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.

The use of biomarkers and molecular methods for the earlier diagnosis of invasive aspergillosis in immunocompromised patients.

Invasive aspergillosis (IA) is an opportunistic infection that is often life threatening in the immunocompromised host. Early diagnosis is critical, especially given the efficacy and availability of several new anti-fungal therapies. Current (2008) diagnostic criteria have limited ability to detect early infection and are aimed at establishing disease. Although histopathology and culture techniques have traditionally been used to make a proven diagnosis of IA, their dependence on tissue samples and slow turnaround times hamper early confirmation of IA. Serologic detection of circulating galactomannan and 1,3-ß-D-glucan fungal biomarkers show promise for improving the diagnosis of IA, and their use is included in the EORTC/MSG diagnostic criteria for IA. Numerous studies have evaluated the diagnostic performance of these two biomarkers and shown that they have suboptimal sensitivity when used alone for early diagnosis of proven IA. Currently available molecular assays also suffer from a lack of standardization. Evaluation of the use of different combinations of test methods to enhance diagnostic accuracy is also being done but prompt, accurate diagnosis of IA remains a clinical and diagnostic challenge. The clinical validity and limitations of biomarkers and current molecular methods for the early diagnosis of IA are summarized in this review with respect to the different patient populations at risk for this serious infection.

Subacute bacterial endocarditis caused by Cardiobacterium hominis: A case report.

Cardiobacterium hominis, a member of the HACEK group of organisms, is an uncommon but important cause of subacute bacterial endocarditis. First-line therapy is a third-generation cephalosporin due to rare beta-lactamase production. The authors report a case involving endovascular infection due to C hominis that initially tested resistant to third-generation cephalosporins using an antibiotic gradient strip susceptibility method (nitrocephin negative), but later proved to be susceptible using broth microdilution reference methods (a 'major' error). There are limited studies to guide susceptibility testing and interpretive breakpoints for C hominis in the medical literature, and the present case illustrates some of the issues that may arise when performing susceptibility testing for fastidious organisms in the clinical microbiology laboratory.

Le Cardiobacterium hominis, qui appartient aux organismes du groupe HACEK, est une cause d'endocardite bactérienne subaiguë peu fréquente, mais importante. La céphalosporine de troisième génération en est le traitement de première ligne, en raison d'une rare production de bêta-lactamase. Les auteurs rendent compte d'un cas d'infection endovasculaire à C hominis qui a d'abord été considéré comme résistant aux céphalosporines de troisième génération d'après la méthode de susceptibilité par bandelette contenant un gradient d'antibiotique (négative à la nitrocéphine), mais qui s'y est révélé susceptible selon les méthodes de microdilution de référence (une erreur « majeure ¼). Peu de publications traitent des études pour orienter les tests de susceptibilité et les seuils d'interprétation du C hominis, et le présent cas démontre quelques problèmes qui peuvent surgir lors de tests de susceptibilité d'organismes difficiles à isoler au laboratoire de microbiologie clinique.

Filling in the gaps of clerkship with a comprehensive clinical skills curriculum.

Although the clinical clerkship model is based upon sound pedagogy, including theories of social learning and situated learning, studies evaluating clinical performance of residents suggests that this model may not fully meet the learning needs of students. Here our objective was to design a curriculum to bridge the learning gaps of the existing clerkship model and then evaluate the impact of this on performance on clerkship summative evaluations. We followed Kern's framework to design our curriculum and then compared performance on the clerkship objective structured clinical examination (OSCE), all summative clerkship multiple choice question (MCQ) examinations, and the Medical Council of Canada Qualifying Examination (MCCQE) Part 1 before and after the introduction of our curriculum. In the 2 years following the introduction of our clinical skills curriculum the mean score on the clerkship OSCE was significantly higher than in the 2 years prior to our curriculum [67.12 (5.3) vs. 62.44 (4.93), p < 0.001, d = 0.91]. With the exception of the surgical clerkship MCQ, performance on all clerkship summative MCQ examinations and MCCQE Part 1 was significantly higher following the introduction of our curriculum. In this study we found a significant improvement in the performance on clerks on summative evaluations of knowledge and clinical skills following the introduction of our clinical skills curriculum. Given the unpredictable nature of clinical rotations, the clerkship will always be a risk of failing to deliver the intended curriculum-so medical schools should continue to explore and evaluate ways of changing the delivery of clerkship training to improve learning outcomes.

Point prevalence study of antibiotic susceptibility of genital group B streptococcus isolated from near-term pregnant women in Calgary, Alberta.

