Speech to Parliamentary Scientific Committee

Portcullis House, London

22 January 2008

Professor Hugh Pennington, President MRSA Action UK

MRSA, New, Yet Old

When asked to become President of MRSA Action UK I accepted without hesitation. The decision had nothing to do with my own status as an MSSA carrier (I have been one since my medical student days) but was due to the privilege of becoming formally associated with an organisation typical of the best British special interest groups - ones which exert beneficial effects on policy far outweighing their sparse resources - and because of its aim, which is to prevent the preventable.

It is hard to think of a better example of Hegel's principle - " what experience and history teach is this - that people and governments never have learned anything from history, or acted on principles deduced from it" - than MRSA. Its history also exemplifies another principle - that the relationship between science, practice, and policy is hardly ever simple or straightforward. Perhaps most disappointing of all, is that although the story of MRSA science has been one dominated by British discoveries, we currently languish at the bottom of the international league of success in controlling it in our hospitals.

MRSA stands for methicillin  resistant Staphylococcus aureus. Medical bacteriology became a science in the late nineteenth century, It was dominated by  Germans. They discovered most of the important organisms. The big exception was S. aureus, which was first identified and named in 1880 by Alexander Ogston, a surgeon at Aberdeen Royal Infirmary. Ogston was an enthusiastic proponent of the antiseptic methods developed by Joseph Lister in Glasgow in the late 1860s and early 1870s. My estimate is that of all the preventive measures introduced against the staphylococcus, its impact has never since been matched. Before its introduction the mortality rate of "cold" - non-traumatic - orthopaedic operations done by the most experienced surgeons was about 9%. Wound infection was virtually universal. In 1884 William MacEwen reported his series of 804 antiseptic limb-bone operations at Glasgow Royal Infirmary. Only 8 became infected, and only 3 died, one of pneumonia, one of tuberculosis, and one of diphtheria.

Lister's carbolic worked against the staphylococcus.  But it was toxic. Not only did it wreck the hands, it was absorbed through the skin and damaged the kidneys. When a surgeon started to pass black urine it was time for him to take a holiday. Alternative antiseptics came in. Research done in the 1890s showed that hand hygiene with alcohol worked well against S. aureus. Its therapeutic index - comparison of its staphylococcal killing power against its ability to cause dermatitis - was good. It was widely adopted. But rubber gloves were introduced and its use fell away.

In the 1930s the standard multi-volume British bacteriology textbook was the Medical Research Council's System of Bacteriology. Alexander Fleming wrote the chapter on Staphylococcus.Its preparation required him to do some research. It led to the discovery of penicillin in 1928. And the first patient to be treated in its first clinical trial by Howard Florey and his team at Oxford had a staphylococcal infection. Albert Alexander was a policeman. An infection of his face from a rose thorn scratch had spread to his lungs and shoulder. He first received penicillin on 12 February 1941, and improved dramatically. But even with the recycling of penicillin from his urine, the supply ran out, and he relapsed, dying of staphylococcal septicaemia on 15 March.

Fleming discovered the first naturally-occurring penicillin-resistant staphylococci in 1942. Then they were uncommon. However, important research by the bacteriologist Mary Barber at the Hammersmith Hospital in London showed that not only  did they increase proportionately soon after the introduction of penicillin ( from 12.5% in April-November 1946 to 38% by February-June 1947) but that the rise was not caused by the organisms becoming resistant while patients were being treated. It was due to the spread of a resistant strain in the hospital. Such strains made penicillinase, a penicillin-destroying enzyme. In response a penicillin derivative resistant to the enzyme, methicillin, was developed by the Beecham Research Laboratories in Surrey. It was thought that penicillinase production was the only way for a staphylococcus to become resistant to penicillin, so resistance to methicillin would not develop. But within a year such strains appeared, at Guildford. The first MRSA outbreak occurred two years later, in 1963, at Queen Mary's Hospital for Children at Carshalton. Eight wards were affected; thirty seven patients were infected and one died. Gordon Stewart was its bacteriologist at the time. He closed his account of the outbreak with prescient words: " Lastly, and most important, patients harbouring these rare strains must be isolated, vigorously treated, and preferably should be sent out of hospital as soon as possible." The organism continued to cause problems, however, and bacteriologists to warn. A 1985 account of a two-year outbreak at the Royal Free Hospital concluded "Several authors have reported failure to contain MRSA infection without an isolation unit;: hospitals without such facilities or, as at this hospital, unable to finance the staffing of a unit, may find that this epidemic MRSA will pose a considerable threat to their clinical practice."

MRSA are antibiotic resistant because they have acquired a gene, mec A, that allows them to build cell walls (a process blocked by penicillin antibiotics) in the presence of methicillin. At least eleven different MRSA have evolved independently in different parts of the world. A turning point for the UK was the appearance of two epidemic strains, EMRSA 15 and 16. EMRSA 16 was first seen in Kettering in 1992.It spread quickly. In 1994 it was causing problems in 21 London hospitals. By 2000 it was common throughout Britain, and was spreading internationally. The voluntary reports to the Health Protection Agency (and its predecessor, the Public Health Laboratory Service) of staphylococcal bloodstream infections in England, Wales and Northern Ireland are informative. In 1992 116 isolates were resistant and 4462 sensitive. In 2003, 6085 were resistant and 8560 sensitive. A simple way of monitoring the scale of the problem is to measure the ratio of the two. It is reasonably accurate because it automatically takes account of changes in hospital practice that affect staphylococcal infections as a whole. Resistant strains became commoner. By 1999 they accounted for 40% of S.aureus isolates. It is still the same today. But in the Netherlands it is about 1%. Why is this?

The Dutch and Scandinavian success in controlling MRSA has been due to their policy of "search and destroy". Key elements are the treatment of MRSA carriers  in single rooms with barrier precautions, the screening and precautionary isolation of high-risk patients (eg those from endemic places like the UK) until negative test results come, the vigorous investigation of all patients and healthcare workers in a ward if any patient becomes a carrier, and the closure of a ward to new patients if there is evidence of the transmission of infection. Hand disinfection is not mentioned in Dutch guidelines because it is already being done assiduously. Using mathematical modelling the Dutch have concluded that their success has been due to their combined approach - no single measure will work on its own - and that if applied to the UK it would bring our MRSA levels to theirs within 6 to 12 years.

During the first three decades of their evolution UK MRSA caused local outbreaks. A degree of complacency developed; "search and destroy" was deemed to be too expensive. When EMRSA 15 and 16 appeared they were not taken seriously enough. Old habits die hard; policy makers have only just begun to give isolation the attention it needs.

Staphylococci grow well on agar plates. But saying that exhausts virtually all that is straightforward about them. All attempts to develop vaccines have failed. We do not know why some people carry S.aureus for life and others not, neither do we understand why EMRSA are such successful nosocomial pathogens. For the overwhelming majority of patients infected in hospital, the precise route of transmission is never established. Is aerial transmission important? We do not know. Will the new community MRSA strains establish themselves in hospitals? We can only guess.

Some complain that MRSA have become political. Their analysis is right, but their judgment wrong. All infections have a political dimension. Consider foot and mouth disease. Even before it ceased to be endemic in Britain, in 1889, the Government had a vigorous stamping out policy - search and destroy. It has spent billions. If only we had had the same for MRSA!

(c) Professor Hugh Pennington

January 22 2008