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Cryptococcosis caused by the Cryptococcus neoformans-Cryptococcus gattii complex is an important opportunistic infection in people with immunodeficiency, including in the haematology/oncology setting. This may manifest clinically as cryptococcal meningitis or pulmonary cryptococcosis, or be detected incidentally by cryptococcal antigenemia, a positive sputum culture or radiological imaging. Non-Candida, non-Cryptococcus spp. rare yeast fungaemia are increasingly common in this population. These consensus guidelines aim to provide clinicians working in the Australian and New Zealand haematology/oncology setting with clear guiding principles and practical recommendations for the management of cryptococcosis, while also highlighting important and emerging rare yeast infections and their recommended management.

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.To describe our experience managing IFIs via OPAT, including assessment of risk factors associated with unplanned readmissions.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.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.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.

ERG11 sequencing of 28 Candida auris clade III isolates revealed the presence of concomitant V125A and F126L substitutions. Heterologous expression of Erg11-V125A/F126L in Saccharomyces cerevisiae led to reduced fluconazole and voriconazole susceptibilities. Generation of single substitution gene variants through site-directed mutagenesis uncovered that F126L primarily contributes to the elevated triazole MICs. A similar, yet diminished pattern of reduced susceptibility was observed with long-tailed triazoles posaconazole and itraconazole for V125A/F126L, F126L, Y132F, and K143R alleles.

Candida auris is an emerging drug-resistant yeast responsible for hospital outbreaks. This statement reviews the evidence regarding diagnosis, treatment and prevention of this organism and provides consensus recommendations for clinicians and microbiologists in Australia and New Zealand. C. auris has been isolated in over 30 countries (including Australia). Bloodstream infections are the most frequently reported infections. Infections have crude mortality of 30-60%. Acquisition is generally healthcare-associated and risks include underlying chronic disease, immunocompromise and presence of indwelling medical devices. C. auris may be misidentified by conventional phenotypic methods. Matrix-assisted laser desorption ionisation time-of-flight mass spectrometry or sequencing of the internal transcribed spacer regions and/or the D1/D2 regions of the 28S ribosomal DNA are therefore required for definitive laboratory identification. Antifungal drug resistance, particularly to fluconazole, is common, with variable resistance to amphotericin B and echinocandins. Echinocandins are currently recommended as first-line therapy for infection in adults and children ≥2 months of age. For neonates and infants

Whole-genome sequencing clustered Australian Candida auris isolates from sporadic cases within clade III. Case isolates were genomically distinct; however, unexpectedly, those from 1 case comprised 2 groups separated by >60 single nucleotide polymorphisms (SNPs) with no isolate being identical, in contrast to outbreaks where isolates from any 1 individual have differed by

In less than a decade, C. auris has emerged in health care settings worldwide; this species is capable of colonizing skin and causing outbreaks of invasive candidiasis. In contrast to other Candida species, C. auris is unique in its ability to spread via nosocomial transmission and its high rates of drug resistance. As part of the public health response, whole-genome sequencing has played a major role in characterizing transmission dynamics and detecting new C. auris introductions. Through a global collaboration, we assessed genome evolution of isolates of C. auris from 19 countries. Here, we described estimated timing of the expansion of each C. auris clade and of fluconazole resistance, characterized discrete phylogeographic population structure of each clade, and compared genome data to sensitivity measurements to describe how antifungal resistance mechanisms vary across the population. These efforts are critical for a sustained, robust public health response that effectively utilizes molecular epidemiology., Candida auris has emerged globally as a multidrug-resistant yeast that can spread via nosocomial transmission. An initial phylogenetic study of isolates from Japan, India, Pakistan, South Africa, and Venezuela revealed four populations (clades I, II, III, and IV) corresponding to these geographic regions. Since this description, C. auris has been reported in more than 30 additional countries. To trace this global emergence, we compared the genomes of 304 C. auris isolates from 19 countries on six continents. We found that four predominant clades persist across wide geographic locations. We observed phylogeographic mixing in most clades; clade IV, with isolates mainly from South America, demonstrated the strongest phylogeographic substructure. C. auris isolates from two clades with opposite mating types were detected contemporaneously in a single health care facility in Kenya. We estimated a Bayesian molecular clock phylogeny and dated the origin of each clade within the last 360 years; outbreak-causing clusters from clades I, III, and IV originated 36 to 38 years ago. We observed high rates of antifungal resistance in clade I, including four isolates resistant to all three major classes of antifungals. Mutations that contribute to resistance varied between the clades, with Y132F in ERG11 as the most widespread mutation associated with azole resistance and S639P in FKS1 for echinocandin resistance. Copy number variants in ERG11 predominantly appeared in clade III and were associated with fluconazole resistance. These results provide a global context for the phylogeography, population structure, and mechanisms associated with antifungal resistance in C. auris.

