Tag Archives: antimicrobial resistance

“Are we too protective of new antibiotics?”

Antimicrobial Resistance, Antimicrobial Stewardship, Confessions of a Microbiologist, ,

By reserving new antibiotics for the sickest of the sick and for the most resistant of resistant organisms, are we essentially making them commercially non-viable?

To be honest I am not really surprised that pharmaceutical industries do not want to invest in development of new antibiotics. Such drugs will only be necessary for a small proportion of the population and unlike many other drugs (e.g. cardiac, arthritis drugs) will only be given for a short duration (i.e. 1-2 weeks).

And then, as antimicrobial stewards, we make matters even worse by insisting that these antibiotics need to be fiercely protected in order to prevent or at least delay the development of antimicrobial resistance.

The consequence of this is that any new antibiotic needs to be priced at ridiculous levels to even have a chance at being commercially viable. Hospitals and governments baulk at such prices and subsequently the new antibiotic becomes almost impossible to get hold of. Industry then has to charge even more to make a return, and thus, a vicious cycle is started.

Have a look at the list of new antibiotics from 2000-202 below:
  • 2000: Linezolid (Zyvox) — The first oxazolidinone, a new class effective against vancomycin-resistant enterococci (VRE) and MRSA.
  • 2003: Daptomycin (Cubicin) — The first lipopeptide approved for skin and skin structure infections.
  • 2005: Tigecycline (Tygacil) — First glycylcycline, a derivative of minocycline designed to overcome resistance.
  • 2010: Ceftaroline fosamil (Teflaro) — First cephalosporin with activity against MRSA.
  • 2011: Fidaxomicin (Dificid) — A macrocyclic antibiotic for Clostridioides difficile.
  • 2012: Bedaquiline (Sirturo) — First diarylquinoline for multi-drug resistant tuberculosis (MDR-TB).
  • 2014: Dalbavancin (Dalvance) & Oritavancin (Orbactiv) — Lipoglycopeptides for acute bacterial skin and skin structure infections (ABSSSI).
  • 2014: Tedizolid (Sivextro) — A second-generation oxazolidinone.
  • 2014: Ceftolozane/tazobactam (Zerbaxa) — Cephalosporin/β-lactamase inhibitor combination.
  • 2015: Ceftazidime/avibactam (Avycaz) — Novel β-lactamase inhibitor combination for serious Gram-negative infections.
  • 2017: Meropenem/vaborbactam (Vabomere) — Combination targeting carbapenem-resistant Enterobacteriaceae (CRE).
  • 2017: Delafloxacin (Baxdela) — An anionic fluoroquinolone with activity against MRSA.
  • 2017: Ozenoxacin (Ozanex) — Topical quinolone.
  • 2018: Plazomicin (Zemdri) — Next-generation aminoglycoside.
  • 2018: Eravacycline (Xerava) — Novel synthetic fluorocycline.
  • 2018: Omadacycline (Nuzyra) — Aminomethylcycline for pneumonia and skin infections.
  • 2018: Sarecycline (Seysara) — Tetracycline for acne.
  • 2019: Cefiderocol (Fetroja) — Siderophore cephalosporin for MDR Gram-negative infections.
  • 2019: Lefamulin (Xenleta) — First systemic pleuromutilin for community-acquired pneumonia (CABP).
  • 2019: Pretomanid — Nitroimidazole for extensively drug-resistant TB (XDR-TB)

Then work out how many antibiotics on this list are available for use at your local hospital? In my local hospital in New Zealand, I could comfortably count on one hand the number of antibiotics from the above list that are available for me as a clinical microbiologist to recommend without multiple barriers to prescribing. The majority are just not available in New Zealand at all…

I would argue that increasing the range of antibiotic classes that are available for use is much more important than restricting the use of new antibiotics.

I am not claiming that we shouldn’t have good antimicrobial stewardship, of course we should. Neither am I claiming that antimicrobial resistance to new antibiotics will not develop if we use them, of course it will. However, if we have more classes of antibiotics available, then one would expect classes that are used infrequently over a certain time period to recover a degree of susceptibility.

I think we need to be encouraging the use of new antibiotics so that they are sufficiently used to get an idea of their efficacy, and so that any developing resistance can be effectively monitored.

If we reserve new antibiotics only for when there are no other options available, then in a country like New Zealand, we might only be using them a few times each year.

