Tigecycline, as a novel antibiotic for nosocomial ... - ROWER

dactylonomyskittlesBiotechnology

Feb 12, 2013 (4 years and 8 months ago)

137 views



TIGECYCLINE, AS A NOVEL ANTIBIOTIC FOR NOSOCOMIAL
PERSONNEL INFECTION CAUSED BY
Klepsiella sp.


S. Plessas, Democritus University of Thrace, Faculty of Agricultural Development, Department of
Food Science and Technology, Laboratory of Microbiology, Bio
technology and
Hygiene,GR68200, Orestiada, Greece,

splessas@agro.duth.gr


I. Mantzourani, Democritus University of Thrace, Faculty of Agricultural Development,
Department of Food Science and Technology, Laboratory of Microbiology, Biotechnology and
Hygien
e,GR68200, Orestiada, Greece,

imantzou@agro.duth.gr

A. Alexopoulos, Democritus University of Thrace, Faculty of Agricultural Development,
Department of Food Science and Technology, Laboratory of Microbiology, Biotechnology and
Hygiene,GR68200, Orestiada,
Greece,

alexopo@agro.duth.gr

C. Voidarou, Democritus University of Thrace, Faculty of Agricultural Development, Department
of Food Science and Technology, Laboratory of Microbiology, Biotechnology and
Hygiene,GR68200, Orestiada, Greece,

cvoidarou@yahoo.gr

E. Bezirtzoglou, Democritus University of Thrace, Faculty of Agricultural Development,
Department of Food Science and Technology, Laboratory of Microbiology, Biotechnology and
Hygiene,GR68200, Orestiada, Greece,

empezirt@agro.duth.gr



ABSTRACT

Increasing

antimicrobial resistance is a complicating factor in the treatment of
infections
-

mostly in the hospital setting.

Nosocomial personnel could be
infected by various strains, leading to reduced availability of staff and
increased overtimes. Thus the recove
ry of the infected nosocomial personnel
is fatal for the efficient operation of the hospital. The development of a serious
infection in hospital usually takes up to 48 hours to identify and face the
bacteria responsible. Efficacious antibiotics are necessa
ry in order to deal in
these critical early stages of treatment.
Tigecycline is a novel antimicrobial
agent for potential use encompassing a broad spectrum of bacterial
pathogens, including multi
-
resistant organisms. Preliminary results are
presented in th
is study concerning the susceptibility of 47

Klebsiella

spp. The
strains were collected through employees of hospitals infected and
minimum
inhibitory concentrations (MICs)
were determined

using the microdilution
method. The results are quite satisfied rev
ealing the efficiency of tigecycline
against several antibiotics that were also tested. 51% of the strains were
found susceptible to tigecycline, while the second following antibiotic was
levofloxacin which was found susceptible to 45% of the strains. More

specific
the average score for tigecycline (MICs) was 0.06, while for levofloxacin was
3.5 respectively. The results indicate that tigecycline may represent a suitable
option most notably for the empiric treatment of bacterial infections reducing at
the s
ame time the cost of various antibiotics cocktails used for resistant or
unknown strains. However, it is conceivable that the antibiotic

should be used
judiciously as it is a broad spectrum antibiotic for controlling the profile of the
nosocomial infection
s.


Key Words:

T
igecycline,
Klebsiella
,
antibiotics, multiresistance


INTRODUCTION


Infections that are acquired in a hospital are referred to as nosocomial

ones
. The term
nosocomial infections is not including only the approach of disease coming from the

he
ath
care professionals to the patients, but also any intra
-
hospital occurring disease.

Infections
acquired by the intra
-
hospital
personnel
constitute a

severe
problem with social, economical
and moral aspects.

Cross infection
from the patient or the med
ical and other health
-
care
personnel pose an increasing challenge to hospitals acquired infections.

Pathogen microorganisms springing from any hospital environment or
inanimate objects
should be the causing agent.


Breaches in infection control measures an
d the lack of vaccination of healthcare workers
should be associated to the spreading of this type of infection.

