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Journal of Antimicrobial Chemotherapy (1982) 10, 543-547
The susceptibility of Yersina to eleven antimicrobials
Francisco Soriano and Josefa Vega
Departamento de Microbiologia, Fundacion Jimenez Diaz, Universidad Autonoma deMadrid, Avenida de Reyes Catolicos 2, Madrid-3, Spain
The susceptibility of Yersinia pseudotuberculosis, Y. enterocolitica, Yersinia-likeorganisms and atypical strains of Yersinia against gentamicin, streptomycin, sul-phamethoxazole, trimethoprim, trimethoprim-sulphamethoxazole, chloramphe-nicol, tetracycline, doxycycline, ceftriaxone, ceftazidime, moxalactam andn-f-thienamycin has been studied. All the 167 strains tested were highly sensitiveto ceftriaxone, ceftazidime, moxalactam and n-f-thienamycin (MIC ^ 0-5 mg/1).There were no strains resistant to gentamicin, trimethoprim and the combinationof trimethoprim-sulphamethoxazole. There were 17-5% sulphamethoxazole and16-7% streptomycin resistant strains among Y. enterocolitica and all the strepto-mycin resistant strains were resistant to sulphamethoxazole. There appears to becross resistance as 22 of the 23 sulphamethoxazole resistant strains were alsostreptomycin-resistant. Therefore, sulphamethoxazole and streptomycin cannotbe recommended for the empiric treatment of Y. enterocolitica infections.
Introduction
Yersinia enterocolitica is being isolated with increasing frequency from clinicalspecimens in Spain and other parts of the world. Human infections by Y. pseudo-tuberculosis are less frequent but this micro-organism is responsible for the 8-4% ofyersiniosis seen in our hospital (Soriano et al., 1981). The clinical manifestationsof yersiniosis are varied but the most prominent symptoms include diarrhoea, acutemesenteric adenitis, septicaemia, erythema nodosum, arthritis and enteric fever-likesyndrome. Streptomycin (Johnson, 1974), tetracycline, chloramphenicol or cotri-moxazole (Hughes & Guerrant, 1979) have been recommended for the treatment ofsevere and acute mesenteric adenitis or enteric fever-like syndrome and gentamicinor chloramphenicol for sepsis (Boyce, 1979).
There are few antimicrobial susceptibility data in the literature and often refer toparticular antimicrobial agents. The purpose of this study was to obtain quantitativeantimicrobial information using the agar dilution method for determining minimalinhibitory concentrations (MICs) of old and new drugs. A previous paper dealingwith the antimicrobial susceptibility of Y. enterocolitica to old and some new beta-lactam antibiotics as well as clavulanic acid, has been reported by us (Gaspar &Soriano, 1981).
Material and methods
Strains. One hundred and sixty-seven strains of Yersinia were studied and groupedas follows: group I (15 Y. pseudotuberculosis), group II (75 recent clinical strains
543O3O5-7453/82/I2O543+O5 $02.00/0 © 1982 The British Society for Antimicrobial Chemotherapy
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Tab
le I
. Ant
imic
robi
al s
usce
ptib
ility
of
167
Yer
sini
a st
rain
s
Gro
up
Y. p
seud
otub
ercu
losi
s (1
5)*
Y. e
nter
ocol
itic
a hu
man
path
ogen
(75)
t
Y. e
nter
ocol
itic
a fro
mco
llect
ions
(56
)$
Gen
eric
gent
amic
inst
rept
omyc
insu
lpha
met
hoxa
zole
trim
etho
prim
trim
.-su
lpha
m. (
1/10
)tr
im.-
sulp
ham
. (1/
20)
chlo
ram
phen
icol
tetr
acyc
line
doxy
cycl
ine
ceft
riax
one
ceft
azid
ime
mox
alac
tam
n-f.
thie
nam
ycin
gent
amic
inst
rept
omyc
insu
lpha
met
hoxa
zole
trim
etho
prim
trim
.-su
lpha
m. (
1/10
)tr
im.-
sulp
ham
. (1/
20)
chlo
ram
phen
icol
tetr
acyc
line
doxy
cycl
ine
ceft
riax
one
ceft
azid
ime
mox
alac
tam
n-f.
