Select Committee on Science and Technology Seventh Report


Visit to Public Health Laboratory Service Headquarters, Colindale, 22 July 1997

1.    Six members of the Sub-Committee, with staff, met at the headquarters of the Public Health Laboratory Service (PHLS) in Colindale, for informal briefing on PHLS's work on infections resistant to antibiotics.

2.    Professor Brian Duerden, Deputy Director, introduced PHLS. PHLS is funded by the Department of Health and the Welsh Office to provide microbiology and epidemiology services in England and Wales. It has two central facilities in Colindale, the Central Public Health Laboratory (CPHL—microbiology) and the Communicable Diseases Surveillance Centre (CDSC—epidemiology), and 48 Public Health Laboratories at NHS hospitals around the country. There are Reference Laboratories at CPHL, and some of the PHLs have Reference Units for particular infections. PHLS has close contact with the many NHS clinical microbiology laboratories which are not PHLs, and with the corresponding services in Scotland, Northern Ireland and the Irish Republic.

3.    PHLS can track the micro-organisms causing disease and monitor their resistance to antimicrobial agents in three ways:

      (i)  general surveillance: all laboratories regularly report all cases of specified infections to the centre;

      (ii)  Reference Laboratories receive micro-organisms and data for more detailed investigations; they may in turn rely on a network of "sentinel laboratories" for specific surveillance;

      (iii)  special "snapshot" surveys of limited duration, organised from the centre.

4.    These processes are not without problems. First, they depend on voluntary reporting; PHLS would like to see legislation for mandatory reporting. Secondly, they do not provide "denominator" data: i.e. how reported cases compare with the situation in the population at large. Thirdly, they are skewed by the tendency for most Reference Laboratories (other than the Laboratory for Enteric Pathogens: see below) to see only "interesting" cases, including cases exhibiting resistance. Fourthly, they depend on different laboratories working to standards and definitions which are both reliable and compatible. All PHLS and NHS laboratories are regularly tested with blind samples sent round by NEQAS; the British Society for Antimicrobial Chemotherapy (BSAC) currently has a group working on standard methods for the UK (with PHLS input); and the EU and the USA have a task force on co-ordinated surveillance; but the situation remains far from perfect.

5.    Dr Barry Cookson, Director, Laboratory for Hospital Infection, CPHL, spoke about methicillin-resistant Staphylococcus aureus (MRSA). SA is present in the nose of one person in three (persistent in one in ten, otherwise transient), and is not usually resistant; but resistance develops rapidly, usually in the context of a hospital. SA colonises skin but usually cannot invade it unless there is a wound; if it does invade, and sepsis arises, it becomes serious. SA is spread by direct contact.

6.    "We are running out of antibiotics." In the 1970s MRSA in the UK was checked, by a combination of gentamicin and better infection control; but in the 1980s MRSA developed gentamicin-resistance. In the UK MRSA can still be treated with vancomycin and a number of other antibiotics. But in some parts of the world vancomycin may be the only effective antibiotic, and low-level vancomycin-resistant MRSA has emerged in Japan.

7.    MRSA prevalence varies widely between countries, regions, hospitals, and even individual wards. However two recent strains, EMRSA-15 and -16, have spread across the UK and crossed to Holland. EMRSA-16 can be virulent; it is the first strain with two super-antigens, and can cause chest infections in particular.

8.    Ways to control MRSA include infection control, policies to control use of antibiotics, and other factors such as staff to patient ratios; but no system is wholly reliable. Nurses are crucial, since they have most direct contact with patients. Any survey of MRSA in a hospital must take account of how many carriers brought it in with them. Many serious cases arise from auto-infection, e.g. in a patient already carrying MRSA who undergoes surgery and whose lesions are then invaded as they heal.

9.    Dr David Livermore, Head, Antibiotic Reference Unit, CPHL (from 1st September 1997), described the work of the ARU: it tests "difficult" organisms for susceptibility or resistance to antibiotics, and checks surprising results from other laboratories; it monitors and researches resistant strains, and provides advice; and it supplies strains for use by NEQAS.

10.    ARU is trying to move from snapshot surveys, which are resource-intensive, to continuous local monitoring. As noted above, this depends on quality assurance (QA); susceptibility-testing in the UK is much less uniform than in the USA. BSAC and PHLS are currently testing new methods, and PHLS hope to have sentinel laboratories in place by the end of 1998.

11.    Dr Livermore mentioned penicillin-resistance in Streptococcus pneumoniae (= pneumococcus). In the UK resistance has risen to about 4 per cent. Iceland has suffered a dramatic rise, from one per cent in 1980 to 30 per cent in 1990. This is believed to have originated via travellers returning from Spain.

12.    Dr Livermore also mentioned resistance to vancomycin. Because of how this antibiotic works (it binds to a substrate rather than an enzyme), resistance was thought to be impossible. However in about 1987 there emerged the vancomycin-resistant enterococcus (VRE); how this came about is a mystery. As to why, it happened while avoparcin, a related antibiotic, was being used in Europe as an animal growth-promoter. This "can't have helped"; but the human and animal strains of enterococcus concerned are not the same; and the USA has more VRE than Europe, although avoparcin is not used there. Plasmid transfer of vancomycin-resistance to MRSA is now a "substantial risk", and has been demonstrated in the laboratory on the skin of a mouse; but the low-level VRSA found in Japan is not due to gene transfer and probably arose by mutation.

