Association of microbiological factors with mortality in Escherichia coli bacteraemia presenting with sepsis/septic shock: A prospective cohort study.

OBJECTIVES: This study aimed to determine the association of E. coli microbiological factors with 30-day mortality in BSI patients presenting with a dysregulated response to infection (i.e., sepsis or septic shock). METHODS: Whole genome sequencing was performed on 224 E. coli isolates of patients with sepsis/septic shock, from 22 Spanish hospitals. Phylogroup, sequence type, virulence, antibiotic resistance and pathogenicity islands were assessed. A multivariable model for 30-day mortality including clinical and epidemiological variables was built, to which microbiological variables were hierarchically added. The predictive capacity of the models was estimated by the area under the receiver operating characteristic curve (AUROC) with 95% confidence intervals (CI). RESULTS: Mortality at day 30 was 31% (69 patients). The clinical model for mortality included (adjusted OR; 95% CI) age (1.04; 1.02-1.07), Charlson index ≥3 (1.78; 0.95-3.32), urinary BSI source (0.30; 0.16-0.57) and active empirical treatment (0.36; 0.11-1.14) with an AUROC of 0.73 (95% CI, 0.67-0.80). Addition of microbiological factors selected clone ST95 (3.64; 0.94-14.04), eilA gene (2.62; 1.14-6.02) and astA gene (2.39; 0.87-6.59) as associated with mortality, with an AUROC of 0.76 (0.69-0.82). CONCLUSIONS: Despite having a modest overall contribution, some microbiological factors were associated with increased odds of death and would deserve being studied as potential therapeutic or preventive targets.

Whole-genome characterisation of Escherichia coli isolates from patients with bacteraemia presenting with sepsis or septic shock in Spain: a multicentre cross-sectional study.

BACKGROUND: Escherichia coli is the most frequent cause of bloodstream infections (BSIs). About one-third of patients with BSIs due to E coli develop sepsis or shock. The objective of this study is to characterise the microbiological features of E coli blood isolates causing sepsis or septic shock to provide exploratory information for future diagnostic, preventive, or therapeutic interventions. METHODS: E coli blood isolates from a multicentre cross-sectional study of patients older than 14 years presenting with sepsis or septic shock (according to the Third International Consensus Definitions for Sepsis and Septic Shock criteria) from hospitals in Spain between Oct 4, 2016, and Oct 15, 2017, were studied by whole-genome sequencing. Phylogroups, sequence types (STs), serotype, FimH types, antimicrobial resistance (AMR) genes, pathogenicity islands, and virulence factors were identified. Susceptibility testing was performed by broth microdilution. The main outcome of this study was the characterisation of the E coli blood isolates in terms of population structure by phylogroups, groups (group 1: phylogroups B2, F, and G; group 2: A, B1, and C; group 3: D), and STs and distribution by geographical location and bloodstream infection source. Other outcomes were virulence score and prevalence of virulence-associated genes, pathogenicity islands, AMR, and AMR-associated genes. Frequencies were compared using χ² or Fisher's exact tests, and continuous variables using the Mann-Whitney test, with Bonferroni correction for multiple comparisons. FINDINGS: We analysed 224 isolates: 140 isolates (63%) were included in phylogenetic group 1, 52 (23%) in group 2, and 32 (14%) in group 3. 85 STs were identified, with four comprising 44% (n=98) of the isolates: ST131 (38 [17%]), ST73 (25 [11%]), ST69 (23 [10%]), and ST95 (12 [5%]). No significant differences in phylogroup or ST distribution were found according to geographical areas or source of bloodstream infection, except for ST95, which was more frequent in urinary tract infections than in other sources (11 [9%] of 116 vs 1 [1%] of 108, p=0·0045). Median virulence score was higher in group 1 (median 25·0 [IQR 20·5-29·0) than in group 2 (median 14·5 [9·0-20·0]; p<0·0001) and group 3 (median 21 [16·5-23·0]; p<0·0001); prevalence of several pathogenicity islands was higher in group 1. No significant differences were found between phylogenetic groups in proportions of resistance to antibiotics. ST73 had higher median virulence score (32 [IQR 29-35]) than the other predominant clones (median range 21-28). Some virulence genes and pathogenicity islands were significantly associated with each ST. ST131 isolates had higher prevalence of AMR and a higher proportion of AMR genes, notably blaCTX-M-15 and blaOXA-1. INTERPRETATION: In this exploratory study, the population structure of E coli causing sepsis or shock was similar to previous studies that included all bacteraemic isolates. Virulence genes, pathogenicity islands, and AMR genes were not randomly distributed among phylogroups or STs. These results provide a comprehensive characterisation of invasive E coli isolates causing severe response syndrome. Future studies are required to determine the contribution of these microbiological factors to severe clinical presentation and worse outcomes in patients with E coli bloodstream infection. FUNDING: Instituto de Salud Carlos III.

