While sat in the cystic fibrosis multidisciplinary team (MDT) meeting a tricky clinical question was asked…
 
“We have a patient with an infective exacerbation of their cystic fibrosis with Burkholderia multivorans but she is allergic to Ceftazidime and Meropenem and gets bad gastrointestinal symptoms with tetracyclines. What do you think?” asked the Respiratory Consultant.
 
I really like these types of MDTs when I have to scratch my head and try to work out a solution but this one was a bit of a puzzler. I know Ceftazidime and Meropenem are often used to treat infections with Burkholderia spp. and that Minocycline is also an option, but what to do when these can’t be used? I had to admit I didn’t know for sure and that I would have to go and look at the literature and get back to them. So off I went to consultant the “Interweb”.

Antibiotic resistance is a major threat to public health. This isn’t just my opinion but also that of Dame Sally Davies, the Chief Medical Officer for England, as well as the World Health Organisation and other numerous national and international groups. It is not only the treatment of infections that will become impossible but perhaps an even greater threat is that surgery will no longer be possible without an unacceptable risk that the patient will die from a postoperative infection; who would want a surgeon to operate on their bowel without the availability of antibiotics to stop bowel bacteria causing peritonitis afterwards?

So having been thinking about a case of fusarium keratitis last week I started to wonder whether the new antifungal Isavuconazole might have a role to play. I then got to thinking that it would be good to write a summary of Isavuconazole for a blog… so here it is…. :-)

I was walking down the corridor when one of the Medical Registrars walked passed looking perplexed, we said hello and passed on by, then he called after me “oh can I ask your opinion on…” A standard start to many a query for a Microbiologist! But this question was different, he was reading around the subject of endocarditis and was frustrated by the “guidelines” put out there by the expert bodies… he went on “their advice is sometimes different and even contradictory! How do you know what to follow?”
 
I agreed, which didn’t seem to satisfy him at all. So let me explain further in this blog, as it will take longer than a passing corridor conversation, unless you have the old Victorian corridors still, I may be able to explain it in the time it takes to walk one of those, ah the days when we all got more exercise at work.

Sometimes you come across an idea so brilliant and yet so simple that you think to yourself “I wish I’d thought of that!” Well that’s what happened to me at the Federation of Infection Societies annual conference at the beginning of December.
 
I guess I should start by saying I have no affiliation to, or sponsorship from, any company, pharmaceutical or otherwise. I can therefore say I am totally objective, but I was impressed!
 
So what was it I was so impressed by? Well, it’s a beta-lactamase… What, a beta-lactamase!?! But they’re bad, they breakdown antibiotics and stop them working, how can they be a good thing? Well, before we consider the beta-lactamase let’s think about why antibiotics can be bad for you.

The microbiologist had gone to review a patient on the wards when they were stopped and asked for an opinion about a different patient. This patient was being treated for infective endocarditis caused by Staphylococcus aureus and had been on IV Teicoplanin for 2 weeks because they said they were allergic to penicillin. The current problem was that the patient’s renal function was deteriorating and it was thought that the Teicoplanin might be part of the problem (although the patient was also on a few other nephrotoxic drugs but these couldn’t be stopped easily).
 
The Microbiologist knew that the best antibiotic for the infection was a penicillin, Flucloxacillin, so decided to try and get to the bottom of the penicillin allergy story. Side effects from antibiotics are common (e.g. diarrhoea and vomiting) but do not usually represent allergy. They sat down with the patient and asked them to describe what happened when they were last given a penicillin.

On the ward round a patient reported to the doctor that she had developed diarrhoea on the antibiotics that had been given for her community acquired pneumonia (CAP). She had already had 5 days of antibiotics and other than the diarrhoea was feeling much better. The doctor noted the patient was afebrile and looked at the blood tests which showed the white blood cell count and C-reactive protein had reduced considerably. Knowing that the hospital antibiotic guidelines said the treatment for CAP was seven days the doctor decided to call the Microbiologist for advice.
 
The Microbiologist went through the story and the said “okay, you can stop the antibiotics”.
 
“But the guidelines say we should give seven days”, replied the doctor.

​“Yes, but the patient is better” replied the Microbiologist.
 
“So why do the guidelines say seven days then” persisted the doctor.
 
Good point thought the Microbiologist…
 
So why do we have defined durations for courses of antibiotics? Why do these appear to be carved in stone so that no doctor or patient dares to deviate from the principal of “you must finish the course of antibiotics”? Surely the correct length of course is whatever makes the patient feel better?

Okay, it may not look like much but the antibiotic in the diagram above may just represent the saviour of antimicrobial therapy! Or rather, the method by which this antibiotic was created may be what really saves us! I’m very excited!!!
 
The picture shows a modified version of the antibiotic Vancomycin from a paper in Proceedings of the National Academy of Sciences of the United States of America (PNAS… unfortunate acronym!). The authors Okano et al have “manufactured” this new version of Vancomycin to have potent activity against normally Vancomycin-resistant bacteria.

I think I might have missed my calling in life. In the past there were explorers searching out new lands, then plant hunters looking for the next new thing to put in your garden, and now there are “antibiotic hunters”! I want to be one!! Let me explain why…
 
An article in one of Nature’s associated magazines called Biofilm and Microbiomes (B&M) caught my eye; “Komodo dragon-inspired synthetic peptide DRGN-1 promotes wound-healing of a mixed-biofilm infected wound”1. What a catchy title?!
 
The Komodo dragon (Varanus komodoensis) is a massive monitor lizard found on only five islands in Indonesia; Komodo, Rinca, Flores, Gili Motang, and Padar. They grow up to 3 metres long and weigh about 70kg. They have been around for millions of years, a bit like alligators and crocodiles, but are much more dinosaur like than these. They are also capable of short sprints up to 20mph and that’s nearly as fast as Usain Bolt. How do I know all this? I’ve been to Komodo and Rinca to see Komodo dragons and they are amazing.