Ignacio Martin-Loeches

Trinity College Dublin | TCD · Department of Clinical Medicine

Purpose: To determine its cumulative incidence, identify the risk factors associated with Major Adverse Cardiovascular Events (MACE) development, and its impact clinical outcomes. Materials and methods: This multinational, multicentre, prospective cohort study from the ISARIC database. We used bivariate and multivariate logistic regressions to e...

Background: Ventilator-associated pneumonia (VAP) represents a transitory status of immunoparalysis, and we hypothesized that ventilator-associated tracheobronchitis (VAT) could share also some degree of immune response to a respiratory infection. Research design and methods: A prospective observational study in five medical ICUs to evaluate imm...

Background Acute respiratory failure (ARF) is the leading cause of intensive care unit (ICU) admission in patients with Acute Myeloid Leukemia (AML) and data on prognostic factors affecting short-term outcome are needed. Methods This is a post-hoc analysis of a multicenter, international prospective cohort study on immunocompromised patients with...

Background Pneumocystis jirovecii pneumonia (PJP) is an opportunistic, life-threatening disease commonly affecting immunocompromised patients. The distribution of predisposing diseases or conditions in critically ill patients admitted to intensive care unit (ICU) and subjected to diagnostic work-up for PJP has seldom been explored. Materials and m...

The aim of this study is to investigate the effectiveness of prolonged versus standard course oseltamivir treatment among critically ill patients with severe influenza. A retrospective study of a prospectively collected database including adults with influenza infection admitted to 184 intensive care units (ICUs) in Spain from 2009 to 2018. Prolong...

Background High-flow nasal oxygen (HFNO) is increasingly used in patients with acute hypoxemic respiratory failure. It is uncertain whether a broadened Berlin definition of acute respiratory distress syndrome (ARDS), in which ARDS can be diagnosed in patients who are not receiving ventilation, results in similar groups of patients receiving HFNO as...

The aim of this analysis was to compare ventilation management and outcomes in invasively ventilated patients with acute hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19) between the first and second wave in the Netherlands. This is a post hoc analysis of two nationwide observational COVID-19 studies conducted in quick succes...

Antimicrobial resistance (AMR) is associated with increased mortality and resources consumption in critically ill patients. However, the causality of AMR in this mortality remains unclear. This opinion paper aims to overview the effects of multidrug resistant (MDR) pathogens on the outcomes of critically ill patients, considering different variable...

Acute respiratory distress syndrome (ARDS) is a severe organ failure occurring mainly in critically ill patients as a result of different types of insults such as sepsis, trauma or aspiration. Sepsis is the main cause of ARDS, and it contributes to a high mortality and resources consumption both in hospital setting and in the community. ARDS develo...

Therapeutic plasma exchange (TPE) is a therapeutic intervention that separates plasma from blood cells to remove pathological factors or to replenish deficient factors. The use of TPE is increasing over the last decades. However, despite a good theoretical rationale and biological plausibility for TPE as a therapy for numerous diseases or syndromes...

Background In the RESTORE-IMI 2 trial, imipenem/cilastatin/relebactam (IMI/REL) was noninferior to piperacillin/tazobactam in treating hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia. This post hoc analysis was conducted to determine independent predictors of efficacy outcomes in the RESTORE-IMI 2 trial, to assist in...

Background The optimal time to intubate patients with SARS-CoV-2 pneumonia has not been adequately determined. While the use of non-invasive respiratory support before invasive mechanical ventilation might cause patient-self-induced lung injury and worsen the prognosis, non-invasive ventilation (NIV) is frequently used to avoid intubation of patien...

It is evident that the admission of some patients with sepsis and septic shock to hospitals is occurring late in their illness, which has contributed to the increase in poor outcomes and high fatalities worldwide across age groups. The current diagnostic and monitoring procedure relies on an inaccurate and often delayed identification by the clinic...

Around one-third of patients diagnosed with COVID-19 develop a severe illness that requires admission to the Intensive Care Unit (ICU). In clinical practice, clinicians have learned that patients admitted to the ICU due to severe COVID-19 frequently develop ventilator-associated lower respiratory tract infections (VA-LRTI). This study aims to descr...