Efficacy and safety of a structured de-escalation from antipseudomonal ß-lactams in bloodstream infections due to Enterobacterales (SIMPLIFY): an open-label, multicentre, randomised trial.

BACKGROUND: De-escalation from broad-spectrum to narrow-spectrum antibiotics is considered an important measure to reduce the selective pressure of antibiotics, but a scarcity of adequate evidence is a barrier to its implementation. We aimed to determine whether de-escalation from an antipseudomonal ß-lactam to a narrower-spectrum drug was non-inferior to continuing the antipseudomonal drug in patients with Enterobacterales bacteraemia. METHODS: An open-label, pragmatic, randomised trial was performed in 21 Spanish hospitals. Patients with bacteraemia caused by Enterobacterales susceptible to one of the de-escalation options and treated empirically with an antipseudomonal ß-lactam were eligible. Patients were randomly assigned (1:1; stratified by urinary source) to de-escalate to ampicillin, trimethoprim-sulfamethoxazole (urinary tract infections only), cefuroxime, cefotaxime or ceftriaxone, amoxicillin-clavulanic acid, ciprofloxacin, or ertapenem in that order according to susceptibility (de-escalation group), or to continue with the empiric antipseudomonal ß-lactam (control group). Oral switching was allowed in both groups. The primary outcome was clinical cure 3-5 days after end of treatment in the modified intention-to-treat (mITT) population, formed of patients who received at least one dose of study drug. Safety was assessed in all participants. Non-inferiority was declared when the lower bound of the 95% CI of the absolute difference in cure rate was above the -10% non-inferiority margin. This trial is registered with EudraCT (2015-004219-19) and ClinicalTrials.gov (NCT02795949) and is complete. FINDINGS: 2030 patients were screened between Oct 5, 2016, and Jan 23, 2020, of whom 171 were randomly assigned to the de-escalation group and 173 to the control group. 164 (50%) patients in the de-escalation group and 167 (50%) in the control group were included in the mITT population. 148 (90%) patients in the de-escalation group and 148 (89%) in the control group had clinical cure (risk difference 1·6 percentage points, 95% CI -5·0 to 8·2). The number of adverse events reported was 219 in the de-escalation group and 175 in the control group, of these, 53 (24%) in the de-escalation group and 56 (32%) in the control group were considered severe. Seven (5%) of 164 patients in the de-escalation group and nine (6%) of 167 patients in the control group died during the 60-day follow-up. There were no treatment-related deaths. INTERPRETATION: De-escalation from an antipseudomonal ß-lactam in Enterobacterales bacteraemia following a predefined rule was non-inferior to continuing the empiric antipseudomonal drug. These results support de-escalation in this setting. FUNDING: Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases; Spanish Clinical Research and Clinical Trials Platform, co-financed by the EU; European Development Regional Fund "A way to achieve Europe", Operative Program Intelligence Growth 2014-2020.

Antibiotic use and outcome in patients with negative blood cultures, a new target population for antimicrobial stewardship interventions: A prospective multicentre cohort (NO-BACT).

OBJECTIVES: To evaluate the appropriateness of antimicrobial treatment and the risk factors for mortality in patients with negative blood cultures (BC), in order to evaluate whether this population would be a suitable target for antimicrobial stewardship (AMS) interventions. METHODS: A multicentre prospective cohort study of patients with negative BC in three Spanish hospitals between October 2018 and July 2019 was performed. The main endpoints were the appropriateness of antimicrobial treatment (evaluated by two investigators according to local guidelines) and 30-day mortality. Cox-regression was performed to estimate the association between variables and 30-day mortality. RESULTS: Of 1011 patients in whom BC was obtained, these were negative in 803 (79%) and were included; 30-day mortality was 9% (70 patients); antibiotic treatment was considered inappropriate in 299 (40%) of 747 patients evaluated at day 2, and in 266 (46%) of 573 at day 5-7. The variables independently associated with increased risk of 30-day mortality were higher age (HR 1.05; 95% CI 1.03-1.07), neoplasia (HR 2.73; 95% CI 1.64-4.56), antibiotic treatment in the 48 h prior to BC extraction (HR 2.06; 95% CI 1.23-3.43) and insufficient antibiotic coverage at day 2 after BC obtainment (HR 2.35; 95% CI 1.39-4.00). Urinary, catheter and biliary sources of infection were associated with lower risk (HR 0.40; 95% CI 0.20-0.81). CONCLUSIONS: Antimicrobial treatment is frequently inappropriate among patients with negative BC; insufficient antibiotic coverage at day 2 was associated with mortality. These results suggest that patients with negative BC are a suitable population for AS interventions. SUMMARY: Antimicrobial treatment in patients with negative blood culture was frequently inappropriate, and inappropriate coverage at day 2 was associated with increased risk of death. These data support the consideration of this population as a potential target for antimicrobial stewardship interventions.