Moreover, antimicrobial

resistant pathogens (Biedenbach, Moet and Jones, 2004:59) involved in this type of diseases
pose a binomial problem a
ssociated both in the effective treatment of the patient and in
development of precaution measures to be taken
.



Tigecycline is a novel antimicrobial agent (Noskin ,2005:303)(Pankey,2005:470) for potential
use encompassing a broad spectrum of bacterial pa
thogens, including multi
-
resistant
organisms(
Murphy et al.,
2000:3022
;
Lefort

et al
.,

2003:216
;
Nannini

et al.,
2003:529)



The present study concerns the susceptibility profile of 47

Klebsiella

collected through
employees of hospitals.



MATERIAL AND METHO
DS


Initially, 3 to 5 similar morphologically colonies
of
Klebsiella

were chosen through totally 29
petri dishes that were collected from

staff of hospitals infected by
Klebsiella
,
which was
isolated from various tissues

and
minimum inhibitory concentratio
ns (MICs)
were determined

using the microdilution method
. The organism was inoculated in 5ml of demineralized water,
which was prior sterilized. The inoculum suspension was vortexed for 5 to 10 seconds and
was s
tandardized to a 0.5 McFarland s
tandard.
An a
liquot of
10
μ
l of inoculum was pipetted
and transferred to 11ml of sterilized Cation Adjusted Mueller
-
Hinton Broth. Then the inoculum
was inverted for 8 to 10 times and the inoculum was pipetted (100

μ
l in each well) in totally 64
wells filled with differe
nt concentrations of antibiotics using a 8
-
12 channel pipettor. A sealer
was placed over the plate and the panel was incubated in the incubator for approximately 24h
at 37
0
C. The panels were read using a TREK viewer and the results were recorded directly t
o
a planned susceptibility report form. The antibiotics used were:
amoxycillin
+
clavulanic

acid
,
piperacillin
/
tazobactan
,
levofloxacin
,
ceftriaxone
,
cefepime

ampicillin
,
amikacin
,
minocycline
,
ceftazidime
,
meropenem and
t
igecycline at different concentratio
ns. Totally the
concentrations

used for each antibiotic is presented at Table 1.











Table 1:


Antibiotics used for the present study in their respective concentrations.



ANTIBIOTIC

Low concentration (
μ
g⽭/F

䡩杨⁣o湣敮瑲慴a潮

(
μ
术glF

A浯xyc楬汩n
+
c
l慶ul慮ic

慣id

M
K

J
M
K



J


mi灥r慣楬汩港n慺潢慣瑡t

〮M㘯㐠


〮M㈯2

〮M㔯㐠


ㄲ8⼴

䱥v潦o潸慣in

〮MM8
J
〮Mㄵ

〮〳
J
8

䍥晴物慸潮e

〮〶
J
〮㈵

〮M
J


䍥晥灩浥

〮M
J
4

8
J


A浰ic楬汩n

〮M
J



A浩k慣in

〮M
J
1

2
J


䵩湯cyc汩湥

〮M
J



䍥晴Czi摩浥

8
J



Tig
散yc汩湥

〮MM8
J
2

4
J


䵥r潰敮em

〮〶
J






RESULTS


Forty seven

samples of
Klebsiella

isolated from infected hospital employees from various
tissues were examined regarding susceptibility in various antibiotics. As it can be shown from
Table 2, tigecycl
ine was by far the most efficient antibiotic agent. Specifically, tigecycline
exhibited the lower average MIC values, which was found at a concentration of 1.6
μ
g/ml
followed by meropenem (6,2
μ
g/ml), levofloxacin (3,4
μ
g/ml ) and minocyclin (4,2
μ
g/ml).

A
ll
the other antibiotics used for this study exhibited higher MIC values.



