Difficulties in demonstrating superiority of an antibiotic for multidrug-resistant bacteria in nonrandomized studies

Clin Infect Dis. 2014 Oct 15;59(8):1142-7. doi: 10.1093/cid/ciu486. Epub 2014 Jun 30.


The discovery and development of new antimicrobials is critically important, especially as multidrug-resistant bacteria continue to emerge. Little has been written about the epidemiological issues in nonrandomized trials aiming to evaluate the superiority of one antibiotic over another. In this manuscript, we outline some of the methodological difficulties in demonstrating superiority and discuss potential approaches to these problems. Many of the difficulties arise due to confounding by indication, which we define and explain. Epidemiological methods including restriction, matching, stratification, multivariable regression, propensity scores, and instrumental variables are discussed.

Keywords: antibiotics; epidemiology; nonrandomized studies; research design; superiority.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use*
  • Bacterial Infections / drug therapy*
  • Bacterial Infections / microbiology*
  • Clinical Trials as Topic*
  • Drug Resistance, Multiple, Bacterial*
  • Humans
  • Treatment Outcome


  • Anti-Bacterial Agents