Tag Archives: antimicrobial usage

“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

“Use and Abuse”

Antimicrobial Resistance, ,

You can produce sophisticated and comprehensive antimicrobial resistance surveillance data.

You can adhere to the best infection control policies in the country.

You can have a “search and destroy” policy for multi-resistant organisms.

and you can even develop and bring out a new antibiotic every couple of years….

But unless you control antibiotic consumption (usage), you will always be fighting an uphill battle.

In order to control antibiotic consumption you need to know how  many antibiotics are being used in the first place.

One of the problems is that antimicrobial resistance surveillance data is produced by microbiologists. Antibiotic consumption data is produced by pharmacists. Antibiotic consumption data even in this day and age can still be difficult to get hold of. Sometimes I wonder if the companies selling the antibiotics to the hospitals have a much better handle on consumption data than the microbiologists do!

Microbiologists and pharmacists need to talk to each other more. It is such a key relationship in the antimicrobial stewardship world.

Antibiotic usage needs to be surveyed and controlled not only at an individual level, but at a national level. Communities and hospitals, humans and animals. It all adds up… Too often I have sat in conferences and seen pretty graphs of antimicrobial resistance data, without complementary antibiotic consumption data to put the resistance data into context. I find it all a bit frustrating…

If reducing antibiotic usage was easy it would already have happened. It’s not easy , and there are good reasons for this. (See this article). This is where objective data is key to monitoring and measuring change. Feedback to the “prescriber” is critical.

Every antimicrobial stewardship committee in the world needs to be aware of their consumption data. Otherwise they are simply not doing their job. Surveillance of antibiotic consumption does not seem to get the same profile as resistance data. This is a shame. I would actually argue that it is the more important of the two….

Michael