Skip to main page content

• HOME
• Current Issue
• Archive
• Alerts
• About ASM
• Contact us
• Tech Support
• Journals.ASM.org

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhanel, G. G. Articles by Hoban, D. J. Search for Related Content PubMed PubMed Citation Articles by Zhanel, G. G. Articles by Hoban, D. J.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, June 2003, p. 1875-1881, Vol. 47, No. 6
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.6.1875-1881.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Antimicrobial Resistance in Haemophilus influenzae and Moraxella catarrhalis Respiratory Tract Isolates: Results of the Canadian Respiratory Organism Susceptibility Study, 1997 to 2002

George G. Zhanel,^1,2,3 Lorraine Palatnick,³ Kimberly A. Nichol,^1,3 Don E. Low,⁴ The CROSS Study Group, and Daryl J. Hoban^1,3*

Department of Medical Microbiology, Faculty of Medicine, University of Manitoba,¹ Departments of Medicine,² Clinical Microbiology, Health Sciences Centre, Winnipeg, Manitoba,³ Mount Sinai Hospital, Toronto, Ontario, Canada⁴

Received 30 September 2002/ Returned for modification 11 February 2003/ Accepted 8 March 2003

Top Abstract Introduction Materials and Methods Results Discussion References

 
A total of 7,566 unique patient isolates of Haemophilus influenzae and 2,314 unique patient isolates of Moraxella catarrhalis were collected between October 1997 and June 2002 from 25 medical centers in 9 of the 10 Canadian provinces. Among the 7,566 H. influenzae isolates, 22.5% produced ß-lactamase, while 92.4% of the 2,314 M. catarrhalis isolates produced ß-lactamase. The incidence of ß-lactamase-producing H. influenzae isolates decreased significantly over the 5-year study period, from 24.2% in 1997-1998 to 18.6% in 2001-2002 (P < 0.01). The incidence of ß-lactamase-producing M. catarrhalis isolates did not change over the study period. The overall rates of resistance to amoxicillin and amoxicillin-clavulanate for H. influenzae were 19.3 and 0.1%, respectively. The rank order of cephalosporin activity based on the MICs at which 90% of isolates were inhibited (MIC₉₀s) was cefotaxime > cefixime > cefuroxime > cefprozil > cefaclor. On the basis of the MICs, azithromycin was more active than clarithromycin (14-OH clarithromycin was not tested); however, on the basis of the NCCLS breakpoints, resistance rates were 2.1 and 1.6%, respectively. Rates of resistance to other agents were as follows: doxycycline, 1.5%; trimethoprim-sulfamethoxazole, 14.2%; and chloramphenicol, 0.2%. All fluoroquinolones tested, including the investigational fluoroquinolones BMS284756 (garenoxacin) and ABT-492, displayed potent activities against H. influenzae, with MIC₉₀s of ≤0.03 µg/ml. The MIC₉₀s of the investigational ketolides telithromycin and ABT-773 were 2 and 4 µg/ml, respectively, and the MIC₉₀ of the investigational glycylcycline GAR-936 (tigecycline) was 4 µg/ml. Among the M. catarrhalis isolates tested, the resistance rates derived by using the NCCLS breakpoint criteria for H. influenzae were <1% for all antibiotics tested except trimethoprim-sulfamethoxazole (1.5%). In summary, the incidence of ß-lactamase-positive H. influenzae strains in Canada is decreasing (18.6% in 2001-2002), while the incidence of ß-lactamase-positive M. catarrhalis strains has remained constant (90.0% in 2001-2002).

Top Abstract Introduction Materials and Methods Results Discussion References

 
Haemophilus influenzae and Moraxella catarrhalis are recognized as important causes of community-acquired respiratory infections, including community-acquired pneumonia, acute exacerbations of chronic bronchitis, acute sinusitis, and acute otitis media (1, 5, 9, 13, 14, 22). Due to the extensive use of the protein-conjugated type b capsular polysaccharide vaccine in developed countries, H. influenzae infections are caused by non-type b strains (7, 8, 10, 23). As community-acquired respiratory tract infections are treated empirically (with no knowledge of the antibiotic susceptibilities of a specific isolate from a patient), knowledge of present and local resistance rates is essential in determining effective therapy (1, 14). Ongoing systematic surveillance studies provide clinicians with knowledge of these resistance rates, allowing determination of the optimal treatment.

