Susceptibility of hamsters to clostridium difficile isolates of differing toxinotype

Clostridium difficile is the most commonly associated cause of antibiotic associated disease (AAD), which caused ~21,000 cases of AAD in 2011 in the U.K. alone. The golden Syrian hamster model of CDI is an acute model displaying many of the clinical features of C. difficile disease. Using this model we characterised three clinical strains of C. difficile, all differing in toxinotype; CD1342 (PaLoc negative), M68 (toxinotype VIII) and BI-7 (toxinotype III). The naturally occurring non-toxic strain colonised all hamsters within 1-day post challenge (d.p.c.) with high-levels of spores being shed in the faeces of animals that appeared well throughout the entire experiment. However, some changes including increased neutrophil influx and unclotted red blood cells were observed at early time points despite the fact that the known C. difficile toxins (TcdA, TcdB and CDT) are absent from the genome. In contrast, hamsters challenged with strain M68 resulted in a 45% mortality rate, with those that survived challenge remaining highly colonised. It is currently unclear why some hamsters survive infection, as bacterial and toxin levels and histology scores were similar to those culled at a similar time-point. Hamsters challenged with strain BI-7 resulted in a rapid fatal infection in 100% of the hamsters approximately 26 hr post challenge. Severe caecal pathology, including transmural neutrophil infiltrates and extensive submucosal damage correlated with high levels of toxin measured in gut filtrates ex vivo. These data describes the infection kinetics and disease outcomes of 3 clinical C. difficile isolates differing in toxin carriage and provides additional insights to the role of each toxin in disease progression

Parameters for the mathematical modelling of Clostridium difficile acquisition and transmission: a systematic review

INTRODUCTION: Mathematical modelling of Clostridium difficile infection dynamics could contribute to the optimisation of strategies for its prevention and control. The objective of this systematic review was to summarise the available literature specifically identifying the quantitative parameters required for a compartmental mathematical model of Clostridium difficile transmission. METHODS: Six electronic healthcare databases were searched and all screening, data extraction and study quality assessments were undertaken in duplicate. Results were synthesised using a narrative approach. RESULTS: Fifty-four studies met the inclusion criteria. Reproduction numbers for hospital based epidemics were described in two studies with a range from 0.55 to 7. Two studies provided consistent data on incubation periods. For 62% of cases, symptoms occurred in less than 4 weeks (3-28 days) after infection. Evidence on contact patterns was identified in four studies but with limited data reported for populating a mathematical model. Two studies, including one without clinically apparent donor-recipient pairs, provided information on serial intervals for household or ward contacts, showing transmission intervals of <1 week in ward based contacts compared to up to 2 months for household contacts. Eight studies reported recovery rates of between 75%-100% for patients who had been treated with either metronidazole or vancomycin. Forty-nine studies gave recurrence rates of between 3% and 49% but were limited by varying definitions of recurrence. No study was found which specifically reported force of infection or net reproduction numbers. CONCLUSIONS: There is currently scant literature overtly citing estimates of the parameters required to inform the quantitative modelling of Clostridium difficile transmission. Further high quality studies to investigate transmission parameters are required, including through review of published epidemiological studies where these quantitative estimates may not have been explicitly estimated, but that nonetheless contain the relevant data to allow their calculation

Sepsis after elective surgery - Incidence, aetiology and outcome.

To access publisher's full text version of this article click on the hyperlink belowBackground: Sepsis requiring admission to intensive care (ICU) is a rare complication of elective surgery, but is associated with high morbidity and mortality. The aim of this study was to describe the incidence and outcome of sepsis following elective surgery. Methods: This was a retrospective, observational study where all admissions to Icelandic ICUs during calendar years 2006, 2008, 2010, 2012, 2014 and 2016 were screened, identifing patients with sepsis following elective surgery (ACCP/SCCM criteria). The number of elective operations performed at the largest center (Landspitali) during the study years were collected. Descriptive statistics were used to assess the incidence and outcome of patients with sepsis after elective surgery. Results: During the study years, 88 patients were admitted to Icelandic ICUs with sepsis following elective surgery. Of those, 80 were operated at Landspitali, where the incidence of sepsis was 0.19% per elective procedure, highest following pancreaticoduodenectomies (14%, CI 6-25) and esophagectomies (13%, CI 4-27), but the greatest number of patients (30% (26/88)) developed sepsis after a colorectal procedure. The most common infection sources were the abdomen (65% (57/88)) and lungs/mediastinum (22% (19/88)), frequently polymicrobial (58% (36/62) of patients with cultures). The incidence of insufficient empirical antibiotics was high (50% (30/60)). The median ICU and hospital length-of-stay were 5.5 and 26 days and the 28-day and 1-year mortality rates were 16% (14/88) and 41% (36/87), respectively. Conclusions: Incidence of sepsis following elective surgery is low in Iceland but mortality is high. Initial antimicrobial therapy needs careful consideration in these hospital-acquired, often polymicrobial infections. Keywords: Sepsis; nosocomial infections; post-operative complications; surgery.Landspitali Haskolasjukrahu

Risk factors for Clostridium difficile toxin-positive diarrhea: a population-based prospective case-control study.

