Antibiotic susceptibility patterns among respiratory isolates of Gram-negative bacilli in a Turkish university hospital.

Abstract

Gram-negative bacteria cause most nosocomial respiratory infections. At the University of Cumhuriyet, we examined 328 respiratory isolates of Enterobacteriaceae and Acinetobacter baumanii organisms in Sivas, Turkey over 3 years. We used disk diffusion or standardized microdilution to test the isolates against 18 antibiotics.
We cultured organisms from sputum (54%), tracheal aspirate (25%), and bronchial lavage fluid (21%). The most common organisms were Klebsiella spp (35%), A. baumanii (27%), and Escherichia coli (15%). Imipenem was the most active agent, inhibiting 90% of Enterobacteriaceae and A. baumanii organisms. We considered approximately 12% of Klebsiella pneumoniae and 21% of E. coli isolates to be possible producers of extended-spectrum beta-lactamase. K. pneumoniae isolates of the extended-spectrum beta-lactamase phenotype were more resistant to imipenem, ciprofloxacin, and tetracycline in our study than they are in other regions of the world.
Our results suggest that imipenem resistance in our region is growing.

Full text

Page 1

BioMed Central
Page 1 of 5
(page number not for citation purposes)
BMC Microbiology
Open Access
Research article
Antibiotic susceptibility patterns among respiratory isolates of
Gram-negative bacilli in a Turkish university hospital
Ugur Gonlugur*1, Mustafa Zahir Bakici2, Ibrahim Akkurt1 and
Tanseli Efeoglu1
Address: 1Department of Chest Diseases, Cumhuriyet University Medical School, 58140, Sivas, Turkey and 2Department of Microbiology,
Cumhuriyet University Medical School, 58140, Sivas, Turkey
Email: Ugur Gonlugur* - gonlugur@e-kolay.net; Mustafa Zahir Bakici - zbakici@cumhuriyet.edu.tr;
Ibrahim Akkurt - gonlugur@cumhuriyet.edu.tr; Tanseli Efeoglu - tefeoglu@hotmail.com
* Corresponding author
Abstract
Background: Gram-negative bacteria cause most nosocomial respiratory infections. At the
University of Cumhuriyet, we examined 328 respiratory isolates of Enterobacteriaceae and
Acinetobacter baumanii organisms in Sivas, Turkey over 3 years. We used disk diffusion or
standardized microdilution to test the isolates against 18 antibiotics.
Results: We cultured organisms from sputum (54%), tracheal aspirate (25%), and bronchial lavage
fluid (21%). The most common organisms were Klebsiella spp (35%), A. baumanii (27%), and
Escherichia coli (15%). Imipenem was the most active agent, inhibiting 90% of Enterobacteriaceae and
A. baumanii organisms. We considered approximately 12% of Klebsiella pneumoniae and 21% of E.
coli isolates to be possible producers of extended-spectrum beta-lactamase. K. pneumoniae isolates
of the extended-spectrum beta-lactamase phenotype were more resistant to imipenem,
ciprofloxacin, and tetracycline in our study than they are in other regions of the world.
Conclusions: Our results suggest that imipenem resistance in our region is growing.
Background
Nosocomial bacterial pneumonia is frequently pol-
ymicrobial, with gram-negative bacilli predominating [1].
Because delays in antimicrobial treatment can lead to
adverse outcomes, the choice of empirical therapy is vital.
Many effective antimicrobial agents are available, but the
treatment of nosocomial pneumonia remains challeng-
ing. We recently reported the antibiotic-resistance patterns
of respiratory isolates of Pseudomonas aeruginosa in our
region [2]. The current study investigates the distribution
and drug resistance of other gram-negative bacteria in the
respiratory secretions of hospitalized patients.
Results
Table 1 and Table 2 present the antibiotic susceptibility
patterns of our isolates. The most common organisms
were Klebsiella spp (35%), A. baumanii (27%), and E. coli
(15%). We also isolated rare organisms such as Stenotro-
phomonas maltophilia, Burkholderia spp, and Hafnia alvei.
