In-Vitro Susceptibility of 1982 Respiratory Tract Pathogens and 1921 Urinary Tract Pathogens Against 19 Antimicrobial Agents: a Canadian Multicentre Study

Home , Cefonicid

Journal of Antimicrobial Chemotherapy (1999) 43, Suppl. A, 3–23 JAC In-vitro susceptibility of 1982 respiratory tract pathogens and 1921 urinary tract pathogens against 19 antimicrobial agents: a Canadian multicentre study

Joseph M. Blondeaua*, Y. Yaschuka, M. Sutera, David Vaughanb and the Canadian Antimicrobial Study Group

aDivision of Clinical Microbiology, Saskatoon District Health and St Paul’s Hospital (Grey Nuns) and the University of Saskatchewan, Saskatoon, Saskatchewan; bAnti-Infective Division, Bayer Health Care, Toronto, Ontario, Canada

A total of 3903 pathogens from 48 Canadian medical centres were tested against 19 antimicrobial agents. Five agents showed activity against 90% of all 1982 respiratory tract pathogens tested (ciprofloxacin, 90%; cefoperazone, 91%; ticarcillin/clavulanate, 92%; ceftazidime and imipenem, 93% each). Nine agents had 90% activity against Enterobacteriaceae from respiratory tract infection (cefotaxime and ticarcillin/clavulanate, 90% each; aztreonam, ceftizoxime and ceftriaxone, 91% each; ceftazidime, 93%; ciprofloxacin, 97%; imipenem and netilmicin, 98% each). Similarly, five agents had activity against 90% of all 1921 urinary tract pathogens tested (ciprofloxacin and ticarcillin/clavulanate, 90% each; cefoperazone and netilmicin, 91% each; imipenem, 99%). Nine agents had 95% activity against Enterobacteriaceae from urinary tract infection (ciprofloxacin, 95%; cefotetan, 97%; aztreonam, cefotaxime, ceftazidime, ceftizoxime, ceftriaxone and netilmicin, 98% each; imipenem, 99%). Seventeen agents had activity against 95% of Staphylococcus aureus strains. Susceptibility of Pseudomonas aeruginosa isolates ranged from 2% to 91%.

Introduction Urinary tract infections (UTI) represent a major health problem, affecting an estimated 10–20% of women at some Pneumonia is a significant cause of morbidity and mortal- point during their lifetime.3 In contrast, the prevalence of ity.1 These infections may be categorized into community- UTI in healthy men is 0.1%. Up to 42% of all hospital- acquired or nosocomial pneumonia with the pathogenesis acquired infections are of the urinary tract.4 Escherichia and aetiology varying depending on age, co-morbid ill- coli is the organism most commonly isolated from UTI in nesses and predisposing risk factors, such as previous or both compromised and immunocompetent patients. Other current antimicrobial therapy. Therapeutic management is Enterobacteriaceae, Pseudomonas spp., Staphylococcus based on the type of pneumonia, duration of symptoms spp. and Enterococcus spp. are also significant causes of and, therefore, probable aetiology. Empirical treatment is UTI, their prevalence depending on the age and condition often initiated before availability of laboratory results, of the host.5 which may not yield a pathogen.2 Nonetheless, Haemo - Management of both pneumonia and UTI has become philus influenzae, Moraxella catarrhalis and Streptococcus complicated by increasing antimicrobial resistance.6–10 pneumoniae are commonly isolated from patients with Moreover, it has become important to define local, national either community- or hospital-acquired pneumonia.1 and international rates of resistance for a range of patho- Similarly, patients suffering from acute exacerbations gens. It is important to define resistance rates for pathogens of chronic bronchitis, acute or chronic otitis media, and recovered from a variety of infections since it has been sinusitis are often treated empirically for the same patho- shown that differential resistance rates exist for specific gens. pathogens and antimicrobial agents recovered from dif-

*Corresponding address: Department of Clinical Microbiology, Royal University Hospital, 103 Hospital Drive, Saskatoon, Saskatchewan, Canada S7N 0W8. Tel: 1-306-655-6943; Fax: 1-06-655-6947; E-mail: [email protected]

3 © 1999 The British Society for Antimicrobial Chemotherapy J. M. Blondeau et al. ferent types of infections11,12 and institutions.11–13 Finally, Results with increasing antimicrobial resistance, baseline data will serve as an important reference for monitoring changes in Respiratory tract pathogens resistance. There are limited national Canadian data on The total number of isolates and their susceptibility to 19 antimicrobial resistance amongst pathogens recovered antimicrobial agents are outlined in Table I. P. aeruginosa from respiratory tract infections (RTI) and UTI. In the (cumulative data from two studies), H. influenzae, S. current study, we determined the in-vitro susceptibility of aureus, Klebsiella spp., S. pneumoniae and Enterobacter approximately 3903 pathogens to 19 antimicrobial agents spp. were the most frequently recovered organisms. Of the recovered from patients with RTI or UTI. isolates tested, 1533 were Gram-negative and 449 Gram- positive; 1188 were from inpatients and 620 were from outpatients (the patient location for 174 P. aeruginosa iso- Materials and methods lates was not available). Five agents had activity against 90% of all isolates tested: these were ciprofloxacin The pathogens reported in this study represent the cumula- (90%), cefoperazone (91%), ticarcillin/clavulanate (92%), tive data from two studies. Initially, a total of 15 medical ceftazidime and imipenem (93% each). Isolates from centres, representing all ten Canadian provinces and nearly patients with cystic fibrosis were excluded. all major population areas in Canada, were recruited to As expected, activity against Gram-negative respiratory provide geographical sampling. Each centre tested approx- tract pathogens depended on the agent tested. All agents imately 100 strains of bacteria from patients with RTI and except carbenicillin (88%), mezlocillin (86%), and ticar- an additional 100 isolates from patients with UTI. In total, cillin (87%) had activity against 95% of Haemophilus 1507 clinical isolates from patients with RTI and 1499 clin- spp. All agents had activity against 97% of M. catarrhalis. ical isolates from patients with UTI were collected between Similarly, all antimicrobials had activity against 90% of October 1993 and April 1994. A maximum of 50 E. coli Klebsiella spp. except carbenicillin (2%), chloramphenicol isolates from patients with UTI were collected from each (83%), mezlocillin (67%) and ticarcillin (7%). Susceptibil- site. For subsequent collection of Pseudomonas aeruginosa ity of Enterobacter spp. to the agents tested was variable, isolates, 48 medical centres representing all ten Canadian with only three agents having 90% activity: ciprofloxacin provinces, the Northwest Territories and nearly all major (97%), imipenem (98%) and netilmicin (97%). The activ- population areas were recruited. This increased the total ity of the third-generation cephalosporins against Entero - number of tested pathogens from RTI to 1982 and from bacter spp. was comparable, with rates varying from 78% to UTI to 1921. All additional P. aeruginosa isolates were 83%. Only ciprofloxacin (100%) and imipenem (100%) shipped to and tested at the study coordinator’s (J.M.B.) had activity against 90% of Citrobacter spp., whereas laboratory. Only fresh clinical isolates were eligible for activity varied from 31% to 88% for the other agents inclusion in the study, and duplicate isolates from the same tested. Susceptibility ranged from 2% to 91% for P. aeru - patient were not permitted. The clinical validity of the ginosa and the following seven agents had 84% activity: isolates was determined by local laboratory criteria, and carbenicillin, 92%; ceftazidime, 89%; cefoperazone, 84%; organisms were identified by reference or comparable ciprofloxacin, 86%; imipenem, 90%; ticarcillin and ticar- methods. There was no selection process in the study cillin/clavulanate, 91% each. Overall, nine agents had design that would increase the likelihood of collecting 90% activity against the Enterobacteriaceae: cefotaxime resistant isolates. Following testing, all isolates were stored. and ticarcillin/clavulanate, 90% each; aztreonam, cefti- All sites used the same protocol for in-vitro suscepti- zoxime and ceftriaxone, 91% each; ceftazidime, 93%; bility testing, and all supplies and media were provided by ciprofloxacin, 97%, imipenem and netilmicin, 98% each. the study coordinator. Following testing, the susceptibility Against Streptococcus pyogenes, all agents except aztre- results and the organisms were shipped to the study coordi- onam and ciprofloxacin (78%) had 90% activity. Simi- nator. MICs were determined for all isolates by the larly, 96% of all agents except aztreonam and mezlocillin Microscan MIC Plus Type 2 Panel with the following 19 (71%) had greater activity against 96% of S. aureus. antibiotics: amoxycillin/clavulanate, ampicillin/sulbactam, Susceptibility rates of S. pneumoniae to all agents were aztreonam, carbenicillin, cefamandole, cefonicid, cefo- 93%, except for aztreonam and ciprofloxacin (80%). taxime, cefoperazone, cefotetan, ceftazidime, ceftizoxime, ceftriaxone, chloramphenicol, ciprofloxacin, imipenem, Urinary tract pathogens mezlocillin, netilmicin, ticarcillin and ticarcillin/clavulanate.11 Testing was performed according to the manufac- E. coli, P. aeruginosa, Enterococcus spp. and Klebsiella spp. turers’ instructions, and interpretation was in accordance were the most frequently recovered urinary tract patho- with MIC interpretive criteria published by the NCCLS.14 gens (Table II). There were 1592 Gram-negative and For Haemophilus spp., M. catarrhalis, S. pneumoniae 329 Gram-positive isolates tested, including 1033 from and Streptococcus spp., haemophilus inoculum broth was inpatients and 887 from outpatients (patient location for used. one isolate was not available).

