Incidence, susceptibility and outcomes of candidemia in adults living in Calgary, Alberta, Canada (2010-2018).

BACKGROUND: Candidemia is increasing in frequency and is associated with high mortality. We sought to determine the burden of illness, the population it affects and its resistance profile in our region. METHODS: The Calgary Zone (CZ) provides all care for residents of Calgary and surrounding communities (~ 1.69 million) via five tertiary hospitals each served by a common single laboratory for acute care microbiology. All adult patients in the CZ with at least one Candida spp.-positive blood culture between January 1, 2010, and December 31, 2018, were identified using microbiological data from Calgary Lab Services, the laboratory that processes > 95% of all blood culture samples in the CZ, were reviewed for the study. RESULTS: The overall annual incidence of candidemia among individuals living in the CZ was 3.8 per 100,000 persons (Median age 61 years (IQR 48-72) and 221/455 (47.4%) were female). C. albicans was the most common species (50.6%), followed by C. glabrata, (24.0%). No other species accounted for more than 7% of cases. Overall mortality at 30, 90, and 365 days was 32.2, 40.1, and 48.1% respectively. Mortality rate did not differ by Candida species. Of individuals who developed candidemia, more than 50% died within the next year. No new resistance pattern has emerged in the most common Candida species in Calgary, Alberta. CONCLUSIONS: In Calgary, Alberta, the incidence of candidemia has not increased in the last decade. C. albicans was the most common species and it remains susceptible to fluconazole.

Clinical outcomes of polyvalent immunoglobulin use in solid organ transplant recipients: A systematic review and meta-analysis.

Polyvalent immunoglobulin is commonly used for desensitization and treatment of antibody-mediated rejection in kidney transplantation but its impact on other outcomes is not known. This systematic review investigated the impact of immunoglobulin prophylaxis on infection, rejection, graft loss, and death following kidney transplantation. A comprehensive literature search located 18 studies (n = 8 randomized controlled trials). None examined the effect of immunoglobulin prophylaxis in transplant recipients with hypogammaglobulinemia. Quality of included studies was variable with high to very high risk of bias. In the randomized trials, immunoglobulin use did not reduce cytomegalovirus infection (OR 0.68 [0.39, 1.21]; 6 studies, n = 295), rejection (OR 0.96 [0.50, 1.82]; 4 studies, n = 187), or graft loss (OR 1.03 [0.46, 2.30]; 6 studies, n = 265). In non-randomized studies, immunoglobulin did not reduce cytomegalovirus infection (OR 0.63 [0.20, 1.94]; 6 studies, n = 361) or death (OR 1.32 [0.05, 38.79]; 3 studies, n = 222) but reduce rejection (OR 0.47 [0.24, 0.94]; 4 studies, n = 268) and graft loss (OR 0.15 [0.05, 0.43]; 2 studies, n = 118). Data were scarce and sample size of current evidence was small. Adequately powered randomized trials are needed to determine if immunoglobulin is an effective intervention to reduce infection, rejection, graft loss, or death following kidney transplantation with and without hypogammaglobulinemia.

Clinical outcomes of polyvalent immunoglobulin use in solid organ transplant recipients: A systematic review and meta-analysis - Part II: Non-kidney transplant.

Immunoglobulin (IG) is commonly used to desensitize and treat antibody-mediated rejection in solid organ transplant (SOT) recipients. The impact of IG on other outcomes such as infection, all-cause mortality, graft rejection, and graft loss is not clear. We conducted a similar systematic review and meta-analysis to our previously reported Part I excluding kidney transplant. A comprehensive literature review found 16 studies involving the following organ types: heart (6), lung (4), liver (4), and multiple organs (2). Meta-analysis could only be performed on mortality outcome in heart and lung studies due to inadequate data on other outcomes. There was a significant reduction in mortality (OR 0.34 [0.17-0.69]; 4 studies, n = 455) in heart transplant with hypogammaglobulinemia receiving IVIG vs no IVIG. Mortality in lung transplant recipients with hypogammaglobulinemia receiving IVIG was comparable to those of no hypogammaglobulinemia (OR 1.05 [0.49, 2.26]; 2 studies, n = 887). In summary, IVIG targeted prophylaxis may decrease mortality in heart transplant recipients as compared to those with hypogammaglobulinemia not receiving IVIG, or improve mortality to the equivalent level with those without hypogammaglobulinemia in lung transplant recipients, but there is a lack of data to support physicians in making decisions around using immunoglobulins in all SOT recipients for infection prophylaxis.

