An ongoing dialogue on HIV/AIDS, infectious diseases,
September 18th, 2008
C. diff: The cure for antibiotic abuse
Even with market doom-and-gloom dominating the news, there’s a good article in yesterday’s Wall Street Journal on Clostridium difficile (C. diff). It gives an accurate summary (in lay language) of the problem, several pertinent clinical anecdotes, and quotations from national experts.
But this part in particular caught my eye:
She says that among other measures, the hospital has cut its post-operative antibiotic doses for all joint-replacement surgeries to two from three to avoid C. diff infections.
No offense intended, but anytime “routine” antibiotic use is reduced on surgical patients, it’s notable. Practically reportable. (One might question why any post-operative antibiotic doses are given at all — but we’ll take this small victory anyway.)
Human beings love antibiotics — all of us are guilty of this love affair, health care providers and patients alike. (This is a great cartoon!) My first introduction to this phenomenon was during a medicine rotation in medical school, when the esteemed senior physician on rounds obviously had a bad cold. After a particularly noisy bout of sneezing (and what was he doing in the hospital, one might wonder), he confessed that the cold he could deal with — but the nausea from the erythromycin he’d prescribed for himself “just in case” was driving him crazy.
But this new “hypervirulent” C. diff has changed the equation, in a way that warnings about antibiotic side effects and risk of resistance never could. One of my friends, a maxillofacial surgeon, thinks long and hard about every antibiotic prescription ever since one of his patients had severe C diff — requiring a colectomy and prolonged ICU stay — after a brief outpatient course of clindamycin.
And those unfortunate patients who have had C diff have been thoroughly cured of any “just in case” mentality towards antibiotics for sniffles, colds, sore throats, minor sinus issues, and coughs. Alas, a case of C diff is more effective than “Your cold is caused by a virus; antibiotics don’t work for viruses,” which oddly has little traction at all.
September 10th, 2008
Yes, TNF blockers increase infection risk. Now what?
So the FDA has issued (another) warning about TNF (tumor necrosis factor) blockers and increased infection risk, this time focusing on fungal infections, in particular histoplasmosis. TNF blockers are used for treatment of rheumatoid arthritis, Crohn’s Disease, ankylosing spondylitis, psoriasis, and a wide range of other autoimmune diseases, both in approved and in off-label use.
ID/HIV specialists of a certain age can easily remember the first patients they had who, after starting PI-based combination therapy (note I don’t say “HAART”), literally got their life back. Went from imminent death to joining the living again. It was miraculous. A similar thing happened when TNF blockers entered clinical trials, then were approved by the FDA.
No, the TNF blockers don’t usually reverse a fatal illness like the antiretrovirals. But their effect, while perhaps not literally life-saving, is nearly as profound. It doesn’t much matter what the disease is; for patients with severe RA, or Crohn’s, or whatever, going from a life of chronic pain and disability to feeling normal again is, well, a miracle of almost comparable magnitude to the reversal of AIDS with antiretroviral therapy.
That’s why seeing patients with serious infectious complications from these drugs is so challenging. It’s not just about treating the infection. It’s also about managing the post-infection life.
And coming up with a sensible, compassionate answer to the inevitable question, “When can I start the Enbrel [or Remicade, or Humira, or Cimzia …] again?” — is certainly one of the hardest things I do.
September 5th, 2008
West Nile Virus and Friday Night Lights
The town of Braintree, just south of Boston, has cancelled Friday night high school football games until the first frost of the year due to concerns about West Nile. Apparently the campus has a lake and wetlands, good breeding grounds for mosquitoes. “This is all in the name of safety,” says the school headmaster.
(If someone were doing a presentation on “How Massachusetts Differs from Texas”, this move is Exhibit 1.)
When West Nile encephalitis first appeared in Boston in the Summer of 2000, there were newspaper articles about how parents would rush their children from house to car on summer evenings to avoid mosquito bites; lots of debate over the relative safety of various chemical repellents; people scrutinized their neighbors’ yards for suspicious bird baths or, worse, old tires with stagnant water.
This all seemed to me a variant on a commonly-observed inability for us humans to figure out relative risk. Which was more dangerous, a few mosquito bites on a summer evening, or the drive in the car? We fear what we can’t control — especially creepy microbes, bugs, germs, yuck — and if anything can be done to reduce this risk further, even if it’s from a 1 in a million to a 1 in 10 million chance, let’s do it. (See rabies prevention, for another example.)
