Longer than 2 hours to antibiotics is associated with doubling of mortality in a multinational community-acquired bacterial meningitis cohort

To optimally define the association between time to effective antibiotic therapy and clinical outcomes in adult community-acquired bacterial meningitis. A systematic review of the literature describing the association between time to antibiotics and death or neurological impairment due to adult community-acquired bacterial meningitis was performed. A retrospective cohort, multivariable and propensity-score based analyses were performed using individual patient clinical data from Australian, Danish and United Kingdom studies. Heterogeneity of published observational study designs precluded meta-analysis of aggregate data (I2 = 90.1%, 95% CI 71.9–98.3%). Individual patient data on 659 subjects were made available for analysis. Multivariable analysis was performed on 180–362 propensity-score matched data. The risk of death (adjusted odds ratio, aOR) associated with treatment after two hours was 2.29 (95% CI 1.28–4.09) and increased substantially thereafter. Similarly, time to antibiotics of greater than three hours was associated with an increase in the occurrence of neurological impairment (aOR 1.79, 95% CI 1.03–3.14). Among patients with community-acquired bacterial meningitis, odds of mortality increase markedly when antibiotics are given later than two hours after presentation to the hospital.

Time-to-antibiotics and clinical outcomes in patients with sepsis and septic shock: a prospective nationwide multicenter cohort study

Background Timely administration of antibiotics is one of the most important interventions in reducing mortality in sepsis. However, administering antibiotics within a strict time threshold in all patients suspected with sepsis will require huge amount of effort and resources and may increase the risk of unintentional exposure to broad-spectrum antibiotics in patients without infection with its consequences. Thus, controversy still exists on whether clinicians should target different time-to-antibiotics thresholds for patients with sepsis versus septic shock. Methods This study analyzed prospectively collected data from an ongoing multicenter cohort of patients with sepsis identified in the emergency department. Adjusted odds ratios (ORs) were compared for in-hospital mortality of patients who had received antibiotics within 1 h to that of those who did not. Spline regression models were used to assess the association of time-to-antibiotics as continuous variables and increasing risk of in-hospital mortality. The differences in the association between time-to-antibiotics and in-hospital mortality were assessed according to the presence of septic shock. Results Overall, 3035 patients were included in the analysis. Among them, 601 (19.8%) presented with septic shock, and 774 (25.5%) died. The adjusted OR for in-hospital mortality of patients whose time-to-antibiotics was within 1 h was 0.78 (95% confidence interval [CI] 0.61–0.99; p = 0.046). The adjusted OR for in-hospital mortality was 0.66 (95% CI 0.44–0.99; p = 0.049) and statistically significant in patients with septic shock, whereas it was 0.85 (95% CI 0.64–1.15; p = 0.300) in patients with sepsis but without shock. Among patients who received antibiotics within 3 h, those with septic shock showed 35% (p = 0.042) increased risk of mortality for every 1-h delay in antibiotics, but no such trend was observed in patients without shock. Conclusion Timely administration of antibiotics improved outcomes in patients with septic shock; however, the association between early antibiotic administration and outcome was not as clear in patients with sepsis without shock.

Time-To-Antibiotics and Clinical Outcomes in Patients With Sepsis and Septic Shock: A Prospective Nationwide Multicenter Cohort Study

Background It is unclear whether the administration of antibiotics within 1 hour could improve patient outcomes in sepsis, and whether the association of time to antibiotics administration and clinical outcomes are different for sepsis and septic shock. Methods This study analyzed prospectively collected data from an ongoing multicenter cohort of patients with sepsis identified in the emergency department. Adjusted odds ratios (ORs) were compared for in-hospital mortality of patients who had received antibiotics within 1 h to that of those who did not. Spline regression models were used to assess the association of time-to-antibiotics as continuous variables and increasing risk of in-hospital mortality. The differences in the association between time-to-antibiotics and in-hospital mortality were assessed according to the presence of septic shock. Results Overall, 3,035 patients were included in the analysis. Among them, 601 (19.8%) presented with septic shock, and 774 (25.5%) died. The adjusted OR for in-hospital mortality of patients whose time-to-antibiotics was within 1 h was 0.78 (95% confidence interval [CI], 0.61–0.99; p=0.046). The adjusted OR for in-hospital mortality was 0.66 (95% CI, 0.44–0.99; p=0.049) and statistically significant in patients with septic shock, whereas it was 0.85 (95% CI, 0.64–1.15; p=0.300) in patients with sepsis but without shock. Among patients who received antibiotics within 3 h, those with septic shock showed 35% (p=0.042) increased risk of mortality for every 1-h delay in antibiotics, but no such trend was observed in patients without shock. Conclusion Timely administration of antibiotics improved outcomes in patients with septic shock; however, the association between early antibiotic administration and outcome was not as clear in patients with sepsis without shock.