Ten Issues for Updating in Community-Acquired Pneumonia: An Expert Review.

Community-acquired pneumonia represents the third-highest cause of mortality in industrialized countries and the first due to infection. Although guidelines for the approach to this infection model are widely implemented in international health schemes, information continually emerges that generates controversy or requires updating its management. This paper reviews the most important issues in the approach to this process, such as an aetiologic update using new molecular platforms or imaging techniques, including the diagnostic stewardship in different clinical settings. It also reviews both the Intensive Care Unit admission criteria and those of clinical stability to discharge. An update in antibiotic, in oxygen, or steroidal therapy is presented. It also analyzes the management out-of-hospital in CAP requiring hospitalization, the main factors for readmission, and an approach to therapeutic failure or rescue. Finally, the main strategies for prevention and vaccination in both immunocompetent and immunocompromised hosts are reviewed.

Effectiveness of fosfomycin trometamol as oral step-down therapy for bacteraemic urinary tract infections due to MDR Escherichia coli: a post hoc analysis of the FOREST randomized trial.

BACKGROUND: Fosfomycin is a potentially attractive option as step-down therapy for bacteraemic urinary tract infections (BUTI), but available data are scarce. Our objective was to compare the effectiveness and safety of fosfomycin trometamol and other oral drugs as step-down therapy in patients with BUTI due to MDR Escherichia coli (MDR-Ec). METHODS: Participants in the FOREST trial (comparing IV fosfomycin with ceftriaxone or meropenem for BUTI caused by MDR-Ec in 22 Spanish hospitals from June 2014 to December 2018) who were stepped-down to oral fosfomycin (3 g q48h) or other drugs were included. The primary endpoint was clinical and microbiological cure (CMC) 5-7 days after finalization of treatment. A multivariate analysis was performed using logistic regression to estimate the association of oral step-down with fosfomycin with CMC adjusted for confounders. RESULTS: Overall, 61 patients switched to oral fosfomycin trometamol and 47 to other drugs (cefuroxime axetil, 28; amoxicillin/clavulanic acid and trimethoprim/sulfamethoxazole, 7 each; ciprofloxacin, 5) were included. CMC was reached by 48/61 patients (78.7%) treated with fosfomycin trometamol and 38/47 (80.9%) with other drugs (difference, -2.2; 95% CI: -17.5 to 13.1; P = 0.38). Subgroup analyses provided similar results. Relapses occurred in 9/61 (15.0%) and 2/47 (4.3%) of patients, respectively (P = 0.03). The adjusted OR for CMC was 1.11 (95% CI: 0.42-3.29, P = 0.75). No relevant differences in adverse events were seen. CONCLUSIONS: Fosfomycin trometamol might be a reasonable option as step-down therapy in patients with BUTI due to MDR-Ec but the higher rate of relapses would need further assessment.

Antimicrobial resistance in Gram-negative bacilli in Spain: an experts’ view / Resistencia a antimicrobianos en bacilos gramnegativos en España: una visión de expertos

Background: Antibiotic resistance in Gram-negative bacilli poses a serious problem for public health. In hospitals, in addition to high mortality rates, the emergence and spread of resistance to practically all antibiotics restricts therapeutic options against serious and frequent infections. Objectives: The aim of this work is to present the views of a group of experts on the following aspects regarding resistance to antimicrobial agents in Gram-negative bacilli: 1) the current epidemiology in Spain, 2) how it is related to local clinical practice and 3) new therapies in this area, based on currently available evidence. Methodology: After reviewing the most noteworthy evidence, the most relevant data on these three aspects were presented at a national meeting to 99 experts in infectious diseases, clinical microbiology, internal medicine, intensive care medicine, anaesthesiology and hospital pharmacy. Results and conclusions: Subsequent local debates among these experts led to conclusions in this matter, including the opinion that the approval of new antibiotics makes it necessary to train the specialists involved in order to optimise how they use them and improve health outcomes; microbiology laboratories in hospitals must be available throughout a continuous timetable; all antibiotics must be available when needed and it is necessary to learn to use them correctly; and the Antimicrobial Stewardship Programs (ASP) play a key role in quickly allocating the new antibiotics within the guidelines and ensure appropriate use of them. (AU)

