ANTIBIOTICS AND IATROGENIC DISEASE
By T. E. Roy, M.D.Department of Bacteriok’gy, the Hospital for Sick Children, and the Department of Bacteriology, the
University of Toronto
164 IATROGENIC DISEASE
ADDRESS: 555 University Avenue, Toronto, Ontario, Canada.
That the early feeding of egg white favors
the development of sensitization is widely
accepted. Some pediatricians-myself in-
cluded-feel that the too early introduction
of other solid foods also favors the develop-
ment of allergy.
The matter of adenoid-tonsillectomy in
the allergic child is one of frequent con-
cern. Some physicians feel that this opera-
tion should not be done in allergic children,
or in children of allergic parents, during
the height of the pollen season, as pollen
sensitization is then more likely to occur.
This may be a valid precaution, especially
in areas where the pollen count rises to
great heights. Not valid, in my opinion, is
the avoidance of needed adenoid-tonsillec-
tomy simply because the child is allergic-
on the theory the allergy may be flared up-
or the performance of the operation rou-
timely in allergic children. I believe the in-
dications for operation are the same in al-
lergic and non-allergic children; the reten-
lion of obstructing adenoid tissue is no more
logical in an allergic child than in one who
is nonallergic.
Finally, I would like to venture the view
that just as the retention of obstructive ade-
noid tissue is not logical, retention of a
pet to which a patient is sensitive is equally
illogical. There is no question, in my mind,
that by condoning such an arrangement we
physicians have permitted a great deal of
T HE A5SOCIATION of the term “iatrogenic
disease” with the clinical use of anti-
biotics poses many problems.
Physicians generally are familiar with
most of the untoward reactions that may
follow the use of antibiotics, and many ex-
asthma to persist in our patients. I have
seen much more harm done in this way
than is done psychologically by the removal
of the dog or cat from the homes of asth-
matic children. Our patients and their par-
ents are like ourselves in wanting to have
their cake and eat it, too. They would like
to get rid of asthma, while keeping the
cause of it. The attempt to do so is no more
successful in this situation than it is in oth-
ers like it. As physicians, it behooves us
not to become party to this type of self-
deception.
A discussion of this type would not be
complete without mentioning the potential
danger of giving horse serum or other serum
to sensitized patients. Such sensitization
may have been induced by previous ad-
ministration of serum or may have occurred
naturally, as in the case of a horse-sensitive
asthmatic. It is, therefore, necessary to ques-
tion the recipient about known sensitivity to
horses, as well as previous administration
of serum. Intradermal testing of such pa-
tients will reveal those in whom serum ad-
ministration may be dangerous. Foremost
among these is the horse-sensitive asthmatic
whose skin test is markedly positive. Ordi-
nary delayed serum sickness in a previously
untreated patient following therapeutic
doses of diphtheria or tetanus antitoxin is
an example of justifiably induced iatrogenic
disease.
cellent reviews of the subject are to be
found in the literature.14
One cannot divorce the undesirable ef-
fects of antibiotics from the beneficial ones
and, in this light, therapy becomes a calcu-
lated risk. If the probable discomforts or
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AMERICAN ACADEMY OF PEDIATRICS - PROCEEDINGS 165
dangers outweigh the probable advantages,
the cure may be worse than the disease, and
one is then dealing with true iatrogenic dis-
ease.
Probabilities of this kind cannot be as-
sessed easily with antibiotics because reac-
tions vary so much with type of drug, dose,
course, method of giving and in different
patients. Certain reports may be biased one
way or the other because of personal preju-
dices or unusual series. Some ill effects are
undoubtedly related to unwise, improper
or careless use of the drug; others are not.
So true incidences are not accurately
known. Reactions where antibiotics are be-
ing used needlessly for trivial infections or
for unnecessary prophybaxis are particularly
deplorable while risks are justified when
dealing with severe infections known to re-
spond. Evaluation is difficult with infections
of borderline severity and those prone to
exceptionally severe secondary bacterial
complications.
