Annual Report: Table 1. Antimicrobial Susceptibility Results for 2,488 Isolates of S. pneumoniae Collected Nationally, 2005 MIC (µg/ml)

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Streptococcus pneumoniae Annual Report: 5 In 5, a total of, isolates of pneumococci were collected from 59 clinical microbiology laboratories across Canada. Of these, 733 (9.5%) were isolated from blood cultures or CSF, 95 (.1%) from lower respiratory tract specimens, 35 (1.3%) from conjunctival swabs, 19 (.%) from ear swabs, 1 (.9%) from cerebrospinal fluid, and 11 (.5%) from other sites. Of the,79 isolates for which ages of patients were available, 5 (.%) were from patients <17 years of age, 1 (.%) were from patients between 17 to years of age, and 13 (3.%) were from patients 5 years of age. The results of in vitro susceptibility testing are found in Tables 1 and below. Table 1. Antimicrobial Susceptibility Results for, Isolates of S. pneumoniae Collected Nationally, 5 MIC (µg/ml) Intermediate Resistant 5s 9s Range No. (%) No. (%) Penicillin..5. - 1 (.5) 11 (.) Erythromycin.1 1.1-5 (.) 7 (19%) Clindamycin - 3 9 (.) (.) Telithromycin.15.15.15-1 (.) 1 (.) Ceftriaxone non-meningeal meningeal - - (1.) 9 (.) (.) (1.) TMP/SMX.5.5-1 1 (.1) 39 (1.) Ciprofloxacin 1.5 - - 57 (.3) Levofloxacin 1 1.5-3 (.1) 3 (1.5) Moxifloxacin.1.1.3-1 (.7) 17 (.7) Ciprofloxacin: Intermediate MIC=, Resistant MIC> Table. In Vitro Activities of Several Antimicrobials Against, Isolates of S. pneumoniae Collected Nationally, 5 MIC (µg/ml).15.3..1.5.5 1 1 3 Penicillin 113 a 11 5 7 3 Erythromycin 7 a 5 1 1 7 93 3 13 5 b Clindamycin 79 a 9 5 7 17 b Ceftriaxone 9 a 39 9* TMP/SMX 197 a 17 7 1 57 b Ciprofloxacin 9 175 17 7 1 11 b Levofloxacin 57 155 3 9 17 5 5 b Moxifloxacin a 5 5 153 1 1 1 b Gatifloxacin a 5 17 11 3 5 1 3 b Telithromycin 13 a 9 1 7 1 19 1 1 Underlined number denotes NCCLS intermediate category where applicable a MICs for these isolates were less than or equal to the value given b MICs for these isolates were greater than or equal to the value given * NCCLS intermediate for meningitis NCCLS intermediate for non-meningitis

In 5, we found that 15.1% of S. pneumoniae were penicillin non-susceptible,.5% fell in the intermediate category (MIC =.1 to 1 µg/ml), and.% were penicillin resistant (MIC µg/ml) (Table 1). Figure 1 shows the evolution of penicillin non-susceptible pneumococci over last several years. Figure 1. Percentage of Penicillin Non-Susceptible S. pneumoniae in Canada: 19-5 1 1 1 % intermediate resistance % high-level resistance 19 1993 199 1995 199 1997 199 1999 1 3 5 Figures and 3 show distribution of non-susceptible isolates with regards to sterile versus nonsterile sites and age 15 and > years. Figure. Percentage of Non-susceptible Sterile Site vs. Non-sterile Site Isolates of S. pneumoniae, 5 Non-susceptible 1 1 1 1 Sterile Non-sterile Pen Erythro Clinda Ceftriaxone Cipro

Figure 3. Percentage of Non-susceptible Isolates of S. pneumoniae in Ages <15 and >, 5 5 non-susceptible 15 5 Age <=15 yrs Age > yrs Pen Erythro Clinda Ceftriaxone Cipro The prevalence of resistance in various regions or provinces across Canada is shown in Table 3 and Figure. Rates of intermediate susceptibility varied from 1.9% in Alberta to 1.5% in Newfoundland. Rates of resistance varied from 5.7% in PEI to 13.9% in Manitoba. Table 3. Percentage of Intermediate/Resistant S. pneumoniae Isolates by Geographic Region in Canada in Atlantic Canada BC Prairies Ontario Quebec Canada Penicillin.5/. 9./3.3 11./7. 9./.1 1./. 1.5/. Erythromycin./19. /15..3/19.1.1/1. 1./. /5.5 Clindamycin./. /..3/.3./7.7 1./13..3/. Ceftriaxone: nonmeningeal meningeal 1./../1. / 3.3/ 1.7/ 7.7/1.7 1./ 3./1. 1./../. 1.5/.9.9/.3 TMP/SMX.1/1. 5./13../1../../1..1/1.5 Ciprofloxacin.5/.3 13./1.1 1.3/.3 9./.7./..7/1. Levofloxacin.1/.5 /1.1 /.3.1/1.5 /1..3/.3 Moxifloxacin.7/.7 /1.1 1.7/..7/../. /.3 Gatifloxacin./1.3 /1.1 /.3./1.3 /1. /.3 Ciprofloxacin: Intermediate MIC=, Resistant MIC> Using the NCCLS interpretive criteria for non-meningeal isolates ( 1// ) 3, we found that only 1.% of isolates had intermediate susceptibility to ceftriaxone and.% were resistant (Table 1). Forty-four isolates had MICs µg/ml, while none had MICs of µg/ml or greater (Table ). Figure shows the trend in ceftriaxone resistance in pneumococci over the last decade. 3

