Mel DeCorby

Antimicrobial-Resistant Pathogens in Intensive Care Units in Canada: Results of the Canadian National Intensive Care Unit (CAN-ICU) Study, 2005-2006

ABSTRACT Between 1 September 2005 and 30 June 2006, 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 β-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 blaCTX-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.

Antimicrobial susceptibility of 3931 organisms isolated from intensive care units in Canada: Canadian National Intensive Care Unit Study, 2005/2006

We tested the in vitro activity of 15 antimicrobials against Gram-positive cocci and 12 antimicrobials against Gram-negative bacilli versus 3931 isolates (20 most common organisms) obtained between September 1, 2005, and June 30, 2006, from 19 intensive care units (ICUs) across Canada. The most active (based upon MIC only) agents against methicillin-resistant Staphylococcus aureus and methicillin-resistant Staphylococcus epidermidis were dalbavancin, daptomycin, linezolid, tigecycline, and vancomycin with MIC(90) (microg/mL) of 0.06 and < or =0.03, 0.25 and 0.12, 2 and 1, 0.5 and 0.5, and 1 and 2, respectively. The most active agents against vancomycin-resistant enterococci were daptomycin, linezolid, and tigecycline with MIC(90) (microg/mL) of 1, 4, and 0.12, respectively. The most active agents against Escherichia coli were amikacin, cefepime, meropenem, piperacillin/tazobactam, and tigecycline with MIC(90) (microg/mL) of 4, < or =1, < or =0.12, 8, and 0.5, respectively. The most active agents against extended-spectrum beta-lactamase-producing E. coli were meropenem and tigecycline with MIC(90) (microg/mL) of < or =0.12 and 1, respectively. The most active agents against Pseudomonas aeruginosa were amikacin, cefepime, meropenem, and piperacillin/tazobactam with MIC(90) (microg/mL) of 16, 32, 16, and 64, respectively. The most active agents against Stenotrophomonas maltophilia were tigecycline and trimethoprim/sulfamethoxazole with MIC(90) (microg/mL) of 4 and 4, respectively. The most active agents against Acinetobacter baumannii were fluoroquinolones (e.g., levofloxacin), meropenem, and tigecycline with MIC(90) (microg/mL) of 0.5, 1, and 2, respectively. In conclusion, the most active agents versus Gram-positive cocci and Gram-negative bacilli obtained from Canadian ICUs were daptomycin, linezolid, tigecycline, dalbavancin and amikacin, cefepime, meropenem, piperacillin/tazobactam, and tigecycline (not P. aeruginosa), respectively.

Dalbavancin and telavancin: novel lipoglycopeptides for the treatment of Gram-positive infections

Two glycopeptide analogues of vancomycin and teicoplanin have been developed with improved pharmacokinetic/pharmacodynamic parameters. Dalbavancin was derived from teicoplanin, and telavancin is a derivative of vancomycin. The half-life of dalbavancin in humans is 147–258 h (6–11 days) allowing for weekly administration. Dalbavancin possesses more potent in vitro activity than vancomycin or teicoplanin. Dalbavancin has been investigated in uncomplicated and complicated skin and skin structure infections (SSSIs) in clinical trials and has demonstrated equivalent or superior (versus vancomycin only) efficacy versus comparators. Telavancin exhibits a dual mechanism of action, low potential for resistance development and is active against resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). Clinical trials involving SSSIs have demonstrated equivalent or superior (versus vancomycin for MRSA) efficacy compared with a standard therapy. Both telavancin and dalbavancin show promise as alternative treatments for patients with serious infections caused by resistant Gram-positive pathogens.