In a study conducted in 1997 and 1998 (23), we described the prevalences of ß-lactamase-producing H. influenzae and M. catarrhalis isolates to be 24.0 and 94.2%, respectively. The present report describes the results of an ongoing annual study, the Canadian Respiratory Organism Susceptibility Study (CROSS) (22, 23). This study included isolates from 25 medical centers from all regions of Canada that participated from 1997 to 2002 inclusive. The purpose of this study was to assess the incidence of ß-lactamase production in H. influenzae and M. catarrhalis isolates over a 5-year study period. In addition, the activities of 25 antimicrobials against these isolates were assessed.

Top Abstract Introduction Materials and Methods Results Discussion References

 
Between October 1997 and June 2002, a total of 7,566 unique patient isolates of H. influenzae and 2,314 unique patient isolates of M. catarrhalis were collected from 25 medical centers in major population centers in 9 of the 10 Canadian provinces. Each study site was asked to collect and submit 100 H. influenzae isolates and 30 M. catarrhalis isolates per year (one isolate per patient). All isolates were deemed to be significant by individual laboratory protocols and were collected from respiratory tract specimens only (22, 23). Organisms from each center were identified as H. influenzae by the criteria used at the local site and, where necessary, were further identified by the coordinating laboratory (Health Sciences Centre, Winnipeg, Manioba, Canada) by standard methodologies such as colonial morphology, Gram staining characteristics, and X- and V-factor requirements. Similarly, colonial morphology, Gram staining characteristics, as well as oxidase and DNase production were used by the coordinating laboratory to confirm the identity of each M. catarrhalis isolate. All isolates were sent to the coordinating laboratory on Amies semisolid transport medium containing charcoal (Difco Laboratories, Detroit, Mich.). Each isolate was then stocked in skim milk and stored at -70°C in preparation for antibiotic susceptibility testing. Production of ß-lactamase was assessed by use of a cefinase disk test (Becton Dickinson Microbiology Systems, Cockeysville, Md.). Twenty-five antimicrobial agents (amoxicillin, amoxicillin-clavulanate, cefotaxime, cefuroxime, cefaclor, cefprozil, cefixime, imipenem, azithromycin, clarithromycin, telithromycin, doxycycline, trimethoprim-sulfamethoxazole [TMP-SMX], ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, gemifloxacin, chloramphenicol, linezolid, ertapenem, ABT-773, ABT-492, BMS284756 [garenoxacin], and GAR-936 [tigecycline]) were obtained as laboratory-grade powders from the respective manufacturers. Stock solutions were prepared and dilutions were made by the National Committee for Clinical Laboratory Standards (NCCLS) method (15, 16). Following two subcultures from frozen stocks, antimicrobial susceptibilities were determined by the NCCLS-approved broth microdilution method (15, 16). The plates were incubated in ambient air at 35°C for 24 h prior to reading of the results. MICs were interpreted by using NCCLS breakpoints (16), and colony counts were determined periodically to confirm the inocula. Quality control was ensured by using appropriate quality control organisms from the American Type Culture Collection.

Top Abstract Introduction Materials and Methods Results Discussion References

 
The demographics of the patients whose isolates were used in CROSS are described in Table 1. The numbers of H. influenzae and M. catarrhalis isolates recovered from respiratory sources varied from 1,107 to 2,166 and 341 to 643 isolates per year, respectively, over the 5-year study period. In each year of the study, ≥90% of the isolates were isolated from sputum specimens, bronchoalveolar lavage specimens, or endotracheal secretions. Approximately 55 to 61% and 39 to 45% of the isolates were obtained from inpatients and outpatients, respectively, and approximately 40 and 60% of the isolates submitted were from females and males, respectively. The breakdowns of the isolates submitted by age group were approximately 22 to 24% from individuals ≤16 years of age, 33 to 39% from individuals 17 to 64 years of age, and 38 to 43% from individuals ≥65 years of age. Table 1 indicates that the demographics of the patients from whom isolates were recovered did not change over the 5-year study period.