Contexto: La resistencia a los antibióticos en bacilos gramnegativos representa un grave problema de salud pública. En el hospital, además de unas elevadas tasas de mortalidad, la aparición y propagación de resistencias a la práctica totalidad de los antibióticos limita las opciones terapéuticas frente a infecciones graves y frecuentes. Objetivos: Este trabajo tiene por objetivo dar a conocer la visión de un grupo de expertos en los siguientes aspectos respecto a la resistencia a agentes antimicrobianos en bacilos gramnegativos: 1) la epidemiología actual en España, 2) su relación con la práctica clínica local y 3) las novedades terapéuticas en este ámbito, fundamentada en la evidencia actualmente disponible. Metodología: Tras la revisión de la evidencia más destacada, los datos más relevantes de estos 3 aspectos fueron presentados en una reunión nacional ante 99 expertos en enfermedades infecciosas, microbiología clínica, medicina interna, medicina intensiva, anestesiología y farmacia hospitalaria. Resultados y conclusiones: De debates locales posteriores entre estos expertos se extrajeron conclusiones al respecto entre las que se destacan que la aprobación de nuevos antibióticos hace necesaria la formación de los especialistas implicados para optimizar su uso y mejorar los resultados en salud; los laboratorios de Microbiología de los hospitales deben estar disponibles en horario continuado; todos los antibióticos deben estar disponibles para cuando sean necesarios y se debe aprender a usarlos de forma correcta; y los Programas de Optimización del Uso de Antimicrobianos (PROA) desempeñan una labor clave en ubicar de forma ágil los nuevos antibióticos en las guías y asegurar un uso apropiado de los mismos. (AU)

Antimicrobial stewardship in hospitals: Expert recommendation guidance document for activities in specific populations, syndromes and other aspects (PROA-2) from SEIMC, SEFH, SEMPSPGS, SEMICYUC and SEIP.

In 2012, The Spanish Societies of Infectious Diseases and Clinical Microbiology (SEIMC), Hospital Pharmacy (SEFH), and Preventive Medicine, Public Health and Healthcare Management (SEMPSGS) lead a consensus document including recommendations for the implementation of antimicrobial stewardship (AMS) programs (AMSP; PROA in Spanish) in acute care hospitals in Spain. While these recommendations were critical for the development of these programs in many centres, there is a need for guidance in the development of AMS activities for specific patient populations, syndromes or other specific aspects which were not included in the previous document or have developed significantly since then. The objective of this expert recommendation guidance document is to review the available information about these activities in these patient populations or circumstances, and to provide guidance recommendations about them. With this objective the SEIMC, SEFH, SEMPSPGS, the Spanish Society of Intensive Care Medicine (SEMICYUC) and the Spanish Pediatric Infectious Disease Society (SEIP) selected a panel of experts who chose the different aspects to include in the document. Because of the lack of high-level evidence in the implementation of the activities, the panel opted to perform a narrative review of the literature for the different topics for which recommendations were agreed by consensus. The document was open to public consultation for the members of these societies for their comments and suggestions, which were reviewed and considered by the panel.

Predictors of inappropriate antimicrobial prescription: Eight-year point prevalence surveys experience in a third level hospital in Spain.

Antibiotic stewardship programs (ASP) have already demonstrated clinical benefits. We aimed to describe the Point Prevalence Surveys (PPS) methodology implemented in our hospital as an efficient tool to guide ASP strategies. Annually repeated PPS were conducted from 2012 to 2019 at a 750-bed university hospital in South Spain. Key quality indicators and inappropriateness of antimicrobial treatment, defined strictly according to local guidelines, were described. Variables associated with inappropriate treatment were identified by bi/multivariable analysis. A total of 1,600 patients were included. We found that 49% of the prescriptions were inappropriate due to unnecessary treatment (14%), not first line drug recommended (14%), inadequate drug according to microbiological results (9%), unsuitable doses (8%), route (3%) or duration (7%). Samples collection presented a significant protective effect together with sepsis presentation at onset and intensive care unit admission. However, age, receiving an empirical treatment and an unknown or urinary source of the infections treated were independent risk factors for inappropriateness. Site and severity of infection were documented in medical charts by prescribers (75 and 61% respectively). PPS may allow identifying the main risk factors for inappropriateness. This simple methodology may be useful for ASP to select modifiable factors to be prioritized for targeted interventions.