Whole-genome sequencing clustered Australian Candida auris isolates from sporadic cases within clade III. Case isolates were genomically distinct; however, unexpectedly, those from 1 case comprised 2 groups separated by >60 single nucleotide polymorphisms (SNPs) with no isolate being identical, in contrast to outbreaks where isolates from any 1 individual have differed by

Objectives: Most outpatient parenteral antimicrobial therapy (OPAT) services use a hospital-based model of care in which patients remain in proximity to large hospitals facilitating clinical review. We aimed to evaluate clinical outcomes and complication rates for patients living in geographically isolated locations managed by telemedicine-supported OPAT. Methods: This was a retrospective cohort study. Results: Between 2011 and 2015, we delivered 88 episodes of care involving 83 adult patients resulting in 2261 days of OPAT. The median age was 56 years, 8 of 83 (10%) were indigenous Australian and the median Charlson comorbidity index score was 2 (IQR 1-4). The median distance of patients' residence from our hospital was 288km (IQR 201-715) and the median duration on the programmewas 26 days (IQR 14-34). Bone and joint infections accounted for 75% of infections treated. Favourable clinical outcomes (improvement or cure) were achieved in 87% of patients and the unplanned, OPAT-related readmission rate was 8%. Nineteen percent and 10% of patients had drug-related and line-related adverse effects, respectively. Conclusions: Despite a complex case mix, our adverse event and readmission rates are similar to the published literature describing a non-telemedicine model to deliver OPAT. High rates of favourable clinical outcomes and likely cost benefits suggest that telemedicine-supported OPAT is an efficacious and safe substitute for inpatient care in our setting.

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.

Baseline chest computed tomography (BCT) in high-risk hematology patients allows for the early diagnosis of invasive pulmonary aspergillosis (IPA). The distribution of BCT implementation in hematology departments and impact on outcome is unknown. A web-based questionnaire was designed. International scientific bodies were invited. The estimated numbers of annually treated hematology patients, chest imaging timepoints and techniques, IPA rates, and follow-up imaging were assessed. In total, 142 physicians from 43 countries participated. The specialties included infectious diseases (n = 69, 49%), hematology (n = 68, 48%), and others (n = 41, 29%). BCT was performed in 57% (n = 54) of 92 hospitals. Upon the diagnosis of malignancy or admission, 48% and 24% performed BCT, respectively, and X-ray was performed in 48% and 69%, respectively. BCT was more often used in hematopoietic cell transplantation and in relapsed acute leukemia. European centers performed BCT in 59% and non-European centers in 53%. Median estimated IPA rate was 8% and did not differ between BCT (9%, IQR 5&ndash, 15%) and non-BCT centers (7%, 10%) (p = 0.69). Follow-up computed tomography (CT) for IPA was performed in 98% (n = 90) of centers. In high-risk hematology patients, baseline CT is becoming a standard-of-care. Chest X-ray, while inferior, is still widely used. Randomized, controlled trials are needed to investigate the impact of BCT on patient outcome.

Background: Endemic to soils of Northern Australia, 'Burkholderia pseudomallei' is the Gramnegative pathogen responsible for melioidosis, which causes a clinical spectrum ranging from pneumonia and/or cutaneous infection to disseminated disease with fulminant septicaemia. Incident cases peak after monsoonal rains, particularly in individuals with immune dysfunction. Early diagnosis of melioidosis is challenging for clinicians, given its ability to mimic many other diseases and high clinical (associated mortality) impact. Objectives: The aim of this paper is to provide general practitioners with an overview of melioidosis, covering epidemiology, risk factors for infection, clinical disease spectrum, diagnostic techniques and an approach to management, including public health aspects. Discussion: Primary care physicians play a key role in early disease recognition, initial patient stabilisation, request of appropriate clinical samples (particularly blood cultures) and prompt commencement of efficacious antibiotics. Patient education is paramount during high-risk periods, chiefly for patients with diabetes and/or those who engage in hazardous alcohol use, living in endemic areas of Australia.

Antifungal susceptibilities of non-Aspergillus filamentous fungal pathogens cannot always be inferred from their identification. Here we determined, using the Sensititre(®) YeastOne(®) YO10 panel, the in vitro activities of nine antifungal agents against 52 clinical isolates of emergent non-Aspergillus moulds representing 17 fungal groups in Australia. Isolates comprised Mucorales (n = 14), Scedosporium/Lomentospora spp. (n = 18) and a range of hyaline hyphomycetes (n = 9) and other dematiaceous fungi (n = 11). Excluding Verruconis gallopava, echinocandins demonstrated poor activity (MICs generally >8 mg/L) against these moulds. Lomentospora prolificans (n = 4) and Fusarium spp. (n = 6) demonstrated raised MICs to all antifungal drugs tested, with the lowest being to voriconazole and amphotericin B (AmB), respectively (geometric mean MICs of 3.4 mg/L and 2.2 mg/L, respectively). All Scedosporium apiospermum complex isolates (n = 14) were inhibited by voriconazole concentrations of ≤0.25 mg/L, followed by posaconazole and itraconazole at ≤1 mg/L. Posaconazole and AmB were the most active agents against the Mucorales, with MIC90 values of 1 mg/L and 2 mg/L, respectively, for Rhizopus spp. For dematiaceous fungi, all isolates were inhibited by itraconazole and posaconazole concentrations of ≤0.5 mg/L (MIC90, 0.12 mg/L and 0.25 mg/L, respectively), but voriconazole and AmB also had in vitro activity (MIC90, 0.5 mg/L and 1 mg/L, respectively). Differences in antifungal susceptibility within species and between species within genera support the need for testing individual patient isolates to guide therapy. The Sensititre(®) YeastOne(®) offers a practical alternative to the reference methodology for susceptibility testing of moulds.

