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

Cardiobacterium hominis endocarditis: A case report and review of the literature

The present case report describes the clinical course of a patient who presented with Cardiobacterium hominis endocarditis. A review of the literature follows the case presentation. C hominis, a fastidious Gram-negative bacillus, is a member of the HACEK group of microorganisms (Haemophilus species, Actinobacillus actinomycetemcomitans, C hominis, Eikenella corrodens and Kingella kingae). Endocarditis caused by C hominis is uncommon and generally follows a subacute course. Patients may present with constitutional symptoms, symptoms related to valvular destruction or symptoms secondary to embolic events. Diagnosis requires identification of the pathogen from blood or vegetation by either culture or molecular techniques. Blood cultures may require prolonged incubation, highlighting the importance of incubating blood cultures for at least two to three weeks in patients with suspected endocarditis. In the past, C hominis was generally sensitive to penicillin. However, reports of beta-lactamase-producing C hominis have appeared in the literature over the past decade. The current recommendation for first-line treatment is a third-generation cephalosporin (ceftriaxone) for four weeks (six weeks if a prosthetic valve is in place)

Severe skin rash associated with atazanavir

Three cases of severe rash associated with the use of atazanavir are described. In all cases, the rash was maculopapular and pruritic. Rash onset occurred eight to 11 days after initiation of therapy, and resolved with atazanavir discontinuation. Clinicians prescribing atazanavir should be aware of this potential adverse effect

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

Isolation of multiple carbapenemase-producing Gram-negative bacilli from a patient recently hospitalized in Nigeria

A 29-year-old female transferred to a tertiary care hospital in Winnipeg, Canada, after a prolonged period of hospitalization in Nigeria was found to be colonized with a VIM-2-producing Pseudomonas aeruginosa, a NDM-1-producing Klebsiella pneumoniae, and an OXA-181-producing Escherichia coli. Detection of carbapenemase-producing organisms from a rectal swab was accomplished by screening with chromogenic media, followed by confirmation with the Rapid CARB Screen kit (Rosco Diagnostica, Taastrup, Denmark). This case illustrates the need for clinical microbiology laboratories to have a protocol in place to screen patients for carbapenemase producers, even in countries where these organisms are rarely encountered

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

Anaplasmosis: An emerging tick-borne disease of importance in Canada

Human Granulocytic Anaplasmosis (HGA) is an infection caused by the intracellular bacterium Anaplasma phagocytophilum. As a tick-borne disease, the public health impact of HGA continues to increase with range expansion of the disease vector. The clinical presentation of HGA is often a non-specific febrile illness. The presence of leukopenia, thrombocytopenia, and mild hepatic injury are frequently noted on laboratory investigations, which can be important diagnostic clues in attaining an appropriate diagnosis. Herein we present three cases of HGA, highlighting the spectrum of disease by which HGA can manifest. Although each case has their unique features, we outline important shared clinical elements to facilitate an empiric diagnosis while definitive laboratory investigations are pending. Our case series further serves to highlight the critical importance of prompt antimicrobial treatment to reduce morbidity and potential mortality. Keywords: Anaplasma phagocytophilum, Human granulocytic anaplasmosis, HGA, Tick-borne illness, Zoonosis, Canad

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