AMERICAN
ACADEMY
OF
PEDIATRICS
PROCEEDINGS
ANTIBIOTIC
PROPHYLAXIS
By Horace L. Hodes, M.D.
1)(’partnment of Pediatrics, sfount Sinai Hospital, New )ork
Prcscmitod at the Annual \kctimlg of the Amiierican Aca(lcmny of Pediatrics, October 23, 1958, as part
of a Svlmlposiummn on Infectioums I)iseascs.
ADDRESS: 5th Aventme amld 100th Street, New York 29, New York.
126
PmmIATRIcs, July 1959
Ped #{237}a!
tics
Voujui 24 JULY 1959 NUMBER 1
M
U(lI has l)ceml vnitten about the abuse of amitil)iotics, and mmmcli that I shallsay will ie Omi this subject. To redress the balance somrievhat, I shall begin by quoting
sOifle interesting statistical (h1tl cite(l I))’ Gep-lert.’ According to this author, the average child experiences 1(X) illnesses by the time he reaches 10 ‘ears of age. Yet, after the new-bonii 1)eniod, a niortalitv of only 1 is cx-p(riemice(l. This remarkable resimlt is cer-taimilv (lime, in l)lrt at least, to the use of
antil)iotics. \Ve must conclude that antibi-otics have l)een a boon to man, particularly to infants and children.
AlitibK)tics are vonc1erful drugs, an(l we have accomphshe(I wonders with them. As Table I illustrates, p1iirmiiacetmtical firms miiamiumfactumre antibiotics Iv the ton,2 and it is certaimi that \ve physicians l)rescnile them for our l)ltients il-i large clulntities. In addi-tiomi, P(rsms who are not physicians give antibiotics in smiiall quantities to our pa-tiemits (Tables II auid III).
A large IltIflll)er of I)r(’I)ar(ltins of each antibiotic are comiirnercially avai lable (Table
IV). Antibiotics are marketed in fixed
com-l)iuiations also, and SOliTle )liy5icians employ
these combinations regularly. According to
Kempe3 there are omi the market 69
anti-bacterial preparations which contain from
two to five amitibiotics in combination. I
need not enumerate the reasons for the
belief that this is a very unsatisfactory state
of affairs.
There is reason to believe that even we pediatricians may be using antibiotics too mnuch and that sometimes we may be using them improperly. \Ve are attempting to make them accomplish certain feats which
they can not accomplish, and we are
doubtedly using them unnecessarily in
cer-tam circumstances. In this way we may be
causing harm to our patients, both directly
and indirectly. The direct harm arises from
the fact that antibiotics, like other drugs, cause harmful side effects. When we use antibiotics needlessly, we CXO5C our
pa-tients to unnecessary risk of these side effects.
\Ve may also cause indirect but eventual
‘I’.BII 1*
.‘xli imu I’I( PIO)D( (TI( )N
Pounds Approx. Value
‘1’.BI.l’ I1l
EXTENSION OF I‘s:s (o.’
29 3,200
14
,
000 636,000756,000 860,000
3‘800
375,200 494,000 417,600 440,000 490,000 137,000,000 58,000,000 63,000,000 11,400,000 35,000,000 40,000,000 187,000,000 150,000,000 19,000 ,000
2,284,000 272,000,000
ice
* Fromui Welch.’
t Chlortetracycline, Tetracycline, Oxytetracycline,
Chioramphemuicol.
more generally effective antistaphylococcic agent than any now available. In this
con-nection, Lepper et al. have shown that the
percentage of erythromycin-resistant strains
of staphylococci recovered from a hospital
Samples
District ---
----Tested Positive
Conc. t
-__________
.u/ml (Ate.)
* Fromn Wehch.’
population rose from 0 to 70sf after erythro-mycin had been used for about 5 months.