Reactions may be mild or severe; none is
negligible. Oxytetracycline, for example, is
considered to be relatively harmless. Still,
Jackson and his colleagues5 reported that
58% of patients with pneumonia showed un-
toward effects attributable to this antibiotic.
Most reactions were mild, but the antibiotic
was believed to have contributed in large
measure to the fatal outcome in five of the
seven patients who died in the 91 cases.
Tissue irritation and pain from injected
drug is often regarded as warranted tempo-
rary inconvenience to the patient. The in-
tensity of these reactions is usually less with
the soluble preparations such as potassium
pencillin and streptomycin than with re-
pository forms such as procaine penicillin,
benzathine penicillin C and suspension of
chboramphenicol. The pain from some, nota-
bly bacitracin and polymyxin B, is disguised
by mixing with procaine. There is often
neglect of the deleterious mental and physi-
cal effects that pain might have on sick in-
dividuals particularly if bong courses of
therapy are given.
Not all local irritant reactions are so
easily disregarded. Residual areas of degen-
eration and fibrosis in muscles have been
seen, but are seldom booked for. Sterile
abscesses have followed the injection of
preparations in oil. One report suggests,
maybe wrongly, that metastasizing fibro-
sarcomas arose in two patients at the sites
of intramuscular injections of penicillin in
sesame oil because of a carcinogenic effect
from the oil.6 Four papers71#{176} describe se-
vere neuritis in 15 infants and adults where
sensory losses and/or disabling motor pa-
ralyses followed intramuscular injections of
penicillin, streptomycin or tetracycline. The
disabilities persisted for months in some
cases and in a few seemed permanent. The
sciatic nerve was involved most frequently,
following intragluteal injections, but the
deltoid region was affected in five cases. In
some patients the immediate onset of symp-
toms suggested a more or less mechanical
type of injury; in others, notably after in-
jection of penicillin, the symptoms appeared
only after several days, leading to a belief
that the effect was rebated to the known
toxicity of penicillin for nerve tissue.’1 We
are aware of several unreported cases. This
complication is admittedly of infrequent
occurrence, but the consequences are dis-
astrous.
Toxicity to the central nervous system
evidenced by spasms, convulsions and coma
and by persisting paralyses in survivors, has
followed intrathecal injections of penicil-
un where the dose greatly exceeded 5,000
to 10,000 units.12 Somewhat similar reac-
tions have resulted from excessive intrathe-
cal doses of streptomycin.13 Febrile reac-
tions with pleocytosis in the spinal fluid
are often seen with usual intrathecal doses.
Most antibiotics can be given orally, thus
avoiding painful and other tissue reactions,
but with certain drugs this unfortunately
results in a higher incidence of various
gastrointestinal complications that are more
troublesome and significant than those after
parenteral use. The so-called “broad spec-
trum” drugs are the chief offenders, though
others may be involved, and these side ef-
fects are not always controllable by adjust-
ments of dosage. The mechanisms underly-
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166 IATROGENIC DISEASE
ing these complications are poorly under-
stood. Some of the effects are rebated to a
change in the normal bacterial flora of the
tract;14 others are not. Some may be due to
a direct irritation of the gut or to an upset
in the absorption or utilization of certain of
the vitamin B components.
Nausea or nausea and vomiting may be
very upsetting, occurring in 15% of Jackson’s
series5 with oxytetracycine. Various forms
of gbossitis and stomatitis are seen; these
occurred in 2% in Jackson’s series.
But far more troublesome, persistent and
sometimes serious are the disturbances of
the lower intestinal tract. The incidence of
anorectal-colonic side effects has been esti-
mated as about 20% in those taking broad
spectrum antibiotics, though much less with
other drugs. In Turell’s experience,15 about
57% of those showing upsets of the lower
gastrointestinal tract have perianal pruritis
alone, about 27% have diarrhea and 16%
have both pruritis and diarrhea.
