New guidelines for hospital-acquired pneumonia/ventilator-associated pneumonia: USA vs. Europe.

PURPOSE OF REVIEW: The International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia were published in 2017 whilst the American guidelines for Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia were launched in 2016 by the Infectious Diseases Society of America/ATS. Both guidelines made updated recommendations based on the most recent evidence sharing not only some parallelisms but also important conceptual differences. RECENT FINDINGS: Contemporary therapy for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) emphasizes the importance of prompt and appropriate antimicrobial therapy. There is an implicit risk, when appropriate means broad spectrum, that liberal use of antimicrobial combinations will encourage the emergence of multidrug resistant (MDR), extensively drug-resistant (XDR) and pandrug-resistant bacteria (PDR) and generate untreatable infections, including carbapenemase resistant infections. SUMMARY: American and European guidelines have many areas of common agreement such as limiting antibiotic duration. Both guidelines were in favour of a close clinical assessment. Neither recommended a regular use of biomarkers but only in specific circumstances such as dealing with MDR and treatment failure. Risk factor prediction for MDR differed and whilst American guidelines focus on organ failure, the European ones did it in local ecology and septic shock.

Severe Pneumococcal Pneumonia Causes Acute Cardiac Toxicity and Subsequent Cardiac Remodeling.

RATIONALE: Up to one-third of patients hospitalized with pneumococcal pneumonia experience major adverse cardiac events (MACE) during or after pneumonia. In mice, Streptococcus pneumoniae can invade the myocardium, induce cardiomyocyte death, and disrupt cardiac function following bacteremia, but it is unknown whether the same occurs in humans with severe pneumonia. OBJECTIVES: We sought to determine whether S. pneumoniae can (1) translocate the heart, (2) induce cardiomyocyte death, (3) cause MACE, and (4) induce cardiac scar formation after antibiotic treatment during severe pneumonia using a nonhuman primate (NHP) model. METHODS: We examined cardiac tissue from six adult NHPs with severe pneumococcal pneumonia and three uninfected control animals. Three animals were rescued with antibiotics (convalescent animals). Electrocardiographic, echocardiographic, and serum biomarkers of cardiac damage were measured (troponin T, N-terminal pro-brain natriuretic peptide, and heart-type fatty acid binding protein). Histological examination included hematoxylin and eosin staining, immunofluorescence, immunohistochemistry, picrosirius red staining, and transmission electron microscopy. Immunoblots were used to assess the underlying mechanisms. MEASUREMENTS AND MAIN RESULTS: Nonspecific ischemic alterations were detected by electrocardiography and echocardiography. Serum levels of troponin T and heart-type fatty acid binding protein were increased (P < 0.05) after pneumococcal infection in both acutely ill and convalescent NHPs. S. pneumoniae was detected in the myocardium of all NHPs with acute severe pneumonia. Necroptosis and apoptosis were detected in the myocardium of both acutely ill and convalescent NHPs. Evidence of cardiac scar formation was observed only in convalescent animals by transmission electron microscopy and picrosirius red staining. CONCLUSIONS: S. pneumoniae invades the myocardium and induces cardiac injury with necroptosis and apoptosis, followed by cardiac scarring after antibiotic therapy, in an NHP model of severe pneumonia.

Mildly elevated lactate levels are associated with microcirculatory flow abnormalities and increased mortality: a microSOAP post hoc analysis.

BACKGROUND: Mildly elevated lactate levels (i.e., 1-2 mmol/L) are increasingly recognized as a prognostic finding in critically ill patients. One of several possible underlying mechanisms, microcirculatory dysfunction, can be assessed at the bedside using sublingual direct in vivo microscopy. We aimed to evaluate the association between relative hyperlactatemia, microcirculatory flow, and outcome. METHODS: This study was a predefined subanalysis of a multicenter international point prevalence study on microcirculatory flow abnormalities, the Microcirculatory Shock Occurrence in Acutely ill Patients (microSOAP). Microcirculatory flow abnormalities were assessed with sidestream dark-field imaging. Abnormal microcirculatory flow was defined as a microvascular flow index (MFI) < 2.6. MFI is a semiquantitative score ranging from 0 (no flow) to 3 (continuous flow). Associations between microcirculatory flow abnormalities, single-spot lactate measurements, and outcome were analyzed. RESULTS: In 338 of 501 patients, lactate levels were available. For this substudy, all 257 patients with lactate levels ≤ 2 mmol/L (median [IQR] 1.04 [0.80-1.40] mmol/L) were included. Crude ICU mortality increased with each lactate quartile. In a multivariable analysis, a lactate level > 1.5 mmol/L was independently associated with a MFI < 2.6 (OR 2.5, 95% CI 1.1-5.7, P = 0.027). CONCLUSIONS: In a heterogeneous ICU population, a single-spot mildly elevated lactate level (even within the reference range) was independently associated with increased mortality and microvascular flow abnormalities. In vivo microscopy of the microcirculation may be helpful in discriminating between flow- and non-flow-related causes of mildly elevated lactate levels. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01179243 . Registered on August 3, 2010.

