Katy Town

Decreased susceptibility to cephalosporins among gonococci: data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) in England and Wales, 2007–2011

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.

Risk factors for antimicrobial-resistant Neisseria gonorrhoeae in Europe.

Background The European Gonococcal Antimicrobial Surveillance Programme performs antimicrobial resistance surveillance and is coordinated by the European Centre for Disease Prevention and Control. This study used epidemiological and behavioral data combined with the gonococcal susceptibility profiles to determine risk factors associated with harboring resistant gonococci in Europe. Methods From 2009 to 2011, gonococcal isolates from 21 countries were submitted to the European Gonococcal Antimicrobial Surveillance Programme for antimicrobial susceptibility testing. Patient variables associated with resistance to azithromycin, cefixime, and ciprofloxacin were identified using univariate and multivariable logistic regression analyses of odds ratios. Geometric means for ceftriaxone and cefixime minimum inhibitory concentrations (MICs) were compared for patients of different sexual orientation and sex. Results A total of 5034 gonococcal isolates were tested from 2009 to 2011. Isolates exhibiting resistance to cefixime (MIC > 0.125 mg/L) and ciprofloxacin (MIC > 0.5 mg/L) were significantly associated with infection in heterosexuals (males only for ciprofloxacin), older patients (>25 years of age), or those without a concurrent chlamydial infection in the multivariable analysis. The geometric mean of cefixime and ceftriaxone MICs decreased from 2009 to 2011, most significantly for men who have sex with men, and isolates from male heterosexuals exhibited the highest MICs in 2011. Conclusions The linking of epidemiological and behavioral data to the susceptibility profiles of the gonococcal isolates has allowed those at higher risk for acquiring antimicrobial resistant Neisseria gonorrhoeae to be identified. Improved data numbers and representativeness are required before evidence-based risk groups can be identified, and subsequent focused treatments or public health intervention strategies can be initiated with confidence.

Drifting towards ceftriaxone treatment failure in gonorrhoea: risk factor analysis of data from the Gonococcal Resistance to Antimicrobials Surveillance Programme in England and Wales

Objectives Treatment of Neisseria gonorrhoeae is threatened by the emergence of antimicrobial resistance. We analysed data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) in England and Wales to identify groups most at risk of reduced susceptibility to the currently recommended first-line therapy, ceftriaxone. Methods Data from GRASP between 2007 and 2013 on ceftriaxone susceptibility and strain types were analysed. Risk factors associated with isolates exhibiting a ceftriaxone minimum inhibitory concentration (MIC) of ≥0.015 mg/L (CTR ≥0.015 mg/L) were identified using logistic regression. Results One third of isolates from men who have sex with men (MSM) (1279/4203) and 9.9% from heterosexuals (458/4626) exhibited CTR ≥0.015 mg/L. Between 2007 and 2013, the modal MIC for isolates remained at 0.004 mg/L for MSM but increased from 0.002 to 0.004 mg/L for heterosexuals. Among MSM, CTR ≥0.015 mg/L was associated with Asian ethnicity (crude OR: 1.42; 95% CI 1.07 to 1.88) and previous gonorrhoea (1.34; 1.16 to 1.54). Among heterosexuals, CTR ≥0.015 mg/L was associated with older age (35+ years: 4.31; 3.34 to 5.55), ≥6 sexual partners (1.58; 1.01 to 2.44) and sex abroad (2.23; 1.71 to 2.91). CTR ≥0.015 mg/L was less likely in isolates from heterosexuals of black Caribbean or African ethnicity (0.29; 0.20 to 0.41, 0.66; 0.43 to 0.99), with a concurrent chlamydial infection (0.25; 0.19 to 0.34) or women (0.57; 0.46 to 0.71). Over 600 isolates (CTR ≥0.015 mg/L) were typed; the majority were in Genogroup 1407, containing sequence type 1407. Conclusions The emergence and spread of gonorrhoea with reduced susceptibility to ceftriaxone seems a realistic prospect, most likely in those involved in ‘rapid-transmission’ or bridging sexual networks.

Can previous first-line therapies for Neisseria gonorrhoeae be targeted to specific patient subgroups to treat gonorrhea?

