Moving towards a standardized definition of antimicrobial resistance: a comparison of the antimicrobial susceptibility profile of difficult-to-treat resistance (DTR) versus multidrug-resistant (MDR) Pseudomonas aeruginosa clinical isolates (CANWARD, 2016-2021).

Pseudomonas aeruginosa clinical isolates demonstrating difficult-to-treat resistance (DTR) and multidrug-resistant (MDR) phenotypes were evaluated by broth microdilution. Susceptibility was lower for all antimicrobials versus DTR relative to MDR isolates. Ceftazidime-avibactam, ceftolozane-tazobactam, and imipenem-relebactam susceptibility was 35.9%, 64.5%, and 47.0% for DTR isolates and 60.5%, 80.6%, and 71.5% for MDR isolates.

Direct cost of health care for individuals with community associated Clostridium difficile infections: A population-based cohort study.

BACKGROUND: Even though the incidence of community-acquired Clostridium difficile infection (CDI) is reported to be increasing, few studies have reported on the healthcare costs of community-acquired CDI. We estimated cost of care for individuals with community-associated CDI and compared with that for matched controls without CDI in the time period of six months before to one year after CDI. METHODS: All individuals in the province of Manitoba, diagnosed with CDI between July 2005 and March 2015 were matched up to 4 individuals without CDI. Health care utilization and direct costs resulting from hospitalizations, physician reimbursement claims and prescriptions were determined from the population based provincial databases. Quantile regressions were performed to determine predictors of cost of individuals with community associated CDI. RESULTS: Of all CDIs, 30-40% in each period of the study had community-associated CDI; of which 12% were recurrent CDIs. The incremental median and 90th percentile cost of care for individuals with community-associated CDI was $800 and $16,000 respectively in the six months after CDI diagnosis. After adjustment for age, co-morbidities, sex, socioeconomic status and magnitude of health care utilization prior to CDI, the median incremental cost for recurrent CDI was $1,812 and that for a subsequent episode of CDI was $3,139 compared to those with a single community-associated CDI episode. The median cost for a prescription of Vancomycin was $316 (IQR 209-489). CONCLUSIONS: Health care costs of an episode of community-associated CDI have been much more than the cost of antibiotic treatment. Our study provides population-based data for formal cost effectiveness analysis for use of newer treatments for community-associated CDI.

In vitro activity of oritavancin against Gram-positive pathogens isolated in Canadian hospital laboratories from 2011 to 2013.

Gram-positive pathogens isolated in 15 Canadian hospital laboratories between 2011 and 2013 were tested for susceptibility to oritavancin and comparative antimicrobial agents using the Clinical and Laboratory Standards Institute broth microdilution method. Oritavancin demonstrated in vitro activity equivalent to, or more potent than, vancomycin, daptomycin, linezolid, and tigecycline against the isolates of methicillin-susceptible Staphylococcus aureus (n=1460; oritavancin MIC90, 0.06 µg/mL; 99.7% oritavancin-susceptible), methicillin-resistant S. aureus (n=427; oritavancin MIC90, 0.06 µg/mL; 99.5% oritavancin-susceptible), Streptococcus pyogenes (n=132; oritavancin MIC90, 0.25 µg/mL; 99.2% oritavancin-susceptible), Streptococcus agalactiae (n=156; oritavancin MIC90, 0.12 µg/mL; 100% oritavancin-susceptible), and Enterococcus faecalis (n=304; oritavancin MIC90, 0.06 µg/mL; 98.7% oritavancin-susceptible) tested.

In vitro activity of plazomicin against 5,015 gram-negative and gram-positive clinical isolates obtained from patients in canadian hospitals as part of the CANWARD study, 2011-2012.

Plazomicin is a next-generation aminoglycoside that is not affected by most clinically relevant aminoglycoside-modifying enzymes. The in vitro activities of plazomicin and comparator antimicrobials were evaluated against a collection of 5,015 bacterial isolates obtained from patients in Canadian hospitals between January 2011 and October 2012. Susceptibility testing was performed using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method, with MICs interpreted according to CLSI breakpoints, when available. Plazomicin demonstrated potent in vitro activity against members of the family Enterobacteriaceae, with all species except Proteus mirabilis having an MIC90 of ≤1 µg/ml. Plazomicin was active against aminoglycoside-nonsusceptible Escherichia coli, with MIC50 and MIC90 values identical to those for aminoglycoside-susceptible isolates. Furthermore, plazomicin demonstrated equivalent activities versus extended-spectrum ß-lactamase (ESBL)-producing and non-ESBL-producing E. coli and Klebsiella pneumoniae, with 90% of the isolates inhibited by an MIC of ≤1 µg/ml. The MIC50 and MIC90 values for plazomicin against Pseudomonas aeruginosa were 4 µg/ml and 16 µg/ml, respectively, compared with 4 µg/ml and 8 µg/ml, respectively, for amikacin. Plazomicin had an MIC50 of 8 µg/ml and an MIC90 of 32 µg/ml versus 64 multidrug-resistant P. aeruginosa isolates. Plazomicin was active against methicillin-susceptible and methicillin-resistant Staphylococcus aureus, with both having MIC50 and MIC90 values of 0.5 µg/ml and 1 µg/ml, respectively. In summary, plazomicin demonstrated potent in vitro activity against a diverse collection of Gram-negative bacilli and Gram-positive cocci obtained over a large geographic area. These data support further evaluation of plazomicin in the clinical setting.

