Research and analysis

HPR volume 11 issue 45: news (15 December)

Updated 15 December 2017

PHE calls on anyone travelling to Romania, Italy or Germany this Christmas to ensure they are up to date with their MMR jab

People planning to travel to Europe this winter are being urged to ensure they are fully protected against measles – particularly if travelling to Romania, Italy or Germany, where large outbreaks are currently ongoing [1].

Since November, measles outbreaks have been declared in Leeds, Liverpool, Birmingham, Manchester and Surrey that are linked to importations from the outbreaks in Europe. All of the cases have been reported in children and adults who have not received two doses of the MMR vaccine. PHE local health protection teams are working closely with the NHS and local authorities to raise awareness of the measles outbreaks among health professionals and local communities.

PHE has reiterated that parents should take up the offer of MMR vaccination for their children at 1 year of age, and as a pre-school booster at 3 years and 4 months of age. MMR vaccine is available to all adults and children who are not up to date with their two doses. Anyone who is not sure if they are protected should check with their GP practice. The vaccine can also be given from six months of age before travel to a high risk country.

Those planning to travel over the Christmas period should check NaTHNaC travel health advice [3].

References

1. “PHE calls on travelling to Romania, Italy and Germany this Christmas to ensure they are up to date with their MMR jab” (PHE press release), 13 December 2017.
2. “Measles outbreaks confirmed in five areas across UK” (PHE website news story), 30 November 2017.
3. NaTHNaC website. Measles in Europe: a reminder for seasonal travellers to ensure they are up to date with measles vaccine, 28 November 2017.

Surgical site infection surveillance in NHS hospitals in England: 2016/17 annual report

A new report presenting cumulative incidence data on surgical site infections for 17 categories of surgical procedures summarises data collected by 221 NHS hospitals and nine independent NHS Treatment centres in England, between April 2012 and March 2017, as part of PHE’s SSI surveillance programme [1].

Surveillance of SSI in orthopaedic surgery is mandatory for NHS Trusts in England. Surveillance in the additional 13 surgical categories, covering gastro-intestinal, cardiac, neurosurgery, gynaecology, vascular and other general surgery procedures, is undertaken according to local priorities.

Surveillance of SSIs is undertaken using standard definitions for infections that affect the superficial incisional site, the deeper incisional layers or involving the joint or organ-space [2]. Patients are systematically, prospectively followed-up to identify infections occurring within 30 days of surgery or within one year if a prosthetic implant is used.

The report includes an analysis of data quality indicators, trends in the SSI incidence, risk factors for SSI and microbial aetiology. An accompanying supplement lists the orthopaedic SSI incidence by NHS Trust, also available in due course from PHE’s Fingertips website.

