Real-life experience with ceftolozane/tazobactam in Canada: results from the CLEAR (Canadian LEadership on Antimicrobial Real-life usage) registry.

Objectives Ceftolozane/tazobactam is a cephalosporin/β-lactamase inhibitor combination with activity against Gram-negative bacilli. We report the use of ceftolozane/tazobactam in Canada using a national registry. Methods The CLEAR registry uses REDCapTM (Research Electronic Data Capture) (online survey, https://is.gd/CLEAR_ceftolozanetazobactam) to capture details associated with clinical use of ceftolozane/tazobactam. Results Data from 51 patients treated in 2020 with ceftolozane/tazobactam are available. Infections treated included hospital-acquired bacterial pneumonia (37.3% of patients), ventilator-associated bacterial pneumonia (15.7%), bone/joint infection (11.8%), complicated intra-abdominal infection (7.8%) and complicated skin and skin structure infection (7.8%). 17.6% of patients had bacteremia and 47.1% were in intensive care. Ceftolozane/tazobactam was primarily used as directed therapy for Pseudomonas aeruginosa infections (92.2% of patients). Ceftolozane/tazobactam was used because of resistance to (86.3%), failure of (11.7%), or adverse effects from (2.0%) previously prescribed antimicrobials. Ceftolozane/tazobactam susceptibility testing was performed on isolates from 88.2% of patients. Ceftolozane/tazobactam was used in combination with another antimicrobial active versus Gram-negative bacilli in 39.2% of patients (aminoglycosides [15.7%], fluoroquinolones [7.8%] and colistin/polymyxin B [7.8%]). The dosage regimen was customized in all patients based on their creatinine clearance. Treatment duration was primarily >10 days (60.8% of patients) with microbiological success in 60.5% and clinical success in 64.4% of patients. 7.8% of patients had adverse effects not requiring drug discontinuation. Conclusions In Canada, ceftolozane/tazobactam is used as directed therapy to treat a variety of severe infections caused MDR P. aeruginosa. It is commonly used in combination with other antimicrobials with relatively high microbiological/clinical cure rates, and an excellent safety profile

Fosfomycin: A First-Line Oral Therapy for Acute Uncomplicated Cystitis

Fosfomycin is a new agent to Canada approved for the treatment of acute uncomplicated cystitis (AUC) in adult women infected with susceptible isolates of E. coli and Enterococcus faecalis. We reviewed the literature regarding the use of oral fosfomycin for the treatment of AUC. All English-language references from 1975 to October 2015 were reviewed. In Canada, fosfomycin tromethamine is manufactured as Monurol5 and is available as a 3-gram single dose sachet. Fosfomycin has a unique chemical structure, inhibiting peptidoglycan synthesis at an earlier site compared to -lactams with no cross-resistance with other agents. Fosfomycin displays broad-spectrum activity against ESBL-producing, AmpC-producing, carbapenem-non-susceptible, and multidrug-resistant (MDR) E. coli. Resistance to fosfomycin in E. coli is rare (<1%). Fosfomycin is excreted unchanged in the urine by glomerular filtration with peak urinary concentration ∼4000 g/mL and remains at concentrations >100 g/mL for 48 hours after a single 3-gram oral dose. No dosage adjustments are required in elderly patients, in pregnant patients, or in either renal or hepatic impairment. Fosfomycin demonstrates a favorable safety profile, and clinical trials have demonstrated efficacy in AUC that is comparable to ciprofloxacin, nitrofurantoin, and trimethoprim-sulfamethoxazole. Fosfomycin's in vitro activity against common uropathogens, including MDR isolates, its favorable safety profile including pregnancy patients, drug interactions, and clinical trials data demonstrating efficacy in AUC, has resulted in Canadian, US, and European guidelines/authorities recommending fosfomycin as a first line agent for the treatment of AUC

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

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

Characterization of Pseudomonas aeruginosa Isolates Obtained from Patients in Canadian Hospitals: Results of the CANWARD 2007 Study

INTRODUCTION: Pseudomonas aeruginosa is an important nosocomial pathogen. The purpose of the present study was to evaluate the antimicrobial susceptibility profile of P aeruginosa isolates obtained from patients in different areas of Canadian hospitals. METHODS: From January to December 2007 inclusive, 12 sentinel hospitals across Canada submitted clinical isolates from patients attending emergency rooms, medical wards, surgical wards and intensive care units (ICUs) (the Canadian Ward Surveillance Study [CANWARD 2007]). Each centre was asked to submit clinical isolates (consecutive, one per patient per infection site) from blood (n=360), respiratory (n=200), urine (n=100) and wound/intravenous (n=50) infections. Susceptibility testing was performed using Clinical and Laboratory Standards Institute broth microdilution methods. Multidrug-resistant (MDR; resistant to at least three different antimicrobial classes) isolates were typed by pulsed-field gel electrophoresis. RESULTS: In total, 451 P aeruginosa isolates were collected (representing 7% of all CANWARD 2007 isolates). The rank order of antimicrobial susceptibility was as follows (percent susceptible): amikacin (93.1%) = piperacillin/tazobactam (93.1%) > meropenem (87.4%) > cefepime (69.4%) > ciprofloxacin (67.2%) > gentamicin (66.1%) > levofloxacin (60.5%). Reduced susceptibility to cefepime, meropenem and levofloxacin was observed more frequently among ICU isolates (P<0.05). Thirty-four isolates (7.5%) were MDR. MDR isolates were more likely to be obtained from patients in an ICU (P=0.003) and less likely to come from a bloodstream source (P=0.008). Excluding colistin (polymyxin E), amikacin and piperacillin/tazobactam, followed by meropenem, were the most active antimicrobials evaluated versus the MDR isolates. All of the MDR isolates were susceptible to colistin. The majority of MDR isolates were genetically unrelated. CONCLUSIONS: P aeruginosa is common among clinical specimens from patients in Canadian hospitals. Of the antipseudomonal antimicrobials evaluated, amikacin, meropenem and piperacillin/tazobactam demonstrated the greatest in vitro activity. Isolates with reduced antimicrobial susceptibility and MDR isolates were more often obtained from ICU patients. All of the MDR isolates remained susceptible to colistin

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▿

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