Derivation and Validation of a Novel Severity Scoring System for Pneumonia at Intensive Care Unit Admission.

BACKGROUND: Severity stratification scores developed in intensive care units (ICUs) are used in interventional studies to identify the most critically ill. Studies that evaluate accuracy of these scores in ICU patients admitted with pneumonia are lacking. This study aims to determine performance of severity scores as predictors of mortality in critically ill patients admitted with pneumonia. METHODS: Prospective cohort study in a general ICU in Brazil. ICU severity scores (Simplified Acute Physiology Score 3 [SAPS 3] and Sepsis-Related Organ Failure Assessment [qSOFA]), prognostic scores of pneumonia (CURB-65 [confusion, urea, respiratory rate, blood pressure, age] and CRB-65 [confusion, respiratory rate, blood pressure, age]), and clinical and epidemiological variables in the first 6 hours of hospitalization were analyzed. RESULTS: Two hundred patients were included between 2015 and 2018, with a median age of 81 years (interquartile range, 67-90 years) and female predominance (52%), primarily admitted from the emergency department (65%) with community-acquired pneumonia (CAP, 80.5%). SAPS 3, CURB-65, CRB-65,and qSOFA all exhibited poor performance in predicting mortality. Multivariate regression identified variables independently associated with mortality that were used to develop a novel pneumonia-specific ICU severity score (Pneumonia Shock score) that outperformed SAPS 3, CURB-65, and CRB-65. The Shock score was validated in an external multicenter cohort of critically ill patients admitted with CAP. CONCLUSIONS: We created a parsimonious score that accurately identifies patients with pneumonia at highest risk of ICU death. These findings are critical to accurately stratify patients with severe pneumonia in therapeutic trials that aim to reduce mortality.

Multifocal tuberculosis-associated immune reconstitution inflammatory syndrome - a case report of a complicated scenario.

BACKGROUND: Tuberculosis (TB)-associated Immune reconstitution inflammatory syndrome (TB-IRIS) is an aberrant inflammatory response in TB patients with advanced human immunodeficiency virus coinfection, after antiretroviral therapy commencement. CASE PRESENTATION: We present a rare case of a 51-year-old woman living with HIV who developed a series of TB-IRIS events occurring at multiple sites sequentially, highlighting the clinical complexity in diagnosis and management. CONCLUSION: This case illustrates how complicated a clinical scenario of successive TB-IRIS episodes can be, in terms of clinical management.

The microbiome of the critically ill patient.

PURPOSE OF REVIEW: Advances in the understanding of the human microbiome outside of the ICU have led investigators to consider the role of the microbiome in critical illness. The picture that is being elucidated is one of dysbiosis occurring at multiple sites in the critically ill patient. This review describes the changes that occur in the various microbiomes of a critically ill patient, the implications of these changes and shows how advances in the understanding of dysbiosis may lead to microbiome-targeted therapies. RECENT FINDINGS: Critically ill patients undergo dysbiosis at several organ sites including the skin, gastrointestinal system and the lungs with loss of microbial diversity and a propensity for potentially pathogenic organisms to dominate a particular microbiome. These microbiome changes appear to be predictive of clinical outcome. While the use of fecal microbial transplantation has been demonstrated to be an effective treatment for recurrent Clostridium difficile infection, the use of fecal microbial transplantation and other microbiome modifying therapies may have a role in managing critical illness in the ICU. SUMMARY: A growing understanding of the microbiome in the critically ill may modify current dogma regarding the pathogenesis of sepsis and other life-threatening conditions seen in the ICU, thereby fundamentally changing antibiotic stewardship and the management of the critically ill patient.

An innovative system for 3D clinical photography in the resource-limited settings.

BACKGROUND: Kaposi's sarcoma (KS) is the most frequently occurring cancer in Mozambique among men and the second most frequently occurring cancer among women. Effective therapeutic treatments for KS are poorly understood in this area. There is an unmet need to develop a simple but accurate tool for improved monitoring and diagnosis in a resource-limited setting. Standardized clinical photographs have been considered to be an essential part of the evaluation. METHODS: When a therapeutic response is achieved, nodular KS often exhibits a reduction of the thickness without a change in the base area of the lesion. To evaluate the vertical space along with other characters of a KS lesion, we have created an innovative imaging system with a consumer light-field camera attached to a miniature "photography studio" adaptor. The image file can be further processed by computational methods for quantification. RESULTS: With this novel imaging system, each high-quality 3D image was consistently obtained with a single camera shot at bedside by minimally trained personnel. After computational processing, all-focused photos and measurable 3D parameters were obtained. More than 80 KS image sets were processed in a semi-automated fashion. CONCLUSIONS: In this proof-of-concept study, the feasibility to use a simple, low-cost and user-friendly system has been established for future clinical study to monitor KS therapeutic response. This 3D imaging system can be also applied to obtain standardized clinical photographs for other diseases.

