Why Nonoxynol-9 May Have Failed to Prevent Acquisition of Neisseria gonorrhoeae in Clinical Trials

In Brief Objectives: To understand why clinical trials failed to demonstrate efficacy of nonoxynol-9 in preventing gonorrhea. Goal: To test the hypothesis that nonoyxnol-9 failed to prevent acquisition of Neisseria gonorrhoeae because most isolates are resistant to killing by nonoyxnol-9 at the level attainable with intravaginal use. Study: The lowest concentrations of nonoxynol-9 required to kill or inhibit growth of clinical isolates of N gonorrhoeae and Lactobacillus were determined. Results: Most strains (17 of 25) of N gonorrhoeae (68%) were resistant to the highest concentration of nonoxynol-9 tested (20%). L crispatus (100%), L jensenii (90%), and L iners (79%) were also resistant to nonoxynol-9. Conclusions: N gonorrhoeae and H2O2-producing strains of vaginal lactobacilli were not killed by nonoxynol-9 at concentrations greater than those achievable in vivo. Earlier studies that formed the basis for subsequent trials most likely did not detect resistance because too few isolates were evaluated. Large numbers of clinical isolates should be examined before the initiation of clinical trial using microbicidal products. Most clinical and reference strains of Neisseria gonorrhoeae and vaginal Lactobacillus are resistant to killing by nonoxynol-9 (N-9) in vitro. This may explain why nonoxynol-9 failed to prevent gonococcal acquisition in clinical trials of N-9.