Thesis (M.A.)--Boston University / PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / Gandida albicans strain 105 from a normal human and strain 582 (from the American type Culture Collection) were used for studying the effect in vitro of pH, various amounts of carbon dioxide, nitrogen, and composition of media on filamentation in this yeast-like organism. The yeast phase of the organism was maintained on a glucose, glycine, yeast extract (GGY) medium (1%; 1%; 0.5%) at 37°C. The experiments were conducted on both solid and liquid media. All cultures were incubated at 37°C. for 48 hours. The two strains of c. albicans, although similar to one another in their yeast forms, behaved differently toward the environmental conditions used; strain 582 responded more readily to the factors inducing filament formation than did strain 105. Increasing the pH above 6.5 to 7.0, 7.5 and 8.0 induced maximum filamentation in strain 582, whereas no filaments were produced by strain 105. All the aerobic cultures on solid GGY medium showed alkalinity and were positive for ammonia at the end of the incubation period. In liquid media, no alkalinity was observed at any pH values. Presence of 75% carbon dioxide in the atmosphere increased filamentation in strain 582 to a maximum degree, and induced mycelial formation in strain 105. With 94% or 95% carbon dioxide, growth and filamentation decreased in both strains. None of the CO2 cultures showed alkalinity at the end of the incubation period. Moreover, all the CO2 cultures were negative for ammonia. Growth under nitrogen (9J%) was less than that of the aerobic cultures. However, colonies appeared larger in size. Nitrogen stimulated filamentation in strain 105 only at a pH of 8.0, whereas strain 582 formed a maximum amount of filaments at pH values of 7.0 to 8.0. All the solid cultures under nitrogen showed alkalinity, while the liquid cultures were acid at all pH values. The occurrence of deamination in a medium without glucose in both strains of C. albicans showed that this organism was able to use glycine its source of both nitrogen and carbon. However, only a sparse growth was obtained in a medium lacking glucose. Strain 105 did not form filaments in such a medium, while strain 582 did so. Since more filaments were produced by the latter strain when a fresh subculture on a GGY medium was transferred to a medium without glucose, it was concluded that possibly glucose is required for both growth and filamentation. Comparative studies of the effect of a medium containing mannose with a glucose medium showed the two sugars behaved similarly with regard to fermentation and filament induction in both strains or c. albicans. Under conditions where glucose induced filamentation (e.g., with C02 or N2), mannose also induced filamentation. The decreased growth in the presence of oleic or stearic acid in a concentration of 40 micrograms per liter was attributed to the toxic effect of the fatty acids. Moreover, it was noted that the two acids had different effects on filamentation in the two strains. Oleic acid in a solid GGY medium induced hyphal formation in strain 105 only under nitrogen; without glucose, oleic acid did not bring about filamentation under any of the atmospheric conditions tested. In liquid media, oleic acid induced filamentation for strain 105 only when glucose was omitted. With strain 562, oleic acid promoted filamentation in both liquid and solid media with or without glucose, except for solid cultures incubated under nitrogen in the absence or glucose. Stearic acid did not stimulate filamentation in strain 105 under any conditions, but did increase hypha! formation in strain 582. In the presence of stearic acid, maximum filamentation occurred in aerobic cultures wnen glucose was absent. Although maximum filamentation occurred with an increase in the pH of the medium under aerobic conditions, in the presence of 75% C02, under nitrogen or in the presence of stearic acid in a medium without glucose, yeast cells were also present, indicating that this Y to f transformation was not complete. / 2031-01-01

Orientador: Ruben Pablo Schocken-Iturrino / Coorientador: Luis Guilherme de Oliveira / Banca: Alessandra Aparecida Medeiros / Banca: Lilian Cristina Makino / Banca: Fernando Antonio de Ávila / Banca: Caroline Peters Pigatto De Nardi / Resumo: A infecção por Clostridium difficile é na maioria das vezes de manifestação subclínica em leitões jovens. E como atualmente este agente tem tido grande importância na medicina veterinária e possivelmente potencial zoonótico, o objetivo desta pesquisa foi avaliar a transmissão de C. difficile por via naso-nasal e aerógena em leitões jovens, utilizando analises microbiológicas, histopatológicas e moleculares. Leitões foram divididos em três grupos (Infectado, Sentinela e Controle), e distribuídos em baias isoladoras. Os grupos Infectados receberam inóculo 109 UFC.mL-1 e 108UFC.mL-1 de C. difficile 096 para