Research and analysis

HPR volume 9 issue 41: news (20 November)

Updated 29 December 2015

1. English Surveillance Programme for Antimicrobial Utilisation and Resistance annual report

The second annual report of the English Surveillance Programme for Antimicrobial Utilisation and Resistance (ESPAUR), published by PHE [1], supplements the first report’s data on antibiotic use/prescribing and resistance in the calendar years 2010 to 2013 with new data for 2014; it also reviews antimicrobial stewardship activities pursued in primary and secondary care and considers personal and professional engagement activities, as anticipated by the five year AMR strategy for England published in 2013 [2].

ESPAUR was established in 2013 after PHE was charged with delivering on four of the seven key areas of the UK strategy for 2013-2018 [3].

The key function of the programme is to collate antimicrobial resistance and use data; determine trends in both use of antibiotics and the extent of proliferation of resistant strains associated with those drugs; and also to monitor antimicrobial stewardship programmes and research and public/professional engagement. The first report had provided baseline data on national and regional antibiotic resistance and use, covering the period 2010 to 2013, against which future changes in prescribing practices and resistance could be compared [3].

Key findings of the second report are that:

1.1 on usage

• total antibiotic consumption (measured as defined daily dose of antibiotics per 1000 inhabitants per day) in England has increased by 6.5% since 2011: from 21.6 DDD per 1000 inhabitants per day (2011), to 23 DDD per 1000 inhabitants per day in 2014; in absolute terms, total consumption increased by 2.4% between 2013 and 2014
• the number of prescriptions dispensed in the community declined in both 2013 and 2014 and are now at a lower level than in 2011
• antibiotic use measured in primary care increased when measured by DDD and decreased when measured by prescription, suggesting that longer courses or higher doses are being used
• prescribing to hospital inpatients increased significantly by 11.7%, and to hospital outpatients by 8.5%, between 2011 and 2014
• use of broad spectrum antibiotics (those whose use is likely to drive growth in antibiotic resistance) decreased significantly in primary care

1.2 on resistance

• between 2010 and 2014, the rate of bloodstream infections caused by Escherichia Coli and Klebsiella Pneumoniae increased by 15.6% and 20.8% respectively
• the number of antibiotic resistant E. Coli bloodstream infections has increased overall between 2010 and 2014
• there was a 23% reduction in Streptococcal Pneumoniae bloodstream infections between 2010 and 2014, possibly related to increased pneumococcal vaccination rates

1.3 on stewardship

• in 2014, 60% of clinical commissioning groups (CCGs) and 87% of NHS acute trusts had reviewed the national antimicrobial stewardship toolkits for primary or secondary care; however, only 13% of CCGs and 46% of acute trusts had implemented an action plan to deliver antimicrobial stewardship activities

1.4 on public and professional engagement

• within the first three months of its launch, the UK-wide Antibiotic Guardian campaign attracted pledges from more than 10,000 members of the public and healthcare professionals on prudent antibiotic use

1.5 EU wide data published

As far as the proliferation of antibiotic-resistant infections is concerned, the new ESPAUR data suggest that the situation in England in most respects mirrors that across the European Union and EEA.

On antibiotic usage, for example, ECDC reports a continuing large inter-country variation in consumption across the EU [4]: several member states report significant reductions in consumption and ESPAUR data indicate that consumption of cephalosporins and quinolones in England is the lowest in the EU [1].

Nevertheless, a common phenomenon reported by both ECDC and ESPAUR is the continuing rise in consumption in hospitals, which is a major driver of the spread of multidrug-resistant bacteria responsible for healthcare-associated infections.

1.6 References

1. ESPAUR (16 November 2015). English surveillance programme antimicrobial utilisation and resistance (ESPAUR) 2015 report. See also PHE press release: New ESPAUR report reveals continued rise in antibiotic resistant infections
2. DH (2013). UK five-year antimicrobial resistance strategy 2013 to 2018.
3. ESPAUR (2014). English surveillance programme antimicrobial utilisation and resistance (ESPAUR) 2014 report.
4. ECDC (19 November 2015). European Antimicrobial Resistance Surveillance Network (EARS-Net) annual report. See also: ECDC publishes 2014 surveillance data on antimicrobial resistance and antimicrobial consumption in Europe.

2. Surveillance of antimicrobial resistance in Neisseria Gonorrhoeae

The following summarises latest findings from the Gonococcal Resistance to Antimicrobial Surveillance Programme (GRASP) survey, and related surveillance data

Gonorrhoea, caused by infection with the bacterium Neisseria Gonorrhoeae, is the second most common bacterial sexually transmitted infection in England and, in 2014, was the most common STI diagnosed among men who have sex with men (MSM). New cases continue to increase with 34,958 cases reported in 2014, a 19% increase from 2013 [1]. Over half (55%) of diagnoses in heterosexuals occurred in those aged 15 to 24 years. Gonorrhoea presents a significant public health threat: untreated infection may cause pelvic inflammatory disease and lead to tubal infertility, highlighting the need to maintain effective management [2].