In vitro activity of ceftolozane-tazobactam against Pseudomonas aeruginosa isolates obtained from patients in Canadian hospitals in the CANWARD study, 2007 to 2012.

The in vitro activity of ceftolozane in combination with tazobactam (fixed concentration of 4 µg/ml) was evaluated against 2,435 Pseudomonas aeruginosa clinical isolates obtained from across Canada using Clinical and Laboratory Standards Institute broth microdilution methods. The MIC50 and MIC90 values for ceftolozane-tazobactam were 0.5 µg/ml and 1 µg/ml, respectively (a 32-fold-lower MIC90 than that for ceftazidime). Eighty-nine percent (141/158) of multidrug-resistant isolates were inhibited by ≤8 µg/ml of ceftolozane-tazobactam.

Evaluation of an algorithmic approach in comparison with the Illumigene assay for laboratory diagnosis of Clostridium difficile infection.

The following three diagnostic algorithms were evaluated in comparison with the Illumigene assay as a stand-alone test for Clostridium difficile detection: glutamate dehydrogenase antigen screen (GDH) followed by toxin A/B antigen testing (Tox A/B) with the cell cytotoxicity assay for discordant specimens (algorithm 1), GDH followed by the Illumigene (algorithm 2), and GDH followed by Tox A/B with the Illumigene for discordant specimens (algorithm 3). A total of 428 stool specimens submitted to three clinical microbiology laboratories in Manitoba, Canada, for C. difficile detection between June 2011 and April 2012 were included in the study. The prevalence of C. difficile in the stool specimens was 14.7% (63/428) based on toxigenic culture (microbiologic reference standard). The sensitivity and specificity of the Illumigene for C. difficile detection were 73.0% and 99.7%, respectively. The corresponding sensitivities and specificities were 65.1% and 100.0% for algorithm 1, 68.3% and 100.0% for algorithm 2, and 69.8% and 100.0% for algorithm 3. Using algorithm 1, a cell cytotoxicity assay was required for toxin detection in 37% of positive tests, prolonging turnaround time. However, the predictive value of a positive test based on a clinical reference standard (all tests positive or cytotoxigenic culture positive and clinical disease on chart review) was slightly higher with algorithm 1 than with the Illumigene assay as a stand-alone test or as part of an algorithm (algorithms 2 and 3). Based on a reduction in turnaround time, simplicity, and acceptable sensitivity and specificity, we recommend algorithm 2 (screening with the GDH antigen test and confirmatory testing with the Illumigene).

Re-evaluation of rejection criteria for endotracheal tube (ETT) specimens from adult patients.

The purpose of this study was to determine optimal criteria for microbiology laboratory screening of endotracheal tube (ETT) specimens submitted for bacterial culture from adult patients. ETT specimens from adult patients that were received by two microbiology laboratories were prospectively evaluated and subdivided into one of three study arms with the following criteria: <10 squamous epithelial cells (SECs) per low-power field with bacteria seen on Gram staining (arm 1), >10 SECs per low-power field with bacteria seen on Gram staining (arm 2) and <10 SECs per low-power field with no bacteria seen on Gram staining (arm 3). A fourth study arm (>10 SECs per low-power field with no bacteria seen on Gram staining) was planned but this arm was terminated due to the paucity of specimens meeting these criteria. Isolate evaluation was performed using standard microbiology protocols. A limited chart review was undertaken at one of the institutions, only reviewing patients from which a potential pathogen was recovered on culture. In total, 141 ETT specimens were evaluated. A potential respiratory pathogen was recovered from 54, 37 and 10 % of specimens in study arms 1, 2, and 3, respectively (P<0.0001, comparing between arm 1 and arm 3). For the 23 patients included in the chart review from whom a potential pathogen was recovered on culture, respiratory infection was considered to be present in 50 % (6/12) of patients in arm 1, 66.6 % (6/9) of patients in arm 2 and 100 % (2/2) of patients in arm 3. Therapy was rarely altered based on culture results. In this study, the ETT specimens submitted for bacterial culture were of limited benefit to clinicians. The data presented here support the use of an absence of bacteria on Gram staining as a rejection criterion for ETT specimens. The criterion of >10 SECs per low-power field should be further evaluated in a prospective study of patients with an unequivocal clinical diagnosis of pneumonia.

