Current viewpoint on the epidemiology of nonfermenting Gram-negative bacterial strains.

PURPOSE OF REVIEW: This article aims to review the epidemiology of nonfermenting Gram-negative bacilli (NFGNB) based on recent literature reports, particularly, of the less common, but with emerging clinical significance species. RECENT FINDINGS: The reported frequency of multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa is increasing, with very significant variability, however, between different countries. Apart from the major NFGNB, that is, A. baumannii and P. aeruginosa, already recognized as of critical importance healthcare risks, several other NFGNB genera have been increasingly associated with diverse severe infections, such as Stenotrophomonas maltophilia, Burkholderia spp., Elizabethkingia spp., Chryseobacterium spp., Achromobacter spp., Alcaligenes spp., Sphingomonas spp., Shewanella spp. and Ralstonia spp., among others. SUMMARY: The exploration of the epidemiology, as well as the pathogenic potential of the of the less frequent, but emerging and increasingly reported NFGNB, is crucial, not only for immunocompromised patients, but also for critically ill patients without overt immunosuppression. As we are heading fast towards a postantibiotic era, such information would contribute to the optimal antimicrobial management, that is, providing prompt, appropriate antimicrobial coverage when needed and, at the same time, avoiding overuse and/or inappropriate use of antimicrobial therapy. Also, it would help to better understand their transmission dynamics and to develop effective prevention strategies.

Severe community-acquired pneumonia in the post COVID-19 era.

PURPOSE OF REVIEW: The aim was to examine and summarize the most recent published literature in the last years stating the advances for treatment options and adjunctive therapies in patients hospitalized with severe community-acquired pneumonia (sCAP). Search was performed in PubMed, including observational studies, randomized controlled trials, systematic reviews and meta-analyses, and international guidelines. RECENT FINDINGS: Regardless of a large number of published CAP guidelines, most of their recommendations are based on low-level evidence.Viruses have an increasing role as sCAP etiology with an impact on mortality. Accordingly, it is imperative to strengthen the demand for vaccines and newer antivirals. Considering an early monitoring of the immune response in patients with severe Influenza, may help to evaluate a personalized immunomodulatory strategy. Despite growing evidence, the use of corticosteroids as an adjunctive therapy in bacterial sCAP continues to be controversial. SUMMARY: Mortality due to sCAP still remains undesirably high. This fact strengthens the need for more high-quality research to increase evidence. It also highlights the need for clinicians to be aware of the level of evidence of the stated recommendations, taking this into consideration before decision making.

Effectiveness of Continuous Cuff Pressure Control in Preventing Ventilator-Associated Pneumonia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: Microaspiration of subglottic secretions is the main pathogenic mechanism for ventilator-associated pneumonia (VAP). Adequate inflation of the endotracheal cuff is pivotal to providing an optimal seal of the extraluminal airway. However, cuff pressure substantially fluctuates due to patient or tube movements, which can induce microaspiration. Therefore, devices for continuous cuff pressure control (CCPC) have been developed in recent years. The purpose of this systematic review and meta-analysis is to assess the effectiveness of CCPC in VAP prevention. DATA SOURCES: A systematic search of Embase, the Cochrane Central Register of Controlled Trials, and the International Clinical Trials Registry Platform was conducted up to February 2022. STUDY SELECTION: Eligible studies were randomized controlled trials (RCTs) and quasi-RCTs comparing the impact of CCPC versus intermittent cuff pressure control on the occurrence of VAP. DATA EXTRACTION: Random-effects meta-analysis was used to calculate odds ratio (OR) and 95% CI for VAP incidence between groups. Secondary outcome measures included mortality and duration of mechanical ventilation (MV) and ICU stay. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. DATA SYNTHESIS: Eleven RCTs with 2,092 adult intubated patients were included. The use of CCPC was associated with a reduced risk of VAP (OR, 0.51). Meta-analyses of secondary endpoints showed no significant difference in mortality but significant differences in durations of MV (mean difference, -1.07 d) and ICU stay (mean difference, -3.41 d) in favor of CCPC. However, the risk of both reporting and individual study bias was considered important. The main issues were the lack of blinding, potential commercial conflicts of interest of study authors and high heterogeneity due to methodological differences between studies, differences in devices used for CCPC and in applied baseline preventive measures. Certainty of the evidence was considered "very low." CONCLUSIONS: The use of CCPC was associated with a reduction in VAP incidence; however, this was based on very low certainty of evidence due to concerns related to risk of bias and inconsistency.