Key findings

• in 2016/17, data on 139,691 procedures and 1,635 surgical site infections (SSIs) detected during inpatient stay or on readmission following the initial operation were collected by 201 NHS hospitals and eight independent sector NHS treatment centres across 17 surgical categories
• mandatory orthopaedic data comprised 108,402 procedures and 681 inpatient/readmission SSIs in 2016/17 collected by 137 NHS Trusts including eight NHS treatment centres
• for the mandatory orthopaedic surveillance, 11 NHS trusts were identified as high outliers in 2016/17. Six NHS trusts and two NHS treatment centre were identified as low outliers. All 19 providers have been contacted and asked to investigate possible reasons
• the cumulative SSI incidence (data from April 2012 to March 2017) varied by surgical category ranging from 9.2% for large bowel surgery to <1% for hip and knee prosthesis
• a significant decrease in the SSI incidence occurred between 2009/10 and 2016/17 for repair of neck of femur (from 1.6% to 1.0%) and reduction of long bone fracture (from 1.5% to 0.7%)
• the SSI incidence remained low for hip and knee prosthesis (<1%) with stabilised trends in both surgical categories in the last three successive years
• a significant decrease in SSI occurred for coronary artery bypass graft (CABG) surgery, from 5.7% in 2009/10 to 3.8% in 2016/17
• spinal surgery showed a significant increase in SSI from 0.9% in 2009/10 to 1.4% in 2016/17 as did cholecystectomy (from 0.9% to 3.0%) over the same period; the increase in SSI in cardiac non-CABG surgery (from 1.0% to 1.7%) reached borderline significance
• Enterobacteriaceae continued to increase, accounting for 29% of SSIs in 2016/17, the highest to date. Staphylococcus aureus and the methicillin-resistant form (MRSA) continued to decrease accounting for 11% and 2% of inpatient-detected SSIs in 2016/17 respectively. Small, steady decreases in methicillin-susceptible S. aureus (MSSA) were observed since 2013/14, stabilising at 9% of SSIs in 2015/16 and 2016/17
• Enterobacteriaceae were the predominant causes of SSIs in large bowel (53%) and CABG surgery (29%) between 2014/15 and 2016/17
• S. aureus was the predominant cause of SSI in orthopaedic and spinal surgery (≥33% of cases), with a small decrease in repair of neck of femur (to 41%, data to 2016/17); although coagulase-negative staphylococci (CoNS) were still predominant in CABG SSIs (26%) although spinal surgery exceeded this proportion for the first time (28%)
• in primary total hip prosthesis, the proportion of SSIs due to S. aureus was highest in the uncemented (44%) compared to the cemented (35%) and hybrid fixation (31%) groups.

The full report and accompanying Trust tables are available from the PHE webpage, Surgical site infections (SSI) surveillance: NHS hospitals in England.

References

1. PHE (12 December 2017). Surveillance of surgical site infections in NHS hospitals in England, 2016 to 2017.
2. PHE (June 2013). Protocol for the surveillance of surgical site infection (version 6).

Mandatory HCAI reports quarterly trends: July-September 2017

PHE’s latest quarterly epidemiological commentary on trends in reports of Staphylococcus aureus (MRSA and MSSA) and Escherichia coli bacteraemia, and of Clostridium difficile infections, mandatorily reported by NHS acute Trusts in England, has been published on the GOV.UK website [1].

The report includes tabular and graphical presentation of data for the July-September 2017 quarter and updates the previous report published in September 2017. Some key facts are listed below.

MRSA bacteraemia

There was a a steep decline of 85% in the incidence rate (per 100,000 population) of all reported cases between April-June 2007 and January-March 2014 from 10.2 to 1.5. However, between January-March 2014 and the most recent quarter (July-September 2017), the incidence rate of all reported cases has fluctuated mainly between 1.3 and 1.5 cases per 100,000 population with the most recent quarter being 1.5 cases per 100,000 population.

The PIR process for all + MRSA bacteraemia cases began in April 2013. Between April 2013 and March 2014, the rates of trust-assigned cases remained stable at 1.2 cases per 100,000 bed-days while the incidence rate of CCG-assigned cases decreased by 22% from 1.0 to 0.7 cases per 100,000 population.

Following the introduction of a third-party assignment category in April 2014, counts – and rates – of CCG-assigned cases decreased from 91 to 89 cases – and 0.7 to 0.6 cases per 100,000 population – between April-June 2014 and June-September 2017. This decrease is mostly due to the introduction of the new assignment category, as several cases which would be classified as CCG-assigned are now classified as third-party assigned.

Over the same period (April-June 2014 to to July-September 2017), counts and incidence rate (per 100,000 bed-days) of trust-assigned cases have remained relatively stable at 73-76 cases and 0.8-0.9 respectively. Similarly within the same period, the counts and incidence rate (per 1000,000 population) of third-party assigned cases increased from 17 to 40 cases and 0.1 to 0.3 respectively.

