The MOBILISE study: utilisation of ambulatory pumps in the inpatient setting to administer continuous antibiotic infusions-a randomised controlled trial.

In the inpatient setting, antibiotics are generally administered via bedside pumps with multiple daily dosing. Utilisation of a continuous antibiotic infusion (CAI) instead might have patient and nursing satisfaction, workflow efficiencies and infection control benefits. We aimed to study the utilisation of CAI in the inpatient setting for routine antibiotic administration. Patients receiving a peripherally inserted central venous catheter (PICC) for antibiotic administration were screened for the study. The patients were randomised to either (1) standard pump and intermittent antibiotic administration (IAA) or (2) CAI via an ambulatory pump. An accelerometer placed on the ankle was used to assess patient activity. Nursing and patient satisfaction surveys were also carried out. Forty patients met the study criteria for enrolment with 21 patients being enrolled in the CAI arm of the study. One hundred and five days of accelerometer recordings were available for analysis. The geometric mean activity was 45 min/day in the standard arm and 64 min/day in the CAI arm. This represented a 42% (95% CI: -14 to 133%, p = 0.16) difference in activity between the two groups. Nursing staff reported that they spent less time throughout their shift attending the antibiotic line or pump in patients who were in the CAI arm of the study (p < 0.001). In addition, patients in this arm of the study were more likely to recommend this method of administration of antibiotics to a family member (p =0.0001). The MOBILISE study showed nursing and patient satisfaction when CAI were utilised in the inpatient setting. A statistically non-significant difference in mobility was seen. The trial was registered (28/03/2018) with the Australia New Zealand Clinical Trials Registry (ACTRN12618000452291).

Septic arthritis post anterior cruciate ligament reconstruction due to Clostridioides difficile.

Clostridioides difficile is an obligate anaerobe ubiquitous in the environment and is of particular interest in the healthcare setting as a cause of healthcare associated infection usually presenting with colitis. Extracolonic manifestations of C. difficile infection are less common with only rare reports of septic arthritis primarily in the setting of relative or overt immunocompromise. This report details the case of a 31-year-old immunocompetent male presenting with clinical features of septic arthritis, three weeks post right knee anterior cruciate ligament (ACL) reconstruction using a native hamstring tendon graft. C. difficile was isolated from two different samples of the synovial tissue from a subsequent arthroscopic washout and synovectomy. The ACL graft was retained. The isolate underwent whole genome sequencing and was found to be tcdA and tcdB gene deficient. Susceptibility testing showed susceptibility to benzylpenicillin and metronidazole. The patient received a two-week course of intravenous benzylpenicillin and four weeks of oral metronidazole. At one-year post cessation of antibiotics the patient has no clinical evidence of recurrence. This is the first known reported case of C. difficile septic arthritis in an immunocompetent patient. It demonstrates successful treatment of post-ACL septic arthritis with a graft retention strategy.

Outcomes of patients with a history of injecting drug use and receipt of outpatient antimicrobial therapy.

People who inject drugs (PWID) are susceptible to endovascular and deep-seated infections which require prolonged antibiotic therapy. There are concerns regarding this cohort's suitability for outpatient parenteral antimicrobial therapy (OPAT), but relatively little published data. Our aim is to publish our outcomes in this setting, to inform other clinicians' decisions regarding PWID in OPAT. We reviewed case records of all PWID in our OPAT service from July 2015 to December 2017. Successful completion of OPAT care was defined as completing the duration of parenteral therapy as planned at the outset, with expected clinical improvement. Data was collected on complications including hospital re-admission, new blood stream infections, patient non-compliance including ongoing non-prescribed intravenous drug use, and staff safety compromise. Twenty-eight of 38 (76.2%) episodes of OPAT care for PWID were completed successfully, with 724 bed days of care provided. The cohort was labour intensive to manage with high rates of re-admission, non-attendance and line-associated infections. There were no adverse events for staff safety, and no patient deaths on the programme. OPAT can be a viable option for PWID provided there is careful patient selection, good patient engagement and sufficient resources allocated for patient management.

