Infection Is Not Associated With Plasma or Cryoprecipitate Transfusion Volumes in Trauma: A Retrospective Study Using the National Trauma Data Bank.

Background: Packed red blood cell (PRBC) transfusion has been shown to increase nosocomial infection risk in the injured population; however, the post-traumatic infectious risk profiles of non-PRBC blood products are less clear. We hypothesized that plasma (fresh frozen plasma [FFP]), platelet (PLT), and cryoprecipitate administration would not be associated with increased rates of nosocomial infections. Patients and Methods: We performed a retrospective, matched, case-control study utilizing the American College of Surgeons National Trauma Data Bank data for 2019. We included all patients who received any volume of PRBC within four hours of presentation. Our outcome of interest was any infection. Controls were matched to cases using individual matching with a desired 1:3 case:control ratio. Bivariable analysis according to infection status, and multivariable logistic regression modeling the development of infection were then performed upon the matched data. Results: A total of 1,563 infectious cases were matched to 3,920 non-infectious controls. First four-hour transfusion volumes for FFP, PLT, and cryoprecipitate in the infection group exceeded those in the control group. The first four-hour FFP transfusion volume (per unit odds ratio [OR], 1.02; 95% confidence interval [CI], 0.99-1.04; p = 0.28) and cryoprecipitate transfusion volume (per unit OR, 1.01; 95% CI, 0.99-1.02; p = 0.43) were similar in cases and controls whereas PLT transfusion volume (per unit OR, 0.92; 95% CI, 0.86-0.98; p = 0.01) was lower in cases of infection than in controls. Conclusions: Fresh frozen plasma, PLT, and cryoprecipitate transfusion volumes were not independent risk factors for the development of nosocomial infection in a trauma population. PLT transfusion volume was associated with less infection.

Desirability of Outcome Ranking and Response Adjusted for Antibiotic Risk (DOOR/RADAR) Post Hoc Analysis Supports Equipoise for Antibiotic Initiation Strategies in Intensive Care Unit-Acquired Pneumonia.

Background: Pneumonia is the most common intensive care unit (ICU)-acquired infection and source of potential sepsis in ICU populations but can be difficult to diagnose in real-time. Despite limited data, rapid initiation of antibiotic agents is endorsed by society guidelines. We hypothesized that a post hoc analysis of a recent randomized pilot study would show no difference between two antibiotic initiation strategies. Patients and Methods: The recent Trial of Antibiotic Restraint in Presumed Pneumonia (TARPP) was a pragmatic cluster-randomized pilot of antibiotic initiation strategies for patients with suspected ICU-acquired pneumonia. Participating ICUs were cluster-randomized to either an immediate initiation protocol or a specimen-initiated protocol where a gram stain was required for initiation of antibiotics. Patients in the study were divided into one of seven mutually exclusive outcome rankings (desirability of outcome ranking; DOOR): (1) Survival, No Pneumonia, No adverse events; (2) Survival, Pneumonia, No adverse events; (3) Survival, No Pneumonia, ventilator-free-alive days ≤14; (4) Survival, Pneumonia, ventilator-free-alive days ≤14; (5) Survival, No Pneumonia, Subsequent episode of suspected pneumonia; (6) Survival, Pneumonia, Subsequent episode of suspected pneumonia; and (7) Death. These rankings were further refined using the duration of antibiotics prescribed for pneumonia (response adjusted for antibiotic risk; RADAR). Results: There were 186 patients enrolled in the study. After applying the DOOR analysis, a randomly selected patient was equally likely to have a better outcome in specimen-initiated arm as in the immediate initiation arm (DOOR probability: 50.8%; 95% confidence interval [CI], 42.7%-58.9%). Outcome probabilities were similar after applying the RADAR analysis (52.5%; 95% CI, 44.2%-60.6%; p = 0.31). Conclusions: We found that patients for whom antibiotic agents were withheld until there was objective evidence (specimen-initiated group) had similar outcome rankings to patients for whom antibiotic agents were started immediately. This supports the findings of the TARPP pilot trial and provides further evidence for equipoise between these two treatment strategies.

Provider Perceptions of Antibiotic Initiation Strategies for Hospital-Acquired Pneumonia.