By contrast, we have the illusion of control over things like car safety, when in fact most car accidents happen suddenly — no warning –- and we have no control at all over the driver trying to find his sunglasses while talking on the cellphone after having a few too many. People are more concerned with feeling safe than being safe — just try to convince the driver of a large SUV otherwise.
This is not to diminish the potential seriousness of West Nile disease — a colleague of mine’s father died of it in California several years ago — but the reality is that so far this year in Massachusetts there have been zero human cases; last year there were 6 (3 encephalitis, 3 fever). Less than 1% of people who become infected with West Nile virus will develop severe illness. Most people who get infected with West Nile do not develop any disease at all, and the elderly — not high school football players — are at the greatest risk for encephalitis.
As a 140-pounder when wet, I can think of lots of good safety reasons reasons not to play high school tackle football on Friday nights — but the risk of West Nile isn’t one of them.
August 22nd, 2008
We have met the enemy … and it is MRSA
In Jerry Groopman’s recent New Yorker piece on antibiotic-resistant bacteria, he quotes Dr. Louis Rice from the Cleveland VA, who uses the term “ESKAPE” bacteria: an acronym for Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanni, Pseudomonas aeruginosa, and Enterobacter.
Nothing against the mostly gram-negative nasties in this list (and the focus of the New Yorker article), but in my opinion there is one bacterial King of Pain, and it is MRSA — methcillin-resistant Staph aureus. Already a hospital-based problem when I began medical school in the 1980s, MRSA is now absolutely everywhere, and I’ll go out on a limb and state that it is the most common and worrisome source of serious infectious suffering we have out there right now.
In this past week alone, I have seen or heard about the following patients (some details slightly changed due to HIPAA, and even more importantly, this list isn’t even all-inclusive):
August 8th, 2008
More from Mexico City
A bit more travelogue from the XVII International AIDS Conference:
- It’s impossible to see everything you want at such a large, sprawling conference, sometimes because of conflicting meetings, sometimes because the room is full, sometimes because of a feeling analagous to being in a giant museum for too many hours — fatigue just takes over. But I’m sure glad I didn’t miss Myron (Mike) Cohen’s plenary session Tuesday AM on HIV Prevention. It’s easy to get cynical about HIV prevention efforts given the number of recent failures in the field (vaccines, acyclovir, microbicides …), but as Cohen pointed out, some things out there are working, and he outlined a very reasonable (and optimistic) strategy for how this epidemic could be controlled. Plus he did it in his typically energetic and entertaining fashion, all the while maintaining absolute academic rigor. Don’t miss his name-brand idea for a combination product containing tenofovir, emtricitabine, and maraviroc — brilliant. Some web casts are worth watching, and this is one of them.
- Missing from this International AIDS Conference were the phonebook-thick abstract listings. Instead, we received the abstracts on CDs, a move that definitely saved lots of trees, sore backs and shoulders, but made it very hard (ok, impossible) to flip through the abstracts. I´m sure this is a direction that more meetings will take, but will definitely take some getting used to. USB drives will be coming soon, as CDs as a storage medium are definitely on the way out.
- Speaking of USB drives, the speaker-ready room was shut down on Wednesday for a while due to — I´m not making this up — a computer virus acquired from some rogue USB drive. Many jokes followed about computer condoms, vaccines, and microbicides, but I´ll leave it right there!
- I’ve already written about food here in Mexico City, but only from the Infectious Diseases perspective. Now I’ll be my mother’s son (she’s a food writer), and say the restaurants have been terrific, the food fresh, interesting-tasting, and reasonably priced, and the service attentive and professional. But — there was one glaring exception, and unfortunately it was the food at the convention center, which consisted mostly of wilted salads, sandwiches with scary soft meat-like products (colored a disturbing faded gray), and (I think, don’t hold me to this) tuna salad. As lines for food during lunchtime were 15-30 minutes long, it became quite easy to skip the mid-day meal or subsist on potato chips, water, and coffee, probably not the healthiest diet on the planet. I got back to my hotel room absolutely famished every day.
- All of these conferences have a theme — this one is “Universal Action Now” (italics theirs). Pretty good. I suppose one could fashion a challenging trivia quiz, asking people to match the theme with the city and date: “Time to Deliver” (Toronto, 2006), “Access for All” (Bangkok 2004), “Knowledge and Commitment for Action” (Barcelona 2002), “Break the Silence” (Durban 2000), “Bridging the Gap” (Geneva 1998) … Good sentiments all, but Durban wins by a mile. Of course if they had the conference in Boston, the theme would be, “Let’s go Red Sox.”