4 In-vitro susceptibility of respiratory and urinary pathogens

Table I. Antimicrobial susceptibilities of 1982 respiratory isolates collected from 15 Canadian medical centres

MIC (mg/L)

Organism MIC50 MIC90 range % Susceptibility

Acinetobacter spp. (20) amoxycillin/clavulanate 4/2 16/8 2/1–32/16 80 ampicillin/sulbactam 2/1 16/8 1/0.5–32/16 85 aztreonam 16 32 4–32 30 carbenicillin 16 128 16–128 85 cefamandole 32 32 16–32 0 cefonicid 16 16 2–16 0 cefotaxime 8 32 2–64 63 cefoperazone 32 32 4–32 0 cefotetan 32 32 8–32 5 ceftazidime 4 8 2–32 90 ceftizoxime 4 32 2–32 70 ceftriaxone 8 32 2–64 70 chloramphenicol 16 16 2–16 20 ciproﬂoxacin 0.25 1 0.25–4 90 imipenem 0.5 0.5 0.5–2 100 mezlocillin 16 64 16–128 60 netilmicin 2 8 2–16 90 ticarcillin 16 64 16–128 86 ticarcillin/clavulanate 16 16 16–128 90 Citrobacter spp. (16) amoxycillin/clavulanate 8/4 32/16 1/0.5–32/16 43 ampicillin/sulbactam 4/2 32/16 2/1–32/16 57 aztreonam 1 32 1–32 71 carbenicillin 128 128 2–128 38 cefamandole 4 32 4–32 57 cefonicid 16 16 2–16 43 cefotaxime 2 32 2–64 64 cefoperazone 4 32 4–32 64 cefotetan 4 32 2–32 71 ceftazidime 1 32 1–32 75 ceftizoxime 2 32 2–32 64 ceftriaxone 2 64 2–64 64 chloramphenicol 4 16 2–16 92 ciproﬂoxacin 0.25 0.25 0.25–0.5 100 imipenem 0.5 1 0.5–2 100 mezlocillin 16 128 16–128 50 netilmicin 2 2 2 100 ticarcillin 64 128 16–128 27 ticarcillin/clavulanate 16 128 16–128 64 Enterobacter spp. (93) amoxycillin/clavulanate 32/16 32/16 1/0.5–32/16 9 ampicillin/sulbactam 16/8 32/16 1/0.5–32/16 45 aztreonam 1 16 1–32 83 carbenicillin 16 128 16–128 72 cefamandole 16 32 4–32 48 cefonicid 16 16 2–16 27 cefotaxime 2 32 2–64 80 cefoperazone 4 32 4–32 81

5 J. M. Blondeau et al.

Table I. Continued

MIC (mg/L)

Organism MIC50 MIC90 range % Susceptibility

Enterobacter spp. (93) continued cefotetan 4 32 4–32 70 ceftazidime 1 32 1–32 83 ceftizoxime 2 32 2–32 78 ceftriaxone 2 64 2–64 81 chloramphenicol 4 16 2–16 86 ciprofloxacin 0.25 0.25 0.25–4 97 imipenem 1 2 0.5–16 98 mezlocillin 16 64 16–128 77 netilmicin 2 2 2–16 97 ticarcillin 16 128 16–128 74 ticarcillin/clavulanate 16 128 16–128 73 E. coli (84) amoxycillin/clavulanate 2/1 8/4 1/0.5–32/16 96 ampicillin/sulbactam 2/1 32/16 1/0.5–32/16 73 aztreonam 1 1 1–64 96 carbenicillin 16 128 16–128 73 cefamandole 4 16 4–32 88 cefonicid 2 16 2–16 87 cefotaxime 2 2 2 100 cefoperazone 4 16 4–32 91 cefotetan 4 4 4 100 ceftazidime 1 1 1–4 100 ceftizoxime 2 2 1–4 100 ceftriaxone 2 2 2 100 chloramphenicol 4 8 2–16 92 ciprofloxacin 0.25 0.25 0.25 100 imipenem 0.5 0.5 0.5 100 mezlocillin 16 128 16–128 75 netilmicin 2 2 2–4 100 ticarcillin 16 128 16–128 74 ticarcillin/clavulanate 16 16 16–64 96 Haemophilus spp. (290) amoxycillin/clavulanate 0.5/0.25 1/0.5 0.5/0.25–16/8 99 ampicillin/sulbactam 0.5/0.25 1/0.5 0.5/0.25–16/8 99 aztreonam 0.5 1 0.5–32 95 carbenicillin 8 32 8–128 88 cefamandole 2 4 2–32 99 cefonicid 1 2 1–16 99 cefotaxime 1 2 1–4 100 cefoperazone 2 4 1–16 100 cefotetan 2 4 1–16 99 ceftazidime 0.5 1 0.25–8 100 ceftizoxime 1 2 1–32 99 ceftriaxone 1 2 1–4 100 chloramphenicol 1 2 1–4 100 ciprofloxacin 0.125 0.25 0.125–2 99 imipenem 0.5 1 0.25–8 99 mezlocillin 8 64 8–128 86 netilmicin 1 2 1–16 99

6 In-vitro susceptibility of respiratory and urinary pathogens

Table I. Continued

MIC (mg/L)

Organism MIC50 MIC90 range % Susceptibility

Haemophilus spp. (290) continued ticarcillin 8 32 8–128 87 ticarcillin/clavulanate 8 16 8–64 99 Klebsiella spp. (102) amoxycillin/clavulanate 2/1 2/1 1/0.5–16/8 99 ampicillin/sulbactam 8/4 8/4 1/0.5–32/16 90 aztreonam 1 1 1–32 97 carbenicillin 128 128 16–128 2 cefamandole 4 8 4–32 92 cefonicid 2 8 2–16 91 cefotaxime 2 2 2–32 99 cefoperazone 4 4 4–32 98 cefotetan 4 4 1–32 99 ceftazidime 1 1 1–32 99 ceftizoxime 2 2 2–32 99 ceftriaxone 2 2 2–64 98 chloramphenicol 2 16 2–16 83 ciproﬂoxacin 0.25 0.5 0.25–4 95 imipenem 0.5 0.5 0.25–4 100 mezlocillin 16 64 16–128 67 netilmicin 2 2 2–16 99 ticarcillin 128 128 16–128 7 ticarcillin/clavulanate 16 16 16–128 98 Moraxella spp. (69) amoxycillin/clavulanate 0.5/0.25 1/0.5 0.5/0.25–1/0.5 100 ampicillin/sulbactam 0.5/0.25 1/0.5 0.5/0.25–1/0.5 100 aztreonam 0.5 2 0.5–16 97 carbenicillin 8 16 8–16 100 cefamandole 2 4 2–8 100 cefonicid 2 4 1–8 100 cefotaxime 1 2 1–2 100 cefoperazone 2 4 2–8 100 cefotetan 2 4 2–8 100 ceftazidime 0.5 1 0.5–2 100 ceftizoxime 1 2 1–2 100 ceftriaxone 1 2 1–2 100 chloramphenicol 1 2 1–2 100 ciproﬂoxacin 0.125 0.25 0.125–2 99 imipenem 0.25 0.5 0.25–0.5 100 mezlocillin 8 16 8–128 100 netilmicin 1 2 1–4 100 ticarcillin 8 16 8–16 100 ticarcillin/clavulanate 8 16 8–16 100 Morganella spp. (6) amoxycillin/clavulanate 32/16 32/16 16/8–32/16 0 ampicillin/sulbactam 32/16 32/16 16/8–32/16 0 aztreonam 1 4 1–4 100 carbenicillin 16 16 16–32 83 cefamandole 32 32 32–32 0 cefonicid 16 16 16 0