View this table: [in this window] [in a new window]

TABLE 1. Isolation of H. influenzae and M. catarrhalis from 1997 to 2002 by specimen source, service, gender, and age

Table 2 describes the incidence of ß-lactamase-producing H. influenzae and M. catarrhalis isolates over the 5-year study period. Among the collection of 7,566 H. influenzae isolates, 22.5% were ß-lactamase positive, while 92.4% of the 2,314 M. catarrhalis isolates were ß-lactamase positive. The incidence of ß-lactamase-producing H. influenzae isolates decreased significantly over the 5-year study period, from 24.2% in 1997-1998 to 18.6% in 2001-2002 (P < 0.01). In contrast, the incidence of ß-lactamase-producing M. catarrhalis isolates did not change over the same period (94.0% in 1997-1998 to 90.0% in 2001-2002; P = 0.75). Table 2 also compares the incidence of ß-lactamase-producing H. influenzae and M. catarrhalis isolates by province or region of Canada. The major observation arising from these data was that considerable variation in the prevalence of ß-lactamase-producing H. influenzae and M. catarrhalis isolates occurred both within and between each province or region in any given year. General trends were also noted, including the observation that the incidence of ß-lactamase-producing H. influenzae isolates declined in all regions of the country over the 5-year study period. In addition, the incidence of ß-lactamase-producing M. catarrhalis isolates remained relatively unchanged in all regions of the country throughout the study period.

View this table: [in this window] [in a new window]

TABLE 2. Incidence of ß-lactamase production by H. influenzae and M. catarrhalis isolates collected across Canada from 1997 to 2002

The in vitro activities of 25 antibiotics against 7,566 H. influenzae isolates are presented in Table 3. The overall rates of resistance to amoxicillin and amoxicillin-clavulanate for H. influenzae were 19.3 and 0.1%, respectively. The proportions of strains found to be ß-lactamase negative but amoxicillin resistant (BLNAR) and ß-lactamase positive and amoxicilin-clavulanate resistant (BLPACR) were 0.1 and 0.2%, respectively. The rank order of cephalosporin activity on the basis of the MICs at which 90% of isolates are inhibited (MIC₉₀s) was cefotaxime > cefixime > cefuroxime > cefprozil > cefaclor. On the basis of the present NCCLS breakpoints, the overall proportions of isolates found to be resistant to cefotaxime, cefixime, cefuroxime, cefprozil, and cefaclor were 0.2, 0.3, 0.5, 1.0, and 7.1%, respectively. No imipenem-resistant strains were isolated. On the basis of the MICs, azithromycin was more active than clarithromycin (14-OH clarithromycin was not tested); however, on the basis of the NCCLS breakpoints, resistance rates were 2.1 and 1.6%, respectively. Rates of resistance to other agents were as follows: doxycycline, 1.5%; TMP-SMX, 14.2%; and chloramphenicol, 0.2%. All fluoroquinolones tested, including the investigational fluoroquinolones BMS284756 (garenoxacin) and ABT-492, displayed potent activities against the H. influenzae isolates, with MIC₉₀s of ≤0.03 µg/ml. The MIC₉₀s of the investigational ketolides telithromycin and ABT-773 were 2 and 4 µg/ml, respectively. Linezolid demonstrated limited activity, and the MIC₉₀ of the investigational glycylcycline GAR-936 (tigecycline) was 4 µg/ml. The distributions of the MICs of selected antibiotics for H. influenzae are displayed in Table 4. As can be observed, a shift to the left in the MIC (a decrease in the MIC) of amoxicillin concurs with the finding that the incidence of ß-lactamase-producing H. influenzae is decreasing. No other MIC shift patterns were observed.

