2117. Fluconazole vs. Echinocandins as Initial Therapy for Candidemia Caused by Fluconazole-Susceptible Species in the Era of Rapid Diagnostic Testing

Abstract Background Echinocandins (ECH) are recommended first-line for initial therapy (IT) of candidemia (CD) over fluconazole (FLU) due to their broad spectrum of activity. This recommendation was made prior to widespread implementation of rapid diagnostic testing (RDT), allowing prompt species identification and targeted therapy. The objective of this study was to compare clinical outcomes in patients with CD caused by FLU-susceptible species who received either FLU or ECH as IT. Methods This was a multicenter, retrospective cohort study of adults with CD caused by C. albicans, C. tropicalis, or C. parapsilosis. Patients who received FLU or ECH as IT for at least 48 hours from May 2012 to October 2018 were included. Patients who died within 48 hours of first positive blood culture were excluded. The primary endpoint was the rate of clinical failure (persistent CD for >72 hours, recurrent infection within 30 days, change in therapy, and all-cause mortality within 30 days). Secondary endpoints included 90-day all-cause mortality and time to culture clearance. A subgroup analysis in critically ill patients was conducted. Results Of the 371 patients evaluated, 128 met criteria for inclusion, 57 received FLU and 71 received ECH. Patients in the ECH group had a higher incidence of sepsis at the time of first positive blood culture (45.1% vs. 19.3%, P = 0.002). A line-associated source was more common in the ECH group (56.3%) vs. urinary source in the FLU group (21.1%). C. albicans was most common in both groups (63%). Clinical failure was similar in the FLU and ECH groups (38.6% vs. 35.2%, P = 0.69). 90-day mortality and time to culture clearance (1.6 vs. 1.5 days, P = 0.63) did not yield significant differences. In the subgroup analysis of critically ill patients, there was a trend suggesting higher rate of failure in patients who received FLU vs. an ECH (60.9% vs. 47.7%, P = 0.31), though underpowered to detect such a difference. Length of stay (LOS) was shorter in patients who received FLU (12 vs. 18 days, P = 0.018). Conclusion FLU as IT for FLU-susceptible CD may be a reasonable option in non-critically ill patients in the setting of RDT. This may lead to shorter LOS given the availability of an oral formulation. Additional prospective studies are needed to validate these conclusions. Disclosures All authors: No reported disclosures.

Download Full-text

Serum anion gap is associated with all-cause mortality among critically ill patients with congestive heart failure

10.1101/2020.07.24.20161463 ◽

2020 ◽

Author(s):

yiyang tang ◽

wenchao lin ◽

lihuang zha ◽

xiaofang zeng ◽

zhenghui liu ◽

...

Keyword(s):

Heart Failure ◽

Congestive Heart Failure ◽

Critically Ill ◽

Subgroup Analysis ◽

Critically Ill Patients ◽

Demographic Data ◽

Cox Proportional Hazards ◽

Anion Gap ◽

High Morbidity ◽

All Cause Mortality

Background: Congestive heart failure (CHF) is a complex clinical syndrome, with high morbidity and mortality. Serum anion gap (SAG) has been known to be associated with the severity of various cardiovascular diseases. However, the role of SAG indicators in CHF is unclear. Methods and results: A retrospective analysis of data from MIMIC-III v1.4 was conducted in critically ill patients with CHF. Clinical information of each patient, including demographic data, comorbidities, vital signs, scores, and laboratory indicators, were successfully obtained. Cox proportional hazards models were performed to determine the relationship between SAG and mortality in CHF patient, the consistency of which was further verified by subgroup analysis. Results: A total of 7426 subjects met the inclusion criteria. In multivariate analysis, after adjusting for age, gender, ethnicity, and other potential confounders, higher SAG was significantly related to an increase in 30-day and 90-day all-cause mortality of critically ill patients with CHF compared with lower SAG (tertile3 vs tertile1: adjusted HR, 95% CI: 1.74, 1.46-2.08; 1.53, 1.32-1.77). In subgroup analysis, the association between SAG and all-cause mortality present similarities in most strata. Conclusion: SAG at admission can be a promising predictor of all-cause mortality in critically ill patients with CHF.

Download Full-text

112. Physiological Signature of Bloodstream Infection in Critically Ill Patients

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.187 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S87-S88

Author(s):

Alex Zimmet ◽

Matthew Clark ◽

Shrirang M Gadrey ◽

Taison Bell ◽

J Randall Moorman ◽

...