7 J. M. Blondeau et al.

Table I. Continued

MIC (mg/L)

Organism MIC50 MIC90 range % Susceptibility

Morganella spp. (6) continued cefotaxime 2 16 2–16 67 cefoperazone 4 4 4–32 83 cefotetan 4 4 4–32 83 ceftazidime 1 8 1–32 83 ceftizoxime 2 32 2–32 67 ceftriaxone 2 8 2–8 100 chloramphenicol 4 4 2–8 100 ciprofloxacin 0.25 0.25 0.25 100 imipenem 4 4 2–8 83 mezlocillin 16 16 16 83 netilmicin 2 2 2 100 ticarcillin 16 16 16–32 83 ticarcillin/clavulanate 16 16 16–32 83 P. aeruginosa (744)a amoxycillin/clavulanate 32/16 32/16 1/0.5–32/16 2 ampicillin/sulbactam 32/16 32/16 1/0.5–32/16 3 aztreonam 4 16 1–32 82 carbenicillin 64 128 16–128 92 cefamandole 32 32 4–32 1 cefonicid 16 16 2–16 1 cefotaxime 32 64 2–64 11 cefoperazone 8 32 4–32 84 cefotetan 32 32 4–32 3 ceftazidime 2 16 1–32 89 ceftizoxime 32 32 2–32 30 ceftriaxone 32 64 2–64 18 chloramphenicol 16 16 2–16 3 ciprofloxacin 0.25 2 0.25–4 86 imipenem 1 8 0.5–16 90 mezlocillin 32 128 16–128 84 netilmicin 8 16 1–16 75 ticarcillin 16 64 16–128 91 ticarcillin/clavulanate 16 64 16–128 91 Pseudomonas spp. (15)a,b amoxycillin/clavulanate 32/16 32/16 8/4–32/16 7 ampicillin/sulbactam 32/16 32/16 1/0.5–32/16 13 aztreonam 32 32 1–32 46 carbenicillin 128 128 16–128 47 cefamandole 32 32 8––32 7 cefonicid 16 16 16 0 cefotaxime 16 64 2–64 33 cefoperazone 16 32 4–32 67 cefotetan 32 32 4–32 27 ceftazidime 2 4 1–8 100 ceftizoxime 32 32 2–32 40 ceftriaxone 8 64 2–64 53 chloramphenicol 16 16 4–16 7 ciprofloxacin 0.25 2 0.25–4 87 imipenem 2 8 0.5–16 80

8 In-vitro susceptibility of respiratory and urinary pathogens

Table I. Continued

MIC (mg/L)

Organism MIC50 MIC90 range % Susceptibility

Pseudomonas spp. (15)a,b continued mezlocillin 32 64 16–128 93 netilmicin 2 16 2–16 80 ticarcillin 128 128 16–128 40 ticarcillin/clavulanate 128 128 16–128 47 Proteus spp. (24) amoxycillin/clavulanate 1/0.5 16/8 1/0.5–16/8 88 ampicillin/sulbactam 1/0.5 16/8 1/0.5–32/16 79 aztreonam 1 1 1–32 96 carbenicillin 16 128 16–128 79 cefamandole 4 32 4–32 75 cefonicid 2 16 2–16 75 cefotaxime 2 64 2–64 88 cefoperazone 4 32 4–32 88 cefotetan 4 4 4–16 96 ceftazidime 1 1 1–32 96 ceftizoxime 2 2 2–8 100 ceftriaxone 2 64 2–64 83 chloramphenicol 4 16 2–16 75 ciproﬂoxacin 0.25 0.25 0.25 100 imipenem 4 8 0.5–16 88 mezlocillin 16 64 16–128 88 netilmicin 2 2 2 100 ticarcillin 16 128 16–128 79 ticarcillin/clavulanate 16 16 16 100 Providencia sp. (1) amoxycillin/clavulanate 32/16 32/16 32/16 0 ampicillin/sulbactam 8/4 8/4 8/4 100 aztreonam 1 1 1 100 carbenicillin 16 16 16 100 cefamandole 4 4 4 100 cefonicid 2 2 2 100 cefotaxime 2 2 2 100 cefoperazone 4 4 4 100 cefotetan 4 4 4 100 ceftazidime 1 1 1 100 ceftizoxime 2 2 2 100 ceftriaxone 2 2 2 100 chloramphenicol 16 16 16 0 ciproﬂoxacin 0.25 0.25 0.25 100 imipenem 1 1 1 100 mezlocillin 16 16 16 100 netilmicin 16 16 16 0 ticarcillin 16 16 16 100 ticarcillin/clavulanate 16 16 16 100 Serratia spp. (31) amoxycillin/clavulanate 32/16 32/16 1/0.5–32/16 10 ampicillin/sulbactam 32/16 32/16 1/0.5–32/16 30 aztreonam 1 1 1–32 94 carbenicillin 16 128 16–128 70

9 J. M. Blondeau et al.

Table I. Continued

MIC (mg/L)

Organism MIC50 MIC90 range % Susceptibility

Serratia spp. (31) continued cefamandole 32 32 4–32 12 cefonicid 16 16 2–16 9 cefotaxime 2 2 2–32 94 cefoperazone 4 8 4–32 97 cefotetan 4 4 4–32 97 ceftazidime 1 1 1–32 97 ceftizoxime 2 2 2–32 94 ceftriaxone 2 2 2–64 94 chloramphenicol 8 16 4–16 52 ciproﬂoxacin 0.25 2 0.25–2 94 imipenem 1 2 0.5–4 100 mezlocillin 16 16 16–128 94 netilmicin 2 4 2–4 100 ticarcillin 16 128 16–128 79 ticarcillin/clavulanate 16 16 16–64 97 S. maltophilia (36) amoxycillin/clavulanate 16/8 32/16 16/8–32/16 0 ampicillin/sulbactam 32/16 32/16 1/0.5–32/16 17 aztreonam 32 32 2–32 8 carbenicillin 64 128 16–128 31 cefamandole 32 32 4–32 3 cefonicid 16 16 2–16 3 cefotaxime 64 64 2–64 6 cefoperazone 32 32 4–32 44 cefotetan 16 32 4–32 47 ceftazidime 8 32 1–32 53 ceftizoxime 32 32 2–32 6 ceftriaxone 64 64 2–64 3 chloramphenicol 8 16 2–16 67 ciproﬂoxacin 4 4 0.5–4 17 imipenem 16 16 16 0 mezlocillin 128 128 16–128 28 netilmicin 16 16 2–16 11 ticarcillin 32 128 16–128 33 ticarcillin/clavulanate 16 32 16–128 83 Enterococcus spp. (8) amoxycillin/clavulanate 1/0.5 1/0.5 1/0.5–2/1 100 ampicillin/sulbactam 1/0.5 1/0.5 1/0.5–4/2 100 aztreonam 32 32 32 0 carbenicillin 16 32 16–32 75 cefamandole 32 32 16–32 0 cefonicid 16 16 16 0 cefotaxime 64 64 64 0 cefoperazone 32 32 8–32 25 cefotetan 32 32 32 0 ceftazidime 32 32 32 0 ceftizoxime 32 32 16–32 0 ceftriaxone 64 64 64 0 chloramphenicol 4 16 4–16 75

