sGuidelines for the Judicious Use of
Antibiotics for Upper Respiratory Infections
and Other Related Diseases in Children.
- Our Proposal -Ver. 3 Apr. 10th2007
Ver. 2 May 1st 2006
Ver. 1 Nov. 1st 2005
Working Group for the Judicious Use of Antibiotics in Pediatric Ambulatory Practice
Akira KUSAKARI (Kusakari Pediatric Clinic), Hajime TAKEUCHI (Mimihara General Hospital, Pediatric Department),
Tatsuo NISHIMURA (Nishimura Pediatric Clinic), Mitsuru FUKAZAWA (Fukazawa Pediatric Clinic), Hitoshi YOSHIDA(Yoshida Pediatric Clinic; also Editor of this publication) JAPAN(In the order of the Japanese alphabet): Contact us

Introduction

ABSTRACTThe common cold
Antibiotics are not needed.
Pharyngitis and tonsillitis
1) Most cases of pharyngitis/tonsilitis are viral infections. There is no need for antibiotics except when group A
beta-hemolytic streptococcus (GABHS) is the causative pathogen.
2) In the case of GABHS infection, benzylpenicillin benzathine is the first-line agent.
Acute otitis media
Follow up with symptomatic treatment only. If the symptoms (otalgia or fever) have not subsided within 48-72 hours,
administrate an antibiotic. In case the symptoms (otalgia, fever or sickness) have worsened during the observation
period, examine the patient immediately.
Acute sinusitis
Most cases of acute sinusitis are viral infections. Do not use antibiotics for the first 10-14 days, even if purulent nasal
discharge is present.
Cough illness/bronchitis
1) Most of cough illness/bronchitis are caused by viral infections. Antibiotics are not justified for the treatment.
2) Erythromycin is recommended if pertussis is suspected.
Fever without source
Observe patient’s condition without administering antibiotics.
However, when one of the findings below is present, intravenous ceftriaxone is our recommendation:1) Infants of 3-12 months old with either a temperature of ≧40°C, or 38.5°C or more and leukocyte count of ≧15,000/µl( or neutrophil count of ≧10,000/µl).
2) Infants of 12-36 months old with a temperature of ≧39°C and leukocyte count of ≧15,000/µl (or neutrophil count of≧10,000/µl).

1INTRODUCTION

infections by individual doctors in Japan and that many
doctors over prescribed antibiotics. This might reflect thefact that they do not share the same standard for the useof antibiotics 6).
Our working group for the judicious use of antibiotics
proposes these Guidelines, incorporating our own
research with studies from other countries. Our objectives
are the judicious use of antibiotics and the reduction ofresistant strains, without adversely affecting patients.
Therefore, our Guidelines are structured to cover not only
upper

Antibiotics, which have been developed through therespiratory

infections(The

CommonCold,wisdom and efforts of mankind, have been saving

Pharyngitis and Tonsillitis), but also other related

thousands of human lives. For a time, it seemed thatdiseases (Cough Illness/Bronchitis, Acute Sinusitis andantibiotics might possibly eradicate all bacterial infections.

Acute Otitis Media), and the risk control of fever (Fever

However, this hope was crushed with the emergence of

without Source) as a part of the treatment method of

antimicrobial-resistant bacteria. We have since learned

serious bacterial infections.

that

the

use

of

antibiotics

inevitably

entailsthe

The subjects of these Guidelines are children over theappearance of more resistant strains of bacteria. Until

age of three months with no underlying conditions suchrecently, new antibiotics have been repeatedly created toascombat the new strains of resistant bacteria. However, itbroncho-pulmonary dysplasia, immotile cilia syndrome

is becoming impossible to continue using this method,and so on. (When treating febrile infants aged less than 3

because bacterial resistance is developing faster thanmonths, see the guidelines by Baraff et al. 7))

immunodeficiency,

immunosuppressive

state,

new antibiotics 1).
The isolations of the resistant bacteria are closely

The Guidelines for the use of antibiotics are as follows:

related with the usage of antibiotics in each country. In

1) Antibiotics should not be prescribed for viral

Japan, not only are a large amount of antibiotics used,diseases. Prescription for the prevention of abut broad-spectrum antibiotics are also used more widely

secondary bacterial infection should also be avoided.

than in other countries. As a result, the rate of resistant2) Even if a bacterial infection is suspected,

bacteria is very high, causing difficulty in treating severe

antibiotics should not be used when the risk ofbacterial infections such as meningitis. Therefore, in

severe complications is low and a recovery withoutorder to continue using antibiotics, it is imperative that we

antibiotics is expected.

establish guidelines and share a basic policy for3) Antibiotics should be used when there is evidenceprescribing and using antibiotics.

ofPrevalence of resistant strains of bacteria in Europe

bacterial

infection

and

the

therapeutic

effectiveness, of antibiotics, has been confirmed.

has been very low, compared to other parts of the world.

4) The use of antibiotics is appropriate when a patientThrough the initiative of the Netherlands, the European

has a fever and the laboratory data suggests a highAntimicrobial Resistance Surveillance System (EARSS)

risk of serious bacterial infection.

has been established leading to a full disclosure of5) Narrow-spectrum antibiotics, whenever possible,

information and the creation of educational programs

should be the first-line of therapy for bacterial

focused on reducing antibiotic resistance 2). Penicillin

diseases.

has

whereas6) When a disease such as sepsis, bacterial

broad-spectrum antibiotics (such as cephalosporin) havemeningitis, or other severe bacterial infections isbeen frequently used in Japan 3). The United States has

suspected, broad-spectrum antibiotics (sufficiently

also made medical guidelines, as one of their national

effective against possible resistant strains) should be

projects, to help solve the problem of the resistant strains.

used until the causative pathogen is revealed.

been

principally

used

in

Europe,These efforts are producing good results 4) 5).
Research data showed a wide variation in theThis set of guidelines is written from the viewpoint ofprescribing rate of antibiotics for upper respiratory

practitioners who see patients on a daily basis, and is2

Pediatrics 2003;111:668-670. [Full Text]

aimed at being adaptable to outpatient settings.
Because the clinical studies on which the Guidelines

6. 草刈 章 (Kusakari A), 他. 小児科外来における上気道

are based may be more beneficial than the Guidelines

炎診療調査―発病72時間以内の初診患者に対する抗themselves, we are including as many references as

菌 薬 使 用 状 況 ― . 外 来 小 児 科 2004;7:122-127 (Inpossible. We hope that the references cited here will be

Japanese)read as well as the Guidelines. (Note: It goes without

7. Baraff

LJ,

et

al.

Practice

guideline

for

the

saying that, when your patient follows an unexpected

management of infants and children 0 to 36 months

course, the plan of treatment should be modifiedof age with Fever without source. Pediatrics

depending on the patient’s condition. The ultimate

1993;92:1-12 [Abstract]

decision of the treatment is left to the attending

Return to the top

physician. )Various opinions regarding the content of these
Guidelines

have

been

collected

from

extensive

THE COMMON COLD

discussions at: Symposium at the Meeting of The Japan
Pediatric Society (Fukuoka, 2003); Symposium at the
Meeting of The Society of Ambulatory and General
Pediatrics of Japan (Oita, 2004) and their workshops (5times in total during 2000-2004) and conferences (Osaka,
2005; Yokohama, 2006). We will further investigate thevalidity of these Guidelines, seek opinions from various
quarters, and revise editions regularly. This edition has
been revised through the valuable contributions of 24

1. Introduction

pediatricians in 18 countries.
The common cold heals without antibiotic treatment.
Note: Leaflets for the patients (written in Japanese),

However, any doctor may think, “Could it be an onset of“Antibiotics and Resistant Bacteria” “Acute Bronchitis”

serious infections?” or “Could it cause a secondary“Children and Otitis Media” from The Society ofbacterial infection?” As a result, antibiotics are too often

Ambulatory and General Pediatrics of Japan are available

prescribedat the following: Noble Press; Tel: +81-3-3398-1904 Fax:

infections. However, with the recent development of+81-3-3398-1905 E-mail: noble@sepia.ocn.ne.jp

various immunodiagnostic methods (rapid diagnostic

toprevent

serious,

but

rare,

bacterial

tests, for example), blood tests using a very small amountof capillary blood, and easier access to medical services

Referencesin Japan, it is possible to offer patients good medical care
1. 吉川昌之介 (Yoshikawa M). 細菌の逆襲

中公新書

without depending on antibiotics.

1234. 東京:中央公論社 1995:260-263 (In Japanese)
2. McKerrow W, et al. Management of sore throat and2. Diagnostic guideline

indications for tonsillectomy. A National Clinical
Guideline. SIGN Publication 1999;34:1-23

The

common

cold

is

an

acute

viral

diseasecharacterized by a generally good condition aside from

[Full Text]

the main symptoms of nasal discharge and congestion.

3. SWEDRES 2001. A report on Swedish antibiotic
medicine.

Other associated symptoms may include a slight sore

STRAMA (the Swedish Strategic Programme for thethroat, a mild cough, and a fever (usually below 38.5 °C).

Rational Use of Antimicrobial Agents) [Full Text](Note: see the Guidelines of Pharyngitis/Tonsillitis or

4. Dowell F, et al. Principles of judicious use of

Cough/ Bronchitis if there is marked redness of the throat

utilisation

andresistance

in

human

or a moderate to severe cough.)antimicrobial agents for pediatric upper respiratory
infections. Pediatrics 1998;101(suppl):163-165[Full Text]

3. Treatment guideline

5. Bauchner H, et al. Promoting the appropriate use of
Antibiotics are not needed to treat the common cold.

oral antibiotics: There is some very good news.

3complications were found in 7% and 8% of the subjects inthe antibiotics and the placebo groups, respectively.

4. Overview

These findings represented no significant difference
between the two groups 8). Furthermore, a meta-analysis

1) Etiology, pathology and symptoms of the common coldof 6 RCTs showed no effect in the alleviation ofsymptoms and concluded that the use of antibiotics is not

In some European and American countries, the term,ofadvisable for the common cold 9) 10). An epidemiologicalrhinosinusitis 1). However, there is another opinion thatstudy also reported that most symptoms of the common

the term, “rhinosinusitis,” is not proper in the cases

cold lasted no longer than 10-14 days; therefore we

without

term,

advice that the course of the disease be monitored“nasopharyngitis,” may be more appropriate, especially inwithout the administration of antibiotics during this period

the case of children 2).

11) 12). (Note: see the Guidelines for “Acute Sinusitis” if“thecommoncold,”

symptoms

isusedsuggestingasasinusitis.

synonymThe

the symptoms persist after this period.)

The causative pathogens of the common cold areviruses. The symptoms start when viruses adhere to the3) Preventing complications through antibiotics

nasal and pharyngeal mucosa or palpebral conjunctiva
and invade the epithelial cells. When macropharges inthe submucous tissue recognize that the viruses have

Cronk et al. investigated the rate of second hospital

invaded the epithelial barrier, inflammation-promoting

visits for the penicillin group and the symptomatic

substances such as prostaglandin are released, causing

treatment group in 2,177 university students. The rates

capillary dilation and mucosal reddness. It also increases

werevascularswollendifference), and therefore the effectiveness of antibiotics

submucosa followed by pain and discomfort of thewere denied 13). An RCT which studied the preventive

pharynx. In the nasal mucosa, viruses cause nasal

effects of antibiotics for complications in 845 children

congestion or clear nasal discharge. Inflammatory

found no difference between a normal dosage, ¼ of acytokines and chemokines secreted by macrophages anddosage, or no dosage of antibiotics in secondary

epithelial cells further promote these biological reactions,occurrences of otitis media, pneumonia, or tonsillitis 14).

and enhance and sustain inflammatory response, by

Lexomboon et al. also disproved the effects of antibiotics

gathering neutrophils and monocytes in the blood until

because there was no difference in duration of fever orthe viruses are completely eliminated. In this way,development of complications (5.1% and 4.6% in thesystemic symptoms such as fever, fatigue, headaches,

antibiotics and the no treatment groups, respectively) 15).

loss of appetite, and muscle pain begin to appear 3).

A meta-analysis of 5 studies (including this trial) also

Within 1-3 days, nasal discharge starts to include

dismissed the preventive effects of complications 16).

epithelial cells, neutrophils, and normal flora, all of which

Dowell et al. reviewed 9 RCTs and reconfirmed that

become purulent without bacterial infection 4). Cough andantibiotics did not have any effect on either the conditions

nasal symptoms are normally resolved in 10-14 days,such

although they may occasionally linger over two weeks 5).

complications such as otitis media or pneumonia 17).

permeability,which

causes

a

26%

as

and

nasal

20%

respectively

discharge

or

the

(no

significant

occurrenceof

The main causative organisms are: rhinoviruses (30%),
coronaviruses (10%), RS virus, influenza viruses (type A4) Differentiation from other diseases

and B), and adenoviruses collectively (10-15%) 6). In
addition, influenza virus type C, enteroviruses, newly

Depending on the progression of symptoms of theidentified human metapneumovirus (hMPV), and novelcommon cold, it may be necessary to refer to each of thehuman coronavirus can be causative agents 7).

other Guidelines:
When nasal discharge or congestion persists over 142) Alleviating symptoms through antibiotics

days, see “Acute Sinusitis”.
When a sore throat is the main symptom, see

Todd et al. studied a randomized control trial (RCT) in“Pharyngitis / Tonsillitis”.

children with the common cold. It showed that the

When an ear pain is present, see “Acute Otitis Media”.

alleviation of purulent nasal discharge was observed after

When a cough is the chief complaint, see “Cough Illness/

5-6 days in 24% and 37% of the subjects, andBronchitis”.

4ed. Philadelphia: Saunders, 2004:140-146

When there is a high fever for which the cause cannot be
specified, see “Fever without Source”.

4.

van Volkenburgh VA, et al. Acute minor respiratory
diseases prevailing in a group of families residing in

Initial symptoms of serious bacterial diseases are likethose of the common cold. It is sometimes quite difficult

Baltimore,

to distinguish bacterial infection from the common cold. In

distribution and clinical description of observed cases.

cases of fever of unknown origin urine and blood tests

Am J Hyg 1933; 17:122-153

should be taken, suspecting urinary tract infection or

5.

