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. 2003 Oct;47(10):3089–3098. doi: 10.1128/AAC.47.10.3089-3098.2003

In Vitro Susceptibilities of Gram-Negative Bacteria Isolated from Hospitalized Patients in Four European Countries, Canada, and the United States in 2000-2001 to Expanded-Spectrum Cephalosporins and Comparator Antimicrobials: Implications for Therapy

Richard P Wenzel 1, Daniel F Sahm 2, Clyde Thornsberry 2, Deborah C Draghi 2, Mark E Jones 2, James A Karlowsky 2,*
PMCID: PMC201113  PMID: 14506014

Abstract

Access to current antimicrobial agent surveillance data is an important prerequisite for the optimal management of patients with hospital-acquired infections. The present study used data collected in 2000 to 2001 from 670 laboratories in Europe (France, Germany, Italy, and Spain), Canada, and the United States to report on the in vitro activities of ceftriaxone, cefotaxime, and comparative agents against >125,000 isolates of gram-negative bacteria from hospitalized patients. All but two isolates of Enterobacteriaceae (one isolate of Proteus mirabilis from France and one isolate of Morganella morganii from Canada) were susceptible to imipenem. The susceptibility of Escherichia coli to ceftriaxone or cefotaxime was ≥97% in each country, and for P. mirabilis, susceptibility was 99% in each country except Italy. In contrast, susceptibility of E. coli to ciprofloxacin varied from 80.5% (Spain) to 94.0% (France); levofloxacin susceptibility ranged from 75.2% (Spain) to 91.6% (United States). Among Klebsiella pneumoniae and Klebsiella oxytoca isolates, ceftriaxone and cefotaxime susceptibilities ranged from 86.6 to 98.7% and 83.5 to 99.7%, respectively, depending upon the country. Considerable geographic variation in the susceptibilities (generally 85 to 95% susceptible) of Serratia marcescens and M. morganii to ceftriaxone and cefotaxime were observed. For S. marcescens, susceptibility to piperacillin-tazobactam varied from 81.5% (France) to 94.1% (Italy) and susceptibility to ciprofloxacin ranged from 66.2% (Germany) to 90.7% (Spain). Enterobacter cloacae and Enterobacter aerogenes were less susceptible to ceftriaxone and cefotaxime than were the other species of Enterobacteriaceae studied. The present study demonstrated that established parenteral expanded-spectrum cephalosporin antimicrobial agents retain significant in vitro activity against many clinically important gram-negative pathogens.

Gram-negative bacteria remain important hospital pathogens, particularly for critically ill patients, and appropriate antimicrobial treatment is often critical to decreasing morbidity and mortality among hospitalized patients with infections (3, 8). Given the propensity for resistance to develop to all available antimicrobial agents, the publication of current antimicrobial susceptibility data are important, particularly for agents or classes of agents that have been frequently used clinically for prolonged periods of time and upon which physicians constantly depend. Expanded-spectrum cephalosporins such as ceftriaxone and cefotaxime are broad-spectrum agents that have been widely prescribed by physicians in Europe, Canada, and the United States for hospitalized patients with a variety of infections for almost 20 years. The intent of the present study was to provide an update on the in vitro activity of expanded-spectrum cephalosporins and comparator antimicrobial agents against gram-negative bacteria from hospitalized patients in France, Germany, Italy, Spain, Canada, and the United States by using The Surveillance Network (TSN) databases (Focus Technologies, Herndon, Va.). The implications of recent surveillance data for the therapy of hospital-acquired infections are discussed.

MATERIALS AND METHODS

In 2000 to 2001, TSN databases assimilated antimicrobial susceptibility testing and patient demographic data from networks of hospitals in several countries, including France (n = 63), Germany (n = 168), Italy (n = 48), Spain (n = 21), Canada (n = 87), and the United States (n = 283), and these were used as the data source for this study (17). Laboratories contributing to TSN databases are all nationally accredited and are invited to participate in TSN based on factors such as hospital type (university teaching hospital or community hospital) and antimicrobial susceptibility testing method used as well as the bed size, patient population, and geographic location of the hospital(s) they serve (17). All isolates reported in TSN were identified at the participating institutions by routine methods in use at each laboratory. Antimicrobial susceptibility testing of patient isolates is conducted onsite by each participating laboratory as a part of its routine diagnostic testing. Only data generated by using nationally approved (Food and Drug Administration-approved in the United States) testing methods with MIC results interpreted according to NCCLS (Germany, Italy, Spain, Canada, and United States) (13) and SFM (Société Francaise de Microbiologie; France) recommendations (18) were included in the datasets analyzed in this study. Antimicrobial agent susceptibility data from Germany and Spain that were interpreted by breakpoints other than those of the NCCLS were excluded from the datasets analyzed; all data in TSN from Italy, Canada, and the United States were interpreted by using NCCLS breakpoints. In addition, a series of quality-control filters (proprietary critical rule sets) were used to screen susceptibility test results for patterns indicative of testing error; suspect results are removed from analysis for laboratory confirmation (17). In TSN, any result from the same patient with the same organism identification and the same susceptibility pattern received within 5 days is considered a repeat culture and is counted only once in the database.

In the present study, TSN results from 1 January 2000 to 31 December 2001 were used to determine the rates of antimicrobial susceptibility for 15 antimicrobial agents among prevalent gram-negative species isolated from hospitalized patients in Europe, Canada, and the United States. Data from patients identified as nursing home residents and hospital outpatients in hospital laboratory information systems were excluded from the analysis. An inpatient isolate was defined as such by each hospital participating in TSN. The TSN database presumes the evidence of infection, but no clinical correlates are applied universally. Thus, the data for gram-negative bloodstream and urine cultures are much more likely to reflect infection causally than the data for isolates from wounds and sputum cultures. Nevertheless, the data from microbiology laboratories are often used to guide therapy in hospital-associated pneumonia and often in skin and soft tissue infections. Overall data from all specimen sources were analyzed, as were susceptibility rates among organisms commonly isolated from patients with specific infection types. Isolate results were reported only for bacterial species-antimicrobial agent combinations in which 50 or more results were available for a specific specimen source in a country. In TSN, all isolates are not tested against all agents and variation can be observed for antimicrobial agents of the same class such as expanded-spectrum cephalosporins (ceftriaxone and cefotaxime) and fluoroquinolones (ciprofloxacin and levofloxacin) for which similar in vitro activities have been previously demonstrated.

RESULTS

The cumulative 2000 to 2001 antimicrobial susceptibilities of eight species of Enterobacteriaceae and Haemophilus influenzae from hospitalized patients are shown (Table 1). Data from both intensive-care unit (ICU) and non-ICU hospital inpatients are combined. All members of the family Enterobacteriaceae were susceptible to imipenem except for one isolate of Proteus mirabilis from France and one isolate of Morganella morganii from Canada. Susceptibility to amikacin exceeded 98% for the majority of species of Enterobacteriaceae in each country studied, and generally, susceptibility to gentamicin was >90%. Escherichia coli susceptibility to ceftriaxone or cefotaxime was 97% or greater in each country studied. In contrast, susceptibility to amoxicillin-clavulanate varied from 69.9% (France) to 85.8% (Spain), susceptibility to ciprofloxacin varied from 80.5% (Spain) to 94.0% (France), and susceptibility to levofloxacin varied from 75.2% (Spain) to 91.6% (United States).

TABLE 1.

