Methicillin-resistant
Staphylococcus aureus (MRSA) isolatedat Fukuoka University Hospital
KenjiThe

SecondDepartment
7-45-1,(ReceivedofInternal1slanakuma,February

Kono

Medicine,

Fukuoka

Jonan-ku,

22,

University,

Fukuoka

School

814-01,

1993• Accepted

AprilofMedicine,Japan

16,1993)

We evaluated 97 cases of infection by methicillin-resistant Staphylococcus aureus at theFukuoka University Hospital, where this infection presents a serious problem. We
evaluated the origin of specimens, coagulase typing, production of toxic shock syndrome
toxin-1 (TSST-1) and susceptibility to various antimicrobial agents isolated at between
February and May 1989. Specimens consisted primarily of sputum and pus. Sixty percent
of all strains produced coagulase type VII.Only 4 strains produced TSST-1. Vancomycin,
rifampicin, clindamycin, and sulfamethoxazole/trimethoprim
showed good antibacterial
activities against MRSA. Coagulase type VIIstrains were resistant to minocycline but
sensitive to erythromycin and clindamycin as compared with those of type IV.
Key words: MRSA, coagulase type, drug susceptibility
Introduction
Nosocomial infection produced by methicillinresistant Staphylococcus aureus (MRSA) is a serious problem in our country. In our institution (an800-bed hospital) , MRSA has become a serious
problem. Though the hospital staff uses measures
to control this infection, its nature changes eachyear". Coagulase type II strains are becoming thepredominant instead of type IV, and are more resistant to various antibiotics than type IV2.3. We evaluated the antimicrobial susceptibility, coagulase
type and production of TSST-1 of 97 clinical isolates of MRSA between February and May 1989,
and identified an outbreak of the coagulase type VII
strain of MRSA.
Clinical isolates
Staphylococcus aureus strains were isolated at thecentral laboratory of our hospital. Clinical isolates
were tested for resistance to oxacillin using the disk
diffusion susceptibility assay method specified by
the National Committee for Clinical Laboratory
Standards (NCCLS)4). Zone size was read after
incubation ior 24 hours . Isolates of S. aureus withzone sizes <10 mm around a disk containing 1,ug

oxacillin100

werestrains

morethandifined

wereevaluated,oncefromas

being

thesame

MRSA.

excluding

Of

those

these,countedpatient.

Methods
The

minimum

drugs

was

wasinhibitory

also

madeproduction.

to

each

methodbyusing

Co.

Tokyo,

agentsweretestedatconcentrations

0.5,

1,2,4,8 andmethicillin,

cefmetazol,

minocycline,

ofloxacin,cin,vancomycin,sulfamethoxazole/trimethoprim.

tionwith
30•Ž.

and

the

the

bacterium,

MIC

was

commertialTokyo,Japan).
analysisplatesofiig/ml.

(EikenThe

0.06,0.12,

agentsweregentamicin,
erythromychloramphenicol,
Aftertheplates

wereevaluated.
TSST-1(Denkafor

theSoci-Japan).Twelve

clindamycin,

ofkitstoJapanimipenem,

thenproduction

using

StatisticalLtd,

rifampicin,

and

at

16

thefrozen&

thetoxin-1

accordingdescribed

Chemotherapy5),

andsyndrome

measuredofJudgement

types,

shockwas

Kagaku0.25,(MIC)

strain.

coagulase

toxic

MIC

microdilutionoffor
asof(TSST-1)

ety

concentration

determineddrug

inoculaincubated

Coagulase
wereSeiken

typedetermined&susceptibility

Co.