A national survey of screening and management of hypogammaglobulinemia in Canadian transplantation centers.

BACKGROUND: Infection remains one of the most common transplant-related causes of death in patients undergoing transplantation. Secondary hypogammaglobulinemia (HGG) as a component of immune suppression and deficiency is associated with both solid organ transplantation (SOT) and hematopoietic cell transplantation (HCT). Available data and clinical experience for the supplementation of immunoglobulin (Ig) in these patients is conflicting, and differing clinical opinion accounts for non-uniform practice in the use of Ig treatment. We aimed to survey lead transplant practitioners for current practice around polyvalent Ig use in post-transplant recipients across Canada. METHODS: We performed a survey study using short questionnaires to estimate rate of screening of HGG, use of polyvalent Ig, and physician's opinion on Ig treatment and infection prevention. Directors of 24 SOT and 23 HCT centers across Canada were invited to participate in the survey via an electronic mail. RESULTS: Overall response rate was 63.8%. Twenty percent of SOT programs routinely measured Ig levels pre-transplant compared to 33% of allogeneic (allo-) and 21% of autologous (auto-) HCT programs. Post-transplant Ig levels were measured in 13%, 75%, and 29% in SOT, allo-HCT, and auto-HCT, respectively. The SOT and auto-HCT groups indicated that they do not prescribe Ig therapy (100% and 86%), contrary to the allo-HCT group (42%). Of the respondents in the SOT, allo-HCT, and auto-HCT groups, 60%, 67%, and 36%, respectively, thought infections could be prevented with intravenous immunoglobulins (IVIg). A majority of respondents indicated they would be interested in participating in a randomized controlled trial evaluating the use of IVIg in the SOT and in both HCT groups (100%, 83%, and 57%, respectively). CONCLUSIONS: Our study shows significant variation in practice between SOT and HCT centers with respect to screening and management of HGG. There is willingness to participate in a randomized controlled trial to address whether Ig treatment reduces infection in post-transplant recipients.

Ten Clinical Pearls in Microbiology: How Effective Collaboration Optimizes Patient Care.

Medical microbiology laboratories play an essential role in patient care-appertaining to infectious diseases diagnostics and treatment, infection prevention, and antimicrobial stewardship. Collaboration between clinicians and the microbiology laboratory can promote and enhance the safety, quality, and efficiency of patient care. We review practical, evidence-informed core concepts to explicate how effective partnership between clinicians and the microbiology laboratory improves patient outcomes.

How is ceftobiprole used in Canada: the CLEAR study final results.

BACKGROUND: We report the final results of the clinical usage of ceftobiprole in patients in Canada from data in the national CLEAR (Canadian Le adership on Antimicrobial Real-Life Usage) registry. RESEARCH DESIGN AND METHODS: The authors review the final data using the national ethics approved CLEAR study. Thereafter, the literature is surveyed regarding the usage of ceftobiprole to treat patients with infectious diseases via PubMed (up to March 2024). RESULTS: In Canada, ceftobiprole is primarily used as directed therapy to treat a variety of severe infections caused by MRSA. It is primarily used in patients failing previous antimicrobials, is frequently added to daptomycin and/or vancomycin with high microbiological and clinical cure rates, along with an excellent safety profile. Several reports attest to the microbiological/clinical efficacy and safety of ceftobiprole. Ceftobiprole is also reported to be used empirically in select patients with community-acquired bacterial pneumonia (CABP), as well as hospital-acquired bacterial pneumonia (HABP). CONCLUSIONS: In Canada, ceftobiprole is used mostly as directed therapy to treat a variety of severe infections caused by MRSA, in patients failing previous antimicrobials. It is frequently added to, and thus used in combination with daptomycin and/or vancomycin with high microbiological/clinical cure rates, and an excellent safety profile.

Ten common misconceptions about antibiotic use in the hospital.