Perianal pruritis is common, even early in
ambulatory patients, and though not fatal
some sufferers almost wish it were. It usu-
ally disappears within 1 or 2 weeks after
discontinuing the drug, but recovery may
be slow in as many as 30%. A few may re-
main problems for several months despite
active treatment with topical cortisone or
other therapies.16
Diarrheal upsets vary from bothersome,
loose, frequent stools to severe, toxic, dys-
enteric-like diseases. The mild upsets, seen
often with trivial treatment for trivial in-
fections, may appear early and persist for
weeks after discontinuing the drug; the Se-
vere types may be rapidly fatal. Dearing
and Heilman17 recorded 7 deaths in 29 such
severely affected patients; 4 in the 12 re-
ceiving antibiotics for preoperative prepa-
ration of the intestine and 3 in the 17 being
treated for various diseases. The fulminat-
ing, disastrous reactions are usually accom-
panied by partial or complete replacement
of the intestinal flora by staphybococci.18
Most such cases of entercolitis will respond
promptly if a suitable antibiotic capable of
suppressing the staphylococcus is given
early, but minor disability may persist for
a long time. Quick tentative confirmation of
the diagnosis of staphybococcal enterocolitis
is best made by a direct microscopic exami-
nation of a stained film of the feces. Re-
placement of the intestinal flora by staphy-
lococci can occur without giving rise to the
disease.
Toxicities directed systematically at spe-
cific organs are seen. Infrequently occur-
ring, miscellaneous, sometimes fatal reac-
tions have been reported for most antibi-
otics, such as damage to the liver by exces-
sive administration of chbortetracycline in-
tr2O or by novobiocin.21 These
are often difficult to assess because factors
related to dose or to the abnormal physio-
logic state of the patient may contribute
greatly to the effects in each individual.
Maybe the action of chboramphenicol on
the hematopoetic system should be men-
tioned here even though further experience
suggests that the dangers from this drug are
not as great as was once thought.2225
Some toxic manifestations, however, al-
most constantly accompany the parenterab
use of certain antibiotics. Included here are
the nephrotoxicity of 2627 the
transient nephrotoxicity from bacitracin,28
and the less marked renal effects from poly-
myxin B.29 These drugs should not be used
or cautiously used in patients with impaired
renal function. The ill-defined paresthesias,
vasomotor and psychic upsets accompany-
ing systemic administration of polymyxin
B29 are examples of neurotoxicities, but the
best known of the neurotoxic effects are the
vestibular and auditory disturbances after
administration of streptomycin and dihydro-
streptomycin.3#{176}33
The ill effects of the streptomycins vary
with the dose, the duration of therapy and
the ability of the kidney to excrete the
drug. From 44 to 96% of patients receiving
a 4-week course of streptomycin may
show vestibular disturbances depending on
whether 1 gm or 2 gm are given daily. This
is largely reversible, but residual defects
may remain in 50% of affected subjects.’�
With dihydrostreptomycin, auditory dis-
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AMERICAN ACADEMY OF PEDIATRICS - PROCEEDINGS 167
turbances become more prominent than
vestibular ones, and while these are slower
to appear they tend to be more irreversi-
ble. The drug, neomycin, is particularly
prone to give irreversible nerve deafness if
given parenterally,26 and many patients may
remain “stone” deaf. These dangers from
streptomycin are disturbing when one con-
siders how frequently fixed combinations of
streptomycin and penicillin are given to in-
fants and how hard it is to recognize early
impairment of the eighth nerve in the very
young.
Drug fever due to antibiotics is proba-
bby common, although seldom recognized
as such. Its significance may be that it is
often responsible for undue prolongation of
a course of therapy.
Reactions to antibiotics attributable to al-
lergic or hypersensitivity mechanisms are
distinct 2, 35 They are, perhaps, re-
bated more closely to iatrogenic disease
than most toxic manifestations of antibiotics
because they may follow the first dose of
the drug, even in individuals who are re-
ceiving such therapy for trivial reasons.
