August 4, 1966

Vol. 275 No. 5
—_———

ety can be performed; decision on the donating of

eyes or other tissues that can restore lost functions _

to the living.
Whatever one may believe about a life after
death, one can scarcely deny that the memory left

in the thoughts of those still living provides-- a

means of achieving some part of it.
As penned by an unknown author:

We eannot know the ending of the path,

Nor quite accept its regimented bliss,

Devoutly planned for life’s long aftermath, -
Nor hold to any certain thing, save this:

They have not gone, nor can they dwell apart,
Who still have place within some living heart.

INFECTIOUS DRUG RESISTANCE

Since the inception of antibiotic therapy, the dra-

matic healing power of antimicrobial agents has
been threatened by the ever more insistent emer-
gence of antibiotic-resistant bacteria. Some of the
clinical! and biologic? problems posed by this phe-
nomenon have been summarized recently. Until
lately, the principal mechanism responsible for drug
resistance was thought to be spontaneous mutation
at a low rate to a particular drug resistance followed
by selection of resistant cells in the presence of the
drug.

Although threatening enough, this mechanism is

slow and cumbersome in comparison with infectious
multiple ‘drug resistance, a newly discovered
process that is intellectually fascinating and thera-
peutically frightening. First recognized in Japan in
1959, infectious multiple drug resistance is ‘a
process by which sets of genes determining resist-
ance to several unrelated antibiotics are transferred.
together from resistant to sensitive strains by cell-
to-cell contact.
: These genes are not located on the bacterial
chromosome, but on extrachromosomal genetic ele-
ments called R factors, which are composed of DNA
but replicate autonomously. R factors contain a re-
gion called RTF (resistance-transfer factor) that de-
termines infectivity and to which the separate
Hrug-resistance genes are attached. R factors resem-
ble viruses without coats, but they are also modified
sex factors since they mediate their own transfer
from cell to cell.

--Transfer occurs not only within species of the.
enteric bacteria but also between groups as diverse
4s shigella,
rella, serratia and the ubiquitous Escherichia coli,
which can serve as a reservoir. Indeed, Esch. coli is

of key importance in facilitating transfer of R factors
from one pathogen to another and from animals to |

humans.

An analogous situation exists in the staphylococci,
where antibiotic therapy has been notoriously. diffi-
cult, Genes for resistance to penicillin, erythromy-
cin, tetracycline, chloramphenicol and kanamycin

THE NEW ENGLAND JOURNAL OF MEDICINE OS 277

. 3, Daua, N.

salmonella, klebsiella, vibrio, pasteu-—

1
I

are carried on extrachromosomal particles called

_ plasmids.2 No RTF’s have been found, but plasmids

are transferred from cell to cell by phages. It may be

the rapid emergence of drug resistance among) the

staphylococci is related to the dissemination of
plasmids by phage transduction.

. The first report of R factors outside Japan came
froin Great Britain in 1962, and by 1965, extensive
surveys of their distribution as well as studies of
their fundamental properties had already been (car-
ried out there* as well as in Japan*; R factors thad
also been reported in other European countries jand
in Israel. However, the first clinical study of R ifac-
tors in the United States, by Kabins and Collen,
appears elsewhere in this issue of the Journal, jand
similar studies are in progress in Boston and New
York. These investigations stress the present wide-
spread occurrence of enteric bacteria harboring R
factors in this country. And they emphasize |the
threat to antibiotic therapy posed by these infec-
tious agents as well as the need to monitor their
spread. :

Both Japanese and British studies have correlated
the precipitous rise in frequency of R factors with
the increasing use of antibiotics not only in clinical
practice but also in the care and feeding of live-
stock. Antibiotics are now incorporated routinely in
livestock feeds, providing a constant selection pres-
sure on R factors that can be readily transferred to
man. It appears that unless drastic measures! are
taken very soon, physicians may find themselves
back in the preantibiotic Middle Ages in the treat-
ment of infectious diseases.

 

a REFERENCES

1, Gill, F. A., and Hook, E. W. Changing patterns of bactetial
resistance to antimicrobial agents. 4m. J. Med. 39:780-795, 1965.
2. Novick, R. P. Extrachromosomal inheritance of antibiotic resist-
ance in Staphylococcus aureus. Advances in Microbiol. (in press). :
Transmissible drug resistance in cpidemic strains of
Salmonella typhimurium, J. Hyy, 60:301-310, 1962.
4. Anderson, FE. §., and M. J. Lewis. Drug resistance and its transfer
in Salmonella typhimurium. Nature (London) 206:579-583, 1965,
5. Idem. Characterization of transfer factor associated with drug
resistance in Salmonella typhimurium. Nature (London) 208:843}849,
1965.

.6, Watanabe,’ T. Infective heredity of multiple drug resistande in -

bacteria. Bacteriol. Rev. 27:87-115, 1963.

POST-TRANSFUSION PURPURA

A sixty case of post-transfusion purpura is/| de-
scribed by Morrison and Mollison in this issue of
the Journal. The infrequency with which this disor-
der occurs places it rather low among the various
causes of postoperative thrombocytopenia, but some
of its implications deserve consideration. Morrison
and Mollison suggest that part of the antibody pro-
duced in response to the Pl4' platelet antigen
crossreacts with a structurally similar antigen on
autologous platelets, resulting in thrombocytopenia
and absorption from the circulation of the cross-
reacting antibody fraction and thereby rendering it