David's New Book

Saturday, December 19, 2015

Infection Control in a Small Hospital

Today I want to continue talking about what its like to work in infection control in a small hospital.  About 70% of all hospitals in the US are under 200 beds and 55% are under 100 beds. I carry out infection control work on a volunteer basis for a hospital near my home with an average census of around 40-50 patients. Since I began working there about four years ago, the hospital has undergone receivership, was purchased by a larger hospital in the area, and our system is now about to merge with another huge health care system in our region. This constant series of administrative earthquakes has challenged our infection control efforts.

We have made enormous progress on a number of fronts. Our hand hygiene program has had huge success with compliance rates now approaching 100%. We have revamped our microbiology procedures to better diagnose patients with pneumonia and to better identify resistant bacteria. Our antibiotic resistance rates among key pathogens remain low. We are revamping our surgical wound infection prevention program in a way that I believe will further reduce our already low rates of infection. And we have made great strides in assuring that patients requiring isolation remain isolated during all their sojourns around the hospital for diagnostic testing and procedures.

Our hospital is one of the highest rated medical centers in our area based a number of criteria including patient safety and infection control.  We do very well on all our external audits including those by the Joint Commission on Accreditation of Hospitals. And I agree that the hospital provides high quality care. I just know that we could do even better.

We do have a number of challenges that I think are directly related to our small size.  Our digital medical records system is badly in need of overhaul. It cannot perform any of the key infection control functions such as microbiology lab surveillance, diagnostic code surveillance for hospital-acquired infection nor can it provide reporting to the National Healthcare Safety Network of CDC.  All of this must be done by hand by our infection control nurse.  Our nurse also carries out daily rounds on all the hospital inpatient units, screens the OR schedule and peruses the emergency room patient and diagnosis list in pursuit of infections that might have been acquired at the hospital and of patients in need of some sort of isolation for colonization or infection by multiply-resistant organisms. She struggles to get all this done without computer support.

Our computer systems also are unable to support our antimicrobial stewardship efforts.  We are unable to determine antibiotic dosing in standard format such as defined daily doses. This makes it almost impossible to follow antibiotic usage trends. The pharmacy staff has been cut continually since I joined such that it is difficult for them to keep up with basic stewardship functions such as assuring that patients are getting the correct doses of the antibiotics that the physician has ordered.  Other functions, like trying to get patients off of unnecessary antibiotics, have fallen by the wayside.

Every time we attempt to bring on new functionality to our system or bring in a new computer system for infection control, we are about to merge and are told that we have to wait for the merger to occur.

My hospital has a small intensive care unit.  It exists to back up our surgeons who refuse to operate (understandably) in a hospital without such a unit.  In fact, our ICU maintains a census of 3-5 patients and there is almost always at least one or two on a ventilator. The problem is that we have only one intensivist.  Obviously, he cannot be there 24/7.  Although this may work well, the reliance on trained physicians assistants, ICU nurses and frequent telephone contact makes me nervous. I would prefer to have enough intensivist coverage such that some trained physician was easily available on a 24/7 basis. To resolve this would require systematic changes that might be forthcoming with the latest merger – but in the meantime, we are still on hold. 

Some might say that we should close the hospital altogether.  But those people do not live in this community.  To the community, the hospital is very important and extremely well liked and, as I noted in the beginning, we provide high quality care for our patients.  



Having worked in a very large hospital system (I was at a university-affiliated VA for 16 years), I now understand the issues confronting both types of systems, large and small. Small hospitals have unique problems that are not appreciated by insurers and key payers like Medicare and Medicaid.  Yet small hospitals comprise the bulk of hospital-based healthcare in the US. We need to start paying more attention to them.

Tuesday, December 8, 2015

The Endgame



 
Is this how it will end for us? We use our absolutely last line antibiotic to attempt to put fat on a pig more quickly and select for a plasmid-mediated resistance gene capable of spreading worldwide? Even more galling is that China is not the only country to do this – count the US in as well.

