The development of mouthwashes without anti-gonococcal activity for controlled clinical trials: an in vitro study

Abstract

Background: The oropharynx plays a major role in the development and spread of antimicrobial resistant Neisseria gonorrhoeae among men who have sex with men. Trials are currently assessing the efficacy of bactericidal mouthwashes as possible therapeutic or preventive options against these pharyngeal gonococcal infections. Controlled clinical trials require the use of a placebo mouthwash without anti-gonococcal activity. So far, no such mouthwash has been described. We describe the development of a mouthwash for this purpose. Methods: The in vitro anti-gonococcal activity of Corsodyl®, Listerine Cool Mint®, Biotene®, phosphate buffered saline and six in-house placebo mouthwashes was evaluated. Three gonococcal isolates from patients with pharyngeal infection were exposed to the mouthwashes for a duration ranging from 30 seconds to 60 minutes. Isolates were then plated onto blood agar (5% horse blood) and incubated for 24 hours (5-7% CO2, 35 ± 2°C). Growth of N. gonorrhoeae was scored on a five-point scale (0 to 4). All experiments were conducted in duplicate. Results: Corsodyl® and Listerine Cool Mint® were bactericidal to all isolates. For the other mouthwashes, the median growth score after 60 minutes of exposure was 4 (interquartile range 4-4) for phosphate buffered saline; 1 (interquartile range 1-3) for Biotene®; and ranged between 0 and 2 for the in-house composed mouthwashes. An in-house composed mouthwash (Placebo 6) performed best, with a growth score of 2 (interquartile range 2-3). Conclusions: All of the evaluated potential placebo mouthwashes were bacteriostatic after gonococcal exposure of 30 to 60 minutes. In-house composed Placebo 6 showed less inhibition on gonococcal growth than Biotene® and the other in-house placebos and demonstrates, in our opinion, a good trade-off between anti-gonococcal properties and taste.

Inhibitory Activity of Antibacterial Mouthwashes and Antiseptic Substances against Neisseria gonorrhoeae

“…Importantly, the one commercially available alcohol-containing mouthwash included in this study (Listerine Cool Mint with 22% alcohol) demonstrated complete inhibition of N. gonorrhoeae in both the PBS and saliva matrices at all time points, likely due to the inhibitory activity of the other antibacterial constituents in the preparation. These findings are consistent with earlier studies ( 6 , 7 ). Further studies would benefit from the inclusion of additional commercially available alcohol-containing mouthwashes to assess the impact of saliva on the inhibition of N. gonorrhoeae in these preparations.…”

“…Some mouthwashes have in vitro bactericidal activity against N. gonorrhoeae ( 6 , 7 ). However, two recent randomized controlled trials using mouthwash did not demonstrate a difference in the incidence of oropharyngeal gonorrhea in individuals receiving a daily preventative mouthwash over a 3-month period ( 8 , 9 ).…”

A cross-sectional study of male and female kissing partners among men who have sex with men

“…35 A retrospective case-control study in New Zealand has shown that the MeNZB vaccine reduced the incidence of gonorrhoea by 31% over 10 years; 36 however, the effectiveness against oropharyngeal gonorrhoea is unknown. Additionally, the use of antiseptic mouthwash has also been proposed as a novel intervention for gonorrhoea; 29,[37][38][39][40][41] however, several clinical trials have demonstrated that daily use of antiseptic mouthwash fails to prevent gonorrhoea acquisition and is an ineffective prevention and treatment. [42][43][44][45][46] Given that kissing practices are common, a public health message is important to reinforce the awareness that gonorrhoea can be transmitted through kissing.…”

Chlorhexidine Mouthwash Fails to Eradicate Oropharyngeal Gonorrhea in a Clinical Pilot Trial (MoNg)

“…Although experiments in mice have suggested that chlorhexidine might effectively prevent genital Ng infection, 12 data for preventive or therapeutic efficacy on human oropharyngeal gonorrhea are lacking. Nevertheless, chlorhexidine's strong in vitro bactericidal effect suggests that it could be more effective than Listerine in killing Ng in the oropharynx 6,8,13,14 …”

“…[1][2][3] As a consequence, several authors have proposed that antiseptic mouthwashes may be used to prevent or treat oropharyngeal gonorrhea. 1,4,5 In vitro studies have established that Ng is highly susceptible to killing by mouthwashes such as Listerine 6,7 and chlorhexidine, [8][9][10] and a randomized controlled trial in men with culture-positive oropharyngeal gonorrhea found that Ng could not be cultured in a significant proportion of men 5 minutes after a single gargling session with Listerine. 7 Despite these initial encouraging results, 3 randomized clinical trials have found that Listerine failed to prevent (PReGo 4 and OMEGA1 11 ) or treat (OMEGA2 5 ) oropharyngeal gonorrhea.…”