Making the most of antibiotics

It was 1928 when the murderous effects on bacteria of a fungus called Penicillium were first noted, heralding the start of the antibiotic era. In the decades since, antibiotics have saved millions of lives, but their effectiveness has been reduced as an increasing number of bacteria become resistant to them. PENNY FANNIN reports on Monash research that seeks to lengthen the lifespan of current antibiotics, resurrect old antibiotics and improve the use of anti-viral compounds.

There are millions of children worldwide with human immunodeficiency virus (HIV). Many children are born with the disease, the infection having been transmitted from mother to baby during birth. Although some HIV-positive mothers receive anti-retroviral drugs to help control the virus, transmission to their babies may still occur.

Now a research team from the Department of Pharmacy Practice in Monash University's Faculty of Pharmacy is looking at the factors involved in the movement of anti-HIV drugs from the maternal circulation across the placenta and to the foetus. PhD researcher Ms Sreeja Sudhakaran is investigating the process of drug transfer with Professor Roger Nation and Dr Craig Rayner from Pharmacy and colleagues from the Royal Women's and Austin hospitals.

Addressing drug resistance: Clockwise from back left, Ms Sreeja Sudhakaran, Dr Jian Li, Dr Craig Rayner and Professor Roger Nation are working to prolong the shelf life of antibiotics. Photo: Melissa Di Ciero

The research has implications for treating mother-to-foetus transfer of HIV, says Professor Nation, head of the Department of Pharmacy Practice. "Usually, drugs pass back and forth across the placenta. But the anti-HIV drug we're currently investigating is prevented from reaching the foetus by the placenta, which actively pumps it back into the mother's bloodstream," he says.

Work is now under way that will hopefully stop this process so the drug can be effectively delivered to the foetus around the birthing time, which is when the risk of HIV transmission is at its highest.

The research is part of a broader mission to identify the best dosing regimes for antibiotics and anti-viral and anti-fungal preparations so they are effective against infection for as long as possible. "In the case of the anti-HIV drug, we hope to develop a novel strategy for reducing HIV transmission," Professor Nation says. "We might find some drugs are less likely to be transported away from the foetus, and these may therefore more readily achieve anti-viral levels in the foetus."

The focus on optimising the effectiveness and lifespan of antibiotics and other drugs has been consolidated at the university by a Monash Research Fund new research area grant that has led to the establishment of a Facility for Anti-infective Drug Development and Innovation (FADDI). FADDI's activities are largely driven by research from the Department of Pharmacy Practice but also involve researchers from the Department of Pharmaceutics.

"The facility is a focal point for grant-driven research but is also attractive to both the Australian and international pharmaceutical industries. The principles we are developing to optimise antibiotic use are going to be of great importance to the industry," Professor Nation says.

Late last year, the research team received two grants from Australia's National Health and Medical Research Council to minimise the development of resistance to, and improve the safety of, two antibiotics -- colistin and linezolid.

"Multi-drug resistance in bacteria is increasing at an alarming rate, and we want to find smarter ways of using antibiotics to minimise the development of resistance and to allow these medicines to be used safely and effectively," Professor Nation says.

He is working with Dr Jian Li and Dr Rayner from Monash as well as Dr Robert Milne from the University of South Australia and Professor John Turnidge and Associate Professor Kingsley Coulthard from the Women's and Children's Hospital in Adelaide to investigate the effectiveness of colistin in treating the lung infections of patients with cystic fibrosis (CF).

In CF patients, lung infections with the bacterium Pseudomonas are a major problem -- and a major cause of death. The antibiotics that have been used to treat these infections are no longer as effective as they used to be because Pseudomonas has developed resistance.

"However, colistin appears to be an effective treatment, and we are investigating how this antibiotic, which has been around for more than 40 years, could best be used to help CF patients," Dr Li says.

Dr Rayner and Professor Nation, in collaboration with colleagues at the Austin and Alfred hospitals, are also trying to find ways of increasing the lifespan of a new 'last line of defence' drug, linezolid, which has been available in Australia for the past two years.

"Linezolid is used to treat Golden Staph infections and vancomycin-resistant infections," Dr Rayner says. "Vancomycin was thought to be the last line of defence, but there are patients who are intolerant to vancomycin and also some Staph infections that don't respond to vancomycin."

"Worryingly, there are signs that resistance to linezolid may occur. We want to increase the usefulness and lifespan of this important last-line antibiotic by developing new dosing strategies that have a reduced possibility of resistance emerging and that are well tolerated by patients." Ms Lauren Boak, a PhD researcher, has recently started work on this project.

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For more information, contact Professor Roger Nation on +61 3 9903 9061 or email roger.nation@vcp.monash.edu.au.