These reactions may take many forms : van-
ous rapid or delayed skin manifestations
running the gamut from simple erythemas
through eczematoid and urticarial eruptions
to exfoliative dermatitis; miscellaneous re-
actions; and anaphylactoid shock that is
often fatal. The risks involved are estimated
variously by different reporters, but the in-
cidences are highest with penicillin, much
lower with streptomycin and very bow with
the others. Novobiocin has produced a high
incidence of skin rashes, possibly allergic
in 637
After an injection of penicillin, it has been
said38 that some reaction may be expected
in 2.5% of children, in 5% of non-allergic
adults and in 15% of individuals with an al-
lergic diathesis. The risk from oral adminis-
tration is less, estimated at about 0.2%. Re-
action rates are said to be increasing by 1%
each year, possibly because of prior sensi-
tizing doses of penicillin. Reactions occur,
however, in individuals not known to have
received penicillin previously.
Anaphylactoid shock has been reported
most frequently after the use of penicillin;
all types of preparations have been involved
including the crystalline potassium salt. Von
Oettingen,1 from the literature published
prior to 1953, lists 127 such penicillin reac-
tions; 46 were fatal. Seventy-two of these
reactions with 24 fatalities were related to
procaine penicillin. There was little to im-
plicate the procaine part of the molecule,
but one might ask how often this relatively
insoluble salt might have been injected in-
advertently into a vein, a danger that has
been shown by Kagan to exist experi-
mentally.39 Almost all anaphybactoid reac-
tions occur after injection of penicillin, but
death has followed oral administration,40
and severe reactions have resulted from skin
contact.41
Estimates of the incidence of hypersensi-
tivity reactions to streptomycin have varied
from 0.4 to 5%. The commonest type is that
reported by the British Ministry of Health42
where skin reactions occurred in 3.5% of
nurses who were handling streptomycin.
Von Oettingen lists seven anaphybactoid
reactions to injected streptomycin with two
fatalities. There was one nonfatal reaction
to chbortetracycline.
There are many other untoward effects
of antibiotics that come about somewhat in-
directly but which may nevertheless be
classified properly as iatrogenic disease.
These are the so-called replacement infec-
tions or supeninfections. Most are related to
disturbances in the normal flora of the body
that follow antibiotic therapy.” On occa-
sions these added infections are of endoge-
nous source, but more frequently their
source is exogenous, and here another fac-
ton enters the picture of iatrogenic disease.
This factor is our inability to protect hos-
pitalized patients from the bacterial en-
vironment of the hospital, an environment
which, because of the very nature of hospi-
tabs, abounds in microorganisms of selected
virulence and of selected patterns of resist-
ance to antibiotics. Cross infection, the
widespread, often indiscriminate use of an-
tibiotics, the emergence of antibiotic-resist-
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168 IATROGENIC DISEASE
ant bacteria are all interrelated phenomena
that lead to the greater prevalence of super-
infections in hospitalized patients than in
those outside hospitals. The chief offenders
in these infections are staphylococci,�3 but
many other microorganisms including Can-
dida albicans may be involved.”
The true incidence of new infections
developing during antibiotic therapy and
as a more or less direct result of that
therapy is not lcnown. Weinstein and col-
leagues,�� in a careful study of 3,095 pa-
tients, estimated the frequency as 2.19%.
These occurred most commonly in children
and usually after giving broad spectrum
antibiotics. They often arose withn a few
days of starting therapy.
Antibiotics are often given for prophy-
laxis, the view being taken that this could
benefit the patient without having harmful
effects. This prophylaxis may be justified
where one is dealing with specific infections
such as those caused by hemolytic strepto-
cocci, or those due to meningococci, gono-
cocci and a few others. There is little justi-
fication for antibiotic prophylaxis against
the bacterial world at large. There is almost
no evidence to support antibiotic prophy-
baxis during most of the common viral in-
fections, including the common cold, atypi-
cal pneumonia, measles or poliomyelitis, nor
during bacterial infections such as pertussis,
or in clean elective surgery or where in-
dwelling catheters or drainage tubes are
used. Weinstein’s studies45 indicate that
such prophylaxis may in fact be harmful.