Susceptibilities of nine species of gram-negative bacteria isolated from hospitalized patients in four European countries, Canada, and the United States to antimicrobialsa

Organism Antimicrobial agent France
Germany
Italy
Spain
Canada
United States
No. of isolates % Susceptible No. of isolates % Susceptible No. of isolates % Susceptible No. of isolates % Susceptible No. of isolates % Susceptible No. of isolates % Susceptible
E. coli Amikacin 75,385 99.4 25,704 99.8 22,884 99.2 17,232 99.8 18,024 99.6 74,220 99.5
Amoxicillin-clavulanate 83,690 69.9 6,205 78.8 21,667 80.6 24,101 85.8 19,286 79.6 45,434 81.2
Ampicillin 33,822 53.6 21,339 58.3 23,263 56.5 19,705 39.2 52,354 64.6 135,321 57.9
Cefepime 30,427 99.6 16,758 99.2 8,955 99.2 12,137 98.4 1,636 99.3 54,041 99.1
Cefotaxime 82,657 99.6 44,149 99.1 19,542 97.1 22,991 98.2 18,927 97.0 54,268 98.3
Cefpirome 14,045 99.6 NAb NA NA NA NA NA NA NA NA NA
Ceftazidime 77,457 99.1 22,800 98.9 23,216 96.5 21,303 98.1 39,585 98.7 81,300 97.0
Ceftriaxone 7,278 99.5 3,193 99.8 10,410 96.7 793 97.4 36,293 98.6 97,940 98.5
Cefuroxime 11,384 92.8 35,157 91.9 7,643 87.0 14,507 91.9 20,340 92.9 54,084 91.7
Ciprofloxacin 64,199 94.0 36,898 88.4 24,201 84.7 23,473 80.5 45,854 93.2 110,811 92.4
Gentamicin 84,261 96.7 41,428 95.2 26,319 92.8 23,967 91.1 46,778 94.8 135,528 95.0
Imipenem 75,852 100 37,172 100 20,230 100 13,254 100 32,838 100 87,433 100
Levofloxacin NA NA 16,582 89.8 2,269 85.2 169 75.2 5,974 90.3 100,223 91.6
Piperacillin-tazobactam 52,063 97.0 42,439 96.5 12,857 96.8 10,674 96.5 37,473 96.6 70,784 95.3
TMP-SMX 82,535 78.6 42,715 73.2 25,640 74.4 24,379 67.6 52,224 83.5 135,210 80.7
K. pneumoniae Amikacin 7,704 96.9 5,915 99.3 4,888 94.2 2,290 98.9 5,663 99.6 28,688 98.4
Amoxicillin-clavulanate 8,382 82.6 1,130 76.8 4,658 79.5 3,158 87.0 5,950 93.1 16,734 90.1
Ampicillin 3,249 0.6 4,424 0.9 4,126 1.4 2,639 0.9 14,605 1.0 46,943 1.3
Cefepime 3,409 95.8 3,925 95.1 1,629 96.6 1,710 87.0 574 98.8 23,462 96.7
Cefotaxime 8,378 96.1 10,088 93.8 4,135 90.4 3,052 91.3 5,919 98.3 21,812 93.6
Cefpirome 1,360 92.8 NA NA NA NA NA NA NA NA NA NA
Ceftazidime 8,105 94.4 5,299 92.4 5,204 83.9 2,823 90.9 11,573 98.4 33,261 90.9
Ceftriaxone 476 90.6 461 98.7 2,695 86.6 119 94.1 9,902 98.7 37,426 94.5
Cefuroxime 1,107 81.4 8,524 86.3 1,499 72.3 1,858 89.1 6,672 90.0 20,816 81.8
Ciprofloxacin 6,889 92.7 8,722 87.2 5,339 91.6 3,032 95.5 13,276 94.8 40,605 92.1
Gentamicin 8,396 97.2 9,631 93.7 5,393 90.1 3,177 89.1 13,837 97.5 49,694 94.1
Imipenem 8,007 100 9,265 100 4,772 100 1,809 100 9,430 100 35,247 100
Levofloxacin NA NA 4,065 93.1 588 92.0 NA NA 2,153 94.8 37,636 92.9
Piperacillin-tazobactam 5,626 92.9 9,893 86.2 2,387 89.7 1,362 89.3 10,959 93.9 30,227 89.5
TMP-SMX 8,140 87.5 9,890 83.3 5,174 82.9 3,193 85.5 14,726 92.5 49,187 89.1
K. oxytoca Amikacin 3,624 98.4 2,990 99.8 795 98.0 840 99.6 1,475 99.8 4,710 99.2
Amoxicillin-clavulanate 3,887 82.7 444 79.1 727 83.9 1,216 84.5 1,447 90.5 2,560 83.5
Ampicillin 1,707 0.7 2,071 3.7 882 3.5 933 2.1 3,598 0.9 7,624 1.2
Cefepime 1,642 97.1 1,815 94.0 602 98.5 563 94.1 110 99.1 3,955 96.5
Cefotaxime 3,879 97.6 4,979 92.7 623 95.5 1,170 96.2 1,620 96.7 3,933 93.1
Cefpirome 748 96.4 NA NA NA NA NA NA NA NA NA NA
Ceftazidime 3,735 98.7 2,555 94.5 929 88.7 1,160 96.8 2,814 98.1 5,790 92.4
Ceftriaxone 291 83.5 327 99.7 518 88.6 NA NA 2,430 97.0 6,133 90.6
Cefuroxime 506 80.6 4,186 80.4 512 75.6 624 84.1 1,791 89.1 4,080 78.6
Ciprofloxacin 3,298 92.5 4,122 88.1 984 93.6 1,195 94.2 3,277 97.3 6,902 91.9
Gentamicin 3,892 96.4 4,818 97.8 993 92.6 1,215 97.9 3,444 97.0 8,162 92.4
Imipenem 3,642 100 4,562 100 837 100 615 100 2,315 100 5,932 100
Levofloxacin NA NA 1,802 92.8 284 95.8 NA NA 492 98.4 5,751 93.1
Piperacillin-tazobactam 2,688 87.2 4,856 80.6 766 88.0 525 89.5 2,716 93.6 4,964 86.2
TMP-SMX 3,769 92.1 4,799 88.9 919 90.4 1,218 91.5 3,637 95.7 8,015 91.0
E. cloacae Amikacin 6,230 97.9 3,838 99.3 2,314 96.6 1,935 99.6 3,197 99.6 15,154 98.3
Amoxicillin-clavulanate 6,410 3.4 814 5.4 2,106 4.8 2,509 1.9 2,742 4.4 7,442 3.5
Ampicillin 2,470 2.8 3,242 9.0 1,941 7.1 1,976 4.3 6,823 1.6 22,307 2.7
Cefepime 3,335 91.7 2,746 96.5 1,245 93.0 1,954 93.8 298 97.3 13,595 92.2
Cefotaxime 6,463 71.3 6,777 72.8 2,145 56.8 1,866 78.8 3,254 75.7 13,373 63.8
Cefpirome 1,241 79.5 NA NA NA NA NA NA NA NA NA NA
Ceftazidime 6,359 70.6 4,096 68.5 2,732 57.5 1,846 74.0 5,427 79.3 18,661 64.9
Ceftriaxone 593 52.8 446 86.8 1,584 61.1 88 72.7 4,821 78.4 18,879 66.9
Cefuroxime 790 32.2 5,553 13.3 979 24.2 1,519 26.3 3,775 40.7 11,373 32.7
Ciprofloxacin 5,657 85.7 5,754 90.5 2,774 77.7 2,479 96.0 6,486 93.6 20,019 87.3
Gentamicin 6,456 89.8 6,449 95.5 2,797 77.1 2,514 99.0 6,652 96.2 24,286 89.5
Imipenem 6,273 100 6,268 100 2,569 100 1,640 100 4,660 100 19,108 100
Levofloxacin NA NA 2,806 92.3 620 68.6 NA NA 1,098 92.3 18,087 88.7
Piperacillin-tazobactam 5,006 73.6 6,682 73.4 1,475 64.3 1,302 74.3 5,427 77.2 15,129 70.0
TMP-SMX 6,202 90.7 6,571 93.0 2,623 86.3 2,527 95.0 6,890 93.2 23,724 86.9
E. aerogenes Amikacin 3,751 71.8 782 99.9 1,241 89.8 503 98.6 805 99.6 6,088 98.5
Amoxicillin-clavulanate 3,996 2.8 198 1.5 1,164 6.4 622 4.0 771 7.1 3,408 5.7
