淋病耐药呈增加趋势,改进处方可延缓耐药

根据英国一项名为GRASP的项目研究,最后一种对淋球菌有效的抗生素正在逐渐失去效力,但是改进处方有助延缓耐药这一趋势。

英格兰公共卫生微生物学服务机构的性传播细菌参考实验室的Catherine A. Ison博士在『柳叶刀』(Lancet)上发表了这项研究。

研究人员从2007至2011年间收集来自英格兰和威尔士26个泌尿生殖医学诊所和24个实验室的7378株淋球菌。其中6176例菌株具有抗微生物易感性方面的信息。

分析显示,547(8.9%)的分离株对头孢克肟的易感性下降,其中,2007至2010年间,易感性下降的分离株从1.5%增加到17.1%。而到了2011年,则又下降到10.8%。

此外,大多数对头孢克肟易感性下降的菌株对头孢曲松和环丙沙星的易感性也出现下降。多变量分析显示,男同性恋对头孢克肟易感性下降的风险异常明显。

GRASP推荐增加头孢曲松剂量至500mg以确保抗菌效力,并同时给予1g口服阿奇霉素去治疗伴随衣原体感染的患者,并提高对淋病的抵抗能力。这一推荐意见使淋球菌对头孢克肟易感性下降的数量在2010至2011年间发生明显下降,并且使得2009年后没有再发现分离株对头孢曲松易感性下降现象。

Background


Effective treatment of gonorrhoea is fundamental to public health control; however, the ability of Neisseria gonorrhoeae to successively develop resistance to different treatments has hampered control efforts. The extended-spectrum cephalosporins—cefixime and ceftriaxone—have been recommended in the UK for treatment of gonorrhoea since 2005. We looked at surveillance data from England and Wales to ascertain the current usefulness of these drugs and to inform changes to national treatment guidelines.

Methods


We obtained data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) for patients attending 26 genitourinary medicine clinics in England and Wales between 2007 and 2011. We did analyses with univariate and multivariable logistic regression methods to identify trends in susceptibility to cephalosporins and risk factors associated with infection with isolates with decreased susceptibility to cefixime, and we assessed changes in prescribing practices. We did molecular typing to investigate genetic relatedness of non-susceptible isolates.

Findings


The prevalence of decreased susceptibility to both cefixime and ceftriaxone rose between 2007 and 2010 but was more noticeable for cefixime (an increase from 1·5% in 2007 to 17·1% in 2010), with a bimodal distribution of minimum inhibitory concentration recorded between 2009 and 2010. By multivariable analysis, isolates with decreased susceptibility to cefixime were associated with infection in men who have sex with men (odds ratio 5·47, 95% CI 3·99—7·48; p<0·0001) and year of isolation (in 2010, 13·08, 7·49—22·8; p<0·0001). Such isolates had a largely clonal population, with most belonging to genogroup G1407 and harbouring the penA mosaic gene. Data from 2011 showed a significant decline in prevalence of isolates with decreased cefixime susceptibility, falling from 17·1% in 2010 to 10·8% in 2011 (p<0·0001), concomitant with the change in prescribing practice in 2010 from cefixime to ceftriaxone plus azithromycin.

Interpretation


Guidance for treatment of gonorrhoea in England and Wales was changed in 2010 to prolong the use of cephalosporins. The decline in prevalence of isolates with decreased cefixime susceptibility cannot be attributed unequivocally to this change in prescribing practice; however, the association is striking.

Funding


Department of Health (England), Public Health England.

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