de infecciones bacterianas en pandemias virales. Sin embargo, se debe estudiar bien la co-infección por S. aureus causante de bacteriemia en pacientes con COVID-19. Métodos. Se analizaron los casos de bacteriemia por S. aureus (BSA) atendidos en el Hospital Miguel Servet (Zaragoza) desde marzo de 2020 hasta febrero de 2021. Se compararon las características clínicas, los factores de riesgo y mortalidad de los pacientes con BSA asociada a COVID-19 respecto los pacientes no-COVID-19. Resultados. Se identificaron 95 pacientes con BSA. El 27,3% fueron COVID-19 positivos. La BSA representó el 9,9% de las bacteriemias, siendo el segundo microorganismo en frecuencia tras E. coli. La bacteriemia nosocomial fue más frecuente en el grupo de pacientes con COVID-19. La fuente de BSA fue desconocida en el 46,2% de los pacientes con COVID-19. La fuente de BSA más frecuente en estos pacientes fue la respiratoria (26,9% vs 0%; P<0,001) seguida de la cutánea (15,5% vs 15,9%; P=1). El desarrollo de sepsis fue más frecuente en los pacientes con COVID-19 (61,5% vs 7,8%; P=0,336) y de ellos, los que recibieron dosis de dexametasona >6 mg/día (62,5% vs 37,5%; P< 0,05). Conclusiones. Nuestros datos sugieren que la BSA influye negativamente en la evolución de los pacientes con COVID-19. Sin embargo, se requieren más estudios y preferiblemente prospectivos para obtener datos sólidos sobre el impacto de la BSA en los pacientes con coronavirus. (AU)

Introduction. The disease caused by SARS-CoV-2 (COVID-19) has been a challenge for healthcare professionals since its appearance. Staphylococcus aureus has been described as one of the main pathogens causing bacterial infections in viral pandemics. However, co- infection with S. aureus causing bacteremia in patients with COVID-19 has yet to be well studied. Methods. We performed a e study of S. aureus bacteremia (SAB) at Hospital Miguel Servet (Zaragoza) from March 2020 to February 2021. The clinical characteristics, mortality and risk factors of adults hospitalized patients with BSA associated COVID-19 compared to patients without COVID-19. Results. A total of 95 patients with SAB were identified. 27.3% were positive for SARS-CoV-2. SAB represented 9.9% of bacteremia, being the second agent in frequency after E. coli. Nosocomial bacteremia was more frequent in the group of COVID-19 patients. The most frequent source of BSA in these patients was the respiratory source (26.9% vs 0%; P<0.001) followed by the skin (15.5% vs 15.9%; P=1). The development of sepsis was more frequent in COVID-19 patients (61,5% vs 7,8%; P=0,336) and among them, who received dexamethasone at doses > 6 mg/day (62.5% vs. 37.5%, P<0.05). Conclusions. Our data suggest that BSA has a negative impact on the evolution of patients with COVID-19. However, further and preferably prospective studies are required to obtain solid data on the impact of BSA on coronavirus patients. (AU)

Long-term impact of an educational antimicrobial stewardship programme in primary care on infections caused by extended-spectrum ß-lactamase-producing Escherichia coli in the community: an interrupted time-series analysis.