I guess I should start at the beginning of this story. We are now living in an era where, according to Jim O’Neill in the UK, 700,000 people globally die of resistant infections every year. The most resistant bacterial pathogens we deal with today are the Gram-negative bacteria like those resistant to our next-to-last line antibiotics, the carbapenems (CRE). Currently, we can treat CRE with tigecycline (sometimes) and most often, with colistin.  Colistin is an old antibiotic discovered around 1947  and marketed in the 1950s.  It was almost never used systemically since it is  neurotoxic and nephrotoxic (causes nerve and kidney damage).  Given that colistin, at least until the emergence of CRE, was never used – no one knew how to use it or even if it actually was effective when given systemically. Since physicians are having to use colistin more and more frequently to treat CRE infections, we are now learning that it can be effective and that there are a few things we can do to lessen its toxic effects. But, no matter what, it is still not a very effective treatment and it remains toxic. On the other hand, until now, we have had nothing else to offer.

Luckily, for some CRE, we now have a new antibiotic, ceftazidime-avibactam, that should work.  The antibiotic was approved last year in the US and will be approved (I presume) in Europe very soon. But it does not cover all CRE – only some of them. Another antibiotic, wending its way through clinical trials at a tectonic pace is aztreonam-avibactam.  This will address another group of CRE. Finally, there is eravacycline – a tetracycline similar to tigecycline with fewer side-effects and the potential for oral use.  But it recently failed a key phase III trial in urinary tract infection and its future is in doubt. Further, most tigecycline-resistant bacteria will also be resistant to eravacycline. Is there resistance to these new antibiotics? Yes.  Will we still need other options including colistin?  Probably.

This brings us back to fattening pigs. A month or so ago, the Lancet reported the emergence of colistin-resistance caused by a gene, mcr-1, found in samples from animals and some human patients in hospitals in China.  This gene is carried on plasmids and can readily spread from one bacterium to another.  It has already been reported outside of China- in Malaysia and now in Europe. The origin of the gene?  Feeding colistin to pigs to promote growth. Who besides China allows this practice?  The United States – that’s who.

Do we even need to use antibiotics to cause more rapid growth of animals?  Probably not.  A raft of studies has shown that with more advanced farming techniques, antibiotics as growth promoters add little (less than 5%) to the value of meat produced. True – that with poor technique like overcrowding and unsanitary conditions, antibiotics seem to be more important – but why don’t we work on bettering conditions for raising animals rather than relying on antibiotics.  Also – if we have to rely on antibiotics to promote growth of animals, it is the height of stupidity to use the one that is our absolute last hope for highly resistant human pathogens.

Unfortunately, even if we could do better in the US – and if we had an effective FDA we could – we also need to address this problem globally, including in China and other Asian countries with whom we have signed a new trade agreement. If we don’t address this now, at home and abroad, we will lose our ability to stay ahead of bacterial resistance altogether.


– and this might just be how it all ends.

Tuesday, November 24, 2015

Pfizer, Allergan and Antibiotics

With the report this week of the discovery of plasmid mediated resistance to colistin, my thoughts turn to the Allergan/Astra-Zeneca pipeline of antibiotics for highly resistant Gram-negative pathogens. Colistin is our absolute last line against these superbugs.  It’s a toxic drug that no one likes to use, that most physicians don’t even know how to use correctly, and that is now threatened with new, emerging resistance emanating from China. Allergan and AstraZeneca are now marketing ceftazidime-avibactam in the US (soon to be approved in Europe I hope) and are developing aztreonam-avibactam (at tectonic speed).  These antibiotics are active against many (but not all) of the Gram-negative superbugs for which colistin therapy is now used most often. We need these drugs to reach patients – and quickly. And that’s where my concerns about the Allergan half of the equation come in.