Ampicillin 1,727 0.4 589 2.0 1,013 2.9 531 3.8 1,820 2.1 9,814 2.9
Cefepime 2,327 85.3 499 98.0 556 94.1 519 95.6 NA NA 5,441 95.8
Cefotaxime 4,029 48.2 1,291 79.0 1,024 58.6 511 74.2 816 80.9 5,335 72.2
Cefpirome 1,131 74.1 NA NA NA NA NA NA NA NA NA NA/PICK>
Ceftazidime 4,051 31.2 705 59.9 1,362 42.3 490 67.1 1,528 83.0 7,853 68.9
Ceftriaxone 404 32.7 103 58.3 780 52.4 NA NA 1,310 85.3 8,138 73.4
Cefuroxime 689 16.4 974 57.6 456 27.0 437 42.8 953 66.4 4,853 55.9
Ciprofloxacin 3,703 34.2 1,116 91.9 1,380 62.1 605 91.1 1,744 94.3 8,655 93.4
Gentamicin 4,028 95.3 1,178 98.3 1,382 87.6 636 96.5 1,798 99.1 10,564 95.5
Imipenem 4,003 100 1,201 100 1,255 100 476 100 1,300 100 7,949 100
Levofloxacin NA NA 568 94.9 269 57.3 NA NA 272 92.7 7,875 94.4
Piperacillin-tazobactam 2,995 45.5 1,277 69.5 758 59.5 377 67.4 1,480 81.4 6,333 72.8
TMP-SMX 3,910 52.7 1,265 94.2 1,316 61.9 637 92.0 1,847 97.0 10,325 95.7
P. mirabilis Amikacin 11,063 97.5 4,979 99.8 4,728 99.0 2,804 99.5 2,476 99.7 13,935 99.3
Amoxicillin-clavulanate 11,920 77.9 1,157 96.7 4,457 83.8 3,906 94.8 3,240 93.9 6,978 96.5
Ampicillin 4,608 60.5 3,876 69.6 4,200 42.6 3,214 60.9 7,070 82.2 23,265 83.5
Cefepime 4,625 98.9 3,368 99.6 1,594 94.2 1,995 99.0 242 96.7 9,735 98.3
Cefotaxime 11,860 99.1 8,504 99.3 4,069 71.9 3,762 99.7 2,614 99.2 10,232 99.4
Cefpirome 1,874 97.8 NA NA NA NA NA NA NA NA NA NA
Ceftazidime 11,298 98.9 4,624 99.1 4,811 87.8 3,464 99.4 5,659 99.1 14,604 98.4
Ceftriaxone 635 99.7 568 98.8 1,846 81.0 91 98.9 5,141 99.5 17,912 99.5
Cefuroxime 1,488 95.2 6,893 97.6 1,358 57.2 2,264 98.1 2,800 98.0 9,246 97.2
Ciprofloxacin 9,866 85.8 7,319 89.1 4,963 73.2 3,833 89.3 6,349 92.4 18,586 84.6
Gentamicin 12,006 92.7 7,930 92.6 5,007 64.9 3,921 89.7 6,653 93.5 23,429 91.4
Imipenem 9,739 99.9 7,168 100 4,197 100 2,057 100 4,661 100 15,453 100
Levofloxacin NA NA 3,336 93.1 390 77.2 NA NA 929 98.5 18,137 85.5
Piperacillin-tazobactam 7,840 99.2 8,456 98.8 2,077 98.2 1,739 99.4 5,344 97.6 13,618 97.7
TMP-SMX 11,595 80.7 8,040 71.8 4,854 54.9 3,952 63.7 7,061 82.0 23,319 83.6
S. marcescens Amikacin 2,180 90.8 1,768 98.8 1,087 97.4 705 98.0 1,775 99.1 8,296 98.2
Amoxicillin-clavulanate 2,229 2.9 447 2.7 981 2.2 908 5.7 1,661 2.9 3,757 1.6
Ampicillin 906 2.0 1,270 7.4 858 7.0 765 8.2 3,612 11.1 12,611 5.9
Cefepime 1,274 98.3 1,212 98.6 610 98.2 754 97.6 133 97.7 7,313 96.8
Cefotaxime 2,252 81.0 2,827 91.2 930 85.7 736 92.1 1,782 93.5 7,194 85.5
Cefpirome 526 97.2 NA NA NA NA NA NA NA NA NA NA
Ceftazidime 2,214 95.8 1,808 92.1 1,279 87.7 673 94.5 3,064 96.3 10,480 89.4
Ceftriaxone 322 65.5 316 53.8 800 85.3 NA NA 2,594 95.7 10,511 90.6
Cefuroxime 296 1.4 2,208 0.6 453 1.8 540 1.9 1,930 1.9 6,228 0.7
Ciprofloxacin 2,034 76.3 2,659 66.2 1,293 88.5 915 90.7 3,559 85.4 11,138 89.5
Gentamicin 2,269 90.0 2,472 90.8 1,294 96.0 928 97.1 3,579 94.0 13,443 94.2
Imipenem 2,194 100 2,794 100 1,252 100 614 100 2,514 100 10,591 100
Levofloxacin NA NA 1,288 83.2 298 96.3 NA NA 563 92.2 10,233 93.5
Piperacillin-tazobactam 1,733 81.5 2,897 85.7 726 94.1 503 91.9 3,125 92.8 9,245 87.8
TMP-SMX 2,105 80.5 2,715 83.7 1,130 87.4 930 96.0 3,671 92.8 13,192 95.5
M. morganii Amikacin 2,975 98.8 1,061 99.6 1,098 98.7 1,041 99.6 666 99.7 3,090 99.0
Amoxicillin-clavulanate 3,128 1.4 254 3.9 1,015 2.9 1,356 1.3 738 1.9 1,515 3.8
Ampicillin 1,092 0.5 871 1.3 916 1.8 1,120 0.8 1,659 1.7 4,897 3.4
Cefepime 1,452 98.1 790 96.3 367 99.2 1,071 97.7 52 100 2,555 97.5
Cefotaxime 3,154 87.8 1,930 89.3 903 69.3 996 89.8 717 87.3 2,441 81.8
Cefpirome 560 93.8 NA NA NA NA NA NA NA NA NA NA
Ceftazidime 3,051 85.5 1,017 86.1 1,160 76.6 975 85.4 1,318 83.5 3,559 75.7
Ceftriaxone 220 90.5 90 95.6 558 86.9 64 96.9 1,224 96.6 3,981 91.9
Cefuroxime 437 8.0 1,627 4.1 345 6.1 763 4.5 787 6.2 2,607 7.8
Ciprofloxacin 2,693 88.5 1,604 90.6 1,176 80.4 1,326 82.9 1,544 91.8 4,068 78.2
Gentamicin 3,162 93.5 1,800 93.6 1,184 83.5 1,367 84.2 1,624 93.6 4,940 84.8
Imipenem 2,948 100 1,638 100 1,078 100 869 100 1,009 99.9 3,636 100
Levofloxacin NA NA 778 93.1 130 89.2 NA NA 237 90.3 3,799 77.6
Piperacillin-tazobactam 2,154 94.2 1,850 94.8 531 94.9 681 95.5 1,222 95.7 3,226 93.1
TMP-SMX 3,034 83.0 1,881 85.7 1,124 67.8 1,372 70.1 1,673 87.2 4,880 74.7
H. influenzae Amoxicillin-clavulanate 3,612 100 2,006 100 424 100 2,327 100 401 100 1,138 99.8
Ampicillin 790 71.3 2,293 93.5 1,041 91.1 2,400 78.8 2,901 78.6 2,857 63.0
Cefepime NA NA NA NA NA NA 513 100 NA NA 84 100
Cefotaxime 3,183 100 2,071 100 448 100 2,308 100 810 100 1,129 100
Ceftazidime NA NA 1,610 100 309 100 NA NA NA NA 108 100
Ceftriaxone 209 100 50 100 449 100 142 100 293 100 2,051 100
Cefuroxime 737 71.4 2,052 98.8 150 95.3 1,493 98.3 1,838 99.4 2,227 96.1
Ciprofloxacin 538 100 2,080 100 580 100 1,756 100 533 100 352 100
Gentamicin 3,001 74.4 NA NA NA NA NA NA NA NA NA NA
Imipenem NA NA 1,996 100 277 100 808 100 NA NA 194 100
Levofloxacin NA NA 769 100 371 100 343 100 104 100 1,163 100
TMP-SMX 3,327 73.4 2,024 84.5 1,037 84.4 1,987 58.1 2,345 81.0 2,756 80.9
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a

Data are cumulative for 2000 to 2001.

b

NA, not available, <50 results were available.

