1. Case two: Outbreak of a PVL producing MRSA
Dr Mark Garvey, Principal Clinical Scientist in Microbiology
Associate Director of Infection Prevention and Control or

2. Overview MRSA Panton Valentine leukocidin (PVL) Case studies
PVL Outbreak
Conclusions

3. Staphylococcus aureus
Gram positive cocci
Frequently coloniser in humans – found in nose of up to 30% of healthy individuals
Opportunistic pathogen:
Wide range of infections including skin and soft tissue infections (SSTI’s), bloodstream infection, pneumonia, endocarditis
Toxins – mediated infection such as Toxic shock syndrome

4. Meticillin-resistant (‘flucloxacillin-resistant’) Staphylococcus aureus (MRSA)
Contains resistance island called Staphylococcal chromosome cassette (SCC)
mec is the genetic element confers resistance to meticillin
mecA encodes for PBP2a; low affinity for meticillin and confers meticillin resistance on S. aureus (ie MRSA)
Six types of SCC harbouring different resistance determinants

5. Problem – route of transmission
The bugs themselves aren’t the problem
Its where they can get to that is
Healthcare is increasingly invasive and we are working with even more vulnerable patients as medical science progresses
MRSA seek and destroy i.e. screen and decolonise
Kiernan M IPS 2018

6. Panton Valentine Leukocidin (PVL)

7. Panton-Valentine Leukocidin
First described in 1894
Pore forming toxin
Leukotoxin produced by S. aureus
2 exoproteins (LukS & LukF)
SSTIs
Garvey MI et al., J Infect Prev 2017

8. PVL: epidemiology & risk factors
2-10% clinical S. aureus isolates are PVL positive
Predominantly associated with community S. aureus (MSSA & MRSA)
Modest disease burden in UK & rest of Europe currently compared with USA
Highly transmissible especially in community
Close contacts e.g. families, social groups, military, gyms.
Garvey MI et al., J Infect Prev 2017

9. UK epidemiology of PVL
UK PVL have been estimated to be carried in less than 2% of clinical isolates of MSSA.
Reference laboratories only receive a small number of selected isolates so this is likely to under estimate the true burden of the disease
In England, the majority of PVL-positive strains have been MSSA
Garvey MI et al., J Infect Prev 2017

10. Questions When to suspect a PVL?
How many do laboratory inhouse PVL testing?
How many send away for PVL testing?

11. When to suspect PVL? S. aureus (MSSA/MRSA) from a patient with:
Recurrent/multiple boils/abscess
Necrotising skin and soft tissue infection
Necrotising pneumonia
Antimicrobial susceptibility patterns are highly variable
Detection of PVL S. aureus infection depends on clinical suspicion of PVL-related syndrome
Especially if <40yrs
Garvey MI et al., J Infect Prev 2017

12. PVL Outbreak

13. Description of cases
Sept 14 – Jan 15: 4 patients acquired PVL MRSA, spa type t852, associated with an index case.
Index case
Admitted to a bay
Admission screen negative for MRSA
Garvey MI et al., J Infect Prev 2017
The index patient was admitted from another Trust for trauma surgery and spent two days on the outbreak ward. The patient had no previous history of admission to the Trust. A wound swab taken on admission
was positive for MRSA, the result being known after the patient was discharged.

14. Patient 1 Patient 1 was admitted on 2 separate occasions
First admission was in the same bay as index case
Patient 1 subsequently acquired MRSA in October 2014 (acquisition)
Garvey MI et al., J Infect Prev 2017
Patient 1 was admitted from another Trust following postoperative complications for a urological problem. Patient 1 also had a second admission to the ward soon after discharge, again for postoperative complications; this admission screen was positive for MRSA. Results of the admission screen were not available until after patient 1 was discharged. The patient had no previous admissions to the Trust.

