, 19 medical centers collected 4,180 isolates recovered from clinical specimens from patients in intensive care units (ICUs) in Canada. The 4,180 isolates were collected from 2,292 respiratory specimens (54.8%), 738 blood specimens (17.7%), 581 wound/tissue specimens (13.9%), and 569 urinary specimens (13.6%). The 10 most common organisms isolated from 79.5% of all clinical specimens were methicillin-susceptible Staphylococcus aureus (MSSA) (16.4%), Escherichia coli (12.8%), Pseudomonas aeruginosa (10.0%), Haemophilus influenzae (7.9%), coagulase-negative staphylococci/Staphylococcus epidermidis (6.5%), Enterococcus spp. (6.1%), Streptococcus pneumoniae (5.8%), Klebsiella pneumoniae (5.8%), methicillin-resistant Staphylococcus aureus (MRSA) (4.7%), and Enterobacter cloacae (3.9%). MRSA made up 22.3% (197/884) of all S. aureus isolates (90.9% of MRSA were health care-associated MRSA, and 9.1% were community-associated MRSA), while vancomycin-resistant enterococci (VRE) made up 6.7% (11/255) of all enterococcal isolates (88.2% of VRE had the vanA genotype). Extended-spectrum ␤-lactamase (ESBL)-producing E. coli and K. pneumoniae occurred in 3.5% (19/536) and 1.8% (4/224) of isolates, respectively. All 19 ESBL-producing E. coli isolates were PCR positive for CTX-M, with bla CTX-M-15 occurring in 74% (14/19) of isolates. For MRSA, no resistance against daptomycin, linezolid, tigecycline, and vancomycin was observed, while the resistance rates to other agents were as follows: clarithromycin, 89.9%; clindamycin, 76.1%; fluoroquinolones, 90.1 to 91.8%; and trimethoprim-sulfamethoxazole, 11.7%. For E. coli, no resistance to amikacin, meropenem, and tigecycline was observed, while resistance rates to other agents were as follows: cefazolin, 20.1%; cefepime, 0.7%; ceftriaxone, 3.7%; gentamicin, 3.0%; fluoroquinolones, 21.1%; piperacillin-tazobactam, 1.9%; and trimethoprim-sulfamethoxazole, 24.8%. Resistance rates for P. aeruginosa were as follows: amikacin, 2.6%; cefepime, 10.2%; gentamicin, 15.2%; fluoroquinolones, 23.8 to 25.5%; meropenem, 13.6%; and piperacillin-tazobactam, 9.3%. A multidrug-resistant (MDR) phenotype (resistance to three or more of the following drugs: cefepime, piperacillin-tazobactam, meropenem, amikacin or gentamicin, and ciprofloxacin) occurred frequently in P. aeruginosa (12.6%) but uncommonly in E. coli (0.2%), E. cloacae (0.6%), or K. pneumoniae (0%). In conclusion, S. aureus (MSSA and MRSA), E. coli, P. aeruginosa, H. influenzae, Enterococcus spp., S. pneumoniae, and K. pneumoniae are the most common isolates recovered from clinical specimens in Canadian ICUs. A MDR phenotype is common for P. aeruginosa isolates in Canadian ICUs.