In addition in most cases
igecycline showed the lowest MIC values than all the other
antibiotics .
Results of MICs values of the different studied antibiotics against the 29
Klebsi
ella

isolates are given on Table 2




Table 2.
(MICs) values of antibiotics studied against
Klebsiella

isolates.



a/a

Mean

Standard deviation

Minimum

Maximum

Amoxycillin+clavulanic
acid

7,87

6,36

1

16

Piperacillin/tazobactan

22,04

29,92

1

64

Levofloxac
in

1,04

1,16

1

4

Ceftriaxone

10,37

13,52

1

32

Cefepime

5,37

6,68

1

16

Ampicillin

9,78

6,16

1

16

Amikacin

7,15

10,97

1

32

Minocycline

3,22

2,79

1

8

Ceftazidime

10,43

3,72

8

16

Tigecycline

0,17

1,34

1

4

Meropenem

1,72

3,01

1

8



DISCUSSION


Tigecycl
ine belongs to a new generation of tetracyclines, which are the glycylcyclines . The
chemical structure of the tigecycycline is reported as a 9
-
t
-
butylglycylamido derivative of
minocycline and seems to be valuable to the developed resistance against tetrac
yclines or
other older antibiotic schemes.


In our experimentation, tigecycline exhibited the lower average MIC values, which was found
at a concentration of 1.6
μ
g/ml followed by meropenem (6,2
μ
g/ml), levofloxacin (3,4
μ
g/ml )
and minocyclin (4,2
μ
g/ml).
This considerable higher activity of tigecycline against all
Klebsiella

strains considering meropenem, levofloxacin minocycline resistant isolates seems to be
embedded on the gene profile (
Schmitz ,Krey ,Sadursky ,Verhoef, Milatovic and
Fluit,2001:239)
(

Bauer , Berens , Projan and Hillen,2004:592)


It is reported that tetracycline resistant genes harbour
tet
M gene ,while presence of
tet

K
gene is correlated with resistance to tetracyclines but susceptibility to minocycline (
Schmitz
,Krey ,Sadursk
y ,Verhoef, Milatovic and Fluit, 2001:239)
( Bauer , Berens , Projan and
Hillen,2004:592)
Moreover, tigecycline showed very high activity against

Klebsiella
pneumoniae

and
Klebsiella oxytoca

ranging from 0.25
μ
g/ml to 1
μ
g/ml(except one strain 4
μ
g/ml).Inte
restingly, this only one strain (isolate 43) showed 4
μ
g/ml seems to be considerably
multi
-
resistant in almost all antibiotics.


These results are in accordance with other researchers demonstrating that tigecycline is
effective as a broad spectrum agent, e
specially in the case of
Klebsiella
(
Bouchillon, Johnson
, Hoban, Johnson, Dowzicky , Wu et al.,2004:119) (Yin, Lazzarini, Li, Stevens and
Calhoun,2005:995)(Van Ogtrop, Andes , Stamstad Conklin, Weiss, Craig , et
al.,200:943)(Edelstein , Weiss and Edels
tein, 2003:533)


Tigecycline showed excellent

in vitro

activity against 50 clinical isolates of
Klebsiella
pneumoniae

producing extended
-
spectrum
β
-
lactamases, plasmid
-
mediated AmpC
-
type
β
-
lactamases, or both. This activity was not affected by porin loss. Porin loss, however, did
affect the activity of imipenem against strains that expressed both types of enzymes (Conejo
,Hernandez and Pascual ,200
8:343)


In order to limit spreading of resistant bacteria, it is obvious that prevention and control
strategies must be determined and respected. The objectives of prevention and control
program are based on the following:

1. Necessity of precaution measur
es to be taken.

2. Indications for hand
-
washing.

3. Decontamination and disinfection level of hospitals, tools, equipment.

4. Strategy to be developed for preserving the health of working personnel, with reducing
display in danger of dispersion to pathogen
ic microorganisms.

5. Developing skills in implementation for the prevention and control program.

6. Instructed nosocomial personnel to the proper use of appliances and aseptic material.



As it is known, there are limited options for treating serious i
nfections caused by multi
-
resistant strains. Tigecyclin seems to be the angular stone in these cases as a valuable
therapeutic agent.



REFERENCES


Bauer G., Berens C., Projan SJ., Hillen W. (2004).

