Antifungal use via outpatient parenteral antimicrobial therapy.

BACKGROUND: Antifungal administration via outpatient parenteral antimicrobial therapy (OPAT) is infrequent. As patients with invasive fungal infections (IFIs) receiving OPAT are at high risk of readmissions, careful, risk-based patient selection and monitoring is important. OBJECTIVES: To describe our experience managing IFIs via OPAT, including assessment of risk factors associated with unplanned readmissions. PATIENTS AND METHODS: A retrospective cohort study of outpatients from two tertiary hospitals in Western Australia managed with parenteral antifungals for the treatment of IFIs from 2012 to 2020. Outcomes assessed were unplanned OPAT-related readmissions; adverse events and achievement of treatment aim at the completion of OPAT. RESULTS: Forty-six patients were included, encompassing 696 OPAT days. Twenty-three (50%) patients received intravenous (IV) liposomal amphotericin B (L-AmB), 23 (50%) received IV echinocandins and one (2%) patient received IV fluconazole. One patient received both IV L-AmB and an echinocandin. Unplanned OPAT-related readmissions occurred in 13 (28%) patients and any adverse event occurred in 19 (41%), most commonly nephrotoxicity amongst patients receiving L-AmB. On univariate analysis, unplanned OPAT-related readmissions were more common in Mucorales infection, L-AmB doses of ≥5 mg/kg and otorhinolaryngologic (ENT) infections. At the completion of OPAT, attainment of treatment aims occurred in 28 (61%) patients. CONCLUSIONS: Patients receiving parenteral antifungals via OPAT experience high rates of unplanned readmissions and adverse events. Risk factor identification may facilitate optimal patient selection and establishment of treatment aims.

Increasing incidence of invasive group A streptococcal disease in Western Australia, particularly among Indigenous people.

OBJECTIVE: To quantify the burden of invasive group A Streptococcus (GAS) disease in Western Australia during 2000-2018. DESIGN, SETTING: Population-based data linkage study: Hospital Morbidity Data Collection (HMDC; all WA public and private hospital records), PathWest pathology data (government-owned pathology services provider), and death registrations. PARTICIPANTS: People with invasive GAS disease, defined by an isolate from a normally sterile site (PathWest) or a hospital-based principal ICD-10-AM diagnosis code (HMDC). MAIN OUTCOME MEASURES: Incidence of invasive GAS disease; median length of hospital stay; all-cause mortality. RESULTS: We identified 2237 cases of GAS disease during 2000-2018; 1283 were in male patients (57%). 1950 cases had been confirmed by GAS isolates from normally sterile tissues (87%; including 1089 from blood [56% of cases] and 750 from tissue [38%]). The age-standardised incidence increased from 2.0 (95% CI, 1.4-2.7) cases per 100 000 population in 2000 to 9.1 (95% CI, 7.9-10.2) cases per 100 000 in 2017 (by year, adjusted for age group and sex: incidence rate ratio [IRR], 1.09; 95% CI, 1.08-1.10). Incidence was consistently higher among Indigenous than non-Indigenous Australians (year-adjusted IRR, 13.1; 95% CI, 11.3-15.1). All-cause 30-day mortality was 5% (116 deaths), and 90-day mortality 7% (156 deaths); 30-day mortality, adjusted for age group and sex, was not statistically significantly different for cases involving Indigenous or non-Indigenous patients (adjusted odds ratio, 0.8; 95% CI, 0.6-1.1). CONCLUSIONS: The incidence of invasive GAS disease in WA increased between 2000 and 2018, particularly among Indigenous Australians. Mandatory notification of invasive GAS disease would therefore be appropriate. The social determinants of differences in incidence should be addressed, and other relevant host, pathogen, and health system factors investigated.

Impact of adherence to surgical and non-surgical components of infective endocarditis guidelines and recommendations.

BACKGROUND: Infective endocarditis (IE) is associated with significant morbidity and mortality. Non-adherence to IE guidelines and recommendations is frequent, and may adversely impact patient outcomes. AIM: To assess the impact of non-adherence to components of existing IE guidelines and recommendations on a composite outcome consisting of any of the following: mortality, unplanned cardiac surgery, embolic event or relapse of positive blood culture within six months of diagnosis. METHODS: A single centre, retrospective cohort study. RESULTS: Amongst 157 patients, there was inconsistent adherence to: initial diagnosis of an infective condition (87%), timely administration of antimicrobial therapy (82%), appropriateness of predominant antimicrobial regime (94%), appropriate management of the portal of entry (86%), multidisciplinary input (75%), end of antimicrobial therapy repeat echocardiography (60%) and adherence to indications for surgery (76%). Inpatient mortality was 12.1% (n = 19) and the composite adverse outcome occurred in 36 (22.9%) patients. In multivariate logistic regression analysis, infection of prosthetic device (adjusted odds ratio [95% confidence interval]; 2.43 [1.07-5.50]) and non-adherence to surgical guidelines (aOR 3.67 [1.60-8.47]) were significantly associated with an adverse outcome. CONCLUSIONS: Our data suggests that adherence to differing components of IE management guidelines and recommendations varies and that non-adherence to surgical aspects of guidelines has the biggest impact in determining outcomes.