Antimicrobial resistance (AMR) in N. Gonorrhoeae threatens effective treatment and control. Strategies to address this challenge are outlined in national, regional and global action plans [3-5]. The guidelines emphasise the importance of high quality surveillance, prompt recognition and effective management of potential treatment failures, and effective communication to allow timely review of treatment guidelines and public health policy. The World Health Organization recommends treatment guidelines are changed once resistance to the first line therapies reaches a prevalence of 5% [5].

In England and Wales, the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) is the national sentinel surveillance programme which collects N. Gonorrhoeae isolates from consecutive patients attending a network of genito-urinary medicine (GUM) clinics between July and September each year. The programme – whose annual report has been published by PHE [6] – informs clinical guidelines by monitoring patterns of susceptibility of N. Gonorrhoeae to antimicrobial agents used for treatment of gonorrhoea. In 2014, 25 GUM clinics in England and two in Wales participated. Public Health England’s Sexually Transmitted Bacterial Reference Unit (STBRU) received 2,581 isolates of which 1,568 were successfully retrieved, tested for antimicrobial susceptibility and matched to clinical data.

For the first time GRASP was supplemented with data on antimicrobial resistance in N. Gonorrhoeae from primary diagnostic laboratories reported to PHE’s Second Generation Surveillance System (SGSS) and the national reference service at PHE’s STBRU. Although each data source has limitations this combined data source provides a greater insight into the epidemiology of antimicrobial resistant N. Gonorrhoeae than was previously possible.

2.1 Resistance to first-line therapy (combination of ceftriaxone and azithromycin)

Current first-line treatment for gonorrhoea involves dual therapy with ceftriaxone (500mg i.m.) and azithromycin (1g p.o.). Dual therapy is recommended because although gonorrhoea can develop resistance to antibiotics rapidly, the organism is unlikely to develop resistance to both types of drug simultaneously.

Ceftriaxone resistance in N. Gonorrhoeae was rare in 2014; no resistant isolates were identified in GRASP while 0.3% of isolates tested by primary diagnostic laboratories were reported to be resistant. The detected prevalence of azithromycin resistance was approximately 1.0%, which was slightly lower than the 1.6% seen in 2013 (see figure). However, in 2015 an outbreak of high level azithromycin resistant (HL-AziR) N. Gonorrhoeae was detected in Leeds. Fourteen cases have been reported in heterosexuals. The isolates identified to date remain susceptible to ceftriaxone, ciprofloxacin and spectinomycin. This ongoing outbreak demonstrates how resistance dynamics within sexual networks can change rapidly and there is growing concern that high level resistance is a threat to current front line dual therapy.

Urgent intervention is required to prevent further dissemination of strains with HL-AziR phenotype. A National Resistance Alert has been sent to all microbiologists requesting that all laboratories should test gonococci for azithromycin resistance and all isolates categorised as resistant to azithromycin (disc zones ≤27mm or MICs >0.5 mg/L) should be referred to STBRU for investigation of possible HL-AziR. If a strain of HL-AziR gonorrhoea is detected, laboratories should notify clinicians promptly so that rigorous efforts can be made to ensure patients are followed up and receive a test of cure, and that their partners are contacted.

2.2 Discussion

The possibility of future treatment failure due to antibiotic resistance is of concern. Continued compliance with recommended therapies is essential to maintain gonorrhoea as a treatable infection. Prescribing in specialist sexual health clinics has complied with national treatment guidelines in most cases but there is growing evidence of sub-optimal prescribing in other settings [7].

To reduce the spread of antimicrobial resistance, all primary diagnostic laboratories should test gonococcal isolates for susceptibility to front-line antimicrobials and refer resistant isolates to STBRU at PHE Colindale for confirmation and follow-up. Sexual health services should also report possible cases of suspected treatment failure to PHE via the online HIV and STI web-portal. Individuals can significantly reduce their risk of any STI by using condoms with all new and casual partners and, if in a high risk group, requesting a test regularly.

Percentage of azithromycin resistant isolates (MIC ≥1 mg/L) by gender and sexual orientation. GRASP clinics: 2004-2014

2.3 Notes

For the purpose of this report: ceftriaxone resistance is defined as isolates with a minimum inhibitory concentration (MIC) ≥0.125mg/L; azithromycin resistance is defined as MIC ≥1mg/l.

2.4 References

1. PHE (2015). Sexually transmitted infections and chlamydia screening in England, 2014, HPR 9(22).
2. Bignell C, Fitzgerald M (2011). UK national guideline for the management of gonorrhoea in adults, 2011. Int J STD AIDS, 2011, 22(10): 541-7.
3. Health Protection Agency (2013). Gonoccocal Resistance to Antimicrobials Surveillance Programme (GRASP) Action Plan for England and Wales: Informing the Public Health Response
4. ECDC (2012). Response plan to control and manage the threat of multi-drug resistant gonorrhoea in Europe.
5. WHO (2012). Global action plan to control the spread and impact of antimicrobial resistance in Neisseria Gonorrhoeae.
6. PHE (2015). Surveillance of antimicrobial resistance in Neisseria Gonorrhoeae: findings from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) survey, and related surveillance data, 2014.
7. Wetten S, Mohammed H, Yung M, Mercer CH, Cassell JA, Hughes G (2015). Diagnosis and treatment of chlamydia and gonorrhoea in general practice in England 2000-2011: a population-based study using data from the UK Clinical Practice Research Datalink. BMJ Open 2015; 5(5).