10 In-vitro susceptibility of respiratory and urinary pathogens

Table I. Continued

MIC (mg/L)

Organism MIC50 MIC90 range % Susceptibility

Enterococcus spp. (8) continued ciprofloxacin 1 2 0.5–4 63 imipenem 1 1 0.5–1 100 mezlocillin 16 16 16 100 netilmicin 16 16 8–16 38 ticarcillin 32 32 32–64 0 ticarcillin/clavulanate 32 64 32–64 25 S. agalactiae (8) amoxycillin/clavulanate 1/0.5 1/0.5 0.5/0.25–1/0.5 100 ampicillin/sulbactam 1/0.5 1/0.5 0.5/0.25–4/2 100 aztreonam 32 32 32 na carbenicillin 16 16 8–32 88 cefamandole 4 4 2–16 88 cefonicid 2 2 1–2 100 cefotaxime 2 2 1–4 100 cefoperazone 4 4 2–4 100 cefotetan 4 8 2–8 100 ceftazidime 1 1 1 100 ceftizoxime 2 2 1–2 100 ceftriaxone 2 2 1–4 100 chloramphenicol 2 4 2–16 88 ciprofloxacin 0.5 2 0.5–2 63 imipenem 0.5 0.5 0.25–0.5 100 mezlocillin 16 16 8–16 100 netilmicin 8 16 4–16 50 ticarcillin 16 16 8–32 88 ticarcillin/clavulanate 16 16 8–16 100 S. aureus (265) amoxycillin/clavulanate 1/0.5 1/0.5 1/0.5–32/16 99 ampicillin/sulbactam 1/0.5 2/1 1/0.5–16/8 99 aztreonam 32 32 1–64 0 carbenicillin 16 16 16128 98 cefamandole 4 4 4–16 99 cefonicid 2 2 2–16 99 cefotaxime 2 2 1–64 99 cefoperazone 4 4 4–32 99 cefotetan 4 4 2–32 99 ceftazidime 8 8 1–32 96 ceftizoxime 2 8 2–32 98 ceftriaxone 2 2 1–64 99 chloramphenicol 4 8 2–16 99 ciprofloxacin 0.25 0.5 0.25–4 96 imipenem 0.5 0.5 0.5–16 99 mezlocillin 16 128 16–128 71 netilmicin 2 2 2–16 99 ticarcillin 16 16 16–128 98 ticarcillin/clavulanate 16 16 16–128 99 Coagulase-negative staphylococci (7) amoxycillin/clavulanate 8/4 8/4 1/0.5–32/16 86 ampicillin/sulbactam 8/4 8/4 1/0.5–16/8 86

11 J. M. Blondeau et al.

Table I. Continued

MIC (mg/L)

Organism MIC50 MIC90 range % Susceptibility

Coagulase-negative staphylococci (7) continued aztreonam 32 32 32 0 carbenicillin 128 128 16–128 29 cefamandole 4 16 4–32 71 cefonicid 16 16 2–16 29 cefotaxime 64 64 2–64 29 cefoperazone 8 32 4–32 71 cefotetan 32 32 4–32 29 ceftazidime 32 32 1–32 43 ceftizoxime 32 32 2–32 29 ceftriaxone 64 64 2–64 29 chloramphenicol 4 8 4–8 100 ciproﬂoxacin 0.25 4 0.25–4 57 imipenem 16 16 0.5–16 29 mezlocillin 64 128 16–128 14 netilmicin 2 4 2–4 100 ticarcillin 128 128 16–128 29 ticarcillin/clavulanate 128 128 16–128 43 S. pneumoniae (95) amoxycillin/clavulanate 0.5–/0.25 0.5/0.25 0.5/0.25–2/1 100 ampicillin/sulbactam 0.5/0.25 0.5/0.25 0.5/0.25–4/2 100 aztreonam 16 16 0.5–16 7 carbenicillin 8 8 8–32 99 cefamandole 2 2 2–4 100 cefonicid 1 1 1–4 100 cefotaxime 1 1 1–2 100 cefoperazone 2 2 2 100 cefotetan 2 2 2–32 99 ceftazidime 0.5 0.5 0.5–8 100 ceftizoxime 1 1 1–2 100 ceftriaxone 1 1 1–2 100 chloramphenicol 1 2 1–8 100 ciproﬂoxacin 1 2 0.125–2 80 imipenem 0.25 0.25 0.25–0.5 100 mezlocillin 8 8 8–16 100 netilmicin 2 8 1–16 99 ticarcillin 8 8 8–128 99 ticarcillin/clavulanate 8 8 8–64 99 S. pyogenes (60) amoxycillin/clavulanate 1/0.5 1/0.5 0.5/0.25–4/2 100 ampicillin/sulbactam 1/0.5 1/0.5 0.5/0.25–4/2 100 aztreonam 8 32 0.5–32 na carbenicillin 16 16 8–128 92 cefamandole 2 4 2–32 95 cefonicid 2 4 1–16 97 cefotaxime 2 2 1–32 98 cefoperazone 4 4 2–32 95 cefotetan 4 16 2–32 90 ceftazidime 1 4 0.25–16 93 ceftizoxime 2 2 1–32 97

12 In-vitro susceptibility of respiratory and urinary pathogens

Table I. Continued

MIC (mg/L)

Organism MIC50 MIC90 range % Susceptibility

S. pyogenes (60) continued ceftriaxone 2 2 1–32 97 chloramphenicol 2 2 1–8 100 ciproﬂoxacin 0.5 2 0.125–4 78 imipenem 0.5 0.5 0.125–4 100 mezlocillin 16 16 8–128 97 netilmicin 4 8 1–16 92 ticarcillin 16 16 8–128 92 ticarcillin/clavulanate 16 16 8–32 95 Streptococcus spp. (8) amoxycillin/clavulanate 1/0.5 1/0.5 1/0.5–2/1 100 ampicillin/sulbactam 1/0.5 1/0.5 0.5/0.25–4/2 100 aztreonam 16 16 16–32 0 carbenicillin 16 16 8–64 83 cefamandole 2 4 2–4 100 cefonicid 2 2 1–8 83 cefotaxime 2 2 1–4 100 cefoperazone 4 4 2–16 83 cefotetan 4 16 2–16 67 ceftazidime 4 4 0.5–8 100 ceftizoxime 2 2 1–8 100 ceftriaxone 2 2 1–4 100 chloramphenicol 2 8 1–8 83 ciproﬂoxacin 0.5 0.5 0.125–2 83 imipenem 0.5 0.5 0.25–0.5 100 mezlocillin 16 16 8–16 100 netilmicin 4 4 1–8 100 ticarcillin 16 32 8–64 67 ticarcillin/clavulanate 16 16 8–16 100

aAzlocillin activity against P. aeruginosa, 90%; Pseudomonas species 83%. bIncludes two isolates of Burkholderia cepacia. NA No NCCLS breakpoint.