P. aeruginosa blood stream infection isolates: A "full house" of virulence genes in isolates associated with rapid patient death and patient survival.

We have recently characterised the epidemiology of P. aeruginosa blood stream infection (BSI) in a large retrospective multicentre cohort study [1]. Utilising corresponding patient BSI isolates we aimed to characterise the genotypic virulence profile of the P. aeruginosa isolates that were associated with rapid death in the non-neutropenic host. Five P. aeruginosa BSI episodes were identified from a larger cohort of P. aeruginosa BSI episodes previously described by McCarthy et al. [1]. The genotypic profile of another 5 isolates from this cohort in whom the non-neutropenic host had survived one year post the BSI was also analysed for comparison. These isolates underwent Illumina whole genome sequencing, de novo assembly and annotation. A comprehensive suite of virulence genes was collated from the Pseudomonas Genome Database (http://www.pseudomonas.com/) and were searched by BLAST based analysis in assemblies of all BSI isolates [2]. There was extensive conservation of virulence genes across all of the BSI isolates studied. The exoU gene was found in two isolates from patients who died rapidly and in one isolate from a patient that survived one year post BSI. The higA and higB genes were detected in all isolates. The exlA gene was not detected in any of the isolates studied. These findings suggest that to cause a BSI that it is only the virulent P. aeruginosa isolate that succeeds. The virulence gene profile seen was independent of patient outcome. Further phenotypic correlation is required to determine if there is any difference in genotypic expression by the BSI isolates that were associated with rapid death of the host and those BSI isolates associated with host survival at one year.

Community-acquired Pseudomonas aeruginosa bloodstream infection: a classification that should not falsely reassure the clinician.

Pseudomonas aeruginosa bloodstream infection (BSI) is predominantly acquired in the hospital setting. Community-onset infection is less common. Differences in epidemiology, clinical features, microbiological factors and BSI outcomes led to the separation of bacterial community-onset BSI into the categories of healthcare-associated infection (HCAI) and community-acquired infection (CAI). Community-acquired P. aeruginosa BSI epidemiology is not well defined in the literature. In addition, it is also not clear if the same factors separate CAI and HCAI BSI caused by P. aeruginosa alone. A retrospective multicentre cohort study was performed looking at P. aeruginosa BSI from January 2008 to January 2011. Strict definitions for HCAI and CAI were applied. Extensive epidemiological, clinical and outcome data were obtained. Thirty-four CAI episodes and 156 HCAI episodes were analysed. The CAI group could be characterised into seven distinct categories based on comorbidities and clinically suspected source of infection. A pre-morbidly healthy group could not be identified. On multivariate analysis, the presence of a rheumatological or a gastrointestinal comorbidity were significantly associated with CAI. There was no significant difference in length of stay or rates of mortality between HCAI or CAI. The clinician should not be falsely reassured regarding outcome by the diagnosis of a community-acquired P. aeruginosa BSI.

Pseudomonas aeruginosa blood stream infection isolates from patients with recurrent blood stream infection: Is it the same genotype?

The type identity of strains of Pseudomonas aeruginosa from primary and recurrent blood stream infection (BSI) has not been widely studied. Twenty-eight patients were identified retrospectively from 2008 to 2013 from five different laboratories; available epidemiological, clinical and microbiological data were obtained for each patient. Isolates were genotyped by iPLEX MassARRAY MALDI-TOF MS and rep-PCR. This showed that recurrent P. aeruginosa BSI was more commonly due to the same genotypically related strain as that from the primary episode. Relapse due to a genotypically related strain occurred earlier in time than a relapsing infection from an unrelated strain (median time: 26 vs. 91 days, respectively). Line related infections were the most common source of suspected BSI and almost half of all BSI episodes were associated with neutropenia, possibly indicating translocation of the organism from the patient's gut in this setting. Development of meropenem resistance occurred in two relapse isolates, which may suggest that prior antibiotic therapy for the primary BSI was a driver for the subsequent development of resistance in the recurrent isolate.