Invasive pulmonary aspergillosis in solid-organ transplant patients in the intensive care unit.

INTRODUCTION: Solid-organ transplantation (SOT) is a well-known risk factor for invasive pulmonary aspergillosis (IPA). We report on the epidemiology and outcome of SOT patients with IPA in an intensive care unit (ICU) setting. METHODS: This is a secondary study based on a subset of SOT patients from a prospective observational multicenter cohort (the AspICU project) including ICU patients with at least one Aspergillus spp. positive culture. Cases were classified as proven, probable, or putative IPA, or as Aspergillus-colonized. Mortality was reported at 12 weeks. RESULTS: The study included 52 SOT patients (of which 18 lung, 17 liver, 12 kidney, and five heart transplants). Sixteen patients had proven IPA, 28 were categorized as putative IPA (of which only five reached a probable IPA diagnosis according to the European Organization for Research and Treatment of Cancer/Mycosis Study Group and Research Consortium criteria), and eight as Aspergillus-colonization. Among patients with IPA, 20 (45.5%) developed IPA during their ICU stay following transplantation whereas 24 patients (54.5%) had a medical ICU admission. Regarding medical imaging, nearly all IPA cases presented with non-specific findings as only nine demonstrated robust findings suggestive for invasive fungal disease. Overall, severity of the disease was reflected by a high prevalence of underlying conditions and acute organ derangements. Mortality among patients with IPA was 68%. Lung transplantation was associated with better survival (50%). CONCLUSION: IPA in SOT patients in the ICU develops in the presence of overall high severity of the disease. It rarely presents with suggestive medical imaging thereby hampering diagnosis. IPA in ICU patients with SOT carries a grim prognosis.

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study.

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 patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). METHODS: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. RESULTS: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83-7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97-2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14-1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25-1.30]). CONCLUSIONS: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable.

Effect of High Altitude on the Survival of COVID-19 Patients in Intensive Care Unit: A Cohort Study.

Purpose: The effect of high altitude ( ≥ 1500 m) and its potential association with mortality by COVID-19 remains controversial. We assessed the effect of high altitude on the survival/discharge of COVID-19 patients requiring intensive care unit (ICU) admission for mechanical ventilation compared to individuals treated at sea level. Methods: A retrospective cohort multi-center study of consecutive adults patients with a positive RT-PCR test for COVID-19 who were mechanically ventilated between March and November 2020. Data were collected from two sea-level hospitals and four high-altitude hospitals in Ecuador. The primary outcome was ICU and hospital survival/discharge. Survival analysis was conducted using semi-parametric Cox proportional hazards models. Results: Of the study population (n = 670), 35.2% were female with a mean age of 58.3 ± 12.6 years. On admission, high-altitude patients were more likely to be younger (57.2 vs. 60.5 years old), presented with less comorbidities such as hypertension (25.9% vs. 54.9% with p-value <.001) and diabetes mellitus (20.5% vs. 37.2% with p-value <.001), less probability of having a capillary refill time > 3 sec (13.7% vs. 30.1%, p-value <.001), and less severity-of-illness condition (APACHE II score, 17.5 ± 8.1 vs. 20 ± 8.2, p < .01). After adjusting for key confounders high altitude is associated with significant higher probabilities of ICU survival/discharge (HR: 1.74 [95% CI: 1.46-2.08]) and hospital survival/discharge (HR: 1.35 [95% CI: 1.18-1.55]) than patients treated at sea level. Conclusions: Patients treated at high altitude at any time point during the study period were 74% more likely to experience ICU survival/discharge and 35% more likely to experience hospital survival/discharge than to the sea-level group. Possible reasons for these findings are genetic and physiological adaptations due to exposure to chronic hypoxia.