Ltd,

was

736

CHEMOTHERAPY

JULY

1993

the remaining 100 strains, 97 strains showed MICsof >16 pg/m1 against methicillin by the microdilu-

Coagulase typeThe distribution of coagulase types appears inFig. 3. Coagulase type VII made up 61.5% (61strains) , mixed type 9,3% (9 strains) , and type VI
6.2% (6 strains) The coagulase type could not be
determined in 22.7% (22 strains) even on incubation for 48 hours.
Production of TSST-1
Production of TSST-1 was observed in 4 strains.
These strains were isolated from the pus of one

tion method performed
nal medicine division.

patient each in the departments of surgery, orthopedics and otorhinology, and from the sputum of

performed using Wilcoxon's t - test. A level of p
<0.05 was accepted as statisticallysignificant.
Resultsof strains

The total number
at our central

laboratoryof S. aureus isolated

was 203. Of these,

134(66%) were methicillin-resistantas determined bydisk diffusion assay. We excluded 34 strains whichwere detected in the same patients. Accordingly,
ofof <8 ;4/mg
mately,at a laboratory
Three strains

were excluded

97 MRSA strainsin the interwith MICs

from the study , Ulti-

were isolated

and evaluat-

ed in this study.
Origin of specimens
Thepercentageof themedical department

strains

categorized

proportion,
23.7% (23 strains) , was detectedsurgery(100 beds) , followed
by 18.7%
from

Fourteen
intensivestrains were isolated from the neonatal
care unit (15 beds) . Of these, 6 strains

screeninginternal

medicineon(18strains)

were recovered

theby

is shown in Fig. 1. The largest

from specimens

the anterior(180 beds).

taken at the time ofnares before the patientdischarged from the hospital.
Most of the isolates were culturedandpus,

38.1%(37strains)

strains), respectively(Fig. 2).

Fig. 1.

Distributionof MRSA

from sputum

and35.1%

by medical(34Fig. 2. Distribution of MRSA by specimen.
Total number of strains= 97

departFig. 3.

ment.
Total

was

number

NICU = neonatalof strains
intensive

=97
care

Coagulase

Fukuokaunit

Totaltypes

University
numberofMRSA

Hospitalof strains=97.

isolatedat

VOL.41

one

NO.7

patient

inDistribution

theThedrug

distributionin4.

antimicrobial
and

was

toresistant16ƒÊg/ml
andororless

totoofloxacin.

However,Theagainstthegood

antibacterial

agents.

Susceptibility

wasantibiotics

1ƒÊg/m1),

noMIC60s

MICsand1ƒÊg/ml),

tostrainallrifampicin,

inof

satisfactoryof(6 strains)

vs.

those

four

antibiotics

isshowninFig.

significantly

more

minocycline

damycin(p <0.05),

of

type

VII

by

coagulase(60strains)

cumulative

Coagulase

MIC

type

to

VII

imipenem(p <0.05),
toanderythromycin(p <0.001)

significantly

more(p <0.001)

than

were

coagulase

andtypeIVclin-strains.

Discussion

with

MRSA

comprized

Staphylococcus
that

atotherinstitutionsishigherthanincidenceof

MRSA

surgery

wasupto66%

of

the

isolatedatourinstitution.

is isolatedataureus

appears

inin

in

MRSA

wasmedicine.
intensive
high.

numberofbeds

inscreened

bynasalculture

in

MRSA

whom

anddicatinga highof

therateSputumypatients

with

low

tumors(datanottype

VII accounted

higherthan

previously

gatorshavereportedfrominvestigators
tal,

which

statedtoat
isthat

32.3%

of

on

which

all

MRSA

the

thehasII2,3).

type

markedly
investi-recentlyA

shiftreport

Universityever,therehave

been

noreports

VII atsuch

a highrateasinwasnothetoxictype,istoatstrains

theMRSAtheceredivi-Severalsame

VII strains

betweenasmalignantof66%,

onfeces.,

coagulasereported1•`3)

type

correlation

4%

KagoshimaThe

surgicalfor

tolocated

pus.

from

regardcoagulaseinMost

such

With

the

symp-

medicinedeveloped

IVwereanddiseases
internal

While

that

infants

non-ambulator-patient

type

are

Six

blood

recoveredforsmallinfantsandnocoagulase

asputum

fromshown).

