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Resistance

Fresh WHO guidelines on gonorrhoea management + latest US surveillance data on gonorrhoea resistance

13 Oct, 16 | by Leslie Goode, Blogmaster

The emergence in various locations of resistant strains of Neisseria gonorrhoeae (Ng) is narrowing the therapeutic options. The recent (July 2016) WHO Guidelines, revised from 2003, reflect the concern both to treat effectively and steward our remaining defences against the infection in a globally coordinated manner.  They recommend either dual therapy with either single dose 250g intra-muscular ceftriaxone or 400g oral cefixime combined with 1g oral azithromycin (preferred options), or else single therapy with either ceftriaxone, cefixime or 2g spectinomycin).  The choice between these options will depend on local considerations, including Ng susceptibility data.   In the event of treatment failure following WHO-recommended dual therapy, they recommend any of: 500mg ceftraxone, 800mg cefixime, 240mg gentamicin, or 2g spectinomycin, each of them in combination with 2g azithromycin.

Reported surveillance data for a given location will be crucially important, then, for determining at local level the best options for treatment.  Given the global dimension of the threat, however, this data may also be potential evidence for global trends.  Hence the wider interest of the latest (2014) US surveillance data from the Gonococcal Isolate Surveillance Project (GISP)).  Hitherto, the US picture (as in the UK) has been one of steady progression (2006-2011) in prevalence of Ng isolates exhibiting reduced susceptibility (cefixime: MIC ≥0.25 μg/mL; ceftriaxone: MIC ≥0.125 μg/mL), interrupted by a decline in 2013; this is the pattern both for cefixime (0.1%-1.4%-0.4%) and ceftriaxone (0.1%-0.4%-0.1%) (see also Kirkcaldy & Bolan (STIs)).

So where do the latest (2014) data point? As regards cefixime, to a return to the pre-2013 upward trend, it seems, with prevalence rising once again from 0.4% to 0.8%; with ceftriaxone, to the maintenance of the 2013 prevalence level (0.1%).  Presumably, it is the prevalence levels of ceftriaxone that, in the US, constitute the primary focus of concern – since, as in the UK, that is the drug currently recommended, along with azithromycin, for dual therapy.  (See  Town & Hughes (STI) for  an equivalent report of ceftriaxone resistance in the UK).  But the greatest surprise of the 2016 GISP report is the sudden rise of decreased susceptibility to azithromycin: from 0.6% prevalence of reduced resistance strains (MIC ≥2.0 μg/mL) in 2013 to 2.5% in 2014.  The report comments that the recommended dual therapy with azithromycin is unlikely to be a contributor to this trend – though it is possible, they argue, that the small increase in the azithromycin monotherapy by US STD clinics over the last decade could have had some influence on the prevalence of azithromycin resistant strains.  There is evidence of high or rising levels of azithromycin resistance in other locations (Dillon & Thakur (STIs); Bala & Ramesh (STIs)), including, recently, the UK (Chisholm & Fifer/STIs).

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