Mucormycosis is the second most common cause of invasive mould infection and causes disease in diverse hosts, including those who are immuno-competent. We conducted a multicentre retrospective study of proven and probable cases of mucormycosis diagnosed between 2004-2012 to determine the epidemiology and outcome determinants in Australia. Seventy-four cases were identified (63 proven, 11 probable). The majority (54.1%) were caused by Rhizopus spp. Patients who sustained trauma were more likely to have non-Rhizopus infections relative to patients without trauma (OR 9.0, p 0.001, 95% CI 2.1-42.8). Haematological malignancy (48.6%), chemotherapy (42.9%), corticosteroids (52.7%), diabetes mellitus (27%) and trauma (22.9%) were the most common co-morbidities or risk factors. Rheumatological/autoimmune disorders occurred in nine (12.1%) instances. Eight (10.8%) cases had no underlying co-morbidity and were more likely to have associated trauma (7/8; 87.5% versus 10/66; 15.2%; p

Thirty five patients were transferred to Royal Perth Hospital (RPH) after the Bali bombings. The patients had severe burn injuries and were considered to be at high-risk of both the carriage and acquisition of multi-resistant organisms (MROs). Whilst seeking to protect the Bali patients with a comprehensive infection control response, we also sought to protect other high-risk patients from nosocomial acquisition of MROs. MROs were detected from 25 (82%) of the 29 Bali patients admitted to RPH. Bali patients were colonised, or infected, with one or more of the following MROs: multi-resistant Acinetobacter baumannii (MRAB) (19 patients), extended-spectrum s-lactamase (ESBL) producing Gram-negative bacteria (15 patients), vancomycin-resistant enterococci (VRE) (nine patients), multi-resistant Pseudomonas aeruginosa (MRPA) (six patients), multi-resistant Chryseobacterium sp. (four patients), and methicillin-resistant Staphylococcus aureus (MRSA) (three patients). Five Bali patients developed a total of eight bacteraemic episodes, with MRPA sepsis contributing to death in two patients. Since the Bali bombings horizontal transmission of Bali MROs has occurred in 41 non-Bali patients in RPH. MRPA has had the greatest clinical impact. Eight non-Bali patients developed a total of 11 bacteraemic episodes, with MRPA sepsis contributing to death in four patients. However, apart from MRPA, we have now controlled transmission of the other MROs in RPH. The emergency response to the Bali disaster required strong leadership, good communication and multi-disciplinary teamwork. The infection control strategy contributed to good outcomes for most Bali bombing patients. However, many patients within the Bali cohort were heavily colonised with MROs, and some developed invasive infection. Subsequent nosocomial transmission of these MROs to non-Bali patients has been a legacy of the Bali tragedy.

Invasive fungal disease (IFD) causes significant morbidity and mortality in patients undergoing allogeneic haemopoietic stem cell transplantation or chemotherapy for haematological malignancy. Much of these adverse outcomes are due to the limited ability of traditional diagnostic tests (i.e. culture and histology) to make an early and accurate diagnosis. As persistent or recurrent fevers of unknown origin (PFUO) in neutropenic patients despite broad-spectrum antibiotics have been associated with the development of IFD, most centres have traditionally administered empiric antifungal therapy (EAFT) to patients with PFUO. However, use of an EAFT strategy has not been shown to have an overall survival benefit and is associated with excessive antifungal therapy use. As a result, the focus has shifted to developing more sensitive and specific diagnostic tests for early and more targeted antifungal treatment. These tests, including the galactomannan enzyme-linked immunosorbent assay and Aspergillus polymerase chain reaction (PCR), have enabled the development of diagnostic-driven antifungal treatment (DDAT) strategies, which have been shown to be safe and feasible, reducing antifungal usage. In addition, the development of effective antifungal prophylactic strategies has changed the landscape in terms of the incidence and types of IFD that clinicians have encountered. In this review, we examine the current role of EAFT and provide up-to-date data on the newer diagnostic tests and algorithms available for use in EAFT and DDAT strategies, within the context of patient risk and type of antifungal prophylaxis used.