All antimicrobial agents had activity against 92% of chloramphenicol (91%), ciprofloxacin (100%), imipenem E. coli except ampicillin/sulbactam (71%), carbenicillin (100%) and netilmicin (93%). Overall, nine agents had (69%), cefamandole (87%), cefonicid (85%), cefopera- activity against 95% of Enterobacteriaceae: aztreonam, zone (86%), mezlocillin (73%) and ticarcillin (70%). cefotaxime, ceftazidime, ceftizoxime, ceftriaxone, netil- Si m i larly, all agents except ampicillin/sulbactam (84%), micin, 98% each; ciprofloxacin, 95%; cefotetan, 97%; carbenicillin (3%), mezlocillin (64%) and ticarcillin (8%) imipenem, 99%. The activity of ticarcillin/clavulanate was had activity against 90% of Klebsiella spp. Only ceftaz- 92%, while carbenicillin (59%) and ticarcillin (61%) were idime and ceftizoxime were active against 100% of Kleb - the least active agents. siella spp. Imipenem and ticarcillin were the least active Of Gram-positive isolates, Enterococcus spp. were the agents against Proteus spp., although each had a suscep- most resistant organisms tested. Only eight agents were tibility rate of 85%. For P. aeruginosa, carbenicillin (90%), active against 50% of Enterococcus spp.; of these, amoxy- cefoperazone (85%), ceftazidime (92%), imipenem cillin/clavulanate and imipenem were the most active (97% (90%), mezlocillin (87%), ticarcillin (91%) and ticarcillin/ each). With the exception of aztreonam and netilmicin, all clavulanate (90%) were the most active. Susceptibility of agents were active against 89% of Streptococcus agalac - P. aeruginosa to ciprofloxacin was 77%. Only four agents tiae. For S. aureus, all agents except aztreonam and had activity against 90% of Enterobacter spp., these were mezlocillin had susceptibility rates of 95%.

13 J. M. Blondeau et al.

Table II. Antimicrobial susceptibilities of 1921 urinary isolates collected from 15 Canadian medical centers

MIC (mg/L)

Organism MIC50 MIC90 range % Susceptibility

Acinetobacter spp. (7) amoxycillin/clavulanate 4/2 16/8 1/0.5–16/8 71 ampicillin/sulbactam 2/1 2/1 1/0.5–2/1 100 aztreonam 16 32 1–32 43 carbenicillin 16 16 16 100 cefamandole 32 32 4–32 14 cefonicid 16 16 8–16 14 cefoperazone 32 32 16–32 29 cefotaxime 8 32 2–32 71 cefotetan 32 32 8–32 14 ceftazidime 4 16 1–16 71 ceftizoxime 8 16 2–32 57 ceftriaxone 8 16 2–32 71 chloramphenicol 16 16 8–16 14 ciproﬂoxacin 0.25 4 0.25–4 57 imipenem 0.5 0.5 0.5 100 mezlocillin 16 32 16–32 57 netilmicin 2 2 2–16 86 ticarcillin 16 16 16 100 ticarcillin/clavulanate 16 16 16–32 86 Citrobacter spp. (46) amoxycillin/clavulanate 16/8 32/16 1/0.5–32/16 39 ampicillin/sulbactam 8/4 32/16 1/0.5–32/16 54 aztreonam 1 2 1–32 89 carbenicillin 16 128 4–128 54 cefamandole 4 32 4–32 63 cefonicid 8 16 2–16 48 cefoperazone 4 32 4–32 78 cefotaxime 2 8 2–64 89 cefotetan 4 32 4–32 89 ceftazidime 1 16 1–32 87 ceftizoxime 2 16 2–32 89 ceftriaxone 2 16 2–64 87 chloramphenicol 4 16 2–16 74 ciproﬂoxacin 0.25 4 0.25–4 78 imipenem 0.5 2 0.5–2 100 mezlocillin 16 128 16–128 67 netilmicin 2 2 2–16 91 ticarcillin 16 128 16–128 59 ticarcillin/clavulanate 16 128 16–128 72 Enterobacter spp. (42) amoxycillin/clavulanate 32/16 32/16 1/0.5–32/16 24 ampicillin/sulbactam 16/8 32/16 1/0.5–32/16 43 aztreonam 1 32 1–32 83 carbenicillin 16 128 16–128 62 cefamandole 8 32 3–32 52 cefonicid 16 16 2–16 38 cefoperazone 4 32 4–32 74 cefotaxime 2 64 2–64 83

14 In-vitro susceptibility of respiratory and urinary pathogens

Table II. Continued

MIC (mg/L)

Organism MIC50 MIC90 range % Susceptibility

Enterobacter spp. (42) continued cefotetan 4 32 4–32 69 ceftazidime 1 32 1–32 83 ceftizoxime 2 32 2–32 74 ceftriaxone 2 64 2–64 81 chloramphenicol 4 8 2–16 91 ciprofloxacin 0.25 0.25 0.25–1 100 imipenem 0.5 2 0.5–2 100 mezlocillin 16 128 16–128 83 netilmicin 2 4 2–16 93 ticarcillin 16 128 16–128 67 ticarcillin/clavulanate 16 128 16–128 79 E. coli (694) amoxycillin/clavulanate 2/1 8/4 1/0.5–32–16 95 ampicillin/sulbactam 2/1 32/16 1/0.5–32/16 71 aztreonam 1 1 1–32 99 carbenicillin 16 128 16–128 69 cefamandole 4 16 4–32 87 cefonicid 2 16 1–32 85 cefoperazone 4 32 4–32 86 cefotaxime 2 2 2–64 99 cefotetan 4 4 1–32 99 ceftazidime 1 1 1–32 99 ceftizoxime 2 2 2–32 99 ceftriaxone 2 2 2–32 99 chloramphenicol 4 8 2–16 93 ciprofloxacin 0.25 0.25 0.25–4 99 imipenem 0.5 0.5 0.5–16 99 mezlocillin 16 128 16–128 73 netilmicin 2 2 2–16 99 ticarcillin 16 128 16–128 70 ticarcillin/clavulanate 16 16 0.5–128 92 Klebsiella spp. (175) amoxycillin/clavulanate 2/1 4/2 1/0.5–32/16 98 ampicillin/sulbactam 8/4 16/8 2/1–32/16 84 aztreonam 1 1 1–32 98 carbenicillin 128 128 16–128 3 cefamandole 4 4 4–32 94 cefonicid 2 4 2–16 93 cefoperazone 4 4 2–32 95 cefotaxime 2 2 2–32 99 cefotetan 4 4 4–32 99 ceftazidime 1 1 8 100 ceftizoxime 2 2 1–2 100 ceftriaxone 2 2 2–64 99 chloramphenicol 4 16 2–16 90 ciprofloxacin 0.25 0.5 0.25–4 95 imipenem 0.5 1 0.25–16 99 mezlocillin 16 128 16–128 64 netilmicin 2 2 2–16 99

15 J. M. Blondeau et al.

Table II. Continued

MIC (mg/L)

Organism MIC50 MIC90 range % Susceptibility

Klebsiella spp. (175) continued ticarcillin 128 128 16–128 8 ticarcillin/clavulanate 16 16 16–32 97 Morganella spp. (21) amoxycillin/clavulanate 32/16 32/16 1/0.5–32/16 5 ampicillin/sulbactam 16/8 32/16 8/4–32/16 10 aztreonam 1 1 1–32 100 carbenicillin 16 32 16–128 86 cefamandole 32 32 4–32 14 cefonicid 16 16 2–16 29 cefoperazone 4 16 4–32 90 cefotaxime 2 2 2–8 100 cefotetan 4 4 4 100 ceftazidime 1 2 1–16 95 ceftizoxime 2 4 2–32 90 ceftriaxone 2 2 2 100 chloramphenicol 4 16 2–16 81 ciproﬂoxacin 0.25 0.25 0.25–4 95 imipenem 4 4 1–8 95 mezlocillin 16 16 16–128 91 netilmicin 2 2 2–16 95 ticarcillin 16 32 16–128 86 ticarcillin/clavulanate 16 16 16–32 91 P. aeruginosa (509)a amoxycillin/clavulanate 32/16 32/16 8/4–32/16 2 ampicillin/sulbactam 32/16 32/16 1/0.5–32/16 1 aztreonam 4 32 1–32 76 carbenicillin 64 128 2–128 90 cefamandole 32 32 4–32 0 cefonicid 16 16 2–16 0 cefoperazone 8 32 4–32 85 cefotaxime 32 64 2–64 9 cefotetan 32 32 4–32 2 ceftazidime 2 8 1–32 92 ceftizoxime 32 32 2–32 3 ceftriaxone 32 64 2–128 22 chloramphenicol 16 16 2–32 1 ciproﬂoxacin 0.25 4 0.25–4 77 imipenem 1 8 0.5–16 90 mezlocillin 32 128 16–128 87 netilmicin 8 16 2–16 77 ticarcillin 32 64 16–128 91 ticarcillin/clavulanate 32 64 16–128 90 Pseudomonas spp. (4)a,b amoxycillin/clavulanate 32/16 32/16 32/16 0 ampicillin/sulbactam 32/16 32/16 32/16 0 aztreonam 32 32 2–32 25 carbenicillin 128 128 32–128 25 cefamandole 32 32 32 0 cefonicid 16 16 16 0