Antimicrobials are one of the most administered medications in hospitals. Thoughtful and rational antibiotic prescribing by clinicians are important in reducing the adverse effects to both the host that takes the antibiotic and also the individuals in the host's community. Principles informing antibiotic prescribing in the hospital are commonly rooted in misconceptions. We review 10 common myths associated with antibacterial usage in hospitalized patients and share contemporary evidence in hopes of enhancing evidence-informed practice in this patient care setting.

Leprosy: Challenges in diagnosis.

Leprosy (Hansen's disease) is caused by Mycobacterium leprae. It affects the skin and peripheral nerves. Incidence and prevalence are underestimated due to challenges in diagnosis and unfamiliarity with the disease in Canada. Untreated disease can lead to permanent nerve damage with subsequent loss of function. We present a case of Hansen's disease with delay in diagnosis and treatment. A 31-year-old female recent immigrant from the Philippines presented with a 2-year history of a palpable erythematous rash on her face and arms. She had a diagnosis of cryoglobulinemic vasculitis associated with her chronic hepatitis B. A course of topical corticosteroids did not alleviate symptoms. The rash had a waxing and waning pattern that was felt to mirror her antiviral therapy. Although hepatitis B cryoglobulinemia has been reported in the remote literature, further studies have failed to illustrate that it is a significant cause of cryoglobulinemia. Retrospective analysis of the case identified that anchoring to the initial diagnosis was the reason for delay in diagnosis and treatment.

La lèpre est causée par le Mycobacterium leprae. Elle touche la peau et les nerfs périphériques. Son incidence et sa prévalence sont sous-estimées en raison du diagnostic difficile à poser et de la méconnaissance de cette maladie au Canada. Non traitée, cette maladie peut provoquer des lésions nerveuses permanentes, suivies d'une perte de fonction. Les chercheurs présentent un cas de maladie de Hansen qui a tardé à être diagnostiqué et traité. Une néo-immigrante de 31 ans des Philippines a consulté à cause d'une éruption érythémateuse palpable qu'elle avait depuis deux ans sur le visage et les bras. Elle avait reçu un diagnostic de vascularite cryoglobulinémique associé à une hépatite B chronique. Une corticothérapie topique n'a pas soulagé les symptômes. L'éruption avait un aspect de creux et de bosses qui semblait refléter l'antivirothérapie. Même si la cryoglobulinémie causée par l'hépatite B est signalée dans des publications isolées, d'autres études n'ont pu démontrer de lien important entre ces deux affections. L'analyse rétrospective du cas a établi que l'association des symptômes avec le diagnostic initial explique le retard de diagnostic et de traitement.

The Risk of Diarrhea and Colitis in Patients With Advanced Melanoma Undergoing Immune Checkpoint Inhibitor Therapy: A Systematic Review and Meta-Analysis.

Checkpoint inhibitors are a first-line therapy for advanced melanoma, though their use is limited by diarrhea and colitis. The aim of our study was to determine the risk of these toxicities associated with immunotherapy in advanced melanoma. Electronic databases were searched through June 2017 for prospective studies reporting the risk of diarrhea and colitis in advanced melanoma treated with anti-programmed death-1 (PD-1) or anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitors. Standardized definitions assessed the grade of diarrhea and colitis. Pooled incidence and weighted relative risk estimates with 95% confidence intervals (CI) were estimated using random effects model. Eighteen studies were included: 6 studies (1537 patients) with PD-1 inhibitors and 15 studies (3116 patients) with CTLA-4 inhibitors. The incidence of all-grade diarrhea was 13.7% (95% CI, 10.1%-17.2%) for anti-PD-1 and 35.4% (95% CI, 30.4%-40.5%) for anti-CTLA-4. The incidence of all-grade colitis was 1.6% (95% CI, 0.7%-2.4%) for anti-PD-1, and 8.8% (95% CI, 6.1%-11.5%) for anti-CTLA-4. When PD-1 inhibitors were compared directly with CTLA-4 inhibitors, the relative risk of all-grade diarrhea was 0.58 (95% CI, 0.43-0.77), and the relative risk of all-grade colitis was 0.16 (95% CI, 0.05-0.51). The rate of therapy discontinuation was numerically higher for anti-CTLA-4 therapy compared with anti-PD-1 therapy. Finally, 2 studies compared combination immunotherapy with anti-CTLA-4 therapy alone. The relative risk of developing all-grade diarrhea and colitis with combination therapy was 1.31 (95% CI, 1.09-1.57) and 1.21 (95% CI, 0.73-1.99), respectively. Diarrhea and colitis are frequent toxicities associated with checkpoint inhibitors, and seem to be most common with CTLA-4 inhibitors.

