Papers by Coleman Rotstein

The Prospective Antifungal Therapy Alliance(®) registry: A two-centre Canadian experience
The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie médicale / AMMI Canada, 2014
The Prospective Antifungal Therapy Alliance(®) registry is a prospective surveillance study that ... more The Prospective Antifungal Therapy Alliance(®) registry is a prospective surveillance study that collected data on the diagnosis, management and outcomes of invasive fungal infections (IFIs) from 25 centres in North America from 2004 to 2008. To evaluate surveillance data on IFIs obtained from study centres located in Canada. Patients with proven or probable IFIs at two Canadian medical centres were enrolled in the registry. Information regarding patient demographics, fungal species, infection sites, diagnosis techniques, therapy and survival were analyzed. A total of 347 patients from Canada with documented IFIs were enrolled in the Prospective Antifungal Therapy Alliance registry. Infections occurred most commonly in general medicine (71.8%), nontransplant surgery (32.6%) and patients with hematological malignancies (21.0%). There were 287 proven IFIs, including 248 Candida infections. Forty-six patients had invasive aspergillosis (IA); all of these were probable infections. Most ...

Low seroconversion after one dose of AS03-adjuvanted H1N1 pandemic influenza vaccine in solid-organ transplant recipients
The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie médicale / AMMI Canada, 2013
Immunocompromised individuals are more susceptible to complications produced by influenza infecti... more Immunocompromised individuals are more susceptible to complications produced by influenza infection. As a result, solid-organ transplant (SOT) recipients were targeted as a priority group to receive AS03-adjuvanted H1N1 influenza vaccine during 2009. To evaluate seroconversion after one dose of adjuvanted pandemic influenza H1N1 (pH1N1) vaccine in SOT recipients. Adult SOT recipients were enrolled to receive one 3.75 μg dose of adjuvanted pH1N1 vaccine. Serological status was tested using a hemagglutination inhibition assay before and two and four weeks postvaccination. The five SOT recipients (one liver, two kidney and two lung transplants) had a median age of 50 years (range 36 to 53 years), and three were male, who were a median time of three years (range two months to 15 years) post-transplant. All patients were on a double or triple immunosuppressive regimen. The prevaccination pH1N1 titre was 1:10 in four patients and 1:40 in one patient. Seroprotection was observed only in on...

The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie médicale / AMMI Canada
Invasive fungal infections are associated with morbidity and mortality in neutropenia secondary t... more Invasive fungal infections are associated with morbidity and mortality in neutropenia secondary to hematological malignancies. Empirical antifungal agents are used to reduce their consequences. Caspofungin is the only echinocandin approved for this indication. Micafungin was compared with caspofungin for the treatment of patients with hematological malignancies and prolonged neutropenia. A retrospective cohort study was conducted involving patients who had hematological malignancies with profound neutropenia for a minimum of 10 days, and received empirical micafungin or caspofungin for a minimum of five days, between April 2005 and November 2009. Successful outcome was based on a composite end point: survival for a minimum of seven days following antifungal cessation, successful treatment of baseline fungal infection, absence of adverse events and absence of breakthrough fungal infection. Fungal infections were defined according to revised definitions of invasive fungal disease from...

The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie médicale / AMMI Canada
Invasive fungal infections cause significant morbidity and mortality in patients with concomitant... more Invasive fungal infections cause significant morbidity and mortality in patients with concomitant underlying immunosuppressive diseases. The recent addition of new triazoles to the antifungal armamentarium has allowed for extended-spectrum activity and flexibility of administration. Over the years, clinical use has raised concerns about the degree of drug exposure following standard approved drug dosing, questioning the need for therapeutic drug monitoring (TDM). Accordingly, the present guidelines focus on TDM of triazole antifungal agents. A review of the rationale for triazole TDM, the targeted patient populations and available laboratory methods, as well as practical recommendations based on current evidence from an extended literature review are provided in the present document.

The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie médicale / AMMI Canada, 2004
Invasive aspergillosis (IA) is a serious fungal infection that affects immunocompromised patients... more Invasive aspergillosis (IA) is a serious fungal infection that affects immunocompromised patients. The Global Comparative Aspergillosis study demonstrated that voriconazole, a new broad-spectrum triazole, had better responses and improved survival compared with conventional amphotericin B deoxycholate (CAB) and other licensed antifungal therapy (OLAT) for the treatment of definite or probable aspergillosis. To compare costs and outcomes of voriconazole and CAB for the treatment of definite or probable aspergillosis in Canada. A cost-consequence decision tree model was designed to reflect the treatment pathways used in clinical practice when using voriconazole or CAB as primary therapy for IA. Therapy included initial treatment with either voriconazole or CAB and then switched to an OLAT in the event of an inadequate response, severe toxicity or intolerance. The principal data source used was the Global Comparative Aspergillosis study. The total cost of voriconazole when compared wit...

