Short vs. Standard Course Outpatient Antibiotic Therapy for CAP in Children

• Clinical Question: Is a 5-day strategy of antibiotics superior to a 10-day strategy for the treatment of non-severe pneumonia in young children demonstrating early clinical response?
• Research Design: Randomized double-blind placebo-controlled superiority trial
  • Superiority trial = aims to show one treatment is clinically better than another
  • Non-inferiority trial = aims to show one treatment is not worse than active control tx
  • Intention to treat analysis = all participants who are randomized are included in the statistical analysis and analyzed according to the group they were originally assigned, regardless of what treatment (if any) they received
• Population: Eight US sites either outpatient clinic, urgent care, or ED
  • Inclusion: Children 6-71 months, diagnosed with uncomplicated CAP, prescribed with amoxicillin, amoxicillin-clavulanate, or cefdinir (IDSA recs), parental report of improvement (no fever, no tachypnea, no severe cough) by days 3-6
  • Exclusion: treatment with antibiotic before diagnosis of CAP, treatment outside of above antibiotic regimen, presence of severe CAP (significant pleural effusion, abscess, empyema, etc.), prior hospitalization during days 1-5 for CAP, history of pneumonia within past 6 months, history of asthma, history of underlying chronic medical condition
• Intervention: Short course antibiotic therapy -> 5 days antibiotics then 5 days of matching placebo  
• Control: Standard course antibiotic therapy -> 10 total days of prescribed antibiotic
• Primary Outcome: Response Adjusted for Duration of Antibiotic Risk (RADAR) measured at first outcome visit (OAV1) on days 6-10
  • RADAR determined by desirability of outcome ranking (DOOR) and ranked participants’ overall experiences
    • DOOR components: adequate clinical response, resolution of symptoms, presence and severity of antibiotic associated adverse effects
  • DOOR/RADAR helps assess the risks and benefits of new strategies to optimize antibiotic use
• Secondary Outcome: RADAR at OAV2 on days 19-25, antibiotic associated adverse effects, quantification of antibiotic resistance genes (sub-study)
• Results: 390 patients assessed, 385 patients enrolled (192 in short course and 193 in standard)
  • . Estimated probability of a more desirable RADAR for the short-course strategy of 0.69 (95% CI, 0.63-0.75)
  • RADAR at OAV2 clinically significant. The probability of a more desirable RADAR in the short-course strategy was 0.63 (95% CI, 0.57-0.69)
  • Antibiotic resistance genes were significantly lower in 5-day course than 10 days
• Conclusion: Shorter courses of antibiotics are superior in treating healthy, clinically improving children diagnosed with uncomplicated CAP
• Strengths: Clinically relevant patient-centered question, multicenter RCT so increases generalizability, placebo and antibiotics were matched for taste and appearance
• Limitations: Studied population is likely a convenience sample with selection bias (only 390 patients in 8 cities over 3 years), strict exclusion criteria, no standard definition or diagnostic criteria for CAP in this trial (viral pneumonia?), no information on diagnostic or radiographic testing (imbalanced testing frequency or imbalanced test results)

ED vs. OR Intubation of Patients Undergoing Hemorrhage Control Surgery

• Clinical Question: Does ED intubation increase the risk of death and major complication for patients undergoing urgent hemorrhage control surgery?
• Research Design: Retrospective cohort study
  • Cohort Study = outcome or disease-free study population is first identified by the exposure or event of interest and followed in time until the disease or outcome of interest occurs
• Population: National Trauma Data Bank
  • Inclusion: 16 years or older, underwent hemorrhage control surgery (received 1u blood in first 4 hours of arrival) at level 1 or 2 trauma centers, to the OR within 60 minutes of hospital arrival
  • Exclusion: suffered pre-hospital cardiac arrest, dead on arrival, non-survivable injuries, underwent ED thoracotomy, suffered severe head/face/neck injuries, presented with GCS <8, centers that performed <10 hemorrhage control surgeries
• Exposure: Endotracheal intubation performed in the ED
• Primary Outcome: in hospital mortality
• Secondary Outcome: total ED dwell time, units of blood transfused in the first 4 hours, major complications (in hospital cardiac arrest, AKI, ARDS, VAPs, severe sepsis)
• Results: 9,667 patients who underwent urgent hemorrhage control surgery at 253 levels 1 or 2 trauma centers in US/Canada
  • Most common procedure was laparotomy (68%), extremity (15%), and thoracotomy (6%)
  • ED intubation was performed in 1,972 patients (20%) and 877 (9%) died
  • • Also associated with longer ED dwell time, greater blood transfusion in first 4 hours, and higher risk of major complications (specifically inpatient cardiac arrest)
  • ED intubations significantly more likely to occur in blunt trauma with higher ISS because of severe injuries to the chest and extremities
  • Low ED intubation hospitals were significant more likely to be level 1, university affiliated trauma centers that perform higher levels of hemorrhage control surgery
• Conclusion: In patients who underwent urgent hemorrhage control at levels 1 and 2 trauma centers, ED intubation was associated with increased odds of mortality and major complications, specifically inpatient cardiac arrest
• Strengths: clinically relevant question, large patient population from multiple centers, reduced confounders by excluding patients with clear clinical indications for intubation such as those that were performed were more likely to be guided by physician discretion
• Weaknesses: reliability of some variables used in the study cannot be confirmed from the database, event-level information not available (may be other clinical indicators associated with mortality), timing of complications is unknown (no temporal association between intubation and cardiac arrest), not all hospitals have the same resources or protocols to maximize patient outcomes