Comparing the Prognostic Impacts of Delayed Administration of Appropriate Antimicrobials in Older Patients with Afebrile and Febrile Community-Onset Bacteremia.

Although prompt administration of an appropriate antimicrobial therapy (AAT) is crucial for reducing mortality in the general population with community-onset bacteremia, the prognostic effects of delayed AAT in older individuals with febrile and afebrile bacteremia remain unclear. A stepwise and backward logistic regression analysis was used to identify independent predictors of 30-day mortality. In a 7-year multicenter cohort study involving 3424 older patients (≥65 years) with community-onset bacteremia, febrile bacteremia accounted for 27.1% (912 patients). A crucial association of afebrile bacteremia and 30-day mortality (adjusted hazard ratio [AHR], 1.69; p < 0.001) was revealed using Cox regression and Kaplan-Meier curves after adjusting for the independent predictors of mortality. Moreover, each hour of delayed AAT was associated with an average increase of 0.3% (adjusted odds ratio [AOR], 1.003; p < 0.001) and 0.2% (AOR, 1.002; p < 0.001) in the 30-day crude mortality rates among patients with afebrile and febrile bacteremia, respectively, after adjusting for the independent predictors of mortality. Similarly, further analysis based on Cox regression and Kaplan-Meier curves revealed that inappropriate empirical therapy (i.e., delayed AAT administration > 24 h) had a significant prognostic impact, with AHRs of 1.83 (p < 0.001) and 1.76 (p < 0.001) in afebrile and febrile patients, respectively, after adjusting for the independent predictors of mortality. In conclusion, among older individuals with community-onset bacteremia, the dissimilarity of the prognostic impacts of delayed AAT between afebrile and febrile presentation was evident.

Prompt antimicrobial therapy and source control on survival and defervescence of adults with bacteraemia in the emergency department: the faster, the better.

BACKGROUND: Bacteraemia is a critical condition that generally leads to substantial morbidity and mortality. It is unclear whether delayed antimicrobial therapy (and/or source control) has a prognostic or defervescence effect on patients with source-control-required (ScR) or unrequired (ScU) bacteraemia. METHODS: The multicenter cohort included treatment-naïve adults with bacteraemia in the emergency department. Clinical information was retrospectively obtained and etiologic pathogens were prospectively restored to accurately determine the time-to-appropriate antibiotic (TtAa). The association between TtAa or time-to-source control (TtSc, for ScR bacteraemia) and 30-day crude mortality or delayed defervescence were respectively studied by adjusting independent determinants of mortality or delayed defervescence, recognised by a logistic regression model. RESULTS: Of the total 5477 patients, each hour of TtAa delay was associated with an average increase of 0.2% (adjusted odds ratio [AOR], 1.002; P < 0.001) and 0.3% (AOR 1.003; P < 0.001) in mortality rates for patients having ScU (3953 patients) and ScR (1524) bacteraemia, respectively. Notably, these AORs were augmented to 0.4% and 0.5% for critically ill individuals. For patients experiencing ScR bacteraemia, each hour of TtSc delay was significantly associated with an average increase of 0.31% and 0.33% in mortality rates for overall and critically ill individuals, respectively. For febrile patients, each additional hour of TtAa was significantly associated with an average 0.2% and 0.3% increase in the proportion of delayed defervescence for ScU (3085 patients) and ScR (1266) bacteraemia, respectively, and 0.5% and 0.9% for critically ill individuals. For 1266 febrile patients with ScR bacteraemia, each hour of TtSc delay respectively was significantly associated with an average increase of 0.3% and 0.4% in mortality rates for the overall population and those with critical illness. CONCLUSIONS: Regardless of the need for source control in cases of bacteraemia, there seems to be a significant association between the prompt administration of appropriate antimicrobials and both a favourable prognosis and rapid defervescence, particularly among critically ill patients. For ScR bacteraemia, delayed source control has been identified as a determinant of unfavourable prognosis and delayed defervescence. Moreover, this association with patient survival and the speed of defervescence appears to be augmented among critically ill patients.

Predictive models for short-term mortality and length of hospital stay among adults with community-onset bacteraemia before and during the COVID-19 pandemic: application of early data dynamics.