15. Patient 2 Patient 2 admitted October 2014 for elective surgery
Acquired MRSA during second admission to Trust
During second admission was in same bay as patient 1
Garvey MI et al., J Infect Prev 2017
Patient 2 was admitted for an elective urological procedure. The patient was discharged for one day and readmitted as an emergency with query infection. The patient had multiple visits to UHB, the last visit to the
outbreak ward being one year previously. During implementation of the weekly MRSA screens this patient was found to be MRSA-positive.

16. Patient 3 Patient 3 complex surgical case admitted in Sept 2014
Found to be MRSA positive in December 2014 (acquisition)
MRSA bacteraemia January 2015
Garvey MI et al., J Infect Prev 2017
Patient 3 was admitted for an elective urological surgery. The patient was a longstanding patient with multiple co-morbidities with previous admissions to the Trust; this patient’s last visit to the outbreak ward was two years
previously. Patient 3 was identified as being positive as part of the weekly MRSA screens; however, the patient was also found to have a skin and soft-tissue infection which was the source of an MRSA bacteraemia.

17. Patient 4 Patient 4 admitted and discharged in December 2014
Patient 4 readmitted to Trust with community acquired pneumonia in February 2015 and was subsequently found to be MRSA positive that month (acquisition), however was on a different ward at the time
Typing revealed same strain as Urology outbreak
MRSA bacteraemia March 2015
Garvey MI et al., J Infect Prev 2017
Patient 4 was an elective urological admission to UHB. The patient had multiple admissions to UHB with the last admission to the outbreak ward being six months previously. Patient 4 was admitted to the outbreak
ward on day 95 for nine days; however, the patient missed the weekly MRSA screens during this period. On day 143, patient 4 was readmitted to the Trust onto a different ward due to a respiratory infection. An MRSA screen on this admission was positive for MRSA.
On examination of the cases all but one of the patients had surgery at UHB. Three of the patients had urological surgery; however, these were never in the same time period or in the same theatre so this was ruled out as a source of
cross-transmission. None of the patients had the same procedures. The only commonality was presence on the same ward during the period of the outbreak. Three of the patients showed signs of infection with MRSA: the index patient and patients 3 and 4. The index patient and patient 3 had skin and soft-tissue infections with MRSA which is indicative of PVL infection; however, patient 4 showed no PVL-like infection. Interestingly, patients 3 and 4 developed
an MRSA bacteriaemia. Patients 3 and 4 had prolonged hospital stay due to their MRSA infection/bacteraemia; they also had multiple co-morbidities and were aged >65 years compared with the other three patients. All the patients with infections were treated with antimicrobials.

18. Outbreak control What would you do if had this situation?
Would you screen staff?
How many undertake staff screening in outbreaks?
What would you do with wondering patients?

19. What was done?
After the second case an outbreak control team was formed
Included DIPC, Infection Control Nurses, ward medical and nursing staff, domestics, PHE, local commissioners, managerial nurses and Trust communications
Screening of all patients in ward to identify other possible cases of transmission
Staff screening with skin complaints e.g. eczema & boils – undertaken after 4th case no staff positives
Improving hand hygiene compliance
Garvey MI et al., J Infect Prev 2017

21. Other key interventions
Adherence to Trust MRSA screening procedures
Local infection prevention control training sessions
Improvement in antimicrobial prescribing
Warning when flucloxacillin is prescribed in MRSA positive patients via electronic prescribing system
Enhanced daily cleaning of bed spaces
Garvey MI et al., J Infect Prev 2017

22. Cleaning & environmental screening
Do you undertake environmental screening?
What do you screen?
When do you undertake?
What do you do with results?