BACKGROUND: There is little evidence on the ecological effect and sustainability of antimicrobial stewardship programmes (ASPs) in primary-care settings. We aimed to determine whether a multimodal, educational ASP would be sustainable in the long-term and reduce the incidence of infections caused by extended-spectrum ß-lactamase-producing Escherichia coli in the community by optimising antibiotic use. METHODS: We did this quasi-experimental intervention study in 214 primary health centres of four primary health-care districts in Andalusia, Spain. Local multidisciplinary teams, comprised of general practitioners, paediatricians, primary-care pharmacists, and epidemiologists, were created in each district and implemented a multimodal, education-based ASP. The core activity of the programme consisted of regular one-to-one educational interviews between a reference interviewing physician and prescribing physicians from each centre on the appropriateness of their most recent (same or preceding day) antibiotic prescriptions based on a structured questionnaire. Appropriate prescribing was defined as compliance of all checklist items with the reference guidelines. An average of five educational interviews were scheduled per prescriber per study year. We did an interrupted time-series analysis to assess the effect of the intervention on quarterly antibiotic use (prescription and collection by the patient) and quality of prescriptions (as defined daily doses per 1000 inhabitants per day) and incidence per 1000 inhabitants of E coli producing extended-spectrum ß-lactamase (ESBL) isolated from urine samples. FINDINGS: The study was done between January, 2012, and December, 2017, in a pre-intervention period of 2012-13 and an intervention period of 2014-17. Throughout the study period, there were 1387 physicians (1116 general practicioners and 271 paediatricians) in the included health centres serving a mean population of 1 937 512 people (299 331 children and 1 638 181 adults). 24 150 educational interviews were done over the 4 years. Inappropriate antibiotic prescribing was identified in 1794 (36·5%) of 4917 educational interviews in 2014 compared with 1793 (26·9%) of 6665 in 2017 (p<0·0001). The intervention was associated with a sustained reduction in the use of ciprofloxacin (relative effect -15·9%, 95% CI -23·9 to -8·0) and cephalosporins (-22·6%, -35·9 to -9·2), and a sustained increase in the use of amoxicillin (22·2%, 6·4 to 38·0) and fosfomycin trometamol (6·1%, 2·6 to 9·6). The incidence density of ESBL-producing E coli decreased by -0·028 cases per 1000 inhabitants (95% CI -0·034 to -0·021) after the start of the programme, reversing the pre-intervention increase and leading to a relative reduction of -65·6% (-68·2 to -63·0) 4 years later. INTERPRETATION: Our data suggest that implementation of a multimodal ASP in primary care that is based on individual educational interviews improves the use of antibiotics and results in a sustained significant reduction of infections by ESBL-producing E coli in the community. This information should encourage the implementation of ASPs in primary care. FUNDING: Instituto de Salud Carlos III, Spanish Government (PI14/01523).

T2Candida MR as a predictor of outcome in patients with suspected invasive candidiasis starting empirical antifungal treatment: a prospective pilot study.

Objectives: We assessed the potential role of T2Candida MR (T2MR) and serological biomarkers [ß-d-glucan (BDG) or Candida albicans germ tube antibodies (CAGTA)], alone or in combination with standard cultures, for identifying patients with suspected invasive candidiasis (IC), who may benefit from maintaining antifungal therapy. Methods: Prospective observational multicentre study including all adult patients receiving empirical antifungal therapy for suspected IC, from January to June 2017. CAGTA, BDG and T2MR were determined at baseline and at +2 and +4 days after enrolment. Primary endpoint was the diagnostic value of CAGTA, BDG and T2MR, alone or in combination with standard culture, to predict diagnosis of IC and/or mortality in the first 7 days after starting antifungal therapy (poor outcome). Results: Overall, 14/49 patients (28.6%) had a poor outcome (7 died within the first 7 days of antifungal therapy, whereas 7 ended with a diagnosis of IC). CAGTA [3/14 (21.4%) versus 8/35 (22.9%), P = 1] and BDG [8/14 (57.1%) versus 17/35 (48.6%), P = 0.75] results were similar in poor- and good-outcome patients. Conversely, a positive T2MR was associated with a higher risk of poor outcome [5/14 (35.7%) versus 0/35 (0.0%) P = 0.0001]. Specificity and positive predictive value of a positive T2MR for predicting poor outcome were both 100%, with a negative predictive value of 79.6%. After testing the combinations of biomarkers/standard cultures and T2MR/standard cultures, the combination of T2MR/standard cultures showed a high capacity to discriminate patients with poor outcome from those with good clinical evolution. Conclusions: T2MR may be of significant utility to identify patients who may benefit from maintaining antifungal therapy.

T2MR contributes to the very early diagnosis of complicated candidaemia. A prospective study.

Objectives: Diagnosis of complicated candidaemia represents a challenge for clinicians since early clinical manifestations may be non-specific and difficult to identify, thus precluding an appropriate treatment. Patients and methods: This was a multicentre prospective study for predicting complicated episodes in patients with bloodstream infection caused by Candida species, while assessing the value of follow-up blood cultures (BCs) and the persistence of positive results for T2Candida MR (T2MR) and blood ß-d-glucan (BDG) tests. Immediately after the first positive BC yielding Candida species, samples were obtained on days 0, +2, +4, +7 and +14, to simultaneously perform follow-up BC, T2MR and BDG. An episode of candidaemia was defined as 'complicated' when (i) it caused septic metastasis; and/or (ii) it was the cause of the patient's death. Results: From January to June 2017, 30 patients were enrolled in the study. Of these, nine (30%) had complicated candidaemia. Values of persistently positive samples for the prediction of complicated episodes for BCs, T2MR and BDG, respectively, were as follows: sensitivity (44.4%, 100%, 100%); specificity (76.1%, 76.1%, 38.9%); positive predictive value (PPV) (44.4%, 64.2%, 40.9%) and negative predictive value (NPV) (76.1%, 100%, 100%). In multivariate analysis, having a positive T2MR within the first 5 days was associated with an almost 37-fold higher risk of developing complicated candidaemia. Conclusions: The T2MR test performed in patients with proven candidaemia may be a better marker of complicated infection than follow-up BCs or BDG. It is possible that this test may change current clinical practice, influencing the length and type of antifungal therapy in this population.