Endothelial adhesion molecules and multiple organ failure in patients with severe sepsis.

OBJECTIVE: To determine if serum levels of endothelial adhesion molecules were associated with the development of multiple organ failure (MOF) and in-hospital mortality in adult patients with severe sepsis. DESIGN: This study was a secondary data analysis of a prospective cohort study. SETTING: Patients were admitted to two tertiary intensive care units in San Antonio, TX, between 2007 and 2012. PATIENTS: Patients with severe sepsis at the time of intensive care unit (ICU) admission were enrolled. Inclusion criteria were consistent with previously published criteria for severe sepsis or septic shock in adults. Exclusion criteria included immunosuppressive medications or conditions. INTERVENTIONS: None. MEASUREMENTS: Baseline serum levels of the following endothelial cell adhesion molecules were measured within the first 72h of ICU admission: Intracellular Adhesion Molecule 1 (ICAM-1), Vascular Cell Adhesion Molecule-1 (VCAM-1), and Vascular Endothelial Growth Factor (VEGF). The primary and secondary outcomes were development of MOF (⩾2 organ dysfunction) and in-hospital mortality, respectively. MAIN RESULTS: Forty-eight patients were enrolled in this study, of which 29 (60%) developed MOF. Patients that developed MOF had higher levels of VCAM-1 (p=0.01) and ICAM-1 (p=0.01), but not VEGF (p=0.70) compared with patients without MOF (single organ failure only). The area under the curve (AUC) to predict MOF according to VCAM-1, ICAM-1 and VEGF was 0.71, 0.73, and 0.54, respectively. Only increased VCAM-1 levels were associated with in-hospital mortality (p=0.03). These associations were maintained even after adjusting for APACHE and SOFA scores using logistic regression. CONCLUSIONS: High levels of serum ICAM-1 was associated with the development of MOF. High levels of VCAM-1 was associated with both MOF and in-hospital mortality.

Meropenem population pharmacokinetics in critically ill patients with septic shock and continuous renal replacement therapy: influence of residual diuresis on dose requirements.

Meropenem dosing in critically ill patients with septic shock and continuous renal replacement therapy (CRRT) is complex, with the recommended maintenance doses being 500 mg to 1,000 mg every 8 h (q8h) to every 12 h. This multicenter study aimed to describe the pharmacokinetics (PKs) of meropenem in this population to identify the sources of PK variability and to evaluate different dosing regimens to develop recommendations based on clinical parameters. Thirty patients with septic shock and CRRT receiving meropenem were enrolled (153 plasma samples were tested). A population PK model was developed with data from 24 patients and subsequently validated with data from 6 patients using NONMEM software (v.7.3). The final model was characterized by CL = 3.68 + 0.22 · (residual diuresis/100) and V = 33.00 · (weight/73)(2.07), where CL is total body clearance (in liters per hour), residual diuresis is the volume of residual diuresis (in milliliters per 24 h), and V is the apparent volume of distribution (in liters). CRRT intensity was not identified to be a CL modifier. Monte Carlo simulations showed that to maintain concentrations of the unbound fraction (fu ) of drug above the MIC of the bacteria for 40% of dosing interval T (referred to as 40% of the ƒ uT >MIC), a meropenem dose of 500 mg q8h as a bolus over 30 min would be sufficient regardless of the residual diuresis. If 100% of the ƒ uT >MIC was chosen as the target, oligoanuric patients would require 500 mg q8h as a bolus over 30 min for the treatment of susceptible bacteria (MIC < 2 mg/liter), while patients with preserved diuresis would require the same dose given as an infusion over 3 h. If bacteria with MICs close to the resistance breakpoint (2 to 4 mg/liter) were to be treated with meropenem, a dose of 500 mg every 6 h would be necessary: a bolus over 30 min for oligoanuric patients and an infusion over 3 h for patients with preserved diuresis. Our results suggest that residual diuresis may be an easy and inexpensive tool to help with titration of the meropenem dose and infusion time in this challenging population.

