606
Experience
and Reason
.
Briefly
Recorded
“In Medicine One must pay attention not to plausible theorizing but to experience and reason together. . . . I agree that theorizing is to be approved, provided that it is based on facts, and systematically makes its deductions from what is observed. . . . But conclusions drawn from unaided reason can hardly be serviceable; only those drawn from observed fact.” Hippocrates: Prece’pts.
. . .
(Short conunumcations of factual material are publz.shed here. Comments and criticism-s appear
u.s Letters to the Editor.)
Antibiotics
and
Their
Effect
on
Bordetella
pertussis
in
the
Nasopharynx
Antibiotic therapy of pertussis in children
has been of doubtful value in altering the
course of the disease. However, such therapy
has been thought to be desirable for at least
one
reason:
appropriate
therapy
might
be
use-ful in eradicating the organisms from the
naso-)harynX, thus hopefull’ diminishing the
corn-municability of the disease. This would appear
to be particularI’ desirable for infants and children hospitalized with pertussis and those
Who cannot be readily isolated from other
sus-cel)tibles. Two recent rel)orts’ .2 have suggested that ampicillin or tetracycline therapy for 5
days is effective iii eradicating Bordetella
per-ttissi-s from the nasopharynx.
The
following
report reviews 1 1 cases
in
which eradicationof these organisms was attempted, largely with-out success.
MATERIALS AND METHODS
All cases
were
seen
at Children’s
Orthopedic
hospital
and
Medical
Center
as
either
out-patients or inpatients, under the direct care of
their
attending
physician.
No
attempt
was
niade to
influence
decisions
regarding
therapy.
Nasopharyngeal specimens were obtained
whenever possible, as frequently as every 2
days in some instances.
A particular
effort
was
made
to
obtain
a
specimen
within
48
hours
after therapy was
discontinued.
Nasopharyngeal
swabs
were
taken
by
hold-ing
a flexible pernasal swab in place in the nasopharynxuntil
the
patient
had
an adequate
paroxysm of coughing, then it was transported
to
the
laboratory
immediately
for
study.
Bordet-Gengou medium was prepared
accord-ing to
standard
methods
with
one
modifica-tion: instead of defibrinated fresh blood,
15 to
20% fresh, whole, human, adult blood was
im-mediately incorporated into the medium
with-out anticoagulant treatment. The methods of
inoculation, and identification of the isolates
were according to standard methods; isolates were confimied by agglutination with
t\pe-specific antiserum.
Two direct smears vere made from each
specimen, one of which ‘as
stained
by
Gram’s
method, aiid the other was examined by using
fluorescein conjugated pertussis antiserum
( Difco)
.1 Two different lots offluorescent-labelled
antiserum
were
tested
with
known
positive and negative control specimens; only
one lot was found to exhibit consistent
speci-ficity,
and
it was used throughout the study.Positive control specimens consisted of smears
of phase 1
B.
pertuss-is organisms. Negativecontrols
included
smears
of
staphylococci,
streptococci, Heinophilus influenzae,
diph-theroids, and nasopharyngeal swabs from
healthy subjects. There were no instances of
positive fluorescence among this group.
RESULTS
The
therapeutic
courses
used
and
their
effects
upon
the
iiasopharyngeal
carriage
of
B.
pertussis are shown in Table I. The dose ofantibiotic was considered to be potentially
ade-quate in at least 8 of the 11 patients (Cases 1,
3, 4, 5, 6, 8, 9, and 1 1
)
.Six of these
patients
received all or part of their therapy during
hospitalization.
Case 5 had a negative fluorescent antibody
(FA)
test
at
the
termination
of
therapy,
but
‘FABLE I
EFFEcT OF ANTiBIOTICS ON
B.
I’ERTUSSIS IN TIlE NASOPHARYNXCase Age Duration of Symptoms Before 2l mo 2 mo 2 mo 3 mo 41 mo 4 mo 10 yr ‘2yr 10 mo 3 wk 3 da l da da 4 wk 3 da Unknown 10 da
4
Swk S wk 1 3 4 .5 6 7 8 9 10 11 Duration of Therapy With Each Antibiotic (da) 9* .5+-6 4 .5 34#{128}-7 1 dose- 6#{128}-6 3 S S 3 3 Follow-up Study FA+,C+ FA+, C+ FA+, Cnd FA+, (‘+FA - , Cud
FA+, C+ FA+,C+ FA+, C+ FA+, C+ FA+, C+ FA+, C+
Ampicillin, 155 mg/kg/day, tM. Kanamycin, 7 mg/kg, I.M. Ampicillin, 155 mg/kg/day, p.o.