Validation of the questionnaire of olfactory disorders (QOD) for the Brazilian population.

BACKGROUND: The incidence of olfactory disorders has increased in recent years, mainly related to COVID-19 infection. In Brazil, over 37 million cases of COVID-19 have been reported, and approximately 10 % of those cases continue to experience olfactory disorders for more than one month. Despite the significant negative impact on well-being, there is currently no validated instrument to assess how olfactory disorders impact the quality of life in Brazil. OBJECTIVES: This study aimed to validate the Questionnaire of Olfactory Disorders (QOD) for Brazilian Portuguese. METHODS: The authors first performed translation, back-translation, expert review, pre-testing, psychometric evaluation and cultural adaptation of the English version of the questionnaire. To assure linguistic and conceptual equivalence of the translated questionnaire, 126 participants from two Brazilian states and varying degrees of olfactory loss answered the QOD and the World Health Organization Quality of Life bref (WHOQOL-bref) questionnaires. The University of Pennsylvania Smell Identification Test (UPSIT®) was used to quantify the olfactory loss. Furthermore, to evaluate the reliability of the Portuguese version a test-retest was performed on a subgroup of patients. The authors observed a high Cronbach's alpha (α = 0.86) for internal consistency of the quality of Life (QOD-QOL) statements. FINDINGS: As expected, there was a negative correlation between QOD-QOL and UPSIT® (Spearman's ρ = -0.275, p = 0.002), since QOL score increases and UPSIT® score decreases with worsening of olfactory function. Correlations were moderate between QOD-QOL and WHOQOL-bref mean (Spearman's ρ = -0.374, p < 0.001) and weak to moderate between the QOD-QOL and Visual Analog Scale of the QOD regarding professional life, leisure, and private life (Spearman's ρ = -0.316, p = 0.000; Spearman's ρ = -0.293, p = 0.001; Spearman's ρ = -0.261, p = 0.004; respectively). CONCLUSION: In conclusion, the authors have demonstrated a high internal consistency and validity of the Brazilian Portuguese version of the QOD for evaluating the quality of life in individuals with olfactory disorders.

Whole-genome surveillance identifies markers of Plasmodium falciparum drug resistance and novel genomic regions under selection in Mozambique.

IMPORTANCE: Malaria is a devastating disease caused by Plasmodium parasites. The evolution of parasite drug resistance continues to hamper progress toward malaria elimination, and despite extensive efforts to control malaria, it remains a leading cause of death in Mozambique and other countries in the region. The development of successful vaccines and identification of molecular markers to track drug efficacy are essential for managing the disease burden. We present an analysis of the parasite genome in Mozambique, a country with one of the highest malaria burdens globally and limited available genomic data, revealing current selection pressure. We contribute additional evidence to limited prior studies supporting the effectiveness of SWGA in producing reliable genomic data from complex clinical samples. Our results provide the identity of genomic loci that may be associated with current antimalarial drug use, including artemisinin and lumefantrine, and reveal selection pressure predicted to compromise the efficacy of current vaccine candidates.

High seroprevalence of Leishmania infantum is linked to immune activation in people with HIV: a two-stage cross-sectional study in Bahia, Brazil.