BACKGROUND: Genital group B streptococcus (GBS) may be transmitted from a colonized mother to her infant if appropriate intrapartum antibiotic prophylaxis is not given. A recent case of GBS neonatal sepsis occurred due to an erythromycin-intermediate strain after empirical use of this drug as intrapartum prophylaxis. OBJECTIVE: To determine the regional antibiotic resistance rates of genital GBS isolates to penicillin, erythromycin and clindamycin. METHODS: A total of 309 genital GBS strains cultured from vaginal/rectal swabs were prospectively isolated and randomly selected between March and May 2011. Etest strips (bioMèrieux, France) were used to determine the minimum inhibitory concentrations to penicillin, erythromycin and clindamycin according to standard methods. All isolates that either demonstrated intermediate or full resistance to erythromycin had a D-test performed to detect inducible resistance to clindamycin. The resistance mechanism for each isolate was inferred from its antibiogram phenotype. RESULTS: All genital GBS isolates were susceptible to penicillin, but high rates of resistance were found to both erythromycin (25%) and clindamycin (22%), mainly due to acquisition of erythromycin ribosomal methylation genes (erm) that result in the MLSB resistance phenotype. Most often the MLSB resistance phenotype was constitutive (MLSB-C; 14.2%) rather than inducible (MLSB-I; 8.1%), and an efflux mechanism (msrA; 3%) was much less common. DISCUSSION: The present article is the first point prevalence study of genital GBS antibiogram profile that has been reported from a Canadian health care region. The high rates of resistance of genital GBS to both erythromycin and clindamycin is mainly due to the acquisition and spread of erm genes conveying the MSLB phenotype. CONCLUSION: Changes to clinical and laboratory practice in the Calgary, Alberta, region were made to prevent additional cases of neonatal GBS sepsis due to inappropriate intrapartum antibiotic prescription.

HISTORIQUE: En l'absence de prophylaxie antibiotique intrapartum, le streptocoque du groupe B (SGB) génital peut être transmis d'une mère colonisée à son nourrisson. Un récent cas de sepsie à SGB néonatal s'est produit en raison d'une souche intermédiaire à l'érythromycine après l'utilisation empirique de ce médicament en guise de prophylaxie intrapartum. OBJECTIF: Déterminer le taux régional de résistance des isolats de SGB génital à la pénicilline, à l'érythromycine et à la clindamycine. MÉTHODOLOGIE: Au total, les chercheurs ont isolé et sélectionné au hasard 309 souches de SGB génital provenant de cultures d'écouvillons vaginaux ou rectaux entre mars et mai 2011. Ils ont utilisé des bandes de test E (bioMèrieux, France) pour déterminer les concentrations inhibitrices minimales à la pénicilline, à l'érythromycine et à la clindamycine, conformément aux méthodes classiques. Pour tous les isolats qui démontraient une résistance intermédiaire ou complète à l'érythromycine, ils ont effectué un test D afin de déceler la résistance inductible à la clindamycine. Ils ont inféré le mécanisme de résistance de chaque isolat à partir du phénotype de l'antibiogramme. RÉSULTATS: Tous les isolats de SGB génital étaient susceptibles à la pénicilline, mais les chercheurs ont observé de forts taux de résistance à la fois à l'érythromycine (25 %) et à la clindamycine (22 %), surtout en raison de l'acquisition de gènes de méthylation ribosomique à l'érythromycine (erm), qui provoquent le phénotype de résistance aux MLSB. La plupart du temps, le phénotype de résistance aux MLSB était d'ordre constitutif (MLSB-C; 14,2 %) plutôt que d'ordre inductible (MLSB-I; 8,1 %). Le mécanisme d'efflux (msrA; 3 %) était beaucoup moins courant. EXPOSÉ: Le présent article est la première étude de prévalence ponctuelle sur le profil antibiogramme du SGB génital provenant d'une région sanitaire canadienne. Les taux élevés de résistance du SGB génital à l'érythromycine et à la clindamycine sont surtout causés par l'acquisition et la propagation des gènes conférant une résistance aux macrolides (erm) transportant le phénotype aux MSLB. CONCLUSION: Des changements à la pratique clinique et de laboratoire ont été apportés dans la région de Calgary, en Alberta, afin d'éviter de nouveaux cas de sepsie à SGB néonatal attribuables à une prescription inadéquate d'antibiotiques pendant la période intrapartum.

Mycobacterium senegalense tissue infection in a child after fish tank exposure.

The present report describes the first known case of an otherwise healthy child who developed a soft tissue infection due to Mycobacterium senegalense - a pathogen usually found in east Africa that is responsible for infecting various animals. The patient presented with nonhealing wounds after sustaining facial lacerations from the shattered glass of a fish tank. The patient responded well to scar revision and antibiotics, with no subsequent relapse.

The effect of gender interactions on students' physical examination ratings in objective structured clinical examination stations.

PURPOSE: Previous studies have reached a variety of conclusions regarding the effect of gender on performance in objective structured clinical examinations (OSCEs). Most measured the effect on students' overall OSCE score. The authors of this study evaluated the effect of gender on the scores of specific physical examination OSCE stations, both "gender-sensitive" and "gender-neutral." METHOD: In 2008, the authors collected scores for 138 second-year medical students at the University of Calgary who underwent a seven-station OSCE. Two stations--precordial and respiratory exams--were considered gender-sensitive. Multiple linear regression was used to explore the effect of students', standardized patients' (SPs'), and raters' genders on the students' scores. RESULTS: All 138 students (69 female) completed the OSCE and were included in the analyses. The mean scores (SD) for the two stations involving examination of the chest were higher for female than for male students (83.2% [15.5] versus 78.3% [15.8], respectively, d = 0.3, P = .009). There was a significant interaction between student and SP gender (P = .02). In the stratified analysis, female students were rated significantly higher than male students at stations with female SPs (85.4% [15.5] versus 76.6% [16.5], d = 0.6, P = .004) but not at stations with male SPs (80.2% [15.0] versus 80.0% [15.0], P = 1.0). CONCLUSION: These results suggest student and SP genders interact to affect OSCE scores at stations that require examination of the chest. Further investigations are warranted to ensure that the OSCE is an equal experience for all students.