Angioinvasive mucormycosis and paradoxical stroke: a case report.

INTRODUCTION: Rhizopus typically results in acute, aggressive and angioinvasive infection, particularly in immunosuppressed individuals. Risk factors include immunosuppression in haematologic malignancy, uncontrolled hyperglycemia, iron overload states, and older chelator agents such as deferoxamine. CASE PRESENTATION: We describe a case of a 33-year-old female with transfusion-dependent beta thalassemia who was started on intravenous deferiprone therapy and subsequently presented with a retropharyngeal abscess. Despite intravenous broad spectrum antibiotics, she continued to deteriorate and developed aphasia. A CT scan of her head showed multiple hypodensities. Blood cultures grew Rhizopus species and a subsequent transesophageal echocardiogram showed a mass in the right atrium with a patent foramen ovale. CONCLUSION: Although deferiprone, a newer iron chelator agent, has antifungal properties in vivo, this case illustrates that angioinvasive Rhizopus infections can occur in patients treated with deferiprone.

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection.

BACKGROUND: Nivolumab (Opdivo™) is a novel IgG4 subclass programmed death-1 (PD-1) inhibiting antibody that has demonstrated breakthrough-designation anti-tumor activity. To date, clinical trials of nivolumab and other checkpoint inhibitors have generally excluded patients with solid organ transplantation and patients with concurrent immunosuppression. However, organ transplant recipients are at high-risk of development of malignancy as a result of suppressed immune surveillance of cancer. CASE PRESENTATION: We illustrate the outcomes of a 63 year-old type I diabetic female patient who developed pulmonary metastatic, BRAF wild-type cutaneous melanoma 10 years after renal transplantation. After downward titration of the patient's immunosuppressive medications and extensive multidisciplinary review, she was treated with nivolumab in the first-line setting. Within 1 week of administration, the patient experienced acute renal allograft rejection, renal failure and concurrent diabetic ketoacidosis due to steroid therapy. Allograft function did not return, but patient made a full clinical recovery after being placed on hemodialysis. Subsequently, the patient had clinical disease progression off therapy and required re-challenge with nivolumab on hemodialysis, resulting in ongoing clinical and radiographic response. CONCLUSIONS: This case illustrates multiple practical challenges and dangers of administering anti-PD1 immune checkpoint inhibitors to patients with solid-organ transplantation including need for titration of immunosuppressive medications, risks of allograft rejection, and treatment during hemodialysis.

Brain reorganization after endovascular treatment in a patient with a large arteriovenous malformation: the role of diagnostic and functional neuroimaging techniques.

We describe a case of brain cortical reorganization after embolization of a large right temporal arteriovenous malformation. A comprehensive imaging protocol, including functional magnetic resonance imaging (fMRI), cortical thickness analysis and 320-row computed tomography (CT) perfusion was used to provide information on brain plasticity and potential steal phenomenon. A 25-year-old man known for a right temporal grade V Spetzler-Martin classification arteriovenous malformation (AVM) presented with left progressive hemiparesis. He underwent functional 3T magnetic resonance imaging (fMRI), cortical thickness analysis, and CT perfusion (CT 320 row, Aquilion ONE, Toshiba, Tokyo, Japan) before and after endovascular treatment. The results were compared to look for modifications in brain perfusion and organization. An improvement in the left hemiparesis and a reorganization of motor function were observed after endovascular treatment. Modifications in the angioarchitecture and perfusion of an extensive AVM may be accompanied by a functional and structural reorganization of the brain. The location in the so-called eloquent regions may not be sufficient to explain the wide spectrum of symptoms that these patients can present. A more comprehensive approach considering a global involvement of the brain in patients with large AVMs is suggested to achieve the best treatment strategy and to stage treatment in incurable AVMs.