Keyword(s):

Blood Culture ◽

Bloodstream Infection ◽

Critically Ill ◽

Positive Blood Culture ◽

Critically Ill Patients ◽

Vital Sign ◽

Physiological Data ◽

Surgical Trauma ◽

Critically Ill Adults ◽

Ill Adults

Abstract Background Bloodstream infection (BSI) is associated with high mortality rates in critically ill patients but is difficult to identify clinically. This uncertainty results in frequent blood culture testing, which exposes patients to additional costs and the potential harms of unnecessary antibiotics. Accordingly, we aimed to identify signatures in physiological data from critically ill adults that characterize BSI. Methods We reviewed all blood culture, vital sign, laboratory, and cardiorespiratory monitoring (CRM) data from patients admitted to the medical and surgical/trauma ICUs at the University of Virginia Medical Center from February 2011 to June 2015. Blood culture results were categorized as positive, negative, or contaminant. For the BSI population, we included data obtained within 12 hours before or 24 hours after the acquisition of a positive blood culture. The control population included data greater than 12 hours before or 24 hours after the acquisition of a positive blood culture, and all data from patients without BSI. We used multivariable logistic regression to identify the physiological characteristics of BSI. Results We analyzed 9,955 ICU admissions with 144 patient-years of vital sign and CRM data (1.3M hourly measurements). The average age was 59 years; the population was mostly Caucasian (81%) and male (56%). There were 5,671 (57%) admissions with ≥1 blood culture, and 744 (7%) had a BSI. The in-hospital mortality rate for patients with BSI was 28% vs. 12% for all others. The physiological signature of BSI was characterized by abnormalities in 12 parameters (Figure 1)—e.g., BSI was more likely in patients with a higher pulse and lower platelets. Several associations were nonlinear—e.g., temperature and WBC had U-shaped relationships with BSI. The internally validated C-statistic was 0.77. Conclusion Statistical modeling revealed a clinically sensible physiological signature of BSI that could assist with bedside decisions regarding the utility of blood culture testing in critically ill adults. Disclosures All authors: No reported disclosures.

Download Full-text

Serum Anion Gap Is Associated with All-Cause Mortality among Critically Ill Patients with Congestive Heart Failure

Disease Markers ◽

10.1155/2020/8833637 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Yiyang Tang ◽

Wenchao Lin ◽

Lihuang Zha ◽

Xiaofang Zeng ◽

Xiaoman Zeng ◽

...

Keyword(s):

Heart Failure ◽

Congestive Heart Failure ◽

Critically Ill ◽

Subgroup Analysis ◽

Critically Ill Patients ◽

Demographic Data ◽

Cox Proportional Hazards ◽

Anion Gap ◽

High Morbidity ◽

All Cause Mortality

Background. Congestive heart failure (CHF) is a complex clinical syndrome, with high morbidity and mortality. Serum anion gap (SAG) is associated with the severity of various cardiovascular diseases. However, the role of SAG indicators in CHF is unclear. Methods and Results. A retrospective analysis of data from Multiparameter Intelligent Monitoring in Intensive Care III version 1.4 was conducted in critically ill patients with CHF. The clinical information of each patient, including demographic data, comorbidities, vital signs, scores, and laboratory indicators, were successfully obtained. Cox proportional hazards models were used to determine the relationship between SAG and mortality in patients with CHF, the consistency of which was further verified by subgroup analysis. Results. A total of 7426 subjects met the inclusion criteria. Multivariate analysis showed that after adjusting for age, gender, ethnicity, and other potential confounders, increased SAG was significantly related to an increase in 30- and 90-day all-cause mortalities of critically ill patients with CHF compared with decreased SAG (tertile 3 versus tertile 1: adjusted hazard ratio, 95% confidence interval: 1.74, 1.46–2.08; 1.53, 1.32–1.77). Subgroup analysis indicated that the association between SAG and all-cause mortality presented similarities in most strata. Conclusion. SAG at admission could be a promising predictor of all-cause mortality in critically ill patients with CHF.

Download Full-text

Procalcitonin as a biomarker of bacterial infection in critically ill patients admitted with suspected Sepsis in Intensive Care Unit of a tertiary care hospital

Pakistan Journal of Medical Sciences ◽

10.12669/pjms.37.7.4183 ◽

2021 ◽

Vol 37 (7) ◽

Author(s):

Afshan Bibi ◽

Nida Basharat ◽

Muhammad Aamir ◽

Zujaja Hina Haroon

Keyword(s):