Background: Acute respiratory failure (ARF) remains the most frequent reason for ICU admission in patients who are immunocompromised. This study reports etiologies and outcomes of ARF in subjects with solid tumors. Methods: This study was a post hoc analysis of the EFRAIM study, a prospective multinational cohort study that included 1611 subject...

Background Traumatic brain injury (TBI) is a public health problem with a high burden in terms of disability and death. Infections are a common complication, with respiratory infections being the most frequent. Most available studies have addressed the impact of ventilator-associated pneumonia (VAP) after TBI; therefore, we aim to characterize the...

Purpose: We aimed to characterize the outcomes of patients with severe meningoencephalitis requiring intensive care. Methods: We conducted a prospective multicenter international cohort study (2017-2020) in 68 centers across 7 countries. Eligible patients were adults admitted to the intensive care unit (ICU) with meningoencephalitis, defined by...

Purpose: We aimed to characterize the outcomes of patients with severe meningoencephalitis requiring intensive care. Methods: We conducted a prospective multicenter international cohort study (2017–2020) in 68 centers across 7 countries. Eligible patients were adults admitted to the intensive care unit (ICU) with meningoencephalitis, defned by a...

PurposeSevere community-acquired pneumonia (sCAP) is associated with high morbidity and mortality, and whilst European and non-European guidelines are available for community-acquired pneumonia, there are no specific guidelines for sCAP.Methods The European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Soc...

Background Severe community-acquired pneumonia (sCAP) is associated with high morbidity and mortality, and while European and non-European guidelines are available for community-acquired pneumonia, there are no specific guidelines for sCAP. Materials and methodology The European Respiratory Society (ERS), European Society of Intensive Care Medicin...

Clinical outcomes from infection with SARS-CoV-2, the cause of the COVID-19 pandemic, are remarkably variable ranging from asymptomatic infection to severe pneumonia and death. One of the key drivers of this variability is differing trajectories in the immune response to SARS-CoV-2 infection. Many studies have noted markedly elevated cytokine level...

Sex and gender dimorphisms are found in a large variety of diseases, including sepsis and septic shock which are more prevalent in men than in women. Animal models show that the host response to pathogens differs in females and males. This difference is partially explained by sex polarization of the intracellular pathways responding to pathogen–cel...

Objectives To assess the relationship between renal function and efficacy/safety of imipenem/cilastatin/relebactam for the treatment of hospital-acquired/ventilator-associated pneumonia (HABP/VABP) from RESTORE-IMI 2 and determine the PTA. Methods Adults with HABP/VABP were randomized 1:1 to IV imipenem/cilastatin/relebactam 1.25 g or piperacillin...

Critically ill COVID-19 patients start developing single respiratory organ failure that often evolves into multiorgan failure. Understanding the immune mechanisms in severe forms of an infectious disease (either critical COVID-19 or bacterial septic shock) would help to achieve a better understanding of the patient’s clinical trajectories and the s...

Introduction Millions of deaths worldwide are a result of sepsis (viral and bacterial) and septic shock syndromes which originate from microbial infections and cause a dysregulated host immune response. These diseases share both clinical and immunological patterns that involve a plethora of biomarkers that can be quantified and used to explain the...

Background: We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, one of the world's largest international, standardized data sets concerning hospitalized patients. Methods: The data set analysed includes COVID-19 patients hospi...

Introduction Patients with community-acquired pneumonia (CAP) admitted to the intensive care unit (ICU) have high mortality rates during the acute infection and up to ten years thereafter. Recommendations from international CAP guidelines include macrolide-based treatment. However, there is no data on the long-term outcomes of this recommendation....

Introduction Ventilator-associated pneumonia (VAP) remains the leading cause of infections treated in the intensive care units (ICU). In a personalised care approach, we hypothesise that the duration of treatment of VAP can be reduced in function of the response to treatment. Methods and analysis The Antimicrobial Stewardship for Ventilator-Associ...

Background: During the first wave of the COVID-19 pandemic, different clinical phenotypes were published. However, none of them have been validated in subsequent waves, so their current validity is unknown. The aim of the study is to validate the unsupervised cluster model developed during the first pandemic wave in a cohort of critically ill patie...