Antimicrobial agents and chemotherapy, 2014
Immunocompromised patients are predisposed to infections caused by influenza virus. Influenza vir... more Immunocompromised patients are predisposed to infections caused by influenza virus. Influenza virus may produce considerable morbidity, including protracted illness and prolonged viral shedding in these patients, thus prompting higher doses and prolonged courses of antiviral therapy. This approach may promote the emergence of resistant strains. Characterization of neuraminidase (NA) inhibitor (NAI)-resistant strains of influenza A virus is essential for documenting causes of resistance. In this study, using quantitative real-time PCR along with conventional Sanger sequencing, we identified an NAI-resistant strain of influenza A (H3N2) virus in an immunocompromised patient. In-depth analysis by deep gene sequencing revealed that various known markers of antiviral resistance, including transient R292K and Q136K substitutions and a sustained E119K (N2 numbering) substitution in the NA protein emerged during prolonged antiviral therapy. In addition, a combination of a 4-amino-acid delet...

Epidemiology and outcomes of invasive candidiasis due to non-albicans species of Candida in 2,496 patients: data from the Prospective Antifungal Therapy (PATH) registry 2004-2008
PloS one, 2014
This analysis describes the epidemiology and outcomes of invasive candidiasis caused by non-albic... more This analysis describes the epidemiology and outcomes of invasive candidiasis caused by non-albicans species of Candida in patients enrolled in the Prospective Antifungal Therapy Alliance (PATH Alliance) registry from 2004 to 2008. A total of 2,496 patients with non-albicans species of Candida isolates were identified. The identified species were C. glabrata (46.4%), C. parapsilosis (24.7%), C. tropicalis (13.9%), C. krusei (5.5%), C. lusitaniae (1.6%), C. dubliniensis (1.5%) and C. guilliermondii (0.4%); 111 infections involved two or more species of Candida (4.4%). Non-albicans species accounted for more than 50% of all cases of invasive candidiasis in 15 of the 24 sites (62.5%) that contributed more than one case to the survey. Among solid organ transplant recipients, patients with non-transplant surgery, and patients with solid tumors, the most prevalent non-albicans species was C. glabrata at 63.7%, 48.0%, and 53.8%, respectively. In 1,883 patients receiving antifungal therapy ...

Resource Utilization and Cost of Treatment with Anidulafungin or Fluconazole for Candidaemia and Other Forms of Invasive Candidiasis
PharmacoEconomics, 2011
Candidaemia and other forms of invasive candidiasis (C/IC) are serious and costly events for hosp... more Candidaemia and other forms of invasive candidiasis (C/IC) are serious and costly events for hospitalized patients, particularly those in the ICU. Both fluconazole and the echinocandins are recommended as first-line therapy for C/IC. Resource use and cost considerations are important in selecting appropriate treatment but little information is available on the economic implications of using echinocandins in this setting. To compare resource utilization and treatment costs (in $US) associated with the echinocandin anidulafungin (200 mg intravenously on day 1, then 100 mg intravenously daily) versus those of fluconazole (800 mg intravenously on day 1, then 400 mg intravenously daily) as first-line treatment for C/IC. Available charts from patients enrolled in a recent clinical trial comparing anidulafungin and fluconazole for C/IC were reviewed. Patients who were in the ICU at study entry were identified, and the following data, collected during the 13-week study period, were compared between treatment groups: global response at end of study treatment, number of days patients survived after hospital discharge ('hospital-free' days), hospital resource use, and C/IC-related costs (year 2008 values) to a US hospital payer. These comparisons were also conducted for all non-ICU hospitalized patients, and for survivors in both study populations. Sensitivity analyses explored the cost impact of variability in the hospitalization costs between ICUs and non-ICU wards and of reduced duration intravenous therapy. Statistical comparisons between the two treatment groups were conducted for clinical outcomes, resource use and cost measures, using regression models. All statistical comparisons were adjusted for baseline co-variates (Acute Physiology and Chronic Health Evaluation [APACHE] II score, absolute neutrophil count and catheter removal status). For ICU patients with C/IC (n = 63), global response was significantly higher for anidulafungin than fluconazole (68.6% vs 42.9%; p = 0.03). ICU patients treated with anidulafungin had an average of 13.9 more hospital-free days (18.2 vs 4.3 days; p = 0.04) than those treated with fluconazole. After adjustment for co-variates, although lower costs were observed for anidulafungin vs fluconazole in ICU patients and in ICU patients who survived, no statistical differences were found. For all hospitalized patients (n = 159), global response was also higher for anidulafungin (78.3% vs 60.5%; p < 0.01). There was no difference in average length of hospitalization (29.6 days) or hospital-free days. After adjustment for co-variates, anidulafungin treatment resulted in an incremental C/IC-related cost of $US2680 (p = 0.73). For hospitalized patients who survived (anidulafungin 81.9%, fluconazole 69.7%), anidulafungin treatment was associated with an incremental cost of $US231 (p = 0.98). Anidulafungin as first-line treatment of C/IC appears to be of particular benefit to ICU patients, improving clinical outcomes and possibly decreasing costs, driven by reduced ICU and hospital stay, when compared with fluconazole. Anidulafungin also yielded significantly improved treatment outcomes in the general inpatient population, with total costs similar to fluconazole.
PharmacoEconomics, 1998
Fluconazole (FLU) is an alternative to amphotericin B (AMB) for the treatment of candidemia in no... more Fluconazole (FLU) is an alternative to amphotericin B (AMB) for the treatment of candidemia in non-neutropenic patients. This agent has similar clinical efficacy but significantly reduced adverse effects compared with AMB. Using the database from a Canadian randomised multicentre comparative trial of FLU versus AMB in the treatment of non-neutropenic patients with candidemia, an economic analysis of antifungal therapy was conducted from a Canadian hospital perspective.
New England Journal of Medicine, 2002
New England Journal of Medicine, 2007
Anidulafungin, a new echinocandin, has potent activity against candida species. We compared anidu... more Anidulafungin, a new echinocandin, has potent activity against candida species. We compared anidulafungin with fluconazole in a randomized, double-blind, noninferiority trial of treatment for invasive candidiasis.