We need to be somewhat less zealous in our antimicrobial stewardship efforts when it comes to new antibiotics. We need to work alongside industry, not against them in maximising the range of antibiotics that are available to us. However, the goal should be sustainable use, not reckless use…

I know solutions have been proposed to the above problem, essentially allowing industry to get a return on their investment regardless of how often the new antibiotic is actually used (i.e. de-linking). I remain unconvinced by such proposals as a long-term solution, as it relies on successive governments to both prioritise and fund such initiatives.

I also know that some (possibly most!) of my colleagues will not agree with me on this particular topic. But when we sit on antimicrobial stewardship committees, we need to consider the whole picture, and not try and protect the sanctity of the new antibiotic at all costs…

Michael

“No Pressure”

Antimicrobial Resistance, ,

Have you ever taken yourself, or one of your children, along to a doctor and then either exaggerated the presenting symptoms in order to increase the chances of being prescribed an antibiotic?

Or have you ever directly asked the doctor to prescribe an antibiotic, either subtly or not so subtly…?

I am guilty as charged, because I am human like everyone else. However I am improving now that a large part of my job is anti-microbial stewardship!

And because doctors are human as well, they often give in to such demands, because they want the patient to leave the consultation having had a positive opinion of them, even if the antibiotic itself will make no difference to the outcome or speed of resolution of infection.

This week is World Antibiotic Awareness Week, an initiative by the World Health Organisation to make people aware of the potential dangers of overuse of antibiotics. There is plenty of useful promotional material available on their website to promote this message.

However, I believe that creating a “No pressure” culture is one of the key elements of antibiotic awareness amongst the general public. This is the concept of allowing your doctor to make an objective decision as to whether an antibiotic is required. I.e. you go to your doctor, relate the symptoms to them as honestly as possible, you do not pressurise the doctor for any particular type of treatment , and accept whatever treatment choices that the doctor makes.

As most of you are aware, antibiotics are completely futile for many of the conditions that a family doctor will see each day.

An antibiotic prescription in general practice should be the exception, not the norm.

Amidst all the various components of antimicrobial stewardship, I believe the key is reducing antibiotic usage by reducing inappropriate or unnecessary antibiotic prescriptions.

This is not just the responsibility of doctors, but of patients as well.

By all means, go to your doctor, but don’t go in the expectation that you will receive an antibiotic. If you end up getting one, so be it, but don’t push for it.

No pressure…

Michael

“Trending…”

Antimicrobial Resistance, Confessions of a Microbiologist, Data Interpretation,

I get the occasional anxious phone call from clinicians concerned about the “rising rates ” of trimethoprim resistance to E. coli…

Not being entirely convinced, I did a (20 year) search for E. coli resistance to trimethoprim at my lab, analysing over 2 million isolates, and came up with the following graph.

capture

 

I couldn’t work out how to insert a trendline into the graph (I am so useless…), but I think you will agree that it is going to be fairly flat.

The antibiotic apocalypse is not arriving in New Zealand anytime soon. In fact the whole concept of “antibiotic resistance” as perceived by the public is horribly generic and oversimplified…

This example above of course is just one microbe/antimicrobial combination out of many hundreds that could have been analysed, but the observation did highlight a couple of things to me:

  • If antibiotic usage is relatively constant in a population over a prolonged period of time, then antimicrobial resistance does not necessarily rise inexorably. (q.e.d.)
  • Always back your claims up with objective data wherever possible. It is the trends which are critical in the surveillance of antibiotic resistance. We are lucky that at my lab we can now search back through 20 years of electronic data. Before 1996 the data was paper based (and likely lost in a basement or incinerated by now!)

If you did a similar exercise for all the possible microbe/anti-microbial combinations (I just might if the Christmas holidays are quiet!), you will find some trends that are upwards, some that are static, and some where the resistance rate is trending downwards.

A bit like Twitter really….

So when someone says to you. “Antibiotic resistance is increasing all the time. In 10 years time, all infections will essentially be untreatable” (I really detest this type of generic, off the cuff, unsubstantiated statement…)

…you should respond with something along the lines of “Exactly which microbe and antimicrobial combination are you talking about?” and “Show me your data…”.

Some infections will be, and already are, untreatable (mostly due to extreme and focused selection pressure), but the chances of a whole bacterial species becoming pan-resistant are remote. There are two main reasons for this. i) Bacteria survive in open systems, and ii) Bacteria need to expend energy to become resistant.

But these are other stories altogether…

Michael