1986;77;932 Pediatrics

MARTHA L. LEPOW
Aplastic Anemia Following Chloramphenicol Therapy Still Happens!

http://pediatrics.aappublications.org/content/77/6/932
the World Wide Web at:
The online version of this article, along with updated information and services, is located on

ISSN: 0031-4005. Online ISSN: 1098-4275.

Print Illinois, 60007. Copyright 1986 by the American Academy of Pediatrics. All rights reserved.
by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village,
it has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked
PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication,
at Indonesia:AAP Sponsored on June 29, 2014 pediatrics.aappublications.org Downloaded from at Indonesia:AAP Sponsored on June 29, 2014 pediatrics.aappublications.org Downloaded from
932 PEDIATRICS Vol. 77 No. 6 June 1986
neous, he should clarify his mistake explicitly in his next
relevant report, so that others will not continue to be
misled.
In Dr Noras 1983 paper he states, . . . as a rule,
the more common the cardiovascular lesion, the more
likely it is to recur in first degree relatives. This is
consistent with and is predicted by various models of
multifactorial inheritance. From that paper table 4 ap-
pears to be the basis for his assertion that common
cardiovascular lesions recur more frequently, but it pro-
vides no such evidence: the differences in recurrence risks
do not even approach statistical significance.3 If the data
from that table are too heterogeneous or unreliable to be
subjected to statistical scrutiny, they can hardly provide
much evidence to support the multifactorial inheritance
hypothesis.
The uniform incidence of ventricular septal defects
and the frequent discordance in identical twins suggest
that these defects occur largely at random. Genetic and
environmental factors appear to be important in some
cases, either individually or in combination. However,
the term multifactorial inheritance should not be used,
because it suggests a specific pattern of inheritance not
followed by ventricular septal defect or congenital heart
defects.
REFERENCES
THOMAS B. NEWMAN, M D , M PH
Departments of Pediatrics and
Epidemiology and International Health
University of California
San Francisco, CA 94143
1. Nora JJ, Nora AH: Genetic epidemiology of congenital heart
diseases. Prog Med Genet 1983;5:91-137
2. Nora JJ: Multifactorial inheritance hypothesis for the etiol-
ogy of congenital heart diseases: The genetic-environmental
interaction. Circulation 1968;38:604-617
3. Newman TB: Etiology of ventricular septal defects: An epi-
demiologic approach. Pediatrics 1985;76:741-749
4. Edwards JH: The stimulation on Mendelism. Acta Genet
1960;10:63-70
Aplastic Anemia Following Chloramphenicol
Therapy Still Happens!
To the Editor.-
Chloramphenicol is still the drug of choice for treat-
ment of ampicillin-resistant Haemophilus influenzae b
meningitis, brain abscess, Rocky Mountain spotted fever
in severely ill patients and young children, and typhoid
fever. Intravenous oral and intraocular routes of admin-
istration have been widely used.
Smith and W ebber have recently reviewed the phar-
macology of chloramphenicol. Reversible erythroid sup-
pression is dose related and more common in children.
Genetic predisposition of the stem cell to inhibition of
nucleic acid synthesis is thought to be the explanation
for the idiosyncratic chloramphenicol-induced bone
marrow aplasia, although Daum et al3 reported a probable
dose-related case. The incidence in the 1960s was esti-
mated to be 1/19,000 to 1/200,000 courses of therapy. It
is manifested by pancytopenia occurring 3 to 12 weeks
after chloramphenicol therapy with slight preponderance
in females. There have been no reported cases in the past
5 years associated with either oral or intravenous admin-
istration. Although there are several promising second or
third generation cephalosporin drugs that may be substi-
tuted in the future for chloramphenicol, their safety and
efficacy in children have not yet been determined.
CASE REPORT
A 4-year-old white girl was admitted to Albany Medical
Center on July 28, 1985, with lethargy, vomiting, and
fever of several days duration.
In April 1985, a malodorous discharge secondary to
right otitis media occurred which was treated first with
amoxicillin, and when an erythematous rash developed,