Randomized, Double‐Blind, Controlled Trial of Pneumococcal Vaccination in Renal Transplant Recipients
The Journal of Infectious Diseases, 2003
Renal transplant recipients are at increased risk for developing invasive pneumococcal disease bu... more Renal transplant recipients are at increased risk for developing invasive pneumococcal disease but may have a poor response to pneumococcal polysaccharide vaccine (PPV23). For them, pneumococcal conjugate vaccine (PCV7) may be more immunogenic. Patients were given a single dose of PPV23 or PCV7 in our randomized, controlled, double-blind trial. Immunogenicity was assessed 8 weeks after vaccination by serotype-specific enzyme-linked immunosorbent assay (ELISA) and opsonophagocytic assay (OPA). Baseline demographics, renal function, time since transplantation, and immunosuppression were comparable. In the PCV7 group, the vaccine response rate was improved for serotypes 23F (P=.046) and 6B (P=.067), and mean fold increases in antibody titer were higher for serotypes 23F (P=.046) and 9V (P=.09). The response rate and mean fold increase in OPA titers were not significantly different between groups. There was a trend toward enhanced immunogenicity for PCV7 by ELISA. However, functional antibody responses were not different.
The Journal of Heart and Lung Transplantation, 2011
The Journal of Heart and Lung Transplantation, 2010
The prognostic significance of hyponatremia in left sided heart failure is well-established. Decr... more The prognostic significance of hyponatremia in left sided heart failure is well-established. Decreased cardiac output stimulates neurohormonal changes which limit water excretion and promote water reabsorption. The degree of hyponatremia parallels disease severity and prognosis. However, this association has not been reported in patients with pulmonary S186

Susceptibility patterns of Candida species recovered from Canadian intensive care units
Journal of Critical Care, 2007
The objective of this study was to determine the speciation and susceptibility patterns of Candid... more The objective of this study was to determine the speciation and susceptibility patterns of Candida species recovered from Canadian intensive care units (ICUs) during a 1-day point-prevalence study on fungal colonization/infection in Canadian ICUs. Blood, urine, respiratory tract, rectal, and wound fungal cultures were performed for 357 patients present at any time during a single-day 24-hour period in 35 Canadian ICUs. Comparative in vitro activities of amphotericin B, fluconazole, itraconazole, voriconazole, posaconazole, micafungin, anidulafungin, and aminocandin were determined. Four hundred fifteen yeasts (409 Candida species and 6 non-Candida yeasts) were recovered. Almost 50% of the patients were found to have positive respiratory tract or rectal cultures. Candida albicans accounted for 72% of the Candida species isolated, followed by Candida glabrata (16%), Candida tropicalis (5%), Candida parapsilosis (3%), Candida krusei (2%), and other Candida species or nonspeciated isolates (2%). Minimum inhibitory concentrations (milligrams per liter) at which 90% of the strains were inhibited were 0.06 for micafungin as well as anidulafungin, 0.12 for voriconazole, 0.25 for itraconazole, posaconazole, as well as aminocandin, 1 for amphotericin B, and 4 for fluconazole. Only 4% of the isolates were resistant to fluconazole and/or itraconazole. Candida albicans is the predominant species colonizing Canadian ICU patients. Overall, the triazoles, both older and new compounds, and the echinocandins have excellent in vitro antifungal activities against Candida species recovered from Canadian ICUs patients.