syndrome.

onlycarriers.

operated

TSST-1,(NICU)

reaction,urine,

theofunit

MRSA

nerveinshocked

isolated

mainlypatients

incidence

allwereThe

departments

Thedischarge.

incentralof

thecarerecoveredwoundsproducedin

NICU,

werewasrate

States7,8).

inflammatory

disorders
Pus

rate

thisatstudiedIthighisofof

similarly

There

proportion

mainlybrovascularsion.

nowas

was

thestrains
hadspecimens

detectionhigheststrains

However,
Unitedinternal

considered

tom-freetheneonatal

thealsoJapan6).

reportedandMRSA

Susceptibility of MRSA to 11 antibiotics.
cefmetazole,
imipenem,
gentamicin,
minocycline,
ofloxacinb. erythromycin,
clindamycin,
vancomycin, rifampicin,
sulfamethoxazole/trimethoprim, chloramphenicol
Total number of strains= 97

strainsofresistantsusceptibleofFig. 4.
a.

MRSA

5.

these

vancomycin

sulfamethoxazole/trimetho-susceptibility

and0.13ƒÊ4g/and2ƒÊg/m1),IV

curvesimipenem

activity
also

Thewerewere(MICsotype

erythromycin,

737

Hospital(MICR80

patterns

minocycline,
theclindamycin(MIC5011

bimodalsusceptibility

dicating

erythromycin,

medicine.

University

prim

showedHowever,againstinternal

susceptibility

Strainsvancomycin.

moreofloxacin.

ofsusceptibility
ofFig.

clindamycin,

mldepartmentofappearsofMRSA at Fukuoka

islandasaccountforthat

facility9)

ofdetection

presentcoagulase

byHospius,up

Howofstudy.
typingtypeThereand

CHEMOTHERAPY

738

Fig. 5.

type of specimen

imipenem

Clindamycin

Minocycline

Erythromycinof MRSA

coagulase

Numberof coagulase

typeVII strains=

60

Numberof coagulase

typeIV strains=

6

Susceptibility(data not shown)

S. aureus coagulase
pus from infected
type VIIis detected

JULY

type IV and VII to fourcline

type IV is detected

mainly inwounds and abcesses")), whilemore frequently
in stool fromepidemiologicalsignificanceof this high rate ofcoagulase type VIIon Kyushu Island. MRSA clinicalagainstauthorthanksto erythromycin

and clindamycin,

facility
damycin.

weresensitive

While several

to erythromycin

and clin-

reports have found minocy-andcaused

IV"),

our

clindamycin

theseMrs.

Murakami

for

Nasu

M,

Goto

microbial

strains

isolated

Kyoko

Ueki

theiragainst

recentlytendencyat

Watanabetion
atbyfindings
wouldbeinourandtechnicalthe475,

aY,

ofMr.

assistance.

et.

isolated
newly

Kuboal.:InvitrochemotherapeuticS.

antiagentsStaphylococcus

openedaureus:university

33: 427•`433,M,hospital.

1985

Ishiyama

H, et.

al.:

Staphylococcus

Chiba

University

Hospital

recent5 years.

Chemotherapy.

Isolaaureus

Observation
35:

467-

1987

TakesueY,

Yokoyama

Methicillin-resistantnosocomial

infections

142,

Goto

of methicillin-resistantduring3)

J.

activity

Chemotherapy2)

betweendrug susceptibility
and coagulase
type
demonstrated
the drug susceptibility
patterns
ofcoagulase type VII-producing strains. The infections
caused by MRSA strains of coagulase type VIIat ourerythromycin

andReferences1)

eventhough MRSA is generally thought to be resistant toerythromycin
and clindamycie
Our correlation

infections

IIAcknowledgements
The

isolates in our hospital were resistant to minocycline , ofloxacin and imipenem,
but were highly
susceptible

againsteffective

Noriyukiandantibiotics.

type

that

tigationthe cause

effective

moresetting.

to reveal

becoagulase

showpatients with food poisoning").
In our hospital there
was no correlation
between coagulase typing andtype of specimen (data not shown) . Further invesis still requiredtoMRSA

1993

1989.