thie
nam
ycin
gent
amic
inst
rept
omyc
insu
lpha
met
hoxa
zole
trim
etho
prim
trim
.-su
lpha
m. (
1/10
)
MIC
ran
ge (m
g/1)
$0-2
5-1
0-5-
20-
5-8
$0-2
5-1
$0-2
5-0-
5$0
-25-
0-5
1-4
1-4
$0-2
5-0-
5$
01
2$0
-12
$0
12
$0-1
2-0-
25
$0-2
5-4
1->
128
2->
128
$0-2
5-1
$0-2
5-16
$0-2
5-32
2-4
1-4
$0-2
5-1
$012
$0-1
2$
01
2$0
-12-
0-5
$0-2
5-16
1->
128
2->
12
80-
25-2
$0-2
5-16
MIC
50 (
mg/
l)
$0-2
52 4 0-
5$0
-25
0-25
2 4$0
-25
$0
12
$0
12
$0
12
$0
12
1 8 8 1 0-5
1 4 4 0-5
$0
12
$0
12
$0
12
0-25
1 8 4 1$0
-25
MIC
*, (m
g/l)
0-5
2 8 1$0
-25
0-5
2 4$0
-25
$0
12
$0
12
$0
12
0-25
2>
128
> 1
28 1 4 8 4 4 1$
01
2$
01
2$
01
20-
5
2>
128
> 1
28 1 4
Yers
inia
-lik
e or
gani
sms
(13)
§
Yers
inia
(at
ypic
al s
trai
ns)
(8)
tnm
.-su
lpha
m.
(1/2
0)ch
lora
mph
enic
olte
trac
yclin
edo
xycy
clin
ece
ftri
axon
ece
ftaz
idim
em
oxal
acta
mn-
f. th
iena
myc
in
gent
amic
inst
rept
omyc
insu
lpha
met
hoxa
zole
trim
etho
prim
trim
, su
lpha
m.
(1/1
0)tr
im,
sulp
ham
. (1
/20)
chlo
ram
phen
icol
tetr
acyc
line
doxy
cycl
ine
ceft
riax
one
ceft
azid
ime
mox
alac
tam
n-f.
thie
nam
ycin
gent
amic
inst
rept
omyc
insu
lpha
met
hoxa
zole
trim
etho
prim
trim
, su
lpha
m. (
1/10
)tr
im,
sulp
ham
. (1
/20)
chlo
ram
phen
icol
tetr
acyc
line
doxy
cycl
ine
ceft
riax
one
ceft
azid
ime
mox
alac
tam
n-f.
thie
nam
ycin
$0-2
5-32
2-16
1-16
$0-2
5-16
=$01
2$0
-12-
0-5
$0-1
2-0-
25=$
012-
0-5
=$0-
25-0
-5\-
\0-
5-16
$0-2
5-0-
5$0
-25-
1=$
0-25
-11-
41-
2$0
-25-
1$
01
2"
$0-1
2-0-
25$
01
2$0
-12-
0-25
$0-2
5-0-
51-
41-
16=$
0-25
-1=$
0-25
-1=$
0-25
-12-
81-
128
$ 0-
25-8
=$01
2$0
-12-
0-25
=$01
2=$
0-12
-0-5
1 4 2 0-5
=$01
2=$
012
=$01
20-
25
$0-2
52 8
$0-2
50-
50-
54 2
=$0-
25=$
012
=$01
2=$
0-12
0-25
=$0-
252 4
=$0-
25$0
-25
$0-2
54 2
$0-2
5$
01
2=£
0-12
=$01
20-
25
8 8 2 1=$
0-12
0-25
=$01
20-
5
=$0-
252 16
=$0-
250-
51 4 2 0-
5$
01
20-
25$
01
20-
25
0-5
4 16 1 1 1 8 128
8$
01
20-
25$
01
20-
5
*, S
erot
ype
1 (5
str
ains
); s
erot
ype
2 (7
str
ains
); o
ther
ser
otyp
es (
3 st
rain
s)t,
Bio
type
4, s
erot
ypes
3 (7
2 st
rain
s); o
ther
bio
- an
d se
roty
pes
(3 s
trai
ns).
