In-vitro activity of cefepime and seven other antimicrobial agents against 1518 non-fermentative Gram-negative bacilli collected from 48 Canadian health care facilities

J. M. Blondeaua,b,c,*, R. Laskowskia, S. Borsosa and The Canadian Afermenter Study Group

a Departments of Clinical Microbiology, St Paul's Hospital (Grey Nuns') and Saskatoon and District Health b Department of Pathology, Royal University Hospital c the Department of Microbiology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada


    Abstract
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Non-fermentative bacilli are primarily nosocomial pathogens, and are also often resistant in vitro to a broad range of antimicrobial agents. In this large Canadian study, we collected 1466 clinical, non-repeat isolates of Pseudomonas aeruginosa, 21 of Acinetobacterspp. and 31 Stenotrophomas maltophilia. MICs of eight antibiotics were determined by the NCCLS microdilution method in a central laboratory. Tobramycin was the most active agent against P. aeruginosa (94.5% susceptible); amikacin and imipenem were the most active against Acetinobacterspp. (100%) and ceftazidime was the most active against S. maltophilia (40.6%). Against each group of isolates, cefepime was active against 87, 86.4 and 15.6%, respectively. This in-vitro study showed that cefepime may be a useful additional agent in the treatment of infections caused by P. aeruginosaand Acinetobacterspp., but not when S. maltophilia is considered pathogenic.


    Introduction
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Non-fermentative Gram-negative bacilli are ubiquitous microorganisms that can be isolated from soil, water, plants and animals, including humans. These organisms have a predilection for moist environments and are often found in the hospital around therapeutic equipment which is exposed to water as well as common utility areas such as sinks, bathtubs and in housekeeping cleaning materials.1

Non-fermentative Gram-negative bacilli are primarily nosocomial pathogens, are associated with infection at any anatomical location and are frequently classified as `opportunistic organisms'. Nosocomial Pseudomonas aeruginosa infections are associated with significant morbidity and mortality.2 Coincidentally, these organisms are often multi-resistant to a broad range of antimicrobial agents,2 and/or have the ability to develop resistance during therapy when a single antibiotic is used.

Cefepime is a broad-spectrum, fourth-generation cephalosporin with significant in-vitro antimicrobial advantages over other ß-lactam antimicrobial agents.3,4 Cefepime is active in vitroagainst the majority of bacterial pathogens that cause infections of the lower respiratory tract, urinary tract, skin and soft tissue and bacteraemia, including non-fermentative Gram-negative bacilli.

To date, there are limited Canadian studies testing large numbers of these organisms against a wide variety of antimicrobial agents. In this study we collected and tested 1466 isolates of P. aeruginosa, 21 isolates of Acinetobacter spp. and 31 isolates of Stenotrophomonas maltophilia against cefepime and seven other antimicrobial agents.

These data will contribute to currently available published literature, and collectively serve to establish baseline information on non-fermentative Gram-negative bacilli and their in-vitro susceptibility to antimicrobial agents from Canadian health care facilities.


    Materials and methods
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Isolates were collected from 48 medical centres representing all 10 Canadian provinces, the North West Territories and nearly all major populated areas in Canada. The number of isolates contributed per institution ranged from 10 to 55. Newly collected clinical isolates were eligible for inclusion in the study and duplicate isolates from the same patients were not permitted. Isolates were collected between July 1994 and December 1995, and there was no selection process in the study design that would increase the likelihood of collecting resistant isolates.

All isolates were tested centrally at the Royal University Hospital in Saskatoon, Saskatchewan, Canada. MICs were determined using the broth microdilution method as recommended by the National Committee for Clinical Laboratory Standards (NCCLS).5 The MIC was defined as the lowest concentration of antimicrobial to allow no growth. The following American type culture collection (ATCC) microorganisms were tested each time susceptibility testing was performed: Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923 and P. aeruginosa ATCC 27853.


    Results
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 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Table I summarizes the in-vitro activity of the eight antimicrobial agents tested against P. aeruginosa. Tobramycin (94.5%) was the most active agent followed by amikacin (93.6%), piperacillin (91.6%) and gentamicin (90%). Resistance rates (at breakpoint) ranged from 4.1% (amikacin) to 10.1% (ciprofloxacin). Susceptibility of isolates to cefepime was 87%.


