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Janson, Sonja
Medial medullary stroke due to neurosyphilis in a newly diagnosed HIV-positive man.
2018-08-01, Katelaris, Anthea L, Janson, Sonja, Ramachandran, Prashanth, Spencer, Emma
This case report presents the clinical record of a 37-year-old man who presented with a dense right hemiplegia, found to be caused by a left medial medullary stroke. The cause of the stroke was unclear, and bacterial endocarditis was initially suspected. However, he was ultimately found to have neurosyphilis on a background of undiagnosed human immunodeficiency virus and was treated with benzylpenicillin. This case report reviews the diagnosis of neurosyphilis and highlights the importance of considering neurosyphilis as a rare but important cause of stroke, especially given the increasing prevalence of syphilis in Australia.
Epidemiology, management and outcomes of Cryptococcus gattii infections: A 22-year cohort.
2023-03-06, O'Hern JA, Koenen, Adrian, Janson, Sonja, Hajkowicz KM, Robertson IK, Kidd SE, Baird, Robert, Tong SYC, Davis JS, Carson P, Currie, Bart, Ralph, Anna
BACKGROUND: Cryptococcus gattii is a globally endemic pathogen causing disease in apparently immune-competent hosts. We describe a 22-year cohort study from Australia's Northern Territory to evaluate trends in epidemiology and management, and outcome predictors. METHODS: A retrospective cohort study of all C. gattii infections at the northern Australian referral hospital 1996-2018 was conducted. Cases were defined as confirmed (culture-positive) or probable. Demographic, clinical and outcome data were extracted from medical records. RESULTS: 45 individuals with C. gattii infection were included: 44 Aboriginal Australians; 35 with confirmed infection; none HIV positive out of 38 tested. Multifocal disease (pulmonary and central nervous system) occurred in 20/45 (44%). Nine people (20%) died within 12 months of diagnosis, five attributed directly to C. gattii. Significant residual disability was evident in 4/36 (11%) survivors. Predictors of mortality included: treatment before the year 2002 (4/11 versus 1/34); interruption to induction therapy (2/8 versus 3/37) and end-stage kidney disease (2/5 versus 3/40). Prolonged antifungal therapy was the standard approach in this cohort, with median treatment duration being 425 days (IQR 166-715). Ten individuals had adjunctive lung resection surgery for large pulmonary cryptococcomas (median diameter 6cm [range 2.2-10cm], versus 2.8cm [1.2-9cm] in those managed non-operatively). One died post-operatively, and 7 had thoracic surgical complications, but ultimately 9/10 (90%) treated surgically were cured compared with 10/15 (67%) who did not have lung surgery. Four patients were diagnosed with immune reconstitution inflammatory syndrome which was associated with age <40 years, brain cryptococcomas, high cerebrospinal fluid pressure, and serum cryptococcal antigen titre >1:512. CONCLUSION: C. gattii infection remains a challenging condition but treatment outcomes have significantly improved over 2 decades, with eradication of infection the norm. Adjunctive surgery for the management of bulky pulmonary C. gattii infection appears to increase the likelihood of durable cure and likely reduces the required duration of antifungal therapy.
Validating a novel three-times-weekly post-hemodialysis ceftriaxone regimen in infected Indigenous Australian patients-a population pharmacokinetic study.
2023-08-02, Tsai, Danny, Zam B B, Tongs C, Chiong F, Sajiv, Cherian, Pawar B, Ashok A, Cooper, Brynley, Tong S Y C, Janson, Sonja, Wallis S C, Roberts J A, Parker S L
OBJECTIVES: To describe the total and unbound population pharmacokinetics of a 2 g three-times-weekly post-dialysis ceftriaxone regimen in Indigenous Australian patients requiring hemodialysis. METHODS: A pharmacokinetic study was carried out in the dialysis unit of a remote Australian hospital. Adult Indigenous patients on intermittent hemodialysis (using a high-flux dialyzer) and treated with a 2 g three-times-weekly ceftriaxone regimen were recruited. Plasma samples were serially collected over two dosing intervals and assayed using validated methodology. Population pharmacokinetic analysis and Monte Carlo simulations were performed using Pmetrics in R. The probability of pharmacokinetic/pharmacodynamic target attainment (unbound trough concentrations ≥1 mg/L) and toxicity [trough concentrations (total) ≥100 mg/L] were simulated for various dosing strategies. RESULTS: Total and unbound concentrations were measured in 122 plasma samples collected from 16 patients (13 female) with median age 57 years. A two-compartment model including protein-binding adequately described the data, with serum bilirubin concentrations associated (inversely) with ceftriaxone clearance. The 2 g three-times-weekly regimen achieved 98% probability to maintain unbound ceftriaxone concentrations ≥1 mg/L for a serum bilirubin of 5 µmol/L. Incremental accumulation of ceftriaxone was observed in those with bilirubin concentrations >5 µmol/L. Three-times-weekly regimens were less probable to achieve toxic exposures compared with once-daily regimens. Ceftriaxone clearance was increased by >10-fold during dialysis. CONCLUSIONS: A novel 2 g three-times-weekly post-dialysis ceftriaxone regimen can be recommended for a bacterial infection with an MIC ≤1 mg/L. A 1 g three-times-weekly post-dialysis regimen is recommended for those with serum bilirubin ≥10 µmol/L. Administration of ceftriaxone during dialysis is not recommended.
