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Augmented renal clearance (ARC) refers to the enhanced renal excretion of circulating solute commonly demonstrated in numerous critically ill subgroups. This study aimed to describe the prevalence of ARC in critically ill Indigenous Australian patients and explore the accuracy of commonly employed mathematical estimates of glomerular filtration. We completed a single-centre, prospective, observational study in the intensive care unit (ICU), Alice Springs Hospital, Central Australia. Participants were critically ill adult Indigenous and non-Indigenous Australian patients with a urinary catheter in situ. Exclusion criteria were anuria, pregnancy or the requirement for renal replacement therapy. Daily eight-hour measured creatinine clearances (CrCLm) were collected throughout the ICU stay. ARC was defined by a CrCLm≥130 ml/min/1.73 m2. The Cockcroft– Gault and Chronic Kidney Disease Epidemiology Collaboration equations were also used to calculate mathematical estimates for comparison. In total, 131 patients were recruited (97 Indigenous, 34 non-Indigenous) and 445 samples were collected. The median (range) CrCLmwas 93.0 (5.14 to 205.2) and 90.4 (18.7 to 206.8) ml/min/1.73 m2in Indigenous and non-Indigenous patients, respectively. Thirty-one of 97 (32%) Indigenous patients manifested ARC, compared to 7 of 34 (21%) non-Indigenous patients (P=0.21). Younger age, major surgery, higher baseline renal function and an absence of diabetes were all associated with ARC. Both mathematical estimates manifest limited accuracy. ARC was prevalent in critically ill Indigenous patients, which places them at significant risk of underdosing with renally excreted drugs. CrCLmshould be obtained wherever possible to ensure accurate dosing.

In the absence of specific data to guide optimal dosing, this study aimed to describe the pharmacokinetics of ceftriaxone in severely septic Australian Indigenous patients and to assess achievement of the pharmacodynamic target of the regimens prescribed. A pharmacokinetic study was conducted in a remote hospital intensive care unit in patients receiving ceftriaxone dosing of 1 g every 12 h (q12h). Serial blood and urine samples were collected over one dosing interval on two consecutive days. Samples were assayed using a validated chromatography method for total and unbound concentrations. Concentration–time data collected were analysed with a non-compartmental approach. A total of 100 plasma samples were collected from five subjects. Ceftriaxone clearance, volume of distribution at steady-state, elimination half-life and elimination rate constant estimates were 0.9 (0.6–1.5) L/h, 11.2 (7.6–13.4) L, 9.5 (3.2–10.2) h and 0.07 (0.07–0.21) h –1 , respectively. The unbound fraction of ceftriaxone ranged between 14% and 43%, with a higher unbound fraction present at higher total concentrations. The unbound concentrations at 720 min from the initiation of infusion for the first and second dosing intervals were 7.2 (4.8–10.7) mg/L and 7.8 (4.7–12.1) mg/L respectively, which exceeds the minimum inhibitory concentration of all typical target pathogens. In conclusion, the regimen of ceftriaxone 1 g q12h is adequate for critically ill Australian Indigenous patients with severe sepsis caused by non-resistant pathogens.

Currently there are no pharmacokinetic (PK) data to guide antibiotic dosing in critically ill Australian Indigenous patients with severe sepsis. This study aimed to determine whether the population pharmacokinetics of meropenem were different between critically ill Australian Indigenous and critically ill Caucasian patients. Serial plasma and urine samples as well as clinical and demographic data were collected over two dosing intervals from critically ill Australian Indigenous patients. Plasma meropenem concentrations were assayed by validated chromatography. Concentration–time data were analysed with data from a previous PK study in critically ill Caucasian patients using Pmetrics. The population PK model was subsequently used for Monte Carlo dosing simulations to describe optimal doses for these patients. Six Indigenous and five Caucasian subjects were included. A two-compartment model described the data adequately, with meropenem clearance and volume of distribution of the central compartment described by creatinine clearance (CL Cr ) and patient weight, respectively. Patient ethnicity was not supported as a covariate in the final model. Significant differences were observed for meropenem clearance between the Indigenous and Caucasian groups [median 11.0 (range 3.0–14.1) L/h vs. 17.4 (4.3–30.3) L/h, respectively; P 0.01]. Standard dosing regimens (1 g intravenous every 8 h as a 30-min infusion) consistently achieved target exposures at the minimum inhibitory concentration breakpoint in the absence of augmented renal clearance. No significant interethnic differences in meropenem pharmacokinetics between the Indigenous and Caucasian groups were detected and CL Cr was found to be the strongest determinant of appropriate dosing regimens.

Background An outbreak of serotype 1 invasive pneumococcal disease (IPD) occurred in Central Australia from October 2010 to the latter part of 2012. Surveillance of serotype 1 carriage was conducted to determine epidemiological features of asymptomatic carriage that could potentially be driving the outbreak. Methods 130 patients and accompanying persons presenting at Alice Springs Hospital Emergency Department consented to nasopharyngeal swab (NPS) collection. NPS were processed by standard methods, including culture, pneumococcal lytA quantitative real-time PCR, serotype 1-specific real-time PCR and multi-locus sequence typing (MLST). Results Pneumococcal carriage was detected in 16% of participants. Carriage was highest in the under 10 year olds from remote communities surrounding Alice Springs (75%). Four NPS were positive for serotype 1 DNA by PCR; 3 were also culture-positive for serotype 1 pneumococci. Serotype 1 isolates had atypical colony morphology on primary culture. All serotype 1 carriers were healthy children 5 to 8 years of age from remote communities. By MLST, serotype 1 isolates were ST306, as were IPD isolates associated with this outbreak. Conclusions During an outbreak of serotype 1 ST306 IPD, carriage of the outbreak strain was detected in 3% NPS collected. All carriers were healthy children 5 to 8 years of age.