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Neisseria gonorrhoeae (NG) has historically been very successful in developing resistance to each antimicrobial used to treat it and is now in the top three antimicrobial resistance (AMR) threats described by the Centre for Disease Control and Prevention.1 Dual therapy with ceftriaxone and azithromycin was introduced in 2011 in the attempt to delay further resistance and this is particularly important as these two antimicrobials are the last reliable options available.2 Worryingly, the emergence of multidrug-resistant gonorrhoea is quickly becoming a reality due to treatment failures, even after dual therapy in the UK and USA.3 ,4 Treatment failures mostly occur in pharyngeal infection. It is now widely accepted that pharyngeal gonorrhoea largely contributes to both the transmission of gonorrhoea and the development of AMR and is a key target area in the control efforts. Furthermore, recent studies suggests that viable gonococci can be isolated from saliva, prompting a re-evaluation of gonorrhoea transmission and control strategies.5
With this in mind, and with no effective vaccine, a new approach to the treatment and control of gonorrhoea should be considered. Antiseptics for example would be an option, perhaps targeting pharyngeal infection in the first instance as topical treatment. The notion of antiseptics for the prevention or treatment of infection is not a new one and is in fact still an important component of infection control in clinical microbiology and dentistry. Even within sexual health, antiseptic compounds have been evaluated and used before the discovery of antibiotics. One of the first reports, in 1917, describes urethral irrigation for the treatment of gonorrhoea, with a solution containing potassium citrate which ended up prolonging the duration of the disease.6 Other compounds used in the pre-antibiotic era for treating gonorrhoea include mercury, silver nitrate, arsenic, antimony, bismuth, gold and various exotic spices but with the discovery of penicillin they were sidelined, especially as the antibiotic was more effective and less toxic.7
Even so, antiseptic compounds are still being researched within sexual health despite the discovery of many antibiotics. This has mainly been as in vitro studies or topical application in the form of vaginal pessaries/gels. For example, Ison et al8 conducted a randomised controlled trial (RCT) in 1987, comparing 2 g oral metronidazole with an intravaginal chlorhexidine pessary for the treatment of bacterial vaginosis (BV) and found equal efficacy. Furthermore, a systematic review of antiseptics and disinfectants for the treatment BV recognised the value of these compounds and called for further research in this area.9 Intravaginal applications of topical antiseptics have also been investigated for Chlamydia trachomatis (CT) and NG, albeit in murine models.10 ,11 A study by Lyons found that three antiseptic compounds, benzalkonium chloride, chlorhexidine and nonoxynol-9, were able to protect against CT infection.10 Importantly, whereas the previous study investigated the protective ability of antiseptics, a study by Spencer et al11 evaluated the efficacy of seven commercial microbicides as a treatment for NG and found that all were successful compared with the control. These studies prove invaluable evidence, even as a proof of principle that there may be alternative options for the treatment of STIs, most importantly gonorrhoea. On the other hand, intravaginal application of antiseptics for the treatment of gonorrhoea has only been evaluated in murine models; the clinical efficacy and safety in humans has not yet been investigated. The vaginal flora is complex and essential in maintaining vaginal health. Any antiseptics used will invariably disrupt the flora as well as the infectious organism and the risk of imbalance and subsequent complications is still a risk to be evaluated.12
Another area of interest that has been considered, perhaps accidentally is antiseptics within commercial lubricants. Two studies describe the inhibitory effect of various antiseptics on the isolation of CT and NG13 ,14 and although the tone of the articles was more in line with lubricants causing false negatives for STI testing, it opens new avenues in terms of the use of lubricants as a preventative measure against STIs. This is especially relevant with the recent evidence suggesting the use of saliva as a lubricant is a risk factor for rectal gonorrhoea in men who have sex with men (MSMs),15 especially as NG can be isolated form saliva.5 This interesting area can be further researched, perhaps as a case-control study comparing MSMs who use commercial lubricants or saliva.
What must not be overlooked, however, is the role of the pharynx in the transmission of NG and development of AMR. There is sufficient evidence to suggest that by targeting pharyngeal gonorrhoea we may be able to control transmission. As antimicrobial penetration in the pharyngeal mucosa is questionable, especially with newly evaluated antimicrobials such as gentamicin, perhaps using antiseptic gargles may prove more effective, as adjunctive therapy. An exciting study presented at the recent BASHH conference by Dr/Professor Kit Fairly evaluated the role of Listerine, a commercial dental mouthwash, as a potential treatment for pharyngeal gonorrhoea. This RCT and further in vitro studies found that Listerine had an inhibitory effect against NG offering a promising alternative to antimicrobials. Of course, Listerine is not the only commercial mouthwash available, so other compounds with different active ingredients can also be evaluated. For example, some mouthwashes contain chlorhexidine, a compound used as a disinfectant also within hospital environments, which is very bactericidal and is also used widely in dental medicine. A study by Tomas et al16 showed that the use of single 0.12% and 0.2% chlorhexidine mouthwashes for as little as 30 s reduced the bacterial viability of salivary flora by up to 95%, taking up to 7 hours to return to normal. The minimum bactericidal concentration of chlorhexidine against NG has been shown to be between 12.5 and 250 µg/mL,17 suggesting that chlorhexidine containing mouthwashes may be very effective.
Antiseptics are not new, but using an ‘old’ area with a ‘new’ context and learning from other healthcare disciplines may help control a rapidly changing micro-organism that has become one of the biggest AMR threats worldwide. Of course, the question remains, if antiseptic mouthwashes are successful, should we aim for complete gonococcal eradication or is infective load reduction sufficient to reduce transmission?
Provenance and peer review Commissioned; internally peer reviewed.
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