International study on microcirculatory shock occurrence in acutely ill patients.

OBJECTIVES: Microcirculatory alterations are associated with adverse outcome in subsets of critically ill patients. The prevalence and significance of microcirculatory alterations in the general ICU population are unknown. We studied the prevalence of microcirculatory alterations in a heterogeneous ICU population and its predictive value in an integrative model of macro- and microcirculatory variables. DESIGN: Multicenter observational point prevalence study. SETTING: The Microcirculatory Shock Occurrence in Acutely ill Patients study was conducted in 36 ICUs worldwide. PATIENTS: A heterogeneous ICU population consisting of 501 patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographic, hemodynamic, and laboratory data were collected in all ICU patients who were 18 years old or older. Sublingual Sidestream Dark Field imaging was performed to determine the prevalence of an abnormal capillary microvascular flow index (< 2.6) and its additional value in predicting hospital mortality. In 501 patients with a median Acute Physiology and Chronic Health Evaluation II score of 15 (10-21), a Sequential Organ Failure Assessment score of 5 (2-8), and a hospital mortality of 28.4%, 17% exhibited an abnormal capillary microvascular flow index. Tachycardia (heart rate > 90 beats/min) (odds ratio, 2.71; 95% CI, 1.67-4.39; p < 0.001), mean arterial pressure (odds ratio, 0.979; 95% CI, 0.963-0.996; p = 0.013), vasopressor use (odds ratio, 1.84; 95% CI, 1.11-3.07; p = 0.019), and lactate level more than 1.5 mEq/L (odds ratio, 2.15; 95% CI, 1.28-3.62; p = 0.004) were independent risk factors for hospital mortality, but not abnormal microvascular flow index. In reference to microvascular flow index, a significant interaction was observed with tachycardia. In patients with tachycardia, the presence of an abnormal microvascular flow index was an independent, additive predictor for in-hospital mortality (odds ratio, 3.24; 95% CI, 1.30-8.06; p = 0.011). This was not true for nontachycardic patients nor for the total group of patients. CONCLUSIONS: In a heterogeneous ICU population, an abnormal microvascular flow index was present in 17% of patients. This was not associated with mortality. However, in patients with tachycardia, an abnormal microvascular flow index was independently associated with an increased risk of hospital death.

A phase 3 randomized double-blind comparison of ceftobiprole medocaril versus ceftazidime plus linezolid for the treatment of hospital-acquired pneumonia.

BACKGROUND: Ceftobiprole, the active moiety of ceftobiprole medocaril, is a novel broad-spectrum cephalosporin, with bactericidal activity against a wide range of gram-positive bacteria, including Staphylococcus aureus (including methicillin-resistant strains) and penicillin- and ceftriaxone-resistant pneumococci, and gram-negative bacteria, including Enterobacteriaceae and Pseudomonas aeruginosa. METHODS: This was a double-blind, randomized, multicenter study of 781 patients with hospital-acquired pneumonia (HAP), including 210 with ventilator-associated pneumonia (VAP). Treatment was intravenous ceftobiprole 500 mg every 8 hours, or ceftazidime 2 g every 8 hours plus linezolid 600 mg every 12 hours; primary outcome was clinical cure at the test-of-cure visit. RESULTS: Overall cure rates for ceftobiprole vs ceftazidime/linezolid were 49.9% vs 52.8% (intent-to-treat [ITT], 95% confidence interval [CI] for the difference, -10.0 to 4.1) and 69.3% vs 71.3% (clinically evaluable [CE], 95% CI, -10.0 to 6.1). Cure rates in HAP (excluding VAP) patients were 59.6% vs 58.8% (ITT, 95% CI, -7.3 to 8.8), and 77.8% vs 76.2% (CE, 95% CI, -6.9 to 10.0). Cure rates in VAP patients were 23.1% vs 36.8% (ITT, 95% CI, -26.0 to -1.5) and 37.7% vs 55.9% (CE, 95% CI, -36.4 to 0). Microbiological eradication rates in HAP (excluding VAP) patients were, respectively, 62.9% vs 67.5% (microbiologically evaluable [ME], 95% CI, -16.7 to 7.6), and in VAP patients 30.4% vs 50.0% (ME, 95% CI, -38.8 to -0.4). Treatment-related adverse events were comparable for ceftobiprole (24.9%) and ceftazidime/linezolid (25.4%). CONCLUSIONS: Ceftobiprole is a safe and effective bactericidal antibiotic for the empiric treatment of HAP (excluding VAP). Further investigations are needed before recommending the use of ceftobiprole in VAP patients. Clinical Trials Registration. NCT00210964, NCT00229008.