All studied Enterobacteriaceae (except Enterobacter spp)
were far more susceptible to ticarcillin-clavulanate than to
ticarcillin alone, which suggests that the primary mecha-
nism of resistance in these organisms is β-lactamase
production.
Published: 22 August 2004
BMC Microbiology 2004, 4:32doi:10.1186/1471-2180-4-32
Received: 25 January 2004
Accepted: 22 August 2004
This article is available from: http://www.biomedcentral.com/1471-2180/4/32
© 2004 Gonlugur et al; licensee BioMed Central Ltd.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Page 2

BMC Microbiology 2004, 4:32http://www.biomedcentral.com/1471-2180/4/32
Page 2 of 5
(page number not for citation purposes)
K. pneumoniae accounted for 79% of Klebsiella isolates.
Klebsiella spp were generally more susceptible to the tested
antimicrobials than were Enterobacter spp, Serratia spp, or
E. coli. The overall resistance rates to the third-generation
cephalosporins (cefotaxime, ceftazidime, and ceftriaxone)
were as follows: Klebsiella spp, 10%–19%; Serratia spp,
16%–33%; and Enterobacter spp, 22%–45%. Serratia spp
were less resistant to third-generation cephalosporins
than Enterobacter spp. E. coli isolates resistant to piperacil-
lin, gentamicin, and the fluoroquinolones accounted for
only 4% of all E. coli isolates. Imipenem was the most
active agent against our isolates.
After imipenem, ciprofloxacin, and the aminoglycosides,
tetracycline was the most active agent against A. baumanii.
Tobramycin was more effective against A. baumanii than
against Enterobacteriaceae. Tobramycin and imipenem
were the most active agents against both gentamicin- and
ciprofloxacin-resistant A. baumanii (Table 3).
Table 1: Susceptibility rates (percentages) of Enterobacteriaceae and Acinetobacter baumanii between January 1999 and November 1999
(Disk diffusion method).
AntibioticsKlebsiella spp (n: 28) E.coli (n: 18)Proteus spp. (n: 10) Enterobacter spp (n: 10)A. baumanii (n: 7)Serratia spp. (n: 6)
Ampicillin
Amoxicillin/clav.
Aztreonam
Piperacillin
Cefazolin
Cefuroxime
Cefotaxime
Ceftazidime
Ceftriaxone
Amikacin
Gentamicin
Tobramycin
Ciprofloxacin
İmipenem
Tetracycline
Cotrimoxazole
- 33.3
33.3
44.4
27.8
66.7
66.7
72.2
72.2
88.9
100.0
100.0
16.6
88.9
100.0
22.2
55.6
-
-
-
-
-
-
-
-
-
-7.1
42.9
32.1
64.3
46.4
67.9
71.4
71.4
92.9
82.1
10.7
92.9
100.0
-
64.3
50.0
50.0
50.0
40.0
90.0
70.0
90.0
100.0
80.0
-
90.0
80.0
20.0
70.0
60.0
30.0
10.0
40.0
100.0
90.0
90.0
100.0
90.0
41.7
70.0
100.0
20.0
100.0
33.3
33.3
-
-
66.7
50.0
50.0
100.0
100.0
33.3
100.0
100.0
16.7
100.0
14.3
-
-
14.3
-
28.6
85.7
14.3
42.9
100.0
-
14.3
Table 2: Susceptibility rates of Enterobacteriaceae and Acinetobacter baumanii between November 1999 and January 2002
(Microdilution technique).
Antibiotics Klebsiella spp (n: 86)A. baumanii (n: 83)E.coli (n: 30)Enterobacter spp (n: 24) Proteus spp. (n: 13)Serratia spp. (n: 13)
MIC50/90 Susc. %MIC50/90Susc. %MIC50/90Susc. %MIC50/90Susc. %MIC50/90 Susc. %MIC50/90Susc. %
Ampicillin
Amoxicillin/
clav.
Aztreonam
Piperacillin
Ticarcillin
Ticarcillin/clav.