Role of the placenta in developmental programming: Observations from models using large animals.

Developmental programming, which proposes that "insults" or "stressors" during intrauterine or postnatal development can have not only immediate but also long-term consequences for healthy and productivity, has emerged as a major biological principle, and based on studies in many animal species also seems to be a universal phenomenon. In eutherians, the placenta appears to be programmed during its development, which has consequences for fetal growth and development throughout pregnancy, and likewise has long-term consequences for postnatal development, leading to programming of organ function of the offspring even into adulthood. This review summarizes our current understanding of the placenta's role in developmental programming, the mechanisms involved, and the challenges remaining.

Activity of ceftolozane/tazobactam against a collection of Pseudomonas aeruginosa isolates from bloodstream infections in Australia.

Pseudomonas aeruginosa is a common pathogen causing nosocomial infection. In particular, bloodstream infection (BSI) is associated with a high rate of morbidity and mortality. Ceftolozane/tazobactam is a new ß-lactam/ß-lactamase antimicrobial with activity against P. aeruginosa as well as multidrug resistant (MDR) Gram negative Enterobacteriaceae. Ceftolozane/tazobactam has frequently been used in salvage therapy for MDR P. aeruginosa infections. The aim of this study was to determine the activity of ceftolozane/tazobactam against P. aeruginosa isolates from BSIs collected from three clinical microbiology laboratories in Queensland, Australia, with a high proportion of isolates demonstrating ß-lactam resistance. Antimicrobial susceptibility testing was performed by broth microdilution using custom made sensititre plates sourced from ThermoFisher Scientific. In addition to ceftolozane/tazobactam, we also tested piperacillin/tazobactam, ceftazidime, cefepime, meropenem, doripenem, imipenem, aztreonam, ciprofloxacin, levofloxacin, gentamicin, amikacin, tobramycin and colistin. Overall, ceftolozane/tazobactam was the most active agent tested [(MIC50/90 = 1/2 µg/mL, 96% susceptible (S)]. Against 44 isolates with resistance to at least one other ß-lactam agent, 40 were susceptible to ceftolozane/tazobactam. Three ceftolozane/tazobactam resistant isolates were susceptible to colistin, with one of those isolates also susceptible to levofloxacin but not to any other antimicrobials tested. One ceftolozane/tazobactam resistant isolate was susceptible only to meropenem and doripenem but was non-susceptible to imipenem. An association was found between fluoroquinolone resistance and aminoglycoside resistance but not with ß-lactam resistance. In summary, ceftolozane/tazobactam was active against most strains tested, including those resistant to other ß-lactams. Laboratories should consider testing P. aeruginosa against ceftolozane/tazobactam in suspected MDR or extensively drug resistant (XDR) infections.

Increased risk of death with recurrent Pseudomonas aeruginosa bacteremia.

This study aimed to characterize recurrent Pseudomonas aeruginosa blood stream infection (BSI). Positive blood cultures for P. aeruginosa were identified over a 3-year period from seven tertiary care hospitals. Patients with recurrent BSI were identified. Extensive epidemiological, clinical and outcome data were obtained. BSI recurrence was found to be uncommon with 9% of patients having a first relapse of BSI. Fourteen percent of these patients went on to have a second relapse of BSI. Significant variables associated with recurrence were the presence of a hematological malignancy or receiving recent corticosteroid therapy. Exposure to anti-pseudomonal beta-lactam therapy in the 30days prior to the BSI was more likely in the patient with the recurrent BSI episode. Recurrence was associated with increased mortality when compared to the primary BSI episode. Knowledge of a patient's prior antibiotic therapy may be useful in ensuring effective empirical therapy in the recurrent BSI episode.

Long-term mortality following Pseudomonas aeruginosa bloodstream infection.

