Transcript No Slide Title

Extreme Variations in Susceptibility (S) of P. aeruginosa (PSA) Among Hospitals in North America (NA), Latin America (LA),
Europe (EU) and the Asia-Pacific (AP): Report from the SENTRY Antimicrobial Surveillance Program, 1997-2000
Poster # 72
AMENDED ABSTRACT
Background: Multi-resistant (R) PSA isolated from blood stream (BSI), respiratory
tract (RTI), skin and soft tissue and urinary tract infections (UTI) has subsequently
increased morbidity and mortality rates worldwide. The SENTRY Program has
gathered global data on pseudomonal isolates for over 4 years to determine
prevailing R trends for 8 key anti-PSA drugs.
Methods: SENTRY participants from four regions (centers); NA (44), LA (14), EU
(30) and AP (18) collected 9,109 PSA isolates that were tested by reference NCCLS
methods against 28 antimicrobials including -lactams  inhibitor, fluoroquinolones
(FQ) and aminoglycosides.
Results: Overall spectrum rank order against PSA was: meropenem
> piperacillin/tazobactam > imipenem > cefepime (CPM) > ceftazidime (CAZ).
Rank order of % S by infection site showed BSI > RTI > UTI with -lactam R
greatest among RTI strains and FQ-R greatest among UTI isolates. FQ activity
ciprofloxacin (CIP; MIC50,  0.25 g/ml) was 2- to 4-fold > levofloxacin (MIC50,
0.5-1 g/ml) but spectrum difference was only 2.2%. PSA showed > S to CPM
compared to CAZ against BSI (84% vs 82%) and RTI (77% vs. 75%) in all regions.
Regional FQ % S ranked AP (84%) > NA (74%) > EU (68%) > LA (54%). A trend
towards decreased S over time in LA (-13%) and NA (-6%) was demonstrated only
for FQs. A decline in S over time for all monitored drugs was found for LA
(-6 to -13%) and EU (-6 to -14%) with a greater drop in tested FQ activity.
Conclusions: Extreme variations have emerged in the S patterns of PSA including:
inter-regional differences (NA and AP most S); escalating R to FQs (all regions);
and declining S to all anti-pseudomonal classes (EU and LA). Continued monitoring
of R, local interventions (infection and formulary controls) and new drug
development appear essential.
JT Kirby, DJ Biedenbach, RN Jones, SENTRY Participants Group
Univ of Iowa, Iowa City, IA; The JONES Group/JMI Laboratories, North Liberty, IA
MATERIALS AND METHODS
A total of 106 medical centers submitted 9,109 isolates of P. aeruginosa to the
SENTRY Antimicrobial Surveillance Program over the four year monitoring period
(1997-2000). SENTRY participants were divided into four regions (no. of centers): NA
(44), LA (14), EU (30) and AP (18). Asia-Pacific strains submitted were collected in
1998 and 1999 only. P. aeruginosa isolated from blood stream (BSI), respiratory tract
(RTI), and urinary tract infections (UTI) were all tested in the monitoring laboratory at
the University of Iowa College of Medicine (Iowa City, Iowa) or JMI Laboratories (North
Liberty, Iowa).
Susceptibility testing.
The minimum inhibitory concentrations (MICs) were determined on each isolate using
the broth microdilution methods outlined by the National Committee for Clinical
Laboratory Standards (NCCLS) [NCCLS, 2000]. Quality control (QC) was achieved by
regular performance testing of the following ATCC strains: Escherichia coli ATCC
25922, Staphylococcus aureus ATCC 29213, P. aeruginosa ATCC 27853,
Streptococcus pneumoniae ATCC 49619, Enterococcus faecalis ATCC 29212, and
others selected by the monitors. Antimicrobials were obtained from USA manufacturers
and included 28 investigational and clinical agents for Gram-negative isolates
dispensed in dry-form panels (TREK Diagnostics, Inc., Westlake, OH). All
interpretations of susceptibility categories were based on criteria of the NCCLS [2001].
RESULTS
 Against P. aeruginosa, the rank order of antimicrobial spectrums was:
INTRODUCTION
 Pseudomonas aeruginosa (PSA) is a Gram-negative aerobic bacillus that exhibits multi-
resistance to antimicrobials and consequently ranks among the top five nosocomial
pathogens. This organism is isolated from all sites or infections (blood, lung, wounds,
urine) based on surveillance data collected by the National Nosocomial Infection
Surveillance (NNIS) system of the Centers for Disease Control and Prevention
[CDC, 1998].