Of 130 patients with measles receiving anti-
biotics prophylactically, 30.4% developed
superimposed bacterial infections whereas
this occurred in only 14.9% of 298 cases not
receiving antibiotic. Complicating infections
developed in only 16% of 165 cases of bulbar
poliomyelitis not receiving drug, but in 53%
of 63 similar cases who were given antibi-
otics. This unwise prophylaxis does little
more than insure that the superimposed in-
fections will be resistant to the antibiotics
used.
The needless prescribing of antibiotics is
wasteful; it is dangerous because reactions
may occur or the patient may become spe-
cifically sensitized. At the army post in the
village of Igloo, South Dakota,�6 two enter-
prising doctors, Nolen and Dille, tried to
determine if an abuse had been made of
antibiotics among the residents of the vil-
lage. There were 763 civilians who had
lived in Igloo for a full 5 years, who had
been employed at the army post. Of these,
only 7.9% had never received antibiotics
during the 5-year period. Among those who
had taken antibiotics, the average number
of occasions each individual had been so
treated was 3.9 times. Fortunately the medi-
cal records of this group were available to
decide if antibiotic use had been warranted.
The two doctors were most gentlemanly,
even allowing a 1#{176}rise above normal in
temperature to be a valid reason for treat-
ment. Despite their generosity, they con-
cluded that antibiotic therapy had not been
indicated on 52.5% of occasions.
We don’t know how much good or how
much harm was done in Igloo, South Da-
kota, but we suspect that there was dis-
honest thinking, albeit not conscious dis-
honesty. There may be a moral to be drawn
from Igloo, but there is no need to spell it
out here.
These then are some of the highlights of
the topic, “Antibiotics and Iatrogenic Dis-
ease.” The dangers and discomforts attend-
ing antibiotic use are many and varied-
sensitization and hypersensitivity reactions,
pain and other local effects, systemic toxic
effects, the hazards of supeninfections and
replacement infections, and others. These
are real hazards that should be stressed as
well as the benefits. Because they are real,
the giving of antibiotics is always a calcu-
lated risk and they should be used only
when there are definite and valid indica-
tions.
REFERENCES
1. von Oettingen, W. F. : Symposium onnewer aspects of antibiotics : Complica-
lions of antibiotic therapy. Am. J. Med.,18:792, 1955.
2. Kagan, B. M., and Faller, L. : Symposium
on clinical advances in medicine; unto-
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AMERICAN ACADEMY OF PEDIATRICS - PROCEEDINGS 169
ward reactions to antibiotics. M. Clin.North America, 39:111, 1955.
3. Kagan, B. M., et al. : Symposium on anti-
microbial therapy. Pediat. Clin. NorthAmerica, May, 1956, p. 221.
4. Finland, M., et al. : True significance and
real incidence of reactions followingclinical use of antibiotics: Panel discus-
sion. Antibiotics Annual 1955-1956, p.
967.5. Jackson, G. G., et al. : Terramycin therapy
of pneumonia: Clinical and bacteriologicstudies in 91 cases. Ann. mt. Med., 35:1175, 1951.
6. Goldenberg, I. S. : Penicillin in sesame oiland fibrosarcoma: A report of two cases.
Cancer, 7:905, 1954.7. Kolb, L. C., and Gray, S. J. : Peripheral
neuritis as a complication of penicillin
therapy. J.A.M.A., 132:323, 1946.
8. Broadbent, T. R., Odom, G. L., and Wood-hall, B. : Peripheral nerve injuries fromadministration of penicillin; report offour clinical cases. J.A.M.A., 140:1008,1949.
9. Matson, D. D. : Early neurolysis in thetreatment of injury of the peripheralnerves due to faulty injection of anti-biotics. New England J. Med., 242:973,1950.
10. Scheinberg, L., and Allensworth, M. : Sci-
atic neuropathy in infants related to
antibiotic injections. PEDIAmIc5, 19:261,1957.