BACKGROUND: Pseudomonas aeruginosa bloodstream infections (BSI) are associated with substantial short-term mortality. There is little data on long-term mortality associated with this BSI. AIM: To describe mortality rates up to one year post infection and the significant factors associated with death. METHODS: Positive blood cultures for P. aeruginosa were identified retrospectively from January 2008 to January 2011 at seven tertiary care hospitals. Extensive epidemiological, clinical and outcome data were obtained. FINDINGS: Three hundred and eighty-eight BSI episodes were included in the analysis. The majority of infections were hospital acquired. The most common patient comorbidities were haematological or oncological. Seventy-eight percent of the cohort had a medical device in situ in the preceding seven days. Sixty-one percent of the cohort received adequate empirical therapy. All-cause mortality was 4% at 48 h, 19% at one month and 38% at one year. Forty-eight-hour mortality was associated with non-hospital-acquired infection, pulmonary comorbidity, recent corticosteroid therapy, and a Pitt bacteraemia score >2. Comorbidities became significantly associated with mortality from seven days post infection. Long-term mortality (defined as mortality at one year) was associated with female sex, haematological or oncological comorbidity, a Charlson comorbidity index >2 and recent corticosteroid therapy. CONCLUSION: The exact role of infection, from this highly virulent pathogen, in the cause of death over time needs to be studied further. It is not clear if patients are dying from or with P. aeruginosa BSI.

Draft Genome Sequence of an IMP-7-Producing Pseudomonas aeruginosa Bloodstream Infection Isolate from Australia.

IMP-7 is one of the two IMP-type carbapenemases that in Pseudomonas aeruginosa are not limited to a geographic area, but it has not been previously reported in the Australian setting. We report here the draft genome sequence of an Australian P. aeruginosa bloodstream infection isolate that contains IMP-7.

Draft Genome Sequences of Two Pseudomonas aeruginosa Bloodstream Infection Isolates Associated with Rapid Patient Death.

The morbidity and mortality associated with Pseudomonas aeruginosa bloodstream infections are significant. New strategies are required to treat such infections. We report here the draft genome sequences of two antibiotic-sensitive P. aeruginosa bloodstream infection isolates that were associated with rapid death in nonneutropenic patients.

Separation of glutathione S-transferase activities with epoxides from the mouse liver h-protein, a major polycyclic hydrocarbon-binding protein.

The C3H mouse liver h-protein is a cytoplasmic protein to which metabolites of carcinogenic polycyclic hydrocarbons bind covalently following i.p. injection. It has a number of physical properties similar to those of the glutathione S-transferases (EC 2.5.1.18). These properties include molecular weight (40,000), number of subunits (2), basic isoelectric point around 8.0, sedimentation coefficient (3.5S), and subcellular localization. In this communication, we have shown that glutathione S-transferase activities with 1,2-epoxy(3-p-nitrophenoxy)propane and benz[a]anthracene 5,6-oxide as substrates were separated from the h-protein on carboxymethylcellulose and isoelectrofocusing columns. The purification of the mouse h-protein as a [3H]-7,12-dimethylbenz[a]anthracene conjugate or as the free form is also described.

Applications of magnetic resonance imaging to food research.

Global food markets are changing in response to consumer demands for more processed foods and higher quality foods. Consumers find processed foods convenient, less prone to spoilage, more portable, nutritionally efficient, and more consistent in quality level than fresh foods. These demands have resulted in food producers working to develop new types of foods and reformulate standard types of foods. A typical type of reformulation would be a reduced-calorie food or an all-natural food product. The characterization of food processes and products is most often accomplished through the use of averaged measurements. An averaged measurement provides a characterization of the process or product with a single value of one variable measured at a specific time. For example, the average moisture content of a food during drying or the shear viscosity of an emulsion at one temperature and one shear rate. Averaged measurements are useful in characterizing a given process and are in many cases sufficient for process design or product development. However, these single point measurements do not provide significant information on the phenomena responsible for controlling product properties during processing or storage. More information on the physical and chemical processes controlling or influencing process performance and product quality should result in both improved production efficiency, improved product quality, and novel products. Magnetic resonance imaging provides new methods and approaches to investigate and quantify the attributes of products as they vary in time and location within the product. The attributes that can be quantified range from the composition of a material (moisture content, fat content), to physical structure and to derived characterizations like the shear-stress shear-rate relationship in fluids.

