15 June 2010

News break: Developing-world drug resistance

This is an addition for archival purposes of a post that originally appeared at Scienceblogs.

The Center for Global Development, a DC think-tank, is releasing what looks like a thoughtful report aimed at refocusing policy debates over drug resistance toward the epidemic's global impact, with particular attention to the the developing world.

From the report's preface:
Problems with drug resistance have moved from the patient's bedside to threaten global public health. Drug resistance has dramatically increased the costs of fighting tuberculosis (TB) and malaria, has slowed gains against childhood dysentery and pneumonia, and threatens to undermine the push to treat people living with HIV/AIDS effectively. Global health funders and development agencies have cause to worry about whether their investments in access to drugs, and global health programming more broadly, are being undone by the relentless advance of drug resistance.

It calls out a sustained lack of leadership:
Past efforts to energize global action to more comprehensively address drug resistance have been sidetracked by poor timing or over-stretched budgets... In an unfortunate coincidence of timing, a WHO Strategy on Antimicrobial Resistance was launched on September 11, 2001. As a result, the action plan prepared for the Strategy did not get carried out, and over time the interest in cross-cutting drug resistance at WHO withered, even while disease-specific attention grew. For many years, the U.S. Government provided support for research, technical support, surveillance, and policy development on drug resistance in developing countries through an annual budget appropriation to the U.S. Agency for International Development (USAID). That support has become narrowed to programming in only a few areas.

It recommends 4 specific steps:
  1. Improve surveillance by collecting and sharing resistance information across networks of laboratories
  2. Secure the drug supply chain to ensure quality products and practices
  3. Strengthen national drug regulatory authorities in developing countries
  4. Catalyze research and innovation to speed the development of resistance-fighting technologies

A policy brief is here and the full report is here.

Bad news: From MRSA to LRSA

This is an addition for archival purposes of a post that originally appeared at Scienceblogs

Via the Journal of the American Medical Association, a report from Spain: the first recorded outbreak, in a Madrid hospital, of Staphylococcus aureus resistant to linezolid (Zyvox), one of only a few drugs still available to treat very serious infections of drug-resistant staph, MRSA. This is bad news.

Background: The M in MRSA stands for methicillin, the first of the semi-synthetic penicillins, created by Beecham Laboratories in 1960 in response to a worldwide 1950s outbreak of penicillin-resistant staph. The central feature of the chemical structure of both penicillin and methicillin is an arrangement of four atoms, known as the beta-lactam ring, that governs both drugs' ability to interfere with bacterial cell-wall synthesis. That structure was copied into the formulas of a number of other drug families -- the cephalosporins, carbapenems and monobactams -- and so MRSA is resistant to them as well. And in addition, the bug has picked up resistance to yet other drug families through horizontal transfer; so increasing the census of new drugs that can treat resistant staph infections is a high priority for drug development. It's especially critical for severe infections such as ventilator-associated pneumonia, osteomyelitis, endocarditis and bacteremia, since all the remaining last-resort drugs have challenges from toxicities to ineffectiveness in certain organs.

Linezolid is a relatively new drug, out since 2000 (and, as a downside, still under patent and, according to patients who have been prescribed it, very expensive). It was the first of a new drug class, the oxazolidinones; since there were no "me too" similarities to older drugs, clinicians hoped that resistance to linezolid would be slow in coming.

No such luck.

The first recognized case of linezolid resistance in staph was recorded in 2001. Still, there have been relatively few cases of LRSA, or staph that possesses both linezolid and beta-lactam resistance: 8 cases in the US to date, 2 in Germany and 1 each in Brazil, Colombia and the UK.They have all been caused by a particular point mutation, G2576T.

This Spanish outbreak, though, had a different cause, the importation of the cfr gene, which also mediates resistance to the older drugs clindamycin and chloramphenicol, apparently on a plasmid, possibly from a staph strain common in cows. The outbreak caused by this new mechanism was as large as the entire known burden of LRSA to date: 12 patients, over 10 weeks in 2008, in 3 linked ICUs, pls 3 patients who were not in intensive care, but had had previous ICU stays. Six of the patients had ventilator-associated pneumonia and 3 were bacteremic. Six died -- though the authors are careful to say that all of these patients were critically ill, with brain tumor and esophageal cancer among other problems, and that LRSA was not directly responsible for all of the deaths.