Antimicrobial resistance in urine and skin isolates in Timor-Leste.
2018-06-01, Marr I, Sarmento N, O'Brien M, Lee K, Gusmao C, de Castro G, Janson, Sonja, Tong SYC, Baird, Robert, Francis, Joshua
High rates of antimicrobial resistance (AMR) are seen throughout Southeast Asia. However, limited AMR data exist for Timor-Leste, which is situated on the south-eastern portion of the Malay Archipelago. The purpose of this study was to identify AMR in bacteria isolated from urine and skin swabs from patients in Dili, the capital of Timor-Leste. Urine and skin swabs were collected from symptomatic patients in Timor-Leste and were processed for bacterial culture. Isolates were processed in Australia using a VITEK®2 system for bacterial identification and to determine antimicrobial susceptibility according to Clinical and Laboratory Standards Institute (CLSI) guidelines. A total of 154 urine isolates and 57 skin isolates were analysed. Of the Enterobacteriaceae, 35% were resistant to ceftriaxone with an extended-spectrum β-lactamase (ESBL)-producing phenotype. Carbapenem resistance was not observed in any of the Gram-negative isolates. Of the Staphylococcus aureus isolates, 11% were of the community-associated methicillin-resistant S. aureus (CA-MRSA) phenotype. A moderately high proportion of Gram-negative urine isolates in Timor-Leste demonstrate phenotypic ESBL production, and a relatively low proportion of S. aureus isolates were methicillin-resistant. Improved understanding of AMR rates in Timor-Leste can help guide antimicrobial prescribing and inform antimicrobial stewardship strategies.
Clinical Presentation and Outcomes Following Infection With Vibrio spp, Aeromonas spp, Chromobacterium violaceum, and Shewanella spp Water-Associated Organisms in Tropical Australia, 2015-2022
2024-06-30, Campbell, Stuart, MacGregor, Kirsten, Smith, Emma, Kanitkar, Tanmay, Janson, Sonja, Baird, Robert, Currie, Bart, Venkatesan, Sudharsan
Water-associated bacterial infections cause a wide spectrum of disease. Although many of these infections are typically due to human host commensal or spp, water exposure can result in infections with environmental gram negatives such as spp, spp, , and spp (collectively VACS).We performed a retrospective analysis of the epidemiology, clinical presentation, and outcomes of deep and superficial infections associated with VACS organisms in our health service between 1 January 2015 and 31 December 2023.We identified 317 patient episodes of infection with VACS organisms over this period. Of these, spp (63%) was the most common, followed by spp (19%), spp (13%), and (5%). The majority were isolated from males (74.4%) and involved the lower limb (67.5%). Mild infections were more common than severe presentations, with only 15 (4.7%) admissions to the intensive care unit and 8 (2.5%) deaths. Colonization occurred in 6.9% of patients, in contrast to the perceived severity of some of these bacteria. Copathogens were common and included (48%) and enteric bacteria (57%). The majority of patients (60%) had no documented water exposure. Initial empiric antimicrobial therapy presumptively covered the susceptibilities of the isolated organisms in 47.3% of patients; however, a lack of VACS-covering empirical therapy was not associated with readmission.The isolation of a VACS organism in our setting was often not associated with documented water exposure, which has implications for empiric antimicrobial therapy. Severe disease and death were uncommon.
Population pharmacokinetics of unbound cefazolin in infected hospitalized patients requiring intermittent high-flux haemodialysis: can a three-times-weekly post-dialysis dosing regimen provide optimal treatment?