View this table: [in this window] [in a new window]

TABLE 3. Antibiotic susceptibilities of 7,566 H. influenzae isolatesa stratified by the presence or absence of ß-lactamase production

View this table: [in this window] [in a new window]

TABLE 4. Distribution of MICs of selected antibiotics for H. influenzae

For M. catarrhalis, the rates of resistance derived by using the NCCLS breakpoint criteria for H. influenzae were <1% for all antibiotics tested except amoxicillin and TMP-SMX (1.5%) (Table 5). No strains were found to be resistant to amoxicillin-clavulanate. The rank order of the activities of the cephalosporins on the basis of the MIC₉₀s was cefotaxime = cefixime > cefuroxime = cefprozil > cefaclor. On the basis of present NCCLS breakpoints for H. influenzae, the overall proportions of isolates found to be resistant to cefotaxime, cefixime, cefuroxime, cefprozil, and cefaclor were 0, 0, 0.3, 0.2, and 0.5%, respectively. No imipenem-resistant strains were isolated. On the basis of the MICs, azithromycin and clarithromycin (14-OH clarithromycin was not tested) were equipotent, and no resistant strains were isolated. The rates of resistance to the other agents tested were as follows: doxycycline, 0.2%; TMP-SMX, 1.5%; and chloramphenicol, 0%. All fluoroquinolones tested, including the investigational fluoroquinolones BMS284756 (garenoxacin) and ABT-492, displayed potent activities against M. catarrhalis, with MIC₉₀s of ≤0.06 µg/ml. The MIC₉₀s of the investigational ketolides telithromycin and ABT-773 were 0.12 µg/ml. Linezolid demonstrated moderate activity, and the MIC₉₀ of the investigational glycylcycline GAR-936 (tigecycline) was 0.5 µg/ml.

View this table: [in this window] [in a new window]

TABLE 5. Antibiotic susceptibilities of 2,314 M. catarrhalis isolatesa

Top Abstract Introduction Materials and Methods Results Discussion References

 
CROSS is an ongoing longitudinal surveillance program that studies the incidence of antibiotic resistance in respiratory pathogens across all regions of Canada (22, 23). As such, it represents a unique opportunity for comparison of rates of antibiotic resistance among isolates from various geographically distributed medical centers, among isolates from patients with different demographic profiles, and by antimicrobial class. From 1997 to 2002, the same 25 medical centers participated in this study. Each year, large numbers of respiratory tract isolates of H. influenzae (1,107 to 2,166) and M. catarrhalis (341 to 643) were isolated and collected during the same time of year (during the winter months). Over the 5-year study period, study demographics remained constant; the specimen type was primarily sputum specimens, bronchoalveolar lavage specimens, and endotracheal secretions. The service breakdown was approximately 55 to 61% inpatients and 39 to 45% outpatients, while the gender breakdown was approximately 40 to 41% female and 59 to 60% male. Breakdown of isolates by patient age was approximately as follows: ≤16 years of age, 20%; 17 to 64 years of age, 40%; and ≥65 years of age, 40% (Table 1).

This study shows that the incidence of ß-lactamase-producing H. influenzae decreased from 24.2% in 1997-1998 to 18.6% in 2001-2002 (Table 2). This finding was confirmed with a shift to the left in the MICs of amoxicillin (Table 4). Previously published studies that have assessed the prevalence of ß-lactamase-producing H. influenzae in Canada have reported prevalences of 31.3% (1997), 28.4% (1992-1993), 26.0% (1991), and 16.9% (1985 to 1987) (8, 10, 17, 19, 23). Numerous studies assessing the prevalence of ß-lactamase-producing H. influenzae isolates in the United States have also been published (7, 8, 10-12, 18). A 1994-1995 study examining the prevalence of ß-lactamase-positive H. influenzae isolates among 1,537 clinical isolates obtained from 30 medical centers in the United States reported a prevalence of 36.4% (7). Doern et al. (8) studied the prevalence of ß-lactamase-producing H. influenzae isolates in the United States in 1997 as part of the SENTRY program, and they reported a prevalence of 34.2%. Doern et al. (8) further commented that the incidence of ß-lactamase-producing H. influenzae strains in North America had leveled off at approximately 30%. In this study, we report that the incidence of ß-lactamase-positive H. influenzae isolates is declining in Canada. One reason why this may be occurring is that Canadian clinicians in outpatient practice are using fewer oral ß-lactams, such as penicillin, amoxicillin, cephalosporins, and amoxicillin-clavulanate, and are preferentially prescribing more new macrolides, such as azithromycin and clarithromycin, and fluoroquinolones, such as ciprofloxacin, levofloxacin, gatifloxacin, and moxifloxacin (3).