13.    Dr Bernard Rowe, Director, Laboratory for Enteric Pathogens, CPHL, regards resistance to antibiotics as "unwelcome but inevitable". He spoke about salmonella, of which there are about 2000 serotypes, causing typhoid, paratyphoid and enterocolitis, most commonly due to food poisoning.

14.    Since 1989, Salmonella typhi has acquired resistance to chloramphenicol; the incidence is now around 30 per cent. Resistance emerged in India and Pakistan, and most cases found in the UK can be traced to infection in SE Asia.

15.    There are about 30,000 cases a year of human salmonella food-poisoning in England and Wales, mostly acquired by eating UK food. As the table shows, multi-drug resistance is now most common in S. typhimurium, the second most prevalent serotype in humans in the UK. A particularly worrying strain is S. typhimurium DT104, which is multi-resistant. This is the major cause of salmonellosis in cattle, sheep, pigs and poultry; it also infects humans, and its spectrum of resistance is widening. Dr Rowe attributes this to use of antibiotics in food animals. For instance, late in 1993 enrofloxacin was licensed for veterinary use; DT104 promptly acquired resistance to the very similar human antibiotic ciprofloxacin. It should be noted that, though highly resistant, DT104 is no more virulent for humans than other salmonellae, and in most cases antibiotics are not required.

16.    Dr Rowe believes that farmers are using antibiotics as a substitute for good hygiene and husbandry; in his view, the ban on use of human antibiotics as animal growth promoters, introduced after the Swann Report of 1969, should be extended to cover prophylaxis. (There is a grey area around "metaphylaxis": treatment of animals believed to be incubating disease.) He detects a recent change of heart on this issue in agribusiness.

Multi-drug resistance in Salmonella in England and Wales, 1990-96
Per cent of salmonellosis in humans 1996 MDR per cent 1990 MDR per cent 1996
S. enteritidis   63  0.8   0.6
S. typhimurium   19  18   90
S. virchow    4  11   19
S. hadar    2   2   56

MDR = Multi-drug resistant, i.e. to four or more antibiotics

17.    Dr Patrick Wall, Consultant Epidemiologist, CDSC, described ENTERNET, a project for international surveillance of food poisoning. ENTERNET, funded by the EU under BIOMED, involves EU member states and also Switzerland and Norway. It began as Salm-Net to monitor salmonellae, and has been extended to take in the antibiotic resistance of salmonellae and E. coli 0157. Participating laboratories commit themselves to acquire a minimum data set, and training in standard methods is provided by PHLS if required. Dr Wall gave striking examples of successful "detective work", identifying international outbreaks of food poisoning and tracing them to their source. Recently the food industry has become more involved with the PHLS in initiatives to improve the safety of food, and PHLS are now working with the supermarkets to develop codes of practice for food production and handling.

18.    Dr Francis Drobniewski, Mycobacterium Reference Unit, Dulwich PHL, spoke about multi-drug resistant tuberculosis (MDR-TB—defined as resistant to isoniazid and rifampicin). TB is responsible for more deaths worldwide than any other infectious disease (3m per year). The emergence of resistance is encouraged by failure of patients to complete antibiotic courses (typically 6 months or longer), by poor prescribing, and by the physiology of certain groups of patients, particularly people with AIDS, among whom MDR-TB causes 80-90 per cent mortality. There have been two recent outbreaks of MDR-TB among people with AIDS in London hospitals (Chelsea and Westminster 1995, St Thomas' 1996); these have given rise to expensive litigation, and a major programme to build negative-pressure isolation rooms. The WHO has set up a Global Surveillance System, involving 22 reference laboratories of which the MRU is one. The MRU has been appointed the WHO European Region Co-ordinating Laboratory in recognition of its work in the field of drug resistance. There is a lot of MDR-TB in Eastern Europe; the eastward expansion of the EU is therefore a cause for concern.

19.    Dr J Watson, Consultant Epidemiologist, CDSC, described MYCOBNET, the UK surveillance system for TB set up in 1995. Data for the whole UK is collected at PHLS CDSC. In the UK as a whole MDR-TB is rare but increasing; it is concentrated in London, among people with AIDS, among recent immigrants (50 per cent of TB patients in the UK were born overseas; screening on or after arrival is impractical), among homeless people (who are particularly prone to non-compliance) and among people who have had TB before. MDR-TB is a global problem; but, as a recent WHO review has shown, data from around the world are patchy and inconsistent.

20.    Dr Ros Stanwell-Smith, Consultant Epidemiologist, CDSC, stressed the need not merely to "count corpses", but to improve the situation by changing behaviour. In her view, PHLS leads the world at the former but could do more of the latter. By way of example, she described how she provides surgeons with prompt and graphic feedback concerning resistant infection of surgical wounds. Hospital policies on use of antibiotics are effective only if staff can be persuaded to follow them; one good way to find out what is actually happening is to ask patients. Continuing education of medical staff is a key activity.

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