Epidemiology, management and outcomes of Cryptococcus gattii infections: A 22-year cohort.

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.

Detection of Mycobacterium leprae by PCR testing of sputa from a patient with pulmonary cryptococcus coinfection in northern Australia.

A case of fever, sepsis, and chest lesions evident on a computed tomography scan of an indigenous man in northern Australia following burns to the feet is described. Sputum PCR testing revealed Mycobacterium leprae, and a fine-needle aspirate of the chest lesions demonstrated Cryptococcus coinfection.

Feasibility of latent tuberculosis infection diagnosis by interferon-γ release assay remote from testing facilities.

Although the tuberculin skin test (TST) has been the mainstay of the diagnosis of latent tuberculosis infection (LTBI) for many decades, interferon-gamma release assays (IGRAs) are gaining acceptance and are more specific for this diagnosis. The characteristics of one such IGRA, the QuantiFERON-TB Gold Whole Blood In-Tube, make it feasible for use in a remote setting. This study performed 62 IGRAs with this test on individuals testing positive by TST, in a clinical setting over 3,000 km from the testing laboratory. Of these, 42 patients (68%) recorded negative results, 19 (31%) were positive, with only 1 result (2%) indeterminate. Negative, and therefore discordant in this study, test results were more common in those known to have been previously vaccinated with bacille Calmette-Guérin. These results are consistent with other reports, indicating that this approach to testing is logistically feasible, and has the potential to complement LTBI screening to assist tuberculosis control programs in settings remote from the testing laboratory.

Does aminoglycoside therapy cause significant acute kidney injury in febrile neutropenia?

Owing to concern about aminoglycoside-related acute kidney injury (AKI) in therapy for febrile neutropenia, the aim of this study was to ascertain the incidence, severity and persistence of AKI secondary to aminoglycoside use for febrile neutropenia at an adult tertiary referral hospital. All admitted adults with neutropenia in a 27-month period were reviewed. Cases of febrile neutropenia due to chemotherapy who received an aminoglycoside were identified and renal function was assessed up to Day 30 after aminoglycoside administration. Transient renal impairment (TRI) was defined as any temporary rise in serum creatinine of >44 µmol/L within 30 days; and persistent, significant renal impairment (PSRI) was defined as an elevation of serum creatinine of >44 µmol/L at Day 30, or death from renal failure or need for dialysis. The Acute Kidney Injury Network (AKIN) stage for all episodes was also determined. Amongst 554 episodes of neutropenia, 148 episodes of chemotherapy-related febrile neutropenia with aminoglycoside treatment were identified. PSRI occurred in six episodes [4.1%; 95% confidence interval (CI) 1.9-8.6%] and TRI occurred in seven episodes (4.7%; 95% CI 2.3-9.4%). No PSRI was attributable to aminoglycoside therapy alone (0%; 95% CI 0-3.2%). Severe sepsis was the main cause of PSRI. Aminoglycoside therapy was the main contributing cause of TRI in two episodes (1.4%; 95% CI 0.2-5.3%). In conclusion, PSRI is a rare complication of aminoglycoside therapy for febrile neutropenia at this institution. AKIN stage 1 AKI is a common complication of febrile neutropenia episodes in which aminoglycosides are administered.