Nebulized Antibiotics for Healthcare- and Ventilator-Associated Pneumonia.

Global emergence of multidrug-resistant and extensive drug-resistant gram-negative bacteria has increased the risk of treatment failure, especially for healthcare- or ventilator-associated pneumonia (HAP/VAP). Nebulization of antibiotics, by providing high intrapulmonary antibiotic concentrations, represents a promising approach to optimize the treatment of HAP/VAP due to multidrug-resistant and extensive drug-resistant gram-negative bacteria, while limiting systemic antibiotic exposure. Aminoglycosides and colistin methanesulfonate are the most common nebulized antibiotics. Although optimal nebulized drug dosing regimen is not clearly established, high antibiotic doses should be administered using vibrating-mesh nebulizer with optimized ventilator settings to ensure safe and effective intrapulmonary concentrations. When used preventively, nebulized antibiotics reduced the incidence of VAP without any effect on mortality. This approach is not yet recommended and large randomized controlled trials should be conducted to confirm its benefit and explore the impact on antibiotic selection pressure. Compared with high-dose intravenous administration, high-dose nebulized colistin methanesulfonate seems to be more effective and safer in the treatment of ventilator-associated tracheobronchitis and VAP caused by multidrug resistant and extensive-drug resistant gram-negative bacteria. Adjunctive nebulized aminoglycosides could increase the clinical cure rate and bacteriological eradication in patients suffering from HAP/VAP due to multidrug-resistant and extensive drug-resistant gram-negative bacteria. As nebulized aminoglycosides broadly diffuse in the systemic circulation of patients with extensive bronchopneumonia, monitoring of plasma trough concentrations is recommended during the period of nebulization. Large randomized controlled trials comparing high dose of nebulized colistin methanesulfonate to high dose of intravenous colistin methanesulfonate or to intravenous new ß-lactams in HAP/VAP due to multidrug-resistant and extensive drug-resistant gram-negative bacteria are urgently needed.

The Effect of Renal Replacement Therapy and Antibiotic Dose on Antibiotic Concentrations in Critically Ill Patients: Data From the Multinational Sampling Antibiotics in Renal Replacement Therapy Study.

BACKGROUND: The optimal dosing of antibiotics in critically ill patients receiving renal replacement therapy (RRT) remains unclear. In this study, we describe the variability in RRT techniques and antibiotic dosing in critically ill patients receiving RRT and relate observed trough antibiotic concentrations to optimal targets. METHODS: We performed a prospective, observational, multinational, pharmacokinetic study in 29 intensive care units from 14 countries. We collected demographic, clinical, and RRT data. We measured trough antibiotic concentrations of meropenem, piperacillin-tazobactam, and vancomycin and related them to high- and low-target trough concentrations. RESULTS: We studied 381 patients and obtained 508 trough antibiotic concentrations. There was wide variability (4-8-fold) in antibiotic dosing regimens, RRT prescription, and estimated endogenous renal function. The overall median estimated total renal clearance (eTRCL) was 50 mL/minute (interquartile range [IQR], 35-65) and higher eTRCL was associated with lower trough concentrations for all antibiotics (P < .05). The median (IQR) trough concentration for meropenem was 12.1 mg/L (7.9-18.8), piperacillin was 78.6 mg/L (49.5-127.3), tazobactam was 9.5 mg/L (6.3-14.2), and vancomycin was 14.3 mg/L (11.6-21.8). Trough concentrations failed to meet optimal higher limits in 26%, 36%, and 72% and optimal lower limits in 4%, 4%, and 55% of patients for meropenem, piperacillin, and vancomycin, respectively. CONCLUSIONS: In critically ill patients treated with RRT, antibiotic dosing regimens, RRT prescription, and eTRCL varied markedly and resulted in highly variable antibiotic concentrations that failed to meet therapeutic targets in many patients.