There is no doubt that the emergence of
strains of antibiotic-resistant staphylococci has resulted from antibiotic therapy, some of which has been unwise. In population groups where antibiotics are used to a
limited extent, there are relatively few
re-sistant strains.5
Prolonged use of broad spectrum
anti-biotics is sometimes necessary, but this form
of treatment may result in a change in
mi-crobial flora that may be of serious
conse-quence to the patient. Freed from the
com-petition of bacteria that are normally
pres-ent, fungi and gram-negative organisms,
which are both pathogenic and
antibiotic-resistant, may prove to be a more serious
threat to life than were the microorganisms
which caused the initial illness. We are
Atlanta 26 1 .006
Baltimore 26 5 .01
Bostomi 31 4 .014
Buffalo 33 5 .007
Chicago 31 2 .018
Cincinnati 25 3 .008
Denver 44 4 .007
Kammsas City ‘(i 1 .006
Los Amugeles 27 6 .03
:t immneapolis 4() 0 0
New ()rleamms (; 2 .011
New York 23 5 .016
Phuilaklplmia 2(; 6 .021
Sami Francisco 36 3 .021
Seattle 5 6 .015
St. Louis ‘27 0 0
Totals 474 55 (11.6%)
* Froni Welch.2
150 38 47 25 15 27
t Mimi. .003 z/ml; Max. .08 M/mI.
Year .1flhil)iO1iC
1943 Penicillin 1944 Penicillin 1945 Penicillin 1951 Penicillin 1953 Pemiicillin 19.54 Pemlicilliml 1946 Streptomycimi
1953 Strep. & DHSM
1954 Strep. & DIISM 1953 Broad spectrummit
1954 Broad spectruint
1954 Feed supplements
19,54 Total all antibiotics (list.)
TABLE 11*
PFNmcmLm.mN mN MARKET MmrK (1955)
In nutrition:
swine, chicks, poults 3,000,000 In animals:
therapeutic, prophylactic uses
cows, beef cattle, calves, swine, chicks, mmmink
As crop sprays:
Blight
apple, pear, waimlut, beans Bacterial diseases
Tobacco, tomatoes, peppers, cherries, spinach, let-tuce, potatoes
As food preservatives:
Vegetables, hamburger, cream fillings, fish, fish fillets,
shrimp, beer fermentation, beef carcasses, chickemis,
TABLE IV*
NUMBER OF PREPAIATmONS
Penicillin Streptomycin, dihydrostreptomycimi Chlortetracycline, tetracycline Oxytetracycline Chioramphenicol Bacitracin 3O2
128 ANTIBIOTIC PROPHYLAXIS
sometimiies ohlige(1 to take this risk, hut we nimist iiot (10 SO imniess it S a necessary risk.
Perhaps the most uncritical use of
anti-l)iOtics has been their use as prophylactic agents. A large portion of the 2,500,000
pounds of antibiotics manufactured
annu-ally is employed in this way. In some cir-cumstances antibiotic prophylaxis is of great value, while in others it is useless or even
harmful. \Ve shall attempt here to sketch in
sOme principles which may guide us in the
use of antibiotics as prophylactic agents. The value of chemoprophylaxis is most firmly established when it is used for
defi-nite exposure to a specific organism. Thus,
exposure to a patient with meningococcic
meningitis or septicemia requires the use
of a stmlfonamide. This is true in the home as vell as in army camps or barracks. The
need for prophylaxis for family contacts is
borne out by our experience with several
otitbreaks of meningococcic meningitis in
Baltimore. We found that 11% of cases of
meningitis were secondary cases. We
em-ploy sulfadiazine, given orally, in a dosage
of 0.5 gm twice daily for a period of 4
days. Nurses and house physicians caring for patients with meningococcic meningitis also should receive chemoprophylaxis.
Family exposure to beta-hemolytic
strep-tococcal infection requires
chemoprophy-laxis. We recommend phenoxymethyl
peni-cillin (Penicillin V), given orally, in dosage
of 200,000 units twice daily for 5 days. We
recommend that similar prophylaxis be used
for dormitory contacts in boarding schools,
l)ut we do not recommend that it be used
for exposure which takes place only in the
classroom.
The valtme of anti-streptococcal
prophy-laxis for patients with rheumatic fever has
been well proven. Sulfonamides were first
used for this purpose and their efficacy was
clearly established. In military life the
emer-gence of many sulfonamide-resistant strains
of beta-hemolytic streptococci diminished
the valtme of sulfonamide prophylaxis.
Sul-fonamide-resistant beta-streptococci are less
frequently encountered in civilian practice.