Ampicillin, I gin/day, p.o.
a Arrows indicate that course of therapy which wa-s given during hospitalization.
FA=fiuorescent antibody test; C=culture; + =positive; - =negative; nd =not (lone.
EXPERIENCE
AND
REASON-BRIEFLY
RECORDED
607
cultures
were
not
done.
Three
patients
were
treated
under
supervision
in the
hospital
with
8, 9, and 10 days of ampicillin, respectively,
and
remained
both
FA
and
culture
positive
for
B.
pertussis.
One
patient
(Case
6),
who
was
treated
with
5 days
of ampicillin
prior
to
admission
to
the
study,
was
found
to
be
FA
and
cultnire
positive
10 days
after
the
therapy
was discontinued and remained positive after
days of additional ampicillin therapy. After
these
results
were
obtained,
this
patient
was
treated
with
an additional
5 days
of ampicillin;
following
this,
the
FA
remained
positive
but
the
culture
was
negative.
The
positive
FA
result
in Case
3 was
found
4 days
after
a 5-day
course
of ampicillin
was
completed.
Cultures
were
not
done
on
this
patient.
The
patient
who
was
treated
with
tetracycline
alone
(Case
7
)
was
found
to
be
FA
and
culture
positive
7 days
following
discontinuation
of therapy.
The
only
older
child
in this
group
(Case
9)
was
a boy
with
Hodgkin’s
disease
who
had
had
a severe
Therapy
Anti&iotic Therapy
Ampicillin, 75 mg/kg/day, p.o.
Ampicillin, 40 mg/kg/day, p.o.
Ampicillin, 90 mg/kg/day, p.o.
Nafcillin, 88/mg/kg/day, p.o. Penicillin-V, 1 ,0O,OO0 units/day, p.o. Ampicillin, 111 mg/kg/day, p.o.
Ampicillin, 75 mg/kg/day, p.o
Ampidilhin, 94 mg/kg/day, p.o. Ampicillin, 75 mg/kg/day, p.o.
Tetracycline, 25 mg/kg/day, p.o.
Procaine Penicillin G, 1 ,200,000 units, l.M.
Streptomycin 0 mg/kg/day, TM. Tetracycline, 30 mg/kg/day, p.o. Ampicillin, 30 mg/kg/day, p.o.
Procaine Penicillin G, 400 ,000 units/day l.M. Streptomycin, W mg/kg/day, I.M.
Tetracycline, 56 mg/kg/day, p.o. Ampidihin, 56 mg/kg/day, p.o.
608
paroxysmal cough for 23 months. During that
period,
he had
also
been
treated
with
cloxacillin
for
6 days
and
erythromycin
for
3 days.
After
the diagnosis was first suspected, he was placed on ampicillin for 6 days but was found to
be
FA
and
culture
positive
at
the
end
of
that
time.
Cases
10
and 11 were treated with avariety of antibiotics for a total of 7 and 9
days, respectively, and were found to be both
FA
and
culture
positive
the
day
following
corn-pletion
of therapy (Table I) . However, whenthese results were made known, Case
10
was
treated with
an
additional
2 days
of
tetracy-dine,
after
which
the
FA
and
culture
both
became negative. Similar therapy was
insti-tuted
for
Case
11,
and
she
also
became
nega-tive
after
3
additional
days
of
tetracycline
therapy.
DIscussioN
It has
been
suggested
that 5 days of therapywith either ampicillin or tetracycline will eradi-cate
B.
l)C11S.siS from the nasopharynx, oftenwithin 48 to 96 hours after the initiation of
therapy.1
The
data
upon
vllich
this
sugges-tion
is based
consist
of
invitro
antibioticsensi-tivity studies of 24 strains of
B.
pertussis
andfour
case
ieports.1
However,
it appears thatoccasionally as many as 8 to 10 days of
ampi-cillin or 7 days of tetracycline therapy may not
always
be
effective.