Nebulized antibiotics for ventilator-associated pneumonia: methodological framework for future multicenter randomized controlled trials.

PURPOSE OF REVIEW: Although experimental evidence supports the use of nebulized antibiotics in ventilator-associated pneumonia (VAP), two recent multicenter randomized controlled trials (RCTs) have failed to demonstrate any benefit in VAP caused by Gram-negative bacteria (GNB). This review examines the methodological requirements concerning future RCTs. RECENT FINDINGS: High doses of nebulized antibiotics are required to reach the infected lung parenchyma. Breath-synchronized nebulizers do not allow delivery of high doses. Mesh nebulizers perform better than jet nebulizers. Epithelial lining fluid concentrations do not reflect interstitial lung concentrations in patients receiving nebulized antibiotics. Specific ventilator settings for optimizing lung deposition require sedation to avoid patient's asynchrony with the ventilator. SUMMARY: Future RCTs should compare a 3-5 day nebulization of amikacin or colistimethate sodium (CMS) to a 7-day intravenous administration of a new cephalosporine/ß-lactamase inhibitor. Inclusion criteria should be a VAP or ventilator-associated tracheobronchitis caused by documented extensive-drug or pandrug resistant GNB. If the GNB remains susceptible to aminoglycosides, nebulized amikacin should be administered at a dose of 40 mg/kg/day. If resistant to aminoglycosides, nebulized CMS should be administered at a dose of 15 millions international units (IU)/day. In VAP caused by pandrug-resistant GNB, 15 millions IU/day nebulized CMS (substitution therapy) should be compared with a 9 millions IU/day intravenous CMS.

Lung and kidney perfusion deficits diagnosed by dual-energy computed tomography in patients with COVID-19-related systemic microangiopathy.

OBJECTIVES: There is increasing evidence that thrombotic events occur in patients with coronavirus disease (COVID-19). We evaluated lung and kidney perfusion abnormalities in patients with COVID-19 by dual-energy computed tomography (DECT) and investigated the role of perfusion abnormalities on disease severity as a sign of microvascular obstruction. METHODS: Thirty-one patients with COVID-19 who underwent pulmonary DECT angiography and were suspected of having pulmonary thromboembolism were included. Pulmonary and kidney images were reviewed. Patient characteristics and laboratory findings were compared between those with and without lung perfusion deficits (PDs). RESULTS: DECT images showed PDs in eight patients (25.8%), which were not overlapping with areas of ground-glass opacity or consolidation. Among these patients, two had pulmonary thromboembolism confirmed by CT angiography. Patients with PDs had a longer hospital stay (p = 0.14), higher intensive care unit admission rates (p = 0.02), and more severe disease (p = 0.01). In the PD group, serum ferritin, aspartate aminotransferase, fibrinogen, D-dimer, C-reactive protein, and troponin levels were significantly higher, whereas albumin level was lower (p < 0.05). D-dimer levels ≥ 0.485 µg/L predicted PD with 100% specificity and 87% sensitivity. Renal iodine maps showed heterogeneous enhancement consistent with perfusion abnormalities in 13 patients (50%) with lower sodium levels (p = 0.03). CONCLUSIONS: We found that a large proportion of patients with mild-to-moderate COVID-19 had PDs in their lungs and kidneys, which may be suggestive of the presence of systemic microangiopathy with micro-thrombosis. These findings help in understanding the physiology of hypoxemia and may have implications in the management of patients with COVID-19, such as early indications of thromboprophylaxis or anticoagulants and optimizing oxygenation strategies. KEY POINTS: • Pulmonary perfusion abnormalities in COVID-19 patients, associated with disease severity, can be detected by pulmonary DECT. • A cutoff value of 0.485 µg/L for D-dimer plasma levels predicted lung perfusion deficits with 100% specificity and 87% sensitivity (AUROC, 0.957). • Perfusion abnormalities in the kidney are suggestive of a subclinical systemic microvascular obstruction in these patients.

