Promoting equitable access to effective treatment for Staphylococcus aureus bacteraemia in Aotearoa: probenecid-boosted oral antibiotic dosing in the SNAP study (PR-O-SNAP)

Staphylococcus aureus bacteraemia (SAB) is one of the most common serious bacterial infections seen in Aotearoa New Zealand. A conservative estimate for the incidence of SAB in the country is around 1100 people per year, which is amongst the highest reported in the developed world.

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Principal Investigator
Dr Max Bloomfield and Dr Genevieve Walls
Aotearoa Clinical Trials Trust, The Peter Doherty Institute for Infection and Immunity, University of Queensland Centre for Clinical Research
Public Contact
Edward Watson
027 630 2782
Project Timeframe/Status
In Process

Whakarāpopoto Rangahau Summary of Research

Staphylococcus aureus bacteraemia (SAB) is one of the most common serious bacterial infections seen in Aotearoa New Zealand. A conservative estimate for the incidence of SAB in the country is around 1100 people per year, which is amongst the highest reported in the developed world. SAB carries a 15-20% mortality, and patients with SAB typically have prolonged hospital stays. SAB disproportionately affects Māori and Pacific Peoples, babies, the elderly, and those living in socioeconomically deprived areas. Current SAB treatment involves prolonged courses (several weeks) of exclusively intravenous (IV) beta lactam antibiotics.

Prolonged IV antibiotics are associated with increased risk of adverse effects and complications, inconvenience for the patient, and cost, compared with oral antibiotics. There is no evidence to demonstrate the superiority of IV administration in terms of clinical outcomes. There are also many areas of Aotearoa New Zealand that have limited access to home-based IV antibiotic therapy (OPAT), meaning patients in these areas with SAB need to travel long distances or remain in hospital for treatment. These areas are commonly more rural, have higher Māori populations and are more socioeconomically deprived. 

The publication of several high-quality studies of early transition to oral antibiotics after a short period of IV treatment (‘early oral switch’) in complicated and uncomplicated Staphylococcus aureus infection scenarios (not necessarily bloodstream infection) has prompted interest in investigating this strategy for SAB treatment. Pre-clinical evidence from work by researchers in Aotearoa New Zealand suggests co-administration of oral beta-lactams with probenecid (probenecid-beta-lactam combination therapy – PCT) significantly improves blood levels of the beta-lactam antibiotic (drug exposure), often to the extent where levels achieved via the oral route could be considered pharmacodynamically ‘equivalent’ to those achieved via IV administration.

This evidence, suggesting PCT is a safe and effective alternative to weeks of IV antibiotic therapy, does not meet the high threshold required to change clinical practice, or be incorporated into SAB treatment guidelines. 

The aim of the proposed study is to produce robust pharmacological and clinical data demonstrating that PCT achieves drug exposure that is equivalent to what is achieved with IV therapy. This would provide evidence supporting the shortening and replacement of prolonged IV antibiotic courses for SAB with oral treatment.  

This project will leverage the existing infrastructure associated with the Staphylococcus aureus network adaptive platform trial (SNAP), which is an international study of SAB that is active in many locations in Aotearoa New Zealand already. Patients enrolled in SNAP who consent to enrolment into the PR-O-SNAP study would have blood samples collected at 2-3 different time points during their treatment to assess drug exposure whilst on IV therapy and PCT. Pharmacodynamic modelling will be used to compare the drug exposure achieved at the different time points.

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Te Hiranga a Rangahau Research Impact

Based on existing evidence it is expected that PR-O-SNAP will demonstrate equivalent drug exposure with PCT compared to IV therapy. The data generated are expected to contribute to changes to evidence-based guidelines for SAB treatment in NZ and worldwide. This is expected to produce benefits both at the individual patient and at a healthcare system level: 

Patient level:  

Enable intravenous access devices to be removed earlier, reducing the risks and complications associated with these e.g. infection, thrombosis. 

Increase options regarding location of care delivery for SAB, including home-based care, with better access to whānau support, earlier return to work, and other activities of daily living. This will particularly be the case in areas with poor access to OPAT services, which tend to be more rural and socially deprived. 

Provide pharmacological data on the drug exposure achieved with beta-lactam antibiotic therapy in Māori and Pacific people. Dosing regimens for these common drugs are predominantly based on overseas populations, with minimal to no representation from Māori or Pacific People. Ethnic differences are known to occur with drug pharmacokinetics.  

Healthcare system level:  

Intravenous treatment is considerably more expensive than oral antibiotic treatment, requires nursing time to administer, and requires administrative and district nursing support to enable delivery at home. It also takes time to arrange OPAT, which delays discharge from hospital, contributing to bed-block. This is highly relevant currently, with inpatient services in NZ under unprecedented strain, and nursing shortages at crisis levels.  

The ability to use oral antibiotics in place of IV would therefore have the potential to greatly reduce these costs and resource requirements. From a purely monetary perspective an extremely conservative estimate of 1 day length of stay reduction per patient with SAB, multiplied by $800/day to stay in hospital = 1100 patients/year x $800 = $880,000 per year saved by the NZ health system (based on inpatient bed costs at Te Whatu Ora - Counties Manukau).  

Furthermore, the results from this study would likely be translatable to other serious infections that are managed with prolonged IV beta-lactam therapy, such as infective endocarditis and complicated bone and joint infections, which would amplify the benefits cited above.

Te Niwha

Kairangahau Research Personnel

Dr Max Bloomfield, Infectious Disease Consultant
Te Whatu Ora – Capital and Coast; Clinical Microbiologist, Awanui Labs Wellington

Dr Genevieve Walls, Infectious Disease Consultant
Te Whatu Ora – Counties Manukau

​​Dr​ Diana McNeill, Tapuika, Ngati Moko, Tuhourangi, Co-investigator
Te Whatu Ora, Counties Manukau  

Dr​ Viliame Tutone, Co-investigator 
Te Whatu Ora, Counties Manukau  

​​Dr​ Hannah Burden, Project Manager 
Aotearoa Clinical Trials   

Associate Professor​ Mei Zhang, Drug Analyst
Te Whatu Ora, Waitaha Canterbury   

Dr Paul Chin, Clinical Pharmacologist
Te Whatu Ora, Waitaha Canterbury 

Project status

In process


Te Whatu Ora hospital locations
Te Toka Tumai Auckland Counties Manukau
Hauora a Toi Bay of Plenty
Capital Coast & Hutt Valley
Waitaha Canterbury​  


Te Niwha