Registration trials of antibacterial drugs for the treatment of nosocomial pneumonia.
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.
Sorbello
Alfred
A
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
Komo
Scott
S
Valappil
Thamban
T
Nambiar
Sumati
S
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
D000900:Anti-Bacterial Agents