Melanie DeCorby

Fluoroquinolone-Resistant Urinary Isolates of Escherichia coli from Outpatients Are Frequently Multidrug Resistant: Results from the North American Urinary Tract Infection Collaborative Alliance-Quinolone Resistance Study

ABSTRACT 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. Fluoroquinolone-resistant isolates of E. coli from urine were frequently multidrug resistant.

Prevalence of Antimicrobial-Resistant Pathogens in Canadian Hospitals: Results of the Canadian Ward Surveillance Study (CANWARD 2008)

ABSTRACT A total of 5,282 bacterial isolates obtained between 1 January and 31 December 31 2008, inclusive, from patients in 10 hospitals across Canada as part of the Canadian Ward Surveillance Study (CANWARD 2008) underwent susceptibility testing. The 10 most common organisms, representing 78.8% of all clinical specimens, were as follows: Escherichia coli (21.4%), methicillin-susceptible Staphylococcus aureus (MSSA; 13.9%), Streptococcus pneumoniae (10.3%), Pseudomonas aeruginosa (7.1%), Klebsiella pneumoniae (6.0%), coagulase-negative staphylococci/Staphylococcus epidermidis (5.4%), methicillin-resistant S. aureus (MRSA; 5.1%), Haemophilus influenzae (4.1%), Enterococcus spp. (3.3%), Enterobacter cloacae (2.2%). MRSA comprised 27.0% (272/1,007) of all S. aureus isolates (genotypically, 68.8% of MRSA were health care associated [HA-MRSA] and 27.6% were community associated [CA-MRSA]). Extended-spectrum β-lactamase (ESBL)-producing E. coli occurred in 4.9% of E. coli isolates. The CTX-M type was the predominant ESBL, with CTX-M-15 the most prevalent genotype. MRSA demonstrated no resistance to ceftobiprole, daptomycin, linezolid, telavancin, tigecycline, or vancomycin (0.4% intermediate intermediate resistance). E. coli demonstrated no resistance to ertapenem, meropenem, or tigecycline. Resistance rates with P. aeruginosa were as follows: colistin (polymyxin E), 0.8%; amikacin, 3.5%; cefepime, 7.2%; gentamicin, 12.3%; fluoroquinolones, 19.0 to 24.1%; meropenem, 5.6%; piperacillin-tazobactam, 8.0%. A multidrug-resistant (MDR) phenotype occurred frequently in P. aeruginosa (5.9%) but uncommonly in E. coli (1.2%) and K. pneumoniae (0.9%). In conclusion, E. coli, S. aureus (MSSA and MRSA), P. aeruginosa, S. pneumoniae, K. pneumoniae, H. influenzae, and Enterococcus spp. are the most common isolates recovered from clinical specimens in Canadian hospitals. The prevalence of MRSA was 27.0% (of which genotypically 27.6% were CA-MRSA), while ESBL-producing E. coli occurred in 4.9% of isolates. An MDR phenotype was common in P. aeruginosa.

Antimicrobial susceptibility of 15,644 pathogens from Canadian hospitals: results of the CANWARD 2007-2009 study.

The CANWARD study (Canadian Ward Surveillance Study) assessed the antimicrobial susceptibility of a variety of available agents against 15 644 pathogens isolated from patients in Canadian hospitals between 2007 and 2009. The most active (based on MIC data) agents against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci were daptomycin, linezolid, tigecycline, and vancomycin (MRSA only) with MIC(90)s (μg/mL) of 0.25 and 2, 2 and 2, 0.5 and 0.12, and 1, respectively. The most active agents against extended-spectrum β-lactamase-producing Escherichia coli were colistin (polymyxin E), doripenem, ertapenem, meropenem, and tigecycline with MIC(90)s (μg/mL) of 1, ≤ 0.12, 0.25, ≤ 0.12, and 1, respectively. The most active agents against Pseudomonas aeruginosa were amikacin, cefepime, ceftazidime, colistin, doripenem, meropenem, and piperacillin-tazobactam with MIC(90)s (μg/mL) of 32, 16, 32, 2, 4, 8, and 64, respectively. Overall, the most active agents versus Gram-positive cocci from Canadian hospitals were vancomycin, linezolid, daptomycin, and tigecycline and versus Gram-negative bacilli were amikacin, cefepime, doripenem, ertapenem (excluding Pseudomonas aeruginosa), meropenem, piperacillin-tazobactam, and tigecycline (excluding Pseudomonas aeruginosa).

