Towards the end of June this year there was a higher than normal number of notifications of E. coli O157 to Public Health England (PHE) which on further investigation were shown to be predominantly a single strain of bacterium. Within a week PHE had declared a national outbreak. Genetic sequencing showed this strain of E. coli O157 was not related to the UK’s normal O157 strains but was similar to those found around the Mediterranean and therefore the conclusion was drawn that the outbreak strain had been imported into the UK.
 
As of last week there have been 160 cases in this outbreak, predominantly in three clusters in the South West, North West and South East of England. Sixty two cases have been admitted to hospital, 7 have developed haemolytic uraemic syndrome and 2 have died. There is an ongoing investigation to find the source of this bacterium which is thought to be mixed salad leaves supplied to the wholesale catering industry; the source has not yet been identified but the focus is on rocket (posh greens).

​The patient was in her early 20s and came to see her GP complaining of a sore throat, fever and pains in her neck. The GP examined the patient and found tender cervical lymphadenopathy and pustular tonsils. A diagnosis of tonsillitis was made and the patient was reassured that it was nothing serious whilst being given a course of Amoxicillin. Would you have given antibiotics and if so why?
 
The next day the patient rang the practice in a panic as she had a rapidly progressive rash. The GP was concerned about the significance of the rash and immediately arranged for the patient to be seen in the Emergency Department.
 
On arrival in hospital the patient did indeed have a wide spread erythematous rash and fever. Bloods were sent to the laboratory and she was started on IV Ceftriaxone as a precaution in case this was meningococcal sepsis. The blood results showed a high lymphocyte count, abnormal mononuclear cells and raised liver enzymes. 

​A very proud moment for Microbiology Nuts and Bolts, yesterday St George’s Medical School and the University of London recognised David Garner’s contribution to delivering medical student teaching during their Graduation Ceremony at the Barbican, London. It was made all the more special knowing that it was the students themselves who voted for him to receive the award. Thank you to the Year of 2016 and we welcome you and all other new doctors to your first roles on the wards next month. 

A 19 year old woman was admitted with a high fever, low blood pressure and confusion. Her parents reported that she had been complaining about diarrhoea earlier in the day. She was started on IV Cefotaxime for possible meningitis whilst awaiting a lumbar puncture. Fluids were started and she was transferred to the Critical Care department for ongoing supportive treatment. Blood tests showed her to be in renal failure with a low white blood cell count. A lumbar puncture was done and her CSF was completely normal.
 
The patient appeared to be septic but there was no obvious focus of infection. She continued to deteriorate and so she was discussed with the Duty Microbiologist and a provisional diagnosis of toxic shock syndrome was made and IV Clindamycin was added to her treatment. The Critical Care team were advised to check for the presence of any skin or soft tissue focus of infection as well as ensure there was no retained tampon.

​Although no soft tissue focus was found a tampon was present and it was removed. At the time there was noted to be a purulent vaginal discharge and vulvovaginitis.

Following removal of the tampon and the addition of Clindamycin the patient slowly began to improve. Culture of the pus from the vagina grew a Staphylococcus aureus sensitive to Clindamycin and so the Cefotaxime was stopped. The patient continued to improve.
 
So what is toxic shock syndrome and why is tampon use relevant? 
Toxic shock syndrome (TSS) is a severe infection with a high mortality even when treated appropriately; without treatment it is almost always fatal.
 
TSS is the combination of fever, rash and shock due to toxins produced by certain strains of bacteria, most commonly Group A Beta-haemolytic Streptococcus and Staphylococcus aureus. The mortality from Group A Beta-haemolytic Streptococcus TSS is approximately 30% whereas for Staphylococcus aureus it is normally much less at around 6%.
 
The source of bacteria causing TSS can sometimes be difficult to find and the site of infection may not be apparent; even small amounts of bacteria can produce a lot of toxins. Toxic shock syndrome has classically been associated with the use of tampons, which become colonised with Staphylococcus aureus releasing toxins into the blood, although this has become a lot less common (90% reduction) since the withdrawal of the specific brands of tampons implicated in the original outbreaks back in the early 1980s. Having said this 50% of cases of Staphylococcal TSS are still related to tampon use.
 
