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15 Sep 2020

Here’s a quick side project before you start your PhD

University of Melbourne Dr Jean Lee, Infectious Diseases Physician and PhD candidate

Staphylococcus epidermidis is the most common bacteria on human skin, found on everyone.

Accordingly, it frequently contaminates diagnostic specimens and many doctors dismiss it. However, serious infections can occur.

In 2012, I was an Infectious Diseases Registrar, and University of Melbourne Professor Ben Howden my Consultant at the Austin Hospital.

We cared for a patient who was the first recognised case in a series of difficult-to-treat S. epidermidis infections.

These cases occurred in unrelated patients and were all serious manifestations (such as a brain abscess) that failed therapy with the first line antibiotic treatment, vancomycin.

When I started my PhD in 2014, determining if there was an outbreak was supposed to be a “quick” side project before starting my PhD on a different organism. However, one finding led to another and this became my entire PhD.

Rather than an outbreak, we discovered three lineages of multidrug-resistant S. epidermidis were endemic in the Austin Hospital. Surprisingly, the Austin wasn’t unique.

These same clones had been globally disseminated for decades, but no one noticed. Some European isolates were even resistant to the last resort antibiotics, making them potentially untreatable.

We found that the mutations causing resistance to the antibiotic rifampicin, that were common to all the clones, also caused vancomycin cross-resistance, explaining why patients failed therapy.

Current guidelines recommend the co-prescription of rifampicin and vancomycin for serious staphylococcal infections, assuming they cross-protect one another. However, our results suggest these guidelines warrant review.

These findings were published last year in Nature Microbiology. Our study demonstrates the unintended consequences of antibiotic use, where an ignored colonising organism has evolved to become resistant to all standard treatment options, driven by rifampicin used as general prophylaxis and antibiotics prescribed to treat other organisms.

Good antimicrobial stewardship remains key against losing remaining treatment options. The research done by our group under University of Melbourne Professors Tim Stinear and Ben Howden attempts to bring infectious diseases from the bedside to the bench, using the laboratory and bioinformatics to answer pertinent clinical questions.

If we are lucky, our findings come full circle to inform clinical practice.

This article was first published in the Celebrating five years of the Doherty Institute Impact Report.

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