treatment was changed to trimethoprim-sulfamethoxaz-
ole. She was asymptomatic until July 13, 1985, when the
malodorous discharge recurred and treatment with tn-
methoprim-sulfamethoxazole was reinstituted. Six days
later the treatment was changed to cefaclor and Cortico-
sporin drops because of increasing fever and dizziness.
There was temporary improvement, but on July 24 her
temperature increased to 38.9#{176}C (102#{176} F) and she had
increasing lethargy, headache, and vomiting. Because of
worsening of symptoms, hospitalization was advised.
Findings on physical examination were: temperature,
36.7#{176}C(98#{176}F); pulse rate, 100 beats per minute; respira-
tory rate, 20 breaths per minute; BP, 140/80. The patient
was obtunded with eyes deviated to the left. She had a
thick purulent malodorous discharge from the right ear
canal. The left ear drum was normal. She had papilledema
ofthe right eye. Initial blood values were as follows: W BC
count, 34,000/ tL with a preponderance of polymorpho-
nuclear leukocytes; hemoglobin, 9.7 g/dL; hematocrit,
28%; platelet count, 890,000/ zL. A computed axial to-
mographic scan showed a large right posterior fossa ab-
scess obliteration of the right mastoid process, no visible
fourth ventricle, and hydrocephalus. The patient under-
went a craniotomy with drainage of the abscess followed
by a right mastoidectomy two days later.
Because of the possible allergy to penicillin, the patient
was given vancomycin 40 mg/kg/d in four divided doses
for 17 days. Following a negative challenge, her treatment
was then changed to intravenous penicillin G aqueous,
1,000,000 units every six hours for 12 days, and then
penicillin VK, 250 mg every six hours for 1 month. She
was also given gentamicin, 7.5 mg/kg/d every eight hours,
because of Gram-negative rods on smear of abscess con-
tents. This was discontinued when aerobic cultures were
negative. Chloramphenicol was given intravenously for 1
week followed by oral administration for a total of 8
weeks. The initial dose was 75 mg/kg/d given every six
hours and decreased with the results of chloramphenicol
levels. The dosage was finally adjusted after 3 weeks to
37 mg/kg/d given every eight hours with a trough level
of 5.2 zg/mL.
at Indonesia:AAP Sponsored on June 29, 2014 pediatrics.aappublications.org Downloaded from
LETTERS TO THE EDITOR 933
Cultures of the abscess revealed aerobic and anaerobic
streptococci, Staphylococcus epider midis and Ba cter oides
fr a gilis.
The patient improved rapidly and within 1 week was
afebrile, alert, and ambulating with a wide base. She had
no hearing on the right side. A repeat computed tomo-
graphic scan on Aug 27, 1985, showed only slight en-
hancement of the posterior fossa and it was determined
to continue the treatment for 8 weeks to assure complete
resolution. Her W BC count at discharge was 4,80O/ L
with 20 polymorphonuclear leukocytes, 60 lymphocytes,
nine mononuclear cells, and eight eosinophils. ESR was
3. The dose of penicillin was lowered with the change to
oral treatment.
She was discharged on oral chloramphenicol and pen-
icillin VK treatment on Aug 29, 1985, which were discon-
tinued on Sept 29, 1985. W eekly blood counts were re-
ported to be normal. She was readmitted on November
5, 1985, with a three-day history ofbruising and a platelet
count of 15,000/ tL. Bone marrow aspiration on Novem-
ber 7 revealed marrow aplasia, and no polymorphonuclear
leukocytes were present in the peripheral blood a few
days later. The patient has received antithymocyte glob-
ulin because there is no suitable donor for bone marrow
transplantation.
REFERENCES
MARTHA L. LEPOW, MD
Department of Pediatrics
The Albany Medical College
of Union University
Albany, NY 12208
1. Jadaiji T, Humphreys RP, Prober CB: Brain abscesses in
infants and children. Pediatr Infect Dis 1985;4:394-398
2. Smith AL, W eber BS: Pharmacology of chloramphenicol:
Symposium on anti-infective therapy. Pediatr Clin North
Am 1983;30:209-236
3. Daum RS, Cohen DL, Smith AL: Fatal aplastic anemia
following dose-related chloramphenicol toxicity. J Pediatr
1979;94:403
Constipation
To the Editor .-
Among the frequently encountered problems of a gen-
eral or referral pediatrician are constipation and/or en-
copresis. W e recently had a patient who presented with
a chief complaint of increased stooling pattern, the cause
ofwhich may be an acceptable addition to the therapeutic