16 In-vitro susceptibility of respiratory and urinary pathogens

Table II. Continued

MIC (mg/L)

Organism MIC50 MIC90 range % Susceptibility

Pseudomonas spp. (4)a,b continued cefoperazone 16 32 4–32 50 cefotaxime 16 64 16–64 0 cefotetan 32 32 32 0 ceftazidime 2 16 2–16 75 ceftizoxime 32 32 32–32 0 ceftriaxone 16 64 8–64 25 chloramphenicol 16 16 16 0 ciprofloxacin 0.25 4 0.25–4 75 imipenem 1 4 1–4 100 mezlocillin 32 128 32–128 75 netilmicin 2 8 2–8 100 ticarcillin 128 128 16–128 25 ticarcillin/clavulanate 64 128 16–128 75 Proteus spp. (75) amoxycillin/clavulanate 1/0.5 4/2 1/0.5–32/16 95 ampicillin/sulbactam 1/0.5 8/4 1/0.5–32/16 91 aztreonam 1 1 1–32 96 carbenicillin 16 64 16–128 89 cefamandole 4 16 4–32 89 cefonicid 2 2 2–16 93 cefoperazone 4 4 1–32 97 cefotaxime 2 2 2–64 99 cefotetan 4 8 4–32 96 ceftazidime 1 1 1–8 100 ceftizoxime 2 2 2–16 97 ceftriaxone 2 2 2–64 97 chloramphenicol 4 16 2–16 85 ciprofloxacin 0.25 0.25 0.25–4 99 imipenem 2 8 0.5–16 85 mezlocillin 16 128 16–128 87 netilmicin 2 2 2 100 ticarcillin 16 128 16–128 85 ticarcillin/clavulanate 16 16 16–128 95 Providencia spp. (10) amoxycillin/clavulanate 32/16 32/16 1/0.5–32/16 30 ampicillin/sulbactam 4/2 32/16 1/0.5–32/16 50 aztreonam 1 1 1 100 carbenicillin 16 16 16–128 90 cefamandole 4 16 4–32 80 cefonicid 2 16 2–16 30 cefoperazone 4 8 4–8 100 cefotaxime 2 2 2 100 cefotetan 4 4 4 100 ceftazidime 1 1 1 100 ceftizoxime 2 2 2 100 ceftriaxone 2 2 2 100 chloramphenicol 16 16 4–16 40 ciprofloxacin 0.5 4 0.25–4 50 imipenem 2 4 0.5–4 100

17 J. M. Blondeau et al.

Table II. Continued

MIC (mg/L)

Organism MIC50 MIC90 range % Susceptibility

Providencia spp. (10) continued mezlocillin 16 16 16–64 90 netilmicin 4 16 2–16 80 ticarcillin 16 16 16–128 90 ticarcillin/clavulanate 16 16 16 100 Serratia spp. (6) amoxycillin/clavulanate 32/16 32/16 8/4–32/16 17 ampicillin/sulbactam 32/16 32/16 4/2–32/16 17 aztreonam 1 32 1–32 83 carbenicillin 16 128 16–128 67 cefamandole 32 32 32–32 0 cefonicid 16 16 16–16 0 cefoperazone 4 32 4–32 83 cefotaxime 2 2 2–16 83 cefotetan 4 4 4 100 ceftazidime 1 1 1–2 100 ceftizoxime 2 2 2–16 83 ceftriaxone 2 2 2–8 100 chloramphenicol 8 16 8–16 67 ciproﬂoxacin 0.25 0.5 0.25–4 83 imipenem 0.5 1 0.5–2 100 mezlocillin 16 16 16–64 83 netilmicin 4 8 2–16 83 ticarcillin 16 32 16–128 67 ticarcillin/clavulanate 16 16 16 100 S. maltophilia (3) amoxycillin/clavulanate 16/8 16/8 16/8 0 ampicillin/sulbactam 32/16 32/16 32/16 0 aztreonam 32 32 32–32 0 carbenicillin 32 128 16–128 2/3 cefamandole 32 32 32 0 cefonicid 16 16 16 0 cefoperazone 32 32 8–32 1/3 cefotaxime 32 32 16–32 0 cefotetan 8 8 4–8 3/3 ceftazidime 2 16 1–16 2/3 ceftizoxime 32 32 16–32 0 ceftriaxone 64 64 64 0 chloramphenicol 4 16 4–16 2/3 ciproﬂoxacin 1 4 0.5–4 2/3 imipenem 16 16 16 0 mezlocillin 128 128 16–128 1/3 netilmicin 16 16 16–16 0 ticarcillin 16 128 16–128 2/3 ticarcillin/clavulanate 16 32 16–32 2/3 Enterococcus spp. (210) amoxycillin/clavulanate 1/0.5 1/0.5 1/0.5–32–16 97 ampicillin/sulbactam 1/0.5 1/0.5 1/0.5–32–16 96 aztreonam 32 32 1–32 1 carbenicillin 16 16 16–128 92

18 In-vitro susceptibility of respiratory and urinary pathogens

Table II. Continued

MIC (mg/L)

Organism MIC50 MIC90 range % Susceptibility

Enterococcus spp. (210) continued cefamandole 16 32 4–32 8 cefonicid 16 16 2–32 2 cefoperazone 16 32 1–32 80 cefotaxime 64 64 2–64 17 cefotetan 32 32 4–32 2 ceftazidime 32 32 1–32 8 ceftizoxime 32 32 2–32 14 ceftriaxone 64 64 2–64 15 chloramphenicol 4 16 2–16 88 ciproﬂoxacin 1 4 0.25–64 65 imipenem 1 2 0.5–16 97 mezlocillin 16 16 16–128 95 netilmicin 8 16 2–16 52 ticarcillin 32 32 16–128 49 ticarcillin/clavulanate 32 32 16–128 40 S. agalactiae (35) amoxycillin/clavulanate 1/0.5 1/0.5 0.5/0.25–32/16 97 ampicillin/sulbactam 1/0.5 1/0.5 1/0.5 100 aztreonam 32 32 1–32 na carbenicillin 16 16 8–16 100 cefamandole 3 4 2–4 100 cefonicid 2 2 1–8 100 cefoperazone 4 4 2–4 100 cefotaxime 2 2 1–2 100 cefotetan 4 4 2–8 100 ceftazidime 0.5 1 0.5–2 100 ceftizoxime 2 2 1–2 100 ceftriaxone 2 2 1–2 100 chloramphenicol 2 2 1–16 94 ciproﬂoxacin 0.5 2 0.25–4 89 imipenem 0.5 0.5 0.25–0.5 100 mezlocillin 16 16 2–16 100 netilmicin 4 16 1–16 71 ticarcillin 16 16 8–16 100 ticarcillin/clavulanate 16 16 8–16 100 S. aureus (20) amoxycillin/clavulanate 1/0.5 1/0.5 1/0.5–8/4 100 ampicillin/sulbactam 1/0.5 2/1 1/0.5–8/4 100 aztreonam 32 32 32 0 carbenicillin 16 16 16–128 95 cefamandole 4 4 4–8 100 cefonicid 2 2 2–16 95 cefoperazone 4 4 4–32 95 cefotaxime 2 2 2–16 95 cefotetan 4 4 4–16 100 ceftazidime 8 8 4–32 95 ceftizoxime 2 4 2–32 95 ceftriaxone 2 2 2–64 95 chloramphenicol 4 8 2–8 100

19 J. M. Blondeau et al.

Table II. Continued

MIC (mg/L)