Maryland,

1928-1930.

Prevalence,

Burroughs M, et al. Respiratory infections. In:

occult bacteremia. As the onset of Kawasaki disease isGershon AA, et al, eds. Krugman’s Infectious

also just a fever, it is difficult to make a precise diagnosis

Diseases of Children. 11th ed. Philadelphia: Mosby,

until its characteristic symptoms such as conjunctival

2004:493-529

hyperemia or injected and dry fissured lips appear.

6.

Gwaltney JM Jr. Virology and immunology of the

Above all, bacterial meningitis is one of the most serious

commoninfections. Making a diagnosis on the first visit is difficult,[Medline]

as a patient’s chief complaint is only a fever without

7.

cold.

Rhinology

1985;

23:265-271

Fouchier RAM, et al. A previously undescribedmeningeal signs. Systemic conditions (whether or not thecoronavirus associated with respiratory disease inchild looks reasonably well and calm, smiles, speaks, orhumans.

plays) should be continually monitored. If conditions

2004;101:6212-6216 [Full Text]

worsen,diagnostic

immediately 18).

tests

shouldbeperformed

8.

Proc

Natl

Acad

Sci

USA

Todd JK, et al. Bacteriology and treatment of purulent

An automatic prescription of oral

nasopharyngitis: a double blind, placebo-controlled

antibiotics (for fear of serious disease) could do moreevaluation. Pediatr Infect Dis 1984; 3:226-232

harm than good to the patient. A study revealed that[Medline]patients treated with oral antibiotics were more likely to

9. Morris P, et al. Antibiotics for persistent nasal

have hearing loss or neural sequelae because thedischarge (rhinosinusitis) in children (Cochrane

medication masked the presence of meningitis andReview).

delayed the start of appropriate treatment 19).

Cochrane

Database

Syst

Rev

2002;4:CD001094 [Medline]

Careful observation of the patient’s condition (a “wait

10. Aroll b, et al. Antibiotics for the common cold andand see approach”), in which the patient could be seen

acute purulent rhinitis (Review). Cochrane Databasewhenever unusual symptoms are observed, produces aof Syst Rev. 2005;3:CD000247
11. 草刈章 (Kuakari A), 他. チャートでみる抗菌薬適正

faster diagnosis (see “Fever without Source”).

使用ガイドライン・急性副鼻腔炎. 外来小児科
2006;9:211-214. (In Japanese)

5. Summary

12. Wald ER, et al. Upper respiratory tract infections in
The common cold heals without antibiotics. Antibiotics

young children: duration of and frequency of

do not prevent secondary bacterial infection. Careful

complications. Pediatrics 1991;87:129-133 [Medline]

observation of the patient (a “wait and see approach”) is

13. Cronk GA, et al. A controlled study of the effect of

the best and quickest way to detect serious bacterial

oral penicillin G in the treatment of non-specificinfections hidden in the common cold. Overuse of theupperadministration of antibiotics delays both the correct

1954;16:804-809

diagnosis and the start of appropriate treatment.

respiratory

infections.

Am

J

Med

14. Townsend EH Jr. Chemophylaxis during respiratory
infections in a private pediatric practice. Am J Dis

References

Child 1960;99:566-573
15. Lexomboon

1.

U,

et

al.

EvaluationoforallyTurner RB, et al. The Common Cold. In:Behrman RE,

administered antibiotics for treatment of upper

et al, eds. Nelson Textbook of Pediatrics. 17th ed.

respiratory infections in Thai children. J Pediatr

Philadelphia: Saunders, 2004:1389-1393

1971;78:772-778

2.

Puhakka T, et al. Sinusitis in the common cold. J
Allergy Clin Immunol, 1998; 102:403-408 [Abstract]pneumonia among young children: lack of effect of3.

Cherry JD. The Common Cold. In:Feigin RD, et al,antibiotic treatment for upper respiratory infections.

eds. Textbook of Pediatric Infectious Diseases. 5th

Pediatr Infect Dis J 1993;12:115-120 [Medline]

16. Gadomski AM. Potential interventions for preventing

5are often swollen with exudate. Cough may also be

17. Dowell SF, et al. Appropriate use of antibiotics forpresent.

URIs in children: Part II. Cough, pharyngitis and thecommoncold.

Am

FamilyPhysician

1998;58:1335-1342 [Full Text]

3. Treatment guideline

18. McCarthy PL, et al. Observation scales to identify
seriousillnessinfebrilechildren.

a) Most cases of pharyngitis/tonsilitis are viral infections.

Pediatrics

There is no need for antibiotics except when GABHS is

1982;70:802-809 [Abstract]the causative pathogen.

19. Kaplan SL, et al. Association between preadmission
oral antibiotic therapy and cerebrospinal fluid findingsb) In the case of GABHS infection, benzylpenicillin

and sequelae caused by Haemophilus influenzaebenzathine (Bicillin G®, 400,000U/g, available in limited

type b meningitis. Pediatr Infect Dis 1986;5:626-632

countries) 50,000U/kg/day (up to 1,600,000U=4g/day), 3[Medline]times orally for 10 days is the first-line agent. If the patientis

Return to the top

allergic

tobeta-lactam

antibiotics,

erythromycin

50mg/kg/day (up to 1200mg/day), 3 times orally for 10
days is the second-line agent.

PHARYNGITIS AND TONSILLITIS

4. Overview
In Europe and America, pharyngitis and tonsillitis arecollectively known as sore throat 1) 2). In Japan, they
have often been separated on clinical diagnosis. However,there is no need to differentiate between them, because
their main difference is the extent and degree of theinflammation.
1) Causative pathogens
As far as the children’s tonsillitis with “exudates” are

1. Introduction

concerned, 12% of the causative pathogens are GABHS,
Pharyngitis and tonsillitis are often associated with high

42% are various viruses, of which 45% are adenoviruses

fever and white exudate on the tonsils; therefore they3). Other microbes isolated and cultured are not identified

tend to be considered as a bacterial infection. However,as causative pathogens. The flora such Haemophilus

many of their causative pathogens are viruses. Group A

influenzae, Staphylococcus aureus, and Streptococcus

beta-hemolytic

ispneumoniae are often isolated from the throat of healthy

treated with antibiotics to prevent rheumatic fever (RF) or

children. They are considered to be carriers of these

poststreptococcal acute glomerulonephritis (PSAGN).

pathogens. When a causative organism is unknown,This

involvement of other viruses difficult to detect may be

infection

streptococcus

accounts(GABHS)for

only

infection

10-20%

ofpharyngitis/tonsillitis at most. It should be noted that thesuspected.

pathogen colonizes in the tonsil of up to 15% of healthyrhinoviruses, coronaviruses, herpes simplex virus (HSV),

children aged 5 to 12 years old.

influenza

Haydenal.

viruses,coxsackieviruses,

Clinical findings of pharyngitis/tonsillitis are easilyetisolatedadenoviruses,

parainfluenza

Ebstein-Bar

virus

viruses,

(EBV)

and

obtained as doctors can observe an affected region

cytomegalovirus as causative organisms for acutedirectly. It has also become possible to specify thepharyngitis 4). Other pathogens such as RS virus andcausative pathogen using various rapid-test methods.

human herpes viruses type 6&7, the causative virus ofexanthema subitum, can also cause pharyngitis.
In 2004-2005, a multi-centered prospective study

2. Diagnostic guideline

concerning about “exudative” tonsillitis was performed inJapan. The causative pathogens were viruses in

The main symptoms of pharyngitis/tonsillitis are sore

63/149(42%)

throat and fever. The pharynx is reddish and the tonsils

6

and

GABHS

in

25/143(17%).

Twopathogens, virus and GABHS, were simultaneously

show strong positive results, it is necessary to rule out adetected in 4 cases. The detected viruses werebacterial infection such as occult bacteremia. A study of

adenoviruses in 48 cases, coxsackieviruses in 6 cases,

patients with positive results of adenovirus (n=143) foundinfluenza viruses and HSV in 3 cases, and parainfluenza

only two cases of complications with bacterial infections:viruses and echo viruses in 2 cases, respectively 5).

one with a urinary tract infection of E. coli, and the other
with

of

Moraxellacatarrhalis(1.4%

bacterial infection, although requiring some attention,

Adenoviruses are most frequently identified as aorganismbycollectively) 9). The possibility of complications with

(1) Adenoviruses (Fig 1.)
causative

bacteremia

pharyngitis/tonsillitis

3)

seems to be rare.

5).

Although a typical pharyngoconjunctival fever can be(2) Other viruses

diagnosed by clinical examination only, there are many
atypical cases. Therefore, it is important to know the

Pharyngitis/tonsillitis due to virus is often associatedendemic situation in order to identify it. Adenovirus

with cough and nasal discharge as well as pharyngeal

infection often causes a high fever of 40 °C or above

symptoms. EBV usually exhibits “membranous” exudate

which lasts 4–5 days. In more than half of the cases,on the tonsil while coxsackieviruses and HSV exhibit only

leukocytes count of ≧ 15,000/µl was observed in the“streaky” exudate. Many of EBV infections are associatedearly stage of the fever, and CRP level also increased

with cervical lymphadenopathy and hepatosplenomegaly.

during the course 6).

Blood test often reveals leukocytosis with increased
atypical lymphocytes. Diagnosis of EBV infection can be
confirmed by serological antibody tests 10). The infection

Fig 1. Tonsillitis due to Adenovirus

with coxsackieviruses is characterized by more than one
Boy , age 10

ulcer of 2-3mm in the soft palate. The endemic often

There are white exudates

occurs in the summer. With HSV infection, gingival

on both tonsils.

swelling/redness and aphthae on the oral mucosa andtongue are usually observed.
(3) GABHS infection
Although it is possible to start the treatment based onclinical symptoms and signs in a typical case, it is

The rapid antigen-detection test is useful for diagnosis.

fundamental to treat this infection after confirming the

A test kit released in 2001 in Japan facilitated the

diagnosis, particularly in an otherwise indistinguishable

diagnosis of adenovirus infection. The use of the test notcase, by a rapid antigen-detection test or a culture.

only reduces the administration of antibiotics but also

However, a study found that the rapid test was positive inhelps to reassure parents by giving the prospect of

18% of the healthy children in an elementary school.

recovery. The sensitivity of the test is reported to beThus, some children are carriers of GABHS, so it is not

70-94%, so a negative result does not completely rule out

always easy to differentiate infection from colonization 11).

a possibility of adenovirus infection. The specificity, on the

As a carrier should not be treated, it is unnecessary toother hand, is 95-100%, and therefore a positive result

use antibiotics when there are no clinical manifestations

confirms adenovirus infection 7). Our study comparing

or characteristic findings of the infection even if the test is

the rapid test with viral isolation also showed that thepositive 12) 13).

sensitivity was 83% and specificity was 98% 5).

The infection occurs most commonly in children of 3

Although there are reports of viral excretion for months

years old or older. An endemic occurs often in winter, but

or infection with mild symptoms only, the facts that thethe first term of the school year could be an endemic

virus is rarely isolated from healthy school children

season(1/174; 0.6%) and that the results of the test becomekindergartens 13). The main symptoms are a fever andnegative after the acute stage indicate that it issore throat, but a headache, fatigue, stomachache,appropriate to consider that the positive result means

nausea and vomiting may also be present. If a cough,adenovirus infection 8).

nasal discharge, stridor, tachypnea or diarrhea is seen,

becausenewcomersenterschoolsor

GABHS infection is not likely to exist 12). Conjunctivitis

Because blood tests (leukocyte count, CRP level) often

7could be added as a rule-out sign. A fever of 38.3°C or

On the contrary, in Scotland UK, where the yearlyhigher is found in 30% of the cases 14). The pharynx is

incidence of RF was 0.6/100,000 (27 cases out ofreddish and the soft palate is often erythematous or

4,400,000), there was no significant difference between

petechial (Fig 2.) The tonsils are also swollen and red,

the group administered with antibiotics and the untreatedsometimes covered with exudate. The tongue’s papillae

group. Thus, it was not proved that antibiotics were

may also be swollen and red (strawberry tongue).

effective to prevent RF. Based on these results, Scottish

Anterior cervical lymphadenopathy with tenderness is an

Intercollegiate Guidelines Network (SIGN) concluded thatimportant diagnostic finding. It is called scarlet fever whenantibiotics were not necessary for the treatment ofa characteristic generalized exanthema appears, but

GABHS infection 2) 18). As there is a discrepancy

there is no difference in the infectivity or prognosis.

between the two nations regarding the treatment of using
antibiotics for RF prevention, it is desirable to review thenecessity in Japan. However, it would be difficult to

Fig 2. GABHS infection

conduct an RCT because the treatment of GABHS
Boy, age 5

infection with antibiotics has been already establishedThe soft palate is erythematous

19).
A preventive effect of antibiotics for PSAGN or

and petechial.

Henoch-Schönlein purpura has been dismissed in Europe
and America. In Japan, however, its effectiveness has
been believed for a long time. In addition, atypical
PSAGN with hypocomplementemia and mild hematuria
occasionally occurs. Considering these possibilities and
The purpose of using antibiotics for GABHS is toexpert opinions in Japan 20) 21), it might be necessary to

alleviate symptoms such as high fever and to prevent

use antibiotics to prevent these diseases. Further reviews

secondary RF. If an epidemic of GABHS occurs, 3% of

are waited.

the pathogen is thought to be certain serotype strains thatare likely to cause a secondary RF (e.g. M protein 1, 3,(4) Bacteria other than GABHS

18 types), and therefore an RF outbreak also is

Although the possibility of involvement by othersuspected to occur. The prevalence of RF in school

bacteria cannot be completely ruled out, other countries

children in the United States is currently only 0.2/100,000,

also don’t recommend antibiotics unless GABHS is

whereas in Africa the prevalence is 1,500 times higher

present 22).