Background: The practice of rapidly initiating antibiotic therapy for patients with suspected infection has recently been criticized yet remains commonplace. Provider comfort level has been an understudied aspect of this practice. Hypothesis: We hypothesized that there would be no significant differences in provider comfort level between the two treatment groups. Methods: We prospectively surveyed critical care intensivists who provided care for patients enrolled in the Trial of Antibiotic Restraint in Presumed Pneumonia (TARPP), which was a multicenter cluster-randomized crossover trial that evaluated an immediate antibiotic initiation protocol compared with a protocol of specimen-initiated antibiotic initiation in ventilated patients with suspected new-onset pneumonia. At the end of each enrollment arm, physicians at each center were surveyed regarding their overall comfort level with the recently completed treatment arm, and perception of adherence. Both a paired and unpaired analysis was performed. Results: We collected 51 survey responses from 31 unique participants. Providers perceived a higher rate of adherence to the immediate initiation arm than the specimen-initiated arm (Always Adherent: 37.5% vs. 11.1%; p = 0.045). Providers were less comfortable waiting for objective evidence of infection in the specimen-initiated arm than with starting antibiotic agents immediately (Very Comfortable: 83.3% vs. 40.7%; p = 0.004). For the smaller paired analysis, there was no longer a difference in comfort level. Conclusions: There may be differences in provider comfort levels and perceptions of adherence when considering two different antibiotic initiation strategies for suspected pneumonia in ventilated patients. These findings should be considered when planning future studies.

Assessing Second Debridement Timing and Mortality in Necrotizing Soft Tissue Infections.

BACKGROUND: Patients with necrotizing soft tissue infection undergo an average of 4-5 debridements per hospital admission. Optimal timing for initial debridement is emergent. Second debridement is universally recommended to occur within 24 hours of the first, but no studies have successfully evaluated this time frame. Prior work has suggested that delays in second debridement are associated with increased mortality, and that few patients receive second debridement within 24 hours. METHODS: We performed a retrospective cohort study at a single center from 01/01/08 to 09/01/2021. The explanatory variable was whether the subject received second debridement within 24 hours of initial debridement. The primary outcome was in-hospital mortality. Baseline characteristics were collected. Subjects were stratified into 2 groups by time between first and second debridement: <24 and ≥24 hours. Variables were compared using Fisher's exact and Wilcoxon rank-sum tests. RESULTS: 77 patients met inclusion criteria. The median overall time to second debridement was 40 hours. 12 subjects received second debridement within 24 hours (15.6%). There was no difference in in-hospital mortality between the <24 (n = 3, 25.0%) and ≥24-hour second debridement groups (n = 4, 6.2%; P = .07). The 2 groups did not differ by secondary outcomes, including total number of debridements, ICU LOS, or wound closure. CONCLUSION: No difference in mortality was observed between subjects undergoing second debridement within 24 vs after 24 hours. Only 16% of subjects received second debridement within the recommended 24-hour time interval. Further study is required to identify the optimal timing of second debridement.

Trial of antibiotic restraint in presumed pneumonia: A Surgical Infection Society multicenter pilot.

BACKGROUND: Pneumonia is the most common intensive care unit-acquired infection in the trauma and emergency general surgery population. Despite guidelines urging rapid antibiotic use, data supporting immediate antibiotic initiation in cases of suspected infection are limited. Our hypothesis was that a protocol of specimen-initiated antibiotic initiation would have similar compliance and outcomes to an immediate initiation protocol. METHODS: We devised a pragmatic cluster-randomized crossover pilot trial. Four surgical and trauma intensive care units were randomized to either an immediate initiation or specimen-initiated antibiotic protocol for intubated patients with suspected pneumonia and bronchoscopically obtained cultures who did not require vasopressors. In the immediate initiation arm, antibiotics were started immediately after the culture regardless of patient status. In the specimen-initiated arm, antibiotics were delayed until objective Gram stain or culture results suggested infection. Each site participated in both arms after a washout period and crossover. Outcomes were protocol compliance, all-cause 30-day mortality, and ventilator-free alive days at 30 days. Standard statistical techniques were applied. RESULTS: A total of 186 patients had 244 total cultures, of which only the first was analyzed. Ninety-three patients (50%) were enrolled in each arm, and 94.6% were trauma patients (84.4% blunt trauma). The median age was 50.5 years, and 21% of the cohort was female. There were no differences in demographics, comorbidities, sequential organ failure assessment, Acute Physiology and Chronic Health Evaluation II, or Injury Severity Scores. Antibiotics were started significantly later in the specimen-initiated arm (0 vs. 9.3 hours; p < 0.0001) with 19.4% avoiding antibiotics completely for that episode. There were no differences in the rate of protocol adherence, 30-day mortality, or ventilator-free alive days at 30 days. CONCLUSION: In this cluster-randomized crossover trial, we found similar compliance rates between immediate and specimen-initiated antibiotic strategies. Specimen-initiated antibiotic protocol in patients with a suspected hospital-acquired pneumonia did not result in worse clinical outcomes compared with immediate initiation. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level II.

