278 Discussion 



Barber: I tried that for a short time, but I tliink again one would 

 have to do this over a very long period. I don't think anyone has 

 carried it on for long enough. 



Westergaard: A clinical point came up in discussion with Danish 

 physicians; they pointed out that when penicillin was made available 

 just after the war it was exceedingly expensive, and there was a tendency 

 to use the lowest possible doses, and this may be one reason why we have 

 built up resistance so fast. If such new drugs or antibiotics are being 

 used, they should preferably be used in the highest possible concentra- 

 tions to avoid a repetition of this. 



Pollock: I think clinicians everywhere would agree about this. 



Knox: Not in the case of streptomycin. 



Westergaard: No, in the case of streptomycin it will not help. 



Hughes: From the clinical point of view, when Fleming was first testing 

 penicillin sensitivity, in 1927-28, already at St. Mary's Hospital the 

 outpatients were carrying a small percentage of resistant strains. As far 

 as I know, when we first had experimental supplies available the position 

 was much the same. But now we have 100 per cent resistant strains in 

 infections arising in the hospital, and in the carriers among our nursing 

 staff. The persistence of the resistant strains in the individual is going 

 to be a long-term affair. Valerie Hurst started a study of babies which 

 R. E. O. Williams and I are continuing. The position is that all babies 

 born in our wards today go out at the end of a fortnight carrying 

 resistant staphylococci. The infection takes place within the first 24 

 hours. Only 40-60 per cent of babies born in their own homes ever 

 carry staphylococci before their schooldays, and of those only a small 

 proportion carry the resistant type. It is quite clear that with the high 

 numbers of children born in hospitals in these days, that we are infecting 

 our own population and are maintaining more or less permanent carriage ; 

 i.e. over a period of 4 or 5 years some are still carrying the identical phage 

 type and resistant strains that they were endowed with in their first 

 couple of days. 



Dr. Barber, have you tried to cut the labour of your work by using 

 mutagenic agents on your strains — X-rays or anything of that sort ? 



Barber: I have tried X-rays without success. 



Pontecorvo : Dr. Barber, you said that it is easy to get in vitro resistance 

 of the non-penicillinase type ; what is the clinical position ? Are resistants 

 from patients exclusively of the penicillinase type ? 



Barber: They are almost exclusively of the penicillinase type. One 

 reason is that the penicillin-tolerant type of organism, i.e. the resistant 

 but not penicillin-destroying one, is almost invariably a weak or nega- 

 tive coagulase producer, and shows all sorts of other characteristics 

 which give it less chance in the human body; it grows more slowly and 

 so on. 



Bishop: Are these mutants that you produce, by a prolonged period 

 of treatment with the drug, stable in the absence of the drug for any 

 long period? 



Barber: Yes, moderately long periods, several months. 



Bishop : The naturally produced ones must be very stable, if children 