Activity of NXL104 in Combination with β-Lactams against Genetically Characterized Escherichia coli and Klebsiella pneumoniae Isolates Producing Class A Extended-Spectrum β-Lactamases and Class C β-Lactamases

ABSTRACT The novel non-β-lactam β-lactamase inhibitor NXL104, in combination with cefepime, ceftazidime, ceftriaxone, amdinocillin, and meropenem, was tested against 190 extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae isolates, 94 AmpC-hyperproducing E. coli isolates, and 8 AmpC/ESBL-coexpressing E. coli isolates. NXL104 restored 100% susceptibility to the partner cephalosporins for all isolates tested. Amdinocillin and meropenem MICs were modestly improved (2 to 32 times lower) by NXL104. These results suggest that NXL104 may be useful in combination with β-lactams for the treatment of infections caused by ESBL- and AmpC-producing Enterobacteriaceae.

Antimicrobial Resistance in Urinary Tract Pathogens in Canada from 2007 to 2009: CANWARD Surveillance Study

ABSTRACT From January 2007 to December 2009, an annual Canadian national surveillance study (CANWARD) tested 2,943 urinary culture pathogens for antimicrobial susceptibilities according to Clinical and Laboratory Standards Institute guidelines. The most frequently isolated urinary pathogens were as follows (number of isolates, percentage of all isolates): Escherichia coli (1,581, 54%), enterococci (410, 14%), Klebsiella pneumoniae (274, 9%), Proteus mirabilis (122, 4%), Pseudomonas aeruginosa (100, 3%), and Staphylococcus aureus (80, 3%). The rates of susceptibility to trimethoprim-sulfamethoxazole (SXT) were 78, 86, 84, and 93%, respectively, for E. coli, K. pneumoniae, P. mirabilis, and S. aureus. The rates of susceptibility to nitrofurantoin were 96, 97, 33, and 100%, respectively, for E. coli, enterococci, K. pneumoniae, and S. aureus. The rates of susceptibility to ciprofloxacin were 81, 40, 86, 81, 66, and 41%, respectively, for E. coli, enterococci, K. pneumoniae, P. mirabilis, P. aeruginosa, and S. aureus. Statistical analysis of resistance rates (resistant plus intermediate isolates) by year for E. coli over the 3-year study period demonstrated that increased resistance rates occurred only for amoxicillin-clavulanate (from 1.8 to 6.6%; P < 0.001) and for SXT (from 18.6 to 24.3%; P = 0.02). For isolates of E. coli, in a multivariate logistic regression model, hospital location was independently associated with resistance to ciprofloxacin (P = 0.026) with higher rates of resistance observed in inpatient areas (medical, surgical, and intensive care unit wards). Increased age was also associated with resistance to ciprofloxacin (P < 0.001) and with resistance to two or more commonly prescribed oral agents (amoxicillin-clavulanate, ciprofloxacin, nitrofurantoin, and SXT) (P = 0.005). We conclude that frequently prescribed empirical agents for urinary tract infections, such as SXT and ciprofloxacin, demonstrate lowered in vitro susceptibilities when tested against recent clinical isolates.

In Vitro Activity of Ceftazidime Combined with NXL104 versus Pseudomonas aeruginosa Isolates Obtained from Patients in Canadian Hospitals (CANWARD 2009 Study)

ABSTRACT The in vitro activity of ceftazidime in combination with NXL104 versus 470 Pseudomonas aeruginosa clinical isolates was evaluated using Clinical and Laboratory Standards Institute (CLSI) broth microdilution methods. Ceftazidime had MIC90s of 8 μg/ml and 32 μg/ml in the presence and absence of NXL104, respectively. Of 25 multidrug-resistant P. aeruginosa isolates, the percentages with a ceftazidime MIC of ≤8 μg/ml with and without NXL104 were 60% and 4%, respectively. These data suggest that the ceftazidime-NXL104 combination may prove useful for treating many P. aeruginosa infections.

In Vitro Activity of Colistin (Polymyxin E) against 3,480 Isolates of Gram-Negative Bacilli Obtained from Patients in Canadian Hospitals in the CANWARD Study, 2007-2008

ABSTRACT The in vitro activity of colistin was evaluated versus 3,480 isolates of gram-negative bacilli using CLSI broth microdilution methods. The MIC90 of colistin was ≤2 μg/ml against a variety of clinically important gram-negative bacilli, including Escherichia coli, Klebsiella spp., Enterobacter spp., Acinetobacter baumannii, and Pseudomonas aeruginosa. All multidrug-resistant (n = 76) P. aeruginosa isolates were susceptible to colistin (MIC, ≤2 μg/ml). These data support a role for colistin in the treatment of infections caused by multidrug-resistant P. aeruginosa.