Change in antimicrobial susceptibility of Escherichia coli urinary tract isolates at a single institution over a period of 10 years.

Urinary tract infections are common. Few published studies have demonstrated the change in Escherichia coli urinary isolate antimicrobial susceptibility over time within a given area and (or) population. The purpose of this study was to evaluate the change in susceptibility of E. coli clinical isolates obtained from urine specimens at a single institution over a period of 10 years. The microbiology laboratory information system at St. Boniface Hospital (Winnipeg, Manitoba, Canada) was searched retrospectively from 1 January 2000 to 31 December 2009, for all E. coli isolates from either a midstream or catheter urine source that had susceptibility testing performed. Only one isolate per patient was included during the entire study period. Antimicrobial susceptibility testing was carried out with either a Microscan instrument (pre-April 2004) or a Vitek instrument (May 2004 onwards). In total, 7353 E. coli urinary isolates were included for evaluation. Ciprofloxacin susceptibility declined significantly, from 99% in 2000 to 85% in 2009 (p < 0.0001). A small but statistically significant decline in susceptibility was also observed for ampicillin, cefazolin, trimethoprim-sulfamethoxazole, gentamicin, and nitrofurantoin. These data suggest that certain antimicrobials recommended for the treatment of urinary tract infections (ciprofloxacin, trimethoprim-sulfamethoxazole) may no longer be optimal.

Activity of NXL104 in combination with beta-lactams against genetically characterized Escherichia coli and Klebsiella pneumoniae isolates producing class A extended-spectrum beta-lactamases and class C beta-lactamases.

The novel non-ß-lactam ß-lactamase inhibitor NXL104, in combination with cefepime, ceftazidime, ceftriaxone, amdinocillin, and meropenem, was tested against 190 extended-spectrum ß-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 ß-lactams for the treatment of infections caused by ESBL- and AmpC-producing Enterobacteriaceae.

In vitro activity of ceftazidime combined with NXL104 versus Pseudomonas aeruginosa isolates obtained from patients in Canadian hospitals (CANWARD 2009 study).

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.

The in vitro activity of colistin was evaluated versus 3,480 isolates of gram-negative bacilli using CLSI broth microdilution methods. The MIC(90) of colistin was < or = 2 microg/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, < or = 2 microg/ml). These data support a role for colistin in the treatment of infections caused by multidrug-resistant P. aeruginosa.

The new fluoroquinolones: A critical review.

OBJECTIVE: This paper reviews the literature available on the new fluoroquinolones - clinafloxacin, gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin, sparfloxacin and trovafloxacin - to compare these agents with each other and contrast them with ciprofloxacin, an older fluoroquinolone. DATA SELECTION: Published papers used were obtained by searching MEDLINE for articles published between 1994 and 1998, inclusive. References of published papers were also obtained and reviewed. Abstracts from scientific proceedings were reviewed. DATA EXTRACTION: Due to the limited data available on several of the agents, criteria for study inclusion in the in vitro, pharmacokinetics and in vivo sections were not restrictive. DATA SYNTHESIS: The new fluoroquinolones offer excellent Gram-negative bacillary activity and improved Gram-positive activity (eg, against Streptococcus pneumoniae and Staphylococcus aureus) over ciprofloxacin. Clinafloxacin, gatifloxacin, moxifloxacin, sparfloxacin and trovafloxacin display improved activity against anaerobes (eg, Bacteriodes fragilis). All of the new fluoroquinolones have a longer serum half-life than ciprofloxacin (allowing for once daily dosing), and several are eliminated predominantly by nonrenal means. No clinical trials are available comparing the new fluoroquinolones with each other. Clinical trials comparing the new fluoroquinolones with standard therapy have demonstrated good efficacy in a variety of infections. Their adverse effect profile is similar to that of ciprofloxacin. Clinafloxacin and sparfloxacin cause a high incidence of phototoxicity (1.5% to 14% and 2% to 11.7%, respectively), grepafloxacin causes a high incidence of taste perversion (9% to 17%) and trovafloxacin causes a high incidence of dizziness (11%). They all interact with metal ion-containing drugs (eg, antacids), and clinafloxacin and grepafloxacin interact with theophylline. The new fluoroquinolones are expensive; however, their use may result in savings in situations where, because of their potent and broad spectrum of activity, they can be used orally in place of intravenous antibiotics. CONCLUSIONS: The new fluoroquinolones offer advantages over ciprofloxacin in terms of improved in vitro activity and pharmacokinetics. Whether these advantages translate into improved clinical outcomes is presently unknown. The new fluoroquinolones have the potential to emerge as important therapeutic agents in the treatment of respiratory tract and genitourinary tract infections.