Urinary Biomarkers and Attainment of Cefepime Therapeutic Targets in Critically Ill Children

INTRODUCTION: The recommended therapeutic target for cefepime (FEP) is the time above MIC (fT>MIC). The frequency of target attainment and risk factor for sub-therapeutic concentrations in children have not been extensively studied. METHODS: We performed a prospective observational pilot study in children in our PICU receiving standard dosing of FEP for suspected sepsis (≥2 SIRS criteria). Three FEP concentrations were measured per subject and a urine sample was collected prior to PK sampling for measurement of urinary biomarkers. We used log linear regression to calculate the fT>MIC for each subject across a range of MIC values (1-16 µg/mL). We compared clinical factors/biomarkers between patients who did and did not achieve 100% fT>MIC for 8 µg/mL (cut-point for Pseudomonas) and tested the correlation between covariates and FEP troughs. RESULTS: 21 subjects were enrolled (median SIRS criteria: 3). PK sampling occurred after a median of 5 doses (range: 3-9). 43% of subjects achieved 100% fT>MIC for an MIC of 8 µg/mL. Younger age (p=.005), higher estimated GFR (p=.03), and lower urinary NGAL (p=.006) and KIM-1 (.03) were associated with failure to attain 100% fT>8 µg/mL. Age (r = 0.53), eGFR (r = -0.58), urinary NGAL (r = 0.42) and KIM-1 (r = 0.50) were significantly correlated with FEP troughs. CONCLUSIONS: A significant proportion of critically ill children failed to attain target concentrations for treatment of Pseudomonas aeruginosa with FEP. Younger patients and those with good kidney function (high GFR, low urinary biomarkers) may be at highest risk for subtherapeutic FEP concentrations.

A Retrospective Study of the Proportion of Women at High and Low Risk of Intrauterine Infection Meeting Sepsis Criteria

The Surviving Sepsis Campaign recently recommended that qSOFA not be used as a single parameter for identification of sepsis. Thus, we evaluated the efficacy of SIRS and qSOFA scores in identifying intrauterine infection. This case–control study evaluates SIRS and qSOFA criteria fulfillment in preterm premature rupture of membranes (n = 453)—at high infection risk—versus elective cesarean—at low infection risk (n = 2004); secondary outcomes included intrauterine infection and positive culture rates. At admission, 14.8% of the study group and 4.6% of control met SIRS criteria (p = 0.001), as did 12.5% and 5.5% on post-operation day (POD) 1 (p = 0.001), with no significant differences on POD 0 or 2. Medical records did not suffice for qSOFA calculation. In the study group, more cultures (29.8% versus 1.9%—cervix; 27.4% versus 1.1%—placenta; 7.5% versus 1.7%—blood; p = 0.001—all differences) and positive cultures (5.5% versus 3.0%—urine—p = 0.008; 4.2% versus 0.2%—cervix—p = 0.001; 7.3% versus 0.0%—placenta—p = 0.001; 0.9% versus 0.1%—blood—p = 0.008) were obtained. Overall, 10.6% of the study group and 0.4% of control met the intrauterine infection criteria (p = 0.001). Though a significant difference was noted in SIRS criteria fulfillment in the study group versus control, there was considerable between-group overlap, questioning the utility of SIRS in intrauterine infection diagnosis. Furthermore, the qSOFA scores could not be assessed.

Evolving Definition and Diagnostic Criteria of Sepsis

For many years, the Systemic Inflammatory Response Syndrome (SIRS) criteria were primarily considered for the diagnosis of sepsis, promoting the importance of inflammation. The definition and dia gnostic criteria of sepsis has undergone a sizeable metamorphosis from the inception of standardized definitions of sepsis in 1991. In 1991, the American College of Chest Physicians (ACCP) and the Society of Critical Care Medicine (SCCM) convened in Chicago and emphasized that sepsis is an ‘ongoing process’ of infection and considered SIRS score of two or more for diagnosis of sepsis. SOFA scoring system is an easily calculated system using parameters that are usually obtained during routine care of patients. This ensures that delays are avoided from requirement of any special investigations, making it reproducible in any number of healthcare settings.

