Current Epidemiology and Clinical Features of Cryptococcus Infection in Patients Without Human Immunodeficiency Virus: A Multicenter Study in 46 Hospitals in Australia and New Zealand.

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.

Risk factors for mortality in patients with diabetic foot infections: a prospective cohort study.

BACKGROUND: An increasing prevalence of diabetes mellitus has led to a high risk of diabetic foot infections (DFI) and associated morbidity. However, little is known about the relationship between DFI and mortality. AIM: To investigate the risk of mortality and associated factors in patients with DFI in an Australian context. METHODS: A prospective cohort study of inpatients with DFI between May 2012 and October 2016 was done at Royal Darwin Hospital, a tertiary referral hospital for the Top End of the Northern Territory. Primary outcome was 1-year mortality with Cox regression analysis undertaken to assess risk factors for mortality. RESULTS: Four hundred and thirteen consecutive adult diabetic patients with 737 admissions were referred to the High-Risk Foot Service for DFI. Cumulative risk of mortality at 1 year was 8.9% (95% confidence interval (CI) 6.4-12.2). On univariable analysis, mortality was associated with older age (hazard ratio (HR) per year increase 1.08, 95% CI 1.06-1.11, P = 0.001), haemodialysis (HR 3.64, 1.74-7.62, P < 0.001), isolation of Pseudomonas aeruginosa (HR 2.32, 1.05-5.12, P = 0.04) and ischaemic heart disease (HR 2.05, 1.04-4.07, P = 0.04), while indigenous status (HR 0.48, 0.25-0.95, P = 0.04) and HbA1c > 7% (HR 0.45, 0.20-0.99, P < 0.05) were protective. After adjusting for confounders, independent risk factors for mortality were haemodialysis (adjusted HR 5.76, 95% CI 2.28-14.59, P < 0.001) and older age (adjusted HR 1.09, 1.06-1.13, P < 0.001). Patients on haemodialysis had a cumulative risk of mortality of 24.5% (95% CI 14.0-40.8) at 1 year. CONCLUSION: There is a high risk of mortality associated with DFI, substantially increased in patients undergoing haemodialysis, highlighting the importance of early and dedicated interventions targeted at this high-risk group.

Australian guideline on management of diabetes-related foot infection: part of the 2021 Australian evidence-based guidelines for diabetes-related foot disease.

BACKGROUND: Diabetes-related foot infections cause substantial morbidity and mortality, both globally and in Australia. There is a need for up-to-date evidence-based guidelines to ensure optimal management of patients with diabetes-related foot infections. We aimed to identify and adapt high quality international guidelines to the Australian context to become the new Australian evidence-based guideline for people with a diabetes-related foot infection. METHODS: Following Australian National Health and Medical Research Council (NHMRC) procedures we identified the 2019 International Working Group on the Diabetic Foot (IWGDF) guidelines as suitable for adaptation to the Australian context. Guidelines were screened, assessed and judged by an expert panel for the Australian context using the guideline adaptation frameworks ADAPTE and Grading of Recommendations Assessment, Development and Evaluation (GRADE). Judgements led to recommendations being adopted, adapted or excluded, with additional consideration regarding their implementation, monitoring and future research for the Australian context. Clinical pathways were then developed to assist implementation. RESULTS: Of 36 original diabetes-related foot infection IWGDF sub-recommendations, 31 were adopted, four were adapted and one was excluded. Adaption was primarily undertaken due to differences or clarification of the sub-recommendations' intended population. One sub-recommendation was excluded due to substantial differences in judgements between the panel and IWGDF and unacceptable heterogeneity of the target population. Therefore, we developed 35 evidence-based sub-recommendations for the Australian context that should guide best practice diagnosis and management of people with diabetes-related foot infection in Australia. Additionally, we incorporated these sub-recommendations into two clinical pathways to assist Australian health professionals to implement these evidence-based sub-recommendations into clinical practice. The six guidelines and the full protocol can be found at: https://www.diabetesfeetaustralia.org/new-guidelines/ . CONCLUSIONS: A new national guideline for the diagnosis and management of people with diabetes-related foot infections were successfully developed for the Australian context. In combination with simplified clinical pathway tools they provide an evidence-based framework to ensure best management of individuals with diabetes-related foot infections across Australia and highlight considerations for implementation and monitoring.