Transcript No Slide Title

Trends in Antimicrobial Susceptibility of Bacterial Pathogens Isolated from Patients with
Blood Stream Infections (BSI) in North America (NA): SENTRY Program, 1997-2000
Poster # 78
AMENDED ABSTRACT
Background: From January 1997 through December 2000, 29,052 blood stream
infections (BSI) bacterial pathogens were reported from 38 SENTRY Program
hospitals in North America.
Methods: Consecutive BSI isolates were sent to the central monitoring laboratory
in Iowa City each month. Identification was confirmed and broth microdilution
susceptibility testing was performed using NCCLS recommended methods.
Results: S. aureus (SA), E. coli (EC) and coagulase-negative staphylococci
(CoNS) were the most common pathogens; 55% of all BSI during the 4-yr period.
Among the top 10 pathogens, 63% were Gram-positive (G+) cocci. The rank order
of the top 10 BSI pathogens was essentially unchanged; however, some important
trends were noted. Between 1997 and 2000, an increase in the % of BSI due to SA
(22.9-28.7%) and Enterococcus spp. (9.5-10.5%) was noted, whereas a decrease
was observed for EC (18.6-16.7%), CoNS (12.8-11.1%) and S. pneumoniae (SPN;
5.6-4.6%). 16 key organism-antimicrobial combinations were evaluated (NCCLS
MICs) for possible trends in resistance. No significant differences were observed
for EC vs ceftazidime (CAZ; 99.2-99.0%) or cefepime (CPM; 99.9-100%);
Klebsiella spp. vs CAZ (96.3-96.4%), CPM (98.8-99.6%), and imipenem (IMP;
100%); Enterobacter spp. vs CPM (99.0-100%). Decreased S was noted for SA vs
oxacillin (77.6-65.6%); CoNS vs oxacillin (29.9-23.7%); Enterococcus spp. vs
vancomycin (87.0-84.2%); P. aeruginosa versus ciprofloxacin (88.9 - 78.8%) and
EC vs ciprofloxacin (97.5-95.2%). In contrast, increased S was noted for SPN
versus penicillin; P. aeruginosa vs CPM, CAZ and IMP and Enterobacter spp. vs
CAZ.
Conclusions: Important changes over time in the spectrum of BSI pathogens in
NA were noted and highlight the G+ cocci as increasingly significant causes.
Likewise, increasing resistance was observed among staphylococci and
enterococci. Ongoing surveillance (SENTRY) remains essential and should be
used to enhance efforts to limit the extent of resistance worldwide.
MATERIALS AND METHODS
Study Design
The SENTRY Antimicrobial Resistance Surveillance Program was established in January 1997. The
monitored infections include bacteremia and fungemia, outpatient respiratory tract infections,
pneumonia, wound infections, and urinary tract infections. Participating institutions include 30 medical
centers in the US, eight in Canada, ten in Latin America, and 24 in Europe. This report will focus on all
BSI isolates from the North America.
Each participant hospital contributed results (organism identification, date of isolation, and antimicrobial
susceptibility profile) on the first 20 consecutive episodes of bacteremia (blood culture isolates from
separate patients that were judged to be clinically significant) in each calendar month of each year. All
isolates were saved on agar slants and sent on a weekly basis to the University of Iowa (Iowa City) for
storage and for further characterization by reference identification and susceptibility testing methods.
Organism Identification
All blood culture isolates were identified at the participating institution by the routine methods in use at
each laboratory. Upon receipt at the University of Iowa, isolates were subcultured to blood agar to
ensure viability and purity. Confirmation of species identification was performed with Vitek (bioMerieux
Vitek, St. Louis, MO) and API (bioMerieux) products or conventional methods as required. Isolates
were frozen at -70C until needed.
Susceptibility Testing
Antimicrobial susceptibility testing of isolates was performed by reference broth microdilution methods
as described by the National Committee for Clinical Laboratory Standards. Microdilution trays were
purchased from Accumed, Inc. (Cleveland, OH). Quality control was performed by testing E. coli ATCC
25922, S. aureus ATCC 29213, P. aeruginosa ATCC 27853, S. pneumoniae ATCC 49619, and
Enterococcus faecalis ATCC 29212. Interpretive criteria for each antimicrobial agent tested were those
published by NCCLS.