Visceral leishmaniasis is an opportunistic disease in HIV-1 infected individuals, unrecognized as a determining factor for AIDS diagnosis. The growing geographical overlap of HIV-1 and Leishmania infections is an emerging challenge worldwide, as co-infection increases morbidity and mortality for both infections. Here, we determined the prevalence of people living with HIV (PWH) with a previous or ongoing infection by Leishmania infantum and investigated the virological and immunological factors associated with co-infection. We adopted a two-stage cross-sectional cohort (CSC) design (CSC-I, n = 5,346 and CSC-II, n = 317) of treatment-naïve HIV-1-infected individuals in Bahia, Brazil. In CSC-I, samples collected between 1998 and 2013 were used for serological screening for leishmaniasis by an in-house Enzyme-Linked Immunosorbent Assay (ELISA) with SLA (Soluble Leishmania infantum Antigen), resulting in a prevalence of previous or ongoing infection of 16.27%. Next, 317 PWH were prospectively recruited from July 2014 to December 2015 with the collection of sociodemographic and clinical data. Serological validation by two different immunoassays confirmed a prevalence of 15.46 and 8.20% by anti-SLA, and anti-HSP70 serology, respectively, whereas 4.73% were double-positive (DP). Stratification of these 317 individuals in DP and double-negative (DN) revealed a significant reduction of CD4+ counts and CD4+/CD8+ ratios and a tendency of increased viral load in the DP group, as compared to DN. No statistical differences in HIV-1 subtype distribution were observed between the two groups. However, we found a significant increase of CXCL10 (p = 0.0076) and a tendency of increased CXCL9 (p = 0.061) in individuals with DP serology, demonstrating intensified immune activation in this group. These findings were corroborated at the transcriptome level in independent Leishmania- and HIV-1-infected cohorts (Swiss HIV Cohort and Piaui Northeast Brazil Cohort), indicating that CXCL10 transcripts are shared by the IFN-dominated immune activation gene signatures of both pathogens and positively correlated to viral load in untreated PWH. This study demonstrated a high prevalence of PWH with L. infantum seropositivity in Bahia, Brazil, linked to IFN-mediated immune activation and a significant decrease in CD4+ levels. Our results highlight the urgent need to increase awareness and define public health strategies for the management and prevention of HIV-1 and L. infantum co-infection.

The impact of body mass index on the prognostic performance of the Simplified Acute Physiology Score 3: A prospective cohort study.

Objective: To assess the Simplified Acute Physiology Score 3 (SAPS3) prognostic score performance across different body mass index categories. Methods: A retrospective cohort study in a general ICU in Brazil. A secondary analysis of medical records was performed with clinical and epidemiological data. Patients were stratified according to their body mass index (BMI) category, and a binary logistic regression was then performed to identify factors independently associated with mortality. SAPS3 accuracy was determined using the area under the receiver operating characteristics curve and the Hosmer-Lemeshow test. A modified Kaplan-Meyer plot was employed to evaluate death probability according to BMI. ICU mortality was evaluated as the primary outcome. Results: A total of 2,179 patients (mean age of 67.9 years and female predominance (53.1%)) were enrolled. SAPS3 was found accurate in all groups except in the underweight (AUC: 0.694 95% CI 0.616-0.773; HL = 0.042). The patients in the underweight group tended to be older, have longer hospital stay, have worse functional status, and have a higher value on prognostic scores. After the adjustments, no statistically significant difference between the BMI groups was noted in relation to mortality, except for the low weight that presented a likelihood of death of 3.50 (95% CI, 1.43-8.58, p = 0.006). Conclusion: This research showed that SAPS3 had poor accuracy in predicting ICU mortality in underweight patients. This group was shown to be an independent risk factor for worse clinical outcomes.

Calibration and validation of the Pneumonia Shock Score in critically ill patients with SARS-CoV-2 infection, a multicenter prospective cohort study.

Background: Prognostic tools developed to stratify critically ill patients in Intensive Care Units (ICUs), are critical to predict those with higher risk of mortality in the first hours of admission. This study aims to evaluate the performance of the pShock score in critically ill patients admitted to the ICU with SARS-CoV-2 infection. Methods: Prospective observational analytical cohort study conducted between January 2020 and March 2021 in four general ICUs in Salvador, Brazil. Descriptive statistics were used to characterize the cohort and a logistic regression, followed by cross-validation, were performed to calibrate the score. A ROC curve analysis was used to assess accuracy of the models analyzed. Results: Six hundred five adult ICU patients were included in the study. The median age was 63 (IQR: 49-74) years with a mortality rate of 33.2% (201 patients). The calibrated pShock-CoV score performed well in prediction of ICU mortality (AUC of 0.80 [95% Confidence Interval (CI): 0.77-0.83; p-value < 0.0001]). Conclusions: The pShock-CoV score demonstrated robust discriminatory capacity and may assist in targeting scarce ICU resources during the COVID-19 pandemic to those critically ill patients most likely to benefit.

A prospective comparison between multidisciplinary healthcare providers' clinical examination and a validated pain scale.