Characterization of methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci and extended-spectrum beta-lactamase-producing Escherichia coli in intensive care units in Canada: Results of the Canadian National Intensive Care Unit (CAN-ICU) study (2005–2006)

BACKGROUND Methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and vancomycin-resistant enterococci (VRE) are important hospital pathogens in Canada and worldwide. OBJECTIVES To genotypically and phenotypically characterize the isolates of MRSA, VRE and ESBL-producing E coli collected from patients in Canadian intensive care units (ICUs) in 2005 and 2006. METHODS Between September 1, 2005, and June 30, 2006, 19 medical centres participating in the Canadian National Intensive Care Unit (CAN-ICU) study collected 4133 unique patient isolates associated with infections in ICUs. Isolates of MRSA underwent mecA polymerase chain reaction (PCR) and Panton-Valentine leukocidin analysis; they were typed using pulsed-field gel electrophoresis. All isolates of E coli with ceftriaxone minimum inhibitory concentrations greater than or equal to 1 mug/mL were tested for the presence of an ESBL using the Clinical Laboratory Standards Institute double-disk diffusion method. Subsequently, PCR and sequence analysis were used to identify bla(SHV), bla(TEM) and bla(CTX-M). Isolates of VRE were tested for the presence of vanA and vanB genes by PCR. RESULTS Of the 4133 ICU isolates collected, MRSA accounted for 4.7% (193 of 4133) of all isolates. MRSA represented 21.9% (193 of 880) of all S aureus collected during the study; 90.7% were health care-associated MRSA strains and 9.3% were community-associated MRSA strains. Resistance rates for the isolates of MRSA were 91.8% to levofloxacin, 89.9% to clarithromycin, 76.1% to clindamycin and 11.7% to trimethoprim-sulfamethoxazole; no isolates were resistant to vancomycin, linezolid, tigecycline or daptomycin. ESBL-producing E coli accounted for 0.4% (18 of 4133) of all isolates and 3.7% (18 of 493) of E coli isolates. All 18 ESBL-producing E coli were PCR-positive for CTX-M, with bla(CTX-M-15) occurring in 72% (13 of 18) of isolates. All ESBL-producing E coli displayed a multidrug-resistant phenotype (resistant to third-generation cephalosporins and one or more other classes of antimicrobials), with 77.8% of isolates resistant to ciprofloxacin, 55.6% resistant to trimethoprim-sulfamethoxazole, 27.8% resistant to gentamicin and 26.3% resistant to doxycycline; all isolates were susceptible to ertapenem, meropenem and tigecycline. VRE accounted for 0.4% (17 of 4133) of all isolates and 6.7% (17 of 255) of enterococci isolates; 88.2% of VRE had the vanA genotype. Isolated VRE that were tested were uniformly susceptible to linezolid, tigecycline and daptomycin. CONCLUSIONS MRSA isolated in Canadian ICUs in 2005 and 2006 was predominately health care-associated (90.7%), ESBL-producing E coli were all CTX-M producers (72% bla(CTX-M-15)) and VRE primarily harboured a vanA genotype (88.2%). MRSA, ESBL-producing E coli and VRE were frequently multidrug resistant.

ESBL genotypes in fluoroquinolone-resistant and fluoroquinolone-susceptible ESBL-producing Escherichia coli urinary isolates in Manitoba.