(300/100,000) 15). It therefore can be reasoned thathygienic conditions and living environment are strongly

2) Retropharyngeal abscess and peritonsillar abscessassociated with the prevalence. In 1985, an epidemic of
RF started in Salt Lake City, Utah, and affected 198

Althoughlessfrequent,

retropharyngeal

andpatients over a 4-year period. However, no relationshipperitonsillar abscess are important as complications or

between the living environment and the prevalence wasdiseases to be differentiated. They are most likely toseen 16). The contributing factors of the RF outbreak still

occur in boys up to 3-4 years old and are characterized

remain to be unsolved.

by the lack of movement of the jaws, torticollis or neck

The basis for use of antibiotics for the prevention of RF

stiffness in addition to nonspecific symptoms such as

is derived from a controlled study conducted during thefever, decreased oral intake and salivation. It is important

endemic of GABHS infection at an air base camp in

to consider a possibility of these two diseases andWyoming in 1949. The subjects were either injected

examine the oral cavity/pharynx carefully wheneverintramuscularly with penicillin G or a placebo, and 2/798

seeing a patient. Although GABHS is a predominant

in the former and 17/804 in the latter group developed RF,

cause of these conditions, Haemphilus influenzae,

thus demonstrating the effectiveness of the preventive

Klebsiella sp. or Mycobacterium sp. are also possible

treatment 17). Other studies followed in the US to confirm

causative microorganisms 23). When these complications

preventive effects on initial or recurrent cases of RF, andare suspected, refer the patient to a specialist of

based on these results, use of antibiotics for theotolaryngology.

prevention of RF has been considered as a standard 1).

8pharynx and use of rapid tests will improve the accuracy

3) Treatment

of diagnoses and promote the judicious use of antibiotics.
There is no need to use antibiotics for viral infections.
References

Even with a high fever, leukocytosis and increased CRP
level, they will heal without antibiotics.

1.

Antibiotics are used for treating GABHS infection.

et al, eds. Nelson Textbook of Pediatrics. 17th ed.

Narrow-spectrum penicillin is the best choice 1) 12). In
Japan,

oral

narrow-spectrum

penicillin

isHayden GF, et al. Acute Pharyngitis. In:Behrman RE,
Philadelphia: Saunders, 2004:1393-1394

only
2.

benzylpenicillin granule. Tablet or capsule is not available.

McKerrow W, et al. Management of sore throat andErythromycin is a universally accepted second-line agent

indications for tonsillectomy. A National Clinicalwhen there is an allergy to beta-lactam antibiotics 24).

Guideline. SIGN Publication 1999; 34:1-23

Careful attention should be payed to the increase in[Full Text]

bacteria strains resistant to macrolide antibiotics in Japan.

3.

Though cephalosporins are effective, they tend to

Putto A. Febrile exudative tonsillitis: viral or
streptococcal? Pediatrics 1987; 80: 6-12 [Abstract]increase the resistance of pneumococcus and other

4.

Hayden GF, et al. Management of the ambulatory

bacteria. It is therefore important to use as few

patient with a sore throat. Curr Clin Top Infect Dis

cephalosporins as possible 14).

1988;9:62-75

Fever subsiding within 24 hours of the treatment is an

5.

Takeuchi H, et al. Exudative tonsillitis - viral isolation

important sign as to the efficacy of diagnosis andand bacterial cultures of 149 cases. The 24thtreatment. Some cases are refractory to treatment or the

Annual Meeting of the European Society for

symptoms are recurrent even if the pathogen is

Paediatric Infectious Diseases (SPID). 2006 Baselsusceptible to penicillin. There are some causes for these[Abstract]

problems. The most common cause is an insufficient

Sessions → Respiratory Tract Infection)

taking of the medicine. Therefore, a dosing instruction for

6.

(See:

Scientific Program → Poster

武内 一 (Takeuchi H) . アデノウイルス 3 型感染症

the patient is very important. When a new infection with

―臨床症状・検査データと流行拡大の特徴―. 日児

other

誌

serotype

of

GABHS

is

suspected,

another

medication of the same penicillin may be effective. When

7.

(in Japanese)

原三千丸 (Hara M), 他. アデノウイルス迅速診断キ

erythromycin has been used, suspect an emergence of a

ットチェック Ad® 改良品の有用性の検討. 小児科臨

resistant strain against macrolides and change to a

床 2005; 58:221-223. (In Japanese)

susceptible antibiotic after a culture. It is also possible

8.

that pharyngitis is caused by another pathogen such as a

Edwards KM, et al. Adenovirus infections in young
children. Pediatrics 1985;76:420-424 [Abstract]virus, and the patient is only a carrier of GABHS 25). This

9.

Rocholl C, et al. Adenoviral infections in children:

is likely to be the case if a typical finding in the pharynx is

The impact of rapid diagnosis. Pediatrics 2004;

absent. Some studies reported that once GABHS invades

113:e51-56 [Full Text]

the mucosal cell, it will not be eliminated by antibiotics

10. 鹿野隆明 (Shikano T), 他. EB ウイルスによる小児and the patient becomes a carrier. However, in any case,

伝 染 性 単核 球 症 の臨 床 的 検討 . 日 児 誌

antibiotics should not be used only on a carrier. Another

2002;106:389-393, (In Japanese)study found that the streptococcus is protected by

11. 中島邦夫 (Nakashima K), 他. 学童の咽頭分離溶血

beta-lactamase produced by the normal flora in the

性 レ ン サ球 菌 の 疫学 的 研 究 . 感 染 症 学

pharynx: however, evidence to consider the presence of

1983;57:1075-1082 (In Japanese)beta-lactamase is vague.

12. Kumar S, et al. Why do general practitioners
prescribe antibiotics for sore throat? Groundedtheory interview study. Br Med J 2003;326:138-143

5. Summary[Full Text]
Most of pharyngitis/tonsillitis are viral infections and only

13. Bisno AL, et al. Practice Guidelines for the diagnosis

a part of them are due to GABHS. Antibiotics areandindicated for GABHS infection, retropharyngeal abscesspharyngitis.

and peritonsillar abscess. We believe that a grasp of the

2002;35:113-125 [Full Text]

endemic situations, precise observation of the patients’management

of

group

ClinicalA

Infectious

streptococcal
Diseases

14. McIsaac WJ. Practical experience with clinical9algorithms for reducing unnecessary antibiotic use

27. Gerber MA, et al. Potential mechanisms for failure toin the management of streptococcal pharyngitis.

eradicate group A streptococci from the pharynx.

Pechere JC, et al. eds. Streptococcal Pharyngitis

Pediatrics 1999;104:911-917 [Full Text]

Optimal Management. Issues Infectious Diseases.

Return to the top

1st ed. Basel: Karger, 2004:36-48 [Extract]
15. Guzman SV. Epidemiology of rheumatic fever and

ACUTE OTITIS MEDIA

rheumatic heart diseases. In: Calleja HB, et al, eds.
Rheumatic fever and rheumatic heart diseases.
Epidemiology, clinical aspects, management andprevention and control programs. Manila: Philippine
Foundation for the Prevention and Control ofRheumatic

Fever/RheumaticHeart

Disease,2001:1-12
16. Gerber MA. Group A Streptococcus. In:Behrman RE,
et al, eds. Nelson Textbook of Pediatrics. 17th ed.
Philadelphia: Saunders, 2004:870-879

1. Introduction

17. Denny FW, et al. Prevention of rheumatic fever;treatment of the preceding streptococcic infection.

Acute otitis media has been one of the disorders for

JAMA 1950; 143:151-153

which antibiotics were frequently prescribed in Japan. It is

18. Howie JG, et al. Antibiotics, sore throats andnow an urgent problem that the disease is becoming

rheumatic fever. JR Coll Gen Pract 1985;35:223-224

intractable due to the increase of antibiotic resistantbacteria.

19. Danchin MH, et al. Treatment of sore throat in lightof the Cochrane verdict: is the jury still out? MJA

Since 1990, in the Netherlands, a policy of essentially

2002; 177: 512-515 [Full Text]

not using antibiotics and following up patients with

20. 武田修明 (Takeda N), 他. 小児期急性糸球体腎炎のsymptomatic treatment only has been practiced 1) 2)

非典型例. 小児科 1997;38:1093-1098 (In Japanese)(modified in 1999). Owing to the principles of restricting

21. 武田修明 (Takeda N), 他. Henoch-Schönlein 紫斑病

the use of antibiotics, the rate of the resistantと溶連菌感染との関連性について. 小児科臨床

pneumococcus was 3% in the Netherlands, which was

2000;53: 1473-1477 (In Japanese)

remarkably low 3). In the United States, administration of

22. Schwartz B, et al. Pharyngitis - principles ofantibiotics had been the basis of therapy, but the 2004

judicious use of antimicrobial agents. Pediatrics

guideline published by the American Academy of

1998;101(suppl):171-174 [Full Text]

Pediatrics (AAP), for the first time, adopted a policy of

23. Goldstein NA, et al. Peritonsillar, retropharyngeal,

restricting the use of antibiotics 4). Our Guideline also

and parapharyngeal abscesses. In:Feigin RD, et al.

employs the same concept as the Netherlands-essentiallyeds. Textbook of Pediatric Infectious Diseases 5th

not using antibiotics.

ed. Philadelphia: Saunders, 2004:178-185
24. WHO Model Prescribing Information. Drugs used in

2. Diagnostic guideline

the treatment of streptococcal pharyngitis andpreventionofrheumaticfever.

Geneva:Acute otitis media is diagnosed by the presence of a

WHO/EDM/PAR/1999.1:1-18

purulent discharge (otorrhea) through a perforation of the25. Kaplan EL, et al. Diagnosis of streptococcal

eardrum, or middle-ear effusion plus symptom and/or

pharyngitis: differentiation of active infection fromfindings of acute inflammation in the middle ear. The

the carrier state in the symptomatic child. J Infectpresence of the effusion is ascertained by a fullness of

Dis 1971;123:490-501

the eardrum or no mobility observed by pneumaticofotoscopy. The symptom of acute inflammation is otalgia

among(causing crying, irritability or pulling of the ear in infants),

persisting group-A streptococcus strains isolated

and its findings are marked redness, strong bulge andfrombulla of the eardrum (Fig.)

26. Neeman

R,

et

al.

internalisation-associatedasymptomatic

1998;352:1974-1977

Prevalence

gene,

prtF1,

carriers.

Lancet[Medline]

10immediately.

Fig. Eardrum Findings
1) Normal eardrum (left)a) In case otorrhea is present: Follow up on the patient,
only by cleaning the external auditory meatus for 7 days.

This photo shows normal

If a fever or otalgia is present, follow the basic rule.

color (pearly gray) and normal
shape of the eardrum.

b) In case otalgia is present: Prescribe acetaminophen
10-15mg/kg/dose orally or suppositorily as analgesic. For
children over 2 years of age, ibuprofen 5mg/kg/dose(authorized dosage in Japan) is also an option. If otalgia
has persisted or worsened, the presence of symptoms

2) Acute otitis media (right)
This eardrum is reddish andand signs suggesting mastoiditis, such as protrusion ofhas a slight bulge due tothe pinna, postauricular swelling, tenderness, pain andmiddle ear effusion. But, it iserythema, must be examined.

difficult to distinguish acuteotitis media from otitis mediac) In case fever is present: Consider the complications

with effusion only by thesewithanotherseriousbacterial

infection,

such

as

findings. The diagnosis of this disease was made by anbacteremia or meningitis. In particular, the patient with aadditional presence of otalgia.

fever of 39°C or above (in children under 3 years of age)or 38.5 °C or above (in children under 1 year of age),should be examined on leukocyte counts. The patient3) Acute otitis media (left)
This patient is diagnosed aswith leukocyte count of ≧15,000/µl (or neutrophil count

acute otitis media based on aof ≧10,000/µl) or with toxic appearance is categorizedstrong bulge of the entire

as a “high risk group” and should be treated according toeardrum, though the degree of

the Guideline of “Fever without Source”. A culture of

redness is mild.

middle-ear

effusion,bypuncturing

thetympanic

membrane as a part of “sepsis work-up”, is an option.
4) Acute otitis media (left)d) Initial antibiotic treatment: The first-line oral antibiotic

slightlyis amoxicillin (AMOX). Administer 60-90mg/kg/day in 3

reddish and has a few bullas.

doses for 5 days. If the symptoms have not improved

These findings are often seen

within 24-48 hours after administration, change to anotherin infants.

oral or parenteral antibiotic. AMOX of standard-doseThiseardrumis(40mg/kg/day for 5 days) should limitedly be used forpatients who are at low risk for infection of resistant

It is sometimes difficult tobacteria or serious bacterial complication.

distinguish acute otitis media from otitis media with
effusion unless there are symptoms of otalgia. In an
indistinguishable case, diagnose as otitis media withe) In case antibiotics are not effective: If the otalgia,

effusion.

fever or sickness have not subsided within 48-72 hours
after the start of antibiotic treatment, a complication suchas mastoiditis without obvious clinical signs (masked
mastoiditis, or occult mastoiditis) may be suspected. In

3. Treatment guideline

thesecases,

consultation

with

or

referraltoanotolaryngologist should be considered.

For children over 6 months of age:
Basic rule: Follow up with symptomatic treatment only. If
the symptoms (otalgia or fever) have not subsided within

For infants under 6 months of age:

48-72 hours, administrate an antibiotic. In case the

Basic rule: Administer antibiotics, especially for infants

symptoms (otalgia, fever or sickness) have worsened

with a fever. There is little data available for the treatment

during the observation period, examine the patientof infants under 6 months of age. This recommendation is,11has disappeared, judge it as a ”complete cure; evaluate

therefore, a tentative one.

after 2 weeks, 4 weeks, 2 months and 3 months.
These assessment criteria are not the treatment goal in

4. Overview

actual medical practice. Acute otitis media treatment’s
1) Diagnosis of acute otitis media and the severity

focus is not necessarily the complete disappearance ofassessment

abnormal eardrum findings, but the disappearance of thesymptoms 8).