Antibiotic Initiation Timing and Mortality in Trauma Patients With Ventilator-Associated Pneumonia.

BACKGROUND: Early antibiotic initiation is considered a cornerstone in the management of ventilator-associated pneumonia (VAP). However, recent data suggests that early antibiotic initiation may not be necessary in all cases. Additionally, the benefits of early antibiotic administration for infection have not been studied in a dedicated trauma population. This study's aim was to evaluate the impact of antibiotic administration timing on in-hospital mortality in trauma patients with VAP. METHODS: This retrospective case-control study identified all trauma patients at a single level 1 academic trauma center from 2016 to 2020. Patients with a TQIP-defined VAP were included and stratified into 2 subgroups by in-hospital mortality. Time interval between airway culture and antibiotic initiation was gathered. Baseline measures of injury and illness severity were collected. Univariate analysis of the data was performed. RESULTS: Forty-five patients met inclusion criteria. Overall, 80% of patients survived admission (n = 36) and 20% of patients did not survive admission (n = 9). There were no significant differences in baseline characteristics or cultured organism between survivors and non-survivors. The median time interval between airway culture and antibiotic initiation was 2 hours (IQR 0-4.5) for survivors, and 0 hours (IQR 0-0) for non-survivors (P = .07). Antibiotics were administered within 1 hour of airway culture for 33.3% of survivors, and 77.8% of non-survivors (P = .02). CONCLUSIONS: In a population of trauma patients with VAP, survivors had antibiotics initiated in more delayed fashion than non-survivors. These findings question the primacy of early antibiotic administration for suspected infection.

Prolonged Therapy Is Not Associated with Delayed Identification of Recurrent Intra-Abdominal Infection.

Background: The Study to Optimize Peritoneal Infection Therapy (STOP-IT) Trial identified an association between prolonged antibiotic therapy and delayed identification of recurrent intra-abdominal infection (IAI). However, this association has not been observed in other studies. The purpose of this study was to evaluate the association between recurrent IAIs and the duration of antibiotic agents. Patients and Methods: Adult patients from 2016 to 2020 who underwent a source control procedure for a colon-related complicated IAI were identified. Patients not meeting the inclusion criteria were excluded. Demographics, comorbidities, post-operative antibiotic duration, and presence of secondary intra-abdominal infection were recorded. The primary outcome was the time to identification of secondary IAI. Delayed identification of recurrent infection was identified as 10 or more days following source control procedure. Statistical analysis using χ2, Fisher exact, and Wilcoxon rank sum were used where appropriate. Results: Seventy-six of the patients identified met inclusion criteria, and 17 (22.4%) of those patients had a recurrent IAI. Patients with recurrent infections were slightly younger (64 vs. 60 years; p = 0.01) and had lower rates of pre-operative anticoagulation (50.8% vs. 17.6%). There were no differences in the initial length of antibiotic therapy after source control between the recurrent infection and non-recurrent groups (p = 0.6). There was a difference in total days of antibiotic use between the two groups, with the recurrent infection group averaging 10 more days of antibiotic use than the non-recurrence group (p < 0.0001). In those patients with a recurrence, there were no differences in median days to identification (9 vs. 11.5 days; p = 0.29) or the rate of those with delayed identification of recurrent infection (44.4% vs. 75%; p = 0.33). Conclusions: Similar to the STOP-IT Trial we failed to identify an association between the duration of post-operative antibiotic agents and recurrent infection. However, we further failed to identify an association between the prolonged post-operative courses and the timing of identification of the recurrent infection. Further evaluation is needed to determine if prolonged therapy delays the identification of recurrent infection.