In fact,
it is unclear from this present series of patients whether therapyhad
any
role
in
altering
the
potential
corn-municability of
B.
pertussis.The
ability
to
isolate organisms from proven cases who areuntreated is known to diminish rapidly after
the fist 3 weeks of illness.6 This is further
supported by
the
recommendation
that
patients
should be consi:lered most contagious during
the period extending from 7 days after
ex-posure
to
3
weeks
after
onset
of
typical
7 In our patients, the one who
ap-peared
to
become
free
of
organisms
after
a
course of thera)y bad already had symptoms
of paroxysmal cough for at least 4 weeks prior
to treatment (Case 5).
There is th possibility that the prescribed
course of antil)iotics was not actually received
in
some instances, eithei- because of parental failure or vomiting. However, it is known thatsix
of
these
patients
received
all
or
part
of
their therapy (luring hospitalization an(l that vomiting as a cause of treatment failure
in
these pttieits was not a problem. Four of these
I)atiellts (Cases
1, 3, 4, and
8)
were
adminis-tered ampicillin in adequate doses for 5 or more
days.
We
conclude
from
these
observations
that,
although
antibiotics
such
as
ampicillin
and
tetracycline may
be
of some
use
in shortening
the
period
of communicability
of B.
pertussis,
further controlled studies are necessary to
establish this fact. Furthermore, it is strongly
recommended
that
no
such
patient
should
be
assumed
to
be
non-contagious
following
a
5-day course of therapy. Such a conclusion can
only
be
made
on
the
basis
of the
cultural
and
perhaps the fluorescent antibody studies at the
time that therapy is terminated.
SUMMARY
Antibiotic therapy of varying dose, type, and
duration was given to
1 1 infants
and
children
with
clinically and laboratory proven pertussis,and
cultures
and
FA
studies
were
used
to
determine
their
nasopharyngeal
carriage
of B.
J)eTtUSSIS organisms. Nine of the 11 patients
were found to still be harboring the organisms
at the conclusion of the initial course of therapy.
It
is
recommended
that
patients
with
per-tussis who are treated with antibiotics should
not be assumed to
be non-contagious
after
ther-apy is completed and that appropriate
bacterio-kgic
or FA
studies
are
essential
in determining
whether
nasopharyngeal carriage still exists.PETER
J.
ADASEK,M.D.
MARIE N. MEYER, MS.
C.
GEORGE RAY, M.D.Departments of Pediatrics and
Microbiology
University of Washington School of
Medicine and
Children’s
Orthopedic
Hospital
amid
Medical Center
Seattle, Washington
ADDRESS FOR REPRINTS:
( C.G.R.)
Children’s
Or-thopedic Hospital and Medical Center, 4800 Sand Point Way N.E., Seattle, Washington 98105.We are grateful to Bristol Laboratories, Syra-cuse, New York, who supplied the fluorescent anti-body conjugates used in this study, and to Drs.
John C. Sherris and Ralph
J.
Wedgwood for their advice (luring the preparation of this manuscript.REFERENCES
1. Nelson,
J.
D., Matteck, B. M., and McNabb, j.: Susceptibility of bordetella pertiissis to ampi-cillin.J.
Pediat., 68:222, 1966.2. Brooksaler, F., and Nelson,
J.
D. : Pertussis. AEXPERIENCE
AND
REASON-BRIEFLY
RECORDED
609
3.
Bradford, W. L. : The Bordetella Group. inDubos,
R.J.,
and
Hirsch,
J.
C., ed. :The
Bordetella
Group,
ed
4.Philadelphia:
J. B.
Lippincott
Company,
1965.4. Whitaker,
J.
A., Donaldson, P., and Nelson,J.
D. : Diagnosis of pertussis by thefluor-escent-antibody method. New Eng.
J. Med.,
263:850, 1960.5. Kendrick, P. L., Eldering, C., and Eveland, W. C. : Fluorescent antibody techniques. Amer.
J.
Dis. Child, 101 : 149, 1961. 6. Krugman, S., and Ward, R. : Infectious Diseasesof Children, ed 4. St. Louis: C. V. ?#{128}Iosby,
Company,
1968.7.
Gordon,
J. E.,
ed.:
Control
of Communicable
Diseases in Man, ed. 10. New York:
Ameri-can
Public
Health
Association,
1965.
Transient
Left
Bundle
Branch
Block
in
a
Neonate
Left ventricular conduction delay, or left
bundle
branch
block
(LBBB)
,is quite
rare
in
children and has not been previously reported
IU
the
neonatal
period.