Clinical phenotypes of SARS-CoV-2: implications for clinicians and researchers.

Patients with COVID-19 present a broad spectrum of clinical presentation. Whereas hypoxaemia is the marker of severity, different strategies of management should be customised to five specific individual phenotypes. Many intubated patients present with phenotype 4, characterised by pulmonary hypoxic vasoconstriction, being associated with severe hypoxaemia with "normal" (>40 mL·cmH2O-1) lung compliance and likely representing pulmonary microvascular thrombosis. Phenotype 5 is often associated with high plasma procalcitonin and has low pulmonary compliance, Which is a result of co-infection or acute lung injury after noninvasive ventilation. Identifying these clinical phenotypes and applying a personalised approach would benefit the optimisation of therapies and improve outcomes.

Adult ICU Triage During the Coronavirus Disease 2019 Pandemic: Who Will Live and Who Will Die? Recommendations to Improve Survival.

OBJECTIVES: Coronavirus disease 2019 patients are currently overwhelming the world's healthcare systems. This article provides practical guidance to front-line physicians forced to make critical rationing decisions. DATA SOURCES: PubMed and Medline search for scientific literature, reviews, and guidance documents related to epidemic ICU triage including from professional bodies. STUDY SELECTION: Clinical studies, reviews, and guidelines were selected and reviewed by all authors and discussed by internet conference and email. DATA EXTRACTION: References and data were based on relevance and author consensus. DATA SYNTHESIS: We review key challenges of resource-driven triage and data from affected ICUs. We recommend that once available resources are maximally extended, triage is justified utilizing a strategy that provides the greatest good for the greatest number of patients. A triage algorithm based on clinical estimations of the incremental survival benefit (saving the most life-years) provided by ICU care is proposed. "First come, first served" is used to choose between individuals with equal priorities and benefits. The algorithm provides practical guidance, is easy to follow, rapidly implementable and flexible. It has four prioritization categories: performance score, ASA score, number of organ failures, and predicted survival. Individual units can readily adapt the algorithm to meet local requirements for the evolving pandemic. Although the algorithm improves consistency and provides practical and psychologic support to those performing triage, the final decision remains a clinical one. Depending on country and operational circumstances, triage decisions may be made by a triage team or individual doctors. However, an experienced critical care specialist physician should be ultimately responsible for the triage decision. Cautious discharge criteria are proposed acknowledging the difficulties to facilitate the admission of queuing patients. CONCLUSIONS: Individual institutions may use this guidance to develop prospective protocols that assist the implementation of triage decisions to ensure fairness, enhance consistency, and decrease provider moral distress.

Antibiotic use in patients with COVID-19: a 'snapshot' Infectious Diseases International Research Initiative (ID-IRI) survey.

BACKGROUND: Antibiotics may be indicated in patients with COVID-19 due to suspected or confirmed bacterial superinfection. OBJECTIVES: To investigate antibiotic prescribing practices in patients with COVID-19. METHODS: We performed an international web-based survey and investigated the pattern of antibiotic use as reported by physicians involved in treatment of COVID-19. SPSS Statistics version 25 was used for data analysis. RESULTS: The survey was completed by 166 participants from 23 countries and 82 different hospitals. Local guidelines for antibiotic use in COVID-19 patients were reported by 61.8% (n = 102) of participants and for 82.9% (n = 136) they did not differ from local community-acquired pneumonia guidelines. Clinical presentation was recognized as the most important reason for the start of antibiotics (mean score = 4.07 and SD = 1.095 on grading scale from 1 to 5). When antibiotics were started, most respondents rated as the highest the need for coverage of atypical pathogens (mean score = 2.8 and SD = 0.99), followed by Staphylococcus aureus (mean score = 2.67 and SD = 1.05 on bi-modal scale, with values 1 and 2 for disagreement and values 3 and 4 for agreement). In the patients on the ward, 29.1% of respondents chose not to prescribe any antibiotic. Combination of ß-lactams and macrolides or fluoroquinolones was reported by 52.4% (n = 87) of respondents. In patients in the ICU, piperacillin/tazobactam was the most commonly prescribed antibiotic. The mean reported duration of antibiotic treatment was 7.12 (SD = 2.44) days. CONCLUSIONS: The study revealed widespread broad-spectrum antibiotic use in patients with COVID-19. Implementation of antimicrobial stewardship principles is warranted to mitigate the negative consequences of antibiotic therapy.