Ninety-nine percent of P. mirabilis isolates from each country except Italy (81.0% and 71.9%, respectively) were susceptible to ceftriaxone or cefotaxime. For Klebsiella pneumoniae and Klebsiella oxytoca, ceftriaxone or cefotaxime susceptibilities ranged from 86.6 to 98.7% and 83.5 to 99.7%, respectively, depending upon the country. Considerable variation in the susceptibilities to ceftriaxone and cefotaxime of Serratia marcescens and M. morganii were also noted for isolates tested within the same country and among countries, but generally, 85 to 95% of isolates of both species were susceptible to ceftriaxone or cefotaxime. For S. marcescens, susceptibility to piperacillin-tazobactam varied from 81.5% (France) to 94.1% (Italy), and susceptibility to ciprofloxacin varied from 66.2% (Germany) to 90.7% (Spain).

Enterobacter cloacae and Enterobacter aerogenes were less susceptible to ceftriaxone and cefotaxime than were the other species of Enterobacteriaceae studied. Susceptibilities to cefepime, ceftriaxone, and cefotaxime were similar for E. coli, K. pneumoniae, K. oxytoca, and P. mirabilis. Cefepime susceptibilities were greater than those to ceftriaxone and cefotaxime for Enterobacter spp., S. marcescens, and M. morganii. All isolates of H. influenzae were susceptible to ceftriaxone, cefotaxime, and cefepime. Ceftazidime nonsusceptibility ranged from 0.9% (France) to 3.5% (Italy) for E. coli and from 1.6% (Canada) to 16.1% (Italy) for K. pneumoniae. Piperacillin-tazobactam susceptibilities exceeded 95% only for E. coli and P. mirabilis in each country. Variations in fluoroquinolone (ciprofloxacin and levofloxacin) susceptibilities were common for all species of Enterobacteriaceae. For example, for E. coli, the range of susceptibilities was from 75.2% (Spain, levofloxacin) to 94.0% (France, ciprofloxacin).

Table 2 provides antimicrobial susceptibility rates for Enterobacteriaceae isolated from hospitalized patients with potentially complicated urinary tract infections. Against E. coli, the most commonly isolated species from patients with potentially complicated urinary tract infections, ceftriaxone susceptibility ranged from 96.9% (Italy) to 99.7% (Germany) and cefotaxime susceptibility ranged from 95.4% (Italy) to 99.3% (France). Ciprofloxacin (range, 70.3 to 91.0%) and trimethoprim-sulfamethoxazole (TMP-SMX) (range, 61.7 to 82.7%) demonstrated greater regional variability against E. coli, and in each country studied, susceptibilities to ciprofloxacin (2.7 to 10.2% lower) and TMP-SMX (0.3 to 5.9% lower) were lower among urinary isolates than among all isolates (Table 1). Lower susceptibilities to ciprofloxacin and TMP-SMX, relative to all isolates, were also generally observed for K. pneumoniae, K. oxytoca, and P. mirabilis. Susceptibility rates to individual agents varied by gram-negative species, and a single country could not be demonstrated to have an overall greater or lower prevalence of susceptible isolates for all agents studied.

TABLE 2.

Susceptibilities of gram-negative bacteria isolated from hospitalized patients with potentially complicated urinary tract infections in four European countries, Canada, and the United States to antimicrobialsa

Organism Antimicrobial agent France
Germany
Italy
Spain
Canada
United States
No. of isolates % Susceptible No. of isolates % Susceptible No. of isolates % Susceptible No. of isolates % Susceptible No. of isolates % Susceptible No. of isolates % Susceptible
E. coli Cefotaxime 9,062 99.3 5,447 98.9 3,944 95.4 1,570 97.8 4,628 96.8 9,821 98.3
Ceftazidime 8,498 98.6 2,474 98.4 4,001 94.1 1,538 98.5 9,025 98.6 15,593 96.7
Ceftriaxone 1,167 99.2 906 99.7 1,440 96.9 NAb NA 7,593 98.2 19,590 98.2
Ciprofloxacin 6,045 91.0 4,017 79.4 4,112 74.8 1,105 70.3 10,060 89.4 22,440 89.7
Gentamicin 9,548 95.4 4,863 93.0 5,268 89.4 1,621 88.4 10,903 94.2 27,780 94.2
TMP-SMX 9,450 78.0 5,357 67.4 5,275 69.4 1,667 61.7 11,433 82.7 27,890 80.4
K. pneumoniae Cefotaxime 1,143 94.7 1,162 92.9 789 85.0 171 95.3 1,453 97.8 3,416 93.6
Ceftazidime 1,090 92.6 559 85.7 987 77.5 169 95.3 2,725 97.7 5,512 90.3
Ceftriaxone NA NA 84 98.8 240 74.2 NA NA 2,173 98.2 6,914 94.3
Ciprofloxacin 771 87.4 921 80.8 996 88.0 71 91.5 3,024 93.5 7,565 90.2
Gentamicin 1,148 97.7 1,111 90.4 1,013 87.3 173 89.6 3,265 96.9 9,396 93.8
TMP-SMX 1,141 84.9 1,151 77.8 1,015 73.8 173 83.8 3,393 90.5 9,402 87.1
K. oxytoca Cefotaxime 624 97.3 564 87.1 50 90.0 72 94.4 322 96.9 580 93.3
Ceftazidime 592 98.8 229 93.0 101 87.1 71 100 592 98.8 987 93.1
Ceftriaxone 57 86.0 NA NA 63 93.7 NA NA 491 98.4 1,113 90.2
Ciprofloxacin 432 88.7 439 74.7 108 88.0 55 89.1 660 95.8 1,325 87.8
Gentamicin 638 94.7 542 95.8 108 96.3 74 97.3 710 96.8 1,559 93.1
TMP-SMX 638 91.7 555 74.6 108 87.0 75 85.3 746 95.8 1,566 89.0
P. mirabilis Cefotaxime 1,684 98.8 1,406 99.2 1,110 63.6 211 100 964 98.8 1,997 99.7
Ceftazidime 1,574 99.0 713 98.9 1,322 84.1 209 99.5 1,955 99.2 2,989 98.8
Ceftriaxone 114 100 66 98.5 280 85.0 NA NA 1,670 99.4 4,056 99.5
Ciprofloxacin 1,192 81.8 1,222 82.0 1,349 64.6 129 78.3 2,176 88.8 4,443 81.5
Gentamicin 1,729 93.2 1,275 88.9 1,364 57.3 216 86.6 2,325 94.2 5,515 90.9
TMP-SMX 1,711 78.4 1,372 64.8 1,363 45.5 221 64.3 2,401 79.1 5,531 81.6
Other Enterobacteriaceae Cefotaxime 2,574 69.2 1,561 78.7 970 61.2 251 79.7 1,320 82.5 4,010 75.2
Ceftazidime 2,495 65.9 734 75.3 1,178 58.7 253 79.4 2,649 86.0 6,415 74.0
Ceftriaxone 294 46.3 130 88.5 297 62.3 NA NA 2,213 86.9 7,405 77.8
Ciprofloxacin 1,790 55.4 1,216 73.5 1,198 55.8 153 83.7 2,956 83.6 8,069 78.9
Gentamicin 2,591 83.0 1,382 89.0 1,215 70.7 261 89.7 3,185 91.6 9,844 88.5
TMP-SMX 2,572 73.7 1,553 80.4 1,223 68.7 265 84.9 3,294 86.0 9,848 83.4
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a

To estimate antimicrobial susceptibilities among patients with complicated urinary tract infections, isolate specimen sources were limited to invasive specimen sources (catheterized urines, suprapubic bladder aspirates, nephrostomy, cystoscopic urine aspirates, and ureter; clean-catch urine and catheter tip isolates were excluded) from ICU and non-ICU inpatients, both males and females ≥18 years of age. The “Other Enterobacteriaceae” category was created for complicated urinary tract infection isolates to include Citrobacter spp., Enterobacter spp., Providencia spp., and Serratia spp. Data are cumulative for 2000 to 2001.

b

NA, not available, <50 results were available.