Intensive Care ◽

Blood Culture ◽

Bacterial Infection ◽

Critically Ill ◽

Positive Blood Culture ◽

Critically Ill Patients ◽

Tertiary Care ◽

P Value ◽

Care Hospital ◽

Significant Difference

Objective: To compare the diagnostic accuracy of procalcitonin (PCT), C- reactive protein (CRP), total leukocyte count (TLC) and lactate in critically ill patients admitted with suspicion of sepsis. Methods: It was a cross sectional study conducted at the department of Chemical Pathology and Endocrinology AFIP, Rawalpindi, in collaboration with Medical and surgical intensive care units (ICU) of CMH Rawalpindi from January 2019 to December 2019. A total of 126 patients of both genders with age above 18 years and fulfilling the inclusion criteria of systemic inflammatory response syndrome (SIRS) were inducted in the study. Results: Out of 126 patients 82 (65%) patients have positive blood culture results. Male predominance was noted in patients with positive blood culture. Out of 82 patients with positive blood culture results 69(84%) patients have positive PCT results as well whereas 13(15%) patients with positive blood culture results have negative PCT values. 57(69%) patients had Gram negative bacterial infection and 25(30%) patients had Gram positive bacterial infection. Significant difference was noted between the medians of PCT in blood culture positive and blood culture negative group (p value< 0.05) whereas no significant difference was found between medians of CRP, TLC and lactate between blood culture positive and blood culture negative patients (p value > 0.05). ROC curve analysis of PCT, CRP and TLC were done, keeping blood culture as reference standard, PCT showed largest area under the curve (AUC) and clearly outperformed TLC and CRP. PCT showed AUC of 0.781 as compared to CRP and TLC, which was 0.568 and 0.617 respectively. PCT showed sensitivity of 93.9%, specificity of 47.7%, positive predictive value (PPV) of 77% and negative predictive value (NPV) of 80.8%. Conclusion: Higher NPV makes it a reliable marker for screening out sepsis in suspected cases. doi: https://doi.org/10.12669/pjms.37.7.4183 How to cite this:Bibi A, Basharat N, Aamir M, Haroon ZH. Procalcitonin as a biomarker of bacterial infection in critically ill patients admitted with suspected Sepsis in Intensive Care Unit of a tertiary care hospital. Pak J Med Sci. 2021;37(7):---------. doi: https://doi.org/10.12669/pjms.37.7.4183 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download Full-text

303. Physiological Changes Due to Bloodstream Infection in Intensive Care Unit Patients Differ According to Transplant Status

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.346 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S149-S150

Author(s):

Alex Zimmet ◽

Douglas Lake ◽

Amanda M Zimmet ◽

Shrirang M Gadrey ◽

Taison Bell ◽

...

Keyword(s):

Logistic Regression ◽

Intensive Care ◽

Blood Culture ◽

Bloodstream Infection ◽

Critically Ill ◽

Positive Blood Culture ◽

Critically Ill Patients ◽

Regression Modeling ◽

Transplant Recipients ◽

Logistic Regression Modeling

Abstract Background Transplant recipients are at increased risk of bloodstream infection (BSI), which often leads to critical illness. Due to immunosuppression, BSI in these patients may manifest with different pathophysiology compared to non-transplant recipients. We aimed to identify different trends in the pathophysiology of critically ill patients with BSI based on transplant status. Methods We reviewed data from patients admitted to the medical and surgical/trauma intensive care units (ICUs) at the University of Virginia Medical Center from 2011 to 2015. We included both solid organ and hematopoietic stem cell transplant recipients. We performed univariate logistic regression modeling to evaluate trends in different physiological features in both transplant and non-transplant recipients in the 96 hours surrounding a positive blood culture. We then performed multivariate logistic regression modeling to identify features independently associated with a positive blood culture in the next 24 hours in transplant recipients. Results We analyzed 9,954 ICU patient-admissions (including 505 transplant recipients), with a total of 144 patient-years of physiological data, 1.3 million hourly measurements, and 15,577 blood culture instances. Of the 1,068 blood culture instances in transplant recipients, 125 (12%) were positive, compared to 1,051 of 14,509 (7%) blood culture instances in non-transplant recipients. Critically ill transplant recipients with BSI had greater abnormalities in vital signs, oxygen requirement, markers of organ damage, APACHE score, and Charlson Comorbidity Index (CCI) compared to non-transplant recipients (Figure 1). Trends in many of these features also differed based on transplant status. The multivariable logistic regression model of BSI in transplant recipients included, in decreasing strength of association: total bilirubin, systolic blood pressure, fraction of inspired oxygen, number of intravenous lines, and CCI. This model had an AUC of 0.75. Figure 1. Trends in pathophysiological abnormalities in 9,954 critically ill patients with BSI based on transplant status, 2011–2015. Each graph demonstrates the average value of the physiological variable over time relative to the acquisition of a positive blood culture. Blue curves depict trends in transplant recipients, while red curves depict trends in non-transplant recipients. We assessed 108 physiological features and show the 24 features with the greatest change around the time of blood culture. Conclusion Critically ill transplant recipients have a higher prevalence of BSI and different pathophysiological manifestations of BSI compared to non-transplant recipients. This may have implications regarding early detection and treatment of BSI in these patients. Disclosures Randall Moorman, MD, Advanced Medical Predictive Devices, Diagnostics, and Displays (Board Member, Shareholder)

