demonstrated to be susceptible to the second generation cephalosporins, cefotiam ... Against S. marcescens strains, the 4 third generation cephalosporins were ...
2314(176)
THE JAPANESE
SUSCEPTIBILITY
OF
AERUGINOSA
JOURNAL
RECENT
AND
CEFTIZOXIME,
OF ANTIBIOTICS
CLINICAL
SERRATIA
ISOLATES
MARCESCENS
CEFMENOXIME,
CEFSULODIN
IN
BETA-LACTAM
OF TO
PSEUDOMONAS
CEFOTAXIME,
LATAMOXEF
COMPARISON
Sept. 1982
XXXV-9
WITH
ANTIBIOTICS
AND
OTHER AND
AMINOGLYCOSIDES YOSHIYUKI KAWAKAMI, YUICIE OKIMURA, NAOKO HORIUCHI and MASAMITSUKANAI Bacteriological Division, Central Clinical Laboratories, Shinshu University Hospital, Matsumoto, 390, Japan (Received for nublication
June 12. 1982)
It has long been considered that cephalosporins have no effect on Serratia marcescens and Pseudomonas aeruginosa strains which produce beta-lactamases8,5). However, the development of second generation cephalosporins has changed this concept. Namely, some strains of S. marcescens were demonstrated to be susceptible to the second generation cephalosporins, cefotiam and cefoxitin21,24,27). In addition, cefsulodin has shown to be highly active against P. aeruginosa strains, in spite of its narrow spectrumn,15,22,28). Moreover, the new semisynthetic third generation cephalosporins, cefotaxime, ceftizoxime, cefmenoxime and latamoxef, that are stable for beta-lactamases, have been reported to have high activity against various Gram negative and positive bacteria 1,2,4, 6-10, 12,18,14,18,17,19,25,26,28). We therefore tested in vitro susceptibility of 100 S. marcescens and 100 P. aeruginosa strains to cefotaxime, ceftizoxime, cefmenoxime, latamoxef and cefsulodin, together with ampicillin, sulbenicillin, cefazolin, cefotiam, cefoxitin and 3 aminoglycosides, gentamicin, tobramycin and amikacin. All of the strains tested were recently isolated from in-, and out-patients at Shinshu University Hospital, Matsumoto, 390, Japan. P. aeruginosa strains were identified as follows; Gram-negative strictly aerobic rods that failed to produce acid from glucose and to produce H2S in the butt of triple sugar iron (TSI) agar. They grew on SIMMONS'citrate agar, gave positive cytochrome oxidase test, and produced apparent diffusible green pigment in KING'S A (Eiken, Tokyo) medium. Criteria used for the identification of S. marcescens strains were as follows; Gram-negative facultatively anaerobic cytochrome oxidase negative motile rods that ferment glucose and sorbitol, but not arabinose and raffinose. They neither produced indole, H2S (in TSI agar) nor urease. Lysine was decarboxylated. They grew on SIMMONS'citrate agar, and excreted gelatinase and extracellular deoxyribonuclease. Susceptibility to 13 antimicrobial agents was tested as follows; Saline suspension of each strain at a concentration of 107 cells/ml was prepared from 18 hours heart infusion agar (Eiken, Tokyo) culture. A loopful of the suspension was streaked onto heart infusion agar (Eiken, Tokyo) plates, containing serially diluted antimicrobial agent from 800 to 0.012 ,ug/ml. The results were read after incubation at 35°C for 24 hours. The minimal inhibitory concentration was taken as complete inhibition of growth. Tables 1 and 2 showed the concentrations of antibiotics required to inhibit the growth of 50% and 90% of the total number of strains examined (MICH and MIC90, respectively). No strain of S. marcescens or P. aeruginosa was inhibited by 800 ,ug/m1 of cefazolin. Against S. marcescens strains, the 4 third generation cephalosporins were uniformly more active than gentamicin, tobramycin, amikacin and the other beta-lactam antibiotics, and were 65- to 510-fold more active than cefotiam and cefoxitin, the second generation cephalosporins. In fact, the MICH values of cefotaxime, ceftizoxime, cefmenoxime and latamoxef were, respectively, 0.78, 0.1, 0.2 and 0.39 ,ug/ml, compared with 50 ,ug/m1of cefoxitin and 200 ,ug/m1 of cefsulodin. Among the 4 third generation cephalosporins, ceftizoxime showed the highest degree of activity, cefmenoxime and latamoxef demonstrated the second, but cefotaxime was slightly less active than the others. It should be noted that
Sept. 1982
THE
Table
Figures
1.
in parentheses
JAPANESE
Susceptibility
indicate
JOURNAL
of 100 strains
MICH
and
OF ANTIBIOTICS
of Serratia
MIC90 for
16 out
XXXV-9
marcescens
of
100 S
of clinical
. marcescens
2315(177) origin
strains
resistant
to
gentamicin Table
2.