MSSA bacteraemia

Since the mandatory reporting of MSSA bacteraemia began in January 2011 there has been a general trend of increasing counts and incidence rates. All reported cases of MSSA bacteraemia increased by 34% from 2,199 to 2,939 between January-March 2011 and July-September 2017. This was accompanied by a 26% increase in incidence rate (per 100,000 population) from 16.8 to 21.2. Conversely, over the same period, the incidence rate of hospital-onset cases remained relatively level, fluctuating between 8-9 cases per 100,000 bed-days while counts of MSSA bacteraemia increased slightly from 735 to 770.

While the number of all reported MSSA bacteraemia increased throughout the surveillance period (January-March 2011 to July-September 2017), the percentage of all reported cases that presented in a healthcare facility (hospital-onset) decreased from 33% to 26% over the same period, indicating that over time there has been a greater increase in community-onset cases compared to hospital-onset cases.

When comparing the most recent quarter with the same period last year (July-September 2016 and July-September 2017), there was a 5% increase in the incidence rate of all reported MSSA bacteraemia from 20.2 to 21.2 cases per 100,000 population) and a similar 6% increase in incidence rate (per 100,000 bed-days) from 8.4 to 8.9.

Escherichia coli bacteraemia

Seasonal peaks are seen in all reported cases of E. coli bacteraemia between July and September each year. Beginning from April-June 2013, each quarter of each year has been higher than the same quarter in the preceding year, implying an increase over the overall time period. The seasonal peaks in all reported cases are due to the seasonality of community-onset cases.

Between July-September 2011 and July-September 2017, all reported cases of E. coli bacteraemia increased by 33% from 8,275 to 10,989 cases. Incidence rate (per 100,000 population) also increased by 28% from 61.8 to 79.1 over the same period. Similarly over the same period, community-onset cases increased by 44% from 6,279 to 9,022 cases. Incidence rate (per 100,000 population) also increased by 38% from 46.9 to 64.9. Unlike community-onset cases, hospital-onset cases decreased slightly from 1,996 to 1,967 cases and associated incidence rate (per 100,000 bed-days) decreased by 4% from 23.7 to 22.8 between July-September 2011 and July-September 2017.

A similar trend is observed when comparing the most recent quarter and the same quarter from the previous year (July-September 2016 - July-September 2017). There was a 1% increase in both counts and incidence rate of all reported cases from 10,892 to 10,989 cases and from 78.4 to 79.1 cases per 100,000 population respectively. Also both counts and incidence rate of community-onset cases increased by from 2% 8,851 to 9,022 cases and from 63.7 to 64.9 cases per 100,000 population respectively. However, over the same period, both counts and incidence rate of hospital-onset cases decreased by 4% from 2,041 to 1,967 cases and from 23.6 to 22.8 cases per 100,000 bed-days respectively.

Klebsiella spp. bacteraemia

Mandatory surveillance of Klebsiella spp. bacteraemia began in April 2017. Since that time (April-June 2017 and July-September 2017), 4,638 case of Klebsiella spp. bacteraemia have been reported at an incidence rate of 16.8 cases per 100,000 population - 15.7 in April-June 2017 and 17.8 in July-September 2017. During this time, 29% (n=1,343) were hospital-onset cases and the incidence rate was 7.8 cases per 100,000 bed-days – 7.1 in April-June 2017 and 8.5 in July-September 2017. The remaining 71% (n=3,295) were community-onset cases, an incidence rate of 11.9 cases per 100,000 population – 11.3 in April-June 2017 and 12.6 in July-September 2017.

Furthermore, over the same period, 57% (2,627/4,638) of all reported Klebsiella spp. bacteraemia were caused K. pneumoniae (the most frequently reported species) compared to 13% (594/4,638) caused by K. oxytoca (the next most frequently reported species).