European Network for ICU-Related Respiratory Infections (ENIRRIs): a multinational, prospective, cohort study of nosocomial LRTI.

PURPOSE: Lower respiratory tract infections (LRTI) are the most frequent infectious complication in patients admitted to the intensive care unit (ICU). We aim to report the clinical characteristics of ICU-admitted patients due to nosocomial LRTI and to describe their microbiology and clinical outcomes. METHODS: A prospective observational study was conducted in 13 countries over two continents from 9th May 2016 until 16th August 2019. Characteristics and outcomes of ventilator-associated pneumonia (VAP), ventilator-associated tracheobronchitis (VAT), ICU hospital-acquired pneumonia (ICU-HAP), HAP that required invasive ventilation (VHAP), and HAP in patients transferred to the ICU without invasive mechanical ventilation were collected. The clinical diagnosis and treatments were per clinical practice and not per protocol. Descriptive statistics were used to compare the study groups. RESULTS: 1060 patients with LRTI (72.5% male sex, median age 64 [50-74] years) were included in the study; 160 (15.1%) developed VAT, 556 (52.5%) VAP, 98 (9.2%) ICU-HAP, 152 (14.3%) HAP, and 94 (8.9%) VHAP. Patients with VHAP had higher serum procalcitonin (PCT) and Sequential Organ Failure Assessment (SOFA) scores. Patients with VAP or VHAP developed acute kidney injury, acute respiratory distress syndrome, multiple organ failure, or septic shock more often. One thousand eight patients had microbiological samples, and 711 (70.5%) had etiological microbiology identified. The most common microorganisms were Pseudomonas aeruginosa (18.4%) and Klebsiella spp (14.4%). In 382 patients (36%), the causative pathogen shows some antimicrobial resistance pattern. ICU, hospital and 28-day mortality were 30.8%, 37.5% and 27.5%, respectively. Patients with VHAP had the highest ICU, in-hospital and 28-day mortality rates. CONCLUSION: VHAP patients presented the highest mortality among those admitted to the ICU. Multidrug-resistant pathogens frequently cause nosocomial LRTI in this multinational cohort study.

Endothelial Damage and the Microcirculation in Critical Illness.

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 of sepsis and many large trials for new treatments have failed to show a benefit. Endothelial dysfunction is possibly one of these biological mechanisms. Glycocalyx damage is measured biochemically. Novel microscopy techniques now mean the glycocalyx can be indirectly visualised, using sidestream dark field imaging. How the clinical visualisation of microcirculation changes relate to biochemical laboratory measurements of glycocalyx damage is not clear. This article reviews the evidence for a relationship between clinically evaluable microcirculation and biological signal of glycocalyx disruption in various diseases in ICU. Microcirculation changes relate to biochemical evidence of glycocalyx damage in some disease states, but results are highly variable. Better understanding and larger studies of this relationship could improve phenotyping and personalised medicine in the future. Damage to the glycocalyx could underpin many critical illness pathologies and having real-time information on the glycocalyx and microcirculation in the future could improve patient stratification, diagnosis and treatment.

Laparoscopic Common Bile Duct Exploration Using a Disposable Bronchoscope.

Laparoscopic common bile duct exploration (LCBDE) remains underutilized in the management of common bile duct (CBD) stones. The exact cause of this under-utilization remains unclear; however, identified barriers to LCBDE implementation include lack of training and unavailability of dedicated instruments. LCBDE is an attractive alternative for stone retrieval in patients with Roux-en-Y gastric bypass given the anatomical difficulty in endoscopic retrograde cholangiopaneatography (ERCP). Direct visualization through choledochoscopy is the method of choice for LCBDE. However, dedicated choledoscopes are expensive and not widely available, which may lead surgeons to seek for alternatives at their particular environment. With the COVID-19 pandemic, disposable bronchoscopes have become widely accessible at our institution, raising the possibility of using one for direct vision of the biliary tract. We present the case of a 61-year-old male with past medical history of Roux-en-Y gastric bypass, who presented to the emergency department with a CBD stone. Successful LCBDE was achieved with the aid of a disposable bronchoscope for direct visualization of the biliary tract. Supplementary Information: The online version contains supplementary material available at 10.1007/s12262-022-03642-7.