2024-11-04, Duke, Carleigh, Parker, Suzanne L, Zam, Betty B, Chiong, Fabian, Sajiv, Cherian, Pawar, Basant, Ashok, Aadith, Cooper, Brynley, Tong, Steven Y C, Janson, Sonja, Wallis, Steven C, Roberts, Jason A, Tsai, Danny
To describe the population pharmacokinetics of cefazolin in infected hospitalized patients requiring intermittent haemodialysis (IHD).This prospective population pharmacokinetic study was conducted in IHD patients prescribed cefazolin 2 g three times weekly. Plasma samples were collected at prespecified timepoints and assayed for total and unbound concentrations using validated LC. Pharmacokinetic modelling and dosing simulations were performed using Pmetrics®. PTA in plasma suitable for MSSA (unbound trough concentrations of ≥2 mg/L for the final 24 h of a 72 h interval) were simulated for different dosing regimens. A PTA of ≥95% was deemed acceptable.A total of 260 cefazolin concentrations (130 total, 130 unbound) were collected from 16 patients (14 female) with a median age of 51 years. The median (IQR) pre-dialysis unbound cefazolin concentration for a 3 day dose interval trough was 17.7 (13.5-31.4) mg/L. The median (IQR) unbound fraction was 0.38 (0.32-0.46). The lowest pre-dialysis unbound concentration was 9.1 mg/L. A two-compartment model with a complex protein-binding component adequately described the data. The mean unbound cefazolin CL during IHD was 16.4 ± 4.26 L/h, compared with 0.40 ± 0.19 L/h when dialysis was off. Duration of time on haemodialysis (TOH) was the only covariate supported in the final model. The 2 g three-times-weekly regimen was associated with a PTA of 99.7% on dosing simulations to maintain unbound concentrations of ≥2 mg/L with TOH of 6 months. The 1 g three-times-weekly post-dialysis was associated with a PTA of 95.4%.A 2 g three-times-weekly post-dialysis cefazolin regimen is supported for MSSA infections.
The Australasian Registry for Severe Cutaneous Adverse Reactions (AUS-SCAR) - Providing a roadmap for closing the diagnostic, patient, and healthcare gaps for a group of rare drug eruptions.
2024-08-01, James, Fiona, Goh, Michelle S, Vogrin, Sara, Ng, Irvin, Douglas, Abby P, Holmes, Natasha E, Chua, Kyra Yl, De Luca, Joseph, Sharma, Pooja, Zubrinich, Celia, Aung, Ar K, Gin, Douglas, Lambros, Belinda, Baker, Chris, Foley, Peter, Chong, Alvin H, Thien, Francis, Fok, Jie S, Su, John, Scardamaglia, Laura, Awad, Andrew, Tong, Steven, Johnson, Douglas, Godsell, Jack, Arasu, Alexis, Barnes, Sara, Ojaimi, Samar, Mar, Adrian, Yun, James, Ange, Nikhita, Tong, Winnie W Y, Carr, Andrew, Loprete, Jacqueline, Katelaris, Constance H, Slape, Dana, Keat, Karuna, West, Timothy A, Lee, Monique, Smith, William, Hissaria, Pravin, Sidhu, Shireen, Janson, Sonja, Venkatesan, Sudharsan, Davies, Jane, Lane, Michael J, Redmond, Andrew M, Robertson, Ivan, Legg, Amy, Fernando, Suran, Boyle, Therese, Li, Jamma, Phillips, Elizabeth J, Cleland, Heather, Kern, Johannes S, Trubiano, Jason A
Severe cutaneous adverse reactions (SCAR) are a group of delayed presumed T-cell mediated hypersensitivities associated with significant morbidity and mortality. Despite their shared global healthcare burden and impact, the clinical phenotypes, genomic predisposition, drug causality, and treatment outcomes may vary. We describe the establishment and results from the first Australasian registry for SCAR (AUS-SCAR), that via a collaborative network advances strategies for the prevention, diagnosis and treatment of SCAR.Prospective multi-center registry of SCAR in Australian adult and adolescents, with planned regional expansion. The registry collects externally verified phenotypic data drug causality, therapeutics and long-term patient outcomes. In addition, biorepository specimens and DNA are collected at participating sites.we report on the first 100 patients enrolled in the AUS-SCAR database. DRESS (50%) is the most predominant phenotype followed by SJS/TEN (39%) and AGEP (10%), with median age of 52 years old (IQR 37.5, 66) with 1:1 male-to-female ratio. The median latency for all implicated drugs is highly variable but similar for DRESS (median 15 days IQR 5,25) and SJS/TEN (median 21 days, IQR 7,27), while lowest for AGEP (median 2.5 days, IQR 1,8). Antibiotics (54.5%) are more commonly listed as primary implicated drug compare with non-antibiotics agent (45.5%). Mortality rate at 90 days was highest in SJS/TEN at 23.1%, followed by DRESS (4%) and AGEP (0%).In the first prospective national phenotypic and biorepository of SCAR in the southern hemisphere we demonstrate notable differences to other reported registries; including DRESS-predominant phenotype, varied antibiotic causality and low overall mortality rate. This study also highlights the lack of standardised preventative pharmacogenomic measures and / diagnostic strategies to ascertain drug causality.ANZCTR ACTRN12619000241134. Registered 19 February 2019.