Pseudomonas aeruginosa bacteraemia

Mandatory surveillance of P. aeruginosa bacteraemia began in April 2017. Since that time (April-June 2017 and July-September 2017), 2057 case of P. aeruginosa bacteraemia have been reported at an incidence rate of 7.4 cases per 100,000 population – 6.9 in April-June 2017 and 8.0 in July-September 2017. During this time, 36% (n=750) were hospital-onset cases and the incidence rate was 4.4 cases per 100,000 bed-days – 4.1 in April-June 2017 and 4.7 in July-September 2017. The remaining 64% (n=1307) were community-onset cases, an incidence rate of 4.7 cases per 100,000 population – 4.3 in April-June 2017 and 5.1 in July-September 2017.

C. difficile infection (CDI)

Since the initiation of C. difficile infection (CDI) surveillance in April 2007, there has been an overall decrease in counts and associated incidence rate of both all reported and hospital-onset cases. Seasonal peaks are present in January-March quarters prior to 2014/15 and the July-September quarters between 2014/15 and 2016/17, this is particularly apparent among hospital-onset cases.

The bulk of this decrease occurred between April-June 2007 and January-March 2012 with a 78% decrease in total (all reported) cases of CDI from 16,864 to 3,711 cases and an associated 79% reduction in incidence rate (per 100,000 population) from 131.6 to 27.9. Subsequently between January-March 2012 and July-September 2017, all reported case reduced by 2% from 3,711 to 3,648 cases and incidence rate reduced by 6% from 27.9 and 26.3.

There were similar but greater reductions among hospital-onset CDI cases - 85% reduction in cases from 10,436 to 1,613 cases and 84% reduction in incidence rate (per 100,000 bed-days) from 112.5 to 18.2 between April-June 2007 and January-March 2012. This was followed by a further 21% decrease in counts (from 1,613 to 1,276 cases) and 19% decrease in incidence rate (from 18.2 to 14.8) between January-March 2012 and July-September 2017.

This shows that there has been a greater decline among hospital-onset CDI cases compared to all reported CDI cases during the surveillance period.

When the most recent quarter is compared with the same quarter last year (July-September 2016 and July-September 2017) both counts and incidence rate (per 100,000 bed-days) of all reported CDI have remained relatively stable at 3,631-3,648 cases and 26.1-26.3 respectively, while both counts and incidence rate (per 100,000 bed-days) of hospital-onset CDI cases both decreased slightly by 2% from 1,247 to 1,276 cases and 14.4 to 14.8 respectively.

Reference

1. PHE (14 December 2017). Quarterly Epidemiological Commentary: MRSA, MSSA and Gram-negative bacteraemia and CDI: quarterly report.

Salmonella Typhi resistant to third-generation cephalosporins (Antimicrobial Resistance Alert)

The following Public Health Resistance Alert – Salmonella Typhi Resistant to Third-generation Cephalosporins Isolated in England from a Traveller Returning from Pakistan – has been developed jointly by PHE and the equivalent health protection bodies of Wales, Scotland and Northern Ireland.

Salmonella Typhi (S. Typhi) resistant to third-generation cephalosporins has been isolated from a traveller returning to the UK from Pakistan. The resistance was conferred via the acquisition of a CTX-M-15 ESBL. The isolate also has mutations conferring resistance to fluoroquinolones.

In response, it is recommended that:

• Diagnostic laboratories should screen presumptive isolates of S. Typhi and S. Paratyphi A for resistance to third-generation cephalosporins.
• Diagnostic laboratories should continue to refer all isolates of presumptive S. Typhi and S. Paratyphi to PHE’s Gastrointestinal Bacteria Reference Unit (GBRU) to enable continuous surveillance of genetic resistance markers. This is free of charge to the NHS laboratories in England and Wales.
• NHS laboratories in Scotland should, instead, forward isolates to the Scottish Salmonella Reference Service, based in the Scottish Microbiology Reference Laboratories, Glasgow.

Background

Public Health England (PHE) reports approximately 300 cases of laboratory-confirmed enteric fever each year, of which >90% are acquired abroad, the majority from travellers returning to the UK from Pakistan, India and Bangladesh [1]. The majority of S. Typhi isolates received by the Gastrointestinal Bacteria Reference Unit (GBRU) are of the globally epidemic and multidrug-resistant (MDR) clone H58, which characteristically shows resistance to chloramphenicol, ampicillin, co-trimoxazole, streptomycin, tetracycline and reduced susceptibility to quinolones [2]. Third-generation cephalosporins are therefore used as first-line therapy to treat complicated cases of enteric fever [3].