via de transmissão naso-nasal e aerógena, respectivamente. Suabes anorretais foram colhidos diariamente para análises microbiológicas e moleculares da excreção nas fezes, utilizou-se técnica de PCR com iniciadores oligonucleotídeos que codificam os genes das toxinas TcdB e TcdA de Clostridium difficile para identificação molecular. Realizou-se eutanásia dos leitões, após 18 dias de infecção experimental, para avaliações histopatológicas e microbiológicos de intestino delgado, cólon, fígado, baço, tonsilas palatinas e linfonodos. Os grupos Infectado e Sentinela da via naso-nasal desenvolveram sinais clínicos de enfermidade, enquanto os animais da via aerógena não apresentaram sinais de infecção. Os leitões avaliados por via naso-nasal foram positivos para o gene TcdB nos grupos Infectado e Sentinela, enquanto os leitões desafiados por via aerógena foram positivos para TcdB ape... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Clostridium difficile infection is most often of subclinical manifestation in young piglets. As this agent has been of great importance in veterinary medicine and also zoonotic potential, the objective of this research was to evaluate the naso-nasal and aerogenic transmission of C. difficile in young pigs, using microbiological, histopathological and molecular analyzes. Piglets were divided into three groups (Infected, Sentinel and Control), and distributed in isolation bays. The infected group received inoculum 109 CFU.mL-1 and 108 CFU.mL-1 of C. difficile 096 for the naso-nasal and aerogenic transmission route, respectively. Anorectal swabs were harvested for microbiological and molecular analyzes of faecal excretion, a PCR technique was used with primers that encode the TcdB and TcdA toxin genes of Clostridium difficile for molecular identification. Euthanasia of piglets after 18 days of experimental infection was performed for histopathological and microbiological evaluations of small intestine, colon, liver, spleen, palatine tonsils and lymph nodes. The Infected and Sentinel groups of the naso-nasal route developed clinical signs of disease, whereas the animals in the aerogenic showed no signs of infection. The naso-nasal piglets were positive for the TcdB gene in the Infected and Sentinel groups, while the pigs challenged by the aerogenic route were positive for TcdB only in the Infected group. In the histopathological analyzes of piglets of the naso-nasal route, several lesions were observed in the target organs of both the Infected group and the Sentinel; in the piglets of the aerogenic histologically evaluated, only the Infected group presented lesions in the organs, and in both routes, the most notable lesions were in the small intestine. Only the naso-nasal route confirmed transmission of Clostridium difficile, including clinical signs ... (Complete abstract click electronic access below) / Doutor

Resumo: A triagem de crianças para bacteriúria assintomática objetivando prevenir pielonefrite e danos renais é amplamente recomendada. Amostras de urina, colhidas sem contaminação, de 500 pré-escolares com idade entre 2 a 7 anos foram submetidas ao teste com cloridrato de trifeniltetrazólio (TTC) e a urocultura. Culturas quantitativas foram realizadas usando dois diferentes meios de cultura: ágar CLED e ágar MacConkey. As colônias foram contadas, após 18-24 horas de incubação à 35-37ºC. O achado de 105 ou mais UFC/mL do mesmo microrganismo foi considerado como positivo. Para realizar o teste com TTC, 4 mL da urina foram misturados com 1 mL da solução aquosa de TTC estéril à 1% e incubados à 35-37ºC por 4 horas. Uma segunda urocultura foi realizada para as crianças que apresentaram resultado positivo. A sensibilidade aos antimicrobianos foi determinada. Uma comparação entre a urocultura e o teste com TTC foi feita, para avaliação do teste. Um questionário foi aplicado para avaliar fatores predisponentes comportamentais e funcionais. A triagem para bacteriúria assintomática, em pré-escolares em Araraquara-SP-Brasil mostrou uma prevalência de 1,4%. Escherichia coli foi o microrganismo mais isolado e a resistência a tetraciclina foi significante. Os resultados mostram que o teste com TTC possui 91,3% de sensibilidade; 64,3% de especificidade; 15,5% de valor preditivo positivo e 99,0% de valor preditivo negativo. Esses valores mostram que este teste pode ser usado como metodologia de triagem. O fato de já ter desenvolvido ITU anteriormente; usar o papel de trás para frente na higienização anal; beber menos de 1L de água por dia; e usar roupa íntima apertada foram considerados possíveis fatores de risco para o desenvolvimento de bacteriúria assintomática. / Abstract: Urinary tract infection (UTI) is the most commom of bacterial infections. Screening children for asymptomatic bacteriuria to prevent pyelonephritis and renal scarring is widely recommended. Urine samples, revealed without contamination, from 500 pre-school children aged 2 to 7 years were