Select Committee on Science and Technology Seventh Report


APPENDIX 4

Visit to Public Health Laboratory Service Headquarters, Colindale, 23 October 1997

1.    Three members of the Sub-Committee, with staff, paid a second visit to PHLS at Colindale.

2.    Dr David Livermore showed us the Antibiotic Reference Unit, where isolates referred from hospitals are tested for susceptibility or resistance. Usually only unusual or problematic isolates are referred (except for TB and salmonella); hence the selectivity of surveillance. We were shown four different kinds of test.

      (i)  The pathogen is cultured on an agar plate, and discs of antibacterial agent are then placed on the plate. A clear circle round the disc indicates susceptibility. This test takes two days; it is cheap (10p per disc); it is only semi-quantitative.

      (ii)  The pathogen is cultured on an agar plate, then the antibacterial agent is introduced on a strip marked with an ascending scale of concentration. This test is more expensive (£1.50 per strip) and no faster, but quantifies the "minimum inhibitory concentration" (MIC).

      (iii)  The pathogen is cultured on a series of plates containing an antibacterial agent in increasing concentrations, to identify the MIC. We saw a computer-assisted technique for reading the plates, but this still relied heavily on human hand and eye.

      (iv)  The pathogen is tested for the presence of genes associated with resistance, using the polymerase chain reaction (PCR). This test is more expensive than tests (i)—(iii) (£5 per test), and only slightly faster; and each test will only show the presence or absence of a single known gene. We saw simple kits in use; automated systems are under commercial development.

3.    We asked about the application of digital imaging to these tests; we were told that automation in microbiology is lagging behind other laboratory disciplines.

4.    Dr Barry Cookson showed us the Laboratory of Hospital Infection, and discussed his survey of infection control teams and MRSA in 1995. He noted that antibiotic policies are best informed by setting information about local prescribing patterns against information about local resistance patterns: paradoxically, in hospitals, microbiological information tends to be good while prescribing information tends to be poor, while in general practice the situation is reversed. He found only three hospitals where antibiotics policies were firmly based on the findings of local surveillance; and he pointed to King's College Hospital as an unusual example of success in using local infection data to negotiate for more resources for infection control. In general practice, PHLS aims to set up a network of 50 sentinel practices; but it is hard to persuade a GP to devote time and money to testing, until empirical treatment has been tried and failed.

5.    Dr Cookson mentioned that, on a surgical ward, the rate of patients colonised with SA who develop infection may be one in four. He commented on the very low incidence of MRSA in the Netherlands: infection control is stringent; and, because of the low incidence, stringent control is affordable. He also commented on the British National Formulary: much good information, but presented in an "unfriendly" fashion. He noted the particular difficulty, in surveillance of MRSA, of establishing the source of infection.

6.    Dr Bernard Rowe showed us the Laboratory of Enteric Pathogens. This is the national reference laboratory for food-borne pathogens, and is linked to other reference laboratories in Europe via ENTERNET, funded by the EU; it is also a WHO Collaborating Centre for resistant strains. The Laboratory receives 95 per cent of all human salmonellas isolated in the UK (except Scotland) and the Republic of Ireland, amounting to 30,000 isolates per year; it receives another 20,000 isolates per year of E. coli and other pathogens; it tests up to 300 isolates per day, and has a database going back 30 years. (Salmonella in animals is notifiable to the Central Veterinary Laboratory under the Zoonoses Regulations.)

7.    Dr Rowe insisted that the problem of resistant salmonella was due to the use of antimicrobials in animal husbandry as prophylactics (treating healthy animals) or "metaphylactics" (treating healthy animals which have been exposed to disease). Resistance in salmonella does not normally threaten the individual patient, because in most cases recovery takes place without treatment; but it increases the survival and spread of salmonella in animals and therefore the overall level of human food poisoning. There was no suggestion that genuinely sick animals should not be treated; and, since the Swann Report of 1969, the use as animal growth-promoters of antibiotics used, or related to those used, in human medicine has been prohibited in the UK.

8.    We heard about the case of apramycin, a veterinary antibiotic for calves. It is now known that use of apramycin gives rise to resistance to gentamicin, an important clinical antibiotic. Apparently, the industry was aware of this, but waited until it was established by published research before voluntarily withdrawing apramycin.

9.    We also heard about the case of enrofloxacin, licensed by MAFF for animal use in 1993, in the face of scientific advice that it would give rise to resistance to ciprofloxacin. Since 1994, Salmonella typhimurium DT 104 has acquired chromosomal resistance to ciprofloxacin. It was suggested that this was a case of "agency capture", and that an independent Food Standards Agency might have acted differently.

10.    Dr John Watson told us about the Communicable Disease Surveillance Centre, of whose respiratory diseases group he is the head. CDSC has recently taken over from OPCS the receipt of statutory notifications of infectious diseases. Dr Watson explained the dual purpose of surveillance: to advise individual doctors how to treat individual cases or groups of cases; and to inform general treatment guidelines.

11.    Dr Watson spoke mostly about TB. UK surveillance of TB is comprehensive, and co-ordinated since 1993 by "MYCOBNET". A detailed survey is conducted every 5 years. Compared with salmonella, TB produces fewer isolates (15,000 in 4 years, compared with 30,000 in one); and isolates seen by the reference laboratory represent a much higher proportion of all cases. (In TB 60 per cent of cases are identified microbiologically, the rest clinically or by X-ray; in salmonella only about one per cent of cases are identified at all.) In the UK, TB resistance to isoniazid is stable at 6 per cent, slightly lower than in the USA; resistance to isoniazid and rifampicin ("multi-drug resistance", MDR) is low (1-2 per cent) but clearly rising.


 
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