Resistance to third-generation cephalosporins has been reported since 2003 from isolated cases in S. Typhi from the Indian subcontinent, Middle East, and Africa. More recently, cases of cephalosporin-resistant S. Typhi have been reported in travellers returning to Germany and Spain, and a case of S. Paratyphi A returning to Japan [4-7]. Of note, given the extent of travel between the UK and Pakistan, there is a large and ongoing outbreak of S. Typhi with CTX-M-15 in the Sindh district of Pakistan.

Basis for alert

PHE’s GBRU undertakes characterisation of all Salmonella isolates using whole genome sequencing (WGS). A presumptive S. Typhi isolated from the blood of a traveller returning from Karachi, Pakistan was received in September 2017. The isolate typed as H58 S. Typhi and had the following resistance determinants: bla_{CTX-M -15}, bla_TEM-1, gyrA [83:S-F], qnrS-1, aac(6’)-Iy, aph(6)-Id, strB, strA, dfrA-7, sul2, sul-1 and cat-A. The CTX-M-15 ESBL gene was associated with an ISEcp1 transposable element (4,9).

Antimicrobial susceptibility testing (AST) confirmed the isolate to be resistant to ceftriaxone (MIC >32 mg/L), ceftazidime (>32 mg/L), ciprofloxacin (2 mg/L), and co-trimoxazole (>32 mg/L). It was susceptible to meropenem (0.06 mg/L), ertapenem (0.015 mg/L), chloramphenicol (2 mg/L), colistin (0.5 mg/L), azithromycin (8 mg/L; no EUCAST breakpoint, but isolates with MICs ≤16 mg/L are regarded as ‘wild-type’), and with a tetracycline MIC <2 mg/L (no EUCAST breakpoint). Supplemental testing confirmed presence of an ESBL and the absence of AmpC.

Action advised

1. Diagnostic laboratories should screen all presumptive isolates of S. Typhi and S. Paratyphi for resistance to third-generation cephalosporins with discs or gradient strips using EUCAST methodology. Testing ceftriaxone or cefotaxime should be sufficient to detect CTX-M-15, which is the dominant ESBL found in the species.
2. Diagnostic laboratories should continue to refer presumptive isolates of S. Typhi and S. Paratyphi to PHE’s GBRU to enable continuous surveillance of genetic resistance markers. This is free of charge to the NHS laboratories in England and Wales.
3. NHS laboratories in Scotland should, instead, forward isolates to the Scottish Salmonella Reference Service, based in the Scottish Microbiology Reference Laboratories, Glasgow.
4. Consideration should be given to starting empirical combination therapy with ceftriaxone plus azithromycin for cases of complicated enteric fever until AST results are available, particularly if there are epidemiological links with areas where cephalosporin resistance has been well recognised.
5. Targeted treatment in a case with confirmed third-generation cephalosporin resistance should include combination treatment with meropenem (1 g 8 hourly IV in adults) plus oral azithromycin (up to 20 mg/kg/day PO) [10]. As there are historic reports of clinical efficacy with temocillin for treatment of enteric fever [11], consideration might be given to a combination of temocillin plus azithromycin.

For further information please contact Dr Gauri Godbole, PHE Gastrointestinal Bacteria Reference Unit: gauri.godbole@phe.gov.uk

Additional information for NHS Scotland

For Scottish diagnostic laboratories, all S. Typhi and S. Paratyphi A isolates should be phenotypically tested for ESBL production locally. Then, as per current normal practice, all isolates shold be submitted to the Scottish Salmonella Reference Laboratory, Glasgow.