submited to the tryphenyl tetrazolium chloride (TTC) test and urine culture. Quantitative urine cultures was performed using two different agar types: CLED and MacConkey. Colonies were count after 18-24 hours of incubation at 35-37ºC. The finding of 105 or more CFU/mL of the same microorganism constituted a positive culture. To perform the TTC test, 4 mL of the urine were mixed with 1 mL of the TTC 1% aqueous sterile solution and incubated at 35-37ºC for 4 hours. We performed a second urine culture for all children with a positive result. Antimicrobial susceptibility was determined. A comparison between the quantitative culture and the TTC test were made, for the evaluation of the test. A questionnaire were used to assess predisposing behavioral and functional abnormalities. The screening survey for asymptomatic bacteriuria in pre-school children in Araraquara-SP-Brazil showed a prevalence of 1.4%. Escherichia coli was the commonest organism isolated and resistence to tetracycline was significant. The results show that the TTC test has sensitivity 91.3%, specificity 64.3%, positive predictive value 15.5% and negative predictive value 99.0%. This test can be use as a screening test. History of the urinary tract infection, inadequate hygiene, poor fluid intake and use of tigh-fitting underwear appear to be risk factors for asymptomatic bacteriuria. / Orientador: Maria Stella Gonçalves Raddi / Coorientador: Antonio Carlos Pizzolitto / Coorientador: Elisabeth Loshchagin Pizzolitto / Banca: Maria Jacira Silva Simões / Banca: Isabel Cristina Affonso Scaletsky / Mestre

The late blight pathogen, Phytophthora infestans, is the most destructive pathogen of its solanaceous hosts potato and tomato. It is a threat to global food security and it is therefore important to understand the cellular and molecular dynamics underlying colonisation of its host plants. This greater understanding will inform strategies to improve host plant resistance. In addition to studying the cell biology of the interaction, it is important to understand the temporal changes in gene expression and regulation during host-pathogen interactions at the earliest infection time points. Previously published transcriptomic studies of P. infestans used two days post infection (dpi) as the earliest sampling time point. Expression of a marker gene (Hmp1) for biotrophy and a selection of effector coding genes has been reported as early as 12 hours post inoculation (hpi), suggesting that infection was initiated before then. Transcriptomic studies of P. infestans have focussed mostly on leaf tissue, and there is still a lack of research on the transcriptome of P. infestans grown in alternative plant tissues such as tubers, or in host cell-free apoplastic fluid. This thesis explores transcriptomic studies of the early, biotrophic stages of potato infection by Phytophthora infestans, which is critical for understanding which genes are involved at what stages of infection development. By using the latest sensitive microarray technology to study the P. infestans transcriptome in an infection time course that remained biotrophic for its duration, a list of 1,707 transcripts of P. infestans were discovered to be differentially expressed. This list included 114 transcripts for RxLR effectors, out of which 26 were detected from 12 hours post infection, including: Avr2, Avr3a, Avrblb1 (ipi01), Avrblb2, and the recently characterised RD2. Also of interest was that transcripts encoding a PAMP (CBEL) detected at 12 hours, were suppressed in the pathogen by 24 hours. Transcripts encoding 55 RxLR effectors were co-expressed (with >95 % correlation coefficient) with the biotrophy marker gene Hmp1, suggesting that these effectors are important throughout the biotrophic stages of infection. QRT-PCR and cell biology data supported the expression of the biotrophy marker gene Hmp1 as early as 12 hours after infection and this was further supported by the co-expression of avirulence genes such as Avr2 and Avr3a. A set of 17 transcripts, including six cytoplasmic effectors (RxLR effectors), as well as a transcript encoding an apoplastic effector (glucanase inhibitor), was found to be infection-specific, supporting the hypothesis that these genes might have roles in establishing biotrophy. By examining pathogen behaviour in tuber tissue, clear cell biology evidence of functional haustoria was found. Gene expression analysis of a selection of leaf infection-related genes suggested that effectors are used to promote infection also in host tuber tissue. However, some cytoplasmic RXLR effector proteins such as PITG_05146 and PITG_15128, which were up-regulated during biotrophic infection of leaf tissue, were not detected during tuber infection, indicating potential differences in pathogenic requirements. A microarray experiment was conducted on in vitro stages of zoospores, and mycelium grown in apoplastic fluid of N. benthamiana, nutrient rich pea broth, and