Adult penicillin allergy programmes in Australian hospitals: a practical guide from the National Antibiotic Allergy Network.
2024-10-23, Hannah, Rory, Mitri, Elise, Katelaris, Constance H, O'Hern, Jennifer, Avent, Minyon, Valoppi, Glenn, Rawlins, Matthew, Frith, Catherine, McMullan, Brendan, Kong, David, Chua, Kyra, Legg, Amy, James, Rod, Janson, Sonja, Hawkins, Carolyn, Randall, Katrina, Ierano, Courtney, Thursky, Karin, Trubiano, Jason A
Penicillin allergy is a significant burden on patient, prescribing and hospital outcomes. There has been increasing interest in the incorporation of penicillin allergy testing (i.e. delabelling) into antimicrobial stewardship (AMS) programmes to reduce the burden of penicillin allergy labels and improve prescribing. In particular, there has been a focus on point-of-care penicillin allergy assessment and direct oral challenge for low-risk phenotypes. The National Antibiotic Allergy Network has provided a guide to assist AMS clinicians with the incorporation of penicillin allergy programmes, in particular direct oral challenge, into Australian hospitals.
Adverse reactions to trimethoprim/sulfamethoxazole for melioidosis eradication therapy: an evaluation of frequency and risk factors.
2024-11-07, Martin, Genevieve, Bramwell, Joshua, Gadil, Eden, Woerle, Celeste, Ewin, Thomas, Davies, Jane, Janson, Sonja, Currie, Bart
Trimethoprim/sulfamethoxazole is the first-line agent for oral eradication therapy for melioidosis but has been associated with toxicity in this context. This study aimed to quantify adverse drug reactions (ADRs) to trimethoprim/sulfamethoxazole when used for treatment of melioidosis, and assess risk factors for ADR development. A retrospective review of antimicrobial associated ADRs was performed in all patients treated for melioidosis in the Northern Territory of Australia from January 2017 - September 2022. Over this time, 268 treatment episodes from 256 individuals were included. The frequency of clinician-attributed ADRs to trimethoprim/sulfamethoxazole (51% of exposed) was higher than for other antimicrobials used (ceftazidime 12%, meropenem 8% and doxycycline 12% of those exposed; p<0.0001). 44% of those treated with trimethoprim/sulfamethoxazole required drug cessation or dose reduction and 5 individuals (2%) had a severe cutaneous adverse reaction, with one fatality. Acute kidney injury was the most frequent ADR (25% of those exposed), with age and pre-existing renal disease independently associated with its development. Here we report very high rates of ADRs attributed to trimethoprim/sulfamethoxazole resulting in frequent discontinuation of this drug as part of oral eradication therapy for melioidosis. Further work is needed to balance the necessity and toxicity of this drug in this clinical context.
Declining soil transmitted helminth detections in an Australian tropical region.
2019-12-01, Hung, Te-Yu, Janson, Sonja, Smith P, Legg A, Baird, Robert
Soil-transmitted helminths (STHs), are recognised neglected tropical diseases and have been endemic in patients in tropical Northern Australia. We reviewed the temporal trends in detections of STHs and Hymenolepis nana in faecal samples from Northern Territory (NT) Government Health facilities, representing patients with acute illnesses and comorbidities between 2008 and 2018. Ascaris lumbricoides is not detected in patients in the NT. The number of faecal samples examined yearly was relatively constant with a median of 4458 (range 4246-4933). Faecal samples from patients under the age of 5 years declined by 45% over the 11 years of the study. Detections of Trichuris trichiura, Strongyloides spp., and hookworm ova fell significantly by 89% (p<0.001), 71% (p<0.001), and 43% (p<0.01), respectively, over the 11 years. Detections of H. nana declined by 33% absolutely, but not significantly, when assessed relative to the reduction in faecal samples from patients under the age of 5 years. The marked reduction in STH numbers coincided with a 10-fold increase in NT dispensing of ivermectin, predominantly used for scabies control, in widely geographically spaced locations throughout the NT, over the 11 years of the study. Our data support previous findings of the beneficial collateral effects of ivermectin therapy. Ivermectin is not recognised as having anti-cestode activity, hence the continued presence of H. nana endemically in the NT, suggests declines in STHs are not related to other changes in health hardware or existing mass drug administration programs. The reduction in T. trichiura detections may not be explained by this association, as unlike Strongyloides spp., the anti-helminthic effect of ivermectin has been less marked.