BACKGROUND: The development of scoring systems to predict the short-term mortality and the length of hospital stay (LOS) in patients with bacteraemia is essential to improve the quality of care and reduce the occupancy variance in the hospital bed. METHODS: Adults hospitalised with community-onset bacteraemia in the coronavirus disease 2019 (COVID-19) and pre-COVID-19 eras were captured as the validation and derivation cohorts in the multicentre study, respectively. Model I incorporated all variables available on day 0, Model II incorporated all variables available on day 3, and Models III, IV, and V incorporated the variables that changed from day 0 to day 3. This study adopted the statistical and machine learning (ML) methods to jointly determine the prediction performance of these models in two study cohorts. RESULTS: A total of 3,639 (81.4%) and 834 (18.6%) patients were included in the derivation and validation cohorts, respectively. Model IV achieved the best performance in predicting 30-day mortality in both cohorts. The most frequently identified variables incorporated into Model IV were deteriorated consciousness from day 0 to day 3 and deteriorated respiration from day 0 to day 3. Model V achieved the best performance in predicting LOS in both cohorts. The most frequently identified variables in Model V were deteriorated consciousness from day 0 to day 3, a body temperature ≤ 36.0 °C or ≥ 39.0 °C on day 3, and a diagnosis of complicated bacteraemia. CONCLUSIONS: For hospitalised adults with community-onset bacteraemia, clinical variables that dynamically changed from day 0 to day 3 were crucial in predicting the short-term mortality and LOS.

Prognostic Effects of Delayed Administration of Appropriate Antimicrobials in Bacteraemic Adults Initially Presenting with Various Body Temperatures.

Purpose: To investigate the different impact of delayed administration of appropriate antimicrobial therapy (AAT) on short-term mortality of bacteraemia patients initially presenting with various body temperatures (BTs). Materials and Methods: A six-year, two-center cohort consisting of adults with community-onset bacteraemia in emergency departments (EDs) was retrospectively collected. Through the multivariable analyses, clinical impacts of delayed AAT, assessed by the time gap between the first dose of AAT and ED arrival, on 30-day mortality (primary outcomes) were respectively examined in the different groups of initial BTs (iBTs). Results: Of the 3171 adults, despite the similarities of delayed AAT in six iBT categories, hourly AAT delay was associated with an average increase in 30-day mortality rates of 0.24% in the group of iBT <36.0℃, 0.40% in the 36.0℃-36.9℃ group, 0.48% in the 37.0℃-37.9℃ group, 0.59% in the 38.0℃-38.9℃ group, 0.58% in the 39.0℃-39.9℃ group, and 0.71% in the ≥40.0℃ group, after respective adjusting independent predictors of mortality. Furthermore, for 589 patients who inappropriately received empirical antimicrobial treatment (ie, delayed AAT ≥ 24 hours), with a cutoff of 34.0℃, each 1℃ increase in iBTs was independently associated with an average increase in 30-day mortality rates of 42%. Conclusion: For adults with community-onset bacteraemia, the iBT-related differences in the prognostic impacts of delayed administration of appropriate antimicrobials might be evident.

Prognostic Effects of Inappropriate Empirical Antimicrobial Therapy in Adults With Community-Onset Bacteremia: Age Matters.

Background: Studies have reported the effects of delayed administration of appropriate antimicrobial therapy (AAT) on the short-term prognosis of patients with bloodstream infections; however, whether there is an age-related difference in these effects remains debated. Methods: In this 4-year multicenter case-control study, patients with community-onset bacteremia were retrospectively categorized into the "middle-aged" (45-64 years), "old" (65-74 years), and "very old" (≥75 years) groups. Two methods were adopted to investigate the prognostic effects of delayed AAT in each age group. First, its effects were, respectively, investigated, after adjustment for the independent predictors of 30-day mortality. Second, patients in each age group were matched by the closest propensity-score (PS), which was calculated by independent predictors of mortality; the survival curves and Pearson chi-square tests were adopted to disclose its effects in each PS-matching group. Results: Each hour of delayed AAT resulted in an average increase in the 30-day crude mortality rate of 0.2% (P = 0.03), 0.4% (P < 0.001), and 0.7% (P < 0.001) in middle-aged (968 patients), old (683), and very old (1,265) patients, after, respectively, adjusting the independent predictors of mortality in each group. After appropriate PS-matching, no significant proportion differences in patient demographics, bacteremia characteristics, severity of bacteremia and comorbidities, and 15-day or 30-day crude mortality rates were observed between three matched groups (582 patients in each group). However, significant differences in survival curves between patients with delayed AAT > 24 or >48 h and those without delayed administration were demonstrated in each age group. Furthermore, the odds ratios of 30-day mortality for delayed AAT > 24 or >48 h were 1.73 (P = 0.04) or 1.82 (P = 0.04), 1.84 (P = 0.03) or 1.95 (P = 0.02), and 1.87 (P = 0.02) or 2.34 (P = 0.003) in the middle-aged, old, and very old groups, respectively. Notably, the greatest prognostic impact of delayed AAT > 24 or >48 h in the very old group and the smallest impact in the middle-aged group were exhibited. Conclusion: For adults (aged ≥45 years) with community-onset bacteremia, the delayed AAT significantly impacts their short-term survival in varied age groups and the age-related differences in its prognostic impact might be evident.