Pfizer has proposed an acquisition of Allergan to create shareholder value.  This will be accomplished, in large part, via savings in corporate taxes since the new company will be headquartered in Ireland – where Allergan is currently located. The Newco will then avoid a large portion of US taxes.  The New York Times article also notes that Pfizer may be planning a split into various bits and pieces where innovative drugs will remain in one company while those facing imminent or current generic competition will be part of another company.

So – you all remember Pfizer.  The company was one of the few to market penicillin just after World War II.  It was also the company that walked away from antibiotics back in 2011 believing antibiotics to be subject to regulatory uncertainty at the time and having no confidence that antibiotics would provide a reasonable return on their research investment. AstraZeneca, Allergan’s partner for the development and marketing of ceftazidime-avibactam and aztreonam-avibactam, has also jettisoned their antibiotic research group to form Entasis.  They maintain an antibiotic development group that is now a separate business unit within AZ.

Allergan’s antibiotic group has no discovery research, but does provide clinical development and microbiology support for their pipeline. Will Pfizer-Allergan keep Allergan’s antibiotic group?  Will they even keep their product pipeline?  Or will this all somehow be re-split or even just jettisoned somehow after the merger?

My sources within Allergan are very convinced that Allergan is committed to the antibiotics space – but will it remain committed under Pfizer?




Given the threats of emerging resistance to the last line antibiotics – the carbapenems – and now the new and potentially devastating threat against colistin, the only backstop for many carbapenem-resistant superbugs – it would be perfectly reasonable for the US government to insist that Allergan’s antibiotic pipeline be kept intact and on time (or even accelerated) for the US market post-merger. Will the US administration take an aggressive stance here?  Stay tuned.

Monday, November 16, 2015

Paris - Timeout



I was just getting ready to write my next blog on Saturday morning when I saw the news on the attacks in Paris. We lived and worked in Paris for three years.  The last time, in 2007-8 when I was working with Novexel, a biotech in a Paris suburb, we rented an apartment in the 11th arrondisement where some of the attacks occurred. The apartment was on the 6th floor (7th for Americans) and looked out over the roofs of the city towards the Eiffel Tower. From our window on Avenue Parmentier, we looked out at the Voltaire metro station and the Mairie (town hall) for the 11th.  The Bataclan, where gunmen and suicide bombers killed at least 89 innocents, is just a few blocks down near rue Voltaire.

As we watched French television news (thanks to the internet), we were taken back to other attacks that are engraved deeply in our emotional history.  In 1995, as I was returning from work near Blvd St. Michel on my bicycle, I passed the scene outside the metro station just after one of the bombs from that August had exploded.  A bistro had been turned into a triage center. There were already several white-draped bodies on the ground. We resolved to stop taking public transportation – but, in reality, it was impossible to function in Paris on foot and bicycle. While the bomb attacks continued sporadically into September, we went about our daily lives like everyone else.  And, like everyone else, we became defiant and worried at the same time. Terrorists are called terrorists for this reason. In the grand scheme of things, they don’t destroy countries; they destroy lives, and for those of us remaining, a certain peace of mind.

We were in France on September 11, 2001. Friends were staying with us and had arisen very early that morning to take a train from Avignon, in the south of France, to Paris to catch their plane back to Phillie. That afternoon, our refrigerator repairman asked if we had heard that there had been some sort of accident involving a plane in New York. We had no television, but we did have an internet connection. We looked and were horrified. Not long after that, we got a call from our friends’ babysitter asking if they had left.  We asked when they were expected and she told us that they were due several hours ago.  She said that she had been able to get no information on their whereabouts.

We found out later that their flight, like many others, had been diverted to Gander, Newfoundland. They were welcomed by the citizens of Gander and taken to a religious camp outside of town where they spent the next six days without their luggage but with their carry-on items.  In their case this was a case of Burgundy wine. They still go back to Gander from time to time to reunite with their Newfoundland friends and others who had been diverted there the day of the attacks.