Table 3 summarizes the susceptibility results for bloodstream isolates. For E. coli, ≥97% of isolates were susceptible to ceftriaxone and cefotaxime in the four European countries studied, Canada, and the United States. Ciprofloxacin susceptibility in E. coli was variable, from 81.0% (Spain) to 93.9% (France), but less variable than isolates from the urinary tract (Table 2). Gentamicin susceptibility varied from 91.5% (Spain) to 96.8% (Germany). For Klebsiella species, 91.2 to 100% of isolates were susceptible to ceftriaxone and 90.9 to 98.1% of isolates were susceptible to cefotaxime. For Pseudomonas aeruginosa, an important opportunistic gram-negative pathogen, a wide range of susceptibility rates were observed geographically: amikacin (81.0 to 97.3%), cefepime (60.1 to 85.0%), ceftazidime (62.7 to 84.6%), ciprofloxacin (66.1 to 82.8%), imipenem (70.6 to 84.4%), and piperacillin-tazobactam (78.1 to 92.4%). In a few instances it seems interesting that the antimicrobial agent-pathogen pairs showed reduced susceptibilities across several antimicrobial agents. For example, in Italy the range of susceptibilities for P. mirabilis for all six antimicrobial agents varied from 52.6 to 78.4%, the lowest range for all the countries studied. However, for S. marcescens, the lowest range was seen in France, with susceptibilities from 69.9 to 90.9% across five antimicrobial agents tested.

TABLE 3.

Susceptibilities of gram-negative bacteria isolated from bloodstream specimens of hospitalized patients in four European countries, Canada, and the United States to antimicrobialsa

Organism Antimicrobial agent France
Germany
Italy
Spain
Canada
United States
No. of isolates % Susceptible No. of isolates % Susceptible No. of isolates % Susceptible No. of isolates % Susceptible No. of isolates % Susceptible No. of isolates % Susceptible
E. coli Cefotaxime 5,265 99.5 2,620 99.6 1,113 97.8 2,175 98.5 1,170 96.8 4,905 98.1
Ceftazidime 4,651 98.7 1,501 99.3 1,698 97.6 2,041 98.4 2,013 98.5 6,892 96.9
Ceftriaxone 813 99.3 186 100 1,363 98.1 492 99.4 1,585 97.9 6,460 98.2
Ciprofloxacin 4,659 93.9 2,072 89.0 1,697 81.3 2,253 81.0 2,280 93.5 7,547 90.9
Gentamicin 5,265 96.4 2,503 96.8 1,689 91.7 2,138 91.5 2,419 94.5 9,022 94.1
TMP-SMX 5,090 77.9 2,524 73.5 1,490 71.5 2,229 66.4 2,535 79.8 8,854 75.7
Klebsiella spp. Cefotaxime 846 95.7 710 95.1 313 93.0 551 90.9 618 98.1 3,143 92.2
Ceftazidime 754 96.3 400 92.5 458 87.3 528 91.1 949 98.4 4,394 89.4
Ceftriaxone 174 94.3 58 100 364 91.2 83 95.2 709 97.7 4,114 91.9
Ciprofloxacin 793 94.3 581 90.9 458 94.5 587 94.0 1,083 96.1 4,663 92.5
Gentamicin 843 98.2 665 96.8 463 92.0 566 89.9 1,177 97.2 5,472 91.8
TMP-SMX 798 90.7 675 86.8 420 85.5 586 84.6 1,215 92.0 5,333 87.2
P. mirabilis Cefotaxime 337 98.8 210 99.5 111 56.8 196 100 52 100 598 99.5
Ceftazidime 297 98.3 131 99.2 171 78.4 182 100 112 100 807 98.1
Ceftriaxone NAb NA NA NA 158 69.6 NA NA 100 100 772 99.7
Ciprofloxacin 298 85.2 174 87.4 174 63.8 206 86.9 134 95.5 849 80.0
Gentamicin 336 93.5 198 90.9 175 52.6 197 90.4 149 92.0 1,044 87.0
TMP-SMX 325 83.7 199 66.8 166 54.2 202 62.4 153 89.5 1,033 77.5
S. marcescens Cefotaxime 166 76.5 162 84.0 110 89.1 90 92.2 92 88.0 759 86.0
Ceftazidime 153 90.9 114 92.1 158 90.5 76 93.4 185 91.9 1,052 90.1
Ceftriaxone NA NA NA NA 119 81.5 NA NA 157 94.9 992 91.8
Ciprofloxacin 156 69.9 155 72.9 158 93.0 98 92.9 215 93.5 1,081 92.1
Gentamicin 167 88.6 114 88.6 159 96.9 95 100 223 91.5 1,256 94.8
TMP-SMX 160 80.0 157 90.5 139 90.7 99 99.0 222 95.5 1,210 96.6
Citrobacter spp. Cefotaxime 132 81.1 107 85.1 57 77.2 56 83.9 67 80.6 403 79.9
Ceftazidime 123 79.7 66 72.7 78 68.0 51 72.6 93 82.8 554 75.6
Ceftriaxone NA NA NA NA 60 75.0 NA NA 64 85.9 516 80.0
Ciprofloxacin 123 90.2 78 93.6 77 90.9 68 89.7 116 92.2 592 89.4
Gentamicin 132 92.4 105 95.2 78 94.9 67 100 116 88.8 683 90.8
TMP-SMX 124 89.5 110 94.6 71 90.1 68 91.2 121 87.6 663 85.7
Enterobacter spp. Cefotaxime 658 72.5 384 78.7 290 56.9 257 70.0 322 73.0 470 72.3
Ceftazidime 616 69.3 237 69.6 419 52.3 251 66.5 519 79.8 653 66.5
Ceftriaxone 158 62.7 NA NA 317 53.3 NA NA 432 78.9 616 69.6
Ciprofloxacin 601 79.7 312 94.9 423 72.3 323 94.4 615 96.1 669 91.8
Gentamicin 652 95.3 354 96.9 421 80.3 305 99.7 612 96.6 795 93.7
TMP-SMX 621 84.5 379 97.1 389 78.7 321 92.2 628 95.1 771 92.7
P. aeruginosa Amikacin 709 81.0 176 94.9 644 84.9 446 97.3 282 90.4 2,480 92.4
Cefepime 635 66.8 206 85.0 436 60.1 401 79.6 NA NA 2,429 80.6
Cefotaxime NA NA 139 13.0 442 9.1 325 7.4 177 21.5 1,416 9.3
Ceftazidime 705 80.0 293 84.6 783 62.7 492 82.1 532 80.8 3,167 80.8
Ceftriaxone NA NA NA NA 503 9.0 NA NA 311 10.0 1,823 12.8
Ciprofloxacin 703 67.0 262 75.2 773 66.1 487 82.8 538 78.1 3,068 73.1
Gentamicin 700 51.6 254 79.9 775 59.5 473 75.3 505 78.6 3,448 78.7
Imipenem 711 81.7 265 84.2 761 70.6 427 82.9 390 84.4 2,988 83.6
Piperacillin-tazobactam 670 78.1 275 92.4 446 81.2 407 86.7 411 88.8 2,495 90.1
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a

Data are cumulative for 2000 to 2001.

b

NA, not available, <50 results were available.