As in previous studies, we noticed a marked variation in the prevalence of ß-lactamase-producing H. influenzae isolates per province or region from year to year (Table 2). This underscores the importance of performing ongoing surveillance studies on an annual basis so as not to overreact to an increase or a decrease in resistance rates over a 1-year period. It is only through systematic, annual, and ongoing surveillance that one can truly assess the patterns of resistance over time and understand the impacts of interventions on antibiotic resistance rates. Although regional variation occurred, some general patterns were observed. This included the observation that the highest prevalence of ß-lactamase-producing H. influenzae isolates occurred in the Maritime provinces and Quebec, while the lowest prevalence of ß-lactamase-producing H. influenzae isolates occurred in western Canada.

The proportions of strains found to be BLNAR and BLPACR were 0.1 and 0.2%, respectively (Table 3). Doern et al. (7) have also previously reported a low prevalence of BLNAR (2.5%) and BLPACR (1.1%) strains, and it appears that the incidence of these isolates is not increasing in North America. Although some have questioned the clinical predictive value of the MICs of oral cephalosporins used to treat localized respiratory tract infections caused by H. influenzae (4), the most active cephalosporins included cefotaxime, cefixime, cefuroxime, and cefprozil, with the rate resistance to cefaclor being 7.1%. Among the new macrolides, the rates of resistance to azithromycin and clarithromycin were 2.1 and 1.6%, respectively. The rates of resistance to the other agents were relatively low, with the rates of resistance to doxycycline, TMP-SMX, and chloramphenicol being 1.5, 14.2, and 0.2%, respectively (Table 3). These rates did not change over the 5-year study period. As would be expected (24), all of the fluoroquinolones consistently possessed excellent activities against H. influenzae. In fact, only one fluoroquinolone-resistant H. influenzae strain was isolated over the 5-year study period.

The prevalence of ß-lactamase-producing M. catarrhalis isolates was 92.4% and did not change over the study period (Table 2). This is consistent with the findings of other North American surveillance studies that have assessed the prevalence of ß-lactamase-producing M. catarrhalis isolates (6, 10, 12, 18, 20, 23), including the SENTRY study, which reported prevalences of ß-lactamase-positive M. catarrhalis isolates of 92.0% in the United States and 92.2% in Canada (8). As with H. influenzae, significant year-to-year variations in resistance were observed between provinces or regions, again emphasizing the importance of annual ongoing surveillance to assess long-term patterns of resistance. With the exception of TMP-SMX (resistance rate, 1.5%), the rates resistance of M. catarrhalis isolates to antibiotics other than amoxicillin were very low (Table 5). As reported previously (8), many ß-lactamase-producing M. catarrhalis strains display only low-level resistance to amoxicillin, likely because of low-level expression of the BRO-2 enzyme (2, 20, 21).

In conclusion, the mean prevalence of ß-lactamase-producing H. influenzae isolates was 22.5% over the study period and decreased significantly from 24.2 to 18.6% over the 5 years. The mean prevalence of ß-lactamase-producing M. catarrhalis isolates was 92.4% and did not change significantly over the 5-year study period.