OBJECTIVE Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli are increasingly common in nosocomial and community settings. Furthermore, fluoroquinolone (FQ) and even multidrug resistance (MDR) appear to be associated with certain ESBL genotypes. The purpose of the present study was to determine which ESBL genotypes are associated with FQ and MDR in E coli urinary isolates in Manitoba. METHODS The authors determined the antimicrobial susceptibility, genetic similarity and ESBL genotype of 27 FQ-resistant and seven FQ-susceptible, ESBL-producing urinary isolates submitted to the clinical microbiology laboratories of two teaching hospitals between October 2000 and April 2005. Susceptibilities to beta-lactams, FQs, trimethoprim-sulfamethoxazole (SXT), doxycycline (DOX), gentamicin (GM) and tigecycline were determined by microbroth dilution; pulsed-field gel electrophoresis (PFGE) was used to determine genetic relatedness, and ESBL genotype was determined by polymerase chain reaction and sequencing. RESULTS Of 34 ESBL-producing organisms, 27 (79.4%) were found to be ciprofloxacin (CIP) resistant, 27 (79.4%) were SXT resistant, eight (23.5%) were GM resistant and 29 (85.3%) were DOX resistant. Twenty-three (67.6%) had MDR, with concomitant resistance to CIP and SXT; 16 had concomitant resistance to CIP, SXT and DOX; and seven (20.6%) had MDR, with concomitant resistance to CIP, SXT, DOX and GM. All isolates were susceptible to tigecycline. Of 27 FQ-resistant ESBL-producing organisms, seven (25.9%) were genotype CTX-M-14, 19 (70.4%) were genotype CTX-M-15 and one (3.7%) was genotype CTX-M-24. Among the seven FQ-susceptible strains, three (42.8%) expressed SHV-type enzymes, three (42.8%) expressed TEM-type enzymes and one (14.3%) expressed CTX-M-9. CTX-M-15 was the most common MDR-associated genotype. Of a total of 19 strains, 18 (94.7%) were resistant to FQs and SXT; 15 (78.9%) were resistant to FQs, SXT and DOX; and five (26.3%) were resistant to FQs, SXT, DOX and GM. PFGE analysis revealed genetic similarity within CTX-M-15-producing isolates only. CONCLUSION CTX-M-15 in E coli is strongly associated with an MDR phenotype compared with other genotypes. CTX-M-14 is associated with FQ resistance only. PFGE suggests clonality of CTX-M-15-producing isolates within and among hospitals.

Prevalence of antimicrobial-resistant pathogens in Canadian hospitals: results of the Canadian Ward Surveillance Study (CANWARD 2007).

BACKGROUND: Canadian hospitals as well as hospitals worldwide are increasingly faced with antibiotic-resistant pathogens, including multidrug-resistant (MDR) strains. OBJECTIVES: To assess the prevalence of pathogens, including the resistance genotypes of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE) and extendedspectrum beta-lactamase (ESBL)-producing Escherichia coli in Canadian hospitals, as well as their antimicrobial resistance patterns. MEtHODS: Bacterial isolates were obtained between January 1, 2007, and December 31, 2007, inclusive, from patients in 12 hospitals across Canada as part of the Canadian Ward Surveillance Study (CANWARD 2007). Isolates were obtained from bacteremic, urinary, respiratory and wound specimens and underwent antimicrobial susceptibility testing. Susceptibility testing was assessed using the Clinical and Laboratory Standards Institute broth microdilution method. RESULTS: In total, 7881 isolates were recovered from clinical specimens of patients attending Canadian hospitals. The 7881 isolates were collected from respiratory (n=2306; 29.3%), blood (n=3631; 46.1%), wounds/tissue (n=617; 7.8%) and urinary (n=1327; 16.8%) specimens. The 10 most common organisms isolated from 76.5% of all clinical specimens were E coli (21.6%), methicillin-susceptible S aureus (13.9%), Streptococcus pneumoniae (8.9%), Pseudomonas aeruginosa (8.0%), Klebsiella pneumoniae (5.8%), MRSA (4.9%), Haemophilus influenzae (4.3%), coagulase-negative staphylococci/taphylococcus epidermidisS (4.0%), Enterococcus species (3.0%) and Enterobacter cloacae (2.1%). MRSA made up 26.0% (385 of 1480) of all S aureus (genotypically, 79.2% of MRSA were health care-associated MRSA and 19.5% were community-associated MRSA), and VRE made up 1.8% of all enterococci (62.5% of VRE had the vanA genotype). ESBLproducing E coli occurred in 3.4% of E coli isolates. The CTX-M type was the predominant ESBL, with CTX-M-15 as the predominant genotype. With MRSA, no resistance was observed to daptomycin, linezolid, tigecycline and vancomycin, while resistance rates to other agents were: clarithromycin 91.4%, clindamycin 61.8%, fluoroquinolones 88.6% to 89.6%, and trimethoprim-sulfamethoxazole 12.2%. With E coli, no resistance was observed to ertapenem, meropenem and tigecycline, while resistance rates to other agents were: amikacin 0.1%, cefazolin 14.2%, cefepime 2.0%, ceftriaxone 8.9%, gentamicin 10.6%, fluoroquinolones 23.6% to 24.5%, piperacillin-tazobactam 1.3% and trimethoprim-sulfamethoxazole 26.6%. Resistance rates with P aeruginosa were: amikacin 7.6%, cefepime 11.7%, gentamicin 20.8%, fluoroquinolones 23.4% to 25.1%, meropenem 8.1% and piperacillin- tazobactam 7.3%. A MDR phenotype (resistance to three or more of cefepime, piperacillin-tazobactam, meropenem, amikacin or gentamicin, and ciprofloxacin) occurred frequently in P aeruginosa (10.6%) but uncommonly in E coli (1.2%), K pneumoniae (1.5%), E cloacae (0%) or H influenzae (0%). CONCLUSIONS: E coli, S aureus (methicillin-susceptible and MRSA), S pneumoniae, P aeruginosa, K pneumoniae, H influenzae and Enterococcus species are the most common isolates recovered from clinical specimens in Canadian hospitals. The prevalence of MRSA was 26.0% (of which genotypically, 19.5% was community-associated MRSA), while VRE and ESBL-producing E coli occurred in 1.8% and 3.4% of isolates, respectively. A MDR phenotype is common with P aeruginosa in Canadian hospitals.

