When medicine runs out of effective antibiotics, what does it do?

It turns to the uneffective ones. And patient care suffers.

People on the front lines of antibiotic resistance – infectious-disease physicians and nurses, and the patients sick or unlucky enough to contract a resistant infection – have been insisting for a while that this is happening. Their alarm has not been much-noticed. A paper published this evening might change that. (Link fixed from earlier.)

Constant readers have heard me say before that one of the positives in the European and Canadian healthcare systems is their electronic health records, which not only permit healthcare workers to make an individual patient's care consistent across offices and hospitals, but also allow researchers to identify trends in diseases and treatment across the system and over many years. Broad electronic healthcare systems, which record details of treatment and diagnosis whether a patient is treated in a local family-practice office or a specialty hospital several cities away, are one of the main reasons that Europe has a much better grasp of its diabetes epidemics than the United States does, and identified the emergence of new resistant organisms much faster than we would have been able to.

Within the broad landscape of American retail medicine, we have one system similar to the European ones: the Veterans Administration. The VA has 152 medical centers, and to keep track of its patients – who are guaranteed care no matter where they move or vacation, and often have complex illnesses – it deploys a systemwide electronic health record.

The paper published today in PLoS ONE by a group of physicians from the University of Utah who also work at the VA Salt Lake City Health Care System, draws data from that record system to provide a glimpse of worsening antibiotic resistance across the country. Because there are no other national health record systems and no consistent national registries, it may be the first such report compiled in the United States.

So it is all the more concerning that the news is not good. The authors find that the use of polymyxin and tigecycline – the drugs of last resort for the most multi-drug-resistant infections – rose steadily between 2005 and 2010 at 127 VA centers: 25 percent for polymyxin B and E, and 400 percent for tigecycline.

That's a sign that multi-drug-resistant infections such as MDR gram-negatives – ones for which the other big-gun drugs such as carbapenems no longer work – are rising in incidence. (Two of the authors, Drs. Makoto Jones and Benedikt Huttner, told me they confirmed that conclusion by matching the prescriptions made for VA patients with lab work done on patients during the same period.) And it's also a warning signal, because it's generally agreed in medicine that after these drugs, there's nothing: The pipeline for gram-negative infections is dry.

What's especially troubling is that these are not great drugs. The polymyxins are more than 50 years old, and there's a reason they have remained viable that long: No one likes to use them. They have a well-documented history of causing kidney damage, and recently have been linked to respiratory arrest as well. Tigecycline, on the other hand, is only a few years old, but clinicians complain that it has limitations, especially in getting concentrations in the bloodstream that are high enough to knock out a bloodborne bacterial infection.

So to recap: The incidence of resistance is rising, and the use of the few remaining drugs is also rising; those drugs don't work very well and there are no other options beyond them; and the more they are used, the more resistance to them will burgeon as well.

"We need to address the problem of the spread of resistance, or we need better drugs," Jones told me. "In fact, probably both."

Cite: Huttner B, Jones M, Rubin MA, et al. Drugs of Last Resort? The Use of Polymyxins and Tigecycline at US Veterans Affairs Medical Centers, 2005–2010. PLoS ONE 7(5): e36649. doi:10.1371/journal.pone.0036649

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