“Stewarding” may be the best policy for prolonging the efficacy of anti-Gonorrhoea drugs

With reports of the growing resistance of Neisseria gonorrhoeae to cephalosporins, currently the last weapon in the antibiotic armoury,  control seems rapidly to be running out of options. Given the 21,183 reported cases in the UK (2011) – over half the EU total for the same year – this is a matter of grave public health concern. Contributions to STI journal have traced the history of gonococcal resistance (sti-Lewis), and assessed the narrowing possibilities for future management (sti-Ross & Lewis).

A recent study (Ison & Lowndes) draws attention – and lends support – to a change in prescribing policy for gonorrhoea in the UK (Guidelines 2011).  In the past, policy has tended to adhere to the dogma that one microbial agent should only be replaced by an alternative when treatment failures due to resistance cross a 5% threshold. Given the availability of two cephalosporin treatment options, oral cefixime and intra-muscular Ceftriaxone, and the far lower levels of non-susceptibility encountered with intra-muscular ceftriaxone, this would have led to continuing use of Cefixime until the 5% threshold of resistance had been reached, and its subsequent replacement with Ceftriaxone.  Yet the 2011 UK guidelines based on data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) adopted the new strategy of “stewarding the first line of antibiotic defence” by shifting pre-emptively to intra-muscular Ceftriaxone and combining with azithromycin or doxicycline in order to “steward” the efficacity of Cefixime as the antibiotic first line of defence.

The study itself analysed GRASP surveillance data from 26 UK clinics respecting prescribing policy and levels of cephalosporin resistance encountered in gonococcal isolates over the period 2007-2011; it also performed molecular typing to investigate the genetic relatedness of resistant isolates.  The findings are particularly interesting because they cover the years following the policy shift.  Prescribing policy seems to have followed the guidelines with the use of cefixime as part of the treatment falling over the years 2010-2011 from 50% to 5% and use of ceftriaxone as part of the treatment rising from 41% to 93%.  Over the same period the proportion of isolates showing decreased susceptibility to Cefixime (defined as a minimum inhibitory concentration of ≥ 0.125 mg/l) fell from 17.1% to 10.8%, suggesting a direct impact of the change of prescribing policy on cefixime resistance.  Molecular typing of non-susceptible isolates suggested a largely clonal population, with most belonging to genogroup G1407 and all but eight harbouring the penA mosaic gene.  Over 86% of these isolates were from MSM (men who have sex with men); on multivariate analysis the association of resistant isolates with MSM infection showed an odds ratio of 5.47. Cefixime resistance, the authors conclude, is at present limited largely if not entirely to the MSM population – though there seems every likelihood of it bridging the gap into the non-MSM population, as has occurred in the past with other antibiotics.  In the meantime the more tactical approach of “stewarding” may offer the best hope of extending the usefulness of cephalosporins pending, hopefully, the development of new treatments in the future (see: sti-Ross & Lewis).

 

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