Nevertheless, penicillin is the antibiotic of
choice for Irotectioml of patients vith
rheu-mnatic fever against beta streptococci. We
employ tablets of phenoxymethyl penicillin,
given orally, in dosage of 200,000 units
twice daily. When there is reason to doubt
that the medication will be taken with
ut-most regularity, we use 1,200,000 units of
benzathine penicillin G, given by
intra-muscular injection once a month.
Children who are sensitive to penicillin
are given sulfonamides in our clinic, but in
some centers the tetracyclines or
erythro-mycin are used for such patients. In any
case, prophylaxis should be continued
with-out interruption throughout the year and
it should be continued through adolescence
and young adult life, at least.
Children who have rheumatic or
congeni-tal heart disease should be protected by
antibiotics against transient bacteremia (and
the risk of subacute endocarditis) which
may occur following dental extraction and
manipulation. The same is true when they
are subjected to tonsillectomy or to surgery
of the urinary or gastrointestinal tracts. For
prophylaxis in these circumstances we
fol-low the recommendation of the American
Heart Association: 600,000 units of aqueous
penicillin and 600,000 units of procaine
penicillin-in-oil containing 2% aluminum
monostearate are given by intramuscular
in-jection 30 minutes before operation.
Gonococcal ophthalmia of the newborn
can be prevented very effectively by
instilla-tion of penicillin into the conjunctivae or
by intramuscular injection of 50,000 units of
aqueous penicillin C. One or other of these
procedures should be carried out in the
delivery room.
It is the practice of some pediatricians
to employ antibiotic prophylaxis in viral
in-fections in an effort to prevent secondary
bacterial invasion. We are of the opinion
that under ordinary circumstances this
pro-cedure is not sound. We do not give
anti-biotics to infants or children who have
un-complicated measles, chicken pox or
adeno-virus infection. Instead we observe the
pa-tient carefully and treat specific bacterial
case of influenza-virus infections of infants, it may he necessary to use antibiotics before we are certain that bacterial invasion has
occurred. Our reason for this belief is that
we have several times found at post mortem, unsuspected and extensive staphylococcal pneumonia in infants stmffering from virus influenza. In these cases the bacterial infec-tion of the lung seems to have occurred in the very early phase of viral infection.
Antibiotics have been employed by some physicians in an attempt to reduce the in-cidence of secondary bacterial infections among children who are suffering from a chronic noninfectious disease, such as
di-abetes and nephrosis. We believe that this is not generally desirable, because the re-suIts do not justify the risks involved. On
the other hand, chemoprophylaxis is prob-ably worth these risks when we are dealing
with fibrocystic disease of the pancreas. In
this disease it is probably safer to attempt prophylaxis than to try to treat each bac-terial infection. The problem is a very
diffi-cult one, requiring careful analysis of each
case. The antibiotics used must be changed frequently, and they should be selected on the basis of frequent examination of the
bacterial population of the upper
respira-tory tract.
There is no doubt that chemoprophylaxis has a place in modern surgery. However,
an objective consideration of the subject
leads one to the conclusion that antibiotic prophylaxis as now used for surgical pa-tients should be curtailed. It is difficult to escape the conclusion that reliance upon antibiotics has led to relaxation of aseptic techniques in the operating room and in the
wards of many of our hospitals. Certainly,
the routine administration of penicillin for
such “clean operations” as herniorrhaphy represents an unwarranted use of antibi-otics. It brings the patient the direct and
indirect disadvantages of antibiotic therapy
without any compensating gain. McKittnick
amid \Vheelock’ have shown that antibiotic prophylaxis in elective surgery has been
in-effective in preventing postoperative com-plications of an infectious nature.
Chemoprophylaxis has been used
exten-sively for patients with second and
third-degree burns. This would seem a logical
procedure, but there is growing
dissatisfac-tion with the results obtained. Only too
often, after prolonged use of antibiotics, one
is left with a patient who is suffering from
extensive infection with antibiotic-resistant
organisms, such as Pseudomonas aeruginosa,
Bacillus proteus or Aerobacter aerogenes.