Interpretation of MRSASelect screening agar at 24 hours of incubation.

An incubation time of 24 h at 35 to 38 degrees C is recommended for the optimal performance of MRSASelect (Bio-Rad) chromogenic screening agar. An additional 24 h is required to capture slow-growing methicillin-resistant Staphylococcus aureus (MRSA). However, the normal hours of operation for most laboratories cannot reliably accommodate 24-h interpretation intervals. Daily agar plate interpretations are more likely to occur around 18 h and 42 h of incubation, which may compromise the performance of the chromogenic agar and negatively impact patient infection control efforts. In order to validate the importance of stringent incubation times to plate performance, we evaluated MRSASelect medium at controlled intervals of 24 and 48 h of incubation, using clinical MRSA-screening swabs. A total of 1,071 MRSA-positive and 2,733 MRSA-negative cultures were selected for analysis. Compared to 48-h-incubation results, the sensitivity and specificity of MRSASelect at 24 h were 98.3% and 98.2%, respectively. Only 19 of 1,071 (1.8%) MRSA-positive isolates required 48 h for detection. Holding 24-h negative plates an additional 24 h resulted in the workup of 253 (6.6%) pink, yet non-MRSA, colonies. The 24-h positive and negative predictive values of MRSASelect, assuming MRSA prevalences of 1, 5, and 10%, were 35.5 and 99.98%, 74.2 and 99.9%, and 85.9 and 99.8%, respectively. MRSASelect medium held for 24-h incubation is a highly sensitive and specific MRSA-screening tool. Further incubation prolongs the turnaround time for results and creates a significant amount of unnecessary work in the laboratory.

Characterization of PgPepO, a bacterial homologue of endothelin-converting enzyme-1.

PgPepO is a homologue of endothelin-converting enzyme-1 (ECE-1), with which it shares 31% identity. PgPepO was isolated from the periodontal pathogen Porphyromonas gingivalis. Recent studies have suggested a link between periodontal and cardiovascular disease, and several groups have suggested that bacterial and viral infections may contribute to the latter. P. gingivalis possesses the ability to invade, and multiply within, aortic endothelial cells and has been localized to atherosclerotic plaques. PgPepO was expressed and purified to homogeneity and we have begun detailed functional analysis, in terms of substrate preference and inhibitor specificity, in order to provide active-site comparisons with other members of the neprilysin (NEP)/ECE family. PgPepO possesses similar substrate specificity to ECE-1 and has been shown to cleave big endothelin-1 (big ET-1), big ET-2 and big ET-3, converting the substrates into their respective mature endothelin peptides. Substance P, angiotensin I, angiotensin II and neurotensin are all cleaved at multiple sites by PgPepO and the kinetics of these reactions have been compared. The potent vasoconstrictor urotensin II is not hydrolysed by PgPepO. Cleavage of bradykinin by PgPepO occurs at the Pro(7)-Phe(8) bond and is inhibited by the NEP and ECE-1 inhibitor phosphoramidon in a pH-dependent fashion (IC(50) =10 microM at pH 7.0) but not by thiorphan, an NEP-specific inhibitor. PgPepO activity is completely inhibited by EDTA. Characterization of this enzyme is important in elucidating possible links between periodontal pathogens and cardiovascular disorders such as atherosclerosis, and provides an opportunity to gain structural information on a bacterial protein with striking similarity to human ECE-1.

Beta-amyloid catabolism: roles for neprilysin (NEP) and other metallopeptidases?

The steady-state level of amyloid beta-peptide (Abeta) represents a balance between its biosynthesis from the amyloid precursor protein (APP) through the action of the beta- and gamma-secretases and its catabolism by a variety of proteolytic enzymes. Recent attention has focused on members of the neprilysin (NEP) family of zinc metalloproteinases in amyloid metabolism. NEP itself degrades both Abeta(1-40) and Abeta(1-42) in vitro and in vivo, and this metabolism is prevented by NEP inhibitors. Other NEP family members, for example endothelin-converting enzyme, may contribute to amyloid catabolism and may also play a role in neuroprotection. Another metalloproteinase, insulysin (insulin-degrading enzyme) has also been advocated as an amyloid-degrading enzyme and may contribute more generally to metabolism of amyloid-forming peptides. Other candidate enzymes proposed include angiotensin-converting enzyme, some matrix metalloproteinases, plasmin and, indirectly, thimet oligopeptidase (endopeptidase-24.15). This review critically evaluates the evidence relating to proteinases implicated in amyloid catabolism. Therapeutic strategies aimed at promoting A,beta degradation may provide a novel approach to the therapy of Alzheimer's disease.