More bad news: There were actually 4 clones of LRSA within this outbreak, with slightly different resistance patterns. Troublingly, one of the 4 had reduced sensitivity to glycopeptides; the chief glycopeptide is vancomycin, which has been the go-to drug for MRSA for 50 years.

The hospital checked its staff and the ICU environments, and found nothing of significance; there was no reservoir in the hospital that was passing this newly resistant strain to patients. With no obvious solution there, they dialed back sharply on their linezolid use, going from more than 200 doses per day in April 2008 to 25 doses per day in June. That aggressive antibiotic stewardship appears to have put the brakes on the outbreak, and after June, no additional cases were recorded.

An accompanying editorial underlines how critical antibiotic stewardship was in controlling this outbreak, while also pointing out how very liberal the hospital was in prescribing linezolid before the outbreak began -- suggesting that if the institution had used its antibiotics more conservatively from the start, this outbreak might not have arisen, or at least not have been as large.
No one doubts the importance of infection-control practices in limiting outbreaks with antibiotic-resistant organisms, but optimizing antibiotic use remains essential for successful control of such outbreaks...No longer can clinicians' unrestricted use of antibiotics and ignoring suggestions from those who attempt to improve or alter antibiotic use be tolerated. Clinicians must understand the sense of urgency about the appropriate use of antibiotics.

Indeed.

(NB, this outbreak was also written up a few months ago in Clinical Infectious Diseases, and was a late-breaker paper at the 2008 ICAAC meeting.)

10 June 2010

Update: Access to dental care

This is an addition for archival purposes of a post that originally appeared at Scienceblogs

A couple of days ago, I talked about the link between a potentially massive hepatitis B outbreak in West Virginia and the lack of access to primary dental care. I was mushy qualitatively descriptive, ahem, about the number of people who lack access to dental insurance.

Comes now the CDC to save the day. In a statistical brief posted today, the National Center for Health Statistics gives a concise but thorough overview of the state of dental insurance in the US. Short version: Ain't pretty.

Crude preliminary population math:
  • There are currently 309 million Americans.
  • Based on census tables from last summer, 39 million are 65 or older (i.e., eligible for Medicare).
  • Based on other census tables from last summer, 52 million are 17 or younger (of which some percentage, based on family income, would be eligible for Medicaid).
  • That leaves, with wiggle room, about 218 million working adults.

According to the NCHS:
  • 172 million non-elderly Americans have private health insurance. (NB, leaving 46 million non-elderly with no health insurance, which matches the usually accepted figures.)
  • Of them, 45 million have no dental coverage -- which, added to the 46 million with no insurance at all, means that more than 90 million Americans have no dental coverage at all. (I believe the technical term for a number that large is a crapton. Maybe a metric crapton.)

In addition:
  • If you have employer-provided health insurance, your chances of having dental coverage are pretty good: 80%.
  • If you have privately purchased insurance of any kind, not so much: 30%.

So, reinforcing Monday's point: There are multiple millions of Americans who get no assistance paying for dental care, which is a largely cash-only business. (And judging from my own experience -- thanks to my childhood in the UK, I have teeth like chalk and consume more than my share of dental care -- dental insurance negotiates discounts. So self-pay dental care is relatively more costly.) And therefore, it is not surprising that thousands of people attended that free dental clinic in northeastern West Virginia, and were potentially exposed to hepatitis B as a result.

08 June 2010

News break: House hearing Wednesday on the antibiotic pipeline

This is an addition for archival purposes of a post that originally appeared at Scienceblogs.




The Subcommittee on Health of the Energy and Commerce Committee of the House of Representatives has announced a hearing for Wednesday: "Promoting the Development of Antibiotics and Ensuring Judicious Use in Humans."

