Role of IP-10 to Predict Clinical Progression and Response to IL-6 Blockade With Sarilumab in Early COVID-19 Pneumonia. A Subanalysis of the SARICOR Clinical Trial.

Background: The Clinical Trial of Sarilumab in Adults With COVID-19 (SARICOR) showed that patients with coronavirus disease 2019 (COVID-19) pneumonia and increased levels of interleukin (IL)-6 might benefit from blockade of the IL-6 pathway. However, the benefit from this intervention might not be uniform. In this subanalysis, we sought to determine if other immunoactivation markers, besides IL-6, could identify which subgroup of patients benefit most from this intervention. Methods: The SARICOR trial was a phase II, open-label, multicenter, controlled trial (July 2020-March 2021) in which patients were randomized to receive usual care (UC; control group), UC plus a single dose of sarilumab 200 mg (sarilumab-200 group), or UC plus a single dose of sarilumab 400 mg (sarilumab-400 group). Patients who had baseline serum samples for cytokine determination (IL-8, IL-10, monocyte chemoattractant protein-1, interferon-inducible protein [IP]-10) were included in this secondary analysis. Progression to acute respiratory distress syndrome (ARDS) according to cytokine levels and treatment received was evaluated. Results: One hundred one (88%) of 115 patients enrolled in the SARICOR trial had serum samples (control group: n = 33; sarilumab-200: n = 33; sarilumab-400: n = 35). Among all evaluated biomarkers, IP-10 showed the strongest association with treatment outcome. Patients with IP-10 ≥2500 pg/mL treated with sarilumab-400 had a lower probability of progression (13%) compared with the control group (58%; hazard ratio, 0.19; 95% CI, 0.04-0.90; P = .04). Conversely, patients with IP-10 <2500 pg/mL did not show these differences. Conclusions: IP-10 may predict progression to ARDS in patients with COVID-19 pneumonia and IL-6 levels >40 pg/mL. Importantly, IP-10 value <2500 pg/mL might discriminate those individuals who might not benefit from sarilumab therapy among those with high IL-6 levels.

[Prevalence and risk factors of methicillin-resistant Staphylococcus aureus colonization among residents living in long-term care facilities in southern Spain]. / Prevalencia y factores asociados a la colonización por Staphylococcus aureus resistente a meticilina en centros de larga estancia en el sur de España.

INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) has become the most important problem related to multiresistant microorganisms in the health care system. Long-term-care facilities (LTCFs) are one of the main reservoirs of this microorganism. The objective of our study was to determine the prevalence and factors associated with MRSA colonization among subjects living in LTCFs in southern Spain. METHODS: During the period from 1st April 2009 to 30th June 2010, all subjects living in 17 LTCFs of our area were included in a cross-sectional study. Patients were screened by using nasal swabs and these were cultured in a chromogenic media. Suspected S. aureus colonies were identified by the latex agglutination test. Testing for antimicrobial identification and susceptibility was performed by an automated system. A logistic regression model was built, in which to be colonized by MRSA was the dependent variable, and covariates were entered if a difference with P<.2 was detected in the bivariate analysis. Residents were classified as MRSA carriers, methicillin-susceptible S. aureus carriers and non-carriers. RESULTS: Seven hundreds and forty-four subjects were included. There were 481 (65%) females. The median (Q1-Q3) age was 81 (74-86) years. Seventy-nine (10.6%) and 67 (9%) were colonized by MRSA and methicillin-susceptible S. aureus, respectively. Significant risk factors for MRSA carriers were recent antibiotic use, previous hospital admission in the last three months, a high comorbidity measured by Charlson index and a history of colonization by MRSA. CONCLUSIONS: The prevalence of MRSA colonization in the LTCFs of our area is similar to that described in others European countries. In our institutions, subjects with recent antibiotic use, a high comorbidity, a history of MRSA colonization and a hospital admission in the last three months are more susceptible to be colonized by MRSA.

Quasiexperimental intervention study protocol to optimise the use of new antibiotics in Spain: the NEW_SAFE project.

INTRODUCTION: Ceftaroline, tedizolid, dalbavancin, ceftazidime-avibactam and ceftolozane-tazobactam are novel antibiotics used to treat infections caused by multidrug-resistant pathogens (MDR). Their use should be supervised and monitored as part of an antimicrobial stewardship programme (ASP). Appropriate use of the new antibiotics will be improved by including consensual indications for their use in local antibiotic guidelines, together with educational interventions providing advice to prescribers to ensure that the recommendations are clearly understood. METHODS AND ANALYSIS: This study will be implemented in two phases. First, a preliminary historical cohort (2017-2019) of patients from 13 Andalusian hospitals treated with novel antibiotics will be analysed. Second, a quasiexperimental intervention study will be developed with an interrupted time-series analysis (2020-2021). The intervention will consist of an educational interview between prescribers and ASP leaders at each hospital to reinforce the proper use of novel antibiotics. The educational intervention will be based on a consensus guideline designed and disseminated by leaders after the retrospective cohort data have been analysed. The outcomes will be acceptance of the intervention and appropriateness of prescription. Incidence of infection and colonisation with MDR organisms as well as incidence of Clostridioides difficile infection will also be analysed. Changes in prescription quality between periods and the safety profile of the antibiotics in terms of mortality rate and readmissions will also be measured. ETHICS AND DISSEMINATION: Ethical approval will be obtained from the Andalusian Coordinating Institutional Review Board. The study is being conducted in compliance with the protocol and regulatory requirements consistent with International Council of Harmonisation E6 Good Clinical Practice and the ethical principles of the latest version of the Declaration of Helsinki. The results will be published in peer-reviewed journals and disseminated at national and international conferences. TRIAL REGISTRATION NUMBER: NCT03941951; Pre-results.