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.Increased incidence and severity of Clostridium difficile infections (CDIs) is of major concern. However, by minimizing known risk factors, the incidence can be decreased. The aim of this investigation was to calculate the incidence and assess risk factors for CDI in our population. A 1-year prospective population-based nationwide study in Iceland of CDIs was carried out. For risk factor evaluation, each case was matched with two age- and sex-matched controls that tested negative for C. difficile toxin. A total of 128 CDIs were identified. The crude incidence was 54 cases annually per 100,000 population >18 years of age. Incidence increased exponentially with older age (319 per 100,000 population >86 years of age). Community-acquired origin was 27 %. Independent risk factors included: dicloxacillin (odds ratio [OR]: 7.55, 95 % confidence interval [CI]: 1.89-30.1), clindamycin (OR: 6.09, 95 % CI: 2.23-16.61), ceftriaxone (OR: 4.28, 95 % CI: 1.59-11.49), living in a retirement home (OR: 3.9, 95 % CI: 1.69-9.16), recent hospital stay (OR: 2.3, 95 % CI: 1.37-3.87). Proton pump inhibitors (PPIs) were used by 60/111 (54 %) versus 91/222 (41 %) (p = 0.026) and ciprofloxacin 19/111 (17 %) versus 19/222 (9 %) (p = 0.027) for cases and controls, respectively. In all, 75 % of primary CDIs treated with metronidazole recovered from one course of treatment. CDI was mostly found among elderly patients. The most commonly identified risk factors were broad-spectrum antibiotics and recent contact with health care institutions. PPI use was significantly more prevalent among CDI patients

Marian Ladre as the Old Charlatan, Yrek Shabelevsky as Petrouchka, H Algeranoff as the Blackamoor, Tatiana Riabouchinska as the Dancer, and artists of the company, in Petrouchka, Covent Garden Russian Ballet, Australian tour, His Majesty's Theatre, Melbourne, 1938 [picture] /

From: Petrouchka : a burlesque in four acts / book by Alexandre Benois and Igor Stravinsky ; music by Igor Stravinsky.; Inscription: "Q34 (6)".; Part of the collection: Hugh P. Hall collection of photographs, 1938-1940.; Petrouchka was performed in Melbourne in October - November 1938.; Choreography by Michel Fokine ; curtain, scenery and costumes by Alexandre Benois.; Also available in an electronic version via the Internet at: http://nla.gov.au/nla.pic-vn3996373. One of a collection of photographs taken by Hugh P. Hall of 28 ballet productions performed by the Covent Garden Russian Ballet (toured Australia 1938-1939) and the Original Ballet Russe (toured Australia 1939-1940). These are the second and third of the three Ballets Russes companies which toured Australasia between 1936 and 1940. The photographs were taken from the auditorium during a live performance in His Majesty's Theatre, Melbourne and mounted on cardboard for display purposes. For conservation and storage, the photographs have been demounted. The original arrangement of the photographs has been recorded, and details are available from the Pictures Branch of the National Library

Risk factors for Clostridium difficile toxin-positive diarrhea: a population-based prospective case-control study

Increased incidence and severity of Clostridium difficile infections (CDIs) is of major concern. However, by minimizing known risk factors, the incidence can be decreased. The aim of this investigation was to calculate the incidence and assess risk factors for CDI in our population. A 1-year prospective population-based nationwide study in Iceland of CDIs was carried out. For risk factor evaluation, each case was matched with two age- and sex-matched controls that tested negative for C. difficile toxin. A total of 128 CDIs were identified. The crude incidence was 54 cases annually per 100,000 population > 18 years of age. Incidence increased exponentially with older age (319 per 100,000 population > 86 years of age). Community-acquired origin was 27 %. Independent risk factors included: dicloxacillin (odds ratio [OR]: 7.55, 95 % confidence interval [CI]: 1.89-30.1), clindamycin (OR: 6.09, 95 % CI: 2.23-16.61), ceftriaxone (OR: 4.28, 95 % CI: 1.59-11.49), living in a retirement home (OR: 3.9, 95 % CI: 1.69-9.16), recent hospital stay (OR: 2.3, 95 % CI: 1.37-3.87). Proton pump inhibitors (PPIs) were used by 60/111 (54 %) versus 91/222 (41 %) (p = 0.026) and ciprofloxacin 19/111 (17 %) versus 19/222 (9 %) (p = 0.027) for cases and controls, respectively. In all, 75 % of primary CDIs treated with metronidazole recovered from one course of treatment. CDI was mostly found among elderly patients. The most commonly identified risk factors were broad-spectrum antibiotics and recent contact with health care institutions. PPI use was significantly more prevalent among CDI patients

Sequential organ failure assessment score (SOFA) scores differ between genders in a sepsis cohort : cause or effect?

Background: Controversy exists regarding the influence of gender on sepsis events and out­come. Epidemiological data from other countries may not always apply to local circum­stances.  The aim of this study was to identify gender differences in patient characteristics, treatment and outcome related to the occurrence of sepsis at admission to the ICU. Methods: A prospective observational cohort study on patients admitted to the ICU over a three-year period fulfilling sepsis criteria during the first 24 hours. Demographic data, APACHE II score, SOFA score, TISS 76, aetiology, length of stay (LOS), mortality rate and aspects of treatment were collected and then analysed with respect to gender differences. Results: There were no gender related differences in mortality or length of stay. Early organ dysfunction assessed as SOFA score at admission was a stronger risk factor for hospital mor­tality for women than for men. This discrepancy was mainly associated with the coagulation sub score. CRP-levels differed between genders in relation to hospital mortality. Infection from the abdominopelvic region was more common among women whereas infection from skin or skin structures were more common in men. Conclusion: In this cohort, gender was not associated with increased mortality during a two year follow up period.  SOFA score at ICU-admission was a stronger risk factor for hospital mortality for women than for men. The discrepancy was mainly related to the coagulation SOFA sub score. Together with differences in CRP-levels this may suggest differences in inflammatory response patterns between genders