The witness line-up is:

  • Janet Woodcock, M.D., Director, Center for Drug Evaluation and Research, Food and Drug Administration
  • Robin Robinson, Ph.D., Director, Biomedical Advanced Research and Development Authority, Department of Health and Human Services
  • Brad Spellberg, M.D., F.I.D.S.A., Associate Professor of Medicine, David Geffen School of Medicine at UCLA and Member, Infectious Diseases Society of America Antimicrobial Availability Task Force
  • Sandra Fryhofer, M.D., Council on Science and Public Health, American Medical Association
  • John S. Bradley, M.D., American Academy of Pediatrics, Chief, Division of Infectious Diseases, Department of Pediatrics, University of California, San Diego, School of Medicine, Clinical Director, Division of Infectious Diseases, Rady Children's Hospital
  • Barry Eisenstein, M.D., F.A.C.P., F.I.D.S.A., Senior Vice President, Scientific Affairs, Cubist Pharmaceuticals
  • Jeffrey Levi, Ph.D., Executive Director, Trust for America's Health

This is the second hearing the Health Subcommittee has had this spring, apparently at the prompting of the chairman of Energy and Commerce, Rep. Henry Waxman, who made the opening statement at the first such hearing in April:
We need to debate the health care bill and review its implementation. But we ought to be able to chew gum and walk at the same time. Because it is not going to make much difference if you have health insurance or not if you are going to die from something that could have been prevented from an antibiotic. And we are seeing more and more antibiotic resistance. (Transcript)

Reading between the lines, I'm going to guess this hearing will lean heavily on the IDSA's campaign to improve market conditions for pharma companies in order to revive antibiotic development (an issue I discussed recently at the old Superbug -- we're working on getting the archives moved over).

07 June 2010

News: SUPERBUG is moving

Constant readers, I have an exciting announcement. After 3 years here on Blogger, SUPERBUG has been invited to join the thoughtful, knowledgeable, chatty and sometimes raucous community over at Scienceblogs. From today, I'll be posting instead at a new page:
http://scienceblogs.com/superbug.

I will keep this site up as a resource, at least until we can work out the mechanics of transferring this blog's archives over to the new page.

You've been such great readers, so thoughtful and thorough. I really hope you'll follow me over to the new location. I would love to engage with you there too.

Sincere thanks to all of you for all your attention, and warmest wishes.

Dept. of Unintended Consequences: Hepatitis B in West Virginia

This is an addition for archival purposes of a post that originally appeared at Scienceblogs.




Via ProMED Mail comes a news report that about 2,000 people in 5 states are being sought by health departments so they can be checked for hepatitis B infection. The potential source: the Mission of Mercy Dental Clinic, a free dental-care fair held just about a year ago in Berkeley County in the far north-east corner of West Virginia. The potentially infected include 1,137 people who were treated at the two-day clinic and 826 of the volunteers who worked there, from West Virginia, Washington, D.C., Virginia, Maryland, Pennsylvania and North Carolina. Three patients and two volunteers have already been diagnosed. The virus in four of the five matched on molecular fingerprinting, suggesting a common source; the fifth patient refused further testing.

Hepatitis B is blood-borne, so on the surface, this is a story of the tragic consequences of some failure somewhere in the clinic's infection-control procedures. (One reason why it caught my eye, since I'm interested in healthcare-associated infections.) Except that it's not -- or not only. It's important to unpick why such an extraordinarily large number of people may have been exposed at one time. Looked at through that lens, it becomes a story about what can happen when we don't fund basic health care in a timely way.

Some background: West Virginia is one of the poorest states in the country and has some of the highest rates of the usually recognized diseases of poverty: tobacco use, chronic kidney disease, asthma, cardiovascular disease. (Look for West Virginia on these CDC maps of incidence of heart disease and stroke.) But it also has extraordinarily high rates of another health problem that ought to be linked in the public mind to low socioeconomic status, but usually isn't: untreated dental disease. Eric Eyre of the Charleston Gazette (disclosure: a friend and fellow Kaiser Foundation Fellow) took a year-long close look at dental disease in the state in 2006-07 (slideshow, stories). If you're squeamish, I advise skipping the one about the woman yanking her own teeth with pliers after a few shots of moonshine.

Dental disease -- that's not just cavities, but tooth loss, bone loss, abscess, Ludwig's angina, septicemia in the most serious cases -- isn't only a problem for West Virginia, though it happens to be worst there. It's a problem all over the US because, without ever intending to, we've allowed dental care to become a primarily cash-based form of medicine.