Prognostic Effects of Delayed Administration of Antimicrobial Therapy in Older Persons Experiencing Bacteremia With or Without Initial Sepsis Presentations.

OBJECTIVES: To investigate the prognostic effects of delayed administration of appropriate antimicrobial therapy (AAT) in older persons experiencing bacteremia with and without initial sepsis syndrome, respectively. DESIGN: A 4-year multicenter cohort study. SETTING AND PARTICIPANTS: Older people (≥65 years of age) with community-onset bacteremia in the emergency department (ED) of 3 participating hospitals. METHODS: Clinical data were retrospectively collected and causative microorganisms were prospectively collected for susceptibilities to determine the period of delayed AAT for each bacteremia episode. Sepsis was defined based on the Sepsis-3 criteria. A multivariable regression model was used to investigate the prognostic effects of delayed AAT, after adjusting independent determinants of 30-day mortality. RESULTS: Of the total 2357 patients, their median (interquartile range) age was 78 (72-84) years and septic patients accounted for 48.4% (1140 patients) of the overall patients. Compared with nonseptic patients, septic individuals exhibited the shorter period of delayed AAT (median, 2.0 vs 2.5 hours; P < .001), longer hospitalization (median, 11 vs 9 days; P < .001), and higher crude mortality rates at 15 (28.9% vs 2.1%; P < .001) and 30 days (34.6% vs 4.0%; P < .001). In multivariable regression analyses, each hour of delayed AAT resulted in average increases in the 30-day crude mortality rates of 0.38% [adjusted odds ratio (AOR) 1.0038; P < .001), 0.42% (AOR 1.0042; P < .001), and 0.31% (AOR 1.0031; P = .04) among overall, septic, and nonseptic patients, respectively. CONCLUSIONS AND IMPLICATIONS: For older persons with community-onset bacteremia, irrespective of whether or not patients experiencing initial sepsis presentations, the prognostic impacts of delayed AAT have been evidenced. Notably, because of the longer period of delayed AAT in patients without fulfilling the Sepsis-3, adopting a stricter sepsis definition and/or early bacteremia predictor to avoid delayed AAT and unfavorable prognoses in patients with bacteremia is necessary.

Is qSOFA Suitable for Early Diagnosis of Sepsis Among Bacteremia Patients in Emergency Departments? Time for a Reappraisal of Sepsis-3 Criteria.

Background: For early recognition of patients with sepsis, quick Sequential Organ Failure Assessment (qSOFA) was proposed by Sepsis-3 criteria as initial sepsis identification outside of intensive care units. However, the new definition has subsequently led to controversy and prompted much discussion for delayed treatment efforts. We aimed to validate Sepsis-3 criteria on bacteremia patients by investigating prognostic impacts of inappropriate administration of empirical antimicrobial therapy (EAT) and delayed source control (SC) compared to Sepsis-2 criteria. Methods: In the multicenter cohort of adults with community-onset bacteremia in emergency departments (EDs), adverse effects of delayed treatment efforts on 30-day mortality were examined in septic and non-septic patients by fulfilling the Sepsis-2 or Sepsis-3 criteria using the Cox regression model after adjusting independent determinants of mortality. Results: Of the 3,898 total adults, septic patients accounted for 92.8% (3,619 patients) by Sepsis-2 criteria (i.e., SIRS criteria). Using Sepsis-3 criteria, 1,827 (46.9%) patients were diagnosed with early sepsis (i.e., initial qSOFA scores ≥ 2) in EDs and 2,622 (67.3%) with sepsis during hospitalization (i.e., increased SOFA scores of ≥ 2 from ED arrival). The prognostic impacts of inappropriate EAT or delayed SC (for complicated bacteremia) were both significant in septic patients with fulfilling the Sepsis-2 or Sepsis-3 (i.e., SOFA) criteria, respectively. Meanwhile, these delayed treatment efforts trivially impact prognoses of non-septic patients recognized by the Sepsis-2 or Sepsis-3 (i.e., SOFA) definitions. Notably, prognostic effects of inappropriate EAT or delayed SC were disclosed for septic patients in EDs, specifically those with qSOFA scores of ≥ 2, and prognostic impacts of delayed treatment efforts remained significant for patients initially recognized early as being non-septic (i.e., initial qSOFA scores of <2). Conclusions: For patients with community-onset bacteremia, inappropriate EAT and delayed SC might result in unfavorable outcomes of patients early identified as being non-septic on ED arrival based on the qSOFA scores (by Sepsis-3 criteria). Accordingly, a more prudent diagnosis of sepsis adopted among bacteremia patients in the ED is necessary.