sterile water. This revealed 13,819 transcripts that were differentially expressed between any two conditions. This list included transcripts encoding 322 RxLR effectors, of which avirulence effectors such as Avr2, Avr3a, and RD2 were highly up-regulated during hyphal growth in apoplastic fluid compared to other in vitro stages. This provides evidence that the apoplast contains chemical signals that induce expression of infection-related genes in P. infestans. Curiously, the leaf infection-specific genes identified in Chapter 3 were not expressed when P. infestans was grown in apoplastic fluid, revealing that additional stimuli are required for induction of all necessary pathogen genes during infection. Future research, building upon the findings from this project, should be focused on the following areas: 1) Explore whether haustoria are produced only in order to deliver effectors or if there are other purposes as well, such as nutrient uptake; 2) The continued exploration of differences between genes co-expressed with Hmp1 during leaf infection, tuber infection, and in apoplastic fluid to further dissect the transcriptional regulation of these genes; 3) Identify whether Hmp1-co-expressed genes of unknown function may play a role in haustorium formation; 4) Investigate, using molecular transformation and cell biology, whether secreted proteins co-expressed with Hmp1 are secreted from haustoria; 5) Investigate the role(s) of infection-specific genes in establishing disease. 6) Transcriptomic studies of P. infestans biotrophic infection of tuber tissue to determine the differences in pathogenic adaptation in this tissue type, compared to leaf infection.

Honey has been used for centuries as a medicine to treat various ailments and infections. A large amount of research has established that honey has potent antibacterial activity. However, the sensitivity to honey of viral species that cause infections has been studied in only a small number of cases. The aim of this study was to obtain data to clarify and extend knowledge obtained from these previous studies of honey's antiviral activity, and especially study those viruses that cause localised infections which have limited or no therapy available, which are suitable to treatment with topically applied honey. The susceptible A549 cell line and viral isolates of Adenovirus serotypes 1, 3, and 8, and Herpes simplex virus serotypes 1 and 2, were provided by the Waikato Hospital Virology Laboratory. A number of types of honey were investigated from a range of sources: Manuka honey with high concentrations of methylglyoxal, unique manuka factor activity, and phenolics, Honeydew and Rewarewa honeys which have high antioxidant activity, and Ling Heather honey which is high in phenolic compounds. These honeys were selected due to their range of characteristic activities in order to make comparisons with antiviral activity. A variety of tests using cell culture were developed to evaluate the sensitivity of the viruses to whole honey. Each test scored and monitored the development of morphological changes to the cells, to observe whether the honey treatment can prevent the development of these changes known as viral cytopathic effect. These included tests for: protection, in which the cells were pre-treated with, and iii incubated either with or without honey; prevention, where honey was used to treat infected cells, and in plaque reduction assays, to examine whether it can reduce the resultant number of plaques; and neutralisation, in which the virus was directly exposed to the honey for a defined period. It was found with each type of test using cell culture that many of the honeys studied can lower the severity of viral cytopathic effect or delay its onset compared with the development observed with virus that was not treated with honey. This can suggest that the antiviral activity may be a feature of more than one type of honey. In general the antiviral effect increased with the concentration of honey and time the virus was exposed to it. Manuka honey M116 at a concentration of 10% was effective in preventing the development of viral cytopathic effect of each of virus, after the viruses at concentrations in excess of the tissue culture infectious dose had been exposed to the honey for 8 hours. Enzyme-linked immunosorbant assays were used to measure the effect the successful treatments found in the extended neutralisation experiments had on viral surface proteins necessary for viral entry into the cells. The results using this technique suggested that there was very little virus present in the samples that had been treated with honey and with the untreated virus. Therefore it could not be shown whether the honey was acting via this mechanism. It is concluded from the findings in this study that honey is likely to be an effective antiviral treatment for the therapy of localised viral infections, this needs to be verified by clinical trials.