Levels of evidence supporting European and American community-acquired pneumonia guidelines.

Optimal clinical decisions should be supported by clinical practice guidelines (CPG) based on evidence generated from randomized clinical trials (RCT). We aimed to evaluate the class and level of evidence (LOE) supporting the international community-acquired pneumonia (CAP) guidelines and their variation over time. The 2019 Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) and the 2011 European Respiratory Society/European Society Clinical Microbiology Infectious Diseases (ERS/ESCMID) CPG and its immediate predecessors (2007 and 2005) were evaluated. The number of recommendations and distribution as LOE A (supported by multiple RCT or a single, large RCT), B (supported by data from a single RCT or observational studies) and C (expert opinion, case studies, or standard of care) was identified. Overall, recommendations for diagnosis, management, and prevention were graded as strong in 51.4%, 62.9%, and 23.5% in spite that they were supported by LOE A in 5.7%, 11.1%, and 52.9%, respectively. In the 2019 ATS/IDSA guidelines (39 recommendations), 7.7% (n = 3) recommendations were classified as LOE A, 30.8% (n = 12) as LOE B, and 61.5% (24%) as LOE C. Across the 2011 ERS/ESCMID guidelines (68 recommendations), 21.2% (n = 14) recommendations were classified as LOE A, 4.6% (n = 3) as LOE B, and 74.2% (n = 49) as LOE C. When comparing with prior versions, the proportion of recommendations that were LOE A did not significantly increase in ERS/ESCMID (21.2% vs 20%) and decreased in ATS/IDSA (7.7% vs 32.0%). In conclusion, large randomized trials or network meta-analysis including comparison of regimens to identify high probability of best cure and mortality is an unmet clinical need on CAP.

Levels of evidence supporting clinical practice guidelines on invasive aspergillosis.

Invasive aspergillosis (IA) is a severe life-threatening infection with challenges in therapy. The aim was to evaluate the level of evidence (LOE) supporting recommendations in clinical practice guidelines (CPGs) of IA and changes over time. Search on CPG on IA released between 2000 and 2019 was done. Last versions were evaluated and compared with previous versions. Recommendations were classified by LOE as A (multiple randomized controlled trial (RCT) or meta-analysis), B (data from a single RCT or observational studies), or C (observational studies with limitations, case series, or expert opinion). Diagnosis recommendations were excluded. Five CPG from three groups of scientific societies were identified: the 2016 Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS), 2017 European Society of Clinical Microbiology Infectious Diseases/European Confederation of Medical Mycology/European Respiratory Society (ESCMID/ECMM/ERS), 2018 Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) CPGs, and their previous versions (2008 IDSA/ATS and 2011 GEMICOMED/SEIMC). ECMID/ECMM/ERS have not published any previous version. From 511 recommendations analyzed, 80 were classified as LOE A (15.7%), 223 LOE B (43.6%), and 208 LOE C (40.7%). Among 238 strong recommendations, only 57 (24.0%) were supported by LOE A. When comparing recent CPGs with previous versions, the proportion of recommendations supported by LOE A did not significantly increase over time (IDSA/ATS: 13.3% [2016] vs. 14.8% [2008], p = 0.798; and SEIMC: 22.6% [2018] vs. 19% [2011], p = 0.568). In conclusion, IA is a condition with an urgent unmet clinical need for more high-quality randomized trials.

Evidence supporting recommendations from international guidelines on treatment, diagnosis, and prevention of HAP and VAP in adults.

