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.

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.