A correct diagnosis is a prerequisite for the judicious3) Effectiveness of antibiotics

use of antibiotics. However, it might not be possible todifferentiate acute otitis media clearly from otitis media
with effusion requiring no antibiotics. Our diagnostic

The Netherland’s guideline, that has drawn much

criteria are based on that of Bluestone et al. 5) and theattention from the world, is based on the two studies

guidelines of the AAP -- both of these require symptoms

conducted by an otolaryngologist, van Buchem and his

or findings suggesting acute illness.

colleagues in Tilburg, a local city of a population of

There is no accurate method of confirming acute onset

150,000 at that time. In 1981, the authors compared anfrom the eardrum findings; therefore, the findings of auntreated group (n=40), a myringotomy-monotherapy

marked redness, strong bulging or the presence of bulla

group (n=36), an AMOX administration-monotherapy

are adopted as a diagnostic sign of acute illness. The

group (n=47) and a combination of myringotomy + AMOX

findings of bulging, or bulla of the eardrum are important,group (n=48). Otalgia was found in 98%, 100%, 94%, andbecause the redness of the eardrum is not frequently

94% of each group respectively at the first visit; after 24

found in infants with acute otitis media. It is also essential

hours it was reduced to 28%, 28%, 28% and 35%; andto know that bilateral hyperemia of the eardrum is often

after 7 days 10%, 11%, 6% and 10%, representing noobserved in crying infants. There are some othersignificant difference between the groups. The rates ofguidelines on which a fever is one of diagnostic criteria

abnormal eardrum findings observed in each group were

for acute illness. Although fever is a symptom observed in

49%, 49%, 40% and 44% respectively after 7 days, and1/3-2/3 patients with acute otitis media, it is impossible to28%, 25%, 10% and 11% after 14 days, showing a

differentiate the fever caused by acute otitis media itself

slightly larger decrease in groups treated with antibiotics,

from that arising from the preceding viral infection.

regardless of myringotomy. This study concluded that

Therefore, we did not include the fever in our criteria.

there was no significant difference on the effectiveness ofantibiotics or myringotomy between these groups 9).

To classify the grades of severity, a method combining
otalgia and fever 6) or one of using the eardrum findings

In 1985, van Buchem et al. published the results ofhas been proposed. However, the most important aim of

4,860 subjects aged 2-12 years treated with a therapeutic

the therapy in the acute stage is to prevent complications

plan of “treat with analgesic only for the first 3-4 days andof serious bacterial infection. For this reason, we willobserve otorrhea for 14 days without antibiotics”; thesecategorize “high risk group” under “Fever without

results later became the base for the guideline of the

Source”.

Netherlands 10). Among these subjects, 126 (2.7%)
whose otalgia or fever persisted for more than 3-4 days(“persistent cases”) were included in an RCT and divided

2) Assessment of treatment effectiveness

into

one

of

the

following

threegroups:

It is necessary to evaluate treatment effectiveness, tomyringotomy-monotherapy,

facilitate comparison with other studies and provision of

myringotomy+AMOX. There was no difference in the rate

appropriate medical care 7). If symptoms of otalgia, feverof otalgia between the three groups after 24 hours, 7 days

and otorrhea have subsided, judge it as a ”remission”

and 14 days. Of all the subjects, 4.5% having anotherwhether or not abnormal findings of the eardrum remain;

bacterial infection not related to acute otitis media, andevaluate after 24hours, 2-3days and 1week. If the

1.5% having otorrhea for more than 14 days, were

aforementioned symptoms and the eardrum findings suchtreated with antibiotics. Including the persistent cases,

as redness or bulging (except for the middle-ear effusion)

more than 90% of all the subjects were resolved by thehave resolved, judge it as an “early stage cure”; evaluate

symptomatic treatment. Only two patients (0.04% of all

after the first and second week. If the middle-ear effusion

the subjects) developed mastoiditis, however, they

12

AMOX-monotherapy,

andrecovered with an outpatient treatment of myringotomy

0.11%) compared to the group with antibiotics (4/566;

and oral administration of AMOX.

0.71%) 17). In any case, the incidence of mastoiditis isvery low, so it never provides a basis for using antibiotics

These two studies made a considerable impact on thefor preventive purpose.

treatment policies in other countries. The 2004 guidelineby the AAP allowed observation without using antibiotics

Bacterial meningitis, complicated with acute otitis

except in seriously ill cases. This did not apply to children

media, may not be caused by the extension of theunder 2 years old, who were thought to be at a higher risk

disease itself or mastoiditis18), but it usually originatesof serious bacterial infections. However, Damoiseaux etfrom the bacterial flora in the nasopharynx and develops

al. reported that there was no problem with the policy of

via bacteremia. Occult bacteremia has been reported toobservation alone even for infants between 6 and 24

be associated with 1.5-3.0% of acute otitis media 19) 20),months old 11).

and two out of 375 cases (0.5%) were also found in a

In addition, there are a number of meta-analyses, each

Japanese study 14). Because the effectiveness of oral

showing that antibiotics have only a minor effect on acuteantibiotics to prevent bacterial meningitis from occult

otitis media, and that most patients recover withoutbacteremia is not sufficient 21), parenteral administration

antibiotics 8) 12) 13).

is needed. In other words, it is important not to overlook
serious bacterial infections including bacteremia inSince the reports from abroad included much data

patients of acute otitis media with fever.

studied when resistant strains of bacteria were few, they
may not be applicable to the current situation in Japan

5) Choice of an antibiotic and the administration period

where the resistant strains of bacteria are a major
problem.

Referringtoasimplecomparative(notrandomized) study of 375 subjects in Japan, antibiotics

Almost all studies regarding treatment methods haveshortened the duration of otorrhea in children over 2

not shown a difference in effects due to variations of theyears of age, but had no effect on the duration of otalgia,

kinds, dosages, or dosing periods of antibiotics 13)

the “remission rate” up to one week, the “early stage

22-28). This may be because antibiotics have little effect.

cure” rate up to two weeks, and the rate of “complete

Our Guideline, therefore, proposes choice and dosage ofcure” up to one, two and three months 14). Concluding

antibiotics

from these results, the effects of antibiotics in Japan, as

pharmacodynamics. The main causative pathogens ofin other countries, may be small.

otitis media are Steptococcus pneumoniae (40%),

based

on

pharmacokinetics

and

The incidence of adverse events (such as vomiting,

Haemophilus influenzae (25%), Moraxella catarrhalis

diarrhea, rash) were 10% in the untreated group vs. 17%(15%). And the increase of resistant strains of thesein the antibiotic administrated group (odds ratio: 1.97)

pathogens is an emerging problem 29) 30). As cases

12).

caused by Haemophilus influenzae and Moraxella
catarrhalis tend to recover without antibiotics, the initialchoice of antibiotics is made to target pneumococcus.

4) Prevention of serious complications

The ratio of penicillin-resistant Steptococcus pneumoniae
Prevention of serious complications such as mastoiditis(PRSP)

andpenicillin-intermediate

Steptococcus

or bacterial meningitis has been cited as rationale forpneumoniae (PISP) has already increased to around 80%

prescribing antibiotics for all patients with acute otitis

in Japan. Therefore, an increased dose of AMOX (60-90

media. The incidence of mastoiditis decreased from 20%

mg/kg/day for 5 days) is the first-line antibiotic for PISP orin the pre-antibiotic era, to less than 0.1% nowadays insome strains of PRSP, because the concentration of thisthe United States where antibiotics had usually been

medicine in the middle-ear effusion is high compared toprescribed for acute otitis media, suggesting that the

cephalosporins 31). However, the patients at very low risk

effects of antibiotics were considerable 15). On thefor infection of resistant bacteria or serious bacterial

contrary, the incidence of mastoiditis was 0.04% in thecomplication, i.e. patients older than 2 years with no

Netherlands where using antibiotics had been restricted.

antibiotic exposure in the preceding 3 months, noTherefore, the decrease of this complication might not be

day-care attendance and no fever, may be treated withattributable to antibiotics 16). In addition, a meta-analysis

AMOX of standard-dose (40mg/kg/day for 5 days) 32) 33).

includingIf this regimen does not prove effective within 24-48h,

2,368

subjects

revealedthatmastoiditis

occurred less frequently in the untreated group (2/1802;

change

13

to

the

second-line

antibiotic.

That

is

cephalosporins

with

a

low

minimum

serious illness.

inhibitory

concentration (MIC) against resistant pneumococcus or
8) Approach to recurrent otitis media

Haemophilus influenzae. However, the actual clinicalefficacy of these medicines is not clear. Period of
medication should be five days, as the length of dosing

Repetitive episodes of acute otitis media increase thedoes not correlate with the complete cure and a longer

parent’s anxiety and burden them with frequent clinic

use of antibiotics may increase resistant strains 25) 28).

visits. Recurrent otitis media is usually defined as 3
episodes of acute otitis media within 6 months or 4 ormore episodes within 1 year. There are several RCTs

6) Medication on holidays

studying the efficacy of different approaches, such as
As acute otitis media is a common disease in thefollowing the patients by observation (treatment is given

emergency medical facilities, the preparation for holiday

when acute symptoms develop), administering preventive

cases is important. Cates, a general practitioner in the UK,

antibiotics,

andinsertion

recommended

Casselbrant

et

al.

“Safety-Net

Antibiotic

Prescription”

oftympanostomy

concluded

that

the

tubes.

preventive(SNAP): a method designed to achieve both the patients’

medication and tympanostomy tube were effective 37).

safety and the restricted use of antibiotics 34). Parents

However, Rosefeld et al. concluded from the results of 12

are handed over a prescription of antibiotics and a leaflet

RCTs that acute otitis media had a tendency to resolve as

explaining that the efficacy of antibiotics is small. In

the child grew, and the choice of treatment should be

addition, the decision to give the antibiotic to theirmade carefully. As a long-term preventive medication or

children after 1-2 days is left to the parents. This method

insertion

proved to be effective on the restriction of antibiotics inproblems, the optimal treatment has not yet been

the follow-up studies 35) 36).

established. Our Guideline, therefore, recommends aoftympanostomy

tube

presents

variousCompared to other countries, access to outpatient“wait and see approach” for one year. Although the

medical service is easy on weekdays in Japan. Therefore

ultimate choice of the treatment is left to the attending

there is no urgent need to introduce the Cates’ method tophysician, the decision should be made after explaining

ourboth the advantages and disadvantages to the parents,

weekdayprogram.

However,considering

theand obtaining their consent 7) 17).

Japanese emergency care system on holidays, SNAPshould be adopted only before holidays.

5. Summary7) Comparison with the Netherland’s guideline
Most cases of acute otitis media recover without
Our Guideline conforms to the guideline of theantibiotics. The conclusions from many RCTs were that

Netherlands 1). The main rationale for adopting a policy

the administration of antibiotics did not provide aof restricting the use of antibiotics is the existence of thislong-term effect directly related to the impairment ofguideline that has been used for more than 10 years

hearing (i.e., residual middle-ear effusion), though a

without problems. We made two modifications: first, theshort-term efficacy (i.e., improvement of otalgia) was

Netherland’s guideline allows the use of antibiotics only

slightly achieved by the therapy. Taking the recent

when otorrhea persists for 14 days; however we changed

increase of resistant bacteria into consideration, a policy

this to 7 days. Regarding otorrhea, 77% resolved after 7of restricting the use of antibiotics should be standardized

days and 87% after 14 days in the report of van Buchem-- and the treatment should focus on both prevention of

et al. 10), and 73% and 87% respectively in Japaneseserious complications and reduction of the otalgia todata 14). This means that the increase of dosing rate may

improve the patient’s quality of life (QOL). Also, as accessbe small even if the observation period was changed fromto outpatient medical services is easier in Japan than in

14

the

other countries, it is quite possible to implement the policy

startof the judicious use of antibiotics without risk to theto7

circumstances

days

in

days.

Therefore,

Japan,

weconsidering

decidedtoadministration after 7days. Second, the procedures forpatients’ QOL and safety.

the treatment of patients with fever were obscure in theguideline of the Netherlands; however, our guideline

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clinical trial. Pediatrics 1991;87:466-474 [Abstract]children with Streptococcus pneumoniae occult

Rosenfeld RM, et al.

bacteremia?

otitis media.

Clinical pathway for acute

OtitisMedia.

Hamilton:seriousAbacterial

infections

meta-analysis.

in

Pediatrics

BC

22. Berman S, et al. Otitis media-related antibiotic

Decker,1999: 235-258

prescribing patterns, outcomes, and expenditures in

Burke P, et al.

aAcute red ear in children: controlled

pediatric

Medicaid

population.

Pediatrics

1997;100:585-592 [Abstract]

trial of non-antibiotic treatment in general practice.
Br Med J 1991;303:558-562 [Full Text]
9.

and1997;99:438-444 [Abstract]

In: Rosenfeld RM. et al, eds.

Evidence-based
8.

第13

23. Takata

GS,

et

al.

Evidence

assessment

of

Therapy of acute otitis

management of acute otitis media: I. The role ofmedia: myringotomy, antibiotics, or neither? A

antibiotics in treatment of uncomplicated acute otitis

double-blindmedia. Pediatrics 2001;108:239-247 [Full Text]

Van Buchem FL, et al.
study

in

children.

Lancet1981;2:883-887 [Medline]
10. Van Buchem FL, et al.

24. Hendrickse WA, et al.
for

Otitis media: a newacuteotitisFive vs. ten days of therapy

media.

Pediatr

InfectDis

J

1988;7:14-23 [Medline]

treatment strategy. Br Med J 1985;290:1033-1037[Full Text]

25. Kozyrskyj AL, et al. Treatment of acute otitis media

11. Damoiseaux RA, et al.

withPrimary care basedashortenedcourseofantibiotics:arandomised, double blind trial of amoxicillin versus

meta-analysis. JAMA 1998;279:1736-1742 [Medline]

placebo for acute otitis media in children aged under

26. Cohen R, et al. Five vs. ten days of antibiotic

2 years. Br Med J 2000;320:350-354 [Full Text]
12. Del Mar C, et al.

therapy for acute otitis media in young children.
Pediatr Infect Dis J 2000;19:458-463 [Medline]

Are antibiotics indicated as initial

treatment for children with acute otitis media? A

27. Cohen R, et al.

meta-analysis. Br Med J 1997;314:1526-1529

of amoxicillin/clavulanate therapy for acute otitis
media:[Full Text]
13. Rosenfeld

RM,

antimicrobial

et

al.