RESULTS
 Frequency of occurrence of bloodstream pathogens. During the four year study period,
(January 1997 through December 2000), a total of 29,052 BSI were reported by North American
SENTRY participants. Table 1 compares the frequencies of occurrence of the 10 most commonly
isolated pathogens during each of the four years, 1997-2000. These organisms and groups
accounted for 91% of all BSI reported from these hospitals during the four year period. The rank
order of the top five pathogens was unchanged from 1997 to 2000. These five organisms or
organism groups (Staphylococcus aureus, Escherichia coli, coagulase-negative staphylococci,
Enterococcus spp. and Klebsiella spp.) accounted for over 70% of all BSI during the four sampling
periods. Notably, between 1997 and 2000, an increase in the percentage of BSI due to S. aureus
(22.9 - 28.7%) and Enterococcus spp. (9.5 - 10.5%) was seen, whereas a decrease was observed
for E. coli (18.6 - 16.7%), CoNS (12.8 - 11.1%) and S. pneumoniae (5.6 - 4.6%).
 Change in susceptibility over time for selected antimicrobial-pathogen combinations, by
INTRODUCTION
The SENTRY antimicrobial resistance surveillance program is designed to track antimicrobial
resistance trends nationally and internationally through a network of sentinel hospitals. Previous
publications from SENTRY have established baseline data regarding the spectrum of pathogens and
antimicrobial resistance profiles of organisms causing bloodstream, respiratory tract, wound, and
urinary tract infections in North and Latin America. These data demonstrate significant regional
differences in antimicrobial susceptibility and confirm the widespread nature and alarming prevalence of
antimicrobial resistance in the Western Hemisphere.
It is important not only to establish the prevalence of antimicrobial resistance at one point in time, but to
provide longitudinal data to track changes over time. The rates of change in resistance by pathogen
and region can help set priorities for focused intervention efforts.
Bloodstream infections (BSI) cause significant morbidity and mortality worldwide. In this paper we
report the frequencies of occurrence and antimicrobial susceptibility profiles of bloodstream infection
(BSI) isolates from the North America medical centers participating in the SENTRY program. The
present study included all BSI from January 1997 through December 2000.
*Corresponding Author: Michael A. Pfaller, M.D.
Medical Microbiology Division, C606 GH, Department of Pathology
University of Iowa College of Medicine, Iowa City, Iowa 52242
Phone: (319) 384-9566
Fax: (319) 356-4916
Email: [email protected]
M.A. Pfaller1, R.N. Jones2, D.J. Diekema2, and M. Beach2
SENTRY Participants Group. Univ of Iowa, Iowa City, IA1; The JONES Group/JMI Laboratories, North Liberty, IA2
region. In order to follow changes in important antimicrobial resistances, we selected a number of
sentinel antimicrobial-organism combinations (adapted from Archibald, et al.(12). A comparison of
susceptibility results over the four year period was made for each of these antimicrobial-organism
combinations in each region (see Table 2).
TABLE 1. Frequencies of occurrence of bacterial pathogens associated
with BSI in participating medical centers in the SENTRY Antimicrobial
Surveillance Program, North America 1997-2000
1997
Rank
1
2
3
4
5
6
7
8
9
10
aPercent
Pathogen
S. aureus
E. coli
CoNS
Enterococcus spp.
Klebsiella spp.
S. pneumoniae
P. aeruginosa
Enterobacter spp.
-streptococcus
viridans group streptococci
Rank
1
2
3
4
5
6
7
8
9
10
cPercent
Pathogen
S. aureus
E. coli
CoNS
Enterococcus spp.
Klebsiella spp.
S. pneumoniae
P. aeruginosa
-streptococcus
Enterobacter spp.
viridans group streptococci
No.
1683
1183
879
721
518
345
306
239
230
120
(%)b
(24.5)
(17.2)
(12.8)
(10.5)
(7.5)
(5.0)
(4.4)
(3.5)
(3.3)
(1.7)
No.