%,
Bio
type
4, s
erot
ype
3 (2
7 st
rain
s); o
ther
bio
- an
d se
roty
pes
(29
stra
ins)
.§,
Inc
lude
ser
otyp
es 2
a, 4
, 5,
6, 7
/13,
10,
14,
16
and
19 k
indl
y pr
ovid
ed b
y Pr
ofes
sor
Win
blad
.
546 F. Soriano and J. Vega
of Y. enterocolitica), group HI (56 Y. enterocolilica strains from collections), groupIV (13 Yersinia-like organisms) and group V (8 atypical Yersinia strains: 4 Y. inter-media, 3 Y. fredrikseni and 1 Y. kristenseni).
Antimicrobials. Standard powders were obtained from the manufacturers: strepto-mycin and tetracycline from CEPA, gentamicin from Schering Co., trimethoprimfrom Wellcome, sulphamethoxazole and ceftriaxone from Roche, chloramphenicolfrom Parke Davis, doxycycline from Pfizer, ceftazidime from Glaxo, moxalactamfrom Lilly and N-formimidoyl thienamycin from Merck Sharp & Dohme.
Sensitivity studies. Doubling dilutions of the antimicrobials were made in Mueller-Hinton agar (Difco) from 128 to 012 mg/1. Trimethoprim and sulphamethoxazolewere combined in two different proportions (1/10 and 1/20). The inoculum was pre-pared from an 18-24 h culture in trypticase soya broth (Difco) adjusted to between10* and 107cfu/ml, and inoculated with a Steers replicator. The plates were incu-bated at 37°C for 18-24 h and the MIC was assessed according to standard methods(Washington & Barry, 1974).
ResultsThe MIC patterns of the eleven drugs and two combinations of trimethoprim-sulphamethoxazole are shown in the table. All the strains were highly sensitive toceftriaxone, ceftazidime, moxalactam and N-formimidoyl thienamycin (MICs equalor less than 0-5 mg/1). There were no strains resistant to gentamicin, trimethoprimand the combination of trimethoprim-sulphamethoxazole (1/10 and 1/20). Most ofthe strains were inhibited by 4 mg/1 tetracycline and 1 mg/1 doxycycline. Chloram-phenicol at 8 mg/1 inhibited 166 out of the 167 strains tested. The susceptibility tostreptomycin varied, Y. pseudotuberculosis, Yersinia-like and atypical Yersiniastrains being sensitive (MIC ^ 4 mg/1) whilst the MIC for Y. enterocolitica variedfrom 1 to > 128 mg/1. The susceptibility to sulphamethoxazole showed a similarpattern, Y. pseudotuberculosis, Yersinia-like and atypical Yersinia strains beinginhibited by concentrations ^ 16 mg/1 but the MIC of this drug against Y. entero-colitica varied from 2 mg/1 to > 128 mg/1. Twenty-two out of the 23 highly sulpha-methoxazole resistant strains (MIC > 128 mg/1) were highly resistant to strepto-mycin (MIC > 128 mg/1). Only one strain was highly resistant to sulphamethoxazolebut moderately resistant to streptomycin (MIC 16 mg/1). There appeared to be cross-resistance between sulphamethoxazole and streptomycin.
There were no important differences in sensitivity to the antimicrobials amongthe five groups of Yersinia organisms except the sulphamethoxazole and strepto-mycin resistant strains which occured only in Y. enterocolitica independently of theirorigin or pathogenicitv. All these strains belonged to serotype 3 and 22 of them tobiotype 4. Sixteen of the 23 sulphamethoxazole-resistant strains were isolated fromclinical infections the others being from collections.
DiscussionThe susceptibility of our Yersinia strains to gentamicin, ceftazidime, chlorampheni-col, doxycycline, tetracycline, trimethoprim and sulphamethoxazole-trimethoprimis similar to that previously described by other authors (Hammerberg, Sorger &Marks, 1977, Juhlin & Winblad, 1981, Raevuori et al., 1978). There are few reportsdealing with the susceptibility of Yersinia strains to moxalactam and Af-formimidoylthienamycin (Verbist & Verhaegen, 1981) and none on ceftriaxone and these threeantibiotics are highly active against Yersinia.