Limited Utility of SIRS Criteria for Identifying Serious Infections in Febrile Young Infants

(1) Background: Young infants have a high risk of serious infection. The Systematic Inflammatory Response Syndrome (SIRS) criteria can be useful to identify both serious bacterial and viral infections. The aims of this study were to evaluate the diagnostic performance of the SIRS criteria for identifying serious infections in febrile young infants and to identify potential clinical predictors of such infections. (2) Methods: We conducted this prospective cohort study including febrile young infants (aged < 90 days) seen at the emergency department with a body temperature of 38.0 °C or higher. We calculated the diagnostic performance parameters and conducted the logistic regression analysis to identify the predictors of serious infection. (3) Results: Of 311 enrolled patients, 36.7% (n = 114) met the SIRS criteria and 28.6% (n = 89) had a serious infection. The sensitivity, specificity, positive predictive value, and positive likelihood ratio of the SIRS criteria for serious infection was 45.9%, 69.4%, 43.5%, 71.4%, 1.5, and 0.8, respectively. Logistic regression showed that male gender, body temperature ≥ 38.5 °C, heart rate ≥ 178 bpm, and age ≤ 50 days were significant predictors. (4) Conclusions: The performance of the SIRS criteria for predicting serious infections among febrile young infants was poor.

73. Identification of Novel Factors Associated with Inappropriate Treatment of Asymptomatic Bacteriuria Treatment in Acute and Long-term Care

Background Inappropriate treatment of asymptomatic bacteriuria (ASB) is a major driver of antibiotic overuse. Demographic and laboratory factors associated with inappropriate antibiotic treatment include older age, pyuria, leukocytosis and dementia. To gain a deeper understanding of inappropriate ASB treatment, we performed an in-depth review of provider documentation capturing a broader range of misleading factors associated with ASB treatment. Methods We reviewed a random sample of 10 positive urine cultures per month per facility from acute or long-term care wards at eight Veteran’s Administration (VA) facilities from 2017-2019 (n=960). Trained chart reviewers classified cultures as UTI or ASB and as treated or untreated. Charts were searched specifically for mention of 8 categories of potentially misleading symptoms that often lead to overtreatment of ASB (e.g. “prior history of UTI”) (Figure legend). We also created a ‘suspected systemic inflammatory response syndrome (SIRS)’ category that included any mention of leukocytosis, tachycardia, tachypnea, subjective or low-grade fever, or hypothermia. Generalized estimating equations logistic regression was used for analysis. Results Our study included 575 cultures from patients that were primarily white (71%) males (94%) from acute medicine units (75.7%) with a mean age of 76. Twenty-eight percent (n=159) of ASB cases received antibiotics. In addition to the usual known predictors, multiple new misleading symptoms were found to be associated with ASB treatment (Table). Novel, independent predictors of ASB treatment included behavioral issues, such as falls or fatigue (odds ratio (OR): 1.8; 95% CI: 1.05-3.07), urine characteristics, such as cloudy or odorous urine (OR: 1.41; 95% CI: 1.13-1.75), voiding issues (OR: 1.86; 95% CI: 1.43-2.41), and a single, free text mention of a SIRS criteria (OR: 1.63; 95% CI: 1.16-2.3). P-values extracted from multivariate regression model (ASB-asymptomatic bacteriuria; NS-not significant; SIRS- systemic inflammatory response syndrome). The following signs or symptoms compose each category: abnormal laboratory findings: acute kidney injury, abnormal creatinine, leukocytosis, pyuria/positive urinalysis, hyperglycemia; abnormal vital sign: bradycardia, tachycardia, atrial fibrillation, hypotension, hypertension, hypoxia, tachypnea, subjective fever or low-grade fever, syncope; behavior issues: falls, confusion lethargy, fatigue, weakness; nonspecific signs or symptoms: nonspecific gastrointestinal, genitourinary, neurological symptoms; voiding issues: decreased urine output, urinary retention, urinary incontinence; urine characteristics: change in color, foul smell, cloudy urine, sediment; SIRS: ordinal variable characterizing if 1 or ≥ 2 of the following were documented by the provider: leukocytosis, tachycardia, tachypnea, subjective or low-grade fever, hypothermia. Conclusion Our in-depth chart review, with attention to misleading symptoms and any documentation of the provider thought process, highlights new factors associated with inappropriate ASB treatment. Patients with even a single SIRS criteria are at risk for unnecessary treatment of ASB; this finding can help design antibiotic stewardship interventions. Disclosures Barbara Trautner, MD, PhD, Genentech (Consultant, Scientific Research Study Investigator)