m odalities applied to constipated children.
A 10-year-old boy, previously in good health, was
brought in because his stool pattern had changed in the
past 4 months. He was an individual who, prior to the
change, went unnoticed as to his bowel habit. It was
within the family norm. However, he began to differ from
the norm by seeming quite insistent about going to the
bathroom each morning, then twice again during school,
and quite often twice more in the evening. On occasion,
there was a sense of urgency about the necessity of using
the bathroom. The stools were always large and loose but
not watery, and no blood or mucus was ever noticed in
them. No other member of the family seemed similarly
affected. He was afebrile. He did not awaken at night
because of abdominal pain. Except for the occasional
sense of urgency just prior to defecation, he had no
abdominal cramps or other pains. His health otherwise
was in good order and he was fully immunized.
On physical examination, the boys height was 54/4 in
and his weight was 31.6 kg (70/4 lb). No abnormalities
were found on physical examination, including rectal
examination. Blood work included a complete blood cell
count and a W estergren sedimentation rate; results were
normal.
During the initial questioning, the patient and his
parents were asked if there had been any change in his
diet, but none was recollected. However, in going over his
daily diet in detail, it was elicited that each evening after
supper a large bowl of popcorn was made and the patient
consumed the largest quantity. The popcorn was made in
a microwave oven and, coincidentally, the microwave had
been purchased at about the time of the onset of his
problem. He was thus on a high-fiber diet, and that was
presumed to be the cause of his increased stool produc-
tion. No further workup was performed, and, as a trial,
he did not eat any popcorn for a week and the problem
resolved.
For those of us who deal with constipated patients, the
traditional methods of using mineral oil, occasional ene-
mas, bran in its various forms and combinations, and
occasional mild stimulants such as senna do not always
meet with great patient compliance. After our experience
with this patient, we have begun to treat constipation
with this form of high-fiber diet. In terms of economy,
the method is inexpensive, and it is safe once the patient
is beyond the age for which foreign body aspiration is a
problem. It is highly acceptable to patients and seems to
have sufficient bulk, both to soften stools and to increase
their volume. It can be bought in a variety of different
tastes and forms, some of which have occasioned appli-
cation of the term gourmet to them. W e have recom-
mended the consumption of one to two qt of popped
popcorn per day and have advised the usual strategy of
continuing the treatment for several months until reg-
ular bowel habits are established. W e, of course, discuss
other aspects of management and are quite pleased so far
with both our compliance rates and patient satisfaction.
DOOLEY CHEN, M D
BRADLEY SULLIVAN, M D
Department of Pediatrics
Marshfield Clinic
Marshfield, W I 54449
at Indonesia:AAP Sponsored on June 29, 2014 pediatrics.aappublications.org Downloaded from
1986;77;932 Pediatrics
MARTHA L. LEPOW
Aplastic Anemia Following Chloramphenicol Therapy Still Happens!

Services
Updated Information &
http://pediatrics.aappublications.org/content/77/6/932
including high resolution figures, can be found at:
Citations
http://pediatrics.aappublications.org/content/77/6/932#related-urls
This article has been cited by 1 HighWire-hosted articles:
Permissions & Licensing
http://pediatrics.aappublications.org/site/misc/Permissions.xhtml
or in its entirety can be found online at:
Information about reproducing this article in parts (figures, tables)
Reprints
http://pediatrics.aappublications.org/site/misc/reprints.xhtml
Information about ordering reprints can be found online:
Online ISSN: 1098-4275.
Copyright 1986 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0031-4005.
American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007.
has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked by the
PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication, it
at Indonesia:AAP Sponsored on June 29, 2014 pediatrics.aappublications.org Downloaded from