If you have a job, you may have dental insurance, though it's a less-common employment benefit than health insurance, and covers comparatively less of the cost of any procedure. If you don't have a job, dental care is entirely out of pocket. If you're poor enough to be on Medicaid, whether or not you have dental coverage depends on which state you live in, because Medicaid dental coverage for adults falls under the portion of Medicaid funded by the states, not the federal government. In the past 12 months, California, Hawaii, Massachusetts, Michigan, Minnesota, North Carolina, and Washington state all cut or tried to cut their contributions to dental Medicaid from their state budgets. If you're the child of a poor family, you are hypothetically entitled to Medicaid-funded dental care, though that depends on being able to find a local dentist willing to accept Medicaid reimbursement; last year, the Government Accountability Office said that children have trouble finding Medicaid-accepting dentists in 43 out of 50 states.

Net result: Untreated dental disease is now the most common disease of childhood, five times more common than asthma according to a 2000 Surgeon General's report, and emergency room visits for dental crises are rising steadily. ERs are not the right place to treat dental problems -- they don't fill cavities or do extractions, though they can drain abscesses and give antibiotics and pain meds -- but as with so much else in US medicine, ERs offer a mandated clinic of last resort when there's nowhere else to go. (For more about the interplay between dental care and ER overcrowding, here's a story I wrote for the June Annals of Emergency Medicine.)

All of that explains why thousands of people from a wide swath of the East Coast were so desperate for free dental care that they were willing to stand in line overnight in a high school parking lot. (The first free dental clinic in West Virginia had to close its doors early after it got 1,100 patients in the first 2 hours.) And also why hundreds of dental-care professionals and students and community volunteers were so eager to help. And why they're all now waiting by the mailbox, wondering whether they're in line for a letter that will tell them where to get tested for infection with a life-long chronic disease.

04 June 2010

The trend in hospital infections - good, bad, or too little data to know?

Some of you may have spotted an announcement last week from the Centers for Disease Control and Prevention about a release of data from the National Healthcare Safety Network (NHSN), a repository of hospital infection data. You can guess the big news in the report from its title,  "First State-Specific Healthcare-Associated Infections Summary Data Report": For the first time, database users are able to calculate healthcare-associated infections (let's call them HAIs for short) by state, as well as nationally.

Good news, you would think. And it is. According to the CDC's announcement (press release, press conference transcript), the national rate of one particular type of HAIs, central line associated bloodstream infections or CLABSIs (like it looks — pronounced "klab-sees") is down 18% from the previous 3 years. Taken together, all HAIs kill at least 100,000 Americans each year (an old number that is probably an underestimate) and cost at least $30 billion per year. CLABSIs are an important component of the spectrum of HAIs and may account for a third of all HAI deaths — so any reduction is a positive development.

And yet: The bigger news about this report, unfortunately, is that it lays bare how little we really know about HAIs, and how little progress has been made in preventing or even documenting them.

Consider:
  • The report includes data from only 17 states
  • The data does not match state to state, so state rates cannot be compared
  • Participation in the NHSN by hospitals is voluntary (except in states that recently have passed mandatory reporting laws) and data is self-reported
  • Hospitals that report to the NHSN are not identified (in fact, unless state laws say otherwise, they are guaranteed anonymity)
  • The NHSN does not collect data on the most problematic HAI organisms, MRSA and C. difficile.
If you think for a moment about how incomplete this data is, and how much the data collection allows hospitals to avoid saying, then Dr. Peter Pronovost's remarks to the Association of Health Care Journalists in April begin to make sense. Pronovost is a MacArthur Fellow for his championship of evidence-based infection prevention, and said (sorry, no verbatim record that I know of, but I live-tweeted his speech) that if hospital infection reporting were truly transparent and truly accountable — right now, it's neither — the problem of HAIs would end tomorrow, because consumers would be so shocked that they would rise up and demand change.

The CDC says there will be additional data and a new comparison with this first snapshot within about 6 months. Again, that's all good news. But it's worth taking a deep look at this report to really understand how little we know — which will also help to explain why this problem so persistently fails to get better.

(NB: The CDC announcement and the relevant background were covered thoughtfully by my friends Dan DeNoon of WebMD and Barbara Feder Ostrov of Reportingonhealth.org, whose post, FWIW, quotes me.)

And, constant readers, an addendum: On Monday, I'll have big news to share about this blog. It's good news and I hope you'll support it. Stay tuned.