EPICO 3.0. Recommendations on invasive candidiasis in patients with complicated intra-abdominal infection and surgical patients with ICU extended stay.

BACKGROUND: Although in the last decade the management of invasive fungal infections has improved, a number of controversies persist regarding the management of complicated intra-abdominal infection and surgical extended length-of-stay (LOS) patients in intensive care unit (ICU). AIMS: To identify the essential clinical knowledge and elaborate a set of recommendations, with a high level of consensus, necessary for the management of postsurgical patients with complicated intra-abdominal infection and surgical patients with ICU extended stay. METHODS: A Spanish prospective questionnaire, which measures consensus through the Delphi technique, was anonymously answered and e-mailed by 30 multidisciplinary national experts, all of them specialists in fungal invasive infections from six scientific national societies; these experts were intensivists, anesthesiologists, microbiologists, pharmacologists and specialists in infectious diseases. They answered 11 questions drafted by the coordination group after conducting a thorough review of the literature published in the last few years. For a category to be selected, the level of agreement among the experts in each should be equal to or greater than 70%. In a second round, 73 specialists attended a face-to-face meeting which was held after extracting recommendations from the chosen topics and in which they validated the pre-selected recommendations and derived algorithm. RESULTS: After the second Delphi round, the following 11 recommendations with high degree of consensus were validated. For "surgical patients" seven recommendations were validated: (1) risk factors for invasive candidiasis (IC), (2) usefulness of blood culture and direct examination of abdominal fluid to start empirical treatment; (3) PCR for treatment discontinuation; (4) start antifungal treatment in patients with anastomotic leaks; (5) usefulness of Candida score (CS) but not (6) the Dupont score for initiating antifungal therapy in the event of anastomotic leakage or tertiary peritonitis, and (7) the administration of echinocandins as first line treatment in this special population. For "surgical ICU extended LOS patients" four recommendations were validated: (1) risk factors for IC, (2) presence of multi-colonization by Candida as a required variable of the CS, (3) starting antifungal treatment with CS≥4, and (4) to perform non-culture-based microbiological techniques in stable septic patients without evident focus. CONCLUSIONS: The diagnosis and management of IC in ICU surgical patients requires the application of a broad range of knowledge and skills that we summarize in our recommendations. These recommendations, based on the DELPHI methodology, may help to identify potential patients, standardize their global management and improve their outcomes.

EPICO 3.0. Empirical antifungal therapy in critically-ill hematology patients.