Comparison of tetracycline and tigecycline
binding to ri
bosomes mapped by dimethylsulphate and

drug
-
directed Fe2+ cleavage of
16S
rRNA

. Journal of Antimicrobial Chemotherapy, 53(4):592

599.


Biedenbach DJ.,

Moet GJ., Jones RN.
(2004).

Occurrence and antimicrobial resistance
pattern comparisons among bloodstrea
m infection isolates from the SENTRY Antimicrobial
Surveillance Program (1997

2002)


Diagnostic Microbiological Infections Disease, 50(1):59

69.


Bouchillon SK., Johnson BM., Hoban DJ., Johnson JL., Dowzicky MJ., Wu DH., (2004).

Determining incidence of e
xtended spectrum beta
-
lactamase producing
Enterobacteriaceae
,
vancomycin
-
resistant
Enterococcus faecium
and methicillin
-
resistant
Staphylococcus aureus
in 38 centres from 17 countries: the PEARLS study 2001

2002

. International Journal of
Antimicrobial Age
nts, 24(2):119

24.


Conejo

MC., Hernandez

JR., Pascual A

.
,(2008)


Effect of porin loss on the activity of
tigecycline against

Klebsiella pneumoniae

producing extended
-
spectrum
β
-
lactamases or
plasmid
-
mediated AmpC
-
type
β
-
lactamases

. Diagnostic Micro
biology and Infectious
Disease
,

61(

3):

343
-
345



Edelstein PH., Weiss WJ., Edelstein MA.
(2003)

Activities of tigecycline (GAR
-
936) against
Legionella pneumophila
in vitro and in gu
inea pigs with
L.
pneumophila
pneumonia

.
Antimicrobial Agents and Chemotherapy, 47(2):533

540.


Lefort A., Lafaurie M., Massias L., Petegnief Y., Saleh
-
Mghir A., Muller
-
Serieys C., et al.
(2003)

Activity and diffusion of tigecycline (GAR
-
936) in experimen
tal enterococcal
endocarditis

. Antimicrobial Agents and Chemotherapy, 47(1):216

222.


Murphy TM, Deitz JM., Petersen PJ., Mikels SM., Weiss WJ. (2000)

T
herapeutic efficacy of
GAR
-
936,
a novel glycylcycline, in a rat model of experimental

endocarditis

. An
timicrobial
Agents and Chemotherapy, 44(11):3022

3027.


Nannini EC., Pai SR., Singh KV, Murray BE. (2003).

Activity of tigecycline (G
AR
-
936), a novel
glycylcycline
against enterococci in the mouse peritonitis model

. Antimicrobial Agents and
Chemotherapy,
47(2):529

532.


Noskin GA. (2005)

Tigecycline: a new glycylcycline for treatment of serious infections

Clinical Infections and Disease, 41(5) (Suppl. 5):S303

14.


Pankey GA. (2005).

Tigecycline


Journal of Antimicrobial Chemotherapy, 56(3):470

80.


Schm
itz FJ., Krey A., Sadursky R., Verhoef J., Milatovic D., Fluit AC.,(2001).”Resistance to
tetracyclines and distribution of tetracycline resistance genes in European S.aureus
isolates”.J ournal of Antimicrobial Chemotherapy, 47:239
-
240


Van Ogtrop ML., Ande
s D., Stamstad TJ., Conklin B., Weiss WJ., Craig WA., et al. (2000).

In
vivo
pharmacodynamic activities of two
glycylcyclines (GAR
-
936 and WAY
152,288) against
various gram
-
positive and gram
-
negativebacteria

. Antimicrobial Agents and Chemotherapy,
44(4):9
43

949.



Yin LY, Lazzarini L, Li F, Stevens CM., Calhoun JH. (2005).

Compar
ative evaluation of
tigecycline
and vancomycin, with and without rifampicin, in the treatment of methicillin
-
resistant
Staphylococcus aureus

experimental osteomyelitis in a rabbit
model

. Journal of
Antimicrobial Chemotherapy, 55(6):995

1002.