11. Pilcher, C., Meacham, W. F., and Smith,
E. R. : Epileptogenic effects of penicillin;an experimental study. Arch. mt. Med.,79:465, 1947.
12. Walker, A. E. : Toxic effects of intrathe-
cal administration of penicillin. Arch.Neurol. & Psychiat., 58:39, 1947.
13. Teng, P. : The selection of antibiotics in
the treatment of purulent infections ofthe central nervous system with particu-
lar reference to their neurotoxicity by
the intracranial or intrathecal route. An-tibiotics Annual 1953-1954, p. 244.
14. Smith, D. T. : The disturbance of the nor-mal bacterial ecology by the administra-
lion of antibiotics with the development
of new clinical syndromes. Ann. Int.Med., 37:1135, 1952.
15. Turell, R., and Maynard, A. de L. : Ano-rectocolonic side-effects of antibiotic
therapy. J.A.M.A., 156:217, 1954.16. Manheim, S. D., and Alexander, R. M.:
Further observations on anorectal corn-plications following aureomycin, terra-mycin and chloromvcetin therapy. New
York J. Med., 54:231, 1954.
17. Dearing, W. H., and Heibman, F. R. : Mi-crocuccic (staphybococcic) enteritis as acomplication of antibiotic therapy: Itsresponse to erythromycin. Proc. StaffMeet., Mayo Clin., 28:121, 1953.
18. Newman, C. R. : Pseudomembranous en-
terocolitis and antibiotics. Ann. mt.Med., 45:409, 1956.
19. Lepper, M. H., et al. : Effect of large dosesof aurecmycin on human liver. Arch.mt. Med., 88:271, 1951.
20. Rutenberg, A. M., and Pinkes, S. : The he-patotoxicity of intravenous aureomycin.
New England J. Med., 247:797, 1952.21. Bridges, R. A., Berendes, H., and Good,
R. A. : Serious reactions to novobiocin.J. Pediat., 50:579, 1957.
22. Lewis, C. N., Putnam, L. E., Hendricks,
F. D., Kerlan, I., and Welch, H. : Chlor-amphenicol (Chloromycetin) in relationto blood dyscrasias with observations on
other drugs: A special survey. Antibiotics
& Chemother., 2:601, 1952.23. Saslaw, S., Doan, C. A., and Schafer, R. L.:
Studies on prolonged administration of
chboramphenicol in monkeys. AntibioticsAnnual 1954-1955, p. 383.
24. Payne, H. M., Bullock, W., Hackney, R. L.,McKnight, H. V., and Syphax, G. B.:
The protracted intramuscular use ofchloramphenicol. Antibiotics Annual1956-1957, p. 359.
25. Woolington, S. S., Adler, S. J., and Bower,A. G. : Five years’ experience with chlor-
amphenicol. Antibiotics Annual 1956-
1957, p. 365.
26. Carr, D. T., Pfuetze, K. H., Brown, H. A.,
Douglass, B. E., and Karlson, A. G.:Neomycin in clinical tuberculosis. Am.Rev. Tuberc., 63:427, 1951.
27. Powell, L. W., Jr., and Hooker, J. W.:Neomycin nephropathy. J.A.M.A., 160:
557, 1956.
28. Longacre, A. B., and Waters, R. : Paren-teral bacitracin in surgical infections.
Am. J. Surg., 81:599, 1951.
29. Kagan, B. M., Krevsky, D., Milzer, A., and
Locke, M. : Polymyxin B and polymyxinE. : Clinical and laboratory studies. J.Lab. & Clin. Med., 37:402, 1951.
30. McDermott, W. : Toxicity of streptomycin.
Am. J. Med., 2:491, 1947.31. O’Connor, J. B., Christie, F. J., and How-
lett, K. S., Jr. : Neurotoxicity of dihydro-
streptomycin; effects of longer-term ther-apy. Am. Rev. Tuberc., 63:312, 1951.
32. Heck, W. E., Lynch, W. J., and Graves,H. L. : A controlled comparison of theeighth nerve toxicity of streptomycin
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SOME COMPLICATIONS OF TRANSFUSION, ENDOCRINETHERAPY AND OXYGEN ADMINISTRATION
By A. L. Chute, M.D., F.R.C.P.(C)Department of Pediatrics, University of Toronto, and the Hospital for Sick Children, Toronto
than withdrawal.