In Vitro Activity of Ceftaroline against Gram-Positive and Gram-Negative Pathogens Isolated from Patients in Canadian Hospitals in 2009

ABSTRACT The in vitro activities of ceftaroline and comparative agents were determined for a collection of the most frequently isolated bacterial pathogens from hospital-associated patients across Canada in 2009 as part of the ongoing CANWARD surveillance study. In total, 4,546 isolates from 15 sentinel Canadian hospital laboratories were tested using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method. Compared with other cephalosporins, including ceftobiprole, cefepime, and ceftriaxone, ceftaroline exhibited the greatest potency against methicillin-susceptible Staphylococcus aureus (MSSA), with a MIC90 of 0.25 μg/ml. Ceftaroline also demonstrated greater potency than ceftobiprole against community-associated methicillin-resistant S. aureus (MRSA) (MIC90, 0.5 μg/ml) and health care-associated MRSA (MIC90, 1 μg/ml) and was at least 4-fold more active than other cephalosporins against Staphylococcus epidermidis; all isolates of MSSA and MRSA tested were susceptible to ceftaroline (MIC, ≤1 μg/ml). Against streptococci, including Streptococcus pneumoniae, ceftaroline MICs (MIC90, ≤0.03 μg/ml) were comparable to those of ceftobiprole; however, against penicillin-nonsusceptible, macrolide-nonsusceptible, and multidrug-nonsusceptible isolates of S. pneumoniae, ceftaroline demonstrated 2- to 4-fold and 4- to 16-fold more potent activities than those of ceftobiprole and ceftriaxone, respectively. All isolates of S. pneumoniae tested were susceptible to ceftaroline (MIC, ≤0.25 μg/ml). Among Gram-negative isolates, ceftaroline demonstrated potent activity (MIC90, ≤0.5 μg/ml) against Escherichia coli (92.2% of isolates were susceptible), Klebsiella pneumoniae (94.1% of isolates were susceptible), Proteus mirabilis (97.7% of isolates were susceptible), and Haemophilus influenzae (100% of isolates were susceptible). Ceftaroline demonstrated less potent activity (MIC90, ≥4 μg/ml) against Enterobacter spp., Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella oxytoca, Serratia marcescens, and Stenotrophomonas maltophilia. Overall, ceftaroline demonstrated potent in vitro activity against a recent collection of the most frequently encountered Gram-positive and Gram-negative isolates from patients attending hospitals across Canada in 2009.

Comparison of Antimicrobial Resistance Profiles among Extended-Spectrum-β-Lactamase-Producing and Acquired AmpC β-Lactamase-Producing Escherichia coli Isolates from Canadian Intensive Care Units

ABSTRACT Resistance profiles were compared among 18 extended-spectrum-β-lactamase-producing (ESBL) and 27 acquired AmpC β-lactamase-producing Escherichia coli isolates collected from Canadian intensive care units from 2005 to 2006. ESBL-producing E. coli isolates were more likely to be gentamicin resistant (P < 0.03), fluoroquinolone resistant (P < 0.0001), and multidrug resistant (P < 0.0001) than AmpC-producing E. coli isolates.

Prevalence of antimicrobial resistant pathogens from blood cultures from Canadian hospitals: results of the CANWARD 2007–2009 study

This study assessed the epidemiology and antimicrobial resistance of pathogens associated with bloodstream infections in Canadian hospitals between 2007 and 2009. Tertiary-care medical centers representing 8 of 10 Canadian provinces submitted bloodstream infection pathogens from patients attending hospital clinics, emergency rooms, medical/surgical wards, and intensive care units. Over 8,000 blood culture pathogens were collected. The 10 most common pathogens (representing 80.9% of all isolates) were Escherichia coli (1856 [22.6%]), Staphylococcus aureus (1457 [17.7%] including 1101 methicillin-susceptible Staphylococcus aureus and 356 methicillin-resistant Staphylococcus aureus), coagulase-negative staphylococci (907 [11.0%]), Klebsiella pneumoniae (600 [7.3%]), Streptococcus pneumoniae (470 [5.7%]), Enterococcus faecalis (360 [4.4%]), Pseudomonas aeruginosa (333 [4.0%]), viridans group streptococci (321 [3.9%]), Enterobacter cloacae (193 [2.3%]), and Streptococcus pyogenes (159 [1.9%]). The most active agents against Gram-negative bacilli were carbapenems (e.g., meropenem and ertapenem) and piperacillin-tazobactam, while for Gram-positive cocci, they were vancomycin, linezolid, and daptomycin.