Intravenous immunoglobulin for severe infections: a survey of Canadian specialists
Journal of Critical Care, 2004
To survey the opinions of Canadian critical care medicine and infectious disease specialists abou... more To survey the opinions of Canadian critical care medicine and infectious disease specialists about the use of intravenous immunoglobulin (IVIG) for the treatment of severe infections. A scenario-based, cross-sectional survey of Canadian critical care medicine and infectious disease specialists was conducted from March to June 2003. The response rate was 291/487 (60%). Respondents were primarily medically trained and most (241/291; 83%) were practicing in large academic referral centers. Physicians reported that they would use IVIG in patients with streptococcal toxic shock syndrome (STSS; 218/288; 76%), streptococcal necrotizing fasciitis without STSS (143/286; 50%), staphylococcal toxic shock syndrome (75/288; 26%), streptococcal soft tissue infection without NF or STSS (31/286; 11%), and septic shock due to intra-abdominal focus (9/283; 3%). The majority (> or =67%) of respondents believed that it would be ethical to randomize patients to IVIG or placebo in a clinical trial in each of the five scenarios. One third (192/286) reported that it would not be ethical to randomize patients with STSS. Canadian specialists commonly report favoring the use of IVIG to treat STSS and necrotizing fasciitis but less commonly endorse this treatment for other infections. Specialist's beliefs surrounding the efficacy of IVIG would challenge but not preclude the conduct of future placebo controlled trials of severe streptococcal infections in Canada.
Journal of Antimicrobial Chemotherapy, 2005
Objective: The objective of this study was to conduct an economic evaluation of voriconazole comp... more Objective: The objective of this study was to conduct an economic evaluation of voriconazole compared with conventional amphotericin B deoxycholate (CAB) using data from a recently reported randomized comparative trial in patients with various underlying immunosuppressive conditions. This trial demonstrated the superiority of voriconazole in terms of clinical response, survival and safety when used as primary therapy for invasive aspergillosis.
Antimicrobial activity of ceftriaxone versus cefotaxime: negative effect of serum albumin binding of ceftriaxone
Journal of Antimicrobial Chemotherapy, 1994
... Swapan K. Nath" *, Gary A. Foster*, Lionel A. Mandellc and Coleman Rotstein ... An a... more ... Swapan K. Nath" *, Gary A. Foster*, Lionel A. Mandellc and Coleman Rotstein ... An aliquot of the mid log phase culture of test organisms was diluted to the 0-5 McFarland turbidity standard, and the suspension was diluted 1: 10 to yield 107 cfu/mL. ...

International Journal of Antimicrobial Agents, 2007
% MRSA % MSSA PVL(+) PVL(−) PVL(+) PVL(−) Infection type, % abscess 70.5 (67/95)* 26.3 (15/57) 68... more % MRSA % MSSA PVL(+) PVL(−) PVL(+) PVL(−) Infection type, % abscess 70.5 (67/95)* 26.3 (15/57) 68.0 (68/100)* 48.2 (79/164) Deep infections, % 33.6 (32/95) 38.6 (22/57) 26.0 (26/100) 34.1 (56/164) WBC > 10 4 , % 32.2 (28/87) 21.3 (10/47) 41.4 (36/87) 31.0 (45/145) Temperature >38ºC 14.7 (14/95)* 42.1 (24/57) 44.0 (44/100) 40.2 (66/164) CRP > 50 mg/dL 28.0 (26/93)* 51.9 (28/54) 36.2 (34/94) 41.4 (67/162) Conclusion: PVL-positive MRSA and MSSA were widely prevalent in cSSSI. The presence of PVL in both MRSA and MSSA was significantly associated with abscess compared to wound infections or cellulitis in this cSSSI trial. Lower fever and CRP levels in patients with PVL-positive MRSA infections may indicate impaired host responses to PVL-positive S. aureus. The presence of PVL was associated with lowest cure rates in patients with MRSA infections; however, cure rates in patients treated with BPR exceeded 90%.
International Journal of Antimicrobial Agents, 2007
Extended therapy with HD-CAP was tolerated without serious hepatic or renal impairment. Reversibl... more Extended therapy with HD-CAP was tolerated without serious hepatic or renal impairment. Reversible hyperbilirubinaemia may infrequently occur during HD-CAP therapy.
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Papers by Coleman Rotstein