ABSTRACT BACKGROUND. There have been few studies conducted in hospitalized patients in Viet nam on the epidemiology of surgical site infections (SSIs) and the impact of hand hygiene practices. This study aimed to assess the impact of a bedside hand sanitizer program on SSIs in orthopaedic and neurosurgical patients. DESIGN. A prospective quasi-experimental study was conducted with an untreated control group design in neurosurgical patients and before-after design in orthopaedic patients. A cost analysis based on data derived from the results of this study was also performed. SETTING. Cho Ray Hospital, a tertiary university hospital in Ho Chi Minh City, Viet nam. PATIENTS. All patients admitted for operation between 11 July and 15 August 2000 (Before), and 14 July and 18 August 2001 (After) were included, except those who had undergone another operation within one month prior to admission or were admitted because of SSIs. INTERVENTION. Bedside hand sanitizers were introduced into the Orthopaedic ward and one Neurosurgical ward (Ward A) from September 2000. Training on proper use was also provided to ward staff. Another Neurosurgical ward (Ward B) was used as a control group with no intervention conducted. RESULTS. A total of 1368 patients were recruited into the study. After intervention, in Ward A of the neurosurgical department, the SSI rate between the two periods was reduced by 54% (8.3% to 3.8%; p=0.09). Superficial SSIs were eliminated after the intervention (p=0.007). Comparison between Ward A (intervention) and Ward B (control) showed that, before the intervention, there was no difference in incidence of SSI between the two wards (Ward A: 8.3%, Ward B: 7.2%, p=0.7); however, after intervention, the incidence of SSI in Ward A was significantly lower than Ward B (3.8% and 9.2%, p=0.04). For orthopaedic patients, the SSI rate between the two periods was reduced by 34% (14.8% to 9.8%; p=0.07). SSI patients had a median post-operative length of stay of 19 days longer than patients without SSI (p&lt0.001). Costs were 2.5 times higher in patients with in-hospital SSI compared to uninfected patients (p&lt0.001). Mean SSI-attributable costs were conservatively estimated at US$368 in neurosurgical patients and US$207 in the orthopaedic patients in the before period. SSIs were responsible for at least 14 percent of the annual budget before intervention. The savings per SSI prevented were estimated at US$332 in neurosurgical patients and US$157 in orthopaedic patients. Annual cost savings arising from the intervention were estimated at US$11,112 in orthopaedic patients and US$19,320 in neurosurgical patients. CONCLUSIONS. The incidence of SSI in the hospital was high. The use of hand sanitizers reduced SSI rates, particularly impacting on the incidence of superficial SSIs. The hand sanitization program was found to be a dominant intervention being both more effective and cost saving as compared with no intervention in both study departments. The use of bedside hand sanitizers should be encouraged in the hospitals in Viet nam, where there often is a lack of other hand-washing facilities. / PhD Doctorate

An animal model of respiratory infection was used to determine the effect of various factors, thought to influence the ability of the host to clear bacteria, on the host?s innate response to an NTHi lung infection. Mucosal immunisation with NTHi has previously been shown to enhance the clearance of NTHi from the lung in an animal model of infection through the increased recruitment of phagocytes. Comparisons of cytokine and chemokine kinetic profiles were made in order to determine differences between innate and acquired immune response and the way in which mucosal immunisation controls the innate immune response to NTHi. Increased production of proinflammatory cytokines and chemokines in the early stages of NTHi lung infection enhanced the ability to clear bacteria from the rat lung in the immune animals through the increased recruitment of phagocytes to the site. Mucosal immunisation was found to alter the cytokine and chemokine mRNA profiles of CD4+ and CD8+ cells, with increased levels of MCP-1 protein being detected in both types of immune cells. An antecedent viral infection has been shown to increase the chance of developing a respiratory bacterial infection. The NTHi model of respiratory infection was used to characterise the effect that a viral infection had on the host response to the host?s innate response to a bacterial infection and the ability to clear the bacteria. The host?s ability to clear NTHi from the rat lung was enhanced by an antecedent viral infection through alterations to the innate immune response and the cytokine and chemokine kinetic profiles. The use of a mutant strain of NTHi deficient in a component of Lipooligosaccharide (LOS), Phosphorylcholine (ChoP), was utilised as a tool to characterise the innate immune response to LOS. Animals challenged with the LOS mutant strain had a reduced inflammatory response to NTHi through the decreased production of pro-inflammatory cytokines and chemokines and the reduced recruitment of phagocytes to the site of infection. This thesis has contributed valuable information to enable a better understanding of the host?s innate immune response to respiratory infection. This study has identified the role of cytokines and chemokines in the innate response to a respiratory bacterial infection and the enhanced ability of the host to clear NTHi from the lung.