As part of the new processing of these isolates by Whole Genome Sequencing at the Reference Laboratory, any diagnostic laboratory-detected phenotypic ESBL-positive isolates can be confirmed by Reference Laboratory sequencing methodology.

Additional information for Northern Ireland

For HSCNI diagnostic laboratories, all S. Typhi and S. Paratyphi A isolates should be phenotypically tested for ESBL production locally. If suggestive of ESBL production, isolates should be sent to PHE’s GBRU via the Belfast Health and Social Care Trust for Category A postage.

References

1. PHE (2017). Enteric fever (typhoid and paratyphoid) England, Wales and Northern Ireland: 2016.
2. Wong VK, Baker S, Connor TR, Pickard D, Page AJ, Dave J, et al (2016). An extended genotyping framework for Salmonella enterica serovar Typhi, the cause of human typhoid. Nature Communications 7: 12827.
3. Threlfall EJ, de Pinna E, Day M, Lawrence J, Jones J (2008). Alternatives to ciprofloxacin use for enteric fever, United Kingdom. Emerg Infect Dis 14: 860-1.
4. Rotimi VO, Jamal W, Pal T, Sovenned A, Albert MJ (2008). Emergence of CTX-M-15 type extended-spectrum beta-lactamase-producing Salmonella spp. in Kuwait and the United Arab Emirates. J Med Microbiol 57: 881-6.
5. Kleine CE, Schlabe S, Hischebeth GTR, Molitor E, Pfeifer Y, Wasmuth JC, et al (2017). Successful therapy of a multi-resistant ESBL (SHV-12)-producing and fluoroquinolone-resistant Salmonella enterica subsp. enterica serovar Typhi infection using combination therapy of meropenem and fosfomycin. Clin Infect Dis 65:1754-6.
6. Mawatari M, Kato Y, Hayakawa K, Morita M, Yamada K, Mezaki K, et al (2013). Salmonella enterica serotype Paratyphi A carrying CTX-M-15 type extended-spectrum beta-lactamase isolated from a Japanese traveller returning from India, Japan. Eur Surveill 18(46) (July).
7. Phoba M-F, Barbé B, Lunguya O, Masendu L, Lulengwa D, Dougan G, et al (2017). Salmonella enterica serovar Typhi producing CTX-M-15 extended spectrum beta-lactamase in the Democratic Republic of the Congo. Clin Infect Dis. 65:1229-31.
8. Mohammad Tahir Yousafzai FN, Sadia Shakoor, Khalid Saleem, Momin Kazi, Denise Garett, Stephen Luby (2017). Outbreak investigation of ceftriaxone resistant S. Typhi in Hyderabad, Pakistan. 10th International Conference on Typhoid and other Invasive Salmonellosis. (4-6 April.)
9. BLAST National Centre for Biotechnology Information.
10. Dolecek C, Phi La TT, Rang NN, Phuong LT, Vinh H, Tuan PQ, et al (2008). A multi-center randomised controlled trial of gatifloxacin versus azithromycin for the treatment of uncomplicated typhoid fever in children and adults in Vietnam. PLoS ONE 3: e2188.
11. Tanphaichitra D, Kanjanapanjapol S, Srimuang S, Robinson OP (1985). Use of temocillin in typhoid fever, hepatobiliary disease and other infections. Drugs 29 suppl 5: 201-5.

Infection reports in this issue of HPR and elsewhere on the PHE website

Vaccine coverage reports

• Quarterly vaccination coverage statistics for children aged up to five years in the UK (COVER programme): July to September 2017
• HPV vaccination coverage in adolescent females in England: 2016/17
• Herpes zoster (shingles) immunisation programme: September 2016 to August 2017

Vaccine-preventable disease reports

• Laboratory confirmed cases of invasive meningococcal infection (England): July to September 2017
• Laboratory confirmed cases of pertussis (England): July to September 2017

Bacteraemia report

• Laboratory surveillance of uncommon pathogens causing bacteraemia in England, Wales and Northern Ireland: 2016.