In Vitro Activities of Ceftobiprole and Doripenem Tested against Frequently Encountered Aerobic and Facultative Gram-Positive and Gram-Negative Bacterial Pathogens Isolated from Patients in Canadian Hospitals in 2007

BACKGROUND: In 2008, ceftobiprole was approved by Health Canada for the treatment of patients with complicated skin and skin structure infections including diabetic foot infections; approval of ceftobiprole by the United States Food and Drug Administration is pending. Doripenem is currently under review by Health Canada and was approved by the United States Food and Drug Administration in 2007 for the treatment of patients with complicated intra-abdominal infections and complicated urinary tract infections, including pyelonephritis. OBJECTIVES: To determine the in vitro activities of ceftobiprole and doripenem using a collection of frequently isolated aerobic and facultative bacteria cultured from patient blood, urine, respiratory and wound specimens in 12 Canadian hospitals in 2007. MEtHODS: Isolates were tested for their susceptibility to a panel of antimicrobial agents using the Clinical and Laboratory Standards Institute broth microdilution method. RESULTS: Ceftobiprole inhibited all isolates of methicillin-resistant Staphylococcus aureus (n=385), methicillin-resistant Staphylococcus epidermidis (n=20), methicillin-susceptible S aureus (n=1095) and methicillin-susceptible S epidermidis (n=108) at a minimum inhibitory concentration (MIC) of 2 μg/mL or less; all isolates of Streptococcus pyogenes (n=105) were inhibited by ceftobiprole at 0.06 μg/mL or less. All isolates of S aureus (MIC 4 μg/mL or less) and S pyogenes (MIC 0.5 μg/mL or less) tested were susceptible to ceftobiprole. Greater than 99% of extended-spectrum beta-lactamase (ESBL)-negative Escherichia coli (n=1528) and Klebsiella pneumoniae (n=436) were susceptible to ceftobiprole (MIC 1 μg/mL or less); against other genera/species of Enterobacteriaceae, susceptibility to ceftobiprole ranged from 80.7% for Enterobacter cloacae (n=166) to 99.2% for Proteus mirabilis (n=119). Ceftobiprole was less active against Pseudomonas aeruginosa (n=633) (90% of isolates inhibited at a concentration of 32 μg/mL [MIC90]) than Enterobacteriaceae. Doripenem inhibited 90% of isolates of E coli (n=1577) and K pneumoniae (n=456), including ESBL-producing isolates (n=69), and E cloacae at a concentration of 0.06 μg/mL or less; doripenem and meropenem had MIC90s of 8 μg/mL for the isolates of P aeruginosa tested. Doripenem demonstrated in vitro activity indistinguishable from that of meropenem against Gram-positive pathogens. CONCLUSIONS: All isolates of methicillin-resistant S aureus tested were susceptible to ceftobiprole (MIC 4 μg/mL or less), differentiating it from any other currently marketed beta-lactam. Doripenem demonstrated potent activity (MIC90 0.5 μg/mL or less) against all isolates of Enterobacteriaceae tested, including ESBL-producing E coli and K pneumoniae, and as potent activity as meropenem (MIC90 8 μg/mL) against P aeruginosa. The current study demonstrated both ceftobiprole and doripenem to be promising broad-spectrum antibacterial agents.