Blood Cultures and Appropriate Antimicrobial Administration after Achieving Sustained Return of Spontaneous Circulation in Adults with Nontraumatic Out-of-Hospital Cardiac Arrest.

We aimed to determine the incidence of bacteremia and prognostic effects of prompt administration of appropriate antimicrobial therapy (AAT) on nontraumatic out-of-hospital cardiac arrest (OHCA) patients achieving a sustained return of spontaneous circulation (sROSC), compared with non-OHCA patients. In the multicenter case-control study, nontraumatic OHCA adults with bacteremia episodes after achieving sROSC were defined as case patients, and non-OHCA patients with community-onset bacteremia in the emergency department were regarded as control patients. Initially, case patients had a higher bacteremia incidence than non-OHCA visits (231/2171, 10.6% vs. 10,430/314,620, 3.3%; p < 0.001). Compared with the matched control (2288) patients, case (231) patients experienced more bacteremic episodes due to low respiratory tract infections, fewer urosepsis events, fewer Escherichia coli bacteremia, and more streptococcal and anaerobes bacteremia. Antimicrobial-resistant organisms, such as methicillin-resistant Staphylococcus aureus and extended-spectrum beta-lactamase-producing Enterobacteriaceae, were frequently evident in case patients. Notably, each hour delay in AAT administration was associated with an average increase of 10.6% in crude 30-day mortality rates in case patients, 0.7% in critically ill control patients, and 0.3% in less critically ill control patients. Conclusively, the incidence and characteristics of bacteremia differed between the nontraumatic OHCA and non-OHCA patients. The incorporation of blood culture samplings and rapid AAT administration as first-aids is essential for nontraumatic OHCA patients after achieving sROSC.

Antimicrobial escalation is not beneficial for Gram-negative bacteremia in adults who remained critically ill after appropriate empirical therapy.

To study whether antimicrobial escalation is beneficial for the outcome of bacteremia patients receiving appropriate but less responsive antimicrobials as empirical therapy, adults with community-onset Gram-negative bacteremia and remained the critical illness after appropriate empirical therapy with third-generation cephalosporins were retrospective enrolled. Clinical outcomes included incidental nosocomial infections, breakthrough bacteremia, and in-hospital crude mortality were compared between patients receiving escalation and non-escalation therapy, after propensity-score (PS) matching at a ratio of 1:3 using independent predictors of 30-day mortality recognized by the multivariate regression model. Initially, the higher proportion of fatal comorbidities (McCabe classification) and 30-day mortality rates was exhibited in the escalation group (51 patients), compared to the non-escalation group (de-escalation, 81; non-switch, 95). After appropriate PS-matching, similar proportions of clinical variables between the escalation (45 patients) and no-escalation (135) groups, in terms of patient demographics, bacteremia severity at onset, severity and types of comorbidities, and bacteremia sources, were observed. Consequently, poorer clinical outcomes, such as the higher rate of incidental nosocomial infections and in-hospital crude mortality as well as the longer length of intravenous antimicrobial administration and hospitalization, were statistically evidenced in the escalation group, compared to the non-escalation group. Conclusively, for patients exhibiting poor responses to appropriate empirical therapy, antimicrobial escalation did not significantly result in improved outcomes; otherwise, clinicians should pay more attention to the strategy of supportive care or adequate control of septic complication.