Candida auris Sternal Osteomyelitis in a Man from Kenya Visiting Australia, 2015.

In Australia in 2015, Candida auris sternal osteomyelitis was diagnosed in a 65-year-old man with a history of intensive care treatment in Kenya in 2012 and without a history of cardiac surgery. The isolate was South Africa clade III. Clinicians should note that C. auris can cause low-grade disease years after colonization.

Adaptation of a hospital electronic referral system for antimicrobial stewardship prospective audit and feedback rounds.

OBJECTIVE: To evaluate the impact of the adaptation of an existing electronic referral application for use in antimicrobial stewardship prospective audit and feedback rounds (antimicrobial rounds). DESIGN: Retrospective, single-centre observational study between March 2015 and February 2016. SETTING: A new quaternary referral centre. STUDY PARTICIPANTS: Adults referred for antimicrobial rounds outside of the intensive care and haematology units. INTERVENTION: Adaptation of an electronic referral application used by medical and allied health staff. A questionnaire-style referral form was designed to capture patient clinical details using a combination of free text and dropdown menus. Clinical pharmacists were educated and granted access to the system. MAIN OUTCOME MEASURES: The proportion of completed electronic referrals of total round reviews by month for the 12 months after implementation. The time from request to completion of reviews. The impact on adherence to advice provided on rounds. The impact on the institutional usage of broad-spectrum antibiotics: glycopeptides, carbapenems, third and fourth generation cephalosporins, fluoroquinolones and piperacillin/tazobactam. RESULTS: Over the study period, the proportion of electronic referrals of completed antimicrobial round reviews increased from 59% to 88% (P < 0.001); 75.7% of accepted electronic referrals were seen within 48 h of request. The proportion of advice ignored fell from 18% to 8.5% (P < 0.001). Piperacillin/tazobactam, fluoroquinolone and glycopeptide usage decreased. CONCLUSIONS: The adaptation of an electronic referral application for antimicrobial rounds was associated with increased adherence to advice and reduction in use in target antibiotics. Our model is now used at other institutions.

New Foci of Spotted Fever Group Rickettsiae Including Rickettsia honei in Western Australia.

We describe the first reported case of spotted fever group rickettsiosis in Western Australia, and two cases of probable Rickettsia honei from a new geographic focus. These findings highlight the need to raise awareness of ricksettsial infection among local clinicians as well as those treating visitors to this region, important for outdoor recreation.

Prevalence, risk factors and sequelae of Staphylococcus aureus carriage in diabetes: the Fremantle Diabetes Study Phase II.

AIMS: To determine the prevalence and associates of Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) carriage in community-based diabetes, and their relationship to hospitalization with S. aureus infection. METHODS: A cross-sectional subset of 660 Fremantle Diabetes Study Phase II patients (mean±SD age 65.1±11.5years, 53.1% males) had nasal/axillary swabs as part of biennial review. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were measured in 358 patients. Those with positive swabs were invited back for a repeat swab. Hospitalizations with S. aureus infections were ascertained from validated data linkage. Multiple logistic regression was used to identify associates of carriage, and Cox proportional hazards modelling was used to determine predictors of subsequent hospitalization. RESULTS: 258 patients (39.1%) were positive for S. aureus and eight (3.1%) carried MRSA. S. aureus carriage was independently associated with being married/in a de facto relationship and inversely with older age and being born overseas (P≤0.043). Repeat swabs in 137 patients (53.1% of those with an initially positive swab) grew S. aureus in 113 (82.5%). Five of eight MRSA-positive patients were re-swabbed, and four were MRSA-positive. Independent predictors of hospitalization with staphylococcal infection after the initial swab were S. aureus carriage (hazard ratio (95% CI) 5.42 (1.49-19.79)), prior hospitalization with S. aureus (4.84 (1.19-19.63)) and Aboriginality (7.20 (1.91-27.17) (P≤0.027). Serum 25(OH)D was not associated with S. aureus carriage or subsequent hospitalization. CONCLUSIONS: S. aureus and MRSA carriage in our patients was consistent with previous general population studies. There were no diabetes-specific risk factors. Persistent colonization may underlie the increased risk of hospitalization with S. aureus.