There is a strong argument for the use of antifungal prophylaxis in high-risk patients given the significant mortality associated with invasive fungal disease, the late identification of these infections, and the availability of safe and well-tolerated prophylactic medications. Clinical decisions about which patients should receive prophylaxis and choice of antifungal agent should be guided by risk stratification, knowledge of local fungal epidemiology, the efficacy and tolerability profile of available agents, and estimates such as number needed to treat and number needed to harm. There have been substantial changes in practice since the 2008 guidelines were published. These include the availability of new medications and/or formulations, and a focus on refining and simplifying patient risk stratification. Used in context, these guidelines aim to assist clinicians in providing optimal preventive care to this vulnerable patient demographic.

OBJECTIVES To assess the risk factors for nephrotoxicity caused by vancomycin continuous infusion in a predominantly Caucasian outpatient population. METHODS This was a retrospective cohort study of 155 patient episodes from December 2006 to December 2011. RESULTS Vancomycin-associated nephrotoxicity (VN) occurred in 26 of 155 (17%) patient episodes. After adjustment for baseline renal function, maximum steady-state vancomycin concentrations ≥32 mg/L [OR 8.7 (95% CI 3.1-29.6), P < 0.001] and angiotensin receptor blockade [OR 9.78 (95% CI 3.1-39.4), P < 0.001] were independently associated with VN. The cumulative dose and duration of vancomycin therapy were not independent predictors of VN. CONCLUSIONS Cessation of angiotensin receptor-blocking medications in selected patient groups, enhanced monitoring and establishing target steady-state concentrations

Background: Longer-term morbidity and outcomes of Cryptococcus gattii infection are not described. We analyzed clinical, microbiological, and outcome data in Australian patients followed for 12 months, to identify prognostic determinants. Methods: Culture-confirmed C. gattii cases from 2000 to 2007 were retrospectively evaluated. Clinical, microbiological, radiological, and outcome data were recorded at diagnosis and at 6 weeks, 6 months, and 12 months. Clinical and laboratory variables associated with mortality and with death and/or neurological sequelae were determined. Results: Annual C. gattii infection incidence was 0.61 per 10⁶ population. Sixty-two of 86 (72%) patients had no immunocompromise; 6 of 24 immunocompromised hosts had idiopathic CD4 lymphopenia, and 1 had human immunodeficiency virus/AIDS. Clinical and microbiological characteristics of infection were similar in immunocompromised and healthy hosts. Isolated lung, combined lung and central nervous system (CNS), and CNS only disease was reported in 12%, 51% and 34% of the cases, respectively. Complications in CNS disease included raised intracranial pressure (42%), hydrocephalus (30%), neurological deficits (27%; 6% developed during therapy) and immune reconstitutionlike syndrome (11%). Geometric mean serum cryptococcal antigen (CRAG) titers in CNS disease were 563.9 (vs 149.3 in isolated lung infection). Patient immunocompromise was associated with increased mortality risk. An initial cerebrospinal fluid CRAG titer of >= 256 predicted death and/or neurological sequelae (P = .05). Conclusions: Neurological C. gattii disease predominates in the Australian endemic setting. Lumbar puncture and cerebral imaging, especially if serum CRAG titers are >= 512, are essential. Long-term follow up is required to detect late neurological complications. Immune system evaluation is important because host immunocompromise is associated with reduced survival.

Background: Scedosporium species are increasingly recognized as a cause of invasive mould disease in haematology patients, but little is known about the hospitalization costs and outcomes attributable to invasive scedosporiosis (SCEDO). Methods: A retrospective case –control study was undertaken during 2002–10 to determine the attributable inpatient costs, length of stay (LOS) and mortality associated with SCEDO in haematology patients. Case patients with SCEDO (n¼ 30) were matched 1: 2 to controls (n¼ 60) according to haematological diagnosis, admission year and age. Diagnostics, antifungal drugs, ward and other SCEDO-related costs were estimated using actual cost data. Median regression modelling was used to adjust for variables that were not accounted for in the matched-pairs analysis. Results: The crude total median cost of treating SCEDO was AU$32 182 per patient versus AU$17 424 per control. In multivariable analysis, SCEDO was associated with median excess costs of AU$23611 (95% CI ¼ AU$17 992–AU$29 231; P,0.001), approximating US$15 509 at purchasing power parity, with prolonged LOS of 13 days (95% CI ¼8.2 –17.8 days; P,0.001). Exclusion of cases and matched pairs with early death further increased the median excess cost and LOS. The cost differential was driven by ward costs (64%, P ¼ 0.005) and antifungal treatment costs (29%, P,0.001). The all-cause inpatient mortality was 38 times higher for the SCEDO cases versus the control group (63.3% versus 1.7%; P,0.001). Conclusions: SCEDO has substantial impact on hospital resource consumption, LOS and mortality in haematology patients. Risk factors and preventative measures for SCEDO should be further studied.

