Tag: #bacteria

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Overhaul of antibiotic pricing – a rational strategy?

Many recent articles have called for overhauling antibiotic pricing as one of the key ways to lure investments in antibiotic development. But, its beneficial effects, in my opinion, are exaggerated.

Alarm bells are being rung with several articles over the last few weeks in the Wall Street Journal, New York Times, and The Washington Post (to name a few) discussing how challenging the climate is for antibiotic developers. Many quoted in these articles call for an overhaul of antibiotic pricing with the central thesis being that such an overhaul will provide much needed revenue and attract investment for struggling antibiotic developers, thus recharging the efforts to combat the antimicrobial crisis. But, will it?

Past efforts to increase drug prices generated a lot of opposition and much hand wringing (see infographic). Those objections were however generally directed towards very expensive cancer drugs or overpricing of drugs. But the fundamental reasons for the opposition have not disappeared.

Certainly, antibiotic developers are struggling. They do not earn anywhere close to the revenue that a successful cancer therapeutic developer would and these struggles are well documented. But what will increasing the price/reimbursement of an antibiotic really do? The thinking goes that if antibiotic developers are successful, it will draw in more money and talent creating a virtual cycle that will be self-sustaining.

But, is it self-sustaining and will it achieve its desired goals? Everyone acknowledges that the two key reasons why antibiotic developers struggle are because (a) hospitals prescribe these new drugs sparingly to avoid building up resistance to them and (b) they try a lower cost alternative first.

When decisions on which antibiotic to use are still based entirely on clinical judgment, i.e. a good educated guess, going with the lower cost option or hoarding a “drug of last resort” is logical and natural. Why do we think that increasing reimbursement will alter this behavior. And unless we do something that changes this dynamic we are not really solving the problem. We are just creating a new special interest.

Antibiotics are the lifeblood of modern medicine. And antimicrobial resistance is a global problem. If the price of the antibiotic were raised, will other countries break patents invoking “national emergencies” much as was done to get inexpensive HIV drugs?

If the drugs are inexpensive in, say India, and are used extensively there because they work, how long do you think it will be before resistance develops for these drugs?

If you went to a physician and after a visual examination, the physician recommends that you undergo cancer treatment because he/she suspects you have cancer, would you do it or would you change physicians? But, this is what we do every single day with infections and antibiotics. And if someone comes along saying the solution is to have pricier drugs, well…

Look, I get the point about reviewing pricing of antibiotics to aid discovery and development of new drugs. They need help. But, these can be one-time efforts. But, overhauling reimbursements of drugs (which sets up a long-term impact) is not the answer to combating antimicrobial resistance. It is not sustainable and will do nothing to change prescribing behaviors. When we can assure appropriate usage of antibiotics, we can influence prescription behavior and then revenues will take care of themselves.

Aha! So how do we assure appropriate usage of antibiotics? The only way I am aware of is by having a diagnostic that can truly guide treatment decisions along with improved awareness and preventive measures that hospitals are already beginning to take. If such a test were available, then physicians would not hoard. They would not try the lower cost option just because it is there. But they will pick the drug because it will provide maximum benefit to the patient. And because we will not be overusing or misusing the antibiotic, resistance spread will be slower. Note that all of these benefits can be achieved without raising drug pricing. So I would say that we should be redoubling efforts to ensure appropriate usage of antibiotics (especially new antibiotics) that meet the needs of hospitals, physicians, and patients and not fiddling with drug pricing.

You might say my position is biased because of my affiliation. It is not. But, the best way to counter my argument would be to provide a better self-sustaining model – one that helps developers, patients, and the healthcare system. Overhauling pricing helps the developers directly and very tenuously, the patients, healthcare system, or society. And as much as I relate with drug developers (having been one), such a strategy (increasing pricing/reimbursements) does not make for good policy.

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Infrared-based bacterial identification – a clinically viable alternative to PCR-based bacterial diagnostics

New Year’s greetings and best wishes for 2020 to all!