 
CROSS surveillance sites and investigators were as follows: Victoria General Hospital, Victoria, British Columbia, P. Kibsey; Vancouver Hospital, Vancouver, British Columbia, D. L. Roscoe; Calgary Lab Services, Calgary, Alberta, D. Church; University of Alberta Hospitals, Edmonton, Alberta, R. P. Rennie; Regina General Hospital, Regina, Saskatchewan, E. Thomas; Royal University Hospital, Saskatoon, Saskatchewan, J. M. Blondeau; St. Boniface Hospital, Winnipeg, Manitoba, G. K. M. Harding; Health Sciences Centre, Winnipeg, Manitoba, D. J. Hoban and G. G. Zhanel; St. Joseph's Hospital, Hamilton, Ontario, D. Groves; Hamilton Health Sciences Centre, Hamilton, Ontario, F. Smaill; McMaster, Hamilton, Ontario, M. Loeb; Mount Sinai Hospital, Toronto, Ontario, D. Low; London Health Sciences Centre, London, Ontario, Z. Hussain; Ottawa General Hospital, Ottawa, Ontario, K. Ramotar; Children's Hospital of Eastern Ontario, Ottawa, Ontario, F. Chan; Montreal Children's Hospital, Montreal, Quebec, J. McDonald; Montreal Jewish General Hospital, Montreal, Quebec, A. Dascal; Maisonneuve-Rosemont, Montreal, Quebec, M. Laverdiere; Montreal General Hospital, Montreal, Quebec, V. Loo; Hotel-Dieu of Montreal, Montreal, Quebec, M. Poisson; Universitaire de Sante de l'Estrie, Sherbrooke, Quebec, J. Dubois; South East Health Care Corp., Moncton, New Brunswick, M. Kuhn; St. John Regional, St. John, New Brunswick, G. Hardy and Y. Yaschuk; Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, K. Forward and R. Davidson; and Queen Elizabeth Hospital, Charlottetown, Prince Edward Island, L. Abbott.

We thank M. Wegrzyn for expert secretarial assistance. Funding for the CROSS study was provided in part by Abbott Laboratories Ltd., Astra Zeneca, Aventis Pharma, Bayer Inc., Bristol-Myers Squibb Pharmaceutical Group, GlaxoSmithKline, Janssen-Ortho Inc., Merck Frosst Canada & Co., Pharmacia Upjohn, Pfizer, and Wyeth.

 
* Corresponding author. Mailing address: Clinical Microbiology, Health Sciences Centre, MS673-820 Sherbrook St., Winnipeg, Manitoba R3A 1R9, Canada. Phone: (204) 787-1191. Fax: (204) 787-4699. E-mail: dhoban{at}hsc.mb.ca.

Top Abstract Introduction Materials and Methods Results Discussion References

 