Organism MIC50 MIC90 range % Susceptibility

S. aureus (20) continued ciprofloxacin 0.25 0.5 0.25–4 95 imipenem 0.5 0.5 0.5–2 100 mezlocillin 16 64 16–128 85 netilmicin 2 2 2 100 ticarcillin 16 16 16–128 95 ticarcillin/clavulanate 16 16 16–32 95 Coagulase-negative staphylococci (61) amoxycillin/clavulanate 1/0.5 8/4 1/0.5–16/8 97 ampicillin/sulbactam 1/0.5 8/4 1/0.5–32/16 98 aztreonam 32 32 32 0 carbenicillin 16 128 16–128 84 cefamandole 4 8 4–32 92 cefonicid 4 16 2–16 82 cefoperazone 4 8 4–32 92 cefotaxime 2 32 2–64 82 cefotetan 16 32 4–32 69 ceftazidime 16 32 1–32 48 ceftizoxime 4 32 2–32 69 ceftriaxone 4 64 2–64 82 chloramphenicol 4 8 2–16 91 ciprofloxacin 0.25 4 0.25–16 71 imipenem 0.5 16 0.25–16 84 mezlocillin 16 64 16–128 84 netilmicin 2 2 2–16 98 ticarcillin 16 128 16–128 82 ticarcillin/clavulanate 16 64 16–128 84 Streptococcus spp. (3) amoxycillin/clavulanate 1/0.5 1/0.5 0.5/0.25–1/0.5 100 ampicillin/sulbactam 1/0.5 1/0.5 1/0.5 100 aztreonam 32 32 32–32 na carbenicillin 16 16 8–16 100 cefamandole 4 4 2–4 100 cefonicid 2 2 1–2 100 cefoperazone 4 4 2–4 100 cefotaxime 2 2 1–2 100 cefotetan 4 4 2–4 100 ceftazidime 1 1 0.5–1 100 ceftizoxime 2 2 1–2 100 ceftriaxone 1 2 1–2 100 chloramphenicol 2 2 1–2 100 ciprofloxacin 2 2 0.5–2 100 imipenem 0.5 0.5 0.25–0.5 100 mezlocillin 16 16 8–16 100 netilmicin 2 4 2–4 100 ticarcillin 16 16 8–16 100 ticarcillin/clavulanate 16 16 8–16 100

NA, No NCCLS breakpoint available. aAzlocillin activity against P. aeruginosa, 90%; Pseudomonas spp., 83%. bIncludes two isolates of Burkholderia cepacia.

20 In-vitro susceptibility of respiratory and urinary pathogens

Against all urinary tract pathogens tested, the five agents 56% of S. pneumoniae were susceptible to ciprofloxacin, with greatest activity were cefoperazone and netilmicin a rate much lower than their earlier finding and from (91% each); ciprofloxacin and ticarcillin/clavulanate (90% our findings in the current study (80%).12 The differences each) and imipenem (99%). Cefonicid (54%), cefaman- in pneumococcal susceptibilities to ciprofloxacin seen dole (57%), cefotetan (63%) and ceftizoxime (65%) were between this study and that of Hoban et al. may relate to the least active agents against all urinary tract isolates the methodology used: the Hoban study used Kirby–Bauer tested. methodology whereas ours used a commercial microbroth dilution method.17 Few Canadian studies have been published on antimi- Discussion crobial resistance amongst urinary tract isolates. Hoban et al.12 also determined the in-vitro activity of ciprofloxacin RTI and UTI are extremely common clinical conditions, against 1854 urinary tract isolates. The current findings often requiring antimicrobial therapy. Increasing anti- were similar to those of Hoban et al. except that cipro- microbial resistance affects the selection and use of anti- floxacin was approximately twice as active against Entero - microbial agents; consequently, knowledge of trends in coccus spp. (65% vs 38%) and slightly less active against antimicrobial resistance is crucial since empirical therapy is coagulase-negative staphylococcus (71% vs 80%) and P. common. Previously, we reported the susceptibility of 4500 aeruginosa (77% vs 91%). The apparently greater suscepti- organisms collected from 15 Canadian medical centres to bility of Enterococcus spp. seen in this study may be related 20 antimicrobial agents.11,15 We also separately reported on to a larger sample size in the current trial or to a dispropor- the frequency of resistance of 1503 isolates of P. aeruginosa tionate collection of either sensitive or resistant isolates to 12 antimicrobial agents.16 Unfortunately, the data from some of the participating centres. Previously, we had presented in those studies do not differentiate between shown that increasing resistance of P. aeruginosa to isolates collected from different sites of infection, and for ciprofloxacin was skewed by disproportionately higher some organisms and antimicrobial agents there are differ- resistance rates in some institutions than in others.11 A ential resistance rates depending on the site of infection.11 similar finding was seen here. For urinary tract isolates, The results reported here represent cumulative suscepti- 77% overall were susceptible to ciprofloxacin. However, 18 bility rates of respiratory and urinary tract pathogens centres had resistance rates 20% (range 25.0–85.7%). collected from Canadian medical institutions. These centres contributed 37.7% of the isolates. The over- Canadian studies that have specifically investigated the all susceptibility to ciprofloxacin of isolates from the susceptibility rates of respiratory and urinary tract remaining 32 centres was 90.2%.16 pathogens to this wide range of antimicrobial agents have Toye and co-workers20 reported antimicrobial resistance not been published previously. Hoban et al.12 reported, in rates among 656 isolates of Klebsiella spp. and 630 of 1995, on the susceptibility of 1529 respiratory tract isolates Enterobacter spp. from hospitalized patients. Comparison against five antimicrobial agents, two of which were also of resistance rates of Klebsiella spp. reported by Toye et al. tested in this study (amoxycillin/clavulanate and cipro- and those found in the current study revealed that rates floxacin). Our results were comparable to those of Hoban were within 5% for ciprofloxacin and within 1–2% for et al. for amoxycillin/clavulanate, our susceptibility results aztreonam, cefotaxime, ceftriaxone and imipenem. For being 3–7% higher for Haemophilus spp. and M. Enterobacter spp., resistance rates for all comparable catarrhalis, and 25% higher for E. coli.12 For ciprofloxacin, agents were within 1–2%, except for ceftazidime, suscepti- the results for Gram-negative organisms were comparable, bility to which was slightly higher in the current trial (83% with one exception: there was a significant decrease in the vs 76%). susceptibility of Stenotrophomonas maltophilia, 17% in the Chamberland et al.21 reported on the susceptibility of 941 our study as compared with 62% in that of Hoban and Gram-negative bacteria, tested against 27 antimicrobial colleagues. agents, from septicaemic patients in Canada. Of the com- For Gram-positive respiratory tract isolates, our results parable agents in the current respiratory and urinary tract for S. pneumoniae are broadly similar to those of several study, the results were within 8% for E. coli for 12 com- previous investigations. Hoban et al. reported in 199517 that parable agents and within 1% for aztreonam, cefotaxime, 85% of S. pneumoniae isolates from five North American ceftazidime, ceftriaxone, ciprofloxacin, imipenem and medical centres were susceptible to ciprofloxacin. In 1996, netilmicin. For Klebsiella, Proteus, Serratia and Enterobac - Forward et al.18 reported that 90% of S. pneumoniae ter spp., our results were consistent with those of Chamber- isolates collected from blood cultures from 58 Canadian land et al. However, there may be some differences since laboratories were susceptible to ciprofloxacin. Simor et al.19 our data are summarized by genera, whereas Chamberland also reported in 1996 that 97% of 1089 isolates of S. pneu - et al. presented the data by individual species. moniae (collected from 39 hospital and private laboratories When comparing the current in-vitro study with that of across Canada) were susceptible to ciprofloxacin. In con- Chamberland et al.,21 susceptibility rates for P. aeruginosa trast, the 1995 study by Hoban et al.12 reported that only during 1993–1994 do not appear to have changed signifi-