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Ciprofloxacin-resistant Escherichia coli isolates (n ‫؍‬ 1,858) from outpatient midstream urine specimens at 40 North American clinical laboratories in 2004 to 2005 were frequently resistant to ampicillin (79.8% of isolates) and trimethoprim-sulfamethoxazole (66.5%); concurrent resistance to cefdinir (9.0%) or nitrofurantoin (4.0%) was less common. Only 10.8% of isolates were resistant to ciprofloxacin alone. Fluoroquinoloneresistant isolates of E. coli from urine were frequently multidrug resistant.The most recently published in vitro surveillance data from centers across the United States and Canada indicate that approximately 10 to 25% of urinary tract isolates of Escherichia coli from female outpatients are resistant to trimethoprimsulfamethoxazole (SXT) (3,7,10,11,12,21,22,25,26). Culture selection and sample selection biases inherent in published urinary isolate surveillance studies and hospital antibiograms have been summarized previously (8). Resistance to SXT may complicate the management of urinary tract infections (20), and physician concern regarding resistance to SXT (24) has resulted in fluoroquinolones and nitrofurantoin being more frequently prescribed as empirical therapy for cystitis (7, 9, 15).Currently, the majority of urinary isolates of E. coli and most other uropathogens causing uncomplicated cystitis and pyelonephritis in the United States and Canada remain susceptible to fluoroquinolones (5,10,11,12,21,22,25,26); however, the prevalence of fluoroquinolone-resistant isolates of E. coli has been reported to be increasing over time in some centers in the United States and Canada (3,7,11,12,13,18,23,25), and resistance rates have been shown to vary markedly by center, with some hospital laboratories reporting Ͼ25% of their E. coli isolates as fluoroquinolone resistant (3,23). Given that a transition in the therapy for outpatient urinary tract infections may be occurring, or appears imminent (7,8,9,15), and that fluoroquinolone-resistant isolates of E. coli are not uncommon in some centers, we determined the in vitro susceptibilities of prospectively collected fluoroquinolone-resistant midstream urine isolates of E. coli from outpatients to other agents used for the treatment of acute cystitis because these isolates may be encountered by clinicians and no prospective study specifically studying fluoroquinolone-resistant isolates has been published.From January 2004 to June 2005, fluoroquinolone-resistant E. coli isolates from midstream urine specimens from outpatients were collected from 30 medical centers in the United States (n ϭ 1,483) and from 10 Canadian medical centers (n ϭ 375) (25). Each isolate was deemed to be a significant urinary tract isolate by each participating laboratory's urine culture algorithm. Isolates and limited demographic information (patient gender and age) were submitted to the Health Sciences Centre in Winnipeg, Canada, where the isolates were confirmed to be E. coli by conventional methodology (17) and where Clinical and Laboratory Standards Institute-specified br...

The mutant prevention concentrations (MPCs) of levofloxacin alone and in combination with ceftazidime, colistin (polymyxin E), meropenem, piperacillin-tazobactam, and tobramycin were established against Pseudomonas aeruginosa. Antibiotic combinations using levofloxacin with any antibiotic with individual activity against P. aeruginosa resulted in synergistic lowering (an at-least-fourfold reduction) of the isolate's MPC.With a limited pool of available antibiotics capable of treating Pseudomonas aeruginosa infections, the suppression of the further emergence of resistance is important. Fluoroquinolones, such as ciprofloxacin and levofloxacin, are routinely used to treat patients with P. aeruginosa infections. Fluoroquinolone resistance can be selected for upon exposure to the fluoroquinolones, leading to dramatic increases in MICs and subsequent treatment failure (3, 4).The manipulation of fluoroquinolone-dosing strategies has been suggested as a way to limit the selection for fluoroquinolone-resistant mutants and preserve this antimicrobial class (1-3, 9, 11). A range of fluoroquinolone concentrations, known as the mutant selection window (MSW), exists in which point mutations are more likely to be selected for. The MSW is bound by the MIC at its lower end and the organism's mutant prevention concentration (MPC) at its upper end. The MPC is the drug concentration required to prevent the emergence of all single-step-mutation, fluoroquinolone-resistant mutants in a population of approximately 10 10 bacterial cells (2, 11). If fluoroquinolone-dosing strategies maintain concentrations above the MPC for a long enough duration, a reduced risk of selecting for single-step-mutation, resistant mutants may result.The addition of a second antibiotic to a fluoroquinolone treatment regime has been shown to lower an organism's MPC (1, 2, 11). In order to survive treatment with two antimicrobials, an organism has to develop spontaneous mutations causing resistance to both drugs, assuming that the two antimicrobials act via different modes of action and that the organism is initially susceptible to both agents (1, 2, 11).We examined this dual-drug MPC hypothesis by determining the MPCs of levofloxacin alone and in combination with other drugs against P. aeruginosa. Additionally, MPCs for the nonfluoroquinolone antimicrobials were established individually to examine whether any MPC changes observed with the dualdrug therapy were due to synergistic (an at-least-fourfold reduction) or additive (a less-than-fourfold reduction) effects. The working hypothesis was that two antimicrobials that possessed different mechanisms of action and that both displayed individual activity against P. aeruginosa would display a reduced MPC in combination relative to the individual antimicrobial MPCs.The P. aeruginosa isolates (46139, 49674, and 36375) were collected as part of the North American Urinary Tract Infection Collaborative Alliance (10). The identity of each isolate was confirmed by the central reference laboratory (Health Sciences Centr...