Cefazolin
Cefuroxime
Cefotaxime
Ceftazidime
Ceftriaxone
Amikacin
Gentamicin
Tobramycin
Ciprofloxacin
İmipenem
Tetracycline
Cotrimoxazole
8/>16
4/>16
10.5
77.9
16/>16
16/>16
7.2
7.2
8/>16
4/>16
10.0
13.3
8/>16
8/>16
4.2
4.2
8/>16
4/>16
15.4
84.6
8/>16
8/>16
-
-
2/>16
16/>64
32/>64
16/128
8/>16
8/>16
8/64
1/>16
16/>32
16/>32
4/16
4/16
1/>2
2/>8
4/>8
1/>2
73.3
60.5
25.6
60.5
77.9
88.4
96.5
84.9
90.7
93.0
89.5
84.9
89.5
95.3
81.4
81.4
8/>16
16/128
16/128
16/128
16/>16
16/>16
16/64
4/>16
16/64
16/>32
4/16
4/16
1/>2
4/>8
4/>8
1/>2
6.0
39.7
7.2
9.6
1.2
3.6
9.6
42.2
12.0
54.2
65.0
91.5
66.2
79.5
56.6
22.9
2/>16
16/128
16/128
16/128
8/>16
8/>16
16/64
1/>16
16/>32
16/>32
4/>8
4/>8
1/>2
2/>8
4/>8
1/>2
66.6
30.0
26.7
40.0
46.7
46.7
73.3
66.7
73.3
93.3
90.0
93.3
66.6
96.6
63.3
53.3
2/>16
16/128
32/128
16/128
8/>16
8/>16
8/64
1/32
8/>32
8/>32
4/>8
4/>8
1/>2
2/>8
4/>8
1/>2
45.8
41.7
54.2
58.3
8.3
12.5
58.3
37.5
50.0
100.0
95.8
41.7
100.0
79.2
79.2
75.0
2/>16
16/>64
32/>64
16/>64
8/>16
8/>16
8/64
1/>16
16/>32
16/>32
4/>8
4/>8
1/>2
2/>8
4/>8
1/>2
92.3
84.6
53.8
92.3
69.2
76.9
100.0
92.3
100.0
100.0
69.2
84.6
100.0
100.0
15.4
23.1
2/16
16/128
32/128
16/128
8/>16
8/>16
8/32
1/>16
8/32
8/>32
4/>8
4/>8
1/>2
2/>8
4/>8
1/>2
84.6
61.5
38.5
61.5
-
-
84.6
76.9
84.6
92.3
84.6
76.9
92.3
69.2
15.4
69.2

Page 3

BMC Microbiology 2004, 4:32http://www.biomedcentral.com/1471-2180/4/32
Page 3 of 5
(page number not for citation purposes)
We observed the ESBL phenotype in 10 E. coli isolates
(20.8%) and 11 K. pneumoniae isolates (12.2%). All K.
pneumoniae and E. coli isolates with the ESBL phenotype
were resistant to tetracycline. Regarding K. pneumoniae iso-
lates, 2 were susceptible to tobramycin, 3 to gentamicin,
and 4 to ciprofloxacin, but 8 were susceptible to amikacin
and imipenem. Regarding E. coli isolates, 4 were suscepti-
ble to tobramycin, 7 to gentamicin, 5 to ciprofloxacin,
and 8 to amikacin, but all were susceptible to imipenem.
Discussion
Contrary to the findings of the Turkish antimicrobial
resistance study group [3], our Klebsiella isolates were
more susceptible to third-generation cephalosporins
(42.6% vs. 81.6% for ceftazidime; 65.8% vs. 85.7% for
cefotaxime), aztreonam (44.0% vs. 65.6%), and ticarcil-
lin-clavulanate (37.0% vs. 60.3%). Klebsiella spp were
81.6% susceptible to ceftazidime in our study; these rates
are 96.6% in North America [4], 86.7% in China [5],
80.5% in Korea [6], 69.4% in Latin America [7], and
51.9% in India [8].