Comparative study of the performance of SOFA and qSOFA versus SIRS criteria for predicting mortality among septic patients admitted to the intensive care unit

Background Sepsis is considered one of a life-threatening condition among intensive care unit (ICU) patients. Although, there are evidence-based management guidelines, sepsis still remains a leading cause of death with in-hospital mortality ranging from 22.8% to 48.7%. Previously sepsis was defined as systemic inflammatory response to infection, which could be diagnosed by meeting two or more Systemic Inflammatory Response Syndrome (SIRS) criteria, along with a known or suspected infection. Even though the SIRS criteria were sensitive, but they were not specific enough to differentiate between sepsis and other inflammatory conditions. Objective To compare between the ability of SOFA score, the quick SOFA (qSOFA) and Systemic Inflammatory Response Syndrome (SIRS) to predict ICU mortality. Patients and Methods Randomized prospective comparative study conducted in El Haram Specialized Hospital. The study included 75 patients. We calculated SOFA, SIRS, and qSOFA scores based on physiological and laboratory data that were collected upon admission to the ICU. Standard criteria were applied with a threshold of 2 or more points for each scoring system. The baseline SOFA score was assumed to be zero for patients without a known preexisting organ dysfunction. The baseline total SOFA score was considered to be 4 for patients undergoing chronic dialysis, and 2 or 3 for cirrhotic patients, depending on baseline bilirubin levels. Results ROC curve analysis between survival and each of SIRS, qSOFA and SOFA, it shows that SOFA score presented the best discrimination with an AUC of 0.993 (95% CI 0.981–100). Conclusion In patients with suspected infection admitted to an ICU, an increase in SOFA score had greater prognostic accuracy for in-hospital mortality than SIRS criteria or qSOFA. These findings suggest that SIRS and qSOFA may have limited use for predicting mortality in an ICU setting.

Sepsis knowledge, skills and attitudes among ward-based nurses

Background: Nurses are in a prime position to identify sepsis early by screening patients for sepsis, a skill that should be embedded into their daily practice. However, compliance with the sepsis bundle remains low. Aims: To explore the effects of sepsis training on knowledge, skills and attitude among ward-based nurses. Methods: Registered nurses from 16 acute surgical and medical wards were invited to anonymously complete a questionnaire. Findings: Response rate was 39% (98/250). Nurses with sepsis training had better knowledge of the National Early Warning Score 2 for sepsis screening, and the systemic inflammatory response syndrome (SIRS) criteria, demonstrated a more positive attitude towards sepsis screening and management, were more confident in screening patients for sepsis and more likely to have screened a patient for sepsis. Conclusions: Sepsis training improves nurses' attitudes, knowledge and confidence with regards to sepsis screening and management, resulting in adherence to evidence-based care, and should become mandatory for all clinical staff.