Central nervous system (CNS) cryptococcosis is most commonly encountered among HIV-infected and other immunosuppressed hosts but is less well-characterized among non-immunosuppressed patients.We conducted a three year, prospective, observational study to compare the clinical manifestations and outcome of CNS cryptococcosis in three patient populations: HIV-infected patients (n = 54), HIV-negative immunosuppressed patients (n = 21), and non-immunosuppressed patients (n = 11).Time from initial symptoms to presentation did not differ between the groups. HIV-infected patients were significantly more likely to present with fevers (p 0.0001), but were less likely to have abnormal mental status, CNS mass lesions and pulmonary involvement (p = 0.001, 0.01 and 0.03, respectively). The clinical manifestations among HIV-negative immunosuppressed patients were generally intermediate to the other groups. Overall, acuity of illness was worse among non-immunosuppressed patients, as measured by APACHE II scores (p = 0.02). Intracranial pressure was higher in HIV-infected and non-immunosuppressed patients than immunosuppressed patients (p = 0.008 and 0.01, respectively). Repeated lumbar punctures were more common among HIV-infected patients (p = 0.01). There was a trend toward more frequent placement of permanent CNS shunts among non-HIV patients (p = 0.05). The mortality rate was greatest for non-immunosuppressed patients (p = 0.04).CNS cryptococcosis in non-immunosuppressed patients was associated with poorer prognosis. Our findings suggest that host immune responses may contribute to pathogenesis of CNS cryptococcosis, with more intact immune function associated with increased CNS-related morbidity and overall mortality.

First-aid education for the management of burns advocates cool running water over burnt skin to limit soft tissue damage. However, the water used may itself constitute a risk. We report three cases of severe invasive and necrotizing infection in patients who used or immersed themselves in contaminated water in an attempt to extinguish the fire following acute major burns. Wound cultures from all patients yielded Aeromonas hydrophila and two yielded Bacillus cereus. One patient had a complex polymicrobial infection, including zygomycosis with Rhizomucor variabilis. All patients were treated aggressively with wound débridement, including one patient who required bilateral lower limb amputations to control progressive infection. All infections were successfully treated and all patients survived their burn injuries. We review the management of burns complicated by exposure to contaminated water leading to burn wound infections. We describe commonly reported organisms from various water sources, the appropriate initial empirical antimicrobial chemotherapy and present the clinician with a proposed algorithm for managing these serious infections.

A 48-year-old insulin-dependent diabetic woman presented with multiple lesions at her insulin injection sites. The lesions had gradually appeared and progressively enlarged over a 7-week period. Her background included 27 years of insulin-dependent diabetes mellitus, complicated by micro-vascular disease with early diabetic nephropathy, sensory peripheral polyneuropathy and grade 1 diabetic retinopathy. Diabetic management had been with a basal-bolus regimen of insulin, but with generally poor diabetic control (glycosylated haemoglobin of 10–11%). The lesions were only associated with her isophane insulin (delivered by a Novojet™ pen system) injection sites; her abdominal neutral insulin (Actrapid™) injection sites were unaffected. She denied any constitutional symptoms. Despite rotating her insulin injection sites, improving her injection site hygiene, and using clean insulin needles and canisters, new lesions continued to occur, and empiric oral antimicrobial therapy including flucloxacillin, erythromycin and amoxycillin/clavulanic acid had been ineffective. On examination she was afebrile and appeared well, however she had multiple erythematous, violaceous, non-tender plaques on the anterior aspect of her thighs (Figure 1). There was no associated lymphadenopathy, and her anterior abdominal wall insulin injection sites were unremarkable. Apart from signs of end-organ diabetic disease the remainder of her examination was normal. Figure 1. Left anterior thigh lesions at the infected insulin injection …

The efficacy of voriconazole in 107 patients with scedosporiosis was analyzed. Principal infection sites were the lungs/sinuses (24%), central nervous system (CNS) (20%), and bone (18%), while 21% of patients had disseminated infection. Solid organ transplantation (22%), hematological malignancy (21%), and surgery/trauma (15%) were the predominant underlying conditions. A successful therapeutic response was achieved in 57% of patients (median, 103 therapy days), with >98% of those responding receiving ≥28 days of therapy. Patients receiving primary therapy showed a 61% response versus 56% for the others. The best therapeutic responses were seen for skin/subcutaneous (91%) or bone (79%) infections, and the lowest for CNS infections (43%). Patients without major immune suppression (72%) or those with solid organ transplantation (63%) or various hematological conditions (60%) showed the best responses by underlying condition. Median known survival time was 133 days (therapy successes, 252 days; failures, 21 days). In all, 43 (40%) patients died, 73% due to scedosporiosis. Patients with Scedosporium prolificans infection had significantly reduced survival times ( P = 0.0259) and were more likely to die from fungal infection ( P = 0.002) than were Scedosporium apiospermum -infected patients. In a subset of 43 patients where voriconazole baseline MICs were available, response to voriconazole was higher for S. apiospermum -infected patients (54% response; MIC 50 , 0.25 μg/ml) than for S. prolificans -infected patients (40% response; MIC 50 , 4.0 μg/ml). Voriconazole demonstrated clinically useful activity in the treatment of both S. apiospermum and S. prolificans infections and was well tolerated.

The spatial distribution of species within an aerosol droplet influences how it interacts with its environment. Despite the ubiquity of multicomponent nanodroplets in natural and technological aerosols, there are no published measurements of their internal structure. Here, we report the first experimental results for structure in aqueous organic nanodroplets based on small angle neutron scattering by high number density aerosols. For H(2)O-n-butanol droplets, fitting of the diffraction patterns confirms the picture of an aqueous core containing approximately 3 mol% alcohol covered by a shell of densely packed alcohol molecules.

Objective:To demonstrate that nosocomial transmission of vancomycin-resistant enterococci (VRE) can be terminated and endemicity prevented despite widespread dissemination of an epidemic strain in a large tertiary-care referral hospital.Interventions:Two months after the index case was detected in the intensive care unit, 68 patients became either infected or colonized with an epidemic strain of vanB vancomycin-resistantEnterococcus faeciumdespite standard infection control procedures. The following additional interventions were then introduced to control the outbreak: (1) formation of a VRE executive group; (2) rapid laboratory identification (30 to 48 hours) using culture and polymerase chain reaction detection ofvanA andvanBresistance genes; (3) mass screening of all hospitalized patients with isolation of carriers and cohorting of contacts; (4) environmental screening and increased cleaning; (5) electronic flagging of medical records of contacts; and (6) antibiotic restrictions (third-generation cephalosporins and vancomycin).Results:A total of 19,658 patient and 24,396 environmental swabs were processed between July and December 2001. One hundred sixty-nine patients in 23 wards were colonized with a single strain of vanB vancomycin-resistantE. faecium.Introducing additional control measures rapidly brought the outbreak under control. Hospital-wide screening found 39 previously unidentified colonized patients, with only 7 more nonsegregat-ed patients being detected in the next 2 months. The outbreak was terminated within 3 months at a cost of $2.7 million (Australian dollars).Conclusion:Despite widespread dissemination of VRE in a large acute care facility, eradication was achievable by a well-resourced, coordinated, multifaceted approach and was in accordance with good clinical governance.

Treatment of invasive fungal infections is increasingly complex. Amphotericin B deoxycholate has long been the mainstay of treatment. However, there has been increasing recognition of both the propensity for nephro-toxicity in haematology, transplant and intensive care patients as well as its adverse impact on morbidity and mortality. This has coincided with the availabilty of newer, and in certain settings, more effective antifungal agents. Although the newer agents clearly cause less nephrotoxicity than amphotericin B, drug interactions, hepatic effects and unique side-effects need to be considered. The spectrum of the newer triazoles and echinocandins varies, highlighting the importance of accurate identification of the causative organism where possible. Consensus Australian guidelines have been developed to assist clinicians with treatment choices by reviewing the current evidence for the efficacy, the toxicity and the cost of these agents.

We report the development and evaluation of a real-time PCR assay using the LightCycler instrument for the detection of C. albicans and A. fumigatus DNA in whole blood. Recently published consensus criteria for the diagnosis of invasive fungal infection (IFI) were used for all patient samples. Unique and published primer pairs were developed and assessed for sensitivity, specificity, and reproducibility to detect C. albicans and A. fumigatus DNA in samples spiked with purified DNA, and whole blood samples from 8 high-risk patients and 45 negative controls. The real-time assay demonstrated an analytical sensitivity of 10 fg of purified C. albicans and A. fumigatus DNA and was found to be specific for each species. The standardized approach was highly reproducible and detected C. albicans and A. fumigatus DNA in two patients with proven IFI and in one patient with a possible IFI. In addition, we report for the first time the use of recently published international consensus criteria for the diagnosis of IFI in the evaluation of a mildly invasive fungal diagnostic assay. Standardized clinical criteria and a more standardized approach to detect fungal DNA in less invasive patient samples, may permit a more reliable comparison of future studies. A rapid real-time detection of fungal DNA in whole blood, combined with standard clinical markers of response, may be more useful for monitoring patients at risk of developing IFI than other diagnostic methods currently available.

A quantitative real-time PCR targeting the Pneumolysin (ply) gene of Streptococcus pneumoniae was developed for the LightCycler instrument using Fluorescence Resonance Energy Transfer (FRET) probes. All common S. pneumoniae serotypes were detected while other bacteria and viruses were not. The sensitivity was determined to be between one and ten target copies per reaction. The PCR was applied to six CSF and 16 whole blood specimens from 17 patients with laboratory proven invasive pneumococcal disease. One hundred percent of CSF specimens and 69% of whole blood specimens were PCR positive. The bacterial loads were determined to be 7.6 to 6.01 x 10(5) copies/microL for the six CSF specimens, and 0.08 to 5.4 x 10(2) copies/microL for the 16 whole blood specimens. Ninety-seven percent of 30 culture and Gram's stain negative CSF specimens and 100% of 50 normal whole blood specimens were PCR negative. This highly sensitive and specific PCR assay has the potential to provide sufficiently rapid results to improve antibiotic treatment of S.pneumoniae infections, while bacterial load quantitation has opened up exciting possibilities for patient management.

Background The International Society for Peritoneal Dialysis (ISPD) guidelines recommend empiric therapy with cefazolin and ceftazidime for peritoneal dialysis (PD)-related peritonitis. Empiric cefazolin therapy may have diminishing efficacy because of emerging methicillin resistance in gram-positive bacteria (GPB). Western Australia also has large numbers of Aboriginal and isolated regional patients, where giving these antimicrobials can be impractical. Objectives To evaluate, based on local antimicrobial resistance patterns, the feasibility of following ISPD guidelines in Western Australia and to identify any subgroups of PD peritonitis patients that may benefit from alternative empiric intraperitoneal antibiotics ( e.g., vancomycin). Study Design Retrospective study of all PD peritonitis episodes in Western Australia from 1 February 2000 to 31 January 2001. Setting Three adult tertiary referral university hospitals and their PD patients in metropolitan Perth and regional Western Australia. Patients All adults on PD in Western Australia. Main Outcome Measure Isolates and antibiograms were analyzed versus patient characteristics, including race and patient demographics. Results 293 patients (28% Aborigines, 32% regional patients) received PD. 145 episodes of PD peritonitis occurred during the study. The overall PD peritonitis rate was 1 episode/16 patient months, with Aborigines having 1 episode/10.5 patient months versus non-Aborigines having 1 episode/17 patient months p (< 0.001). 36% of isolates from PD peritonitis episodes were resistant to cefazolin or ceftazidime. 22% were methicillin-resistant GPB (MR-GPB) [18% coagulase-negative staphylococci (CoNS), 1.6% MR Staphylococcus aureus]; 2.5% were multidrug-resistant gram-negative bacteria (MDR-GNB); 5.7% were polymicrobial (MR-GPB and/or MDR-GNB); and 5.7% were fungal. 63% of CoNS were methicillin resistant. Non-Aboriginal patients yielded MR-GPB in 22% of isolates versus 23% in Aborigines ( p = 0.9). Six of seven cases of fungal peritonitis occurred inAboriginal patients ( p < 0.001). Conclusions In our study population the ISPD guidelines were appropriate for 64% of patients with PD peritonitis. We could not identify specific patient subgroups where empiric cefazolin use could be more effective. High proportions of MR-GPB PD peritonitis episodes, along with local factors, make empiric cefazolin unsuitable for many regional PD patients in Western Australia.

We measured the homogeneous nucleation rates of D2O in a supersonic nozzle. Small angle neutron scattering (SANS) experiments characterized the nanodroplet aerosols and yielded the number density N of particles formed. In these new SANS measurements the number densities were in the range of 4×1011

Small angle neutron scattering (SANS) experiments were used to characterize binary nanodroplets composed of D2O and H2O. The droplets were formed by expanding dilute mixtures of condensible vapor in a N2 carrier gas through a supersonic nozzle, while maintaining the onset of condensation at a fixed position in the nozzle. It is remarkable, given the small coherent scattering length density of light water, that even the pure H2O aerosol gave a scattering signal above background. The scattering spectra were analyzed assuming a log-normal distribution of droplets. On average, the geometric radius of the nanodroplets rg was rg=13 (±1) nm, the polydispersity ln σr was ln σr=0.19 (±0.07), and the number density N was N=(2±0.2)⋅1011 cm−3. The aerosol volume fractions derived from the SANS measurements are consistent with those derived from the pressure trace experiments, suggesting that the composition of the droplets was close to that of the initial condensible mixture. A quantitative analysis of the scattering...

Background Panton Valentine Leukocidin (PVL) has been associated with invasive Staphylococcus aureus soft tissue and pneumonic infections. Methods From September 2007 to January 2009 at Royal Perth Hospital we tested for the PVL gene in S. aureus isolates from an invasive site, a suspected PVL-related soft tissue infection and all MRSA isolates. We could access medical records for 141 PVL positive (PVL + ve) infections and compared these to a control group comprised of 148 PVL negative (PVL-ve) infections. Results In the PVL + ve group 62 isolates were MRSA (48 were ST93-MRSA-IV) and 79 isolates were methicillin-sensitive S. aureus, and in the PVL-ve group 56 were MRSA (50 were WA-MRSA strains) and 92 were methicillin-sensitive S. aureus. We found the presence of PVL to be significantly associated with younger age, aboriginality, intravenous drug use, community acquisition, shorter length of hospital stay and lower mortality at 1 year. Overall PVL + ve infections more often required surgical intervention (73.0% versus 44.6%, p

The last few decades have seen significant changes in health care with increasing numbers of heavily immunocompromised patients. Because of new and more aggressive treatments, patients with severe immune defects are surviving longer and the spectrum of fungal pathogens is increasing. Until relatively recently, Candida albicans and Aspergillus fumigatus were considered the only important nosocomial fungal pathogens. However, non-albicans Candida species and other yeasts, together with an increasing range of moulds apart from A. fumigatus are now reported to cause nosocomial fungal infections. Candidaemia is the fourth most frequent cause of health care associated bloodstream infection in the USA. Candidaemia has a crude mortality of40-80%, and an attributable mortality of approximately 40%. Australian data, although scanty, suggest that invasive fungal infections (IFIs) are also a significant cause of health care associated infections in Australia. The widespread use of azoles for prophylaxis and treatment has been linked with the emergence of non-albicans Candida species and other yeasts. A. fumigatus and a number of other moulds are also important nosocomial pathogens, associated with both prolonged lengths of hospital stay and very high crude mortality rates. Therefore prevention of nosocomial fungal infections is an increasingly important aspect of infection control. Both old and new infection control strategies will need to be implemented to protect our highly immunosuppressed patients particularly from this increasing noscomial threat.

We examined the condensation of H2O, D2O, and four intermediate mixtures (20, 40, 60, and 80 mol % D2O) in a supersonic nozzle. Because the physical and chemical properties of protonated and deuterated water are so similar, this system is ideal for studying the change in condensation behavior as a function of condensible composition. In our experiments dilute mixtures of condensible vapor in N2 are expanded from three different stagnation temperatures resulting in a broad range of onset temperatures (190–238 K) and pressures (27–787 kPa). For a fixed stagnation temperature, the partial pressure required to maintain the onset of condensation at a given location or temperature in the nozzle is consistently higher for H2O than for D2O. In contrast, the supersaturation at fixed onset temperature is usually higher for D2O than for H2O and this difference increases toward lower temperature. The partial pressure at onset for the intermediate mixtures varied linearly between the values observed for the pure compo...

Very recently, Wolk and Strey [J. Phys. Chem. B 105, 11683 (2001)] presented empirical temperature correction functions for calculating homogeneous nucleation rates J of H2O and D2O (1

Tunneled catheters are widely used for the provision of hemodialysis. Long-term catheter survival is limited by tunneled catheter-related infections (CRI). This study assesses the efficacy of catheter-restricted filling with gentamicin and citrate in preventing CRI in hemodialysis patients. A double-blind randomized study was conducted to compare heparin (5000 U/ml) with gentamicin/citrate (40 mg/ml and 3.13% citrate; ratio 2:1) as catheter-lock solutions. A total of 112 tunneled catheters in 83 patients were enrolled at the time of catheter insertion for commencement or maintenance of hemodialysis. The primary end point was CRI. Catheter malfunction, defined as blood flow rate of

Objectives: Knowledge of contemporary epidemiology of candidaemia is essential.We aimed to identify changes since 2004 in incidence, species epidemiology and antifungal susceptibilities of Candida spp. causing candidaemia in Australia. Methods: These data were collected from nationwide active laboratory-based surveillance for candidaemia over 1 year (within 2014-2015). Isolate identification was by MALDI-TOF MS supplemented by DNA sequencing. Antifungal susceptibility testing was performed using Sensititre YeastOne. Results: A total of 527 candidaemia episodes (yielding 548 isolates) were evaluable. The mean annual incidence was 2.41/10 population. The median patient agewas 63 years (56% of cases occurred in males). Of 498 isolates with confirmed species identity, Candida albicans was the most common (44.4%) followed by Candida glabrata complex (26.7%) and Candida parapsilosis complex (16.5%). Uncommon Candida species comprised 25 (5%) isolates. Overall, C. albicans (>99%) and C. parapsilosis (98.8%) were fluconazole susceptible. However, 16.7% (4 of 24) of Candida tropicalis were fluconazole- and voriconazole-resistant and were non-WT to posaconazole. Of C. glabrata isolates, 6.8% were resistant/non-WT to azoles; only one isolate was classed as resistant to caspofungin (MIC of 0.5 mg/L) by CLSI criteria, but was micafungin and anidulafungin susceptible. There was no azole/ echinocandin co-resistance. Conclusions:We report an almost 1.7-fold proportional increase in C. glabrata candidaemia (26.7% versus 16% in 2004) in Australia. Antifungal resistance was generally uncommon, but azole resistance (16.7% of isolates) amongst C. tropicalis may be emerging.