1
1. Bartlett, J. G., R. F. Breiman, L. A. Mandell, and T. M. File, Jr. 1998. Community-acquired pneumonia in adults: guidelines for management. Clin. Infect. Dis. 26:811-838.[Medline]
2
2. Bootsma, H. J., H. van Dijk, J. Verhoef, A. Fleer, and F. R. Mooi. 1996. Molecular characterization of the BRO ß-Lactamase of Moraxella (Branhamella) catarrhalis. Antimicrob. Agents Chemother. 40:966-972.[Abstract]
3
3. Carrie, A., and G. G. Zhanel. 2000. Antibiotic use in a Canadian province. Ann. Pharmacother. 34:459-464.[Abstract]
4
4. Dagan, R., O. Abramson, E. Leibovitz, D. Greenberg, R. Lang, S. Goshen, P. Yagupsky, A. Lieberman, and D. M. Fliss. 1997. Bacteriologic response to oral cephalosporins: are established breakpoints appropriate in the case of acute otitis media? J. Infect. Dis. 176:1253-1259.[Medline]
5
5. Del Beccaro, M. A., P. M. Mendelman, and A. F. Inglis. 1992. Bacteriology of acute otitis media: a new perspective. J. Pediatr. 120:81-84.[CrossRef][Medline]
6
6. Doern, G. V., A. B. Brueggemann, G. Pierce, T. Hogan, H. P. Holley, and A. Rauch. 1996. Prevalence of antimicrobial resistance among 723 outpatient clinical isolates of Moraxella catarrhalis in the United States in 1994 and 1995: results of a 30-center national surveillance study. Antimicrob. Agents Chemother. 40:2884-2886.[Abstract]
7
7. Doern, G. V., A. B. Brueggemann, G. Pierce, H. P. Holley, and A. Rauch. 1997. Antibiotic resistance among clinical isolates of Haemophilus influenzae in the United States in 1994 and 1995 and detection of ß-lactamase-positive strains resistant to amoxicillin-clavulanate: results of a national multicenter surveillance study. Antimicrob. Agents Chemother. 41:292-297.[Abstract]
8
8. Doern, G. V., R. N. Jones, M. A. Pfaller, K. Kugler, and The SENTRY Participants Group. 1999. Haemophilus influenzae and Moraxella catarrhalis from patients with community-acquired respiratory tract infections: antimicrobial susceptibility patterns from the SENTRY antimicrobial surveillance program (United States and Canada, 1997). Antimicrob. Agents Chemother. 43:385-389.[Abstract/Free Full Text]
9
9. Farmer, T., and C. Reading. 1982. ß-Lactamases of Branhamella catarrhalis and their inhibition by clavulanic acid. Antimicrob. Agents Chemother. 21:506-508.[Abstract/Free Full Text]
10
10. Hoban, D. J., G. V. Doern, A. C. Fluit, M. Roussel-Delvallez, and R. N. Jones. 2001. Worldwide prevalence of antimicrobial resistance in Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis in the Sentry antimicrobial surveillance program 1997-99. Clin. Infect. Dis. 32(Suppl. 2):81-93.
11
11. Jones, R. N., M. R. Jacobs, J. A. Washington, and M. A. Pfaller. 1997. A 1994-95 survey of Haemophilus influenzae susceptibility to ten orally administered agents: a 187 clinical laboratory center sample in the United States. Diagn. Microbiol. Infect. Dis. 27:75-83.[CrossRef][Medline]
12
12. Jorgensen, J. H., G. V. Doern, L. A. Maher, A. W. Howell, and J. S. Redding. 1990. Antimicrobial resistance among respiratory isolates of Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae in the United States. Antimicrob. Agents Chemother. 34:2075-2080.[Abstract/Free Full Text]
13
13. Low, D. E. 1998. Resistance and treatment implications: pneumococcus, Staphylococcus aureus and gram-negative rods. Infect. Dis. Clin. N. Am. 3:613-630.
14
14. Mandell, L. A., T. J. Marrie, R. F. Grossman, A. W. Chow, R. H. Hyland, and the Canadian Community Acquired Pneumonia Working Group. 2000. Canadian guidelines for the initial management of community acquired pneumonia: an evidence based update of the Canadian Infectious Diseases Society and the Canadian Thoracic Society. Clin. Infect. Dis. 31:383-921.
15
15. National Committee for Clinical Laboratory Standards. 2000. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved standard M7-A5, 5th ed. National Committee for Clinical Laboratory Standards, Wayne, Pa.
16
16. National Committee for Clinical Laboratory Standards. 2002. Performance standards for antimicrobial susceptibility testing: supplemental tables. M100-S12. National Committee for Clinical Laboratory Standards, Wayne, Pa.
17
17. Scriver, S. R., S. L. Walmsley, C. L. Kau, D. J. Hoban, J. Brunton, A. McGeer, the Canadian Haemophilus Study Group, and D. E. Low. 1994. Determination of antimicrobial susceptibilities of Canadian isolates of Haemophilus influenzae and characterization of their ß-lactamases. Antimicrob. Agents Chemother. 38:1678-1680.[Abstract/Free Full Text]
18
18. Thornsberry, C., P. T. Ogilvie, H. P. Holley, and D. F. Sahm. 1999. Survey of susceptibilities of Streptococcus pneumoniae, Haemophilus influenzae, and Moxarella catarrhalis isolates to 26 antimicrobial agents: a prospective U.S. study. Antimicrob. Agents Chemother. 43:2616-2623.
19
19. Tremblay, L. D., J. L'Ecuyer, P. Provencher, the Canadian Haemophilus Study Group, and M. G. Bergeron. 1990. Susceptibility of Haemophilus influenzae to antimicrobial agents used in Canada. Can. Med. Assoc. J. 143:895-901.[Abstract]
20
20. Wallace, R. J., D. R. Nash, and V. A. Steingrube. 1990. Antibiotic susceptibilities and drug resistance in Moraxella (Branhamella) catarrhalis. Am. J. Med. 88:5S-46S.
21
21. Wallace, R. J., V. A. Steingrube, D. R. Nash, D. G. Hollis, C. Flanagan, B. A. Brown, A. Labidi, and R. E. Weaver. 1989. BRO ß-lactamases of Branhamella catarrhalis and Moraxella subgenus Moraxella, including evidence for chromosomal ß-lactamase transfer by conjugation in B. catarrhalis, M. nonliquefaciens and M. lacunata. Antimicrob. Agents Chemother. 33:1845-1854.[Abstract/Free Full Text]
22
22. Zhanel, G. G., J. A. Karlowsky, L. Palatnick, L. Vercaigne, D. E. Low, the Canadian Respiratory Infection Study Group, and D. J. Hoban. 1999. Prevalence of antimicrobial resistance in respiratory tract isolates of Streptococcus pneumoniae: results of a Canadian national surveillance study. Antimicrob. Agents Chemother. 43:2504-2509.[Abstract/Free Full Text]
23
23. Zhanel, G. G., J. A. Karlowsky, D. E. Low, and D. J. Hoban. 2000. Antibiotic resistance in respiratory tract isolates of Haemophilus influenzae and Moraxella catarrhalis collected from across Canada in 1997-1998. J. Antimicrob. Chemother. 45:655-662.
24
24. Zhanel, G. G., K. Ennis, L. Vercaigne, A. Walkty, A. S. Gin, J. Embil, H. Smith, and D. J. Hoban. 2002. The new fluoroquinolones: focus on respiratory infections. Drugs 62:13-59.[CrossRef][Medline]