Autoantibodies against type I IFNs in patients with critical influenza pneumonia.

Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-α2 alone (five patients) or with IFN-ω (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-α2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-ω. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients <70 yr of age (5.7 vs. 1.1%, P = 2.2 × 10-5), but not >70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-α2 and IFN-ω (OR = 11.7, P = 1.3 × 10-5), especially those <70 yr old (OR = 139.9, P = 3.1 × 10-10). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for ∼5% of cases of life-threatening influenza pneumonia in patients <70 yr old.

Pseudomonas aeruginosa Community-Onset Bloodstream Infections: Characterization, Diagnostic Predictors, and Predictive Score Development-Results from the PRO-BAC Cohort.

Community-onset bloodstream infections (CO-BSI) caused by gram-negative bacilli are common and associated with significant mortality; those caused by Pseudomonas aeruginosa are associated with worse prognosis and higher rates of inadequateempirical antibiotic treatment. The aims of this study were to describe the characteristics of patients with CO-BSI caused by P. aeruginosa, to identify predictors, and to develop a predictive score for P. aeruginosa CO-BSI. Materials/methods: PROBAC is a prospective cohort including patients >14 years with BSI from 26 Spanish hospitals between October 2016 and May 2017. Patients with monomicrobial P. aeruginosa CO-BSI and monomicrobial Enterobacterales CO-BSI were included. Variables of interest were collected. Independent predictors of Pseudomonas aeruginosa CO-BSI were identified by logistic regression and a prediction score was developed. Results: A total of 78patients with P. aeruginosa CO-BSI and 2572 with Enterobacterales CO-BSI were included. Patients with P. aeruginosa had a median age of 70 years (IQR 60−79), 68.8% were male, median Charlson score was 5 (IQR 3−7), and 30-daymortality was 18.5%. Multivariate analysis identified the following predictors of CO-BSI-PA [adjusted OR (95% CI)]: male gender [1.89 (1.14−3.12)], haematological malignancy [2.45 (1.20−4.99)], obstructive uropathy [2.86 (1.13−3.02)], source of infection other than urinary tract, biliary tract or intra-abdominal [6.69 (4.10−10.92)] and healthcare-associated BSI [1.85 (1.13−3.02)]. Anindex predictive of CO-BSI-PA was developed; scores ≥ 3.5 showed a negative predictive value of 89% and an area under the receiver operator curve (ROC) of 0.66. Conclusions: We did not find a good predictive score of P. aeruginosa CO-BSI due to its relatively low incidence in the overall population. Our model includes variables that are easy to collect in real clinical practice and could be useful to detect patients with very low risk of P. aeruginosa CO-BSI.

Risk Factors and Predictive Score for Bacteremic Biliary Tract Infections Due to Enterococcus faecalis and Enterococcus faecium: a Multicenter Cohort Study from the PROBAC Project.

Biliary-tract bloodstream infections (BT-BSI) caused by Enterococcus faecalis and E. faecium are associated with inappropriate empirical treatment and worse outcomes compared to other etiologies. The objective of this study was to investigate the risk factors for enterococcal BT-BSI. Patients with BT-BSI from the PROBAC cohort, including consecutive patients with BSI in 26 Spanish hospitals between October 2016 and March 2017, were selected; episodes caused by E. faecalis or E. faecium and other causes were compared. Independent predictors for enterococci were identified by logistic regression, and a predictive score was developed. Eight hundred fifty episodes of BT-BSI were included; 73 (8.5%) were due to target Enterococcus spp. (48 [66%] were E. faecium and 25 [34%] E. faecalis). By multivariate analysis, the variables independently associated with Enterococcus spp. were (OR; 95% confidence interval): cholangiocarcinoma (4.48;1.32 to 15.25), hospital acquisition (3.58;2.11 to 6.07), use of carbapenems in the previous month (3.35;1.45 to 7.78), biliary prosthesis (2.19;1.24 to 3.90), and moderate or severe chronic kidney disease (1.55;1.07 to 2.26). The AUC of the model was 0.74 [95% CI0.67 to 0.80]. A score was developed, with 7, 6, 5, 4, and 2 points for these variables, respectively, with a negative predictive value of 95% for a score ≤ 6. A model, including cholangiocarcinoma, biliary prosthesis, hospital acquisition, previous carbapenems, and chronic kidney disease showed moderate prediction ability for enterococcal BT-BSI. Although the score will need to be validated, this information may be useful for deciding empirical therapy in biliary tract infections when bacteremia is suspected. IMPORTANCE Biliary tract infections are frequent, and a significant cause of morbidity and mortality. Bacteremia is common in these infections, particularly in the elderly and patients with cancer. Inappropriate empirical treatment has been associated with increased risk of mortality in bacteremic cholangitis, and the probability of receiving inactive empirical treatment is higher in episodes caused by enterococci. This is because many of the antimicrobial agents recommended in guidelines for biliary tract infections lack activity against these organisms. To the best of our knowledge, this is the first study analyzing the predictive factors for enterococcal BT-BSI and deriving a predictive score.