 Ubiquitous in nature, this common human saprophyte turns to a opportunistic pathogen
following the disruption of normal host defense mechanisms such as injuries to clinical
barriers caused by endotracheal tubes, intravenous lines and urinary catheters. Traumatic
injuries such as burns along with the increasing use of invasive surgical procedures and
iatrogenic immunosuppression for oncology patients, has led to the increased involvement
of P. aeruginosa in high hospital morbidity and mortality rates.
 Through the use of data generated from the SENTRY Antimicrobial Surveillance Program
(2000), the purpose of this study was to evaluate the in vitro efficacy of eight key antipseudomonal agents against isolates from blood stream, respiratory tract and urinary tract
infections. These results should help formulate guidelines for effective empiric therapies.
Increased resistance was also monitored from participants in four regions: North America
(NA), Latin America (LA), Europe (EU), and the Asia-Pacific (AP) tracking the current
variations emerging in the susceptibility patterns of PSA and to elucidate inter-regional
differences of the antipseudomonal drug classes.
Ronald N. Jones, M.D.
The JONES Group / JMI Laboratories
345 Beaver Kreek Centre, Suite A, North Liberty, Iowa 52317
Phone: 319-665-3370 Fax: 319-665-3371
[email protected]
meropenem (MERO) > piperacillin/tazobactam (PIP/TAZ) > imipenem (IMP) >
cefepime (CPM) > ceftazidime (TAZ) > gentamicin (GENT) > ciprofloxacin (CIP)
> levofloxacin (LEVO) except with respiratory tract isolates where MERO and
PIP/TAZ were equivalent, and urinary tract infections where TAZ > CPM.
 Percent susceptibility for various infection sites ranked as follows: BSI (most
susceptible) > RTI > UTI for all regions with the -lactam resistance greatest for
RTI isolates and FQ resistance highest among UTI isolates.
 Regional percent susceptibility of FQ’s ranked highest in AP (84%) compared to
NA (74%), EU (68%), and LA (54%) for these year 2000 P. aeruginosa isolates.
TABLE 1. Evolving trends in antimicrobial susceptibility of
Pseudomonas aeruginosa isolates indexed by monitored
geographic region during 1997-2000 (SENTRY Program).
Percent of isolates
 CPM activity was essentially equivalent to TAZ against BSI, RTI and UTI, but
CPM had a slightly superior spectrum against blood (84% versus 82%) and
respiratory tract (77% versus 75%) infections.
 A marked decrease in percent susceptibility (increased resistance) over time
was evident in LA (-6% to -13%) and Europe (-6% to -14%) for all drugs. These
same regions displayed the greatest decline in FQ susceptibility LA (-13%) and
EU (-8%).
Antimicrobial agent
Antimicrobial agent
1997
1998
1999
2000
% S overall
Piperacillin/Tazobactam
Ceftazidime
Cefepime
Imipenem
Meropenem
Gentamicin
Ciprofloxacin
Levofloxacin
90.7
79.6
78.3
86.8
92.4
79.6
79.8
74.4
90.0
81.1
85.6
84.7
90.9
86.6
77.3
73.1
88.4
79.5
84.5
88.4
90.8
86.7
76.1
74.5
88.4
82.5
84.4
87.7
89.6
83.4
73.8
72.6
-2.3
NC
NC
NC
-2.8
NC
-6.0
-1.8
Latin America
1998
1999
2000
% S overall
79.4
66.6
66.2
77.0
83.0
63.6
67.2
63.6
77.1
64.4
67.9
76.7
79.7
61.8
60.8
59.0
73.3
65.8
65.2
73.6
76.0
60.1
60.6
59.3
67.5
60.6
60.6
70.9
72.0
57.1
54.0
54.2
-11.9
-6.0
-5.6
-6.1
-11.0
-6.5
-13.2
-9.4
Europe
Piperacillin/Tazobactam
Ceftazidime
Cefepime
Imipenem
Meropenem
Gentamicin
Ciprofloxacin
Levofloxacin
1997
1998
1999
2000
% S overall
89.5
85.9
79.6
89.4
89.7
77.2
75.4
72.9
85.2
78.0
83.8
79.5
85.9
70.9
72.3
71.9
80.7
71.7
72.4
71.7
73.1
62.4
66.2
66.9
82.0
72.3
71.4
75.5
76.9
68.1
67.8
67.1
-7.5
-13.6
-8.2
-13.9
-12.8
-9.1
-7.6
-5.8
Asia-Pacific
Piperacillin/Tazobactam
Ceftazidime
Cefepime
Imipenem
Meropenem
Gentamicin
Ciprofloxacin
Levofloxacin
aSusceptibility
1997
1998
1999
2000
% S overall
N/A
–
–
–
–
–
–
–
90.2
76.1
81.6
90.0
91.5
82.3
84.8
83.8
87.5
83.7
85.8
86.2
87.8
85.8
83.7
82.6
88.2
82.5
83.5
85.2
90.1
83.7
85.2
83.7
-2.0
NC
NC
-4.8
-1.4
NC
NC
NC
categories per NCCLS criteria [2001].