Clinical

drugs

for

acute

efficacy
otitis

One dose ceftriaxone vs. ten days

clinicalnasopharyngealofefficacy
flora.

andPediatrchangeInfectDis

inJ

1999;18:403-409 [Medline]

media:

metaanalysis of 5400 children from thirty-three

28. Cohen R, et al.

A multicenter, randomized,

randomized trials. J Pediatr 1994;124:355-367

double-blind trial of 5 versus 10 days of antibiotic[Medline]

therapy for acute otitis media in young children. J

15

Pediatr 1998;133:634-639 [Medline]
Acute sinusitis is a disease commonly complicated by

29. Bluestone CD, et al. Ten-year review of otitis media
pathogens.

Pediatr

InfectDis

upper respiratory infection. Most cases are caused byJviruses and recover without antibiotics. However, it

1992;11(suppl):S7-11 [Medline]
30. Block SL．Causative pathogens, antibiotic resistanceseems that antibiotics tend to be prescribed, being based

and therapeutic considerations in acute otitis media．

on the presence of purulent nasal discharge -- because of

Pediatr Infect Dis J 1997;16:449-456 [Medline]

the difficulty in differentiating this condition from bacterial

31. Dowell SF, et al. Acute otitis media: management

sinusitis. We will discuss the current diagnostic practices

and surveillance in an era of pneumococcal

for this disease while referencing overseas clinicalresistance--astudies, and propose a treatment method appropriate forreportfromtheDrug-resistantthis era of resistant bacteria.

Streptococcus pneumoniae. Pediatr Infect Dis J.
1999;18:1-9 [Medline]
32. Arason VA, et al. Do antimicrobials increase the

2. Diagnostic guideline

carriage rate of penicillin resistant pneumococci inchildren? Cross sectional prevalence study. BMJ

The main symptoms of acute sinusitis are rhinorrhea

1996;313:387-391 [Full Text]

and nasal congestion. Purulent nasal discharge andpostnasal drip are also commonly found. Cough and/or

33. Reichler MR, et al. The spread of multiply resistantfever may be present.

Streptococcus pneumoniae at a day care center in
Ohio. J Infect Dis 1992 ;166:1346-1353. [Medline]
34. Cates C. An evidence based approach to reducing

3. Treatment guidelines

antibiotic use in children with acute otitis media:
controlled before and after study. Br Med J 1999;a) Most cases of acute sinusitis are viral infections. Do

318:715-716 [Full Text]

not use antibiotics for the first 10-14 days, even if
purulent nasal discharge is present.

35. Siegel RM, et al. Treatment of otitis media withobservation and a safety-net antibiotic prescription.

b) When at least one of the following conditions is present,

Pediatrics 2003;112:527-531 [Full Text]

antibiotics should be considered:

36. Little P, et al. Pragmatic randomised controlled trialof two prescribing strategies for childhood acute(1) Symptoms persist for 10-14 days without any sign ofotitis media. Br Med J 2001;322:336-342 [Full Text]

improvement (“the 10 day-mark”).
(2) Facial swelling or pain develops.

37. Casselbrant ML, et al. Efficacy of antimicrobial
prophylaxis and of tympanostomy tube insertion for(3) Symptoms and findings worsen with a fever during theprevention of recurrent acute otitis media: results ofcourse of upper respiratory infection.

a randomized clinical trial. Pediatr Infect Dis J(Note: the diagnosis of acute bacterial sinusitis can be

1992;11:278-286 [Medline]

made in children aged one year or older.)Return to the topc) The diagnostic imaging is unnecessary, as it does nothelp to differentiate bacterial from viral origin. Thisdiagnostic measure is only indicated for cases refractory

ACUTE SINUSITIS

to treatments, with complications, or repetitive.
d) Even if it is a bacterial sinusitis, 60-80% of cases
recover without antibiotics. When the general condition is
not serious, observe the patient carefully without
antibiotics. If an antibiotic is to be used, the first-line
medicineisamoxicillin(AMOX).

Administer60-90mg/kg/day in 3 doses for 5 days. If the symptoms
do not improve, change to intravenous ceftriaxione(CTRX) 50mg/kg/day for 1~3 days.
1. Introduction

16

secondary infection, but the frequency of the disease is

4. Overview

very low-estimated about 0.5-5.0% 7-10). If the bacteria
As the paranasal sinuses themselves are not fully

invade into the orbital or intracranial space, a rare but

developed in the infants aged less than one year, these

serious complication such as orbital cellulitis, sinus

Guidelines are applicable to children aged one year or

thrombosis or cerebral meningitis may happen1).

more.

Unlike otitis media or pharyngitis/tonsillitis, the lesionsof paranasal sinuses cannot be directly observed.
Therefore, it is difficult to make a precise diagnosis. The

1) Pathophysiology

chief

symptomsarerhinorrhea,

nasal

congestion,

Paranasal sinuses are cavity structures surrounded bydaytime cough, and fever. In addition, if other symptoms

bone frame and lined with ciliated epithelial cells.

including impairment or loss of smell, ozostomia, facial

Ethmoidal sinuses and maxillary sinuses are present atswelling or pain, toothache in the upper jaw, and abirth, though only the former is air-filled and the latter will

headache are present, bacterial sinusitis is suspected

not be until the age of four or later. Other sinuses develop

11-13). However, characteristic symptoms like these areeven later; sphenoidal sinuses by around five years old

not often found in children 14). Furthermore, bacteria

and frontal sinuses at around seven, fully developing bydetected by the culture of nasal discharge cannot be

puberty 1). Therefore it can be said that sinusitis is lessidentified as the causative pathogen. Aspiration of thelikely to develop at younger ages.

maxillary sinus makes an accurate diagnosis possible,
but it is too invasive to be performed at an outpatient

Paranasal sinuses are normally kept aseptic due to theclinic and should be used for critical cases only.

mucociliary cleaning function. Because the outlets of thecavities that open to the middle nasal meatus are very
narrow passages of 1-3mm, it can be easily occluded by

4) The 10 day-markmucosal edema or certain mechanical factors. The mostfrequent causes of occlusion are viral infections of the

While there is no simple method to differentiate

upper respiratory tract, followed by allergic inflammation.

bacterial from viral sinusitis, Wald et al. paid attention to

Because an occluded paranasal sinus has a negative

the duration of clinical symptoms. Their study showedpressure, it brings in bacterial flora from the nasal meatusthat common cold symptoms caused by viruses subsided

when the occlusion is released, and bacterial sinusitis

or disappeared in 7-10 days in most cases 15).

may develop if the bacterial count is large 2).

Radiographic

examination

of

the

patients

whose

symptoms persisted for 10-30 days revealed that 80% ofthem had the findings of sinusitis 16). Bacterial culture2) Causative pathogens

using aspiration of the maxillary sinus was performed in
The upper respiratory viruses including rhinoviruses,

patients with radiographic evidence and significant

parainfluenza viruses, adenoviruses, and others arebacteria were detected in 70% of them 17). From these

involvedThe

causative

bacteria

areresults, Wald et al. thought that it would be important topneumoniae(35-42%),

etiologically.

Haemophilus

use the duration of symptoms (10-14 days) as the basis

influenzae (21-28%), and Moraxella catarrhalis (21-28%)

for differentiating bacterial from viral sinusitis, and then-- similar to those of acute otitis media. Group A

called this “the 10 day-mark” 7) 18).

Streptococcus

beta-hemolytic

streptococcus(GABHS)(3-7%)

andFurther, the same authors conducted an RCT in whichanaerobes (3-7%) are also observed 3).

patients, diagnosed by the 10 day-mark and radiographic
imaging, were divided into one of the following groups:
amoxicillin (AMOX), amoxicillin potassium clavulanate,2) Differential diagnosis of bacterial from viral sinusitis

and placebo. After 10 days of treatment, the rates ofrecovery/improvement

Acute sinusitis is a very common condition. The

were

83%,

75%,

and

60%,

common cold is also referred to as rhino-sinusitis in which

respectively. Although the antibiotics were effective, moreparanasal sinuses are invaded by viruses causing

than half of the patients improved without the help of theinflammation.

drugs 17).

Viral

infection itself causes mucosal

swelling of the sinus and fluid accumulation, but it heals

Supported by these results, the 10 day-mark is a basis

without antibiotics 4-6). Bacterial sinusitis occurs by afor the current overseas guidelines and textbooks 1) 19)

17

20). We adopted this standard, because our data also

used as a routine examination to avoid excessive X-ray

showed that symptoms such as cough and nasal

exposure 19) 20). Imaging methods should only be useddischarge resolved within approximately 10 days in thefor diagnosis and evaluations in serious or complicatedcases of the uncomplicated common cold 21).

cases or when the symptoms are recurrent.

In rare cases symptoms such as purulent nasal
discharge, headaches, and facial pain become worse,

6) Treatments

accompanied by a high fever of 39 °C or above. As these
symptoms may indicate the onset of serious bacterial

Sinusitis is the fifth common disease for which antibiotics

sinusitis, the imaging methods should be performed forare prescribed in adults, and it is the second or third (after

the accurate diagnosis 1) 19) 20).

otitis media) in children in the United States 3) 22).
However, the medical effectiveness is controversial evenin adults 23). In children, Wald et al. reported that theantibiotics were effective in their RCT 17). However,Fig. Findings of Acute Sinusitis with MRI

fifteen years later Garbutt et al. conducted an RCT with
A: Normal finding

the patients chosen by the 10 day-mark only in

B: The mucosal edema inaccordance with the guidelines of the American Academy

both maxillary sinuses andof Pediatrics 20), using the same medications as Wald etright ethmoidal sinus

al. 24). After 14 days of the treatment, improvement of the

C: The fluid accumulation

symptoms was observed in 79% of amoxicillin group,in ethmoidal and maxillary

81% of amoxicillin potassium clavulanate group and 79%

sinusesof the placebo group. These results showed that
antibiotics were ineffective, in opposition to the data ofKristo A, et al. examined

Wald et al.

60 children with MRI withsymptoms
respiratory

of

acute

infection

This inconsistency appears to be attributable to the6).

uncertainty of the diagnostic criteria. That is, if 80% of theApproximately 60% of thepatients chosen by the 10 day-mark had sinusitis, ofchildrenmajor

which 70% are of bacterial origin, 80% x 70% = 56% ofhad

abnormalities

in

their

all the patients are supposed to have bacterial sinusitis

maxillary andethmoidal

19). Accordingly, about a half of the patients in this groupsinuses(C). The follow-up

had viral sinusitis, for which antibiotics are not expected

MRI scan, taken in theto be effective. This means that an RCT could produce

most affected cases in the first scan, showed that thecompletely different results depending on a smallparanasal sinus abnormalities tended to resolve without

difference in the choice of subjects.
As shown in these studies, screening of patients

antibiotics. (Reproduced with permission from Pediatrics,

by the10day-mark is insufficient and presents problems in

111:e586-e589, CopyrightⒸ2003 by the AAP)

terms of prevention of resistant bacteria. Even in the 10
day-mark condition, a follow-up observation without theuse of antibiotics (a “wait and see approach”) is

5) Diagnostic imaging

recommended when the general physical condition is
Many articles from Europe and America conclude that

good, and there is no facial swelling/pain and other signs

imaging methods such as plain radiography, echography,of severe symptoms 25). As orbital or intracranial

CT, and MRI are unnecessary. Kristo et al. analyzed thecomplications are rare, careful observation of the patientslesions of sinusitis in children with respiratory infection

is recommended, rather than a preventive administration

using MRI. The first MRI images showed that 36/60

of antibiotics. Attention should be paid to the development(60%) had abnormal findings in the maxillary sinuses,of fever, facial pain, bad temper, and periocular redness

though by the second imaging most of the findings

or swelling.

resolved or improved without antibiotics (Fig.) 6). This

In case an antibiotic is used, the first-line medicine isresult demonstrated that diagnostic imaging does not

AMOX. If the symptoms do not improve, change tosupport an indication of antibiotics, and should not be

intravenous CTRX. This therapy is similar to the

18

3.

Guidelines of Acute Otitis Media, because not only are

Sinus and Allergy Health Partnership. Antimicrobial

the causative pathogens of these two diseases the same,

treatment

guidelines

for

acute

but the pathophysiology and healing process of them alsorhinosinusitis. Otolaryngology - Head and Neck

resemble each other. Dosing period of AMOX should be

Surgery

2000;123:S1-S32

bacterial

2004;130:S1-45[Full Text]

five days as well, because there was not any data
showing that the length of dosing correlated with the4.

complete cure. The longer antibiotics are used, the more

Puhakka T, et al. Sinusitis in the common cold. J
Allergy Clin Immunol 1998；102:403-408 [Abstract]resistant strains increase. If this treatment is ineffective

5.

Gwaltney JM Jr, et al. Computed tomographic study

and the symptoms become severe, refer the patient to anofotolaryngologist for a possible aspiration of the paranasal

1994;330:25-30 [Abstract]sinus.

6.

thecommon

cold.

New

Engl

J

Med

Kristo A, et al. Paranasal sinus findings in children
during respiratory infection evaluated with magnetic
resonance imaging. Pediatrics 2003;111:e586-589

5. Summary[Full Text]
It is difficult to define an accurate use of antibiotics in the7.

Ueda D, et al. The ten-day mark as a practicalpatients with acute sinusitis. “The 10 day-mark” is usefuldiagnostic approach for acute paranasal sinusitis infor the screening of patients who should be treated withchildren. Pediatr Infect Dis J 1996;15:576-579

antibiotics. It is important not to prescribe antibiotics for[Medline]

the initial 10-14 days even if there is purulent nasal

8.

discharge. Even though fulfilling the 10 day-mark, if the

Gwaltney JM Jr. Acute community-acquired sinusitis.
Clin Infect Dis 1996; 23:1209-1223

symptoms are not severe, the observation of patients

9.