We returned to the US on the 16th – the first day that flights were allowed to go from Paris to Newark.  After we boarded, the captain came by to every passenger to personally ask if we were OK. On arriving, we flew over the smoking remnants of the towers.  On our drive home, we passed by the parking lot for one of the New Jersey PATH trains that takes commuters to New York every day.  There were scattered cars left by those who would never return home. Our home in the New Jersey suburbs was unchanged – but our lives would never be the same.

Watching French television over the weekend, all of these memories flooded back. We got on email and telephone to check with friends in France. So far, so good – everyone is OK including those living near the Bataclan and the caf├ęs where the attacks took place. Many will know someone, or will know someone who knows someone, who was killed or injured Friday night. No one will ever forget.


While I continue to be passionate in my belief that we need new antibiotics – I was just unable to go there this week.

Friday, November 6, 2015

The Wild West!

Will it get wilder?

I don’t usually read Nicholas Kristoff’s columns in the New York Times – but yesterday he caught my eye. In a poignant story, he recounts the death of a 15-year-old child with emotional problems.  His death was apparently caused by an adverse drug effect from an antidepressant. Kristoff talks about the 7-fold rise in use of antipsychotic drugs among children in the last decade and questions how much of this is based on science and how much on marketing.

At the heart of Kristoff’s story, though, is the debate about allowing pharmaceutical companies to market their drugs for off-label uses. There have been a number of articles on this since a federal judge in Manhattan ruled that the FDA could not block Amarin from promoting its drug for non-approved uses based on our right to free speech.

Why this is a debate escapes me.  The most basic tenant underlying the existence of the FDA is the ability to restrict companies from marketing anything for anything as was occurring in the 19th century.  (Of course, this still occurs for supplements – and how far has that gotten us)? Untold numbers of companies have been fined and occasionally people have gone to jail over violation of this basic power of the FDA to make companies adhere to what they have proven scientifically and what has been shown to have (we hope) an acceptable risk for a reasonable benefit.

The judge’s ruling in the Amarin case seems to have been that as long as the statements used by the company are “truthful” they should be allowed under free speech.  But what does that mean?  What is truthful? If an antibiotic representative told a physician that his/her product, approved for the treatment of epilepsy, had also been shown to be good for patients with arthritis based on a single case report – that would be truthful. Should that be allowed? What if it had been studied in several hundred patients with arthritis in an uncontrolled manner, but had never been approved by the FDA – the statement would still be truthful – but should that be allowed? Finally – what if the drug had been studied in a controlled way, and the study had been submitted to and rejected by the FDA as insufficient?  Should the representative be allowed to quote the results of the study claiming benefit?

Bureau of Chemistry 19th C.
I can tell you that negotiation over the label both here in the US and around the world, is among the most contentious that exists between governments and companies.  It even surpasses pricing discussion in importance for the industry. Why? Because you are not allowed to market what is not included in the label. And to the industry, marketing and promotion is where it’s at.  You need to have something in your label that your competitor does not have.  You have to have that lever – less frequent dosing, better activity shown in the clinic, better spectrum of activity – something that demonstrates that patients and physicians need your product in a way that cannot be satisfied with something else or something less expensive.

At the same time, companies are already allowed to provide physicians with scientific literature on request. In fact, there is an entire FDA guidance on this topic. The FDA recognizes that physicians are allowed, based on their own clinical judgment, to use drugs for purposes not contemplated in the drug label.  The agency therefore provides to the industry criteria under which dissemination of such information is permitted – but in a restricted way.  Articles provided must be from the peer-reviewed literature.  Contradicting articles, if they exist must also be provided.  A list of references on the topic must be provided.  This is all so that the health care provider can judge among all the data, which might be the best choice for his/her patients. What is wrong with this approach?


  If the power to restrict how drugs are marketed is taken away from the FDA – our Wild West of drug pricing and the free-for-all market we allow now will become even wilder.  We will be able to sell anything for anything.  Please – lets not go there.  We already have enough of that from the supplements!