Clinical prediction of bacteremia and early antibiotics therapy in patients with solid tumors

Objective: To investigate the relationship between the systemic inflammatory response syndrome (SIRS), early antibiotic use, and bacteremia in solid-tumor patients. Design, setting, and participants: We conducted a retrospective observational study of adults with solid tumors admitted to a tertiary-care hospital through the emergency department over a 2-year period. Patients with neutropenic fever, organ transplant, trauma, or cardiopulmonary arrest were excluded. Methods: Rates of SIRS, bacteremia, and early antibiotics (initiation within 8 hours of presentation) were compared using the χ2 and Student t tests. Binomial regression and receiver operator curves were analyzed to assess predictors of bacteremia and early antibiotics. Results: Early antibiotics were administered in 507 (37%) of 1,344 SIRS-positive cases and 492 (22%) of 2,236 SIRS-negative cases (P < .0001). Of SIRS-positive cases, 70% had blood cultures drawn within 48 hours and 19% were positive; among SIRS negative cases, 35% had cultures and 13% were positive (19% vs 13%; P = .003). Bacteremic cases were more often SIRS positive than nonbacteremic cases (60% vs 50%; P =.003), but they received early antibiotics at similar rates (50% vs 49%, P = .72). Three SIRS components predicted early antibiotics: temperature (OR, 1.7; 95% CI, 1.31–2.29; P = .0001), tachycardia (OR, 1.4; 95% CI, 1.10–1.69; P < .0001), and white blood-cell count (OR, 1.8; 95% CI, 1.56–2.14; P < .0001). Only temperature (OR, 1.6; 95% CI, 1.09–2.41; P = .01) and tachycardia (OR, 1.5; 95% CI, 1.09–2.06; P = .01) predicted bacteremia. SIRS criteria as a composite were poorly predictive of bacteremia (AUC, 0.57). Conclusions: SIRS criteria are frequently used to determine the need for early antibiotics, but they are poor predictors of bacteremia in solid-tumor patients. More reliable models are needed to guide judicious use of antibiotics in this population.

Microbiological findings in emergency department patients with sepsis identified by the Sepsis-3 criteria: a single-center prospective population-based cohort study

Background Studies comparing the microbiological profiles among sepsis patients identified with either Sequential Organ Failure Assessment (SOFA) score or systemic inflammatory response syndrome (SIRS) criteria are limited. The aim was to examine if there are differences in the microbiological findings among septic patients identified by Sepsis-3 criteria compared to patients identified by the previous sepsis criteria, SIRS, and without organ failure. A secondary purpose was to examine if we could identify microbiological characteristics with increased risk of 28-day mortality. Methods Prospective cohort study of all adult (≥ 18 years) patients admitted with sepsis to the Emergency Department of Slagelse Hospital, Denmark from 1st October 2017 to 31st March 2018. Information regarding microbiological findings was obtained via linkage between a sepsis database and the local microbiological laboratory data system. Data regarding 28-day mortality were obtained from the Danish Civil Registration System. We used logistic regression to estimate the association between specific microbiological characteristics and 28-day mortality. Results A total of 1616 patients were included; 466 (28.8%; 95% CI 26.6%-31.1%) met SOFA criteria, 398 (24.6%; 95% CI 22.5–26.8%) met SIRS criteria. A total of 127 patients (14.7%; 95% CI 12.4–17.2%) had at least one positive blood culture. SOFA patients had more often positive blood cultures compared to SIRS (13.9% vs. 9.5%; 95 CI on difference 0.1–8.7%). Likewise, Gram-positive bacteria (8.6% vs. 2.8%; 95 CI on difference 2.8–8.8%), infections of respiratory origin (64.8% vs. 57.3%; 95 CI on difference 1.0–14%), Streptococcus pneumoniae (3.2% vs. 1.0%; 95% CI on difference 0.3–4.1) and polymicrobial infections (2.6% vs. 0.3% 95 CI on difference 0.8–3.8%) were more common among SOFA patients. Polymicrobial infections (OR 3.70; 95% CI 1.02–13.40), Staphylococcus aureus (OR 6.30; 95% CI 1.33–29.80) and a pool of “other” microorganisms (OR 3.88; 95% CI 1.34–9.79) in blood cultures were independently associated with mortality. Conclusion Patients identified with sepsis by SOFA score were more often blood culture-positive. Gram-positive pathogens, pulmonary tract infections, Streptococcus pneumoniae, and polymicrobial infections were also more common among SOFA patients. Polymicrobial infection, Staphylococcus aureus, and a group of other organisms were independently associated with an increased risk of death.