Dingle JH, et al. Illness in the home: a study of

without antibiotics (a “wait and see approach”) is

25,000 illnesses in a group of Cleveland families.

recommended.

Cleveland, Ohaio. The Press of Western Reserve
University, 1964:347
10. Berg O, et al. Occurrence of asymptomatic sinusitis

Subjoinder:in common cold and other acute ENT-infections.
Rhinology 1986;24:223-225

Although long-term treatment with a small dose of
macrolide is indicated for “chronic” sinusitis in Japan,

11. Brook I, et al. Medical management of acutethere is no sufficient evidence for usage in children andbacterial sinusitis. Recommendation of a clinicalfurthermore, there is a great risk of increasing bacterial

advisory committee on pediatric and adult sinusitis.

resistance.

Ann Otol Rhino Laryngol 2000;109:2-20

Itshould

also

be

noted

that

macrolide-resistant GABHS, Streptococcus pneumoniae,[Full Text]

12. Engels EA, et al. Meta-analysis of diagnostic tests

and Helicobacter pylori are increasing rapidly as theforresult of this macrolide overuse. Therefore, macrolide

2000;53:852-862 [Medline]

acute

sinusitis.

J

Clin

Epidemiolshould be used very sparingly. The efficacy of other

13. Young J, et al. The clinical diagnosis of acutetreatments such as washing of maxillary sinuses orbacterial rhinosinusitis in general practice and its

adenoidectomy is uncertain, and a study reports thattherapeutic

most of sinusitis heals naturally by 10 years old without

2003;56:377-384 [Medline]

any of these treatments 26).

consequences.

J

Clin

Epidemiol

14. Dowell SF, et al. Appropriate use of antibiotics for
URIs in children: PartⅠ. Otitis media and acute

Referencessinusitis.

Am Fam. Physician 1998;58:1113-1118[Full Text]
1.

2.

Pappas DE, et al. Sinusitis. In:Behrman RE, et al,

15. Wald ER, et al. Upper respiratory tract infections in

eds. Nelson Textbook of Pediatrics 17th ed.

young children: duration of and frequency ofPhiladelphia: Saunders, 2004;1391-1393

complications.

Wald ER. Sinusitis. In:Jensen HB, et al, eds.

[Abstract]

Pediatric

Infectious

Diseases.

Principles

Pediatrics

1991;87:129-133

and

16. Wald ER, et al. Comparative effectiveness ofPractice 2nd ed. Philadelphia: W.B. Saunders,amoxicillin and amoxicillin-clavulanate potassium in

2002:760-770

acute paranasal sinus infections in children: a19

double-blind, placebo-controlled trial ． Pediatrics

mostly heal without antibiotics. However, it is often difficult

1986;77:795-800[Abstract]

to predict at the early stage of the diseases whether they

17. Wald ER, et al. Treatment of acute maxillary sinusitis

will develop into pneumonia, as their symptoms are veryin childhood: a comparative study of amoxicillin andsimilar to each other, marked by coughing and a highcefaclor. J Pediatr 1984;104:297-302 [Medline]

fever -- and antibiotics are often prescribed as preventive

18. Wald ER. Acute sinusitis in children. Adv Otolaryngol

measures 1). This approach is not appropriate for thiscurrent era of resistant bacteria. Based on studies in

Head Neck Surg 1988;2:165-188
19. O’Brien KL, et al. Acute sinusitis - principles ofJapan and overseas, our Guidelines propose thejudicious use of antimicrobial agents. Pediatrics

principles for the judicious use of antibiotics for cough1998；101(suppl):174-177

illness/bronchitis.

[Full Text]

20. Subcommittee on Management of Sinusitis andCommittee
practiceon

Qualityguideline:

Improvement.

management

Clinicalof

2. Diagnostic guideline

sinusitis.

Pediatrics 2001;108:798-808 [Full Text]

Cough illness/bronchitis’ main symptom is a cough that21. 草刈章 (Kuakari A), 他. チャートでみる抗菌薬適正

may be accompanied by a fever, sputum or an abnormal

使用ガイドライン・急性副鼻腔炎. 外来小児科

breathing sound. There are no findings of pneumonia by

2006;9:211-214. (In Japanese)

chest radiography.

22. Finkelstein JA, et al. Reduction in antibiotic use
among

US

children ， 1996-2000

2003;112:620-627

Pediatrics

3. Treatment guideline[Full Text]a) Most of cough illness/bronchitis are caused by viral

23. Bucher HC, et al. Effect of amoxicillin-clavulanate inclinicallydiagnosed

acuterhinosinusitis:

infections.

aAntibiotics are not justified for the treatment.

placebo-controlled, double-blind, randomized trial inb)generalrecommended if pertussis is suspected.

practice.

Arch

Intern2003;163:1793-1798[Medline]Med

24. Garbutt JM, et al. A randomized, placebo-controlled

Erythromycin

50mg/kg/day

for

14

days

is

4. Overview

trial of antimicrobial treatment for children withclinicallydiagnosed

2001;107:619-625
25. KahnJ,et2002;110:192-193

acutesinusitis.

Pediatrics

Acute bronchitis is not a defined condition and its[Full Text]al.

clinical definition is vague. We therefore use the term

‘Sinusitis’?

“coughPediatrics

illness/bronchitis”

to

cover

all

symptoms

associated with cough in children.

[Full Text]

26. Otten FW, et al. Long-term follow-up of chronic
1) Causative pathogens

therapy resistant purulent rhinitis in children. Clin
Otolaryngol 1992;17:32-33 [Medline]

Most of the causative pathogens are viruses such as

Return to the top

influenza viruses, parainfluenza viruses, RS virus,
adenoviruses,

rhinoviruses,

coronaviruses,

human

metapneumovirus, etc.; and some are caused by

COUGH ILLNESS/ BRONCHITIS

Mycoplasma pneumoniae, Chlamydia pneumoniae or
Bordetella pertussis 2). In Japan, although there areinsufficient studies to support this idea, Streptococcus
pneumoniae, Haemophilus influenzae, and Moraxella
catarrhalis are also thought to be causative 3). Even if
these pathogens can be isolated from sputum, they are
not considered overseas to be causative in patients with
uncomplicated acute bronchitis 4-6). They are limitedly
defined in the Nelson Textbook of Pediatrics as causative1.

pathogens of only secondary infections 7).

Introduction
Cough illness/bronchitis are common diseases that202) Differentiation from pneumonia
The uncertain definition of acute bronchitis, lack of
The most important process in the treatment of coughbacteriological data, and the high rate of spontaneous

illness/bronchitis is the differentiation from bacterial orrecovery interfere with the establishment of treatment

atypical pneumonia. Fortunately, Staphylococcus aureus

guidelines. There are seven RCTs that studied thepneumonia, which had been feared to be the cause ofeffectiveness of antibiotics on adult patients with wet

empyema is now rare 8). It is not too late to start thecough. Of these, four trials showed that the use oftreatment of patients with pneumonia after its diagnosis isantibiotics slightly shortened the duration of cough, andestablished, except in newborns, immuno-compromised

the patients could return to work sooner 12-15). The

patients or patients with respiratory congenital diseases.

remaining three trials demonstrated no difference in

Symptoms indicative of bacterial pneumonia are higheffectiveness between the antibiotic group and thefever, fatigue, wet cough, and rapid aggravation of theplacebo group 16-18). The meta-analysis of these trials

general conditions. Accompanying tachypnea, nasal alaralso showed a limited effectiveness of antibiotics 19-22).

breathing, retractive breathing, grunting and cyanosis are

Specifically, the analysis of Fahey et al. found little

signs of severe infection 9) 10). Oxygen saturation can bedifference in the rate of improvement of wet cough afterconveniently checked by a pulse oximeter to evaluate the7-11 days of treatment, i.e., 64.0% (228/356) in thenecessity of oxygen or hospitalization. Careful attention isantibiotic group and 60.2% (207/344) in the placebo

required when there are physical findings like moist ralegroup 19). Bent et al. also reported that the duration ofor the attenuation of breath sound. If a blood examination

cough is shortened by only half a day in the antibiotic

shows a high leukocyte count or elevated CRP level, thegroup with no statistically significant difference 20).

possibility of bacterial pneumonia is high 10) 11).

An RCT of 89 children with cough and nasal discharge

Pneumonia caused by atypical pathogens such ascompared the effectiveness of some antibiotics and a

Mycoplasma pneumoniae is characterized by a severe,placebo, and found that antibiotics did not reduce

dry cough with various degrees of fever, though in infants

symptoms 23).

the cough can also be wet. The only accurate method of

Antibiotics are often prescribed to viral bronchitis todiagnosis is chest radiography (Fig.), as physical findings

prevent

are often normal 6). This diagnostic step should be

effectiveness of this approach is also doubtful. Townsend

considered when the fever persists or the cough is severe

et al. conducted an RCT on 781 children with viral upper

even without fever. 2)

respiratory

secondaryinfection

bacterialusing

infection,

some

but

antibiotics

the

and

symptomatic treatments to examine their preventive
effects on secondary bacterial infection. The results
showedthat

incidenceofcomplications

includingpneumonia, otitis media and tonsillitis was 13.5%(57/423) in groups treated with antibiotics and 14.8%(53/358)

in

group

with

symptomatic

treatment,

respectively. No significant difference was detected. Bothgroups had the same number (5 cases) of pneumonia
complcations 24).
Fig.

4) Treatment guideline by causal agents

Mycoplasma pneumoniae pneumonia

Boy, age 5(1) Viral bronchitis

He had a dry cough and normal finding on auscultation.

Viral bronchitis is a respiratory infection that improves

This chest radiography shows consolidation in the left

without antibiotics within approximately two weeks. Its

lower lung field, examined on the 4th day of fever.

main symptom is a cough that occasionally accompanies
sputum and fever. Breath sound is normal, but there may
be wet or dry rale and a prolonged expiration with
3) Efficacy of antibiotics – evidence for treatment

wheezing. Chest radiography may be required to rule out

guideline

pneumonia.

21

Fever is a common symptom in the viral bronchitis.

stipulate that there is no need of antibiotics unless the

Although it usually subsides in 2-3 days, it may last one

cough is severe or complicated by pneumonia 4) 33). An

week even with rhinoviruses. Human viral infection

RCT also did not find out the efficacy of antibiotics 15).

experiments and research showed that the symptoms

Therestarted with a sneeze, fever, pharyngeal pain and myalgia,

bronchiolitis in infants 34), but usually its symptoms were

followed by a cough which lasted for more than 14 days

not severe.

wasareportthat

thispathogencausedin 17% of the subjects 25) 26). Even if the sputum

Chlamydia pneumoniae bronchitis should also be

becomes purulent, it does not necessarily indicate

suspected when the cough persists 35). Because thesecondary bacterial infection 2). A prolonged cough

cough may linger for several weeks to months even withaccompanied by sputum also does not mean that it is atreatment by erythromycin, the effects of antibiotics arebacterial case; most cases are viral. Leukocyte counts

uncertain 10) 35).

and CRP level are usually normal; however adenoviruses

It is difficult in the early stage of the disease to confirm

or RS virus sometimes cause these levels to rise 27).

the presence of bronchitis by these atypical pathogens.

Rapid tests of naso-pharyngeal smear are useful for the

Since it usually heals without antibiotics, antibiotic

diagnosis of Influenza virues A/B, adenoviruses and RS

treatment is unnecessary unless the chest radiography

virus. Most patients recover spontaneously, but caution is

finding shows pneumonia. Considering the drug’s side

needed because the patient’s condition may worsen in

effects and antibiotic resistance, administration for a small

some cases.

effect is not justified.

RS virus infection may cause sudden deterioration of(3) Pertussis

breathing or apnea in infants less than 3 months old. An

Pertussis is characterized by three stages including

accurate diagnosis by rapid test is essential, asbecatarrhal, paroxysmal and convalescent stage. The mostrequired. Palivizumab (Synagis®) is recommended totypical symptom is coughing in paroxysms accompanied

prevent premature infants and infants with congenitalby the characteristic whoop. It is not usually accompanied

heart diseases from serious RS virus infections in Japan.

by a fever. The auscultatory finding of breath sounds is

hospitalizationandoxygenadministration

may

normal in most cases.

Cases of bronchitis caused by adenoviruses thatbe

In its early stage, pertussis is indistinguishable from a

hospitalized. Caution is necessary because an endemic

viral infection, and the diagnosis should be made basedof adenovirus type 7 pneumonia was reported in Japanon an endemic of the disease, vaccination history,

28).

leukocytosis of lymphocyte predominance type, andprogresstosevereviralpneumonia

shouldHowever, cases with good general condition, normal

serological tests or culture. Atypical cases without

chest radiography and blood test results, but with awhoops or leukocytosis are often observed in school

persistent cough and fever are often observed. We would

children and adolescents, in such cases a serological test

propose the “wait and see approach” without antibiotics inis required 36).

such cases.

This may, needless to say, require frequent

Treatment with erythromycin during the catarrhal stage

examinations depending on the patient’s age andshortens the duration of the disease, though it may havecondition.

no obvious effect if the patient is already in paroxysmal
stage 36). Because the diagnosis during the catarrhal
stage is difficult, early treatment is only possible in an(2) Bronchitis caused by atypical pathogens
Although bronchitis due to Mycoplasma pneumoniae

endemic outbreak or secondary family infection. Antibiotic

causes prolonged cough in school children or older 4),

treatment during paroxysmal stage is for the purpose of

the data from PCR tests indicated that this pathogen only

preventing the spread of this infection. Infants of less thanaccounts for 6.3% (13/207) in children with acute6 months of age with symptoms of apnea or cyanosis

bronchitis 29). Patients often have a fever in the earlyrequire hospitalization.

stage, but unlike viral bronchitis, nasal discharge is not
usually seen. It was reported that erythromycin shortened(4) Other causes

the period of cough if taken orally within 4 days of onset

Prolonged

cough

may

be

causedbyairwayof the disease, though a delay in the start of treatment

hypersensitivity or an allergy. Such patients respond to a

reduced such effect 30-32). Some guidelines or textbooks

bronchodilator and the cough will improve 37). If purulent

22

nasal discharge or postnasal drip is present, sinusitis

tract infections: controversy and conundrums. J Clinshould be suspected (see “Acute Sinusitis”). If a coughMicrobiol 2002;40:3115-3120 [Full Text]

persists for 4-8 weeks, rare cases such as foreignmaterialinthebronchiectasis,

airways,ciliary

gastroesopageal

movement3.

reflux,dysfunction,

Ishiwada N. et al. The etiology of acute lower
respiratory infections in infants.

or

and

pulmonary tuberculosis should also be suspected.