BACKGROUND: Although in the past decade the management of invasive fungal infections has improved, a number of controversies persist regarding empirical antifungal treatment in critically-ill hematology patients. AIMS: To identify key clinical knowledge to elaborate a set of recommendations, with a high level of consensus, necessary for the approach to fungal infections in critically-ill hematology patients. METHODS: A Spanish prospective questionnaire, which measures consensus through the Delphi technique, was anonymously answered and e-mailed by 30 multidisciplinary national experts, all specialists in fungal invasive infections from six scientific national societies; intensivists, anesthesiologists, microbiologists, pharmacologists and specialists in infectious diseases. They responded to 10 questions prepared by the coordination group after a thorough review of the literature published in the last few years. For a category to be selected, the level of agreement among the experts in each category must be equal to or greater than 70%. In a second round, 73 specialists attended a face-to-face meeting held after extracting the recommendations from the chosen topics, and validated the pre-selected recommendations and derived algorithm. RESULTS: Assess administering antifungal treatment to patients with high/medium risk factors and fever for over 4 days after onset of antibiotic therapy, and in the event of negative galactomannan or if no detection analysis has been performed and no relevant findings in the sinus and chest computed tomography (CT) have been detected, (1) in the case the patient did not receive prophylaxis, or was administered fluconazole, caspofungin treatment is recommended; (2) in the event the patient received prophylaxis with an azole with activity against filamentous fungi, the administration of liposomal amphotericin B is recommended and caspofungin as second choice therapy; (3) in the event that the prophylaxis received was an echinocandin, liposomal amphotericin B therapy is recommended and voriconazole as second choice. Assess administering antifungal treatment in patients with high/medium risk factors and fever for more than 4 days after onset of antibiotic therapy, and in the event of a positive galactomannan and/or sinus and chest CT suggests fungal infection caused by filamentous fungi, (1) in the event the patient did not receive antifungal prophylaxis or was administered fluconazole, the recommended treatment of choice is voriconazole or liposomal amphotericin B; (2) if the patient received prophylaxis with an azole with activity against filamentous fungi, the administration of liposomal amphotericin B with caspofungin is recommended and monotherapy with liposomal amphotericin B or the combination of voriconazole and anidulafungin are recommended as second choice therapies; (3) in the event an echinocandin was administered as prophylaxis, liposomal amphotericin B or voriconazole are the recommended treatments of choice. Consider the administration of antifungal treatment in patients with high/medium risk factors and fever for more than 4 days after onset of antibiotic therapy, and in the event of a negative galactomannan and the sinus and chest CT suggests fungal infection caused by filamentous fungi, (1) if the patient did not receive prophylaxis or was administered fluconazole, the recommended treatment of choice is liposomal amphotericin B or voriconazole; (2) in the case the patient received prophylaxis with an azole with activity against filamentous fungi, the administration of liposomal amphotericin B is recommended as first choice therapy and liposomal amphotericin B combined with caspofungin as second choice; (3) in the event an echinocandin was administered as prophylaxis, liposomal amphotericin B or voriconazole are the recommended treatments of choice. CONCLUSIONS: The empirical antifungal approach in critically-ill hematology patients requires the application of the broad range of knowledge and skills described in our recommendations and algorithm. These recommendations, based on the DELPHI methodology, may help to identify potential patients, standardize their management and improve overall prognosis.

EPICO 3.0. Management of non-neutropenic patients in medical wards.

BACKGROUND: Although the management of invasive fungal infection (IFI) has improved, a number of controversies persist regarding the approach to invasive fungal infection in non-neutropenic medical ward patients. AIMS: To identify the essential clinical knowledge to elaborate a set of recommendations with a high level of consensus necessary for the management of IFI in non-neutropenic medical ward patients. METHODS: A prospective, Spanish questionnaire, which measures consensus through the Delphi technique, was anonymously answered and e-mailed by 30 multidisciplinary national experts, all specialists (intensivists, anesthesiologists, microbiologists, pharmacologists and specialists in infectious diseases) in IFI and belonging to six scientific national societies. They responded to five questions prepared by the coordination group after a thorough review of the literature published in the last few years. For a category to be selected, the level of agreement among the experts in each category had to be equal to or greater than 70%. In a second round, 73 specialists attended a face-to-face meeting held after extracting the recommendations from the chosen topics, and validated the pre-selected recommendations and derived algorithm. RESULTS: The following recommendations were validated and included in the algorithm: 1. several elements were identified as risk factors for invasive candidiasis (IC) in non-hematologic medical patients; 2. no agreement on the use of the colonization index to decide whether prescribing an early antifungal treatment to stable patients (no shock), with sepsis and no other evident focus and IC risk factors; 3. agreement on the use of the Candida Score to decide whether prescribing early antifungal treatment to stable patients (no shock) with sepsis and no other evident focus and IC risk factors; 4. agreement on initiating early antifungal treatment in stable patients (no shock) with a colonization index>0.4, sepsis with no other evident focus and IC risk factors; 5. agreement on the performance of additional procedures in stable patients (no shock) with sepsis and no other evident focus, IC risk factors, without colonization index>0.4, but with a high degree of suspicion. CONCLUSIONS: Based on the expert's recommendations, an algorithm for the management of non-neutropenic medical patients was constructed and validated. This algorithm may be useful to support bedside prescription.

Global initiative for meticillin-resistant Staphylococcus aureus pneumonia (GLIMP): an international, observational cohort study.