Background: The pivotal ASPECT-NP trial showed ceftolozane/tazobactam was non-inferior to meropenem for the treatment of ventilated hospital-acquired/ventilator-associated bacterial pneumonia (vHABP/VABP). Here, we evaluated treatment outcomes by degree of respiratory or cardiovascular dysfunction. Methods: This was a subset analysis of data fro...

Objectives: To understand differences in antimicrobial use between COVID-19 and non-COVID-19 patients. To compare two metrics commonly used for antimicrobial use: Defined Daily Dose (DDD) and Days of Therapy (DOT). To analyse the order in which antimicrobials were prescribed to COVID-19 patients using process mining techniques. Methods: We analy...

Background: Severe COVID-19 is associated with marked endothelial cell (EC) activation that plays a key role in immunothrombosis and pulmonary microvascular occlusion. However, the biological mechanisms through which SARS-CoV-2 causes EC activation and damage remain poorly defined. Objectives: We investigated EC activation in patients with acute...

Fungal infections have become a common threat in Intensive Care Units (ICU). The epidemiology of invasive fungal diseases (IFD) has been extensively studied in patients severely immunosuppressed over the last 20–30 years, however, the type of patients that have been admitted to hospitals in the last decade has made the healthcare system and ICU a d...

Background: We reviewed the different studies using the terms "refractory septic shock" and/or "catecholamine resistance" and/or "high dose norepinephrine" so as to highlight the heterogeneity of the definitions used by authors addressing such concepts. Method: A systematic review was conducted assessing the papers reporting data on refractory s...

In sepsis and septic shock, guidelines recommend administering antimicrobial therapy within the first hour following diagnosis. This recommendation is based on observational studies suggesting that early antimicrobial therapy was associated with improved outcomes. Consequently, physicians working at the front line are under pressure to decide in a...

Pneumonia is a growing problem worldwide and remains an important cause of morbidity, hospitalizations, intensive care unit admission and mortality. Viruses are the causative agents in almost a fourth of cases of community-acquired pneumonia (CAP) in adults, with an important representation of influenza virus and SARS-CoV-2 pneumonia. Moreover, mix...

Early initiation of a multimodal treatment strategy in the management of vasopressors during septic shock has been advocated to reduce delays in restoring adequate organ perfusion and to mitigate side effects associated with the administration of high-dose catecholamines. We provide a review that summarises the pathophysiology of vasodilation, the...

Background The severe form of COVID-19 can cause a dysregulated host immune syndrome that might lead patients to death. To understand the underlying immune mechanisms that contribute to COVID-19 disease we have examined 28 different biomarkers in two cohorts of COVID-19 patients, aiming to systematically capture, quantify, and algorithmize how immu...

Sepsis is one of the most common and deadly syndromes faced in Intensive Care settings globally. Recent advances in bedside imaging have defined the changes in the microcirculation in sepsis. One of the most advocated interventions for sepsis is fluid therapy. Whether or not fluid bolus affects the microcirculation in sepsis has not been fully addr...

Endothelial integrity maintains microcirculatory flow and tissue oxygen delivery. The endothelial glycocalyx is involved in cell signalling, coagulation and inflammation. Our ability to treat critically ill and septic patients effectively is determined by understanding the underpinning biological mechanisms. Many mechanisms govern the development o...

Background Recent multicenter studies identified COVID-19 as a risk factor for invasive pulmonary aspergillosis (IPA). However, no large multicenter study has compared the incidence of IPA between COVID-19 and influenza patients. Objectives To determine the incidence of putative IPA in critically ill SARS-CoV-2 patients, compared with influenza pa...

Purpose To identify patient, disease and organizational factors associated with decisions to forgo life-sustaining therapies (DFLSTs) in critically ill immunocompromised patients admitted to the intensive care unit (ICU) for acute respiratory failure. Material and methods We performed a secondary analysis of the international EFRAIM prospective st...

Background Ceftolozane/tazobactam, a combination antibacterial agent comprising an anti-pseudomonal cephalosporin and β-lactamase inhibitor, is approved for the treatment of hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP) in adults. Participants in the ASPECT-NP trial received ceftolozane/tazobactam (3 g [2 g ceftolozane/1 g...

Background Ventilator-associated pneumonia caused by Pseudomonas aeruginosa (PA) in hospitalised patients is associated with high mortality. The effectiveness of the bivalent, bispecific mAb MEDI3902 (gremubamab) in preventing PA nosocomial pneumonia was assessed in PA-colonised mechanically ventilated subjects. Methods EVADE (NCT02696902) was a p...