Antimicrobial susceptibility of 6685 organisms isolated from Canadian hospitals: CANWARD 2007.

BACKGROUND: Antimicrobial resistance is a growing problem in North American hospitals as well as hospitals worldwide. OBJECTIVES: To assess the antimicrobial susceptibility patterns of commonly used agents against the 20 most common organisms isolated from Canadian hospitals. METHODS: In total, 7881 isolates were obtained between January 1, 2007, and December 31, 2007, from 12 hospitals across Canada as part of the Canadian Ward Surveillance Study (CANWARD 2007). Of these, 6685 isolates (20 most common organisms) obtained from bacteremic, urinary, respiratory and wound specimens underwent antimicrobial susceptibility testing. Susceptibility testing was assessed using the Clinical and Laboratory Standards Institute broth microdilution method. RESULTS: The most active (based upon minimum inhibitory concentration [MIC] data only) agents against methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE) were dalbavancin, daptomycin, linezolid, telavancin, tigecycline and vancomycin, with MICs required to inhibit the growth of 90% of organisms (MIC90) of 0.06 μg/mL and 0.06 μg/mL, 0.25 μg/mL and 0.25 μg/mL, 4 μg/mL and 1 μg/mL, 0.25 μg/mL and 0.25 μg/mL, 0.5 μg/mL and 0.25 μg/mL, and 1 μg/mL and 2 μg/mL, respectively. The most active agents against vancomycin-resistant enterococci were daptomycin, linezolid and tigecycline with MIC90s of 2 μg/mL, 4 μg/mL and 0.12 μg/mL, respectively. The most active agents against Escherichia coli were amikacin, cefepime, ertapenem, meropenem, piperacillin-tazobactam and tigecycline with MIC90s of 4 μg/mL, 2 μg/mL, 0.06 μg/mL or less, 0.12 μg/mL or less, 4 μg/mL and 1 μg/mL, respectively. The most active agents against extendedspectrum beta-lactamase-producing E coli were ertapenem, meropenem and tigecycline with MIC90s of 0.12 μg/mL or less, 0.12 μg/mL or less and 1 μg/mL, respectively. The most active agents against Pseudomonas aeruginosa were amikacin, cefepime, meropenem and piperacillin-tazobactam with MIC90s of 32 μg/mL, 32 μg/mL, 8 μg/mL and 64 μg/mL, respectively. The most active agents against Stenotrophomonas maltophilia were tigecycline and trimethoprimsulfamethoxazole and levofloxacin with MIC90s of 8 μg/mL, 8 μg/mL and 8 μg/mL, respectively. The most active agents against Acinetobacter baumannii were amikacin, fluoroquinolones (eg, levofloxacin), meropenem, and tigecycline with MIC90s of 2 μg/mL or less, 1 μg/mL, 4 μg/mL and 2 μg/mL, respectively. CONCLUSIONS: The most active agents versus Gram-positive cocci from Canadian hospitals were vancomycin, linezolid, daptomycin, tigecycline, dalbavancin and telavancin. The most active agents versus Gram-negative bacilli from Canadian hospitals were amikacin, cefepime, ertapenem (not P aeruginosa), meropenem, piperacillintazobactam and tigecycline (not P aeruginosa). Colistin (polymyxin E) was very active against P aeruginosa and A baumannii.