Download Full-text

Effect of timing of intubation on clinical outcomes of critically ill patients with COVID-19: a systematic review and meta-analysis of non-randomized cohort studies

Critical Care ◽

10.1186/s13054-021-03540-6 ◽

2021 ◽

Vol 25 (1) ◽

Author(s):

Eleni Papoutsi ◽

Vassilis G. Giannakoulis ◽

Eleni Xourgia ◽

Christina Routsi ◽

Anastasia Kotanidou ◽

...

Keyword(s):

Systematic Review ◽

Mechanical Ventilation ◽

Clinical Outcomes ◽

Critically Ill ◽

Critically Ill Patients ◽

Meta Analysis ◽

Mortality And Morbidity ◽

Icu Admission ◽

All Cause Mortality ◽

Detectable Difference

Abstract Background Although several international guidelines recommend early over late intubation of patients with severe coronavirus disease 2019 (COVID-19), this issue is still controversial. We aimed to investigate the effect (if any) of timing of intubation on clinical outcomes of critically ill patients with COVID-19 by carrying out a systematic review and meta-analysis. Methods PubMed and Scopus were systematically searched, while references and preprint servers were explored, for relevant articles up to December 26, 2020, to identify studies which reported on mortality and/or morbidity of patients with COVID-19 undergoing early versus late intubation. “Early” was defined as intubation within 24 h from intensive care unit (ICU) admission, while “late” as intubation at any time after 24 h of ICU admission. All-cause mortality and duration of mechanical ventilation (MV) were the primary outcomes of the meta-analysis. Pooled risk ratio (RR), pooled mean difference (MD) and 95% confidence intervals (CI) were calculated using a random effects model. The meta-analysis was registered with PROSPERO (CRD42020222147). Results A total of 12 studies, involving 8944 critically ill patients with COVID-19, were included. There was no statistically detectable difference on all-cause mortality between patients undergoing early versus late intubation (3981 deaths; 45.4% versus 39.1%; RR 1.07, 95% CI 0.99–1.15, p = 0.08). This was also the case for duration of MV (1892 patients; MD − 0.58 days, 95% CI − 3.06 to 1.89 days, p = 0.65). In a sensitivity analysis using an alternate definition of early/late intubation, intubation without versus with a prior trial of high-flow nasal cannula or noninvasive mechanical ventilation was still not associated with a statistically detectable difference on all-cause mortality (1128 deaths; 48.9% versus 42.5%; RR 1.11, 95% CI 0.99–1.25, p = 0.08). Conclusions The synthesized evidence suggests that timing of intubation may have no effect on mortality and morbidity of critically ill patients with COVID-19. These results might justify a wait-and-see approach, which may lead to fewer intubations. Relevant guidelines may therefore need to be updated.

Download Full-text

Diagnostic accuracy of the BioFire FilmArray blood culture identification panel when used in critically ill patients with sepsis

Journal of Microbiological Methods ◽

10.1016/j.mimet.2021.106303 ◽

2021 ◽

Vol 189 ◽

pp. 106303

Author(s):

Roxanne Rule ◽

Fathima Paruk ◽

Piet Becker ◽

Matthew Neuhoff ◽

Julian Chausse ◽

...

Keyword(s):

Blood Culture ◽

Diagnostic Accuracy ◽

Critically Ill ◽

Critically Ill Patients ◽

Culture Identification

Download Full-text

A Comparison of Blood Pathogen Detection Among Droplet Digital PCR, Metagenomic Next-Generation Sequencing, and Blood Culture in Critically Ill Patients With Suspected Bloodstream Infections

Frontiers in Microbiology ◽

10.3389/fmicb.2021.641202 ◽

2021 ◽

Vol 12 ◽

Author(s):

Bangchuan Hu ◽

Yue Tao ◽

Ziqiang Shao ◽

Yang Zheng ◽

Run Zhang ◽

...

