Optimised dosing of vancomycin in critically ill Indigenous Australian patients with severe sepsis.

Vancomycin is a commonly used antibiotic due to the high burden of methicillin-resistant Staphylococcus aureus infections. This study aimed to describe the pharmacokinetics (PK) of vancomycin in Australian Indigenous patients with severe sepsis, and advise an optimal dosing strategy. A population PK study was conducted in a remote Australian intensive care unit (ICU). Serial plasma samples were collected over one to two dosing intervals and assayed by validated chromatography. Concentration-time data collected were analysed using Pmetrics® software. The final population PK model was then used for Monte Carlo dosing simulations to determine optimal loading and intermittent maintenance doses. Fifteen Indigenous subjects were included for analysis with a median (interquartile range, IQR) age, weight and creatinine clearance (CrCL) of 43 (34-46) years, 73 (66-104) kg and 99 (56-139) ml/minute respectively. A two-compartment model described the data adequately. Vancomycin clearance (CL) and volume of distribution of the central compartment (Vc) were described by CrCL and patient weight respectively. Median (IQR) CL, Vc, distribution rate constants from central to peripheral, and from peripheral to central compartments were 4.6 (3.8-5.6) litres per hour, 25.4 (16.1-31.3) litres, 0.46 (0.28-0.52)/hour and 0.25 (0.12-0.37)/hour respectively. No significant interethnic PK differences were observed in comparison to published data. Therapeutic loading doses were significantly dependent on both weight and CrCL, whereas maintenance doses were dependent on CrCL. In the absence of severe renal impairment, initiation of maintenance dose eight hours post-loading dose achieved higher probability of target attainment at 24 hours. This is the first report of vancomycin PK in this patient group.

The rise of methicillin resistant Staphylococcus aureus: now the dominant cause of skin and soft tissue infection in Central Australia.

This study aimed to examine the epidemiology and treatment outcomes of community-onset purulent staphylococcal skin and soft tissue infections (SSTI) in Central Australia. We performed a prospective observational study of patients hospitalised with community-onset purulent staphylococcal SSTI (n = 160). Indigenous patients accounted for 78% of cases. Patients were predominantly young adults; however, there were high rates of co-morbid disease. Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) was the dominant phenotype, accounting for 60% of cases. Hospitalisation during the preceding 6 months, and haemodialysis dependence were significant predictors of CA-MRSA infection on univariate analysis. Clinical presentation and treatment outcomes were found to be comparable for methicillin-susceptible S. aureus (MSSA) and methicillin-resistant cases. All MRSA isolates were characterised as non-multi-resistant, with this term used interchangeably with CA-MRSA in this analysis. We did not find an association between receipt of an active antimicrobial agent within the first 48 h, and progression of infection; need for further surgical debridement; unplanned General Practitioner or hospital re-presentation; or need for further antibiotics. At least one adverse outcome was experienced by 39% of patients. Clindamycin resistance was common, while rates of trimethoprim-sulfamethoxazole resistance were low. This study suggested the possibility of healthcare-associated transmission of CA-MRSA. This is the first Australian report of CA-MRSA superseding MSSA as the cause of community onset staphylococcal SSTI.

The Epidemiology of Staphylococcus aureus and Panton-Valentine Leucocidin (pvl) in Central Australia, 2006-2010.

BACKGROUND: The Central Australian Indigenous population has a high incidence of Staphylococcus aureus bacteremia (SAB) but little is known about the local molecular epidemiology. METHODS: Prospective observational study of bacteremic and nasal colonizing S.aureus isolates between June 2006 to June 2010. All isolates underwent single nucleotide polymorphism (SNP) genotyping and testing for the presence of the Panton-Valentine Leucocidin (pvl) gene. RESULTS: Invasive isolates (n = 97) were predominantly ST93 (26.6 %) and pvl positive (54.3 %), which was associated with skin and soft tissue infections (OR 4.35, 95 % CI 1.16, 16.31). Non-multiresistant MRSA accounted for 31.9 % of bacteremic samples and showed a trend to being healthcare associated (OR 2.16, 95 % CI 0.86, 5.40). Non-invasive isolates (n = 54) were rarely ST93 (1.9 %) or pvl positive (7.4 %). CONCLUSIONS: In Central Australia, ST93 was the dominant S.aureus clone, and was frequently pvl positive and associated with an aggressive clinical phenotype. Whether non-nasal carriage is more important with invasive clones or whether colonization occurs only transiently remains to be elucidated.

Human T-cell lymphotropic virus type 1 exposures following blood-borne virus incidents in central Australia, 2002-2012.

We retrospectively audited hospital occupational exposure events over a 10-year period, in a human T-cell lymphotropic virus type 1 (HTLV-1)-endemic area of Central Australia, and report on 53 individuals exposed to HTLV-1 with no transmissions documented (95% confidence interval, 0%-1.5%). This has important implications for the management of exposures including the role of postexposure prophylaxis.

Staphylococcus aureus bacteraemia at Alice Springs Hospital, Central Australia, 2003-2006.

BACKGROUND: Infectious diseases remain the leading cause of death at Alice Springs Hospital (ASH) and Staphylococcus aureus bacteraemia (SAB) is the second most common bloodstream infection. Non-multidrug-resistant, methicillin-resistant S. aureus (nmMRSA) is endemic to the region. AIMS: To determine whether differences exist between racial groups and resistance phenotypes in the clinical manifestations and outcomes of SAB at ASH. METHODS: A retrospective review of medical and pathology records for inpatients with SAB between 1 January 2003 and 31 December 2006. RESULTS: A total of 125 patients (indigenous, 111; non-indigenous, 14) presented with SAB during the study period. Among indigenous patients, there were 95 adults and 16 children. No non-indigenous child was admitted with SAB. The mean annual incidence rate was 160.7/100 000 indigenous population and 8.1/100 000 non-indigenous population (incidence rate ratio 19.9) (P = 0.010). Isolates were predominantly methicillin-susceptible S. aureus (indigenous, 85; non-indigenous, 13). Twenty of 27 MRSA isolates were non-multidrug-resistant. Indigenous adults were more likely to present with an infective focus (indigenous, 75; non-indigenous, 6) (P = 0.004). These were most often skin infections (skin abscesses, 31; scabies, 4). Twenty-seven indigenous adults self-discharged after receiving a median of only 5 days (inter-quartile range (IQR), 3-9) of antibiotic therapy. Ninety-day mortality rates for indigenous and non-indigenous adults were 14.7% and 14.3% respectively. The median age of death for indigenous adults was 50 years (IQR, 37-68). CONCLUSIONS: Indigenous Australians have the highest reported incidence rate of SAB worldwide. This reflects the socioeconomic disadvantage experienced by indigenous Australians whose living conditions predispose to pathogen transmission and limits opportunities to maintain adequate skin hygiene.