Table 4 depicts the cumulative 2000 to 2001 data for the susceptibilities of five species of Enterobacteriaceae, H. influenzae, and P. aeruginosa isolated from lower respiratory tract infection specimens to antimicrobials. Generally, lower respiratory tract isolates of E. coli were 1 to 5% less susceptible than were all isolates combined to expanded-spectrum cephalosporins, ciprofloxacin, gentamicin, and TMP-SMX (Table 1): the same trend was not observed among Klebsiella spp., Enterobacter spp., and S. marcescens. Isolates of P. aeruginosa isolated from the respiratory tract were less susceptible than P. aeruginosa isolates from the bloodstream in each country studied (Table 3) to amikacin (0.4 to 12.9% less), ceftazidime (3.3 to 9.3% less), ciprofloxacin (8.3 to 15.1% less), gentamicin (6.2 to 11.6% less), imipenem (6.8 to 13.4% less), and piperacillin-tazobactam (0.1 to 6.8% less). Cefepime susceptibilities were also lower (8.4 to 12.3%) for P. aeruginosa isolates from the respiratory tract than those from the bloodstream for each country (with data) except Italy, where susceptibilities were slightly lower (1.1%) among bloodstream isolates.

TABLE 4.

Susceptibilities of gram-negative bacteria isolated from lower respiratory tract specimens of hospitalized patients in four European countries, Canada, and the United States to antimicrobialsa

Organism Antimicrobial agent France
Germany
Italy
Spain
Canada
United States
No. of isolates % Susceptible No. of isolates % Susceptible No. of isolates % Susceptible No. of isolates % Susceptible No. of isolates % Susceptible No. of isolates % Susceptible
E. coli Cefotaxime 2,416 99.6 2,631 98.0 685 94.0 815 96.7 1,033 95.5 3,249 95.8
Ceftazidime 2,555 98.4 1,508 97.9 899 93.1 737 97.3 1,418 97.0 4,716 93.8
Ceftriaxone 134 97.8 213 100 674 92.6 NAb NA 1,381 96.8 4,600 96.2
Ciprofloxacin 2,300 93.6 2,200 83.8 934 90.9 841 84.7 1,719 91.2 5,042 88.0
Gentamicin 2,422 96.2 2,548 92.9 931 94.4 836 92.1 1,974 94.0 6,218 90.6
TMP-SMX 2,212 77.0 2,489 73.8 893 79.2 836 72.0 2,005 83.6 6,012 77.3
Klebsiella spp. Cefotaxime 1,160 96.5 3,615 92.7 901 90.0 617 93.0 1,367 97.6 6,506 92.3
Ceftazidime 1,287 94.7 2,065 92.0 1,103 80.3 562 94.3 1,975 98.0 9,459 89.9
Ceftriaxone 89 91.0 180 100 904 86.7 NA NA 1,777 98.0 9,382 92.3
Ciprofloxacin 1,223 92.6 3,164 87.0 1,134 95.2 629 96.5 2,324 94.2 10,198 90.5
Gentamicin 1,157 97.2 3,562 93.8 1,169 89.4 629 93.0 2,568 97.6 12,426 92.3
TMP-SMX 1,048 90.6 3,532 85.7 1,122 88.6 631 88.6 2,625 96.0 12,011 90.6
Citrobacter spp. Cefotaxime 350 77.7 657 81.6 136 87.5 106 88.7 208 78.9 1,024 78.6
Ceftazidime 361 74.0 403 76.7 165 81.8 95 83.2 280 80.4 1,566 72.2
Ceftriaxone NA NA NA NA 131 88.6 NA NA 251 82.9 1,509 75.6
Ciprofloxacin 336 81.6 514 90.3 169 95.3 125 91.2 338 90.8 1,591 88.1
Gentamicin 350 89.7 651 96.5 176 98.9 125 97.6 369 88.9 1,956 91.3
TMP-SMX 321 85.4 641 96.1 163 92.6 125 93.6 379 87.3 1,891 89.6
Enterobacter spp. Cefotaxime 1,806 58.1 2,190 70.8 779 63.5 581 78.0 1,126 79.8 2,413 73.1
Ceftazidime 1,926 49.7 1,421 63.4 979 57.6 579 71.7 1,602 81.8 3,471 70.7
Ceftriaxone 180 40.0 151 74.2 731 64.8 NA NA 1,467 81.1 3,314 73.7
Ciprofloxacin 1,855 59.2 1,920 89.6 988 77.6 689 98.3 1,949 94.3 3,615 93.4
Gentamicin 1,797 94.3 2,213 95.1 1,000 85.7 686 98.7 2,082 96.3 4,394 95.7
TMP-SMX 1,681 71.7 2,140 94.1 955 81.7 688 95.6 2,127 94.9 4,194 96.1
S. marcescens Cefotaxime 806 81.5 1,041 94.5 352 83.8 265 94.3 791 95.2 3,531 85.4
Ceftazidime 808 95.7 728 90.1 492 85.4 239 95.8 1,205 97.2 5,254 88.6
Ceftriaxone 128 68.0 168 51.2 331 88.2 NA NA 994 96.1 5,104 89.4
Ciprofloxacin 792 77.7 1,031 61.7 498 88.4 307 93.2 1,436 86.7 5,406 90.2
Gentamicin 809 90.7 1,003 91.7 495 96.8 307 96.1 1,447 93.6 6,510 93.2
TMP-SMX 706 79.6 977 85.8 429 87.0 307 97.7 1,461 93.0 6,352 95.7
H. influenzae Cefotaxime 2,381 100 1,124 100 336 100 1,776 100 421 100 774 100
Ceftazidime NA NA 837 100 224 100 NA NA NA NA 75 100
Ceftriaxone 159 100 NA NA 334 100 124 100 216 100 1,578 100
Ciprofloxacin 389 100 1,032 100 411 100 1,524 100 420 100 243 100
Gentamicin 2,230 74.2 NA NA NA NA NA NA NA NA NA NA
TMP-SMX 2,492 74.4 1,100 84.7 633 86.3 1,617 60.4 1,736 79.8 2,138 81.0
P. aeruginosa Amikacin 9,072 68.1 2,632 91.7 4,729 80.8 2,857 96.9 4,479 81.2 26,459 85.8
Cefepime 8,534 54.5 3,660 76.6 2,737 61.2 2,991 70.1 805 64.5 24,118 70.7
Cefotaxime NA NA 2,402 5.5 3,538 8.7 1,768 12.7 1,789 25.0 12,781 12.3
Ceftazidime 9,031 70.9 4,873 79.8 5,700 59.4 3,178 73.4 7,666 74.7 32,069 71.5
Ceftriaxone NA NA 88 22.7 3,165 8.8 154 57.1 3,377 16.3 16,504 16.0
Ciprofloxacin 9,057 57.3 4,737 66.0 5,405 57.8 3,182 71.2 7,529 63.0 32,012 61.0
Gentamicin 7,993 42.4 4,581 72.1 5,571 53.3 3,163 65.8 7,516 67.0 35,769 67.1
Imipenem 9,076 69.8 4,435 70.8 5,418 63.1 3,039 71.4 5,416 77.6 30,949 74.0
Piperacillin-tazobactam 8,598 71.3 4,624 88.9 2,916 81.9 2,926 80.2 5,127 88.7 25,157 84.9
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a

Lower respiratory tract isolates included those from sputum, bronchial washings, and tracheal aspirates. Data are cumulative for 2000 to 2001.

b

NA, not available, <50 results were available.