Effect of Combination Antibiotic Empirical Therapy on Mortality in Neutropenic Cancer Patients with Pseudomonas aeruginosa Pneumonia.

To assess the effect of combination antibiotic empirical therapy on 30-day case-fatality rate in neutropenic cancer patients with Pseudomonas aeruginosa (PA) bacteremic pneumonia. This was a multinational, retrospective cohort study of neutropenic onco-hematological patients with PA bloodstream infection (BSI) (2006−2018). The effect of appropriate empirical combination therapy, appropriate monotherapy and inappropriate empirical antibiotic therapy [IEAT] on 30-day case-fatality was assessed only in patients with PA bacteremic pneumonia. Among 1017 PA BSI episodes, pneumonia was the source of BSI in 294 (28.9%). Among those, 52 (17.7%) were caused by a multidrug-resistant (MDR) strain and 68 (23.1%) received IEAT, mainly when the infection was caused by an MDR strain [38/52 (73.1%) vs. 30/242 (12.4%); p < 0.001]. The 30-day case-fatality rate was higher in patients with PA bacteremic pneumonia than in those with PA BSI from other sources (55.1% vs. 31.4%; p < 0.001). IEAT was associated with increased 30-day case-fatality (aHR 1.44 [95%CI 1.01−2.03]; p = 0.042), whereas the use of appropriate combination empirical treatment was independently associated with improved survival (aHR 0.46 [95%CI 0.27−0.78]; p = 0.004). Appropriate empirical monotherapy was not associated with improved overall survival (aHR 1.25 [95%CI 0.76−2.05]; p = 0.39). Combination antibiotic empirical therapy should be administered promptly in febrile neutropenic patients with suspected pneumonia as the source of infection.

Compatibility of prolonged infusion antibiotics during Y-site administration.

BACKGROUND: Antimicrobial resistance is a threat to global public health. The use of prolonged infusions in the hospital setting for certain antimicrobials is widely increasing in order to improve their efficacy and safety, including resistance development. Due to limited vascular access, it is important to clarify whether they can be infused through the same line with other drugs during Y-site administration. AIM: The aim of this review is to update and summarize the evidence on Y-site compatibility of antibacterial agents administered as prolonged infusions in intensive care units (ICUs). STUDY DESIGN: A literature review of PubMed, EMBASE and Trissel's Handbook on Injectable Drugs databases was conducted on the compatibility of selected antimicrobials administered simultaneously at a Y-site connection with parenteral nutrition and other widely used drugs in ICUs. All articles published up to October 30, 2021, in English or Spanish were included, regardless of the type of publication (original articles, case reports, letters, etc.). Eligible antimicrobials were those that can be administered as prolonged infusions: ceftazidime, cefepime, piperacillin/tazobactam, meropenem, ceftolozane/tazobactam, ceftaroline, cloxacillin, ceftobiprole, vancomycin and fosfomycin. RESULTS: A total of 1302 drug-to-drug potential combinations were explored, 196 (15.05%) were found to be incompatible, and in 541 (41.55%), data were not available. The results were presented in a simple 2-dimensional consultation chart as a quick reference for health care professionals. CONCLUSIONS: This review provides useful and reliable information on the compatibility of antimicrobials administered as Y-site infusion with other drugs commonly used in the critical setting. This review contributes to patient safety in nursing practice. RELEVANCE TO CLINICAL PRACTICE: To our knowledge, this is the first review on Y-site compatibility of antimicrobials used as prolonged infusions with other commonly used drugs, including anti-emetics, analgesics and anti-epileptic and parenteral nutrition. The results of the current review need to be addressed to promote the knowledge sharing between health professionals and improve the quality and safety of patients. We believe that this review may serve as a simple and effective 2-dimensional updated drug-to-drug compatibility reference chart for critical care nurses.