Figure. Ceftriaxone-Resistant Pneumococci (According to Non-meningeal Breakpoints),19-5.5 % intermediate* % resistant* 1.5 1.5 19 1993 199 1995 199 1997 199 1999 1 3 5 *Non-meningitis breakpoints used A total of 7 (19%) isolates were macrolide resistant, of which 19(%) were clindamycin resistant. Therefore, % of macrolide-resistant strains had the MLS B phenotype and 5% the M phenotype. The evolution of macrolide resistance over the last several years is shown in Figure 5. Figure 5. Macrolide-Resistant Pneumococci: 19-5 1 1 1 1 19 199 199 1991 199 1993 199 1995 199 1997 199 1999 1 3 5 There were 57 (.3%) isolates that were resistant to ciprofloxacin (Table 1). Ages of patients from whom the ciprofloxacin resistant pneumococci were isolated were available for all 57 isolates. Eleven of the 1 (.5%) isolates from children was ciprofloxacin resistant, compared to of 3 (.3%) from those aged 1 to, and 3 of 13 (3.7%) from those aged >. 3.7% of lower respiratory tract isolates were resistant to ciprofloxacin, compared to 1.% of blood isolates and 1.3% from the remaining sites. Ten of these resistant isolates were penicillin non-susceptible.

The striking increase observed in fluoroquinolone resistance over the years of the study, especially in respiratory isolates from patients > years of age, declined for the first time in 3 and appears to have stabilized. The MIC 9 for each fluoroquinolone tested against the 57 ciprofloxacin-resistant isolates remained stable at: ciprofloxacin, µg/ml; levofloxacin, 3 µg/ml; gatifloxacin, 1 µg/ml; and moxifloxacin µg/ml. Figure. Fluoroquinolone-Resistant Pneumococci: 1997-1.5 1.5 Moxifloxacin Gatifloxacin Levofloxacin 1997 199 1999 1 3 5 Figure 7. Fluoroquinolone-Resistant Pneumococci in Respiratory Isolates from Adults > years: 19-5 Ciprofloxacin Levofloxacin Gatifloxacin Moxifloxacin 7 5 3 1 Percentage of resistant isolates (%) 19 1993 199 1995 199 1997 199 1999 Year 1 3 5 5

Staphylococcus aureus We have continued to collect Staphylococcus aureus isolates since to monitor susceptibility trends. We are currently in the process of completing susceptibility testing on and 5 isolates and reports will be available later this year. The geographic distribution of isolates is shown in table below. Table : Geographic Distribution of CBSN S.aureus isolates 3 5 British Columbia 5 (%) 5 (7%) 35 (%) 33 (%) Alberta (%) 39 (%) (3%) Saskatchewan (3%) 5 (%) (%) Manitoba (7%) 7 (11%) 51 (15%) 59 (%) Ontario 359 (1%) 53 (39%) 1 (37%) 9 (3%) Quebec 3 (9%) 59 (9%) 9 (3%) (%) Atlantic Provinces 13 (%) 13 (1%) 9 (%) 157 (7%) Total 9 1 3 57 CBSN slide presentations available on www.microbiology.mtsinai.on.ca

Reference List and CBSN publications 1. National Committee for Clinical Laboratory Standards.. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, 5th ed. Approved standard M7-A5. National Committee for Clinical Laboratory Standards, Wayne,Pa.. National Committee for Clinical Laboratory Standards.. Performance standards for antimicrobial disk susceptibility tests, 7th ed. Approved standard M-A7. National Committee for Clinical Laboratory Standards, Wayne,Pa. 3. National Committee for Clinical Laboratory Standards.. Performance standards for antimicrobial susceptibility testing. Fourteenth informational supplement, M-S1. Wayne, Pa.. Chen, D., A. McGeer, J. C. de Azavedo, D. E. Low, and The Canadian Bacterial Surveillance Network. 1999. Decreased susceptibility of Streptococcus pneumoniae to fluoroquinolones in Canada. N.Eng.J.Med. 31:33-39. 5. Low, D. E., J. de Azavedo, K. Weiss, T. Mazzulli, M. Kuhn, D. Church, K. Forward, G. Zhanel, A. Simor, and A. McGeer.. Antimicrobial resistance among clinical isolates of Streptococcus pneumoniae in Canada during. Antimicrob Agents Chemother :195-131.. Simor, A. E., M. Louie, and D. E. Low. 199. Canadian national survey of prevalence of antimicrobial resistance among clinical isolates of Streptococcus pneumoniae. Canadian Bacterial Surveillance Network. Antimicrob Agents Chemother :19-193. 7. Powis J, McGeer A, Green K, Vanderkooi O, Weiss K, Zhanel G, Mazzulli T, Kuhn M, Church D, Davidson R, Forward K, Hoban D, Simor A, the Canadian Bacterial Surveillance Network, and Low DE.. Antimicrobial susceptibility among clinical isolates of Streptococcus pneumoniae in Canada during. in press AAC. 7