BACKGROUND: Antibiotic resistance is a major global health problem and pathogens such as meticillin-resistant Staphylococcus aureus (MRSA) have become of particular concern in the management of lower respiratory tract infections. However, few data are available on the worldwide prevalence and risk factors for MRSA pneumonia. We aimed to determine the point prevalence of MRSA pneumonia and identify specific MRSA risk factors in community-dwelling patients hospitalised with pneumonia. METHODS: We did an international, multicentre study of community-dwelling, adult patients admitted to hospital with pneumonia who had microbiological tests taken within 24 h of presentation. We recruited investigators from 222 hospitals in 54 countries to gather point-prevalence data for all patients admitted with these characteristics during 4 days randomly selected during the months of March, April, May, and June in 2015. We assessed prevalence of MRSA pneumonia and associated risk factors through logistic regression analysis. FINDINGS: 3702 patients hospitalised with pneumonia were enrolled, with 3193 patients receiving microbiological tests within 24 h of admission, forming the patient population. 1173 (37%) had at least one pathogen isolated (culture-positive population). The overall prevalence of confirmed MRSA pneumonia was 3·0% (n=95), with differing prevalence between continents and countries. Three risk factors were independently associated with MRSA pneumonia: previous MRSA infection or colonisation (odds ratio 6·21, 95% CI 3·25-11·85), recurrent skin infections (2·87, 1·10-7·45), and severe pneumonia disease (2·39, 1·55-3·68). INTERPRETATION: This multicountry study shows low prevalence of MRSA pneumonia and specific MRSA risk factors among community-dwelling patients hospitalised with pneumonia. FUNDING: None.

EPICO 3.0. Antifungal prophylaxis in solid organ transplant recipients.

BACKGROUND: Although over the past decade the management of invasive fungal infection has improved, considerable controversy persists regarding antifungal prophylaxis in solid organ transplant recipients. AIMS: To identify the key clinical knowledge and make by consensus the high level recommendations required for antifungal prophylaxis in solid organ transplant recipients. METHODS: Spanish prospective questionnaire, which measures consensus through the Delphi technique, was conducted anonymously and by e-mail with 30 national multidisciplinary experts, specialists in invasive fungal infections from six national scientific societies, including intensivists, anesthetists, microbiologists, pharmacologists and specialists in infectious diseases that responded to 12 questions prepared by the coordination group, after an exhaustive review of the literature in the last few years. The level of agreement achieved among experts in each of the categories should be equal to or greater than 70% in order to make a clinical recommendation. In a second term, after extracting the recommendations of the selected topics, a face-to-face meeting was held with more than 60 specialists who were asked to validate the pre-selected recommendations and derived algorithm. MEASUREMENTS AND PRIMARY OUTCOMES: Echinocandin antifungal prophylaxis should be considered in liver transplant with major risk factors (retransplantation, renal failure requiring dialysis after transplantation, pretransplant liver failure, not early reoperation, or MELD>30); heart transplant with hemodialysis, and surgical re-exploration after transplantation; environmental colonization by Aspergillus, or cytomegalovirus (CMV) infection; and pancreas and intestinal transplant in case of acute graft rejection, hemodialysis, initial graft dysfunction, post-perfusion pancreatitis with anastomotic problems or need for laparotomy after transplantation. Antifungal fluconazole prophylaxis should be considered in liver transplant without major risk factors and MELD 20-30, split or living donor, choledochojejunostomy, increased transfusion requirements, renal failure without replacement therapy, early reoperation, or multifocal colonization or infection with Candida; intestinal and pancreas transplant with no risk factors for echinocandin treatment. Liposomal amphotericin B antifungal prophylaxis should be considered in lung transplant (inhalant form) and liver transplant with major risk factors. Antifungal prophylaxis with voriconazole should be considered in lung transplant, and heart transplant with hemodialysis, surgical re-exploration after transplantation, environmental colonization by Aspergillus, or CMV infection. CONCLUSIONS: The management of antifungal prophylaxis in solid organ transplant recipients requires the application of knowledge and skills that are detailed in our recommendations and the algorithm developed therein. These recommendations, based on the DELPHI methodology, may help to identify potential patients, standardize their management and improve overall prognosis.

Procalcitonin (PCT) levels for ruling-out bacterial coinfection in ICU patients with influenza: A CHAID decision-tree analysis.