Clinical practice guidelines (CPGs) are intended to support clinical decisions and should be based on high-quality evidence. The objective of the study was to evaluate the quality of evidence supporting the recommendations issued in CPGs for therapy, diagnosis, and prevention of hospital-acquired and ventilator-associated pneumonia (HAP/VAP). CPGs released by international scientific societies after year 2000, using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology, were analyzed. Number and strength of recommendations and quality of evidence (high, moderate, low, and very low) were extracted and indexed in the aforementioned sections. High-quality evidence was based on randomized control trials (RCT) without important limitations and exceptionally on rigorous observational studies. Eighty recommendations were assessed, with 7 (8.7%), 24 (30.0%), 29 (36.3%), and 20 (25.0%) being supported by high, moderate, low, and very low-quality evidence, respectively. Highest evidence degree was reported for 26 prevention recommendations, with 7 (26.9%) supported by high-quality evidence and no recommendation based on very low-quality evidence. In contrast, among 9 recommendations for diagnosis and 45 for therapy, none was supported by high-quality evidence, in spite of being recommended as strong in 33.3% and 46.7%, respectively. Among HAP/VAP diagnosis recommendations, the majority of evidence was rated as low or very low-quality (55.6% and 22.2%, respectively) whereas among HAP/VAP therapy recommendations, 4/5 were rated as low and very low-quality (40% each). In conclusion, among HAP/VAP international guidelines, most recommendations, particularly in therapy, remain supported by observational studies, case reports, and expert opinion. Well-designed RCTs are urgently needed.

Antimicrobial Stewardship in Hematological Patients at the intensive care unit: a global cross-sectional survey from the Nine-i Investigators Network.

A global cross-sectional survey was performed to gather data on the current treatment of infections caused by multidrug-resistant (MDR) bacteria among hematological patients admitted to ICUs worldwide. The survey was performed in April 2019 using an electronic platform (SurveyMonkey®) being distributed among 83 physicians and completed by 48 (57.8%) responders. ESBL Enterobacteriaceae, carbapenem-resistant K. pneumoniae and carbapenem-resistant P. aeruginosa were the main concerns. Previous MDR infection (34% of responders), MDR colonization (20%) and previous antibiotic exposure within the last 3 months (20.5%) were considered the most relevant risk factors of bloodstream infection (BSI) due to MDR bacteria. In 48.8% of the ICUs, there was no antimicrobial stewardship (AMS) team focused on hematological patients. Updates on local epidemiology of MDR pathogens were provided in 98% of the centers, using phone or verbal communications (56.1% and 53.7%, respectively). In presence of febrile neutropenia, initial therapy consisted of anti-Gram-negative plus anti-Gram-positive antibiotics for 41% of participants. Antibiotic de-escalation and/or discontinuation of therapy were considered as a promising strategy for the prevention of MDR development (32.4%). Factors associated with antibiotic de-escalation were clinical improvement (43.6%) and neutrophil count recovery (12.8%). Infectious Disease consultation and AMS interventions were not determining factors for de-escalation decisions (more than 50% of responders). Infection control and educational programs were valued as necessary measures for implementation by ICU practitioners. These findings should guide future efforts on collaborative team working, improving compliance with adequate treatment protocols, implementing antimicrobial stewardship programs in critically ill hematological patients, and educational activities.

Ventilator-associated pneumonia diagnosis: a prioritization exercise based on multi-criteria decision analysis.