Susceptibility
of
100 strains
of Pseudomonas
aeruginosa
of clinical
origin
the 4 third generation cephalosporins unexceptionally demonstrated the excellent degree of activity in comparison with gentamicin, which has currently been considered as the first choice drug against S . marcescens infections20). In fact , the MIC50 and MIC90 among the 16 gentamicin resistant strains (MIC values, greater than 50 pg/m1) were 0.39 and 3.13 1ig/m1 for cefotaxime and ceftizoxime , 0.78 and 3.13 ttg/m1 for cefmenoxime and 1.56 and 12.5 pg/ml for latamoxef , respectively.A gainst P. aeruginosa strains, cefsulodin was more active than any other agents tested . Tobramycin showed the second highest degree of activity , followed by gentamicin. The 4 third generation cephalosporins were slightly less active than the 3 aminoglycosids examined , but latamoxef was almost as active as amikacin. Fifty percent of P . aeruginosa strains were inhibited by 6.25 tig/ml of latamoxef, 12.5 jug/m1 of cefotaxime and cefmenoxime and 25 aug/m1 of ceftizoxime, respectively. On the other hand, cefazolin, cefotiam , cefoxitin and ampicillin uniformly allowed the growth of all the
2316(178)
TIM. JAPANESE
JOURNAL
OF ANTIBIOTICS
sept. 1982
XXXV-9
P. aeruginosa strains at the concentration of 200 ,ug/ml. In conclusion, cefsulodin demonstrated the highest degree of activity against P. aeruginosa strains among the agents examined. In addition, against S. marcescens and P. aeruginosa strains, thus far reported to be resistant to cephalosporins in current use5,18),cefotaxime, cftizoxime, cefmenoxime and latamoxef were proved to have excellent activities in comparison with presently available bata-lactam antibiotics. Standard powders of antimicrobial agents kindly provided as follows are gratefully acknowledged; cefotaxime from Hoechst Japan, ceftizoxime and cefazolin from Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan, cefmenoxime, cefsulodin and cefotiam from Takeda Industries, Ltd., Japan, latamoxef, gentamicin and tobramycin from Shionogi & Co., Ltd., cefoxitin from Daiichi Seiyaku Co., Ltd., Japan and amikacin from Banyu Pharmaceutical Co., Ltd., Japan. Refbrences 1)
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M.
lactamase-
and
lactam, 2)
J.
E. ; V.
and
other
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R.
K.
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a
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new
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W.
S.;
P.
SYKES, to
PHILLIPS:
and
antibiotic
stability &
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and
in
antibacterial
Chemoth.
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ceftizoxime,
to
20:
Serratia
activity
171•`175,
penicillins
and
a j9-lactamase-stable
:
Susceptibility
of
18 : 832•`833,
moxalactam
of
1981
cephalosporins
in
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Anti-
&
:
Comparative
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corrodens
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Chemoth.
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Eikenella
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newer
1980
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Agents
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MINE,
In
vitro
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by
disk
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1981
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In
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MIYAMOTO
&
Agents
activity
Antimicr.
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MITSUHASHI
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activities.
vitro
1•`, 8,
synergistic
tobramycin,
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Comparative with
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Ceftizoxime
Antimicr.
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169,
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an 1890
1980
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moxalactam
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Antimicr.
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beta-lactamase
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M.
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OKADA,
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DREW:
332,%,
925•`926,
NOMURA,
I.
combined
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-lactam
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1976
Agents
AGYARE
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548,
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MASUYOSHI,
E.
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MATSUMOTO,
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1980
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factor-mediated
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127,
p-Lactamases
590,
cefamandole
strains
Chemoth
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R
123
251,
of
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MITSUHASHI
Agents
&
&
vitro
Jr.:
10:
: 245•`,
GOMBERT
OPFER
activity influenzae
Bacteroides
FARRAR,
S.
134
17 : 583",
540•` K.
&
Antibacterial
parenteral
Chemoth.16:
E.
O'DELL:
OPFER:
In
cephalosporin.
Dis.
E.
vitro
19 : 248•`252,
W.
methods.
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KING,
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M. Inf.
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HALL,
Limited
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betalactam
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KUNO,
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Agents
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Haemophilus
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chloramphenicol
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GIROLAMI, Agents MATrHEw:
N.
L.
&
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J. Antimicr.
SHIPKOWITZ
Chemoth.
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jS-lactamases Chemoth.
R.
R.
454•`460, of 2:
BOWER
Gram-negative
115•`157,
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Antimicrobial
activity
of cefmenoxime
1981
1976
bacteria
and
their
role
in
resistance
sept. 1982
THE JAPANESE
19)
TANAKA,
N.;
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H.
SUGINAKA,
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TRAUB,
19:
W.
S.
KOTANI,
of action 379~401,
H.;
I.
JOURNAL
of
M.
OF ANTIBIOTICS
OGAWA
benzylpenicillin
&
XXXV-9
G . KOSAKI
, apalcillin,
:
iS-Lactam
cefazolin
2317(179)
resistance
and
in
ceftizoxime.
Serratia
mar-
Antimicr.
Agents
1981
KLEBER,
A.
PUHLER
& H.-J.BURKARDT:
Characterization
of a nosocomially
significant ,
multiple
drug-resistant
TSUCHIYA,
K.;
M.
cephalosporin: 568, 22)
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&
vivo
K.;
M.
T.
&
in
Komo:
marcescens.
H.
vivo
ONO,
M.
Chemotherapy TAKEUCHI
antibacterial
activities
L.:
VERBIST,
L.
&
H .
NAGATOMO:
(Basel)
&
T.
.
Antimicr.
cefazolin
Comparison
and
of
in
&
J. VERHAEGEN:
NISHI:
vitro
vitro
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297~312
SCE-963
, 197621)
, a new
Agents
SCE-129
. 13:
&
broad-spectrum
Chemoth.
14:
557•`
. 13:
of
cephalosporin:
137•`145,
cefoxitin:
eight
Antimicr:
A
of N-formimidoyl
In
new
semisynthetic
89•`93,
1977
j9-lactamase-stable &
and
vitro
and
1978
27:
Agents
gentamicin
1978
antipseudomonal
Chemoth
of
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536~539,
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activity
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Agents
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Chemoth.
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1981
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cephamycin
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N.
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glucose-nonfermentative
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the
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READING
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Anti-
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ENCISO,
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thienafrom
no-
Agents