Rictor regulates phosphorylation of the novel protein kinase C Apl II in Aplysia sensory neurons.

Rapamycin-insensitive companion of TOR (Rictor) is a conserved component of target of rapamycin complex 2 (TORC2), a complex implicated in phosphorylation of a number of signal transduction-related kinases, including protein kinase Cs (PKCs) at their 'hydrophobic' site in the carboxy-terminal extension domain. In the marine mollusk, Aplysia californica, an increase in phosphorylation of the novel PKC, Apl II, at the hydrophobic site is associated with a protein synthesis-dependent increase in synaptic strength seen after continuous application of serotonin. To determine if Rictor plays a role in this increase, we cloned the Aplysia ortholog of Rictor (ApRictor). An siRNA-mediated decrease in ApRictor levels in Aplysia sensory neurons led to a decrease in the phosphorylation of PKC Apl II at the hydrophobic site suggesting a role for ApRictor in hydrophobic site phosphorylation. However, over-expression of ApRictor was not sufficient to increase phosphorylation of PKC Apl II. Continuous application of serotonin increased phosphorylation of PKC Apl II at the hydrophobic site in cultured sensory neurons, and this was blocked by Torin, which inhibits both TORC1 and TORC2. Over-expression of ApRictor did not lead to change in the magnitude of serotonin-mediated phosphorylation, but did lead to a small increase in the membrane localization of phosphorylated PKC Apl II. In conclusion, these studies implicate Rictor in phosphorylation of a novel PKC during synaptic plasticity and suggest an additional role for Rictor in regulating the localization of PKCs.

Leadership, consensus decision making and collective behaviour in humans.

This paper reviews the literature on leadership in vertebrate groups, including recent work on human groups, before presenting the results of three new experiments looking at leadership and decision making in small and large human groups. In experiment 1, we find that both group size and the presence of uninformed individuals can affect the speed with which small human groups (eight people) decide between two opposing directional preferences and the likelihood of the group splitting. In experiment 2, we show that the spatial positioning of informed individuals within small human groups (10 people) can affect the speed and accuracy of group motion. We find that having a mixture of leaders positioned in the centre and on the edge of a group increases the speed and accuracy with which the group reaches their target. In experiment 3, we use large human crowds (100 and 200 people) to demonstrate that the trends observed from earlier work using small human groups can be applied to larger crowds. We find that only a small minority of informed individuals is needed to guide a large uninformed group. These studies build upon important theoretical and empirical work on leadership and decision making in animal groups.

Limited role for outpatient parenteral antibiotic therapy for community-acquired pneumonia.

BACKGROUND AND OBJECTIVE: This study examined the potential utility of outpatient parenteral antibiotic therapy (OPAT) as a means of reducing the excessive number of patients hospitalized with low-risk community-acquired pneumonia (CAP). METHODS: A prospective feasibility study was conducted, in which a selection algorithm was applied to a cohort of patients admitted with suspected CAP, to identify a group in whom admission may have been prevented by the use of OPAT. Numbers of potentially suitable patients, inpatient bed days saved and frequency of adverse events that may have led to readmission were measured. RESULTS: There were 118 inpatients treated with confirmed CAP during the study period, of whom 27 had low-risk disease (Pneumonia Severity Index grades I-III). Application of the selection algorithm identified eight (30% of those with low-risk disease) patients who were potentially suitable for OPAT, and this group commonly experienced adverse events during follow up which may have resulted in readmission to hospital. CONCLUSIONS: In many hospitalized patients with CAP, outpatient therapy is precluded by either disease severity or active medical and psychosocial factors. This limits the role of OPAT as a tool for reducing the inpatient burden of CAP.

Flinders Island spotted fever rickettsioses caused by "marmionii" strain of Rickettsia honei, Eastern Australia.

Australia has 4 rickettsial diseases: murine typhus, Queensland tick typhus, Flinders Island spotted fever, and scrub typhus. We describe 7 cases of a rickettsiosis with an acute onset and symptoms of fever (100%), headache (71%), arthralgia (43%), myalgia (43%), cough (43%), maculopapular/petechial rash (43%), nausea (29%), pharyngitis (29%), lymphadenopathy (29%), and eschar (29%). Cases were most prevalent in autumn and from eastern Australia, including Queensland, Tasmania, and South Australia. One patient had a history of tick bite (Haemaphysalis novaeguineae). An isolate shared 99.2%, 99.8%, 99.8%, 99.9%, and 100% homology with the 17 kDa, ompA, gltA, 16S rRNA, and Sca4 genes, respectively, of Rickettsia honei. This Australian rickettsiosis has similar symptoms to Flinders Island spotted fever, and the strain is genetically related to R. honei. It has been designated the "marmionii" strain of R. honei, in honor of Australian physician and scientist Barrie Marmion.