Introduction: Unrecognized pain in the Intensive Care Unit (ICU), due to inadequate assessment and therapeutic management, is associated with increased morbidity and mortality. Despite the availability of validated pain monitoring tools, such as the Critical-Care Pain Observational Tool (CPOT), these scales are not commonly used in clinical practice, with healthcare professionals often relying on their clinical impression. Our study aims to determine the agreement between the pain examination performed by ICU professionals and the CPOT. Methods: Prospective cohort study that included critically ill patients and physicians, nurses and physiotherapists from an ICU in Bahia, Brazil. During bedside clinical rounds, the CPOT score was applied to assess the pain of hospitalized patients, and health professionals were interviewed to ascertain their perception of the patient's pain for a maximum of five consecutive days. Correlations were assessed using the Spearman rank tests. Hierarchical cluster analysis was employed to show the results of CPOT score and pain assessment by healthcare professionals at each study time. And the Kappa statistic was calculated to assess the agreement between the CPOT score vs. the pain assessment by healthcare providers. Results: One hundred one patients were included in the study with median age of 74 years (IQR 61.5-83.5), a predominance of women (55.4%) and a median SAPS 3 score of 45 (IQR 39.5-53.0). The correlation between the professional's pain assessment and the CPOT were mostly statistically significant, ranged from negligible to weak, being the highest index obtained in the evaluation of nurses on day 5 (Kappa index = 0.43, p = 0.005). Physician assessments were significant only in day 1. On the presence of pain, the professionals' assessments and CPOT revealed mild to a moderate agreement. Conclusion: Healthcare professional's pain assessment displayed a weak positive correlation with a validated pain scale and poor agreement amongst members of the ICU team, particularly when the pain was felt to be absent. Thus, this study highlights the importance of routine tools for pain assessment in the ICU for all members of multidisciplinary teams.

Systemic Inflammation Associated with Immune Reconstitution Inflammatory Syndrome in Persons Living with HIV.

Antiretroviral therapy (ART) has represented a major advancement in the care of people living with HIV (PLWHH), resulting in significant reductions in morbidity and mortality through immune reconstitution and attenuation of homeostatic disruption. Importantly, restoration of immune function in PLWH with opportunistic infections occasionally leads to an intense and uncontrolled cytokine storm following ART initiation known as immune reconstitution inflammatory syndrome (IRIS). IRIS occurrence is associated with the severe and rapid clinical deterioration that results in significant morbidity and mortality. Here, we detail the determinants underlying IRIS development in PLWH, compiling the available knowledge in the field to highlight details of the inflammatory responses in IRIS associated with the most commonly reported opportunistic pathogens. This review also highlights gaps in the understanding of IRIS pathogenesis and summarizes therapeutic strategies that have been used for IRIS.

Pragmatic Recommendations for the Management of Anticoagulation and Venous Thrombotic Disease for Hospitalized Patients with COVID-19 in Low- and Middle-Income Countries.

New studies of COVID-19 are constantly updating best practices in clinical care. Often, it is impractical to apply recommendations based on high-income country investigations to resource limited settings in low- and middle-income countries (LMICs). We present a set of pragmatic recommendations for the management of anticoagulation and thrombotic disease for hospitalized patients with COVID-19 in LMICs. In the absence of contraindications, we recommend prophylactic anticoagulation with either low molecular weight heparin (LMWH) or unfractionated heparin (UFH) for all hospitalized COVID-19 patients in LMICs. If available, we recommend LMWH over UFH for venous thromboembolism (VTE) prophylaxis to minimize risk to healthcare workers. We recommend against the use of aspirin for VTE prophylaxis in hospitalized COVID-19 and non-COVID-19 patients in LMICs. Because of limited evidence, we suggest against the use of "enhanced" or "intermediate" prophylaxis in COVID-19 patients in LMICs. Based on current available evidence, we recommend against the initiation of empiric therapeutic anticoagulation without clinical suspicion for VTE. If contraindications exist to chemical prophylaxis, we recommend mechanical prophylaxis with intermittent pneumatic compression (IPC) devices or graduated compression stockings (GCS) for hospitalized COVID-19 patients in LMICs. In LMICs, we recommend initiating therapeutic anticoagulation for hospitalized COVID-19 patients, in accordance with local clinical practice guidelines, if there is high clinical suspicion for VTE, even in the absence of testing. If available, we recommend LMWH over UFH or Direct oral anticoagulants for treatment of VTE in LMICs to minimize risk to healthcare workers. In LMIC settings where continuous intravenous UFH or LMWH are unavailable or not feasible to use, we recommend fixed dose heparin, adjusted to body weight, in hospitalized COVID-19 patients with high clinical suspicion of VTE. We suggest D-dimer measurement, if available and affordable, at the time of admission for risk stratification, or when clinical suspicion for VTE is high. For hospitalized COVID-19 patients in LMICs, based on current available evidence, we make no recommendation on the use of serial D-dimer monitoring for the initiation of therapeutic anticoagulation. For hospitalized COVID-19 patients in LMICs receiving intravenous therapeutic UFH, we recommend serial monitoring of partial thromboplastin time or anti-factor Xa level, based on local laboratory capabilities. For hospitalized COVID-19 patients in LMICs receiving LMWH, we suggest against serial monitoring of anti-factor Xa level. We suggest serial monitoring of platelet counts in patients receiving therapeutic anticoagulation for VTE, to assess risk of bleeding or development of heparin induced thrombocytopenia.