Antimicrobial susceptibilities of gram-negative bacteria isolated from skin and soft tissue specimens are summarized in Table 5 and were similar to the results reported for all isolates (Table 1). In general, isolates of P. aeruginosa isolated from skin and soft tissue specimens were more susceptible to amikacin, cefepime, and imipenem than isolates from the bloodstream (Table 3).

TABLE 5.

Susceptibilities of gram-negative bacteria isolated from skin and soft tissue specimens of hospitalized patients in four European countries, Canada, and the United States to antimicrobialsa

Organism Antimicrobial agent France
Germany
Italy
Spain
Canada
United States
No. of isolates % Susceptible No. of isolates % Susceptible No. of isolates % Susceptible No. of isolates % Susceptible No. of isolates % Susceptible No. of isolates % Susceptible
E. coli Cefotaxime 4,460 99.5 2,827 99.4 638 92.6 2,964 96.1 868 96.3 1,626 96.9
Ceftazidime 3,944 98.6 1,387 99.4 968 93.1 2,756 95.7 1,129 96.8 2,650 95.9
Ceftriaxone 273 98.2 179 100 738 92.7 51 98.0 998 97.1 2,795 97.8
Ciprofloxacin 3,759 92.8 2,485 92.8 1,025 82.1 3,084 77.1 1,373 91.6 3,004 90.6
Gentamicin 4,459 94.9 2,771 96.1 1,022 88.2 3,079 86.1 1,492 92.8 3,712 93.4
TMP-SMX 4,162 75.6 2,709 78.9 906 69.9 3,088 64.1 1,548 84.9 3,669 80.7
Klebsiella spp. Cefotaxime 1,225 96.4 90 95.7 200 88.0 790 86.1 416 98.3 913 93.8
Ceftazidime 1,151 95.3 437 97.3 287 82.6 752 85.5 589 97.8 1,485 90.7
Ceftriaxone 83 88.0 54 100 216 86.6 NAb NA 524 97.9 1,554 93.1
Ciprofloxacin 1,088 94.5 764 92.5 303 90.4 825 94.9 676 93.9 1,667 90.2
Gentamicin 1,227 97.2 895 97.4 302 91.1 822 87.5 722 97.9 2,024 94.1
TMP-SMX 1,129 90.8 876 91.1 267 83.9 825 82.8 767 94.1 1,988 89.4
Citrobacter spp. Cefotaxime 434 83.2 282 85.5 101 73.3 213 82.6 123 77.2 358 75.7
Ceftazidime 403 79.7 158 71.5 144 67.4 198 81.8 146 77.4 563 74.3
Ceftriaxone NA NA NA NA 112 69.6 NA NA 131 71.8 561 77.7
Ciprofloxacin 388 87.1 248 94.0 145 94.5 291 94.2 185 94.1 590 88.5
Gentamicin 437 94.5 281 97.2 144 97.2 291 96.2 191 92.7 729 93.0
TMP-SMX 396 89.9 271 96.3 130 95.4 291 92.1 196 89.8 717 89.4
Enterobacter spp. Cefotaxime 1,486 71.1 494 74.7 282 64.2 630 80.2 408 72.8 195 70.8
Ceftazidime 1,446 66.0 285 70.9 377 59.7 616 76.8 461 77.2 371 69.0
Ceftriaxone 121 57.0 NA NA 244 59.8 NA NA 414 77.1 397 71.0
Ciprofloxacin 1,386 76.9 409 91.9 379 80.0 938 94.4 595 93.6 420 95.2
Gentamicin 1,491 93.1 493 97.8 380 85.5 938 98.2 634 98.0 489 96.1
TMP-SMX 1,356 81.1 469 95.7 324 83.3 939 94.7 641 95.9 480 96.0
Proteus spp. Cefotaxime 2,183 98.8 705 99.3 401 71.1 1,060 99.2 171 99.4 547 96.9
Ceftazidime 1,963 98.8 357 98.9 505 85.0 988 98.9 249 97.6 898 98.7
Ceftriaxone 95 99.0 95 96.8 360 75.6 NA NA 214 99.1 1,048 96.0
Ciprofloxacin 1,880 87.3 603 96.0 530 75.1 1,175 88.5 300 95.7 1,040 88.3
Gentamicin 2,184 93.5 689 97.0 530 58.3 1,172 89.0 318 95.0 1,316 90.7
TMP-SMX 1,894 81.3 659 82.9 459 54.0 1,173 66.5 332 87.7 1,296 84.6
P. aeruginosa Amikacin 4,094 84.0 471 94.3 1,920 75.1 1,869 97.5 632 92.3 2,639 92.6
Cefepime 3,726 71.7 580 87.8 1,227 67.7 1,915 75.3 108 80.6 2,449 80.0
Cefotaxime NA NA 376 6.9 1,168 5.1 1,425 7.2 312 18.6 989 11.4
Ceftazidime 4,090 83.8 864 89.7 2,106 61.2 2,034 77.6 1,548 85.2 3,662 79.3
Ceftriaxone NA NA NA NA 1,305 8.4 NA NA 606 14.2 1,852 13.2
Ciprofloxacin 4,082 70.3 847 77.5 2,102 49.9 2,046 70.5 1,518 74.8 3,520 67.3
Gentamicin 3,541 58.1 816 83.8 2,094 49.0 2,043 71.4 1,425 80.6 3,915 77.5
Imipenem 4,096 83.6 844 84.6 1,931 77.2 1,929 81.0 1,159 87.8 3,393 83.4
Piperacillin-tazobactam 3,835 83.1 775 93.9 1,161 77.3 1,846 84.5 929 92.4 2,863 88.7
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a

Skin and soft tissue infection specimen sources were skin, skin ulcer, decubitis ulcer, subcutaneous biopsy, skin biopsy, abscess, soft tissue, surgical wound, subphrenic abscess, drainage pus, splenic abscess, renal abscess, perirectal abscess, liver abscess, pancreatic abscess, and intraabdominal abscess. Data are cumulative for 2000 to 2001.

b

NA, not available, <50 results were available.

Table 6 presents antimicrobial susceptibilities of E. coli and K. pneumoniae isolated from patients in ICUs. From 93.7% (Italy) to 99.7% (Germany) of E. coli isolates were susceptible to ceftriaxone, and from 94.5% (Italy) to 99.0% (France) of E. coli isolates were susceptible to cefotaxime. For K. pneumoniae, from 79.4% (Italy) to 98.2% (Germany) of isolates were susceptible to ceftriaxone and 80.1% (Italy) to 98.4% (Canada) of isolates were susceptible to cefotaxime. Differences in susceptibilities relative to all isolates were greatest for expanded-spectrum cephalosporins (up to 10% lower susceptibility among isolates from ICUs) and gentamicin (9.5%) for K. pneumoniae. Differences in susceptibility for isolates of E. coli from ICU patients relative to all isolates combined were variable and did not demonstrate an observable trend.

TABLE 6.

Susceptibilities of gram-negative bacteria isolated from ICU patients in four European countries, Canada, and the United States to antimicrobialsa

Organism Antimicrobial agent France
Germany
Italy
Spain
Canada
United States
No. of isolates % Susceptible No. of isolates % Susceptible No. of isolates % Susceptible No. of isolates % Susceptible No. of isolates % Susceptible No. of isolates % Susceptible
E. coli Cefotaxime 6,031 99.0 3,449 98.0 1,105 94.5 1,428 96.6 1,886 96.4 5,745 96.9
Ceftazidime 5,896 98.1 1,769 98.1 1,525 94.3 1,220 97.2 2,861 97.9 9,412 95.6
Ceftriaxone 531 98.9 353 99.7 888 93.7 NAb NA 2,618 97.1 10,182 97.6
Ciprofloxacin 5,504 93.6 2,695 87.8 1,570 89.5 1,321 81.7 3,197 90.9 11,130 90.6
Gentamicin 6,104 95.7 2,783 94.5 1,596 93.6 1,469 90.8 4,332 94.3 13,127 92.7
TMP-SMX 5,841 78.3 3,264 74.7 1,473 77.7 1,476 66.9 4,395 84.9 12,921 79.5
K. pneumoniae Cefotaxime 1,034 94.2 1,505 92.0 598 80.1 496 84.9 817 98.4 4,081 91.4
Ceftazidime 1,061 92.2 838 87.6 759 70.1 451 85.6 1,456 98.1 6,295 88.2
Ceftriaxone 71 85.9 108 98.2 608 79.4 NA NA 1,216 97.9 6,638 92.1
Ciprofloxacin 977 89.1 1,331 84.6 799 91.6 475 91.2 1,595 92.4 7,150 90.4
Gentamicin 1,031 97.9 1,274 89.6 819 81.1 514 79.6 1,857 96.8 8,481 91.4
TMP-SMX 971 88.3 1,450 78.8 759 84.6 514 84.6 1,877 93.2 8,198 88.7
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a

Data are cumulative for 2000 to 2001.

b

NA, not available, <50 results were available.