Although the isolation of Acinetobacter spp in respiratory
specimens may reflect colonization and not necessarily
infection [9], the most common site of nosocomial Aci-
netobacter infection is the lower respiratory tract, especially
in mechanically ventilated patients [10]. Acinetobacter spp
were the second most frequent gram-negative bacilli iso-
lated from patients with pneumonia in Latin America [7].
In our survey, all compounds tested showed decreased
activity among the A. baumanii isolates. Susceptibility to
imipenem was >95% in Canada [11], India [8], and China
[5]; susceptibility was 80.5% in our study and 55.5% in
another study from Turkey [12]. The high prevalence of
respiratory tract infections due to multiresistant A. bauma-
nii will stimulate the use of carbapenems and possibly
increase carbapenem resistance in our region.
Only 75% of our E. coli isolates were susceptible to cipro-
floxacin. However, this rate was greater in Europe (95.2%)
[13], North America (93.3%) [4], and Latin America
(93.9%) [7]. E. coli's susceptibility to ceftazidime was
>95% in Europe [13], North America [4], China [5], and
Korea [6] but only 84.8% in Latin America [7], 69.6% in
our study, and 42.1% in India [8]. Imipenem, the most
active compound, inhibited 97.8% of our E. coli isolates.
Conversely, E. coli strains were not resistant to imipenem
in Europe [13], Latin America [7], India [8], China [5], or
Korea [6].
Enterobacter spp showed high rates of resistance to broad-
spectrum penicillins with or without β-lactamase
inhibitors (41.7% resistance to ticarcillin-clavulanate)
and third-generation cephalosporins (45.2% resistance to
ceftazidime). The high rates of ceftazidime resistance
among Enterobacter spp suggests a high prevalence of sta-
bly derepressed AmpC cephalosporinase-producing
strains. Interestingly, resistance to third-generation cepha-
losporins, aztreonam, and ticarcillin-clavulanate was
higher in our study (28.1%–48.0%) than with the Turkish
antimicrobial resistance study group (13.3%–38.3%) [3].
In their study, no Enterobacter or Serratia isolates were
resistant to imipenem. In our study, however, the rates of
susceptibility to imipenem were 86.2% for Enterobacter
Table 3: Susceptibility (numbers) of imipenem-, gentamicin-, and ciprofloxacin-resistant Acinetobacter baumanii.
All isolates (n: 90)Gentamicin-resistant (n: 30) Imipenem-resistant (n: 18)Ciprofloxacin-resistant (n: 32)
Ampicillin6
6
5
33
6
8
2
3
8
36
10
47
60
58
58
72
47
20
2
3
1
4
2
5
1
-
1
5
1
2
-
24
21
25
17
10
-
-
1
1
-
-
-
1
1
6
1
6
11
17
11
-
10
5
-
-
-
9
1
1
-
-
-
7
-
13
25
28
-
26
6
6
Amoxicillin/clavulanate
Aztreonam
Piperacillin
Ticarcillin
Ticarcillin/clavulanate
Cefazolin
Cefuroxime
Cefotaxime
Ceftazidime
Ceftriaxone
Amikacin
Gentamicin
Tobramycin
Ciprofloxacin
İmipenem
Tetracycline
Cotrimoxazole

Page 4

BMC Microbiology 2004, 4:32http://www.biomedcentral.com/1471-2180/4/32
Page 4 of 5
(page number not for citation purposes)
spp and 76.5% for Serratia spp. Imipenem susceptibility
for these two species was >95% in other parts of the world
[7-10,13]. Moreover, Serratia spp were at least 95% sus-
ceptible to ceftazidime in the United States [14], Canada
[11], India [8], China [5], and Korea [6].