-lactams
Piperacillin/Tazobactam
Ceftazidime
Cefepime
Imipenem
Meropenem
Aminoglycosides
Gentamicin
Quinolones
Ciprofloxacin
Levofloxacin
aSusceptibility
1997
 CIP activity (MIC50,  0.25 g/ml) was two- to four-fold greater than levofloxacin
(LEVO; MIC50, 0.5 - 1 g/ml), but an average difference of spectrum was only
2.2% in all regions for all infection sites.
MIC50/90 in g/ml (%susceptible) by infection site:
susceptiblea
North America
Piperacillin/Tazobactam
Ceftazidime
Cefepime
Imipenem
Meropenem
Gentamicin
Ciprofloxacin
Levofloxacin
TABLE 2. Antimicrobial activity of eight antipseudomonal agents
tested against 9,109 Pseudomonas aeruginosa isolates in the
SENTRY Program (1997-2000).
Blood
Respiratory
Urine
8/>64 (88.0)a
2/>16 (81.5)
2/16 (83.7)
1/8 (87.2)
0.5/4 (90.7)
8/>64 (85.3)
4/>16 (74.5)
4/16 (77.1)
1/>8 (80.9)
0.5/8 (85.3)
8/>64 (86.1)
4/>16 (76.1)
4/>16 (75.8)
2/8 (84.1)
0.5/8 (87.7)
2/16 (81.5)
2/16 (76.0)
2/>16 (69.9)
0.25/>2 (80.0)
0.5/>4 (78.2)
0.25/>2 (73.9)
1/>4 (70.8)
0.25/>2 (63.7)
1/>4 (62.1)
determined using NCCLS [2001] criteria.
CONCLUSIONS

Overall, P. aeruginosa exhibited remarkable variations in susceptibility patterns with NA and
AP showing the greatest susceptibility, and LA and EU exhibiting increased resistance for all
monitored antimicrobial agents.
 All regions showed escalating resistance to fluoroquinolones with the highest rates occurring
in LA and EU.
 Continued global surveillance of P. aeruginosa isolates, especially quinolone-resistant strains
is warranted and new drug development is essential for sustained quality therapy for Gramnegative bacilli.
REFERENCES
Fluit AC, Verhoef J, Schmitz F-J, the European SENTRY Participants. (2000). Antimicrobial
resistance in European isolates of Pseudomonas aeruginosa. Eur J Clin Microbiol Infect
Dis 19:370-374.
Gales AC, Jones RN, Turnidge J, Rennie R, Ramphal R. (2001). Characterization of
Pseudomonas aeruginosa isolates: Susceptibility patterns and molecular typing in the global
SENTRY Antimicrobial Surveillance Program, 1997-1999. Clin Infect Dis 32(Suppl 2):
S146-S155.
National Committee for Clinical Laboratory Standards (2000). Methods for dilution
antimicrobial tests for bacteria that grow aerobically. Approved standard M7-A5.
Wayne, PA:NCCLS.
National Committee for Clinical Laboratory Standards (2001). Performance standards for
antimicrobial susceptibility testing. Supplemental tables, M100-S11. Wayne, PA:NCCLS.
Ramphal R, Hoban DJ, Pfaller MA, Jones RN. (2000). Comparison of the activity of two
broad-spectrum cephalosporins tested against 2,299 strains of Pseudomonas aeruginosa
isolated at 38 North American medical centers participating in the SENTRY Antimicrobial
Surveillance Program, 1997-1998. Diagn Microbiol Infect Dis 36:125-129.
A156-22