23. What we did?
Before enhanced cleaning 16/ 40 sites were positive for MRSA
After enhanced cleaning 6/ 40 sites were positive for MRSA

24. Summary of PVL MRSA outbreak
Molecular typing & whole genome sequencing revealed all five strains were the same spa type t852, MLST CC 22, EMRSA 15 (ST22-IV)
Strain recognised in Indian sub continent as well as UK
Epidemiology suggests person to person transmission occurred
Garvey MI et al., J Infect Prev 2017

25. Final thoughts
Risk of spread of this clone in a healthcare setting is high
Potential pathogenicity of strain seemed to be high – associated in this outbreak with 2 MRSA bacteraemias
Molecular typing of MRSA acquisitions was essential to identify and help control outbreak
Stringent adherence to infection prevention and control practice in outbreaks is key to prevent further spread of healthcare associated infections

26. Thank you
Questions?

27. Supplementary - cleaning

28. Environmental survival of key pathogens on hospital surfaces
Survival times
S. aureus (including MRSA)
7 days to >12 months
Enterococcus spp. (including VRE)
5 days to >48 months
Acinetobacter spp.
3 days to 11 months
Clostridium difficile (spore form)
>5 months
Norovirus
8 hours to 28 days (temperature dependent)
Pseudomonas aeruginosa
6 hours to 16 months
Klebsiella spp.
2 hours to >30 months
Neisseria gonorrhoae
20 seconds
Hota B et al., Clin Infect Dis 2011
Kramer A et al., BMC Infect Dis 2007
Dancer SJ et al. Clin Micro Rev 2014

29. Vickery K et al., J Hosp Infect 2012

30. Contamination of the environment and transmission of pathogens in healthcare settings
Otter JA et al., ICHE 2011

31. Face touching S. aureus Adults touch their face 23 times per hour
44% mucous membrane
36% mouth
31% nose
27% eyes
6% all three
Mouth 4x
Nose 3x
Eye 3x
Kwok et al., AJIC 2015

32. Evidence for organism transfer in clinical environments
Inoculation of cauliflower mosaic virus DNA onto phone in an neonatal unit ICU cubicle
Virus spread to 58% of ward sampling sites within 7 days of inoculation
Spread to all five other cubicles
Door handles in other cubicles became positive first
Oelberg DG et al., Detection of pathogen transmission on neonatal nurseries using DNA markers as surrogate indicators pediatrics (2000)

33. Risk of transmission from previous room occupant
Meta analysis of all studies with evidence of transmission
Pooled acquisition odds for MRSA
1.89 for Gram positives (95% CI: )
Mitchell B et al., J Hosp Infect 2015

34. Transmission of organisms
Prospective cohort study in ICU
Successive occupiers of a room at risk from organisms from previous occupants
Quality audits showed 56% of rooms were not cleaned correctly
Audits were visual only, failure in room door handles (45%), monitor screens (27%) and bedside tables (16%)
Nseir et al., CMI 2010

35. Who does the cleaning of bed spaces in your hospital?

36. MRSA and environment
Doorknobs, bed rails, curtains, touchscreens, keyboards contaminated by hands which transmit to other surfaces
MRSA on door handles of 19% of rooms housing MRSA & 7% of door handles of non-MRSA rooms
Oie S et al., J Hosp Infect 2002
Staff often say ‘but I did not touch the patient’
42% of nurses contaminated gloves with MRSA with no direct contact but by touching objects in rooms of MRSA patients
Boyce JM et al., ICHE 1997

37. How many gloves?
Do you know the at our hospital 23 millions pairs of gloves are used
40% of gloves used in NHS is inappropriate!
Cost savings huge

38. Audit of equipment
Many items of clinical equipment do not receive appropriate cleaning attention
ATP score showed surfaces cleaned by professional cleaning staff was 64% lower than those by other staff (P=0.019)
Do we clean well?
Of 27 items cleaned by clinical staff, 89% failed
This is failure
Training
Allocation of responsibility
Anderson RE et al., J Hosp Infect 2011

39. Questions Do we clean well? Do Doctors clean well?
Or know about importance of cleaning?
What do you think are the most clean areas?
What about stethoscopes?
How do you measure cleaning?

40. Supplementary - final thoughts
Cleaning is a Science
Time to recognize it as such
New RCT-level research on the use of UV-C showed clinically significant reductions in infections
Anderson DJ et al., Lancet 2017