OBJECTIVES: To define which variables upon ICU admission could be related to the presence of coinfection using CHAID (Chi-squared Automatic Interaction Detection) analysis. METHODS: A secondary analysis from a prospective, multicentre, observational study (2009-2014) in ICU patients with confirmed A(H1N1)pdm09 infection. We assessed the potential of biomarkers and clinical variables upon admission to the ICU for coinfection diagnosis using CHAID analysis. Performance of cut-off points obtained was determined on the basis of the binominal distributions of the true (+) and true (-) results. RESULTS: Of the 972 patients included, 196 (20.3%) had coinfection. Procalcitonin (PCT; ng/mL 2.4 vs. 0.5, p < 0.001), but not C-reactive protein (CRP; mg/dL 25 vs. 38.5; p = 0.62) was higher in patients with coinfection. In CHAID analyses, PCT was the most important variable for coinfection. PCT <0.29 ng/mL showed high sensitivity (Se = 88.2%), low Sp (33.2%) and high negative predictive value (NPV = 91.9%). The absence of shock improved classification capacity. Thus, for PCT <0.29 ng/mL, the Se was 84%, the Sp 43% and an NPV of 94% with a post-test probability of coinfection of only 6%. CONCLUSION: PCT has a high negative predictive value (94%) and lower PCT levels seems to be a good tool for excluding coinfection, particularly for patients without shock.

Ventilator-associated pneumonia: issues related to the artificial airway.

Pooling of contaminated secretions above the cuff of the endotracheal tube predisposes patients to ventilator-associated pneumonia (VAP). Subglottic secretion drainage requires a special endotracheal tube that has a separate lumen that opens in the subglottic region above the tracheal tube. A recent meta-analysis of the 5 randomized clinical trials that evaluated the efficacy of removing these secretions found that this technique significantly reduces the incidence of VAP. One cost-effectiveness analysis showed savings of dollar 4,900 per episode of VAP prevented. Greatest benefit is derived by patients requiring fewer than 10 days of mechanical ventilation and not exposed to antibiotic therapy. Maintaining the intracuff pressure between 25 and 30 cm H2O is mandatory to guarantee effective drainage and safety. While silver-coated endotracheal tubes reduce pseudomonas pneumonia in intubated dogs and delay airway colonization in intubated patients, evaluation of studies with a variety of case mixes is warranted to identify subsets likely to benefit from the technique before it is implemented on a large scale. A patient who has a colonized airway and who undergoes percutaneous tracheotomy has an increased risk of VAP, particularly due to Pseudomonas aeruginosa, in the week following the procedure. As many studies suggest that incidence of VAP is highly dependent on the strategies of airway management, health care workers should be alerted to issues related to the artificial airway.

Clinical approach to the patient with suspected ventilator-associated pneumonia.

Management of ventilator-associated pneumonia needs to balance the avoidance of unnecessary antibiotic overuse with the provision of adequate initial empiric therapy. A clinical diagnosis based on new pulmonary opacity and purulent respiratory secretions plus other signs of inflammation is valuable in screening for patients with suspected ventilator-associated pneumonia. A rational strategy starts with immediate initiation of adequate antibiotics and collection of respiratory secretions to evaluate the causative organism. As a minimum, an endotracheal aspirate with direct staining and quantitative cultures should be obtained. Overall, the need to choose adequate antibiotics correctly and expeditiously calls for the use of broad-spectrum antibiotics, but the choice should be narrowed quickly in the light of microbiologic information. However, some patients (those who develop an infection within 5 days of hospitalization, those without recent antibiotic exposure, and those without hospitalization in the past 3 months) are at low risk of infection by resistant organisms. In that subset, adequate initial selection could be a non-pseudomonal third-generation cephalosporin, since antibiotics should target usual community-acquired organisms in addition to some Enterobacteriaceae and Staphylococcus aureus. Coverage of methicillin-resistant S. aureus should be limited only to intensive care units with concomitant index cases and to patients under antibiotic exposure. Patients at risk of Pseudomonas aeruginosa (e.g., 1 week of prior hospitalization or chronic obstructive pulmonary disease) require initial use of a combination of piperacilin/tazobactam and ciprofloxacin, or amikacin plus imipenem, meropenem, or an antipseudomonal cephalosporin. If risk of Acinetobacter baumannii exists, one of these agents should be a carbapenem. After 48 hours of therapy, each patient should be re-evaluated based mainly on resolution of hypoxemia and fever plus the initial microbiologic information. Whereas broad-spectrum therapy is initially warranted in many patients, this treatment may be narrowed considerably as culture results identify the causative organism and its sensitivity. Recent data suggest that reducing overall treatment duration to a maximum of 1 week is safe, effective and is less likely to promote the growth of resistant organisms in patients who are clinically improving. Optimal management should be based on a strategy combining early high doses of an effective agent for a short period of time, which is then simplified in the light of microbiologic information.