From 1997 to 1999, ESBL detection rates in K. pneumoniae
isolates were 45.4% in Latin America, 24.6% in the West-
ern Pacific, 22.6% in Europe, 7.6% in the United States,
and 4.9% in Canada [15]; this rate was 12.2% in our sur-
vey, but the other study from Turkey reported a rate of
60.5% [3]. During this same period, ESBL detection rates
in E. coli isolates were 8.5% in Latin America, 7.9% in the
Western Pacific, 5.3% in Europe, 4.2% in Canada, and
3.3% in the United States [15]; this rate was 20.8% in our
study. The presence of the ESBL phenotype in E. coli iso-
lates decreased susceptibility to the aminoglycosides, tet-
racycline, and ciprofloxacin but not imipenem, suggesting
the presence of other resistance genes in ESBL-encoding
plasmids. Despite the high percentage of ESBL production
in E. coli isolates, antibiotics remained reasonably effec-
tive with these isolates. Imipenem was active against all
ESBL-producing E. coli isolates. E. coli remained 30.0%
resistant to gentamicin; this resistance rate was 75.9% in
the Western Pacific, 57.8% in Latin America, 25.7% in
Europe, and 21.1% in the United States [15].
Only 0.5%–0.7% of ESBL-producing K. pneumoniae iso-
lates were resistant to imipenem in the United States,
Latin America, the Western Pacific region, and Canada
[15]. Our rate (27.2%) was very high in comparison. This
finding may be due to our low number of isolates or our
lack of a confirmation test for the ESBL phenotype. Resist-
ance to tetracycline among ESBL-producing K. pneumoniae
strains was 61.1% in Canada, 55.1% in the Western
Pacific, 52.0% in Latin America, 49.5% in Europe, and
44.4% in the United States [15], but this rate was 100% in
our study. Resistance to ciprofloxacin among ESBL-pro-
ducing K. pneumoniae strains was 44.2% in the Western
Pacific, 34.6% in the United States, 24.3% in Europe,
23.1% in Latin America, 22.2% in Canada, and 63.6% in
our study.
We found only one imipenem-resistant E. coli isolate. It
was resistant to ampicillin, ticarcillin, and piperacillin but
susceptible to ceftazidime, ceftriaxone, and aztreonam.
This profile suggests an oxacillinase with carbapenemase
properties. This finding is interesting because class D
enzymes have been found only in Acinetobacter spp [16].
Two imipenem-resistant Klebsiella spp were resistant to all
β-lactams, including aztreonam. These species were prob-
ably expressed a metallo-β-lactamase with additional
mechanisms (efflux, cephalosporinase hyperproduction)
[16].
The absence of a confirmation test for the ESBL phenotype
limits the impact of our results. On the other hand, it is
known that supplemented media (blood) can alter the
zone diameters for several agents and bacterial species.
Despite these limitations, our data can be used for local
therapeutic choices.
Conclusions
We previously presented the antibiotic susceptibility pat-
terns of 249 respiratory isolates of P. aeruginosa during the
same period [2]. When combined with our current data,
these results show that, in our region, ceftazidime can still
be used for managing respiratory infections due to gram-
negative aerobic bacteria in combination with aminogly-
cosides. It appears that increasing imipenem resistance
may cause serious therapeutic problems in future.
Methods
We collected our data from 01/01/1999 to 01/01/2002 at
the microbiology laboratory of the University of Cum-
huriyet. We processed the data to eliminate duplicate reg-
istrations. We excluded any isolates collected within 7
days when they came from the same specimen source of
the same patient. We initially identified the isolates using
such routine methods as colonial/microscopic morphol-
ogy and enzymatic characteristics. We confirmed species
identification with API-bioMerieux products. We retro-
spectively analyzed antibiotic susceptibility patterns in
238 respiratory isolates of Enterobacteriaceae members
and 90 respiratory isolates of A. baumanii. We accepted all
consecutive isolates because we did not attempt to distin-
guish actual pathogens from colonizing strains. Specimen
types consisted of sputum (54.2%), transtracheal/
endotracheal aspirates (24.6%), and bronchial lavage
fluid (21.2%). We cultured sputum samples that showed
no oral contamination in the presence of sputum puru-
lence or a suspected lower respiratory infection.