Chemotherapy

Journal of Infection

1996;70:470-478(Abstract

written in English)

Administration of antibiotics should be delayed, if possible,

4.

until a correct diagnosis-top priority-is made 4).

O’Brien KL, et al. Cough illness/bronchitis principles of judicious use of antimicrobial agents.
Pediatrics 1998;101(suppl):178-181 [Full Text]

5.

5. Summary

Gonzales R, et al. Principles of appropriate antibiotic
use for treatment of uncomplicated acute bronchitis:background. Ann Intern Med 2001;134:521-529

Most cough illness/bronchitis cases are caused by viral[Abstract]

infections for which antibiotics are unnecessary. Manycases suffering from bronchitis caused by atypical
pathogensrecover

without

antibiotics.

6.

Concerning

Bartlett JG, et al. Practice guidelines for the
management of community-acquired pneumonia inpneumonia, a detailed interview and careful examination,

adults.

chest radiography, and watchful observation helps to2000;31:347-382 [Full Text]

make an early diagnosis. Uniform administration of

7.

ClinicalInfectious

DiseasesOrenstein DM. Bronchitis. In:Behrman RE, et al, eds.

antibiotics in order to prevent pneumonia will only cause

Nelson Textbook of Pediatrics 16th ed. Philadelphia:

a spread of resistant bacteria that will result in difficulty ofW.B. Saunders, 2000:1284-1285

treatment.

8.

中村 明 (Nakamura A). 気管支肺感染症病因診断の問題点ーEBM の時代を迎えてー. 日本小児科学会雑誌 2003;107:1067-1073. (In Japanese)

Subjoinder:
9.

Uehara S, et al. Guidelines for the management of

Croup (laryngotracheobronchitis) results from obstruction

respiratory infectious diseases in children in Japanof the larynx with symptoms such as inspiratory stridor,

2004:36-54 (In Japanese)

dry cough and hoarseness. The pathogens of croup are

10. Baltimore RS. Pneumonia. In:Jensen HB, et al, eds.

viruses, foreign bodies or allergies. Therefore antibiotics

Pediatric

are not indicated. However, it is necessary to make a

Practice 2nd ed. Philadelphia: W.B. Saunders

closer observation of the respiratory condition or to

Infectious

Diseases.

Principles

and2002:794-831

transport to a hospital. In rare cases, croup is followed by

11. Korppi M. Non-specific host response markers in thebacterial tracheitis that may require an artificial airway

differentiation between pneumococcal and viralsuch as intubation or tracheostomy.

pneumonia: what is the most accurate combination?
Pediatr Int 2004;46:545-550 [Medline]

Acute epiglottitis is caused by bacteria such as
Haemophilus influenzae type b. Patient’s chief complaints

12. Dunlay J, et al. A placebo-controlled, double-blind

are a fever, drooling, and pharyngeal pain. There istrial of erythromycin in adults with acute bronchitis. J

usually neither cough nor inspiratory stridor in the early

Fam Pract 1987;25:137-141 [Medline]

stage. The respiratory condition may worsen suddenly

13. Franks P, et al. The treatment of acute bronchitis

and is impossible to treat with oral antibiotics. Intensivewith trimethoprim and sulfamethoxazole. J Famcare, including airway management by intubation, takes

Pract 1984;19:185-190 [Medline]

top priority in this treatment 38).

14. Verheij TJM, et al. Effects of doxycycline in patientswith acute cough and purulent sputum: a double

References

blind placebo controlled trial. Br J Gen Pract
1994;44:400-404 [Full Text]

1.

Kawamoto R, et al. A study of clinical features and

15. King DE, et al. Effectiveness of erythromycin in thetreatment of acute bronchitis by Japanese primary

treatment

care physicians. Fam Pract 1998;15:244-251

acutebronchitis.

J

Fam

Pract

1996;42:601-605. [Medline][Full Text]
2.

of

16. Stott NC, et al. Randomised controlled trial of
antibiotics in patients with cough and purulent

Carroll KC. Laboratory diagnosis of lower respiratory

23

[Abstract]

sputum. Br Med J 1976;2:556-559 [Full Text]
17. Williamson HA. A randomized, controlled trial of

32. Broughton RA. Infections due to Mycoplasma

doxycycline in the treatment of acute bronchitis. J

pneumoniae in childhood. Pediatr Infect Dis J

Fam Pract 1984;19:481-486 [Medline]

1986;5:71-85

18. Brickfield FX, et al. Erythromycin in the treatment of

33. Committee on Infectious Diseases 2001-2003.

acute bronchitis in a community practice. J Fam

Mycoplasma pneumoniae infection. In:Abramson JS,

Pract 1986;23:119-122 [Medline]

et al, eds. Red Book. 26th ed. Elk Grove Village:
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19. Fahey T, et al. Quantitative systematic review of

34. Henderson

randomised controlled trials comparing antibiotic

FW,

et

al.

The

etiologic

andepidemiologic spectrum of bronchiolitis in pediatricwith placebo for acute cough in adults. Br Med J

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35. 沼崎20. Bent S, et al. Antibiotics in acute bronchitis: a

啓 (Numasaki H). クラミジア・ニューモニエ

肺炎. 小児科臨床 2002;55:645-649. (In Japanese)meta-analysis. Am J Med 1999; 107:62-67 [Medline]
21. Orr PH, et al. Randomized placebo-controlled trials

36. Committee on Infectious Diseases 2001-2003.

of antibiotics for acute bronchitis: a critical review ofPertussis. In:Abramson JS, et al, eds. Red Book.

the26th ed. Elk Grove Village: American Academy ofliterature.

J

Fam

Pract

1993;36:507-512

Pediatrics 2003:472-486[Medline]

37. König P. Hidden asthma in childhood. Am J Dis

22. Smucny JJ, et al. Are antibiotics effective treatment

Child 1981;135:1053-1055 [Abstract]

for acute bronchitis? A meta-analysis. J Fam Pract
1998;47:453-460 [Medline]

38. Rotta AT, et al. Respiratory emergencies in children.
Respir Care 2003;48:248-258; discussion 258-260

23. Gordon M, et al. The value of antibiotics in minor[Full Text]

respiratory illness in children. A controlled trial. MedJ Aust 1974;1:304-306

Return to the top

24. Townsend EH Jr, et al . Prevention of complicationsof respiratory illnesses in pediatric practice. A
double-blind study. N Engl J Med 1962;266:683-689

FEVER WITHOUT SOURCE (FWS)

25. Cate TR, et al. Production of tracheobronchitis involunteers with rhinovirus in a small-particle aerosol.
Am J Epidemiol 1965;81:95-105
26. Gwaltney JM Jr, et al. Rhinovirus infections in anindustrial population. II. Characteristics of illness
and antibody response. JAMA. 1967;202:494-500
27. 小西芳樹 (Konishi Y), 他. 当院における RS ウイル
ス迅速検査陽性入院児 2 年間のまとめ. 小児科臨床
2003;56:881-886. (In Japanese)
28. 西村章(Nishimura A), 他. 重症アデノウイルス感染

1. Introduction症 の 治 療 と 管 . 小 児 内 科 1999;31:184-189. (InJapanese)

Most fevers in children are caused by viral infection

29. Morokado M. et al. New PCR for rapid identificationthat can heal without antibiotics. However, there can beof Mycoplasma Pneumoniae in clinical specimens

cases of rare but serious bacterial infections amongfrom children with respiratory tract infections.

febrile children. Early detection and treatment of this

Journalcondition is one of the most important jobs for doctors inofInfection

andChemotherapy

2003;51:289-298 (Abstract written in English)

ambulatory care. However, it is difficult to specify the[Full Text]

causes of the diseases, because many of them have no30. Broome CV, et al. An explosive outbreak ofsymptoms or findings other than fever at the early stage.

Mycoplasma pneumoniae infection in a summer

A precise diagnosis of serious bacterial infection cannot

camp. Pediatrics 1980;66:884-888 [Abstract]

be made until the specific signs of the disease begin topneumoniae

appear -- usually after the first visit to the doctor. In Japan,

infections in children. Arch Dis Child 1978;53:38-42

the doctors tend to prescribe antibiotics to children with

31. Stevens

D,

et

al.

Mycoplasma24fever of unknown origin out of fear of overlooking these

When there is cyanosis, impaired consciousness, lack

infections 1), which is one of the reasons for the spreadin response to stimulation, severe dehydration, orof the resistant bacteria.

complex febrile seizure, conclude it to be a severe
diseaseTherefore, it is important to take appropriate action in9)10):

such

cases

requireimmediate

hospitalization and examination for appropriate treatment.

regards to the possibility of these infections. The
restricted use of antibiotics only for patients with thispossibility would reduce the total amount of antibiotics,

Fig. Oral enanthema (2 cases)

helping to prevent the spread of the resistant strains.
2.

Examination of fever (see “Algorithm” at the end)
These Guidelines are intended for patients who visit an

outpatient clinic within 48 hours from the onset of fever(temperature of 38°C or above).
Symptoms and findings of pharyngitis, tonsillitis,
bronchitis and croup indicate the presence of infection
focus 2). Oral and pharyngeal findings (Fig 1) or skin2) When the general condition is not severerash may provide information for diagnosis of infections
by enteroviruses, herpes virus or HHV6 3). Based on the

Observe patient’s

endemic, the rapid tests of GABHS, influenza viruses

condition

without administering

antibiotics.

type A/B, adenoviruses and RS virus should be used to
specify the causative pathogen 4).

However, when one of the findings below is present, a

Urinalysis is also essential in boys aged less than 1
year and girls aged less than 2 years for the possibility of

blood

cultureandintravenous

ceftriaxone(CTRX)

urinary tract infection. As there is no circumcision custom

50mg/kg once a day are our recommendation:

in Japan, more attention should be paid in boys than ina) Infants of 3-12 months old with either a temperature of

the other countries. As 10-20% of cases with urinary tract≧40°C, or 38.5°C or more and leukocyte count of ≧infection do not accompany pyuria, quantitative culture

15,000/µl ( or neutrophil count of ≧10,000/µl).

using a sample collected by urinary catheter is requiredb) Infants of 12-36 months old with a temperature of ≧for a conclusive diagnosis 5). A sample from a urinary

39°C and leukocyte count of ≧15,000/µl (or neutrophil

bag is not adequate as contamination is inevitable.

count of ≧10,000/µl).

If the cause of fever can be identified, treatment based

Note: oral amoxicillin (AMOX) 60-90mg/kg/day is anotheron the diagnosis should be started. If the cause cannot

available option.

be identified, classify it as “fever without source”.
3) Instructions during the course of treatment orobservation

3. Treatment guideline
These Guidelines are based on the ones by Baraff et al.

a) Case in which a blood culture was performed

and their study of occult bacteremia (OB) 6). The subjects

It takes 24-48 hours to reveal the results of blood

are children, from the age of 3 months with no underlying

culture. When bacteria are detected after 48 hours, thoseconditions such as immunodeficiency. There are no data

are usually not the causative pathogen, but are present

available for children younger than 3 months. The

because of contamination of the culture 11). During thetemperature quoted below is maximum temperature

culture, the patient should be observed carefully. Even if

during the course, as severe bacterial infection can’t be

the fever subsides, it is recommended to check the CRP

ruled out even if temporary decrease in fever is achieved

level within 24 hours. When the CRP level is 5.0mg/dl orby using an antipyretic 7) 8).

above, antibiotic should be continued.

1) When the patient’s general condition is severe

following measures should be taken:

When the result of blood culture is positive, theⅰ) Streptococcus pneumoniae: If the fever persists, the25

patient should be hospitalized for immediate treatment tocondition 15). Serious localized infections such as

prevent serious bacterial complication. If the fever

meningitis, pneumonia, epiglottitis, cellulitis, suppurative

subsides, there are two options: to hospitalize forarthritis and osteomyelitis occur secondarily in 5-15% of

intravenousa

OB cases 16) 17). Among the patients with fever ofsusceptible antibiotic orally for seven days at an

unknown focus, OB occurs more frequently in children

outpatient clinic.

with higher body temperature, leukocyte count, neutrophilⅱ ) Haemophilus influenzae type b (Hib): the patient

count and CRP level 18-20).

antibiotic

therapy,ortoadministershould be hospitalized for immediate treatment to prevent

The first large-scale research on OB was conducted byserious bacterial complication even if the fever has

McGowan et al. in 1973 21). They detected 31 patients

subsided. Hib occasionally causes serious bacterial(4.4%) with bacteremia from 708 febrile children withcomplication even after the fever subsides 12). If severe

unknown focus who were in fairly stable general condition

symptoms develop during the disease’s course, it isof rectal temperature of 37.8°C or more. The precise

necessary to make an appropriate evaluation and treat

diagnosis of bacteremia was not possible only by physicalimmediately.

examination, because they had no other characteristicⅲ) Others: When meningococcus is detected, the rate ofsymptoms and signs than fever. It was revealed later that

subsequentbacterial

serious bacterial infections such as bacterial meningitis

complication is high 13), and the patient in Japan also

occur secondarily in some OB cases, which led to various

tends

to

development
have

complement

anofunderlying

deficiency

14);

serioussuch

asstudies concerning the relationship between OB andhospitalizationisclinical or laboratorial findings.

conditionthus

indicated regardless of the patient’s general condition.