DISCUSSION

The goal of antimicrobial chemotherapy is to facilitate the eradication of infecting organisms from patients in a timely and safe manner while minimizing the emergence and spread of resistance. Best outcomes occur clinically if patients are given empirical therapy to which the organism is susceptible on the day infection is suspected clinically (8, 11). Our data indicate that susceptibility to ceftriaxone, piperacillin-tazobactam, imipenem, and aminoglycosides have remained relatively stable among most species of Enterobacteriaceae from 1996 to 2001 in the United States (10) (Table 1). The potency of ceftriaxone and cefotaxime against E. coli and Klebsiella suggests that single-agent therapy directed against those bacteria may be successful even in severely compromised hosts (25). However, the recent emergence of extended-spectrum β-lactamases and stably derepressed mutants that hyperproduce chromosomal β-lactamases has the potential to diminish the activity of all expanded-spectrum cephalosporins against these pathogens. In the United States, the prevalence of potential extended-spectrum β-lactamase-producing isolates of E. coli and K. oxytoca (MICs of ceftazidime interpreted as intermediate and resistant) increased from 0.9 to 1.6% and from 2.9 to 5.9%, respectively, between 1996 and 2000 (10).

The present report and previous reports indicate that fluoroquinolone susceptibility appears less stable than susceptibility to other classes of antimicrobials and has decreased over time in a consistent stepwise manner for members of the family Enterobacteriaceae, P. aeruginosa, and S. aureus in both the United States and Europe (4, 6, 10, 12). The widespread cumulative use of fluoroquinolones (ciprofloxacin and levofloxacin) may be accelerating the development of resistance to these agents and may be the driving force behind increases in resistance (2, 12, 14, 15). Fluoroquinolone resistance among species of gram-negative bacilli appears to be found more commonly as a component of multidrug-resistant phenotypes than as a single-agent resistance phenotype (16, 24). The potential for commonly encountered gram-negative bacilli to acquire cross-resistance to several antimicrobial agents has been well documented (9, 24).

Infections of the urinary tract are the most common nosocomial infections. They account for approximately 40% of infections and are usually catheter-associated (21). Most bacteriuric episodes in patients with short-term catheterization result from a single species, primarily E. coli. However, K. pneumoniae, P. mirabilis, Staphylococcus epidermidis, enterococci, P. aeruginosa, and Candida are also common. Some clinical data have suggested that antimicrobial treatment of catheterized patients with symptomatic bacteriuria may not be particularly useful in preventing complications (21). While consensus guidelines exist for the management of acute uncomplicated cystitis and pyelonephritis in otherwise healthy adult females (20), consensus guidelines are not currently published to guide the treatment of complicated urinary tract infections. In the present investigation, an average of 97% of E. coli in the countries studied remained susceptible to ceftriaxone and cefotaxime, suggesting that these antimicrobial agents remain an important therapeutic option for complicated urinary tract infections. K. pneumoniae, K. oxytoca, and P. mirabilis were also generally >90% susceptible to ceftriaxone or cefotaxime in the countries studied. Cefotaxime and ceftriaxone susceptibility was lower for these three pathogens in Italy than the other countries studied.

A recent analysis using the concept of attributable mortality (23) suggested that nosocomial bloodstream infections represent a leading cause of death in the United States (22). In the prospective surveillance system called SCOPE, nosocomial bloodstream infections caused by E. coli, Klebsiella spp., Enterobacter spp., Pseudomonas spp., and Serratia spp. had crude mortalities of, respectively, 24, 27, 28, 33, and 26% (5). Early initiation of appropriate antimicrobial agent treatment is critical in decreasing morbidity and mortality among patients with bloodstream infections due to gram-negative organisms (3, 8). The appropriateness of antimicrobial agent therapy should be reviewed within 24 h of the final susceptibility report becoming available from the laboratory (7). Combinations of antimicrobial agents are recommended for empirical therapy of patients with bloodstream infections, particularly for those patients with the most adverse prognostic factors (25). Clinicians need to take into account the different rates of resistance in ICUs and wards as well as the probability of P. aeruginosa when considering empirical therapy for infections with possible Gram-negative bacillary etiologies. Ceftriaxone, cefotaxime, and cefepime all have similar indications for pneumonia, skin and skin structure infections, and urinary tract infections; only ceftriaxone and cefotaxime have an indication for the sepsis syndrome. Our data suggest that the susceptibility of E. coli (>98%), K. pneumoniae (>91%), and P. mirabilis (>99%, except Italy) to ceftriaxone and cefotaxime remains high. However, ceftazidime, cefepime, imipenem, and meropenem appear most active against P. aeruginosa (25) (Table 3).

Pneumonia accounts for 15 to 20% of all hospital-acquired infections (19); in ICUs, pneumonia is generally the most common infection type. Hospital-acquired pneumonia accounts for the majority of deaths attributed to nosocomial infections (19), and Enterobacteriaceae, P. aeruginosa, Streptococcus pneumoniae, H. influenzae, and Staphylococcus aureus are the primary etiologic agents. Ceftriaxone and other nonpseudomonal expanded-spectrum cephalosporins are recommended by the American Thoracic Society for the treatment of patients with mild to moderate hospital-acquired pneumonia, provided that patients do not have risk factors which might alter the likely causative pathogens (1). Nonpseudomonal expanded-spectrum cephalosporins are also recommended for those patients with severe disease, provided that infection occurs within less than 5 days of hospital admission (1). In the present study, susceptibility data for respiratory isolates (Table 4) and isolates from patients in ICUs (Table 6) support such therapies for gram-negative bacilli under current empirical guidelines.

Skin and soft tissue infections in hospitalized patients are most commonly attributable to gram-positive bacteria (S. aureus, Streptococcus pyogenes, Streptococcus agalactiae). However, gram-negative bacteria, including species of Enterobacteriaceae, may also be etiologic agents. In addition to demonstrating almost uniform susceptibility to methicillin-susceptible S. aureus, S. pyogenes, and S. agalactiae (10), susceptibility to expanded-spectrum cephalosporins such as ceftriaxone and cefotaxime is high among Enterobacteriaceae species isolated from skin and soft tissue specimen sources (Table 5).

In conclusion, in an international study of over 125,000 isolates from 670 laboratories, our data suggest that the susceptibilities of Enterobacteriaceae and P. aeruginosa to some classes of antimicrobial agents are decreasing, most notably to the fluoroquinolones (ciprofloxacin and levofloxacin). Certain well-established antimicrobial agents, including parenteral expanded-spectrum cephalosporins, continue to retain high rates of susceptibility against many clinically important gram-negative pathogens. With respect to aminoglycosides, the susceptibility of Enterobacteriaceae to amikacin exceeded 98% and that to gentamicin was over 90%. Resistance to imipenem was identified in only two isolates of Enterobacteriaceae.

Acknowledgments

We thank the institutions participating in TSN databases in France, Germany, Italy, Spain, Canada, and the United States, who make data collection possible.

We also thank F. Hoffmann-La Roche Ltd. for financially supporting this study.

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