---

Antimicrobial Agents and Chemotherapy, June 2003, p. 1875-1881, Vol. 47, No. 6
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.6.1875-1881.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Bulitta, J. B., Landersdorfer, C. B., Kinzig, M., Holzgrabe, U., Sorgel, F. (2009). New Semiphysiological Absorption Model To Assess the Pharmacodynamic Profile of Cefuroxime Axetil Using Nonparametric and Parametric Population Pharmacokinetics. Antimicrob. Agents Chemother. 53: 3462-3471 [Abstract] [Full Text]  
• Sill, M. L., Tsang, R. S. W. (2008). Antibiotic Susceptibility of Invasive Haemophilus influenzae Strains in Canada. Antimicrob. Agents Chemother. 52: 1551-1552 [Abstract] [Full Text]  
• Pankey, G. A. (2005). Tigecycline. J Antimicrob Chemother 56: 470-480 [Abstract] [Full Text]  
• Kasbekar, N., Acharya, P. S. (2005). Telithromycin: The first ketolide for the treatment of respiratory infections. Am J Health Syst Pharm 62: 905-916 [Abstract] [Full Text]  
• Betriu, C., Gomez, M., Rodriguez-Avial, I., Culebras, E., Picazo, J. J. (2005). In vitro activity of tigecycline against ampicillin-resistant Haemophilus influenzae isolates. J Antimicrob Chemother 55: 809-810 [Full Text]  
• Conte, J. E. Jr., Golden, J. A., Kipps, J., Zurlinden, E. (2004). Steady-State Plasma and Intrapulmonary Pharmacokinetics and Pharmacodynamics of Cethromycin. Antimicrob. Agents Chemother. 48: 3508-3515 [Abstract] [Full Text]  
• Reinert, R. R. (2004). Clinical efficacy of ketolides in the treatment of respiratory tract infections. J Antimicrob Chemother 53: 918-927 [Abstract] [Full Text]  
• Morrissey, I., Tillotson, G. (2004). Activity of gemifloxacin against Streptococcus pneumoniae and Haemophilus influenzae. J Antimicrob Chemother 53: 144-148 [Abstract] [Full Text]  
• Waites, K. B., Crabb, D. M., Duffy, L. B. (2003). Comparative In Vitro Susceptibilities and Bactericidal Activities of Investigational Fluoroquinolone ABT-492 and Other Antimicrobial Agents against Human Mycoplasmas and Ureaplasmas. Antimicrob. Agents Chemother. 47: 3973-3975 [Abstract] [Full Text]  

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhanel, G. G. Articles by Hoban, D. J. Search for Related Content PubMed PubMed Citation Articles by Zhanel, G. G. Articles by Hoban, D. J.