COMMENTARY

ID Update 2014: New Threats, Old Antibiotics

John G. Bartlett, MD

Disclosures

May 22, 2014

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Hi, everyone. I am John Bartlett, at the American College of Physicians Internal Medicine 2014 meeting in Orlando, Florida, giving an update on infectious diseases. This will be a "Reader's Digest" version. I'm sorry that I have to go quickly, but there is a lot going on in infectious diseases, and I will try to cover the highlights.

The Growing Problem of Resistance

Of course, the major story of the year, which we have known was coming for a decade, is antibiotic resistance and fear of the inability to treat common infectious diseases that we currently see.

Slide 1 provides a summary of the Centers for Disease Control and Prevention (CDC) report on resistance.[1]

CDC categorized the microbes and the associated threat as urgent, serious, or concerning. I am going to say a couple of things about the ones that are considered urgent. The ones we worry about most are the carbapenemase-producing gram-negative rods.

This is becoming a global problem. There was a transport of patients from India to London with the carriage of this organism that subsequently became an epidemic in London, then in all of England, then in Europe, and then in the United States.[2] I am not sure that that event is the source of all or even most of these bacteria that are so resistant. The prototype in vitro sensitivity testing of this organism shows that it is sensitive to colistin and tigecycline most of the time, and sometimes to aminoglycosides. We have a very limited menu, and the drugs that are advocated are not easy to use. I will come back to that.

Some of the data from the US experience came from an outbreak at the clinical center at the National Institutes of Health (NIH), which was highlighted in the Washington Post.[3] It was a terrible problem and took an incredible effort to eliminate. They eventually did, but not until they built a wall around the patients. They did an enormous amount of gumshoe epidemiology to try to sort it out. In the end, there were 18 cases and 6 deaths in 6 months.

To give you some idea about the magnitude of what we may be looking at, there is an epidemic of carbapenem-resistant Enterobacteriaceae (CRE) in Chicago.[5] The center of the bullet is a long-term acute care hospital, with dissemination of that organism to hospitals, patients, nursing homes, and chronic care facilities. I think that is what we are really worried about.

As soon as this type of a resistance mechanism gets legs, it can show up on virtually any doorstep. The problems that we have with resistance are the dearth of antibiotics and the abuse of antibiotics.

We push the problem with our use of antibiotics, and we need to restrain the use of antibiotics. In terms of new antibiotics, we haven't had any new ones. We haven't had a new class of drugs for gram-negative rods in 4 decades.[6] That is why we're confronted with such a problem in that category.

But there is a bit of light at the end of the tunnel. The US Food and Drug Administration (FDA) advisory board has just approved 2 new drugs, which is unusual and wonderful to see.

Tedizolid phosphate (Sivextro™) is a drug that is very much like linezolid except that it is given once a day. Dalbavancin (Dalvance™) is an interesting drug that has a half-life of 6.5 days. You inject it and the patient is covered for a week, and then after one more dose the patient has gotten 2 weeks of therapy. That has some unique properties in terms of potential use. They don't really answer the question that I was asking about resistance in gram-negative bacilli.

Responding to Antibiotic Resistance

What can you do? I'll tell you what you can do. We have to work hard to be smart about how we use antibiotics.

One of the things we have to do is to make sure that patients are aware of the potential harm in their insistence on the use of antibiotics. Most of the abuse is for viral respiratory tract infections -- you all know that. One idea that has legs is for doctors to post a sign in their office that says, "Dr. Jones will prescribe antibiotics only according to current guidelines." I would advocate that to be part of practice now.

Other things to advocate are the use of procalcitonin to know when to start or stop antibiotics, the use of short-course antibiotics, the use of modern molecular diagnostics, and, of course, infection control.

Procalcitonin is kind of a new test to many people. The serum level goes up with bacterial replication and goes down when they stop replicating, so it helps you to know when to start or stop antibiotics. A fine study by Schuetz and colleagues[7] included [more than] 4000 patients in randomized trials. The researchers examined the use of procalcitonin and found a good take-home message: If you have a patient with a pulmonary infiltrate and you have procalcitonin, you are going to use antibiotics, probably regardless of the actual procalcitonin level. These researchers showed that people are going to use the antibiotic anyway, but it will help you know when to stop.

In regard to bronchitis, exacerbations of chronic bronchitis and upper respiratory tract infections, and sinusitis, it helps to know when to start. Then you could do the test again and say to the patient, "I have evidence that you do not have a bacterial infection."

One of the antibiotics that we need to learn to use (because most have not used it) was approved by the FDA in 1961, and that is colistin.[8]

Here is some guidance on how to use it at present time. We tend to underdose it, but it does have a fair amount of nephrotoxicity. In one study, about 50% of patients who received the recommended dose wound up with renal toxicity.[9] So you have to be very careful about how it is used.

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