Cryptococcal immune reconstitution inflammatory syndrome following alemtuzumab therapy.

Alemtuzumab is a lymphocyte ablative agent that may cause susceptibility to severe opportunistic infections similar to those seen in AIDS. Pathogen-specific immune reconstitution syndromes can complicate antiretroviral therapy and immune recovery in HIV-infected patients. We present the first reported case of immune reconstitution syndrome associated with T lymphocyte recovery after alemtuzumab therapy.

Predation risk as a driving force for sexual segregation: a cross-population comparison.

Sexual segregation is widespread throughout the animal kingdom. Although a number of hypotheses have been proposed to account for observed patterns, the generality of the mechanisms remains debated. One possible reason for this is the focus on segregation patterns in large mammals such as ungulates, where the majority of studies are descriptions of a single population. Here, we present the results of a cross­population comparison of patterns of sexual segregation in the Trinidadian guppy, Poecilia reticulata. We relate observed patterns to experimental quantification of predation risk and sexual harassment of females by males in eight populations. We find that the degree of segregation increases with predation risk, with deeper waters becoming increasingly female biased. Furthermore, we observed that levels of male harassment are lower in deeper water but only in those rivers that contain major guppy predators. We conclude that sexual segregation in guppies is consistent with the predation risk hypothesis: sexual segregation results from a combination of predation risk driving males (the more vulnerable sex) into less risky habitats and females gaining benefits of reduced sexual harassment by remaining in high­predation environments.

Mnk is a negative regulator of cap-dependent translation in Aplysia neurons.

To investigate the mechanisms underlying regulation of eukaryotic initiation factor 4E (eIF4E) phosphorylation in Aplysia neurons, we have cloned the Aplysia homolog of the vertebrate eIF4E kinases, Mnk1 and -2. Aplysia Mnk shares many conserved regions with vertebrate Mnk, including putative eukaryotic initiation factor 4G binding regions, activation loop phosphorylation sites, and a carboxy-terminal anchoring site for MAP kinases. As expected, purified Aplysia Mnk phosphorylated Aplysia eIF4E at a conserved carboxy-terminal serine and over-expression of Aplysia Mnk in sensory neurons led to increased phosphorylation of endogenous eIF4E. Over-expression of Aplysia Mnk led to strong decreases in cap-dependent translation, while generally sparing internal ribosomal entry site (IRES)-dependent translation. However, decreases in cap-dependent translation seen after expression of Aplysia Mnk could only be partly explained by increases in eIF4E phosphorylation. In Aplysia sensory neurons, phosphorylation of eIF4E is reduced during intermediate memory formation. However, we found that this physiological regulation of eIF4E phosphorylation was independent of changes in Aplysia Mnk phosphorylation. We propose that changes in eIF4E phosphorylation in Aplysia neurons are a consequence of changes in cap-dependent translation that are independent of regulation of Aplysia Mnk.

Not only 'Flinders Island' spotted fever.

AIM: To demonstrate that Flinders Island spotted fever (FISF), a spotted fever group rickettsial infection caused by Rickettsia honei, is found not only on Flinders Island (Bass Strait), Tasmania, but elsewhere in south-east Australia. METHODS: Cases of FISF were identified by rickettsial serology, culture and the detection of rickettsial DNA via PCR. Isolates and PCR products were sequenced to identify the aetiological agent as R. honei. RESULTS: Three new cases of FISF were detected outside of Flinders Island. One on Schouten Island, south of the Freycinet Peninsula, Tasmania, and two in south-eastern South Australia (McLaren Vale and Goolwa). CONCLUSIONS: These cases show that FISF extends beyond Flinders Island and most likely has the same distribution across south-east Australia as its vector, the reptile tick Aponomma hydrosauri. FISF should be considered as a differential diagnosis in patients from south-eastern Australia presenting with fever, headache and rash following a tick bite.

A new focus of Rickettsia honei spotted fever in South Australia.

We recently diagnosed rickettsial spotted fever in four patients from the south-eastern coastal region of South Australia near Adelaide, an area not known to be endemic for this infection. All infections were acquired within the geographic range of Aponomma hydrosauri, the tick vector of Rickettsia honei. Infection by R. honei was confirmed in two patients. This extension of the known geographic range of R. honei infection may be explained, in part, by alterations in host-parasite ecology.