In 1983, Dershewitz et al. studied whether it was

When one of the following bacteria is detected:

possible to predict the occurrence of OB in children by

Salmonella,

streptococcus

both interview and physical examination at the first visit in(GABHS), Group B streptococcus (GBS), Staphylococcus,

Group

A

beta-hemolytic

patients of 3-24 months old with temperatures higher thanMoraxella catarrhalis and Haemophilus influenzae other

39.5°C and without serious general condition 22). The

than Hib, the patient should be hospitalized for adequate

results showed that the blood cultures were indeed

evaluation, even though contamination is possible.

positive in 10 of 110 cases (9.1%) suspected OB,
whereas those were also positive in 15 of 578 cases(2.6%) not suspected OB. These results demonstratedb) Case in which a blood culture was not performed
Observation should be continued for 6-48 hours. Whenthat it was difficult to exactly predict OB in advance. Most

the fever persists, the CRP level should be checked. Ifof these cases had been misdiagnosed as upper

the result is 5.0mg/dl or above, treatment should be

respiratory infection, otitis media or others until positive

started in consideration for the possibility of serious

blood culture results were obtained. One of these patientsbacterial infection.

had bacterial meningitis 24 hours later.
Concerning the laboratory findings predictive of OB,
Bass et al. examined children between 3 and 36 months

4. Overview

of the age with fever without source in 1993 18). Blood
1) Occult Bacteremia and Guidelines

cultures were obtained from children with (a) rectal
temperature of 40°C or above, or (b) rectal temperature

Although fever without source is mostly due to viralof 39.5°C or above and leukocyte count of 15,000/µl or

infection, a small number of the cause can be OB or otherabove, and then diagnosed 60 cases of OB. Of these,

severe bacterial infection in an early stage. As OB is a

5/182 (2.7%) cases with leukocyte count of <15,000/µl

disorder with relatively high frequency, it has been

had OB, whereas 55/331 (16.6%) cases with leukocyte

studied in many clinical trials as a model disease for thecount of ≧15,000/µl had OB. In addition, the incidence of

beginning of severe bacterial infection. Our Guidelines

OB increased in proportion to the rise of the leukocyte

are also based on these OB findings.

counts.

OB is defined as bacteremia with the only symptom of

Fleisher et al., in their research on treatment efficacy

fever, occasionally associated with the symptoms of the

on OB, compared CTRX 50mg/kg by intramuscularcommon cold or otitis media, and one with no findings ofinjection and AMOX 60mg/kg by oral administration 23).

obvious localized infection or deteriorated general

The results showed that CTRX prevented secondary26

infection and shortened fever’s duration more effectively.

pathogens.

Based on these results, in 1993, Baraff et al. publishedpneumococcus is relatively good: in the patients whotheir guidelines proposing the following: when a childreceive no antibiotics, serious local infections occur inbetween 3-36 months old has a fever of unknown origin

10%, and bacterial meningitis occurs in 2% 15). On theof ≧39°C, blood examination should be performed evenother hand, OB caused by Hib has a poor prognosis with

if the general condition is not severe. If the leukocyte

an incidence of bacterial meningitis more than 10 times

count is ≧15,000/µl, perform a blood culture consideringthat of pneumococcus 13). Mean leukocyte counts by

the possibility of OB, and administer CTRX 50mg/kg bythese two different pathogens are 21,500/µl in OB caused

intramuscular injection 6). Since then, these guidelines

by pneumococcus 18), and 15,100/µl in OB caused byhave been used widely in the emergency outpatient units

Hib 12). The increase of leukocytes is not often observedin the United States.

in OB of Hib; therefore it is occasionally difficult to detect

There

were

historicaltransitions

of

The

prognosisofOB

causedbyit using the criterion of leukocyte count of 15,000/µl or

causative

pathogens of OB in the United States: before Hib vaccine

more.

was introduced in 1990s, 80% was pneumococcus, 10%

Our group performed blood cultures from 71 patients with

was Hib, the remaining 10% was salmonella, GABHS,

high fever without source, of which 4 cases (5.6%) weremeningococcus and group B streptococcus, collectively

positive for pneumococcus. In all the 4 cases the15). After the introduction of Hib and pneumococcal

leukocyte count was ≧ 15,000/µl, and there was no

vaccines, the incidence of OB itself has decreased

positive blood cultures in cases with <15,000/µl 26).

dramatically in the United States 24) 25).

These results showed that the standard of leukocyte
count 15,000/µl was useful for detection of OB in JapanThe rates of sequelae of OB differ greatly by causative

Table. Acute Illness Observation Scales (Reproduced with permission from Pediatrics, 70:802-809, CopyrightⒸ1982 by the AAP)
Observation Items

Normal（ score;1）

Moderate Impairment（ score;3）

Severe Impairment（ score;5）

Quality of cry

Strong with normal toneorContent and not crying

Whimperingor
Sobbing

Weakor
MoaningorHigh piched

Reaction to parent stimulation(Effect on crying when held, patted
on back, jiggled on lap, or carried)

Cries briefly, then stops
orContent and not crying

Cries off and on

Continual cryorHardly responds

State variation(Going from awake to asleep orasleep to awake)If awake, then stays awakeor
If asleep and stimulated,then wakes up quickly

Eyes close briefly, then awakens
orAwakens with prolonged stimulation

Will not rouse
orFalls to sleep

Color

Pink

Pale hands, feetorAcrocyanosis(Blue hands and feet)

Pale
or
Blue
or
Ashen(Gray)or
MottledHydration(Moisture in skin,eyes,mouth)

Skin normal andeyes, mouth moist

Skin, eyes normal and mouth slightly
drySkin doughy or tented andeyes may be sunken and dryeyes and mouth

Response to social overtures(Being held, kissed, hugged, touched,talked to , comforted)

Smilesor
Alerts(2months or less)Brief smileor
Alerts briefly(2months or less)No smile, face anxious
orDull, expressionlessor
No alerting(2months or less)27

as well. In addition, a study of 175 febrile children with

criterion 26), including 65% of all OB cases 15).

leukocyte count ≧ 15,000/µl and fever without source

Antibiotics are expected to improve prognosis for thesefound 20 cases of pneumococcal OB and 3 Hib cases.

patients.

Bacterial meningitis followed one Hib case 27).TheThe remaining 70% with leukocyte count of <15,000/µl

current incidence of OB is similar to that of the United

includes 35% of the OB cases, though they are

States before the introduction of Hib vaccine andundetectable in our Guidelines. As the odds of these

therefore OB appears to be a major cause of serious

cases being OB are low, it is not practical to perform

bacterial infections in Japan even now.

blood cultures and administer antibiotics for all thesecases. The “wait and see approach” is recommended.

2) Limits of the Guidelines
3) Blood examination(1) Limits of clinical findings for detecting severe
Blood examination data is required to decide treatment

bacterial infection
When a doctor sees a patient with fever, an

options based on these Guidelines. Risk assessment byassessment of systemic condition should be taken first.

this method is essential (even though it may be painful

For an experienced doctor, it is not difficult to make an

and cost more). It is possible to measure both

exact judgment by physical examination only, perhaps

leukocyte/neutrophil

without the help of Table (Acute Illness Observation

simultaneously using only 20µl of capillary blood sample

Scales: AIOS) 10). According to McCarthy who developedby a commercially available instrument. The pain would

these scales, the sensitivity of them for detecting abe minimal if the blood were collected from a fingertip or

serious bacterial infection when used with the patient’s

an ear lobe using a blood-collecting needle for diabetes

clinical(Fig 2.) 30).

history,

carefulinterviewing

andphysicalcountsandexamination is 90% 28). This means that 10% isundetectable from clinical findings.
Because medical services are so easily accessible inFig 2. How to collect blood from a fingertip

Japan, patients tend to visit clinics in the early stage of afever, before serious symptoms have developed. In the1) Prick the fingertip using

research of Takeuchi et al., the rates of the symptoms

a disposable lancet for

observed on the first day of bacterial meningitis were as

diabetes.

follows: vomiting (56.7%), convulsion (7.5%), and one ormore meningeal signs such as neck stiffness andKernig’s sign, or anterior fontanelle bulging (11.1%).
Although vomiting is often observed from the early stage,
this is not a symptom specific to meningitis. It is not2) Gently massage fromfrequent at all to observe the meningeal signs that aretheconsidered more diagnostic. It is therefore difficult topuncture site to obtain the

diagnose bacterial meningitis on the first day of the illness

requiredwhen the patient’s general condition is not serious 29).

and draw up blood into a

hand

to
blood

near

the

volume,capillary tube - EDTA (orIn bacterial meningitis and other serious bacterial

heparin) coated.

infections, the systemic conditions become worse as timegoes by. Therefore, it is important to make an evaluationof severity at appropriate intervals.

3) Put blood into a micro
tube.

(2) Limits of laboratory finding for detecting OB
These Guidelines use a leukocyte count of ≧15,000/µl
as the criterion for administrating antibiotics. Thirty
percent of the cases of fever without source confirm this

28

CRP

level

may

have

been

effectivefor

preventing

possiblecomplications secondary to OB in the era of a few or no4) The instrument draws

resistant bacteria. However, the resistant strains ofup blood.

pneumococcus and Hib (common causative agents forOB) are increasing rapidly,

and the conventional

approach will soon be ineffective in Japan.
With the widespread use of medical equipment, it is
now possible to manage a risk control of fever by both
rapid blood examinations and rapid antigen tests in theoutpatient settings. In these Guidelines, we propose aprinciple of not administering antibiotics to the cases withleukocyte count of <15,000/µl, with the exception of bothBlood culture is possible with only 0.5-2.0ml of blood®

sample using the BACTEC bottle for children. Except for

infants of less than 12 months old with fever of ≧40°C

special cases, the culture needs to target only aerobic

and cases with bad general condition.

bacteria. The CO2 sensor underneath the bottle reacts if

Prescribing oral antibiotics without risk assessment tothe bacteria are cultured. The positive results are

all febrile children will result in an increase of resistantobtained after 12-24 hours.

bacteria and difficulty in treatment of OB and otherserious bacterial infections. Oral antibiotics have possible
effects of slightly decreasing risks of pneumococcal OB

4) Administration method31). However, they are not only ineffective on OB due toWhen a severe bacterial infection is suspected,
intravenously

Hib, but also the use of them may delay the correctwhenever possible. Since this method is more efficient

diagnosis, and result in a poor prognosis if bacterial

than oral administration for taking the drug into the body,meningitis has already developed 32). Therefore, it is notthere is a quicker increase of the drug concentration inrecommended to prescribe antibiotics to all febrile

the blood. Therefore, better effects are expected. CTRX

children.

antibiotics

shouldbeadministeredis recommended, as it has a long half-life of 7.5 hours,
and sustains effective blood concentration for 24 hours

Subjoinder:

after administration -- features suitable for outpatient
treatment.

Baraff’s guidelines (the basis for our Guidelines) are
now intended in the United States only for children who
have not received Hib and pneumococcus vaccines.

5. Instructions for the practice of these Guidelines

These vaccines should also be introduced in Japan assoon as possible to prevent serious bacterial infections

Careful observation on the course of the disease is

and to reduce the use of antibiotics.

most important for the judicious use of antibiotics. It is notpossible to identify all cases of serious bacterial infection

References

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草刈 章 (Kusakari A), 他. 小児科外来における上気

patient carefully and use their discretion to decide the

道炎診療調査―発病72時間以内の初診患者に対する

optimal treatment. The ultimate decision of the use of

抗 菌 薬 使 用 状 況 ― . 外 来 小 児 科 2004;7:122-127.

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(In Japanese)
2.

Greenes DS, et al. Low risk of bacteremia in febrilechildren with recognizable viral syndromes. Pediatr

6. Summary

Infect Dis J 1999;18:258-261 [Medline]
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原三千丸 (Hara M). 症状から見たウイルス感染症診断学. 小児内科 2005;37:31-37. (In Japanese)

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in daily practice and the fear of serious bacterial

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吉村 速 (Yoshimura H). 迅速診断キットの利用法.
小児内科 2005;37:38-41. (In Japanese)

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29

Shaw KN, et al. Prevalence of urinary tract infection

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Ann Emerg Med 1998;31:679-687 [Medline]30

Algorithm for the management of child 3-36 months of age with fever without source

STEP

１

General condition
YES

Immediate hospitalization

Is there cyanosis, impaired consciousness, lack in response to

and examination for

stimulation, severe dehydration, or complex febrile seizure ?

appropriate treatment

NO
STEP

z

２

Seek a focus of infection

Oral & pharyngeal findings or skin rash may provide information for
diagnosis of infections by enteroviruses, herpes virus or HHV6.

z
z

YES

Symptoms and findings of pharyngitis, tonsillitis, bronchitis and croup
indicate the presence of infection focus.

Treatment based on

Based on the endemic, the rapid tests of GABHS, influenza viruses

the diagnosis

type A/B, adenoviruses and RS virus should be used to specify thecausative pathogen.
z

Urinalysis is essential in boys aged less than 1 year and girls aged lessthan 2 years for the possibility of urinary tract infection.
NO

STEP

３

Consider whether a blood culture should be obtainedz

Watchful observation without antibiotics is fundamental.

zBut, when one of the findings below is present, go to STEP 5.

a)Infants of 3-12 months old with either a temperature of ≧40°C, or 38.5°C or more and leukocyte count ofb)

Infants of 12-36 months old with a temperature of ≧39°C and leukocyte count of ≧15,000/µl ( or≧15,000/µl ( or neutrophil count of ≧10,000/µl).
neutrophil count of ≧10,000/µl).
Present

Not present
STEP

z
z

4

STEP

Watchful observation

５

Treatment

Observation should be continued for 6-48 hours without

The optimal treatment is a blood culture and intravenous

antibiotics.

ceftriaxone (CTRX) 50mg/kg once a day.

When the fever persists, and CRP level is 5.0mg/dl orNote: oral amoxicillin (AMOX) 60-90mg/kg/day is anotherabove, treatment should be started in consideration foravailable option.

the possibility of serious bacterial infection.

During the culture, the patient should be observed carefully.

Blood culture positive(Modified from 中西奈美:トレンドビュー
方は最小限に.

－抗菌薬処

日経メディカル 2005;454:24-25)

Hospitalization is recommended31