The Interplay Between Systemic Inflammation, Oxidative Stress, and Tissue Remodeling in Tuberculosis.

Significance: Excessive and prolonged proinflammatory responses are associated with oxidative stress, which is commonly observed during chronic tuberculosis (TB). Such condition favors tissue destruction and consequently bacterial spread. A tissue remodeling program is also triggered in chronically inflamed sites, facilitating a wide spectrum of clinical manifestations. Recent Advances: Since persistent and exacerbated oxidative stress responses have been associated with severe pathology, a number of studies have suggested that the inhibition of this augmented stress response by improving host antioxidant status may represent a reasonable strategy to ameliorate tissue damage in TB. Critical Issues: This review summarizes the interplay between oxidative stress, systemic inflammation and tissue remodeling, and its consequences in promoting TB disease. We emphasize the most important mechanisms associated with stress responses that contribute to the progression of TB. We also point out important host immune components that may influence the exacerbation of cellular stress and the subsequent tissue injury. Future Directions: Further research should reveal valuable targets for host-directed therapy of TB, preventing development of severe immunopathology and disease progression. Antioxid. Redox Signal. 34, 471-485.

Evaluation of ELISA-Based Multiplex Peptides for the Detection of Human Serum Antibodies Induced by Zika Virus Infection across Various Countries.

Zika virus (ZIKV) is a mosquito-borne Flavivirus with a positive-sense RNA genome, which are generally transmitted through the bite of an infected Aedes mosquito. ZIKV infections could be associated with neurological sequelae that, and otherwise produces similar clinical symptoms as other co-circulating pathogens. Past infection with one member of the Flavivirus genus often induces cross-reactive antibodies against other flaviruses. These attributes complicate the ability to differentially diagnose ZIKV infection from other endemic mosquito-borne viruses, making it both a public health issue as well as a diagnostic challenge. We report the results from serological analyses using arbovirus-specific peptides on 339 samples that were previously collected from 6 countries. Overall, we found that our multiplexed peptide-based ELISA was highly efficient for identifying ZIKV antibodies as early as 2 weeks post infection, and that it correlates with microneutralization, plaque reduction neutralization tests (PRNTs) and commercial tests for ZIKV in previously characterized samples. We observed that seropositivity varied by patient cohort, reflecting the sampling period in relation to the 2015-2016 ZIKV outbreak. This work evaluates the accuracy, specificity, and sensitivity of our peptide-based ELISA method for detecting ZIKV antibodies from geographically diverse regions. These findings can contribute to ongoing serological methods development and can be adapted for use in future studies.

Pragmatic Recommendations for Therapeutics of Hospitalized COVID-19 Patients in Low- and Middle-Income Countries.

The therapeutic options for COVID-19 patients are currently limited, but numerous randomized controlled trials are being completed, and many are on the way. For COVID-19 patients in low- and middle-income countries (LMICs), we recommend against using remdesivir outside of a clinical trial. We recommend against using hydroxychloroquine ± azithromycin or lopinavir-ritonavir. We suggest empiric antimicrobial treatment for likely coinfecting pathogens if an alternative infectious cause is likely. We suggest close monitoring without additional empiric antimicrobials if there are no clinical or laboratory signs of other infections. We recommend using oral or intravenous low-dose dexamethasone in adults with COVID-19 disease who require oxygen or mechanical ventilation. We recommend against using dexamethasone in patients with COVID-19 who do not require supplemental oxygen. We recommend using alternate equivalent doses of steroids in the event that dexamethasone is unavailable. We also recommend using low-dose corticosteroids in patients with refractory shock requiring vasopressor support. We recommend against the use of convalescent plasma and interleukin-6 inhibitors, such as tocilizumab, for the treatment of COVID-19 in LMICs outside of clinical trials.