Keyword(s):

Next Generation Sequencing ◽

Blood Culture ◽

Critically Ill ◽

Critically Ill Patients ◽

Pathogen Detection ◽

Bloodstream Infections ◽

Digital Pcr ◽

Droplet Digital Pcr ◽

Next Generation ◽

Generation Sequencing

Metagenomic next-generation sequencing (mNGS) and droplet digital PCR (ddPCR) have recently demonstrated a great potential for pathogen detection. However, few studies have been undertaken to compare these two nucleic acid detection methods for identifying pathogens in patients with bloodstream infections (BSIs). This prospective study was thus conducted to compare these two methods for diagnostic applications in a clinical setting for critically ill patients with suspected BSIs. Upon suspicion of BSIs, whole blood samples were simultaneously drawn for ddPCR covering 20 common isolated pathogens and four antimicrobial resistance (AMR) genes, mNGS, and blood culture. Then, a head-to-head comparison was performed between ddPCR and mNGS. A total of 60 episodes of suspected BSIs were investigated in 45 critically ill patients, and ddPCR was positive in 50 (83.3%), mNGS in 41 (68.3%, not including viruses), and blood culture in 10 (16.7%) episodes. Of the 10 positive blood cultures, nine were concordantly identified by both mNGS and ddPCR methods. The head-to-head comparison showed that ddPCR was more rapid (~4 h vs. ~2 days) and sensitive (88 vs. 53 detectable pathogens) than mNGS within the detection range of ddPCR, while mNGS detected a broader range of pathogens (126 vs. 88 detectable pathogens, including viruses) than ddPCR. In addition, a total of 17 AMR genes, including 14 blaKPC and 3 mecA genes, were exclusively identified by ddPCR. Based on their respective limitations and strengths, the ddPCR method is more useful for rapid detection of common isolated pathogens as well as AMR genes in critically ill patients with suspected BSI, whereas mNGS testing is more appropriate for the diagnosis of BSI where classic microbiological or molecular diagnostic approaches fail to identify causative pathogens.

Download Full-text

301. Penicillin Versus Cefazolin or Anti-staphylococcal Penicillins for Penicillin-Susceptible Staphylococcus aureus Bacteremia

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.344 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S149-S149

Author(s):

Mohammed Aldhaeefi ◽

Jeffrey Pearson ◽

Sanjat Kanjilal ◽

Brandon Dionne

Keyword(s):

Staphylococcus Aureus ◽

Blood Culture ◽

Positive Blood Culture ◽

Medical Center ◽

Academic Medical Center ◽

Similar Distribution ◽

Clinical Failure ◽

Staphylococcus Aureus Bacteremia ◽

Definitive Therapy ◽

Significant Difference

Abstract Background Staphylococcus aureus bacteremia is a significant cause of mortality. Penicillin (PCN) may have a role in the treatment of penicillin-susceptible Staphylococcus aureus (PSSA) bacteremia as it has a narrower spectrum of activity than cefazolin and is better tolerated than antistaphylococcal penicillins (ASPs). The aim of this study is to evaluate the safety and effectiveness of PCN versus cefazolin or ASPs in the treatment of PSSA bacteremia. Methods This is a single-center, retrospective study at a tertiary academic medical center. All patients with a PSSA blood culture from January 1, 2012 to September 1, 2019 were screened. Patients were excluded if they were treated with a definitive antibiotic (defined as antimicrobial therapy received 72 hours after positive blood culture) other than the study comparators, or if they received combination antibiotic therapy >72 hours from the initial positive blood culture result. The primary outcome was 60-day clinical failure, which was a composite endpoint of change in antibiotic after 72 hours of definitive therapy, recurrence of PSSA bacteremia, infection-related readmission, or all-cause mortality. Results Of 277 patients with PSSA bacteremia, 101 patients were included in the study; 62 (61%) were male and 11 (11%) had a β-lactam allergy. At baseline, 40 patients (40%) had hardware, 25 (25%) had an intravenous line, 6 (6%) were on dialysis, and 4 (4%) had active IV drug use, with similar distribution across antibiotic groups. Penicillin was the most common antibiotic used (Table 1). There was a significant difference among groups with respect to the 60-day clinical failure (log-rank p=0.019). In terms of unadjusted 60-day clinical failure, penicillin had similar outcomes to cefazolin (95% CI -0.29 to 0.104, p=0.376), however, it had statistically significant better outcomes in comparison to the ASPs, nafcillin or oxacillin (95% CI 0.023 to 0.482, p=0.031) (Table 1). Table 1. 60-day outcomes of PSSA bacteremia Conclusion Penicillin is effective and safe in the treatment of PSSA bacteremia and may be preferable to antistaphylococcal penicillins Disclosures All Authors: No reported disclosures

Download Full-text