title: Registration trials of antibacterial drugs for the treatment of nosocomial pneumonia.
abstract: Since 1989, 12 registration trials have been submitted to the US Food and Drug Administration to support the clinical efficacy of 8 antibacterial drugs for the treatment of nosocomial pneumonia. Six trials used noninferiority designs, whereas the others were equivalence trials or lacked a prespecified hypothesis. Patients with nosocomial pneumonia and ventilator-associated pneumonia were frequently enrolled in the same clinical trials. Enrolled patients were predominantly male and had mean Acute Physiology and Chronic Health Evaluation II scores of 12-18. The investigator's assessment of clinical response was the primary end point, which was usually measured 7-14 days after study drug completion. Clinical cure rates among the intent-to-treat population for nosocomial pneumonia and ventilator-associated pneumonia ranged from 37% to 69% and 25% to 58%, respectively. All-cause mortality ranged from 8% to 28%. Pseudomonas aeruginosa, Acinetobacter species, and methicillin-resistant Staphylococcus aureus were common bacterial pathogens. The design, implementation, and limitations of the clinical trials and implications for future clinical research are discussed.
authors.affiliation: Office of Antimicrobial Products, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland 20993, USA. alfred.sorbello@fda.hhs.gov
authors.forename: Alfred
authors.initials: A
authors.lastname: Sorbello
authors.forename: Scott
authors.initials: S
authors.lastname: Komo
authors.forename: Thamban
authors.initials: T
authors.lastname: Valappil
authors.forename: Sumati
authors.initials: S
authors.lastname: Nambiar
mesh_terms: D018806:APACHE; D000150:Acinetobacter / Q000302:isolation & purification; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003428:Cross Infection / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification; D012107:Research Design; D013211:Staphylococcus aureus / Q000302:isolation & purification; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents