Search

Background International consensus definitions for invasive aspergillosis (IA) in research are rigorous, yet clinically significant cases are often excluded from clinical studies for not meeting proven/probable IA case definitions. To better understand reasons for the failure to meet criteria for proven/probable infection, we herein review 47 such cases for their clinical and microbiological characteristics and outcomes. Methods Data on 47 cases that did not meet consensus IA definitions but were deemed significant were derived from a retrospective, observational, multicenter survey of 382 presumed IA cases across Australasia, of which findings of 221 proven/probable infections were recently published. The clinical, microbiological, and radiologic characteristics of these cases were analyzed. Mortality outcomes were compared with those of 221 proven/probable cases. Results Of 47 cases studied, 15 lacked classical host factors; 22 exhibited only a single positive Aspergillus polymerase chain reaction result; 7 lacked typical IA radiologic findings on chest computed tomography; and 3 had borderline galactomannan optical density indices (<1.0 but ≥0.5) in bronchoalveolar lavage fluid. The median age of patients was 61 years (IQR, 52–68); 34 were male (72%). Seven patients (15%) required intensive care admission. All patients had lung as the primary site of infection. Antifungal treatment was initiated in 42 patients (89%). All-cause 90-day mortality was 33%, similar to the 30% mortality in the comparative cohort (n = 221). Conclusions Our findings highlight the limitations of current consensus definitions for IA. Notably, the mortality of patients not meeting these definitions was similar to that of patients with proven/probable IA. Further studies, especially of patients with a single positive Aspergillus polymerase chain reaction result and those without host factors, are needed to determine if future consensus definitions may benefit from modifications. [ABSTRACT FROM AUTHOR]

Prior to a more detailed analysis of Japanese law in the context of repair and recycle, the authors provide a comparative overview over the conflict between intellectual property rights and what is now known as the 'right to repair'. [ABSTRACT FROM AUTHOR]

Background Patients without human immunodeficiency virus (HIV) are increasingly recognized as being at risk for cryptococcosis. Knowledge of characteristics of cryptococcosis in these patients remains incomplete. Methods We conducted a retrospective study of cryptococcosis in 46 Australian and New Zealand hospitals to compare its frequency in patients with and without HIV and describe its characteristics in patients without HIV. Patients with cryptococcosis between January 2015 and December 2019 were included. Results Of 475 patients with cryptococcosis, 90% were without HIV (426 of 475) with marked predominance in both Cryptococcus neoformans (88.7%) and Cryptococcus gattii cases (94.3%). Most patients without HIV (60.8%) had a known immunocompromising condition: cancer (n = 91), organ transplantation (n = 81), or other immunocompromising condition (n = 97). Cryptococcosis presented as incidental imaging findings in 16.4% of patients (70 of 426). The serum cryptococcal antigen test was positive in 85.1% of tested patients (319 of 375); high titers independently predicted risk of central nervous system involvement. Lumbar puncture was performed in 167 patients to screen for asymptomatic meningitis, with a positivity rate of 13.2% where meningitis could have been predicted by a high serum cryptococcal antigen titer and/or fungemia in 95% of evaluable cases. One-year all-cause mortality was 20.9% in patients without HIV and 21.7% in patients with HIV (P =.89). Conclusions Ninety percent of cryptococcosis cases occurred in patients without HIV (89% and 94% for C. neoformans and C. gattii , respectively). Emerging patient risk groups were evident. A high level of awareness is warranted to diagnose cryptococcosis in patients without HIV. [ABSTRACT FROM AUTHOR]

Time-to-positivity (TTP) may assist in predicting the outcome of candidaemia. We analysed a candidaemia dataset collected prospectively in Australia over 1 year (2014–2015). TTP was defined as the period from blood culture sampling to the blood culture flagging positive. Of 415 candidaemia episodes, overall, 30-day mortality was 29% (120/415); mortality with Candida albicans was 35% (59/169), C. glabrata complex, 37% (43/115), C. tropicalis, 43% (10/23), Pichia kudriavzevii 25% (3/12), and C. parapsilosis complex 7% (5/71). Each day of increased TTP multiplied the odds ratio (OR) of survival at 30 days by a factor of 1.32 [95% confidence interval (CI) 1.06–1.69]. Shorter TTP was associated with increased mortality, with 1-day TTP associated with 30-day mortality 37% (41/112) (95%CI: 28%–46%) and 5-day TTP 11% (2/18) (95%CI: 2%–36%). Lay Summary: Time-to-positivity is a measure that is available to clinicians when patients are identified as having candida in their bloodstream. Our data support the association of a shorter time to positivity with higher mortality. [ABSTRACT FROM AUTHOR]

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 <3 SNPs. Multidrug resistance was absent. High within-host genetic heterogeneity should be considered when investigating C. auris infections. [ABSTRACT FROM AUTHOR]

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 288 km (IQR 201-715) and the median duration on the programme was 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. [ABSTRACT FROM AUTHOR]

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 2.41/105 population. The median patient age was 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. [ABSTRACT FROM AUTHOR]

Cutaneous disease is the third most frequent manifestation of mucormycosis. The clinical manifestations of and subsequent mortality due to cutaneous mucormycosis are dependent on the mode of acquisition and the host immune status. Here, we describe the epidemiology, clinical presentation, microbiology, and outcomes of 16 cutaneous mucormycosis infections managed in an Australian tertiary hospital over a 15-year period. The proportion with localized (56%), deep (38%), and disseminated (6%) cutaneous disease as well as the overall mortality (25%) were consistent with findings reported in the published literature. Two novel forms of hospital-acquired infection were reported following a sacral pressure sore and insertion of a foreign body during a bone graft procedure. The majority of patients were immunocompetent (75%) and/or suffered trauma (56%) with associated environmental contamination. A novel finding was that motor vehicle accidents (MVAs) accounted for 78% of all trauma-related cases, suggesting MVAs should receive greater recognition as a potential precipitant of cutaneous mucormycosis. Aggressive decontamination and debridement of devitalized tissue following trauma is therefore likely to play an important role in the prevention of this rare but potentially devastating infection. [ABSTRACT FROM PUBLISHER]

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 <30 mg/L to avoid excessive vancomycin exposure may reduce the risk of VN. [ABSTRACT FROM PUBLISHER]

Induction amphotericin plus 5-flucytosine is indicated for Cryptococcus gattii lung (2 weeks) and neurologic disease (6 weeks), followed by fluconazole (total course 6–12 and 18 months, respectively). Shunting for raised intracranial pressure is frequent. Immune reconstitution inflammatory syndrome occurs in 9% of cases.Background. We describe antifungal therapy and management of complications due to Cryptococcus gattii infection in 86 Australian patients followed for at least 12 months.Methods. Patient data from culture-confirmed cases (2000–2007) were recorded at diagnosis, 6 weeks, 6 months, and 12 months. Clinical, laboratory, and treatment variables associated with raised intracranial pressure (ICP) and immune reconstitution inflammatory syndrome (IRIS) were determined.Results. Seven of 10 patients with lung infection received amphotericin B (AMB) induction therapy (6 with 5-flucytosine [5-FC] for a median of 2 weeks); median duration of therapy including azole eradication therapy was 41 weeks, with a complete/partial clinical response in 78%. For neurologic disease, 88% of patients received AMB, 78% with 5-FC, for a median of 6 weeks. The median total course was 18 months. Nine patients receiving fluconazole induction therapy were reinduced with AMB plus 5-FC for clinical failure. Raised ICP (31 patients) was associated with initial abnormal neurology, and neurologic sequelae and/or death at 12 months (both P = .02); cerebrospinal fluid drains/shunts were placed in 58% of patients and in 64% of 22 patients with hydrocephalus. IRIS developed 2–12 months after starting antifungals in 8 patients, who presented with new/enlarging brain lesions. Risk factors included female sex, brain involvement at presentation, and higher median CD4 counts (all P < .05); corticosteroids reduced cryptococcoma-associated edema.Conclusions. Induction AMB plus 5-FC is indicated for C. gattii neurologic cryptococcosis (6 weeks) and when localized to lung (2 weeks). Shunting was often required to control raised ICP. IRIS presents with cerebral manifestations. [ABSTRACT FROM PUBLISHER]

Neurological disease, with or without lung infection, is common in sporadic Cryptococcus gattii infection (85%; raised intracranial pressure [42%]; hydrocephalus [30%]; neurological deficits [27%]). Immunocompromised patients had increased mortality risk. Cerebrospinal fluid cryptococcal antigen titers ≥256 predicted death and/or neurological sequelae in central nervous system infection.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. [ABSTRACT FROM AUTHOR]

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 (n = 30) were matched 1 : 2 to controls (n = 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$23 611 (95% CI = 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 = 8.2–17.8 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 = 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. [ABSTRACT FROM PUBLISHER]

Alzheimer's disease is commonly regarded as a loss of memory for past events. However, patients with Alzheimer's disease seem not only to forget events but also to express false confidence in remembering events that have never happened. How and why false recognition occurs in such patients is currently unknown, and treatments targeting this specific mnemonic abnormality have not been attempted. Here, we used a modified object recognition paradigm to show that the tgCRND8 mouse-which overexpresses amyloid β and develops amyloid plaques similar to those in the brains of patients with Alzheimer's disease-exhibits false recognition. Furthermore, we found that false recognition did not occur when tgCRND8 mice were kept in a dark, quiet chamber during the delay, paralleling previous findings in patients with mild cognitive impairment, which is often considered to be prodromal Alzheimer's disease. Additionally, false recognition did not occur when mice were treated with the partial N-methyl-d-aspartic acid receptor antagonist memantine. In a subsequent experiment, we found abnormally enhanced N-methyl-d-aspartic acid receptor-dependent long-term depression in these mice, which could be normalized by treatment with memantine. We suggest that Alzheimer's disease typical amyloid β pathology leads to aberrant synaptic plasticity, thereby making memory representations more susceptible to interfering sensory input, thus increasing the likelihood of false recognition. Parallels between these findings and those from the literature on Alzheimer's disease and mild cognitive impairment suggest a mechanism underlying false recognition in these patients. The false recognition phenomenon may provide a novel paradigm for the discovery of potential therapies to treat the mnemonic dysfunction characteristic of this disease. [ABSTRACT FROM AUTHOR]

We performed a retrospective review of cases of cerebral cryptococcosis among patients admitted to 12 Australian teaching hospitals between 1985 and 1992. Of 118 cases identified, 35 occurred in immunocompetent hosts. When cases due to Cryptococcus neoformans variety neoformans were compared with those due to Cryptococcus neoformans variety gattii, we found that the latter tended to occur in healthy hosts whose residence or job was located in a rural area, and cerebral mass lesions and/or hydrocephalus and pulmonary mass lesions were more common. For a subgroup of patients with infection due to C. neoformans variety gattii, multiple enhancing lesions were observed on cerebral computed tomograms, and papilledema, high CSF and serum cryptococcal antigen titers, and a worse prognosis (despite prolonged amphotericin B therapy and intraventricular shunt insertion) were also noted. No significant difference in clinical course or outcome in terms of variety of C. neoformans was noted for patients with cryptococcal meningitis whose computed tomographic scans appeared normal on presentation. [ABSTRACT FROM PUBLISHER]

This international collaborative survey identified culture-confirmed legionellosis in 508 patients with sporadic community-acquired legionellosis. Legionella pneumophila constituted 91.5% of the isolates. Serogroup 1 was the predominant serogroup (84.2%), and serogroups 2-13 (7.4%) accounted for the remaining serogroups. The Legionella species most commonly isolated were L. longbeachae (3.9%) and L. bozemanii (2.4%), followed by L. micdadei, L. dumoffii, L. feeleii, L. wadsworthii, and L. anisa (2.2% combined). L. longbeachae constituted 30.4% of the community-acquired Legionella isolates in Australia and New Zealand. [ABSTRACT FROM AUTHOR]