Executive summary of outpatient parenteral antimicrobial therapy: Guidelines of the Spanish Society of Clinical Microbiology and Infectious Diseases and the Spanish Domiciliary Hospitalisation Society / Resumen ejecutivo del tratamiento antimicrobiano domiciliario endovenoso: guía de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica y la Sociedad Española de Hospitalización a Domicilio

Outpatient parenteral antimicrobial therapy (OPAT) programmes make it possible to start or complete intravenous antimicrobial therapy for practically any type of infection at home, provided that patient selection is appropriate for the type of OPAT programme available. Although the clinical management of infections in the home setting is comparable in many respects to that offered in conventional hospitalization (selection of antibiotics, duration of treatment, etc.), there are many aspects that are specific to this care modality. It is essential to be aware of them so that OPAT continues to be as safe and effective as inpatient care. The objective of this clinical guideline is therefore to provide evidence- and expert-based recommendations with a view to standardizing clinical practice in this care modality and contribute to a progressive increase in the number of patients who can be cared for and receive intravenous therapy in their own homes

Los programas de tratamiento antibiótico domiciliario endovenoso (TADE) permiten iniciar o completar el tratamiento antimicrobiano por vía endovenosa de prácticamente cualquier tipo de infección en el domicilio, siempre y cuando se realice una selección del paciente acorde al tipo de programa de TADE que se dispone. Aunque hay aspectos del manejo clínico de las infecciones en el domicilio que son superponibles en la mayoría de los casos a la realizada en la hospitalización convencional (selección de la antibioterapia, duración del tratamiento, etc.), existen numerosos aspectos que son específicos de esta modalidad asistencial. Resulta imprescindible conocerlos para que el TADE siga siendo igual de eficaz y seguro que la hospitalización convencional. El objetivo de esta guía clínica es por tanto, proporcionar recomendaciones basadas en la evidencia realizadas por expertos para homogeneizar la práctica clínica de esta modalidad asistencial y contribuir a que se incremente progresivamente el número de pacientes que pueden ser atendidos y recibir tratamiento endovenoso en su propio domicilio

Executive summary of outpatient parenteral antimicrobial therapy: Guidelines of the Spanish Society of Clinical Microbiology and Infectious Diseases and the Spanish Domiciliary Hospitalisation Society.

Outpatient parenteral antimicrobial therapy (OPAT) programmes make it possible to start or complete intravenous antimicrobial therapy for practically any type of infection at home, provided that patient selection is appropriate for the type of OPAT programme available. Although the clinical management of infections in the home setting is comparable in many respects to that offered in conventional hospitalization (selection of antibiotics, duration of treatment, etc.), there are many aspects that are specific to this care modality. It is essential to be aware of them so that OPAT continues to be as safe and effective as inpatient care. The objective of this clinical guideline is therefore to provide evidence- and expert-based recommendations with a view to standardizing clinical practice in this care modality and contribute to a progressive increase in the number of patients who can be cared for and receive intravenous therapy in their own homes.

Análisis de la calidad de uso de antimicrobianos en el servicio de urgencias de un hospital de tercer nivel / Analysis of quality antimicrobial agent use in the emergency department of a tertiary care hospital

Objetivo. Describir los factores modificables relacionados con el tratamiento antimicrobiano (TA) inadecuado en el área de observación de urgencias (AOU), que se puedan constituir en dianas de intervención para un programa de optimización del uso de antimicrobianos (PROA) específico en el servicio de urgencias (SU). Métodos. Estudio transversal de puntos de prevalencia seriados (PPS) de todas las prescripciones antimicrobianas de los pacientes ingresados en el AOU de febrero a marzo de 2015. La variable principal fue la inadecuación del TA evaluada en base a la guía local de referencia por dos evaluadores. Resultados. Se analizaron 406 TA. Los principales síndromes clínicos encontrados fueron: neumonía (24%), infecciones urinarias (22%) e infecciones del tracto respiratorio inferior no neumónicas (22%). El 51,5% de los TA fue inadecuado. La falta de obtención de muestras microbiológicas antes del TA (61%), no describir el «foco infeccioso» en la historia clínica del paciente (73%) y la ausencia de criterios de sepsis (58%) se asociaron a un TA inadecuado. Conclusiones. El TA adecuado fue inferior al 50%. La presentación grave del cuadro infeccioso, el registro del foco en la historia clínica y la obtención de muestras microbiológicas se relacionaban independientemente con una mejor calidad en la prescripción antimicrobiana. Estos factores pueden constituir dianas para el desarrollo de un PROA específico en el SU