Dynamics of fluid/particulate mixtures in tube flow.

Magnetic resonance imaging (MRI) techniques have been utilized to experimentally measure the velocity profile of fluid/particulate mixtures as a function of flow rate, particle loading, and particle size. The experimental velocity profiles in tube flow were described by a power law model; the power law parameter decreased as flow rate, particle loading, and particle size increase. This work is relevant to aseptic processing of particulate foods.

Turbulent pipe flow studied by time-averaged NMR imaging: measurements of velocity profile and turbulent intensity.

A time-averaged method to obtain quantitative measurements in turbulent flow by phase flow encoding NMR imaging is introduced. With this method time-averaged velocity profiles and turbulence intensities can be determined. Time-averaged velocity profiles for pipe flow of water driven by a constant pressure gradient at Reynolds numbers from 1200 to 9400 were visualized. A precise correlation between the pixel intensity of the time-averaged NMR flow image and the local turbulence intensity of the flow is derived. The measured turbulence intensities are in agreement with published data obtained using other experimental methods.

The genetic toxicology of Kathon biocide, a mixture of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one.

Kathon biocide, an aqueous solution containing a mixture of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one in an approximate ratio of 3:1, was tested for mutagenic activity in Salmonella typhimurium, L5178Y mouse lymphoma cells in culture and Drosophila melanogaster. Tests also were conducted for chromosome aberrations in vivo on mouse bone marrow cells, for DNA damage/repair in primary rat hepatocytes in culture, and for morphological transformation in C3H 10T1/2 cells in culture. Kathon biocide produced point mutations in the absence of a rat-liver metabolizing system in bacteria (strain TA 100) and mammalian cells in culture. In the presence of rat-liver metabolizing system a 10-fold higher concentration was required to induce point mutations in mammalian cells in culture. No mutagenic activity was observed with the metabolizing system and S. typhimurium. Negative results were obtained in the sex-linked recessive lethal assay in Drosophila, the in vivo cytogenetic assay in mice, the unscheduled DNA synthesis assay in cultured rat hepatocytes, and the in vitro cell transformation assay.

Genetic toxicology of acrylic acid.

Acrylic acid was tested for gene mutations in the in vitro CHO/HGPRT assay, for chromosome aberrations in CHO cells in culture, and for potential to induce unscheduled DNA synthesis in rat hepatocytes in culture. In vivo assays performed included the Drosophila sex-linked recessive lethal assay by both the feeding and injection routes, the in vivo cytogenetic assay in rat bone marrow cells after both a 1-day and 5-day oral dosing regimen, and a dominant lethal assay in mice by both an acute and 5-day dosing regimen. All results were negative (non-mutagenic) except for the in vitro chromosome aberration assay. This latter result is consistent with the previously reported possible clastogenic activity suggested by the results of the mouse lymphoma L5178Y TK locus assay in which a predominance of small-colony mutants was observed (Moore et al., Environmental and Molecular Mutagenesis 1988, 11, 49-63). The rapid clearance of acrylic acid in animals and the weight of evidence of genetic toxicity testing, including negative in vivo data in both somatic and germ cells, indicate a lack of genetic toxicity of acrylic acid in vivo.

Phase volume measurements using magnetic resonance imaging.

The phase distribution of components in both model and actual food systems has been quantified using Magnetic Resonance Imaging. We present measurements of effective moisture diffusivities, vertical mass distributions in foams, and crystallization of water and lipid components. The interpretation of this information allows one to quantify the interactions of various components and structural features within a sample. These measurements are made noninvasively and nondestructively and can be repeated over time to obtain information on the dynamics of the system.