We confirmed susceptibility to 18 antimicrobial agents
using disk diffusion according to the National Committee
for Clinical Laboratory Standards (NCCLS) guidelines
[17], except insofar as we supplemented Mueller-Hinton
agar with 5% defibrinated blood. We aerobically
incubated the inoculated plates at 35°C and evaluated
them after 24 h. For quality control of the disk diffusion
tests, we used E. coli ATCC 25922 and Staphylococcus
aureus ATCC 25923 strains. The disks (Oxoid) contained
the following antimicrobials: ampicillin (10 µg), ampicil-
lin/sulbactam (20 µg), piperacillin (100 µg), aztreonam
(30 µg), cefazolin (30 µg), cefuroxime (30 µg), cefotaxime
(30 µg), ceftriaxone (30 µg), ceftazidime (30 µg), ami-
kacin (30 µg), gentamicin (10 µg), tobramycin (10 µg),
ciprofloxacin (5 µg), imipenem (10 µg), tetracycline (30
µg), and cotrimoxazole (25 µg). Until November 1999,
our microbiology laboratory based susceptibility rates on

Page 5

Publish with BioMed Central and every
scientist can read your work free of charge
"BioMed Central will be the most significant development for
disseminating the results of biomedical research in our lifetime."
Sir Paul Nurse, Cancer Research UK
Your research papers will be:
available free of charge to the entire biomedical community
peer reviewed and published immediately upon acceptance
cited in PubMed and archived on PubMed Central
yours — you keep the copyright
Submit your manuscript here:
http://www.biomedcentral.com/info/publishing_adv.asp
BioMedcentral
BMC Microbiology 2004, 4:32http://www.biomedcentral.com/1471-2180/4/32
Page 5 of 5
(page number not for citation purposes)
disk zone sizes; thereafter, we used a coordinating labora-
tory to determine the minimal inhibitory concentrations
(MICs) of these 18 antimicrobial agents, accomplished
with a standardized microdilution technique (Sceptor
System, Becton Dickinson Microbiology System). We
used this system to determine MICs for all strains. We
used the NCCLS criteria to identify possible extended-
spectrum β-lactamase (ESBL)-producing strains of Kleb-
siella spp and E. coli when MICs were increased (2 mg/mL)
with ceftazidime and/or ceftriaxone and/or aztreonam
[18], but we lacked a test to confirm the ESBL phenotype.
We classified our results into two categories. We labeled
strains deemed susceptible by the disk diffusion method
or microdilution technique as susceptible. We labeled all
resistant and intermediate isolates as resistant. We divided
the number of resistant isolates by the total number of
isolates that had undergone susceptibility testing.
Authors' contributions
UG had primary responsibility for study design, collection
of data, and writing the manuscript. IA, MZB, TE had
intellectual contribution as well as the writing of manu-
script. All authors read and approved the final
manuscript.
Acknowledgements
We thank Cem Celik, Nurgul Turkmen, and Muhtereme Kilavuz for their
technical assistance. No portion of this work supported by a foundation.
References
1.American Thoracic Society: Hospital-acquired pneumonia in
adults: diagnosis, assessment of severity, initial antimicrobial
therapy, and preventative strategies. Am J Respir Crit Care Med
1996, 153:1711-1725.
2. Gonlugur U, Bakici MZ, Ozdemir L, Akkurt I, Icagasioglu S, Gultekin
F: Retrospective analysis of antibiotic susceptibility patterns
of respiratory isolates of Pseudomonas aeruginosa in a Turk-
ish University Hospital. Ann Clin Microbiol Antimicrob 2003, 2:5.
3.National Committee for Clinical Laboratory Standards: Perform-
ance standards for antimicrobial disk susceptibility tests.
Approved Standard M2-A6 61997.
4.National Committee for Clinical Laboratory Standards: Perform-
ance standards for antimicrobial susceptibility testing;. eight
informational supplement M100-S8 1998.
5.The Turkish antimicrobial resistance study group, Pfaller MA, Korten
V, Jones RN, Doern GV: Multicenter evaluation of the antimi-
crobial activity for seven broad-spectrum β-lactams in Tur-
key using the Etest method. Diagn Microbiol Infect Dis 1999,
35:65-73.
6.Hoban DJ, Biedenbach DJ, Mutnick AH, Jones RN: Pathogen of
occurrence and susceptibility patterns associated with pneu-
monia in hospitalized patients in North America: results of
the SENTRY antimicrobial surveillance study. Diagn Microbiol
Infect Dis 2000, 45:279-285.