Due to the impetus given by life-saving
170 IATROGENIC DISEASE
ADDRESS: 555 University Avenue, Toronto, Ontario, Canada.
and dihydrostreptomycin. Ann. Otob.Rhin. & Laryng., 62:101, 1953.
33. Winston, J. : Clinical problems pertainingto neurotoxicity of streptomycin groupof drugs. Arch. Otolaryng., 58:55, 1953.
34. Jongkees, L. B. W., and Hulk, J. : The ac-
tion of streptomycin on vestibular func-tion. Acta oto-laryng., 38:225, 1950.
35. Kern, A. R., and Wimberbey, N. A., Jr.:
Penicillin reactions: Their nature, grow-ing importance, recognition, manage-ment and prevention. Am. J. M. Sc.,226:357, 1953.
36. Welch, H., Lewis, C. N., Putnam, L. E.,and Randall, W. A. : A study of the
sensitizing potential of novobiocin. An-tibiotic Med., 3:27, 1956.
37. Breese, B. B., Disney, F. A., and Talpey,W. B. : Novobiocin in the treatment of
beta-hemolytic streptococcal infections
in children. Antibiotic Med., 4:347,1957.
38. Brown, E. A. : The prevention of anaphy-lactic reactions to penicillin (Editorial).Antibiotic Med., 1:439, 1955.
39. Kagan, B. M., Nierenberg, M., Goldberg,D., and Milzer, A. : Studies of penicillinin pediatrics. III. Procaine penicillin G
COMPLICATIONS OF TRANSFUSION
I N NO FIELD has medical opinion reversed
itself so completely as in that of blood
letting versus blood replacement.
A short time ago while visiting the re-
constructed colonial town of Williamsburg,
one saw the tools of the old barber sur-
geons. A copy of a manuscript on the wall
stated that George Washington was bled
on several occasions during his terminal ill-
ness, without seeming benefit.
In this paper, I would like to emphasize
some of the ills of blood replacement rather
in sesame oil, in peanut oil with 2%aluminum monostearate and in water
with sodium carboxymethylcellulose. PE-
DIATRICS, 5:664, 1950.40. Welch, H., Lewis, C. N., Kerlan, I., and
Putnam, L. E. : Acute anaphylactoid re-actions attributable to penicillin. Anti-biotics & Chemother., 3:891, 1953.
41. Ruskin, E. R. : Penicillin anaphylaxis fol-lowing percutaneous absorption. NewYork J. Med., 54:1519, 1954.
42. A Report from the Ministry of Health:Sensitization of nursing staffs to anti-
biotics. Bnit. M. J., 2:39, 1953.43. Rogers, D. E. : The current problem of
staphylococcal infections. Ann. Int.Med., 45:748, 1956.
44. Weinstein, L., Goldfield, M., and Chang,T. : Infections occurring during chemo-therapy; a study of their frequency, typeand predisposing factors. New EnglandJ. Med., 251:247, 1954.
45. Weinstein, L. : The chemoprophylaxis of in-
fection. Ann Int. Med., 43:287, 1955.
46. Nolen, W. A., and Dille, D. E. : Use andabuse of antibiotics in a small commu-mty. New England J. Med., 257:33,1957.
transfusions during the war, blood transfu-
sion has become universally available in all
parts of the country. This has not proved an
unmixed blessing, however, for the dangers
associated with blood transfusion have also
been greatly multiplied thereby.
The factors which give rise to these dan-
gers are as follows : 1) those associated with
donor; 2) those associated with stored
blood; 3) those associated with act of trans-
fusion; 4) those associated with recipient.
1 . Factors Associated with Donor
1. Homologous serum jaundice.
2. Allergic reactions.
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1958;22;164Pediatrics T. E. Roy
ANTIBIOTICS AND IATROGENIC DISEASE
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