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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 eradication

of 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 nasopharynx

until

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 of

fluorescent-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. Negative

controls

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 of

antibiotic 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

(2)

‘FABLE I

EFFEcT OF ANTiBIOTICS ON

B.

I’ERTUSSIS IN TIlE NASOPHARYNX

Case 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.

(3)

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 a

variety 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, when

these 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 therapy

with either ampicillin or tetracycline will eradi-cate

B.

l)C11S.siS from the nasopharynx, often

within 48 to 96 hours after the initiation of

therapy.1

The

data

upon

vllich

this

sugges-tion

is based

consist

of

in

vitro

antibiotic

sensi-tivity studies of 24 strains of

B.

pertussis

and

four

case

ieports.1

However,

it appears that

occasionally 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 therapy

had

any

role

in

altering

the

potential

corn-municability of

B.

pertussis.

The

ability

to

isolate organisms from proven cases who are

untreated 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 that

six

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. A

(4)

EXPERIENCE

AND

REASON-BRIEFLY

RECORDED

609

3.

Bradford, W. L. : The Bordetella Group. in

Dubos,

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 the

fluor-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 Diseases

of 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 an

acquired

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-tients

were

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 in

older 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 treated

only

with

aspirin.

The

family

history

was

noncon-tributory and the mother’s electrocardiogram was

normal.

Prior

to delivery

there

was

no evidence of

fetal

distress

and

the fetal

heart rate remained

be-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, a

para-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 umbilical

cord had

three

normal

vessels.

On

routine

physical

examination

at

6 hours of

age,

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 first

heart

sound and a widely spit second heart sound that remained split

throughout

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 was

iso-lated

from

stool

and

throat

swabs

processed

in

rhe-sos monkey kidney cells, HEp-2 cells, and

new-born

mice.#{176} Chest roentgenograms on

the first and

fourth days of life were within normal limits. The

initial

electrocardiogram,

which

was

taken

at the

age of 6 hours ( Fig. 1

)

, was interpreted as complete

LBBB.

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, the

Q

RS duration was 0.13 seconds and there was pro-longation of the P9 interval to 0.14 seconds. The

pattern of ventricular (lepolarization and the ST

and

T wave changes were compatible with

corn-plete

LBBB. However, the initial 0.02 second

vec-tor of the QRS was unusual in direction, pointing

to

the

right,

anteriorly and inferiorly, resulting in

a tiny q wave in lead I, AVL and V. The pattern

of LBBB

was not influenced by changes in heart

rate 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,

(5)

1969;44;606

Pediatrics

Peter J. Adasek, Marie N. Meyer and C. George Ray

in the Nasopharynx

Bordetella pertussis

Antibiotics and Their Effect on

Services

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(6)

1969;44;606

Pediatrics

Peter J. Adasek, Marie N. Meyer and C. George Ray

in the Nasopharynx

Bordetella pertussis

Antibiotics and Their Effect on

http://pediatrics.aappublications.org/content/44/4/606

the World Wide Web at:

The online version of this article, along with updated information and services, is located on

American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397.

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