Insusceptibility of Yersinia 547
The high percentage of Y. enterocolitica strains resistant to sulphamethoxazole(17-5%) and streptomycin (16-7%) with MICs higher than 128 mg/1 was unexpected.Twenty-two out of the 23 sulphamethoxazole resistant strains showed cross resist-ance with streptomycin. It has been reported (Raevuori et ai, 1978) that 99% of Y.enterocolitica strains were inhibited by 8 mg/1 streptomycin and most of the strainsstudied by others (Hammerberg et ai, 1977) were sensitive to sulphamethoxazole(MIC ^ 6-25 mg/1) with no highly resistant strains to this drug. Our results, usingsimilar methods showed 17-5% Y. enterocolitica strains resistant to sulphamethoxa-zole which does not appear to be due to the inoculum effect described with this drug(Hammerberg et ai, 1977). The high level of sulphamethoxazole resistance (MIC> 128 mg/1) and its cross resistance with streptomycin seems to be plasmid-mediated.
Trimethoprim was the most active component of the trimethoprim-sulpha-methoxazole mixture, the ratio 1/10 being more effective than that 1/20 owing tothe higher proportion of trimethoprim.
According to our results, sulphamethoxazole and streptomycin cannot be rec-ommended for the empiric treatment of severe cases of mesenteric adenitis or entericfever-like syndrome whilst tetracycline, doxycycline, chloramphenicol or trimetho-prim can. On the other hand, cefamandole, cefoxitin, cefoperazone (Gaspar &Soriano, 1981) and especially cefotaxime, ceftriaxone, ceftazidime, moxalactam andTV-formimidoyl thienamycin could be alternative drugs for the treatment of Yersiniasepticaemia.
References
Boyce, J. M. (1979). Yersinia species. In Principles and Practice of Infectious Diseases(Mandell, G. L., Douglas Jr. R. G. & Bennett, J. E., Eds), pp. 1792-800. John Wiley& Sons, New York.
Gaspar, M. C. & Soriano, F. (1981). Susceptibility of Yersinia enterocolitica to eight beta-lactam antibiotics and clavulanic acid. Journal of Antimicrobial Chemotherapy 8, 161-4.
Hammerberg, S., Sorger, S. & Marks, M. I. (1977). Antimicrobial susceptibilities of Yersiniaenterocolitica biotype 4, serotype 0 :3 . Antimicrobial Agents and Chemotherapy 11,566-8.
Hughes, J. M. & Guerrant, R. L. (1979). Systemic syndromes complicating gastrointestinalinfections. In Principles and Practice of Infectious Diseases (Mandell, G. L., Douglas Jr.,R. G. & Bennett, J. E., Eds), pp. 890-907. John Wiley & Sons, New York.
Johnson, J. E. (1974). Pasteurella infections including plague. In Harrison's Principles ofInternal Medicine 7th edn. (Wintrobe, M. M. el ai, Eds), pp. 823-7. McGraw-HillKogakusha Ltd. Tokyo.
Juhlin, I. & Winblad, S. (1981). Susceptibility to mecillinam and other antibiotics of 28O-serotypes of Yersinia enterocolitica. Journal of Antimicrobial Chemotherapy %, 291-''.
Raevuori, M., Harvey, S. M., Pickett, M. J. & Martin, W. J. (1978). Yersinia enterocolitica:in vitro antimicrobial susceptibility. Antimicrobial Agents and Chemotherapy 13,888-90.
Soriano, F., Ponte, M. C , Rivas, M. C , Oliva, H. & Gaspar, M. C. (1981). Infeccion humanapor Yersinia enterocolitica y pseudotuberculosis en Espana. Analisis de 80 casosrecientes. Revista Clinica Espahola 161, 215-22.
Verbist, L. & Verhaegen, J. (1981). In vitro activity ofn-formimidoyl thienamycin in compari-son with cefotaxime, moxalactam and ceftazidime. Antimicrobial Agents and Chemo-therapy 19, 402-6.
Washington, J. A. & Barry, A. L. (1974). Dilution test procedures. In Manual of ClinicalMicrobiology 2nd edn (Lennette, E. H., Spaulding, E. H. & Truant, J. P., Eds), pp. 410-7.American Society for Microbiology, Washington, D.C.
(Manuscript accepted 21 June 1982)
