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      Is previous azithromycin treatment associated with azithromycin resistance in Neisseria gonorrhoeae? A cross-sectional study using national surveillance data in England

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          Abstract

          Objectives

          It has been suggested that treatment of STIs with azithromycin may facilitate development of azithromycin resistance in Neisseria gonorrhoeae (NG) by exposing the organism to suboptimal doses. We investigated whether treatment history for non-rectal Chlamydia trachomatis (CT), non-gonococcal urethritis (NGU) or NG (proxies for azithromycin exposure) in sexual health (GUM) services was associated with susceptibility of NG to azithromycin.

          Methods

          Azithromycin susceptibility data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP 2013–2015, n=4606) and additional high-level azithromycin-resistant isolates (HL-AziR) identified by the Public Health England reference laboratory (2013–2016, n=54) were matched to electronic patient records in the national GUMCAD STI surveillance dataset (2012–2016). Descriptive and regression analyses were conducted to examine associations between history of previous CT/NGU/NG and subsequent susceptibility of NG to azithromycin.

          Results

          Modal azithromycin minimum inhibitory concentration (MIC) was 0.25 mg/L (one dilution below the resistance breakpoint) in those with and without history of previous CT/NGU/NG (previous 1 month/6 months). There were no differences in MIC distribution by history of CT/NGU (P=0.98) or NG (P=0.85) in the previous 1 month/6 months or in the odds of having an elevated azithromycin MIC (>0.25 mg/L) (Adjusted OR for CT/NGU 0.97 (95% CI 0.76 to 1.25); adjusted OR for NG 0.82 (95% CI: 0.65 to 1.04)) compared with those with no CT/NGU/NG in the previous 6 months. Among patients with HL-AziR NG, 3 (4%) were treated for CT/NGU and 2 (3%) for NG in the previous 6 months, compared with 6% and 8%, respectively for all GRASP patients.

          Conclusions

          We found no evidence of an association between previous treatment for CT/NGU or NG in GUM services and subsequent presentation with an azithromycin-resistant strain. As many CT diagnoses occur in non-GUM settings, further research is needed to determine whether azithromycin-resistant NG is associated with azithromycin exposure in other settings and for other conditions.

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          Most cited references21

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          Sexually transmitted infections: challenges ahead.

          WHO estimated that nearly 1 million people become infected every day with any of four curable sexually transmitted infections (STIs): chlamydia, gonorrhoea, syphilis, and trichomoniasis. Despite their high global incidence, STIs remain a neglected area of research. In this Commission, we have prioritised five areas that represent particular challenges in STI treatment and control. Chlamydia remains the most commonly diagnosed bacterial STI in high-income countries despite widespread testing recommendations, sensitive and specific non-invasive testing techniques, and cheap effective therapy. We discuss the challenges for chlamydia control and evidence to support a shift from the current focus on infection-based screening to improved management of diagnosed cases and of chlamydial morbidity, such as pelvic inflammatory disease. The emergence and spread of antimicrobial resistance in Neisseria gonorrhoeae is globally recognised. We review current and potential future control and treatment strategies, with a focus on novel antimicrobials. Bacterial vaginosis is the most common vaginal disorder in women, but current treatments are associated with frequent recurrence. Recurrence after treatment might relate to evidence that suggests sexual transmission is integral to the pathogenesis of bacterial vaginosis, which has substantial implications for the development of effective management approaches. STIs disproportionately affect low-income and middle-income countries. We review strategies for case management, focusing on point-of-care tests that hold considerable potential for improving STI control. Lastly, STIs in men who have sex with men have increased since the late 1990s. We discuss the contribution of new biomedical HIV prevention strategies and risk compensation. Overall, this Commission aims to enhance the understanding of some of the key challenges facing the field of STIs, and outlines new approaches to improve the clinical management of STIs and public health.
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            Statistical analysis of correlated data using generalized estimating equations: an orientation.

            J Hanley (2003)
            The method of generalized estimating equations (GEE) is often used to analyze longitudinal and other correlated response data, particularly if responses are binary. However, few descriptions of the method are accessible to epidemiologists. In this paper, the authors use small worked examples and one real data set, involving both binary and quantitative response data, to help end-users appreciate the essence of the method. The examples are simple enough to see the behind-the-scenes calculations and the essential role of weighted observations, and they allow nonstatisticians to imagine the calculations involved when the GEE method is applied to more complex multivariate data.
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              UK national guideline for the management of gonorrhoea in adults, 2011.

              The British Association for Sexual Health and HIV (BASHH) UK gonorrhoea guideline has been updated in 2011. It offers advice on diagnosis, treatment and health promotion for anogenital and pharyngeal gonorrhoea. Nucleic acid amplification tests (NAATs) are now being used more for diagnosis and are increasing detection rates in the pharynx and rectum. First line treatment using ceftriaxone with azithromycin is now advised, along with routine test of cure (TOC). The aim is to slow the spread of resistant gonorrhoea now that fewer antibiotics remain effective. A patient information leaflet has been developed.
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                Author and article information

                Journal
                Sexually Transmitted Infections
                Sex Transm Infect
                BMJ
                1368-4973
                1472-3263
                August 20 2018
                September 2018
                September 2018
                March 06 2018
                : 94
                : 6
                : 421-426
                Article
                10.1136/sextrans-2017-053461
                29511067
                736587f0-6a4f-43be-9785-cb92db5c2aef
                © 2018
                History

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