Objective. To describe modifiable factors related to inappropriate antimicrobial treatment in the observation area of an emergency department to explore practices that can be targeted for change through a program to improve emergency use of antimicrobial agents, the PROA program in its spanish observations. Methods. Cross-sectional serial point-prevalence study of all antimicrobial prescriptions for patients under observation in the department in February and March 2015.The main outcome measure was the frequency of antimicrobial treatment that was inappropriate according the center's guidelines. Two evaluators assessed appropriateness. Results. We analyzed 406 antimicrobial treatments. The main clinical syndromes were pneumonia (24%), urinary infections (22%), and nonpneumonia lower respiratory infections (22%). We found that 51.5% of the antimicrobial treatments were inappropriate. Factors associated with inappropriate prescriptions were a failure to analyze microbiologic samples before treating (61%), failure to specify the focus of infection in the case records (73%), and failure to meet the definition of sepsis (58%). Conclusions. Fewer than half the antimicrobial treatments were appropriate as prescribed. Signs of serious infection, specification of the focus of infection in the patient's records, and the analysis of biologic samples were independent predictors of quality care (appropriate antimicrobial prescription). These factors can be targeted for training in the development of a specific emergency department program to improve this aspect of care

Analysis of quality antimicrobial agent use in the emergency department of a tertiary care hospital. / Análisis de la calidad de uso de antimicrobianos en el servicio de urgencias de un hospital de tercer nivel.

OBJECTIVES: To describe modifiable factors related to inappropriate antimicrobial treatment in the observation area of an emergency department to explore practices that can be targeted for change through a program to improve emergency use of antimicrobial agents, the PROA program in its spanish observations. MATERIAL AND METHODS: Cross-sectional serial point-prevalence study of all antimicrobial prescriptions for patients under observation in the department in February and March 2015.The main outcome measure was the frequency of antimicrobial treatment that was inappropriate according the center's guidelines. Two evaluators assessed appropriateness. RESULTS: We analyzed 406 antimicrobial treatments. The main clinical syndromes were pneumonia (24%), urinary infections (22%), and nonpneumonia lower respiratory infections (22%). We found that 51.5% of the antimicrobial treatments were inappropriate. Factors associated with inappropriate prescriptions were a failure to analyze microbiologic samples before treating (61%), failure to specify the focus of infection in the case records (73%), and failure to meet the definition of sepsis (58%). CONCLUSION: Fewer than half the antimicrobial treatments were appropriate as prescribed. Signs of serious infection, specification of the focus of infection in the patient's records, and the analysis of biologic samples were independent predictors of quality care (appropriate antimicrobial prescription). These factors can be targeted for training in the development of a specific emergency department program to improve this aspect of care.

OBJETIVO: Describir los factores modificables relacionados con el tratamiento antimicrobiano (TA) inadecuado en el área de observación de urgencias (AOU), que se puedan constituir en dianas de intervención para un programa de optimización del uso de antimicrobianos (PROA) específico en el servicio de urgencias (SU). METODO: Estudio transversal de puntos de prevalencia seriados (PPS) de todas las prescripciones antimicrobianas de los pacientes ingresados en el AOU de febrero a marzo de 2015. La variable principal fue la inadecuación del TA evaluada en base a la guía local de referencia por dos evaluadores. RESULTADOS: Se analizaron 406 TA. Los principales síndromes clínicos encontrados fueron: neumonía (24%), infecciones urinarias (22%) e infecciones del tracto respiratorio inferior no neumónicas (22%). El 51,5% de los TA fue inadecuado. La falta de obtención de muestras microbiológicas antes del TA (61%), no describir el «foco infeccioso¼ en la historia clínica del paciente (73%) y la ausencia de criterios de sepsis (58%) se asociaron a un TA inadecuado. CONCLUSIONES: El TA adecuado fue inferior al 50%. La presentación grave del cuadro infeccioso, el registro del foco en la historia clínica y la obtención de muestras microbiológicas se relacionaban independientemente con una mejor calidad en la prescripción antimicrobiana. Estos factores pueden constituir dianas para el desarrollo de un PROA específico en el SU.