Recommended Design Features of Future Clinical Trials of Antibacterial Agents for Hospital‐Acquired Bacterial Pneumonia and Ventilator‐Associated Bacterial Pneumonia

Influence of Bronchoscopy on the Diagnosis of and Outcomes from Ventilator-Associated Pneumonia

“…The same was true when only analyzing patients that received an initial diagnostic bronchoscopy. Trauma patients who received a therapeutic bronchoscopy, irrespective of diagnostic procedure, had significantly more days of antibiotic therapy (median: 12; interquartile range (IQR): 9-17; p = 0.009) compared with those that only underwent a diagnostic procedure (median: 10; IQR: [8][9][10][11][12][13][14]. When only considering patients who received an initial diagnostic bronchoscopy, those who also received a therapeutic bronchoscopy also had a longer duration of antibiotic therapy (median: 11; IQR: 9-17 vs. median: 9; IQR: 8-13; p = 0.01).…”

“…tract culture as the standard for diagnosis but the exact method of procurement is not well-defined [13]. Bronchoalveolar lavage, especially when combined with quantitative culture, has been shown to be a highly accurate method of diagnosis, particularly in the trauma setting [14.15].…”

Considerations in Undertaking a Clinical Development Program for Hospital‐Acquired Bacterial Pneumonia and/or Ventilator‐Associated Bacterial Pneumonia

“…The following concepts are essential for development programs: (1) require highly robust, carefully interpreted, enabling Table 2 data (as discussed above); (2) increase the likelihood of bacterial pneumonia by requiring microbiological confirmation in the primary analysis population, as was done in the recent FDA Guidance for CABP; (3) accept data from certain types of phase 3 clinical trials of parenteral agents in the treatment of CABP as pivotal for the HABP and/or VABP indications; and (4) consider that proof of efficacy and safety in VABP could be extrapolated to HABP, but not vice versa. The last concept derives from observations by Ambrose et al [3] that populations with VABP exhibit marked bimodal characteristics with regard to pathogen susceptibility and pharmacokinetics, because of the inhomogeneity in patient subpopulations.…”

“…Fortunately, the data presented at the HABP and VABP workshop and summarized in the consensus position paper of the Infectious Diseases Society of America, American Thoracic Society, American College of Chest Physicians, and Society of Critical Care Medicine make it clear that validated methods and/or tools are available to design, conduct, and analyze HABP and/or VABP trials, although additional work is needed in some areas (eg, rapid diagnostics and clinical outcome measures other than all-cause mortality) [4]. Data and conclusions from future trials conducted for the HABP and/ or VABP indications should be better able to withstand rigorous scientific examination and, therefore, should be acceptable to regulators worldwide and relevant to current and future medical practice.…”

U.S. bans antibiotics use for enhancing growth in livestock

“…The availability of effective antibiotics is necessary to enable modern medical advances that range from intensive care unit medicine to aggressive surgeries, cancer chemotherapy, care for premature neonates, and organ transplantation. Loss of antibiotic efficacy threatens to return society to a time when one in ten patients with a skin infection died and one in three patients with pneumonia died (greater than 10-fold higher death rates compared to the antibiotic era (Spellberg, 2010;Spellberg et al, 2008b;Spellberg et al, 2009). Without effective antibiotics, medicine would be paralyzed by an inability to treat infections resulting from intensive specialty care (Spellberg, 2010;Spellberg et al, 2008a;Spellberg et al, 2011;Spellberg et al, 2013).…”