In
adult
populations,
epidemiologic studiesl,2 suggest
that
LBBB
is
usually anacquired
condition
that
results
from
organic heart disease,
and
the
incidence
is
probably less than 1 per 10,000 individuals.
In
children
this
electrocardiographic
pattern
may
be
associated
with
diphtheria;
rheu-matic, viral, or bacterial rnyocarditis;4
congeni-tal heart disease; drug toxicity;8 surgical trauma;#{176}’10
diffuse
myocardial
disease;
and
nivocardial 1 “Benign” LBBB, or left
ventricular conduction delay in patients with
no
evidence
of
heart
disease,
has
been
described in a few 2, 12
and
even
as
a
familial occurrence.13 Since most
of
these
pa-tientswere
over
35
years
of age,
it is possible
that
the
conduction
delay
was
due
to
an
acquired
disease.
Congenital
anatomic
defects
of
the
conduction
fibers
may
account
for
some
of these
incidents,
similar
to that
described
in
right bundle branch 415
The
purpose
of
this report is to describe a neonate
with
tran-sient LBBB and to compare
the
findings
in
this infant to those which are usually seen inolder individuals.
CASE REPORT
A 14-month-old Negro male has been followed since birth at Grady Memorial Hospital. He was
the
product
of
a full-term,
normal
delivery.
His
mother
was a 13-year-old sero-negative,primigra-vida whose course was uneventful, except for a
short illness during the eighth month of
preg-nancy. This
illness
consisted
of coryza,
cough,
and
malaise
persisting
for
2 weeks and was treatedonly
with
aspirin.
The
family
history
wasnoncon-tributory and the mother’s electrocardiogram was
normal.
Prior
to delivery
there
was
no evidence offetal
distress
and
the fetal
heart rate remainedbe-tween
130 and
144 beats per minute during labor.The mother received 50 mg each of merpendine
hydrochloride and hvdroxyzine intramuscularly 4
hours
prior to delivers-. At the same time, apara-cervical
injection of carbocaine was performed,using less than 200
mg.
One minute after the de-livery the infant’s Apgar was 10 and the umbilicalcord had
three
normal
vessels.On
routine
physical
examination
at
6 hours ofage,
the
infant
appeared
normal
in every
respect.
However, the first heart sound was
almost
inaudi-ble and,
because
of this,
an electrocardiogram
was
obtained.
The
heart
rate
was 138 per minute;res-Pirations were
32
per minute; temperature was 98.6#{176}F ( rectal) ;blood
pressures were(
RA)
70/50 and(
RL) 70/55; weight was 2.85 kg; length was 49 cm. Examination was negative, except for a mirkedly diminished firstheart
sound and a widely spit second heart sound that remained splitthroughout
the respiratory
cycle.
The
initial
hema-tocrit was 50% and the white blood cell count was normal. Lupus erythematosus P’P were negative. Routine cultures of the nasopharynx, blood, and
stools
revealed
no growth.
Serum
immunoglobulin
NI ( 1gM ) levels
were
normal and no virus wasiso-lated
from
stool
and
throat
swabs
processed
inrhe-sos monkey kidney cells, HEp-2 cells, and
new-born
mice.#{176} Chest roentgenograms onthe first and
fourth days of life were within normal limits. The
initial
electrocardiogram,
which
wastaken
at the
age of 6 hours ( Fig. 1)
, was interpreted as completeLBBB.
During the nursery period the infant
remained
asym})tomatic and gained weight as expected.Re-peat
electrocardiograms
revealed
unusual
altera-tions. On
the
initial
tracing
at
6 hours of age, theQ
RS duration was 0.13 seconds and there was pro-longation of the P9 interval to 0.14 seconds. Thepattern of ventricular (lepolarization and the ST
and
T wave changes were compatible withcorn-plete
LBBB. However, the initial 0.02 secondvec-tor of the QRS was unusual in direction, pointing
to
the
right,
anteriorly and inferiorly, resulting ina tiny q wave in lead I, AVL and V. The pattern
of LBBB
was not influenced by changes in heartrate and persisted until the third hospital day; the
QRS duration had decreased on the third hospital
day to 0.10 seconds and the ST-T direction
be-came
more
normal
( Fig.
1 )
.The
mean
QRS
vector
was posteriorly oriented and was approximately 0
a?sIilton H. Hatch, Sc.D., Enterovirus Infections Unit, National Communicable Disease Center,