1917
1118
739
703
494
306
261
239
234
102
(%)d
(28.7)
(16.7)
(11.1)
(10.5)
(7.4)
(4.6)
(3.9)
(3.6)
(3.5)
(1.5)
 In summary, we have provided longitudinal data on pathogen frequency and
antimicrobial susceptibility profiles of the most important organisms causing BSI in North
America from 1997 - 2000. These data demonstrate the increasing prominence of Grampositive cocci as BSI pathogens.
 Likewise, increasing resistance was observed among staphylococci and enterococci. In
contrast, the activity of ceftazidime, cefepime, and the carbapenems against the
Enterobacteriaceae and P. aeruginosa appears stable.
 Resistance to ciprofloxacin among P. aeruginosa increased significantly from 7.5% in
1997 to 17.3% in 2000.
 Ongoing surveillance remains essential and should be used to limit the extent of
resistance world-wide.
of 6,878 isolates
2000
No.
1945
1315
935
763
597
349
335
287
279
136
(%)c
(25.5)
(17.2)
(12.2)
(10.0)
(7.8)
(4.6)
(4.4)
(3.8)
(3.7)
(1.8)
Rank
1
2
3
4
5
6
7
8
9
10
dPercent
of 7,635 isolates
Pathogen
S. aureus
E. coli
CoNS
Enterococcus spp.
Klebsiella spp.
P. aeruginosa
S. pneumoniae
Enterobacter spp.
-streptococcus
Serratia spp.
of 6,685 isolates
TABLE 2. Antimicrobial susceptibility in blood stream isolates from SENTRY
1997 through 2000 for selected antimicrobial-pathogen combinations
ACKNOWLEDGEMENTS
The authors wish to thank K. Meyer for her assistance in the preparation of this manuscript.
The authors express their appreciation to all SENTRY site participants. Participants contributing data/isolates to the study included: The
Medical Center of Delaware, Wilmington, DE, (L. Steele-Moore); Clarion Health Methodist Hospital, Indianapolis, IN, (G. Denys); Henry
Ford Hospital, (C. Staley); Summa Health System, Akron, OH (J.R. Dipersio); Good Samaritan Regional Medical Center, (M. Saubolle);
Denver General Hospital, Denver, CO, (M.L. Wilson); University of New Mexico Hospital, Albuquerque, NM, (G.D. Overturf); University of
Illinois at Chicago, Chicago, IL, (P.C. Schreckenberger); University of Iowa Hospitals and Clinics, Iowa City, IA, (R.N. Jones); Creighton
University, Omaha, NE, (S. Cavalieri); Froedtert Memorial Lutheran Hospital-East, Milwaukee, WI, (S. Kehl); Boston VAMC, Boston, MA
(S. Brecher); Columbia Presbyterian Medical Center, New York, NY, (P. Della-Latta); Long Island Jewish Medical Center, New Hyde Park,
NY, (H. Isenberg); Strong Memorial Hospital, Rochester, NY, (D. Hardy); Kaiser Regional Laboratory, Berkeley, CA, (J. Fusco); Sacred
Heart Medical Center, Spokane, WA, (M. Hoffmann); University of Washington Medical Center, Seattle, WA, (S. Swanzy); Barnes-Jewish
Hospital, St. Louis, MO, (P.R. Murray); Parkland Health & Hospital System, Dallas, TX, (P. Southern); The University of Texas Medical
School, Houston, TX, (A. Wanger); University of Texas Medical Branch at Galveston, Galveston, TX (B. Reisner); University of Louisville
Hospital, Louisville, KY, (J. Snyder); University of Mississippi Medical Center, Jackson, MS, (J. Humphries); Carolinas Medical Center,
Charlotte, NC, (S. Jenkins); University of Virginia Medical Center, Charlottesville, VA, (K. Hazen); University of Alberta Hospital, Edmonton,
Alberta, CAN,( R. Rennie); Health Sciences Centre, Winnipeg, Manitoba, CAN, ( D. Hoban); Queen Elizabeth II Health Sciences Centre,
Halifax, Nova Scotia,CAN, (K. Forward); Ottawa General Hospital, Ottawa, Ontario, CAN, (B. Toye); Royal Victoria Hospital, Montreal,
Quebec, CAN, (H. Robson); Microbiology Laboratory C.E.M.I.C.,
This study was supported by a research and educational grant from Bristol-Myers Squibb Company.