The aim was to provide global experts ranking on priorities in diagnostic tools for VAP in clinical practice. A multiple criteria decision analysis (MCDA) was performed to identify diagnosis tools for VAP diagnosis. Priority factors were identified after literature review. An international, multidisciplinary expert panel reviewed variables and ranked diagnostic tools. Experts from ten European hospitals participated. Regarding bedside clinical practices, seven required chest X-ray use in all patients, whereas six reported the use of blood cultures and endotracheal aspirate in all patients. Invasive techniques were routinely performed in seven sites. CRP, PCT, and Gram stains were performed in all patients by 5, 2, and 8, respectively. Impact on patient outcomes, safety, and impact on the decision to start antibiotic therapy were ranked as the top three relevant concerns (7.7/10, 7/10, and 6.9/10, respectively). Chest X-ray was ranked as the most important imaging technique to diagnose VAP (score 251.7). Apart from blood cultures, endotracheal aspirate culture was identified as the main collection method for the microbiological testing (scores of 274.8 and 246.8, respectively). Mini-BAL was the preferred invasive technique with a score of 208. Top three biomarkers were CRP (score 184.3), PCT (181.3), and WBC (166.4). Gram stain (192.5) was prioritized among laboratory diagnostic techniques. Using MCDA, it is recommended to perform a combination of diagnostic techniques including images (chest X-ray), culture of clinical specimens (blood cultures and endotracheal aspirate), and biomarkers (CRP or PCT) for VAP diagnosis at the bedside. Gram stain was ranked as the preferred laboratory technique.

Treatment of ventilator-associated pneumonia (VAP) caused by Acinetobacter: results of prospective and multicenter ID-IRI study.

Ventilator-associated pneumonia (VAP) due to Acinetobacter spp. is one of the most common infections in the intensive care unit. Hence, we performed this prospective-observational multicenter study, and described the course and outcome of the disease. This study was performed in 24 centers between January 06, 2014, and December 02, 2016. The patients were evaluated at time of pneumonia diagnosis, when culture results were available, and at 72 h, at the 7th day, and finally at the 28th day of follow-up. Patients with coexistent infections were excluded and only those with a first VAP episode were enrolled. Logistic regression analysis was performed. A total of 177 patients were included; empiric antimicrobial therapy was appropriate (when the patient received at least one antibiotic that the infecting strain was ultimately shown to be susceptible) in only 69 (39%) patients. During the 28-day period, antibiotics were modified for side effects in 27 (15.2%) patients and renal dose adjustment was made in 38 (21.5%). Ultimately, 89 (50.3%) patients died. Predictors of mortality were creatinine level (OR, 1.84 (95% CI 1.279-2.657); p = 0.001), fever (OR, 0.663 (95% CI 0.454-0.967); p = 0.033), malignancy (OR, 7.095 (95% CI 2.142-23.500); p = 0.001), congestive heart failure (OR, 2.341 (95% CI 1.046-5.239); p = 0.038), appropriate empiric antimicrobial treatment (OR, 0.445 (95% CI 0.216-0.914); p = 0.027), and surgery in the last month (OR, 0.137 (95% CI 0.037-0.499); p = 0.003). Appropriate empiric antimicrobial treatment in VAP due to Acinetobacter spp. was associated with survival while renal injury and comorbid conditions increased mortality. Hence, early diagnosis and appropriate antibiotic therapy remain crucial to improve outcomes.

A novel id-iri score: development and internal validation of the multivariable community acquired sepsis clinical risk prediction model.

We aimed to develop a scoring system for predicting in-hospital mortality of community-acquired (CA) sepsis patients. This was a prospective, observational multicenter study performed to analyze CA sepsis among adult patients through ID-IRI (Infectious Diseases International Research Initiative) at 32 centers in 10 countries between December 1, 2015, and May 15, 2016. After baseline evaluation, we used univariate analysis at the second and logistic regression analysis at the third phase. In this prospective observational study, data of 373 cases with CA sepsis or septic shock were submitted from 32 referral centers in 10 countries. The median age was 68 (51-77) years, and 174 (46,6%) of the patients were females. The median hospitalization time of the patients was 15 (10-21) days. Overall mortality rate due to CA sepsis was 17.7% (n = 66). The possible predictors which have strong correlation and the variables that cause collinearity are acute oliguria, altered consciousness, persistent hypotension, fever, serum creatinine, age, and serum total protein. CAS (%) is a new scoring system and works in accordance with the parameters in third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). The system has yielded successful results in terms of predicting mortality in CA sepsis patients.