We believe that chemoprophylaxis for burns
should be given up, and that reliance should
be placed upon strict isolation and careful
aseptic methods. We should determine the
bacterial flora by frequent examination of
the burned areas, and we should treat
spe-cific infections (as they occur) with the most
effective antibiotic available.
I do not wish to leave the impression that
chemoprophylaxis has no place in surgery.
There are several well defined surgical
con-ditions in which it has a very important
place. Isoniazide, streptomycin and
para-aminosalicylic acid should be employed in
preparation for operations for tuberculous
infection of the lung, bronchi or lymph
glands. It appears to be true also that
anti-biotics are of value in preparing the
in-testine for extensive surgery, as the
mci-dence of post-operative peritonitis has been
reduced by their use.
It is the practice in some clinics to use
antibiotic prophylaxis for patients with
neurologic disease that has caused paralysis
of the respiratory muscles. Our belief is that
this is not in the long run a desirable
prac-tice. We prefer to treat each respiratory
in-fection as we meet it. We attempt, as soon
as possible, to isolate the causative bac-teria in each instance, so that we may em-ploy the most effective antibiotic. Patients
with paralysis of the bladder are treated in
a similar manner. We have learned from a
long and trying experience with patients
with poliomyelitis that chemoprophylaxis
does not prevent urinary tract infections
when bladder dysfunction is present.
At-tempts at chemoprophylaxis almost
invani-ably lead to eventual infection with
130 ANTIBIOTIC PROPHYLAXIS
at our command. In these cases it is better
to make frequent bacteriologic examinations
of the urine and to use an appropriate
anti-biotic in large doses as the need arises.
We shall turn next to the place of
anti-biotics in hospital nurseries. Full-term
in-fants born after normal labor should
re-ceive no prophylaxis except that given to
prevent gonorrheal ophthalmia.
The question of chemoprophylaxis for
premature infants has raised considerable
controversy. No clear-cut data have been presented thus far which establish the value
of antibiotic prophylaxis for premature
in-fants. In fact, a number of papers report
negative results. For example, Stoppelman7
gave penicillin plus streptomycin to one
group of prematures, and penicillin plus
a sulfonamide to a second group. She found
no effect on the incidence of positive
cul-tunes for streptococci as compared with
con-trol infants. The occurrence of cultures
showing a heavy growth of staphylococci was actually greater in the treated groups
than it was in the untreated group.
Simi-larly, Gialdroni-Grassi et al.8 found that
antibiotic prophylaxis had only minor effects
on the bacterial flora of the nose and throat
of premature infants. By the end of the
sec-ond week of life, 60% of infants had
co-agulase-positive staphylococci in the nose.
The result was the same in a group treated
with penicillin pltms stneptomycin, a
sulfona-mide-treated group, an
oxytetracycline-treated group and a saline-treated group. A different result, of course, might have been found if erythromycmn had been used.
It is undeniably true that premature
in-fants often do not show systemic signs of acute infection. For this reason serious
in-fection is frequently overlooked in these
in-fants, especially during the first few days
of life. Because of this fact, many hospitals
administer antibiotics to premature infants
who weigh under 1,800 gm. If this is done,
Alexander recommends that therapeutic dosage of antibiotics be used, because in
these circumstances one is often treating
hidden disease, rather than attempting to
prevent infection. Alexander proposed the
use of chloramphenicol and sulfadiazine.
This combination of drugs is effective
against most gram-negative organisms and
most strains of staphylococci. It should be
noted that recent data and experience have
shown that for premature infants the dose
of chioramphenicol should not exceed 25
mg/kg/day; doses larger than this have
caused severe toxic symptoms.1#{176}
Some authorities are opposed to the use
of chemoprophylaxis for even small
prema-tunes. Levin&1 uses antibiotics for
pnema-tunes only if amniotic membranes have been
ruptured for more than 24 hours before
de-livery, or if the infant has been transferred
from another hospital to the premature
cen-ten, on if there is definite evidence of
infec-tion. On our premature service we have
wavered with pendulum-like motions
be-tween Dr. Levine’s views and those
cx-pressed by Dr. Alexander. More objective
data are needed on this important issue.
The last question for which we have
space concerns chemoprophylaxis for
staph-lococcal and enteropathogenic E. coli
in-fections in the hospital nursery.