We had ended last year, coincidentally, pondering why wide spread application of PCR-based tests in bacterial diagnostics has been elusive and identified a couple of key features that limit their use. It seems appropriate to start the new year with a discussion on one technology that can address those limitations – Infrared-based identification (IR).

What, you might be wondering, – that dilapidated instrument I vaguely recall using in undergraduate chemistry lab? Well, not quite that instrument but yes, one that utilizes the same fundamental principles.

The concept of using IR for identifying bacteria is not new. The earliest reference that we have been able to find dates back to 1950s! But, instrumental and computational limitations held back the potential for using this technology for identifying bacteria until the early 1980s. Naumann and colleagues took advantage of computational advances to demonstrate the ability of this technology to identify bacteria rapidly. Since then the use of IR for rapid and reliable identification of microbes to the strain level have been well documented. Reference databases to facilitate rapid identification of microorganisms are already available with some containing as many as 7000 strains.

How does the technology work?
IR, as you may recall, is a widely used vibrational spectroscopy technique that is used to identify compounds, even those present in mixtures. It is routinely used in raw material testing in the pharmaceutical and other industries as well as in testing of milk and milk products. All of the components that make up a bacterium (proteins, lipids, sugars, etc.) contribute to an IR “fingerprint” (see figure below). The nature and concentration of these components differ from one strain to another resulting in unique IR-fingerprints. This bacterial fingerprint has been used to differentiate between multiple bacterial species and strains including differentiating between antibiotic-resistant and -susceptible strains.

Bacterial fingerprint obtained by Infrared spectroscopy. Each species and strain has a different composition and hence a unique fingerprint.

How does it compare to PCR-based identification?
Two key limitations of PCR-based tests that we had discussed previously were clinical sensitivity of the test and cost per test. If a PCR-test yielded a negative result, the clinician would not have any actionable information. On the other hand, with IR-based identification, the profile of a bacteria is very distinctive and its absence clearly indicates the absence of bacteria in the sample. In such a case, the clinician can actively consider whether administering antibiotics will be of any benefit to the patient. In the case of a positive result, the actions are similar to that with a PCR-based test with several important benefits. These are:

  • the result is available in ≤ 10 minutes
  • No custom labels or reagents are needed lowering the cost per test
  • It does not require specialized laboratory for operation
  • The bacteria is intact and viable after the analysis
  • Antibiotic resistance can be determined
  • The number of species and strains that are identified can be easily expanded without requiring new primers or antibiodies. This is done as a software update that consists of the fingerprint of the new bacteria and adjustments to the recognition algorithm, if needed.

You might be wondering at this stage why, if IR has all these benefits, there has not been any IR-based commercial instrument for use in bacterial ID? There are commercial instruments from Bruker, Thermo, and others that are used for bacterial ID in food safety testing. However the methodology used today requires bacteria to be cultured prior to identification (i.e. the same as most PCR-based tests). In addition, the bacteria has to be separated from the matrix components in order to make an accurate ID. Owing to these reasons, the technology has not yet seen widespread adoption for clinical use.

It is this aspect that we have impacted with the development of our separation cartridge. As mentioned previously, our separation cartridge can isolate and concentrate intact bacteria directly from blood with minimal manual intervention. The isolated bacteria can be identified using any technique. Using it upstream of IR however, permits rapid and sensitive identification of bacteria directly from patient sample without using any bacteria-specific labels or reagents. This combination of our separation cartridge and IR-based identification will, we believe, permit rapid, inexpensive, and hypothesis-free detection and identification. We aim to demonstrate this in 2020.

As we have said before, it’s not that IR (or any other ID technique) has to wholly replace PCR-based tests. The problem is large enough that multiple solutions will be needed. But, given the history of limited gains in developing effective PCR-based bacterial ID tests, the more diagnostic options we have, the better we can aid physicians in making the best decisions for treatment while slowing the spread of antimicrobial resistant bacteria. IR-based identification presents a compelling case to be a key diagnostic option.