T ,KodamaS .

aureus(MRSA)

Chemotherapy

37:Tet.

al.:in137-VOL.41

NO .7

MRSAat FukuokaUniversity4)

National
Committee for Clinical Laboratory
Standards.
Performance Standards for Antimicrobial Disk Susceptibility Tests . 4th ed. Villanova, Pa: NCCLS; 1990
5) Japan Society of Chemotherapy . Standard
method for dilution antimicrobial susceptibility
tests for bacteria (Microdilutionmethod) .
Chemotherapy 38: 103-105, 1990 (in Japanese)6) Nagatake T, Matumoto K, Shishido H, et, al.:Causative organisims of hospital-acquired
pneumonia and infected pressure sores . Infection due
to methicillin-resistant
Staphylococcus aureus .
Chemotherapy 34: 240?249, 1986
7) Lentino J R, Hennein H, Krause S, et. al.: A
comparison of pneumonia caused by gentamicin ,methicllin-resistantand gentamicin , methicillinsensitive Staphylococcus aureus: epidemiologic andclinical studies. Infection Control 6: 267?272,
1985
8) Faoagali J L, Thong M L, Grant D: Ten year's
exprience with methicillin-resistant
Staphylococcus aureus in a large Australian hospital, J .

Hospital739

Iiosp, Infect. 20: 113?119, 1992
Nishi J, Yoshinaga M, Mogi, A et, al,:
Nosocomial infection due to methicillin-resistant
S. aureus (MRSA) at the Kagoshima University
Hospital. J. Jpn. Assoc, Infect. Dis. 65: 1123?
1135, 1991
10) Hayashi K, Tokuchi M, Sawa K et. al.: Bacteriological and epidemiologicalstudies on Staphylococcal food poisoning outbreaks occurred inShiga prefecture during 1974-1983. Rep. Shiga
Pref. Inst. Pub. Hlth. & Environ. Sci, 19: 33'43, 1984
11) Goto K: Studies on the relationship between Staphylococcus aureus inhabited in human and staphylococcal food poisoning.1. Coagulase types
and crystal violet ring test of isolates from clinical specimen. J. Jpn. Assoc. Infect. Dis. 55: 576582, 1981?
12) Nagatake T, Yoshida T, Taguchi M, et. al.:Chemotherapeutic effect on respiratory infections
with methicillin-resistant
Staphylococcus aureus .
Chemotherapy 38: 371?380, 1990
9)福 岡 大 学 病 院 に お い て 分 離 さ れ たmethicillin‑resistant
Staphylococcus

auzeus(MRSA)株

向野賢の検 討治

福岡大学医学部第2内 科*

福 岡 大 学 病 院 に て1987年2月
cusdromecureus(MRSA)97株

か ら5月に つ い て,検toxin‑1(TSST‑1)産

生 性,種ま で に 分 離 さ れ たmethicillin‑resistant

Staphylococ‑

体 の 由 来,コshockが60%を占 め た 。TSST‑1をで あ っ た 。 薬 剤 感 受 性 で はvancomycin,rifampicin,clindamycin

感 受 性 を 示 し た 。 ま た,コ
耐 性,erythromycinお*福 岡 市 城 南 区七 隈7‑45‑1

ア グ ラ ー ゼVII型

よ びclindamycin感syn‑々 の 抗 菌 剤 感 受 性 に つ い て 検 討 し た。 喀 疲 と膿 が 主 な

分 離 検 体 で あ っ た 。 コ ア グ ラ ー ゼ 型 別 で は,VII型
は,4株

ア グ ラ ー ゼ 産 生 性,toxic

株 は,コ

ア グ ラ ー ゼIV型

受 性 を 示 した 。

,ST合産 生 した の剤が良 好 な

株 に 比 し てminocyciine