Environmental sampling protocol devised and implemented to resolve a nosocomial outbreak due to carbapenem-resistant Klebsiella oxytoca.

We describe a method for investigating wet foci in the hospital environment of a nosocomial outbreak due to carbapenem-resistant Klebsiella oxytoca. By searching in areas that are usually inaccessible, by immersing sampling swabs in thioglycolate broth, and by concentrating the sampled water, reservoirs of infection that would have gone unnoticed can be detected.

Efficacy of continuous positive airway pressure treatment on 5-year survival in patients with ischaemic stroke and obstructive sleep apnea: a randomized controlled trial.

The main purpose of the present analysis is to assess the influence of introducing early nasal continuous positive airway pressure (nCPAP) treatment on cardiovascular recurrences and mortality in patients with a first-ever ischaemic stroke and moderate-severe obstructive sleep apnea (OSA) with an apnea-hypopnea index (AHI) ≥20 events h(-1) during a 5-year follow-up. Patients received conventional treatment for stroke and were assigned randomly to the nCPAP group (n = 71) or the control group (n = 69). Cardiovascular events and mortality were registered for all patients. Survival and cardiovascular event-free survival analysis were performed after 5-year follow-up using the Kaplan-Meier test. Patients in the nCPAP group had significantly higher cardiovascular survival than the control group (100 versus 89.9%, log-rank test 5.887; P = 0.015) However, and also despite a positive tendency, there were no significant differences in the cardiovascular event-free survival at 68 months between the nCPAP and control groups (89.5 versus 75.4%, log-rank test 3.565; P = 0.059). Early nCPAP therapy has a positive effect on long-term survival in ischaemic stroke patients and moderate-severe OSA.

Analysis of genes involved in L-ascorbic acid biosynthesis during growth and ripening of grape berries.

Recent data indicate the existence of at least three L-ascorbic acid (AsA) biosynthetic pathways in plant cells. Studying their occurrence in different plant organs and species may help to decipher the precise role(s) of AsA in plant cell physiology. In grape berries, AsA is of particular importance since it is known to be the precursor of tartaric acid, an essential component of the grape fruit. The concentration of AsA increases during development of the fruit to reach a maximum at the full ripe stage. We followed the expression of genes related to the various AsA biosynthetic pathways in this plant organ during fruit ontogeny by real time RT-PCR. Among them, a gene (VvGalUR), showing high homology to one from strawberry encoding a D-galacturonate reductase, was up-regulated during fruit ripening in parallel to the AsA content increase. Cloning of the corresponding full length cDNA showed highest similarity to the strawberry gene (FaGalUR). Moreover, VvGalUR gene expression in grape was also up-regulated by high light, a condition that increased AsA content in grape fruits, while none of the genes involved in the other possible biosynthetic pathways analyzed increased their transcript levels. The results are discussed in relation to the presence of several AsA biosynthetic pathways in grape fruits.

Cloning and characterization of a root sunflower peroxidase gene putatively involved in cell elongation.

A cDNA-encoding a peroxidase (Helianthus annuus POX (HaPOX)1) was isolated and characterized from the roots of sunflower seedlings. This gene exhibited homology with other peroxidases from several higher-plant species, and its expression in the root growth was particularly abundant during cell expansion. To elucidate the precise functions of HaPOX1 in sunflower root, we examined its expression pattern in response to several plant growth regulators. Expression of HaPOX1 is down-regulated by abscisic acid (ABA), whereas indole-3-acetic acid (IAA) induced its expression. These results suggest that HaPOX1 expression is differentially regulated by phytohormonal components of signaling cascades. Since IAA appears to participate in the regulation of HaPOX1 expression, we postulate that the peroxidase encoded by HaPOX1 may be involved in the reactions that promote cell elongation during the early stage of root growth.