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Table I. In-vitro activity of eight antimicrobial agents against 1466 strains of P. aeruginosa
 
Table II summarizes the in-vitro activity of eight antimicrobial agents against 21 strains of Acinetobacterspp. and 31 strains of S. maltophilia. All Acinetobacter spp. isolates were susceptible to amikacin and imipenem, while cefepime was the most active cephalosporin (86.4%). Piperacillin/tazobactam was the least active agent, with only 42.9% of isolates susceptible at breakpoint. For S. maltophilia, susceptibility rates for the eight agents ranged from 9.1% (piperacillin/tazobactam) to 40.6% (ceftazidime).


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Table II. In-vitro activity of eight antimicrobial agents against 21 strains of Acinetobacter spp. and 31 strains of S. maltophilia
 

    Discussion
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 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Antimicrobial resistance is common amongst non-fermentative Gram-negative bacilli. Several Canadian studies have tested these organisms against a limited number of antimicrobial agents. Chamberland et al.6 tested the susceptibilities of 78 isolates of P. aeruginosa, collected from septicaemic patients throughout Canada, to 28 antimicrobial agents. Six agents are comparable with this current study. Chamberland's results for comparable agents are as follows: amikacin, 87%; ceftazadime, 88%; ciprofloxacin, 100%; gentamicin, 58%; imipenem, 89% and tobramycin, 99%. Against Acinetobacter calcoaceticusfor the same agents, the results were 100, 56, 100, 94, 100 and 94%, respectively. Hoban et al.7 tested 138 P. aeruginosa isolates from respiratory tract specimens collected from 18 Canadian medical centres and found 90% to be susceptible to ciprofloxacin. In the same study, 103 P. aeruginosa isolates were also collected from urinary tract specimens and 91% were found to be susceptible to ciprofloxacin. Hoban and Jones8 tested 500 P. aeruginosa isolates collected from five medical centres (four in the USA, one in Canada) and found 85% to be susceptible to ciprofloxacin and 89% susceptible to gentamicin. Blondeau et al.9 tested 390 isolates of P. aeruginosa, collected from 15 Canadian medical centres, to 19 antimicrobial agents. Three agents are comparable with this current study. In the study by Blondeau et al.9, 92% of isolates were susceptible to ceftazadime, compared with 79% to ciprofloxacin and 89% to imipenem. Forty-nine Acinetobacter spp. and 57 S. maltophilia isolates were also tested in their study.9 Susceptibility to ceftazadime, ciprofloxacin and imipenem for Acinetobacter spp. was 88, 78 and 98%, respectively, while for S. maltophiliait was 58, 18 and 2%, respectively. Finally, Forward et al.10 tested 1240 P. aeruginosa isolates, 201 Acinetobacterspp. and 244 S. maltophilia isolates, collected from 61 Canadian hospitals, to eight antimicrobial agents—three of which are comparable with this current study. For P. aeruginosa, susceptibility rates for ceftazadime, gentamicin and piperacillin/tazobactam were 95, 88 and 96%, respectively, compared with 54, 69 and 27%, respectively, for S. maltophilia, and 88, 94 and 90%, respectively, for Acinetobacter spp.

While susceptibility data for these organisms have been published for the majority of antimicrobial agents tested in this study, only limited Canadian data exists for cefepime. Scriver et al.11 collected and tested 228 nosocomial P. aeruginosa isolates from 10 Canadian medical centres. The following resistance rates were determined: ceftazidime, 11.7%; cefepime, 28.6%; piperacillin/trazobactam, 10.9%; imipenem, 23.3%; gentamicin, 15.1%; tobramycin, 2.7% and ciprofloxacin, 4.8%. The susceptibility results recorded in this study are similar (within 2.5–2.6%) to those reported by Scriver et al.11 for ceftazidime, piperacillin/tazobactam and tobramycin, but not for the remaining agents. With the exception of ciprofloxacin, all other agents had higher resistance rates to comparable agents in the study of Scriver et al. versus this current investigation. The most dramatic differences seen between these studies were for cefepime (28.6% resistant versus 6.4% in our study) and imipenem (23.3% versus 5.2%). This difference may relate simply to the observation that our study involved collection of isolates from both in-patients and out-patients while the work of Scriver et al. was based on nosocomial isolates only. Also, the difference in the number of isolates tested, 1466 versus 228, may also account for some of the differences in resistance.