Invasive pulmonary aspergillosis (IPA) is a serious condition resulting in significant mortality and morbidity among patients in intensive care units (ICUs). There is a growing number of at-risk patients for this condition with the increasing use of immunosuppressive therapies. The diagnosis of IPA can be difficult in ICUs, and relies on integratio...

The demographics and outcomes of ICU patients admitted for a COVID-19 infection have been characterized in extensive reports, but little is known about antimicrobial stewardship for these patients. We designed this retrospective, observational study to investigate our hypothesis that the COVID-19 pandemic has disrupted antimicrobial stewardship pra...

Objective To determine if the use of corticosteroids was associated with Intensive Care Unit (ICU) mortality among whole population and pre-specified clinical phenotypes. Design A secondary analysis derived from multicenter, observational study. Setting Critical Care Units. Patients Adult critically ill patients with confirmed COVID-19 disease a...

The rapid increase in antibiotic(ATB) resistance among Gram-negative bacilli(BGN), especially in strains of Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii, with high resistance patterns (XDR), poses a huge threat to health systems worldwide. In the last decade, different ATBs have been developed against XDR, some of which c...

Background Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in...

Split ventilation (using a single ventilator to ventilate multiple patients) is technically feasible. However, connecting two patients with acute respiratory distress syndrome (ARDS) and differing lung mechanics to a single ventilator is concerning. This study aimed to: (1) determine functionality of a split ventilation system in benchtop tests, (2...

Background Ventilator-associated pneumonia (VAP) is common in patients with severe SARS-CoV-2 pneumonia. The aim of this ancillary analysis of the coVAPid multicenter observational retrospective study is to assess the relationship between adjuvant corticosteroid use and the incidence of VAP. Methods Planned ancillary analysis of a multicenter retr...

Infections due to Klebsiella pneumoniae have been increasing in intensive care units (ICUs) in the last decade. Such infections pose a serious problem, especially when antimicrobial resistance is present. We created a task force of experts, including specialists in intensive care medicine, anaesthesia, microbiology and infectious diseases, selected...

Purpose of review: Coronavirus disease (COVID-19)-associated pulmonary aspergillosis (CAPA) may concern up to one third of intensive care unit (ICU) patients. The purpose of this review is to discuss the diagnostic criteria, the pathogenesis, the risk factors, the incidence, the impact on outcome, and the diagnostic and therapeutic management of C...

In this narrative review, we discuss the relevant issues of therapeutic plasma exchange (TPE) in critically ill patients. For many conditions, the optimal indication, device type, frequency, duration, type of replacement fluid and criteria for stopping TPE are uncertain. TPE is a potentially lifesaving but also invasive procedure with risk of adver...

Background: The Fungal Infections Definitions in Intensive Care Unit (ICU) patients (FUNDICU) project aims to provide standard sets of definitions for invasive fungal diseases in critically ill, adult patients. Objectives: To summarize the available evidence on the diagnostic performance of clinical scores and laboratory tests for invasive candi...

Therapeutic drug monitoring (TDM) represents a real need for the present days. There is a huge amount of discussion around personalised medicine and probably this is very relevant in determining the right concentration of antibiotics in some populations. Patients with the most severe spectrum of infections, sepsis and septic shock, currently have w...

Objective To determine whether the prior usage of the flu vaccine is a risk factor for bacterial co-infection in patients with severe influenza. Design This was a retrospective observational cohort study of subjects admitted to the ICU. A propensity score matching, and logistic regression adjusted for potential confounders were carried out to eval...

Objective To determine the incidence and impact of Aspergillus spp. isolation (AI) on ICU mortality in critically ill patients with severe influenza pneumonia during the first 24 h of admission. Design Secondary analysis of an observational and prospective cohort study. Setting ICUs voluntary participating in the Spanish severe Influenza pneumoni...

Background Ventilator-associated lower respiratory tract infections (VA-LRTI) are common in patients with severe SARS-CoV-2 pneumonia. The aim of this ancillary analysis of the coVAPid multicenter observational retrospective study is to assess the relationship between corticosteroid adjuvant administration and the incidence of VA-LRTI. Methods Plan...