1156 NELA – Time to Antibiotics

Introduction Early administration of antibiotics is vital in patients that have intra-abdominal sepsis. The National Emergency Laparotomy Audit (NELA) 2019 found only 19% of patients with suspected sepsis received antibiotics in the first hour. The aim of this project was to audit the current time to antibiotics in patients who underwent an emergency laparotomy in our District General Hospital (DGH) in Wales. Method This was a retrospective audit of all patients that underwent an emergency laparotomy between January to July 2019. Data was collected from the NELA database and Clinical Notes. Results 33 patients underwent an emergency laparotomy, 2 patients were excluded leaving a total of 31 patients. 55% of patients received antibiotics prior to theatre. 61% of patients triggered the systemic inflammatory response syndrome (SIRS) criteria on admission but only 47% of these patients received antibiotics. Of those that received antibiotics only 16% had them prescribed within 1 hour of arriving to the hospital. 41% of patients waited over an hour from the antibiotics being prescribed to receiving them and 1 patient did not receive the antibiotics at all. Conclusions This project shows there are many areas for improvement. Although antibiotics maybe prescribed, clear communication with nursing staff is important, so that they can be given in a timely manner. It is also important simple measures, like working cannulas, do not prevent administration of antibiotics. Re-audit of these results is vital after education. Some patients may not require antibiotics – but missing those that do could cost lives!

Time to Antibiotics in Pediatric Patients with Fever in Neutropenia during Chemotherapy for Cancer -- Data from the Prospective Multicenter SPOG 2015 FN Definition Study

Background. Fever in neutropenia (FN) remains an unavoidable, potentially lethal complication of chemotherapy. Timely administration of empirical broad-spectrum intravenous antibiotics has become standard of care. But the impact of time to antibiotics (TTA), the lag period between recognition of fever or arrival at the hospital to start of antibiotics, remains unclear. Here we aimed to analyze the association between TTA and safety relevant events (SRE) in data from a prospective multicenter study. Procedure. We analyzed the association between time from recognition of fever to start of antibiotics (F-TTA) and SRE (death, admission to intensive care unit (ICU), severe sepsis and bacteremia) with three-level mixed logistic regression. We adjusted for possible triage bias using a propensity score and stratified the analysis by severity of disease at presentation. Results. We analyzed 266 FN episodes, including 53 (20%) with SRE, reported in 140 of 269 patients recruited from April 2016 to August 2018. F-TTA (median, 120min; interquartile range, 49 to 180min) was not associated with SRE, with a trend for less SREs in episodes with longer F-TTA. Analyses applying the propensity score suggested a relevant triage bias. Only in patients with severe disease at presentation there was a trend for an association of longer TTA with more SRE. Conclusion. We found little evidence that longer TTA leads to a higher risk of poor clinical outcome in pediatric patients with FN, except for those with severe disease at presentation. We saw strong evidence for triage bias which could only be partially adjusted.

Delays in time to antibiotics in inpatient oncologic neutropenic fever do not predict decreased overall survival.

e18765 Background: Neutropenic fever (NF) is relatively common oncologic emergency. Present expert consensus is that anti-pseudomonas gram-negative antibiotics should be administered within 60 minutes of detecting NF. To date studies investigating this relationship in neutropenic fever patients have been either limited in size, or have failed to reliably establish a relationship between time to antibiotics (TTA) and clinical outcomes.While some studies have shown an association between TTA and outcomes in NF patients admitted from the Emergency Department, such studies do not control for the time that patients may have been febrile in the community. To address these factors, we conducted a retrospective study on the effect of TTA on mortality in oncologic patients who developed NF as inpatients. Methods: We performed retrospective chart review of all cases of NF at an NCI designated Cancer Center between 7/1/2016 and 3/27/2019. NF was defined as temperature of 101˚ F on one occasion, or 100.4˚ F sustained over 60 minutes, with an absolute neutrophil count (ANC) less than 500. TTA and survival were calculated via chart abstraction; patients lost to follow up within 180 days were censored to the 180-day mortality group. Relationship between TTA and overall survival (OS) was analyzed via multivariable Cox regression. We excluded patients that had non-cancer related NF, were transferred from another institution with NF, were admitted from the ED with NF, or transitioned to hospice. Only the first instance of NF in any admission was analyzed. Results: A total of 187 eligible cases were identified during the study period, mean age was 57.6 +/- 13.6, 100 (53.5%) cases were in males, 114 (61.0%) cases in Caucasians, 53 (28.3%) in Black People. The 3 most common disease subtypes were acute leukemia (42.8%), plasma cell dyscrasias (27.8%), and lymphoma (16.6%). TTA showed no significant correlation with OS at any timeframe studied. Low Charlson Comorbidity Index ( < 3) correlated with increased survival through ̃360 days, however the effect was non-significant at longer timeframes. Immediate antibiotic treatment ( < 40 mins) correlated with poorer patient prognosis and significantly decreased OS (HR 3.08;CI: 1.30-7.28; p 0.010). Conclusions: TTA was not associated with OS in our study. For inpatients with NF, even hours long TTA may not be long enough to result in adverse clinical outcomes. Unlike NF patients presenting to the ED, where true TTA may often be many hours or even days prior to arrival, a few hours-long TTA in the hospital may not be sufficiently long enough to cause significant patient harm. Interestingly, in our cohort, those who received antibiotics quickly had adverse outcomes. It may be that in patients who were clinically unstable, TTA was shorter given the urgency of the situation. Ultimately, this study’s findings question the applicability of the 60-minute guideline when used in the inpatient setting.