This current study is important because a large number of isolates have been tested against a wide variety of antimicrobial agents likely to be suitable for treatment of patients infected with non-fermentative Gram-negative bacilli—especially P. aeruginosa. To our knowledge, this is the largest Canadian study to date that has examined the in-vitro susceptibility of cefepime against non-fermentative Gram-negative bacilli. Our data suggest that cefepime is a useful agent for treating patients infected with P. aeruginosa and Acinetobacter spp.; however, its use, where infection by S. maltophiliaoccurs, is unlikely.


    Notes
 
* Correspondence address. Department of Clinical Microbiology, Royal Univeristy Hospital, 103 Hospital Avenue, Saskatoon, Saskatchewan, Canada S7N0W8. Tel: +1-306-655-6943; Fax: +1-306-655-6947; E-mail: blondeauj{at}sdh.sk.ca Back


    References
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
1 . Botzenhart, K. & Doring, G. (1993). Etiology and epidemiology of Pseudomonas aeruginosa. In Pseudomonas aeruginosa as an Opportunistic Pathogen (Camapa, M., Bendinell, M. & Friedman, H., Eds), pp. 1–18. Plenum Press, New York, NY.

2 . Pollack, M. (1990). Pseudomonas aeruginosa. In Principles and Practices of Infectious Diseases, 3rd edn (Mandell, G. L., Douglas, R. G. & Bennett, J. E., Eds), pp. 1673–91. Churchill Livingston, New York, NY.

3 . Clarke, A. M., Zemcov, S. J. & Wright, J. M. (1985). HR 810 and BMY-28142, two new cephalosporins with broad-spectrum activity: an in-vitro comparison with other ß-lactam antibiotics. Journal of Antimicrobial Chemotherapy 15, 305–10.[Abstract]

4 . Tsuji, A., Maniatis, A., Bertram, M. A. & Young, L. S. (1985). In-vitro activity of BMY-28142 in comparison with those of other ß-lactam antimicrobial agents. Antimicrobial Agents and Chemotherapy 27, 515–9.[ISI][Medline]

5 . National Committee for Clinical Laboratory Standards. (1997). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically—Fourth Edition: Approved Standard M7-A4. NCCLS, Wayne, PA.

6 . Chamberland, S., L'Ecuyer, J., Lessard, C., Bernier, M., Provencher, P., Bergeron, M. G. et al. (1992). Antibiotic susceptibility profiles of 941 Gram-negative bacteria isolated from septicemic patients throughout Canada. The Canadian Study Group. Clinical Infectious Diseases 15, 615–28.[ISI][Medline]

7 . Hoban, D. J. & Jones, R. N. (1995). Canadian ofloxacin susceptibility study: a comparative study from 18 medical centers. Canadian Ofloxacin Study Group. Chemotherapy 41, 34–8.[ISI][Medline]

8 . Hoban, D. J. & Jones, R. N. (1993). The North American component (USA, Canada) of an international comparative MIC trial monitoring ofloxacin resistance. Drugs 45, Suppl. 3, 167–9.

9 . Blondeau, J. M., Yaschuk, Y., Smith, J. A., Noble, M. A., Kibsey, P., Horsman, G. B. et al. (1996). Canadian ciprofloxacin susceptibility study: comparative study from 15 medical centers. Antimicrobial Agents and Chemotherapy 40, 1729–32.[Abstract]

10 . Forward, K. R., Low, D. E., Laverdiere, M., Rennie, R., Simor, A. E. & Franks, P. A. (1997). Study of the comparative activity of piperacillin/tazobactam with currently available antibiotics against 8206 aerobic isolates. Canadian Journal of Infectious Diseases 8, 147–53.

11 . Scriver, S. R. & Low, D. E. (1995). Comparative activity of several antimicrobial agents against nosocomial Gram-negative rods isolated across Canada. Canadian Journal of Infectious Diseases 6, 76–82.

Received 4 November 1998; returned 29 March 1999; revised 19 May 1999; accepted 1 June 1999