7.Xu Y, Chen M, Biedenbach DJ, Deshpande LM, Jones RN, The Chi-
nese antimicrobial resistance study group: Evaluation of the in
vitro antimicrobial activity of cefepime compared to other
broad-spectrum β-lactams tested against recent clinical iso-
lates from 10 Chinese hospitals. Diagn Microbiol Infect Dis 1999,
35:135-142.
8.The Korean antimicrobial resistance study group, Lewis MT, Bieden-
bach DJ, Jones RN: In vitro evaluation of broad-spectrum β-
lactams tested in medical centers in Korea: Role of fourth-
generation cephalosporins. Diagn Microbiol Infect Dis 1999,
35:317-323.
Sader HS, Jones RN, Gales AC, Winokur P, Kugler KC, Pfaller MA,
Doern GV, the SENTRY Latin America study group: Antimicrobial
susceptibility patterns for pathogens isolated from patients
in Latin American medical centers with a diagnosis of pneu-
monia: Analysis of results from the SENTRY antimicrobial
surveillance program (1997). Diagn Microbiol Infect Dis 1998,
32:289-301.
The India antimicrobial resistance study group, Mathai D, Rhomberg
PR, Biedenbach DJ, Jones RN: Evaluation of the in vitro activity
of six broad-spectrum β-lactam antimicrobial agents tested
against recent clinical isolates from India: a survey of ten
medical center laboratories. Diagn Microbiol Infect Dis 2002,
44:367-377.
Struelens MJ, Carlier E, Maes N, Serruys E, Quint WG, van Belkum A:
Nosocomial colonization and infection with multiresistant
Acinetobacter baumannii: outbreak delineation using DNA
macrorestriction analysis and polymerase chain reaction-fin-
gerprinting. J Hosp Infect 1993, 25:15-32.
Forster DH, Daschner FD: Acinetobacter species as nosocomial
pathogens. Eur J Clin Microbiol Infect Dis 1998, 17:73-77.
Blondeau JM, Yaschuk Y, Suter M, Vaughan D: In vitro susceptibil-
ity of 1982 respiratory tract pathogens and 1921 urinary
tract pathogens against 19 antimicrobial agents: a Canadian
multicentre study. Canadian antimicrobial study group. J Anti-
microb Chemother 1999, 43:3-23.
Aksaray S, Dokuzoguz B, Guvener E, Yucesoy M, Yulug N, Kocagoz
S, Unal S, Cetin S, Calangu S, Gunaydin M, Leblebicioglu H, Esen S,
Bayar B, Willke A, Findik D, Tuncer I, Baysal B, Gunseren F,
Mamikoglu L: Surveillance of antimicrobial resistance among
gram-negative isolates from intensive care units in eight hos-
pitals in Turkey. J Antimicrob Chemother 2000, 45:695-699.
Fluit AC, Verhoef J, Schmitz FJ: The European SENTRY Partici-
pants, Frequency of isolation and antimicrobial resistance of
gram-negative and gram-positive bacteria from patients in
intensive care units of 25 European university hospitals par-
ticipating in the European arm of the SENTRY antimicrobial
surveillance program 1997–1998. Eur J Clin Microbiol Infect Dis
2001, 20:617-625.
Jones RN, Jenkins SG, Hoban DJ, Pfaller MA, Ramphal R: In vitro effi-
cacy of six cephalosporins tested against Enterobacteriaceae
isolated at 38 North American medical centres participating
in the SENTRY antimicrobial surveillance program 1997–
1998. Int J Antimicrob Agents 2000, 15:111-118.
Winokur PL, Canton R, Casellas JM, Legakis N: Variations in the
prevalence of strains expressing an extended-spectrum β-
lactamase phenotype and characterization of isolates from
Europe, the Americas, and the Western Pacific region. Clin
Infect Dis 2001, 32:94-103.
Nordmann P, Poirel L: Emerging carbapenemases in Gram-
negative aerobes. Clin Microbiol Infect 2002, 8:321-331.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.