Background Gonorrhea treatment is challenging because of the emergence of resistance, treatment failure with existing drugs, and the lack of alternative agents. This study investigates the feasibility of targeting previously recommended antimicrobials to specific population subgroups where the prevalence of infection susceptible to these antimicrobials is above the World Health Organization cautionary treatment threshold of 95%. Methods Descriptive data from the Gonococcal Resistance to Antimicrobials Surveillance Programme for England and Wales were analyzed to investigate patient characteristics associated with infection with susceptible isolates using univariate and multivariable analyses. Results Of 6173 isolates from 2007 to 2011, 4684 (82%) were susceptible to penicillin, 3899 (68%) to ciprofloxacin, and 5240 (91%) to cefixime. All subgroups of the MSM population had fewer than 95% of isolates susceptible to penicillin, ciprofloxacin, or cefixime. Higher proportions of isolates from heterosexual patient subgroups were susceptible to these antimicrobials. Multivariable models identified the following associations between patient characteristics and infection with susceptible isolates: patients aged 13 to 24 years (penicillin: 92.3% susceptible adjusted odds ratio and associated 95% confidence interval [aOR CI] 1.84–2.97; ciprofloxacin: 88.3%, aOR CI 2.22–3.39; cefixime: 98.7%, aOR CI 1.29–3.52) patients of black ethnicity (penicillin: 93.9%, aOR CI 2.72–4.91; ciprofloxacin: 92.0%, aOR CI 3.94–6.7; cefixime: 99.1%, aOR CI 1.78–6.4), and patients with concurrent chlamydia (penicillin: 93.9%, aOR CI 1.8–3.22; ciprofloxacin: 91.7%, aOR CI 2.71–4.58; cefixime: 99.0%, aOR CI 1.27–4.54). Conclusions This study demonstrated that of the previous first-line therapies, cefixime would be the only antimicrobial suitable for use for infection in heterosexual patients alone.

Screening for gonorrhoea using samples collected through the English National Chlamydia Screening Programme and risk of false positives: a national survey of Local Authorities

Objectives To investigate use of dual tests for Chlamydia trachomatis and Neisseria gonorrhoeae on samples collected through the National Chlamydia Screening Programme (NCSP) in England. Design and setting During May–July 2013, we delivered an online survey to commissioners of sexual health services in the 152 upper-tier English Local Authorities (LAs) who were responsible for commissioning chlamydia screening in people aged 15–24 years. Main outcome measures (1) The proportion of English LAs using dual tests on samples collected by the NCSP; (2) The estimated number of gonorrhoea tests and false positives from samples collected by the NCSP, calculated using national surveillance data on the number of chlamydia tests performed, assuming the gonorrhoea prevalence to range between 0.1% and 1%, and test sensitivity and specificity of 99.5%. Results 64% (98/152) of LAs responded to this national survey; over half (53% (52/98)) reported currently using dual tests in community settings. There was no significant difference between LAs using and not using dual tests by chlamydia positivity, chlamydia diagnosis rate or population screening coverage. Although positive gonorrhoea results were confirmed with supplementary tests in 93% (38/41) of LAs, this occurred after patients were notified about the initial positive result in 63% (26/41). Approximately 450–4500 confirmed gonorrhoea diagnoses and 2300 false-positive screens might occur through use of dual tests on NCSP samples each year. Under reasonable assumptions, the positive predictive value of the screening test is 17–67%. Conclusions Over half of English LAs already commission dual tests for samples collected by the NCSP. Gonorrhoea screening has been introduced alongside chlamydia screening in many low prevalence settings without a national evidence review or change of policy. We question the public health benefit here, and suggest that robust testing algorithms and clinical management pathways, together with rigorous evaluation, be implemented wherever dual tests are deployed.

A survey of the use of text messaging for communication with partners in the process of provider-led partner notification

Objectives Partner notification (PN) is important for sexually transmitted infection (STI) control. With developments in technology, such as text messaging, contacting partners is now easier. This study investigates the frequency and acceptability of text messaging in UK sexual health clinics for STI provider-led PN. Methods A questionnaire was distributed to health advisers (HAs), cascaded by the Society of Sexual Health Advisers and posted on their website. Results 65 questionnaires were returned. Most HAs use telephone for the first and second provider-led PN attempt (61, 94% and 51, 78%, respectively) with text messaging as preferred second choice (19, 29% and 32, 49%, respectively). Overall, 56 clinics (86%) used text messaging at some stage, even if not the preferred option. 29 (52%) clinics had text messaging guidelines and 31 (55%) used messaging templates. Messages varied; 33 (59%) request partner make contact, 11 (20%) mention risk of infection, 9 (16%) name the infection and 20 (36%) use a combination of messages. Six (10%) had contact with their Caldicott Guardian about text messaging. No confidentiality concerns were reported and no complaints were reported from partners about receiving unsolicited text messages. Conclusions Text messaging is widely used and is an important and acceptable tool for STI provider-led PN. It is the second preferred method for contacting partners after telephone for first and second provider-led PN attempts. A small number of clinics never use it. Message content varied; few named the infection. Concerns about confidentiality or negative impact for the partner were not reported. National guidance for the use of text messaging for provider-led PN is needed.

Prevalence of and factors associated with MDR Neisseria gonorrhoeae in England and Wales between 2004 and 2015: analysis of annual cross-sectional surveillance surveys.