Not every Group A Beta-haemolytic Streptococcus or Staphylococcus aureus is capable of causing TSS. In order to cause TSS the bacteria have to produce exotoxins which act as superantigens. These superantigens bypass the normal immune response to antigens and cause lots of T cells to release massive amounts of inflammatory cytokines which then cause capillaries to leak and damage tissues.
 
How does TSS present?
TSS is a clinical diagnosis; there is no specific “laboratory test” for TSS. TSS is confirmed by the presence of the 5 clinical features below; a probable case is suggested by the presence of 4 out of the 5 features. It is still useful to send infected pus or tissue to the laboratory for culture to try and identify the causative bacterium and guide further treatment and public health control measures. In cases of suspected Staphylococcal TSS in women it is also worth sending genital swabs to try and isolate Staphylococcus aureus. Any suspected bacteria can be tested at reference laboratories for the ability to produce exotoxins and cause TSS although this takes time and is not helpful in the initial management of the patient.
 
Clinical Features

• Fever >39°C
• Hypotension (often unresponsive to fluids)
• Erythroderma (resembling sun burn)
• 3 organ failure from the following:
  • Renal (acute renal failure)
  • Gastrointestinal (diarrhoea)
  • Neurological (encephalopathy)
  • Cardiac (decreased cardiac output)
  • Hepatic (liver failure)
  • Haematogenous (anaemia, thrombocytopaenia)
• Desquamation 1-2 weeks after illness

 
Many patients with Group A Beta-haemolytic Streptococcal TSS have severe soft tissue infection where pain is more than the physical findings would suggest, and often follows minor trauma at the site. It is thought that the minor trauma occurs in someone who happens to have a brief bacteraemia with the bacterium which settles in the soft tissue due to the localised trauma and then sets up the severe infection.
 
What is the treatment of TSS?
The mainstay of treatment of TSS is supportive care for shock and urgent surgical assessment with a view to surgical resection if the source of infection is apparent, especially when infection follows minor trauma. If a tampon is present in the genital tract this should be removed.
 
Antibiotics are used to target the main causative bacteria, Group A Beta-haemolytic Streptococcus and Staphylococcus aureus. The duration of treatment depends on how quickly the patient responds but rarely needs to be more than 10-14 days.

Both Clindamycin and Linezolid have the benefit of not only damaging the causative bacteria but also inhibiting protein synthesis thereby reducing the amount of toxin the bacterium produces. IV Benzylpenicillin is usually added if Group A Beta-haemolytic Streptococcus is the most likely pathogen and the patient is not allergic to Beta-lactams.
 
Many Microbiologists (including myself) would also consider using IV Immunoglobulin (IVIg) 2g/kg PLUS a further dose 72 hours after if the patient is not improving. The use of IVIg for toxin mediated disease like TSS is an accepted indication as covered in the Clinical Guidelines for Immunoglobulin Use 2nd Edition 2008 produced by the Department of Health UK. IVIg binds the bacterial toxin in the blood stream and helps to prevent it causing damage. In my experience IVIg works very well and often helps stabilise the patient and bring the infection under control much more quickly.
 
Control of TSS in the community
Group A Beta-haemolytic Streptococcus is highly contagious and outbreaks occur in households, schools, nursing homes and other institutions. As a result TSS is a notifiable disease in the UK and there are published guidelines on the investigation and management of contacts of cases of severe Group A Beta-haemolytic Streptococcus infections.
 
There is no specific guideline for Staphylococcal TSS but it is good practice to let the public health team know about cases in case there is a localised outbreak going on. Anyone who either has TSS due to Staphylococcus aureus or who is a household contact found to be a nasal carrier of the same strain of bacteria should be given topical mupirocin ointment to eradicate the carrier state.
 
About 10 days after our patient was admitted the skin on her hands and feet started to peel and the diagnosis of TSS was finally confirmed. Further analysis of the Staphylococcus aureus isolated from the patient confirmed the ability to produce an exotoxin. The patient eventually made a full recovery and went home. Having been decolonised with Mupirocin and Clindamycin there is no particular need for her to avoid future use of tampons although many such patients choose not to “just in case”. If tampons are used they should be of the lowest absorbency and changed regularly, at least 8 hourly or 3 times a day.