Pragmatic Recommendations for the Management of COVID-19 Patients with Shock in Low- and Middle-Income Countries.

As some patients infected with the novel coronavirus progress to critical illness, a subset will eventually develop shock. High-quality data on management of these patients are scarce, and further investigation will provide valuable information in the context of the pandemic. A group of experts identify a set of pragmatic recommendations for the care of patients with SARS-CoV-2 and shock in resource-limited environments. We define shock as life-threatening circulatory failure that results in inadequate tissue perfusion and cellular dysoxia/hypoxia, and suggest that it can be operationalized via clinical observations. We suggest a thorough evaluation for other potential causes of shock and suggest against indiscriminate testing for coinfections. We suggest the use of the quick Sequential Organ Failure Assessment (qSOFA) as a simple bedside prognostic score for COVID-19 patients and point-of-care ultrasound (POCUS) to evaluate the etiology of shock. Regarding fluid therapy for the treatment of COVID-19 patients with shock in low-middle-income countries, we favor balanced crystalloids and recommend using a conservative fluid strategy for resuscitation. Where available and not prohibited by cost, we recommend using norepinephrine, given its safety profile. We favor avoiding the routine use of central venous or arterial catheters, where availability and costs are strong considerations. We also recommend using low-dose corticosteroids in patients with refractory shock. In addressing targets of resuscitation, we recommend the use of simple bedside parameters such as capillary refill time and suggest that POCUS be used to assess the need for further fluid resuscitation, if available.

Temporal variations in bacterial community diversity and composition throughout intensive care unit renovations.

BACKGROUND: Inanimate surfaces within a hospital serve as a reservoir of microbial life that may colonize patients and ultimately result in healthcare associated infections (HAIs). Critically ill patients in intensive care units (ICUs) are particularly vulnerable to HAIs. Little is known about how the microbiome of the ICU is established or what factors influence its evolution over time. A unique opportunity to bridge the knowledge gap into how the ICU microbiome evolves emerged in our health system, where we were able to characterize microbial communities in an established hospital ICU prior to closing for renovations, during renovations, and then after re-opening. RESULTS: We collected swab specimens from ICU bedrails, computer keyboards, and sinks longitudinally at each renovation stage, and analyzed the bacterial compositions on these surfaces by 16S rRNA gene sequencing. Specimens collected before ICU closure had the greatest alpha diversity, while specimens collected after the ICU had been closed for over 300 days had the least. We sampled the ICU during the 45 days after re-opening; however, within that time frame, the alpha diversity never reached pre-closure levels. There were clear and significant differences in microbiota compositions at each renovation stage, which was driven by environmental bacteria after closure and human-associated bacteria after re-opening and before closure. CONCLUSIONS: Overall, we identified significant differences in microbiota diversity and community composition at each renovation stage. These data help to decipher the evolution of the microbiome in the most critical part of the hospital and demonstrate the significant impacts that microbiota from patients and staff have on the evolution of ICU surfaces. Video Abstract.

Factors Associated with Mortality in Critically Ill Patients Diagnosed with Hospital Acquired Infections.

OBJECTIVE: Evaluate host and pathogen factors associated with mortality in those with hospital acquired infections (HAI) in a tertiary intensive care unit in Brazil. METHODS: Observational and analytical cohort single center study in a general intensive care unit (ICU) in Northeastern Brazil between January 2016 and August 2018, including those over 18 years of age admitted to the ICU found to have a HAI. RESULTS: A total of 165 patients were included, with a mean age of 72 years and male predominance (53.3%) and observed mortality of 46%. Mortality in those with HAI was significantly associated with older age, increased ICU length of stay and readmission to the ICU in univariate analysis. Multivariate analysis revealed that development of septic shock and obtundation during ICU admission was significantly associated with an increased risk of death (OR: 6.94, 95% CI 1.23-39.27, OR: 2.48, 95% CI 1.17-5.29, respectively). A trend towards mortality risk was noted in those with increased age and prior cardiovascular disease. Surprisingly, mortality risk was independent of site of infection, type of pathogen and antibiotic resistance. Furthermore, having more than one HAI over the course of the ICU admission did not impact mortality. CONCLUSION: Risk of death in those with HAI is associated with obtundation and septic shock, in addition to vasopressor use. Host factors, rather than pathogen-specific characteristics or infecting site, impact risk of death related to HAI in the ICU.