21 J. M. Blondeau et al. cantly for aztreonam, cefoperazone, ceftazidime, imi- Acknowledgements penem and netilmicin. Our findings for ceftazidime and imipenem are also consistent with those of Forward et al.18 We thank Jonathan Harris, Teresa Tartaglione and Joan For ciprofloxacin we found that 86% of P. aeruginosa Hinchcliffe for editorial contributions. This work on anti- respiratory isolates were susceptible, while Chamberland microbial agents is supported by unrestricted grants from et al. reported 100% susceptibility amongst 47 isolates.21 ten pharmaceutical companies including Bayer. The Cana- Hoban and co-workers reported in 199512 a 4–10% inci- dian Respiratory Tract Pathogens Study Group and Sites dence of resistance to ciprofloxacin for P. aeruginosa from were as follows: Vancouver General Hospital (J. Smith), Canadian medical centres, whereas Hoban et al. in 199317 Vancouver, British Columbia; Metro NcNari Laboratories found that 15% of P. aeruginosa from five North American (J. Brittante), Vancouver, British Columbia; Chilliwack medical centres were resistant. Coronado et al.13 reported General Hospital (L. Holliday), Chilliwack, British that 4.7% of 8517 P. aeruginosa isolates collected between Columbia; Matsqui Sumas Hospital (M. Peterson), 1989 and 1992 were ciprofloxacin-resistant. In the UK, Abbotsford, British Columbia; Kelowna General Hospital Tillotson et al.22 reported on a 6 year surveillance of cipro- (M. Jeans), Kelowna, British Columbia; Royal Inland Hos- floxacin-resistant P. aeruginosa and found an increase in pital (K. R. Wagner), Kamloops, British Columbia; Prince resistance from 1.4% to 11.1%. Recently, Forward et al.18 George General Hospital (L. Coult), Prince George, reported on the in-vitro susceptibility of 2747 aerobic blood British Columbia; Alberta Children’s Hospital (D. culture isolates from 58 Canadian laboratories. In that Church), Calgary, Alberta; Rockyview General Hospital study, susceptibility of P. aeruginosa to ciprofloxacin was (L. Stafford), Calgary, Alberta; Foothills Hospital/Provin- 97%. Coronado et al.13 found that resistance was higher cial Laboratory (C. Johnson), Calgary, Alberta; Stirrat from respiratory tract isolates, whereas we found that Laboratories (S. Bracken), Edmonton, Alberta; Misercor- resistance was higher in UTI. The reduction in P. aeru - dia Grey Nuns Hospital (P. Kibsey), Edmonton, Alberta; ginosa susceptibility rates to 86% in this study may be due Victoria Union Hospital (E. Engle), Prince Albert, to several different factors. The number of isolates tested in Saskatchewan; St Paul’s Grey Nuns’ Hospital (J. Blon- this study was approximately seven times higher than the deau), Saskatoon, Saskatchewan; Saskatoon City Hospital number tested in previous studies. This larger sampling (A. Warner), Saskatoon, Saskatchewan; Royal University may represent a more accurate indication of resistance Hospital (P. Tilley), Saskatoon, Saskatchewan; Medical rates in Canada. Additionally, we previously reported that Arts Laboratory (J. Thaier), Saskatoon, Saskatchewan; the incidence of ciprofloxacin-resistant P. aeruginosa was Pasqua Hospital (J. Kirsch), Regina, Saskatchewan; not uniformly distributed, some individual centres having Regina General Hospital (E. Thomas), Regina, Saskat- resistance rates that were 7–19% higher than the national chewan; Yorkton Regional Health Centre (B. Burgford), average.11 This was also observed in this study. For respira- Yorkton, Saskatchewan; Brandon Regional Hospital tory tract isolates, although 86% of isolates overall were (M. Yorke), Brandon, Manitoba; Health Sciences Centre susceptible to ciprofloxacin, 13 centres had resistance rates (D. Hoban), Winnipeg, Manitoba; Misercordia General 20% (range 26.7–65.6%) and these centres contributed Hospital (P. Landolfe), Winnipeg, Manitoba; St Boniface 23.3% of isolates. The overall susceptibility from the General Hospital (G. Harding), Winnipeg, Manitoba; remaining 37 centres was 91%. These observations, com- Sunnybrook Medical Centre (A. Simor), Toronto, Ontario; bined with those seen in the susceptibility rates of urinary Mount Sinai and Princess Margaret Hospitals (D. Low), isolates, indicate the importance of defining hospital-spe- Toronto, Ontario; St Joseph’s Health Centre (S. Krajden), cific resistance rates in addition to summaries based on Toronto, Ontario; University Hospital (D. Colby), Lon- national and international data. don, Ontario; Hamilton General Hospital (L. Vaillan- On the basis of the results from this study and in com- court), Hamilton, Ontario; Chedoke–McMaster Hospital parison with results from previous surveys, we conclude (N. Lamuthe), Ottawa, Ontario; Ottawa Civic Hospital that resistance to broad-spectrum antimicrobial agents for (P. Jessamine), Ottawa, Ontario; Ottawa General Hospital respiratory or urinary tract pathogens, does not appear to (N. Lamuthe), Ottawa, Ontario; Hopital Maissonneuve– be increasing significantly in Canadian medical centres. Rosemont (M. Laverdiere), Montreal, Quebec; Centre One exception is the increase in penicillin-resistant Hospitalier St Joseph (D. Archand), TroisRiviere, Quebec; S. pneumoniae recently described by Simor et al.19 (11.7% Centre Hospitalier Universitaire de Sherbrooke (Y. overall; 8.4% intermediate, 3.3% high level) and Blondeau Racine), Sherbrooke, Quebec; Hôpital du Saint-Sacrement et al.23 (13% overall, all intermediate resistance). The (G. Murray), Quebec City, Quebec; Edmonston Regional concern over increasing antimicrobial resistance mandates Hospital (F. Volpe), Edmonston, New Brunswick; St John a need to continue monitoring resistance at the same insti- Regional Hospital (J. MacDonald), St John, New tutions on a regular basis. If changes in resistance rates are Brunswick; The Moncton Hospital (M. Kuhn), Moncton, detected, it will provide an opportunity to address these New Brunswick; Northeast Health Network (J. Miller), changes in relationship to patterns of empirical antimicro- Bathurst, New Brunswick; Halifax Infirmary/Camp Hill bial use. Complex (S. MacDonald), Halifax, Nova Scotia; Yar-

22 In-vitro susceptibility of respiratory and urinary pathogens mouth Regional Hospital (S. Stephan), Yarmouth, Nova 13. Coronado, V. G., Edwards, J. R., Culver, D. H., Gaynes, R. P. & Scotia; Cape Breton Regional Hospital (R. Lewis), Sydney, the National Nosocomial Infections Surveillance (NNIS) System. Nova Scotia; Prince County Hospital (S. MacMillan), Sum- (1995). Ciprofloxacin resistance among nosocomial Pseudomonas aeruginosa and Staphylococcus aureus in the United States. Infec- merside, Prince Edward Island; Central Newfoundland tion Control and Hospital Epidemiology16, 71Ð5. Regional Health Centre (E. White), Grand Falls, New- 14. National Committee for Clinical Laboratory Standards. (1994). foundland; The General Hospital (W. Brown), St John, Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria Newfoundland; St Clare’s Mercy Hospital (J. Martin), St that Grow Aerobically: Approved Standard M7-A7. NCCLS, Villa- John’s, Newfoundland; Stanton Yellowknife Hospital (N. nova, PA. Fraley), Yellowknife, Northwest Territories. This work 15. Blondeau, J. M., Suter, M. & the Canadian Antimicrobial Resis- was presented, in part, at the Sixty-Second Annual Inter- tance Group. (1997). Antimicrobial susceptibilities of Canadian iso- national Scientific Assembly of the American College of lates of Haemophilus influenzae, Streptococcus pneumoniae and Chest Physicians, San Francisco, CA, 27–31 October 1996 Moraxella catarrhalis: comparison of 3 test methods. In Proceedings and at the Ninety-First Annual Meeting of the American of the Twentieth International Congress of Chemotherapy, Sydney, Australia, 1997. Abstract P001Ð4204, p. 52. Organizing Committee Urological Association, Orlando, FL, 4–9 May 1996. of the International Congress of Chemotherapy, Victoria, Australia. 16. Blondeau, J. M., Shiplett, M. E. & the Canadian Study Group. (1995). 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