Mast cells (MCs), normally classified into connective tissue MCs and mucosal MCs, are highly granulated cells found in the interface between the interior and the exterior environment of our body, e.g. skin, airways and gastro-intestinal tract. They react to bacteria, parasites, viruses, and allergens by degranulation and release of premade and newly synthesized inflammatory mediators. The MC-proteases (tryptases, chymases and carboxypeptidase A), histamine and serglycin (SG) proteoglycans are premade mediators. Among these, SG is also expressed in a variety of other immune and non-immune cells. Heparin and chondroitin sulphate glycosaminoglycan chains confer highly negative charge to SG, by which MC-proteases are retained in secretory granules. Deletion of SG cause impaired packing and storage of most MC-proteases. During challenge with Toxoplasma gondii the SG-deficient mice showed significant lower inflammatory cytokine levels in comparison to wild-type mice. Results were consistently similar in vitro, bringing forward the importance of SG in inflammatory cytokine and innate immune responses towards T. gondii. Infection with Trichinella spiralis in SG-/- mice caused increased intestinal enteropathy, a tendency of delayed worm expulsion and increased larval burden in the muscle tissue as compared to wild-type animals. An altered TH2 cytokine response was also observed, and all these effects were not repaired by wild-type MC reconstitution of the SG-/- mice. Altogether, our results suggest that SG is important for tissue homeostasis, and that SG expressing cells seem capable of switching from a SG-dependent storage mode to a SG-independent secretory mode upon infection. The chymase (MCPT4) expressed by connective tissue MC has been implicated to have a protective role during infection and in limiting inflammation. We explored a protective role by inducing T. gondii infection in the Mcpt4-null mice, and found MCPT4-mediated recruitment of neutrophils and eosinophils via control of cytokine signaling. Endogenous proteins “alarmins” released by dead cells can trigger tissue and cell damage. We conclusively show that chymase efficiently degrades Hsp70 both in vitro and in vivo and that the degradation of other alarmins, e.g. HMGB1, biglycan and IL-33 may also depend on chymase.

Background: The incidence of inadequate empiric antibiotic therapy (IET) and its clinical importance as a risk factor for hospital mortality in Canadian solid-organ transplant patients remains unknown. Methods: This retrospective cohort study evaluated all patients admitted to a transplant unit from May/2002-April/2004. Therapy was considered adequate when the organism cultured was found to be susceptible to an antibiotic administered within 24 hours of the index sample collection time. Univariate and multivariate regression analyses were conducted to determine associations between potential determinants, IET, and mortality. Results: IET was administered in 169/312 (54%) transplant patients. Regression analysis demonstrated that an increasing duration of IET (adjusted OR at 24h, 1.33; p < 0.001), ICU-associated infections (adjusted OR, 6.27; p < 0.001), prior antibiotic use (adjusted OR, 3.56; p = 0.004), and increasing APACHE-II scores (adjusted OR, 1.26; p < 0.001), were independent determinants of hospital mortality. Conclusions: IET is common and appears to be an important determinant of hospital mortality in the Canadian transplant population.

Background: The incidence of inadequate empiric antibiotic therapy (IET) and its clinical importance as a risk factor for hospital mortality in Canadian solid-organ transplant patients remains unknown. Methods: This retrospective cohort study evaluated all patients admitted to a transplant unit from May/2002-April/2004. Therapy was considered adequate when the organism cultured was found to be susceptible to an antibiotic administered within 24 hours of the index sample collection time. Univariate and multivariate regression analyses were conducted to determine associations between potential determinants, IET, and mortality. Results: IET was administered in 169/312 (54%) transplant patients. Regression analysis demonstrated that an increasing duration of IET (adjusted OR at 24h, 1.33; p < 0.001), ICU-associated infections (adjusted OR, 6.27; p < 0.001), prior antibiotic use (adjusted OR, 3.56; p = 0.004), and increasing APACHE-II scores (adjusted OR, 1.26; p < 0.001), were independent determinants of hospital mortality. Conclusions: IET is common and appears to be an important determinant of hospital mortality in the Canadian transplant population.