% Susceptible (No. Tested)
Organism
Antimicrobial Agent
1997
1998
1999
2000
S. aureus
Oxacillin
77.6 (1802)
72.2 (1683)
69.3 (1945)
65.6 (1917)
CoNS
Oxacillin
29.9 (1008)
23.2 (879)
25.6 (935)
23.7 (739)
Enterococcus spp.
Vancomycin
87.0 (745)
86.4 (721)
85.4 (763)
84.2 (703)
S. pneumoniae
Penicillin
Levofloxacin
65.8 (441)
99.3 (441)
81.2 (345)
99.7 (345)
78.2 (349)
NA
78.2 (261)
100.0 (261)
Ceftazidime
Cefepime
Ciprofloxacin
99.2 (1461)
99.9 (1461)
97.5 (1461)
98.6 (1183)
99.7 (1183)
97.4 (1183)
99.4 (1315)
99.8 (1315)
95.4 (1315)
99.0 (1118)
100.0 (1118)
95.3 (1118)
Klebsiella spp.
Ceftazidime
Cefepime
96.3 (592)
98.8 (592)
95.4 (518)
99.4 (518)
96.3 (597)
98.8 (597)
96.4 (494)
99.6 (494)
P. aeruginosa
Ceftazidime
Cefepime
Imipenem
Ciprofloxacin
86.9
88.3
87.5
88.9
83.0
87.9
91.8
85.9
(306)
(306)
(306)
(306)
85.1
88.1
90.7
85.4
(335)
(335)
(335)
(335)
88.2
89.5
92.2
78.8
75.2 (230)
99.1 (230)
77.7
99.0
(287)
(287)
81.2 (239)
99.2 (239)
E. coli
 Among the four most prevalent causes of gram-negative BSI, no increase in resistance to cefepime
or the carbapenems was seen between 1997 and 2000. Susceptibility to ceftazidime increased by 1
- 6% among isolates of Klebsiella spp., P. aeruginosa, and Enterobacter spp. Ciprofloxacin activity
against E. coli BSI decreased slightly from 97.5% susceptible in 1997 to 95.2% in 2000. Importantly,
ciprofloxacin activity against P. aeruginosa decreased by approximately 10% (88.9-78.8%) between
1997 and 2000.
Rank
1
2
3
4
5
6
7
8
9
10
bPercent
Pathogen
S. aureus
E. coli
CoNS
Enterococcus spp.
Klebsiella spp.
S. pneumoniae
P. aeruginosa
Enterobacter spp.
-streptococcus
Serratia spp.
 Among the S. pneumoniae BSI isolates, high level resistance to penicillin (MIC,  2 g/ml)
decreased from 9.4% in 1997 to 7.6% in 2000. Likewise, ~ 99% of S. pneumoniae isolates were
susceptible to levofloxacin over the four year study period.
(%)a
(22.9)
(18.6)
(12.8)
(9.5)
(7.5)
(5.6)
(4.6)
(4.0)
(3.5)
(1.5)
1999
 There was a moderate increase in vancomycin-resistance among the Enterococcus spp. BSI
isolates between 1997 and 2000: 11.5% to 14.5%.
No.
1802
1461
1008
745
592
441
359
312
277
120
of 7,854 isolates
 Oxacillin resistance among Staphylococcus spp. (both S. aureus and CoNS) increased over the four
year time period. In 1997, 22.4% of S. aureus BSI isolates were oxacillin-resistant; this increased to
34.4% by 2000. Oxacillin-resistance among CoNS increased from 70.1% in 1997 to 76.3% in 2000.
1998
CONCLUSIONS
Enterobacter spp.
Ceftazidime
Cefepime
(359)
(359)
(359)
(359)
77.9 (312)
100.0 (319)
(306)
(306)
(306)
(306)
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