When a strain of staphylococcus of phage
type 80/81 causes disease in one or more
infants in a nursery for newborns, it must be
considered that a potentially serious
out-break may be starting. It has been
demon-strated, only too often, that
chemoprophy-laxis may not prevent progression of the
epidemic. Nevertheless, along with other
measures, antibiotic prophylaxis probably
should be employed. In this situation it
must be realized that the antibiotic may
de-lay or hide symptoms of infection, and all
infants receiving the drug should be
con-sidened as infected and contagious.
Further-more, after the infant has left the hospital,
overt disease may appear. The danger to
siblings and parents in such cases has
he-come well known to all pediatricians.
Chemopnophylaxis has been used in
at-temnpts to control nursery outbreaks of E.
coli diarrhea. Neomycin, given by motmth,
131
for this itmrse. It should be noted,
how-ever, that imi controlling these outbreaks
many other control measures have been
used in addition to antibiotics. Furthermore,
we have encountered a number of
entero-)athogenic E. coli which are quite insensi-tive to neomycin.
SUMMARY
Chemoprophylaxis is very effective and should be used freely after known exposure to dangerous bacteria which are very
sensi-tive to an antibiotic. Into this category falls
prophylaxis against beta-streptococcal, me-ningococcal and gonococcal infections.
The value of preventing beta-hemolytic
streptococcal infections in children who
have suffered an attack of rheumatic fever is estal)lished beyond a doubt.
Antibiotics generally should not be used
during an acute viral infection for
protec-tion against possible secondary bacterial
in-vasion.
In general, antibiotic prophylaxis should
not be used to attempt to reduce the
in-cidence of bacterial infections in children
who are suffering from a chronic disease of nonbacterial origin, such as diabetes or
nephrosis.
The use of antibiotic prophylaxis in sur-gery should be limited to certain specific in-dications. It should not be used in “clean” elective surgery.
Antibiotic prophylaxis may be of value
for small premature infants during the first
week of life, but much more data on this
point are required. For full-term newborn infants chemoprophylaxis has only limited usefulness, except for ophthalmia
neona-torum. In the light of present knowledge,
antibiotic prophylaxis should be used to
help control outbreaks of staphylococcal and E. coli diseases in the nursery.
REFERENCES
1. Geppert, L.
J.
: Composition of pediatricpractice at a permanent Army base in
the antibiotic era. PEDIA’rnlcs, 22:336,
1958.
:. Welch, H. : Antibiotics 1943-1955: their
development and role in present-day
society, in The Impact of the Antibiotics
on Medicine and Society, edited by
Galdston, I. New York, Internat. Univ. Press, 1958, pp. 70-87.
3. Kempe, C. H. : Pediatric use of antibiotic
agents.
J
Pediat., 53:19, 1958.4. Lepper, M. H., Dowling, H. F., Jackson,
G. G., Moulton, B., and Spies, H. W.:
Effect of antibiotic usage in the hospital on the incidence of antibiotic-resistamit strains among personnel carrying staphy-lococci. J. Lab. & Cliii. Med., 42:832,
1953.
5. Thomson, E. : The present position of
anti-biotic therapy. M. J. Australia, 1:418, 1956.
6. McKittrick, L. S., and Wheelock, F. C.:
The routine use of antibiotics in
dee-tive abdominal surgery. Sung., Gynec.
& Obst., 99:376, 1954.
7. Stoppelman, M. R. H. : Effect of antibiotics
on nasopharyngeal flora of premature
in-fants. Am.
J.
Dis. Child., 88:339, 1954.8. Gialdroni-Grassi, C., Pryles, C. V., and
Finland, M. : A controlled study of the
use of antimicrobials in premature
in-fants. PEDimIcs, 18:899, 1956.
9. Alexander, H. E. : In Premature and
new-born infants. Report of a seminar.
Co-ordinated by Day, R. L., and
Silver-man, W. A. PEDIATRICS, 20: 143, 1957.
10. Kretchmer, N. : Practical therapeutic
im-plications of immaturity (Commentary).
PEDIATRICS, 23:638, 1959.
1 1. Levine, S. Z., Imi Premature and newborn
infants. Report of a seminar.