Objectives To describe trends in prevalence, susceptibility profile and risk factors for MDR Neisseria gonorrhoeae (MDR-NG) in England and Wales. Methods Isolates from 16 242 gonorrhoea episodes at sexual health clinics within the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) underwent antimicrobial susceptibility testing. MDR-NG was defined as resistance to ceftriaxone, cefixime or azithromycin, plus at least two of penicillin, ciprofloxacin and spectinomycin. Trends in resistance are presented for 2004-15; prevalence and logistic regression analyses for MDR-NG cover the period of the most recent treatment guideline (ceftriaxone plus azithromycin), 2011-15. Results Between 2004 and 2015, the proportion of N. gonorrhoeae isolates fully susceptible to all antimicrobial classes fell from 80% to 46%, with the proportion resistant to multiple (two or more) classes increasing from 7.3% to 17.5%. In 2011-15, 3.5% of isolates were MDR-NG, most of which were resistant to cefixime (100% in 2011, decreasing to 36.9% in 2015) and/or azithromycin (4.2% in 2011, increasing to 84.3% in 2015). After excluding azithromycin-resistant isolates, modal azithromycin MICs were higher in MDR versus non-MDR isolates (0.5 versus 0.125 mg/L), with similar results for ceftriaxone (modal MICs 0.03 versus ≤0.002 mg/L). After adjustment for confounders, MDR-NG was more common among isolates from heterosexual men, although absolute differences in prevalence were small [4.6% versus 3.3% (MSM) and 2.5% (women)]. Conclusions N. gonorrhoeae is becoming less susceptible to available antimicrobials. Since 2011, a minority of isolates were MDR-NG; however, MICs of azithromycin or ceftriaxone (first-line therapies) for many of these were elevated. These findings highlight the importance of continued antimicrobial stewardship for gonorrhoea.

Detection of Chlamydia trachomatis in rectal specimens in women and its association with anal intercourse: a systematic review and meta-analysis.

Objectives Chlamydia trachomatis is the most commonly diagnosed bacterial STI. Lack of prevalence and risk factor data for rectal chlamydia in women has testing and treatment implications, as azithromycin (a first-line urogenital chlamydia treatment) may be less effective for rectal chlamydia. We conducted a systematic review of studies on women in high-income countries to estimate rectal chlamydia prevalence, concurrency with urogenital chlamydia and associations with reported anal intercourse (AI). Design Systematic review and four meta-analyses conducted using random-effects modelling. Data sources Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, PsycINFO and the Cochrane Database were searched for articles published between January 1997 and October 2017. Eligibility criteria Studies reporting rectal chlamydia positivity in heterosexual women aged ≥15 years old in high-income countries were included. Studies must have used nucleic acid amplification tests and reported both the total number of women tested for rectal chlamydia and the number of rectal chlamydia infections detected. Conference abstracts, case reports and studies with self-reported diagnoses were excluded. Data extracted included setting, rectal and urogenital chlamydia testing results, AI history, and demographics. Results Fourteen eligible studies were identified, all among diverse populations attending sexual health services. Among routine clinic-attending women, summary rectal chlamydia positivity was 6.0% (95% CI 3.2% to 8.9%); summary concurrent rectal chlamydia infection was 68.1% in those who tested positive for urogenital chlamydia (95% CI 56.6% to 79.6%); and of those who tested negative for urogenital chlamydia, 2.2% (95% CI 0% to 5.2%) were positive for rectal chlamydia. Reported AI was not associated with rectal chlamydia (summary risk ratio 0.90; 95% CI 0.75 to 1.10). Conclusions High levels of rectal chlamydia infection have been shown in women with urogenital chlamydia infection. The absence of association between reported AI and rectal chlamydia suggests AI is not an adequate indicator for rectal testing. Further work is needed to determine policy and practice for routine rectal testing in women.

Chlamydia and HIV testing, contraception advice, and free condoms offered in general practice: a qualitative interview study of young adults’ perceptions of this initiative

Background Opportunistic chlamydia screening is actively encouraged in English general practices. Based on recent policy changes, Public Health England piloted 3Cs and HIV in 2013–2014, integrating the offer of chlamydia testing with providing condoms, contraceptive information, and HIV testing (referred to as 3Cs and HIV) according to national guidelines. Aim To determine young adults’ opinions of receiving a broader sexual health offer of 3Cs and HIV at their GP practice. Design and setting Qualitative interviews were conducted in a general practice setting in England between March and June 2013. Method Thirty interviews were conducted with nine male and 21 female patients aged 16–24 years, immediately before or after a routine practice attendance. Data were transcribed verbatim and analysed using a thematic framework. Results Participants indicated that the method of testing, timing, and the way the staff member approached the topic were important aspects to patients being offered 3Cs and HIV. Participants displayed a clear preference for 3Cs and HIV to be offered at the GP practice over other sexual health service providers. Participants highlighted convenience of the practice, assurance of confidentiality, and that the sexual health discussion was appropriate and routine. Barriers identified for patients were embarrassment, unease, lack of time, religion, and patients believing that certain patients could take offence. Suggested facilitators include raising awareness, reassuring confidentiality, and ensuring the offer is made in a professional and non-judgemental way at the end of the consultation. Conclusion General practice staff should facilitate patients’ preferences by ensuring that 3Cs and HIV testing services are made available at their surgery and offered to appropriate patients in a non-judgemental way.

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

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.