(I guess I’m getting a bit homesick.)
August 4th, 2008
Mexico City: Drive on the right … most of the time
Some early and completely non-scientific observations from the XVII AIDS Conference, taking place now in Mexico City:
- Everyone said getting to and from the Banamex Convention Center would be difficult, and of course they were right. Mexico City is the largest city in the Western Hemisphere, has a road/traffic system that makes driving in Boston seem downright peaceful by comparison (that is hard to do), and of course none of the hotels are anywhere near the meeting. But it’s not as if we haven’t been through this before — namely, here in Bangkok and here in Rio, to cite some recent examples. So no big deal. But … I did experience something traffic-wise that was truly bizarre: On the drive in from the airport, the cab driver took a right turn onto a street and drove on the left for around a tenth of a mile, while the oncoming traffic was on the right — and it was actually planned that way, pefectly legal. To repeat (if that wasn’t clear): we were driving British style. According to the cab driver, it’s because left turns off some roads have become so congested that they simply moved that lane from the right to the left; after the busy intersection passed, we moved back to the right. I kid you not.
- What do Infectious Diseases specialists from the United States eat and drink when they’re in Mexico City? If my completely haphazard survey is any guide, we’re all over the map (ahem) when it comes to food safety while traveling. One colleague said she couldn’t live without salad, and the idea of visiting Mexico without a margarita (requires ice) was too depressing even to consider; another said he was sticking by the rules, eating only thoroughly cooked foods and drinking bottled beverages from “reputable sources,” whatever that means. (Maybe this.) One other said that the street food was one of the best reasons to visit Mexico to begin with. So far my approach has been pure pragmatism and selfishness: if there’s a tasty low E coli option available, great — but if not, and something looks too delicious to pass up, I’ll take my chances.
- The weather in Mexico City is wonderfully, delightfully cool in August. For some reason, I expected a summertime furnace, but it’s much cooler here than in Boston due to the altitude. Was I the only one in the world who didn’t know that?
Back with more later, maybe with some “real” content.
July 25th, 2008
Word salad: Jalapenos, abacavir, doripenem, and PAVE
Some miscellaneous recent items from the ID/HIV world jumbling around this Friday:
- Tomatoes are off the hook — it’s the jalapenos that likely caused the recent salmonella outbreak. Since this is the only time of year that tomatoes are even edible in this part of the world, I for one am quite relieved. I am sure many are wondering how bacteria could survive on those very hot peppers.
- HLA-B*5701 testing is now “officially” recommended before abacavir use to reduce the risk of hypersensitivity — it’s now in the package insert. We started doing this test two years ago (at the strong encouragement of some British and Australian colleagues), and it makes all the difference in the world when prescribing this drug — the counseling to patients about the safety of abacavir drops from a 30-minute terrifying review of possible death to a 5-minute, “this could happen, but it won’t.” Two further thoughts: 1) It’s too bad we didn’t have this tool available sooner (likely lots of debate within the boardrooms of the manufacturer on the pros and cons from a sales perspective); and, 2) Let’s hope that other companies can learn from this lesson and, if such tests are potentially available to improve patient safety, they move ahead quickly to validate them.
- Oh, and the other abacavir label change is related to the DAD data and the possible association between abacavir use and cardiac disease. Not much has changed since I last covered this issue, but one wonders what we’ll hear soon, either confirming or refuting this association. (Or likely, both confirming and refuting it.)
- In other FDA news, an advisory panel was split on whether to recommend approval of doripenem for treatment of nosocomial and ventilator-associated pneumonia — but overall narrowly favored approval. (No action by the FDA yet.) Not going to get into details of this particular drug or indication — the FDA’s decision is unlikely to change clinical practice in the short run — but isn’t it peculiar that we have a gazillion (stealing a word from one of our ID Fellows who speaks California-ese) cephalosporins, but only 4 carbapenems? And no oral option? Hey, imipenem was approved by the FDA in the mid 1980s! I asked a medicinal chemist about this a few years ago, and apparently it’s not so easy to synthesize these drugs — but the rise in ESBL-producing gram negatives certainly could (and should) spur further drug development.
- Last, the NIH halted plans to conduct the PAVE 100 HIV vaccine trial. The reason, obviously, is that this adenovirus-based vaccine strategy is similar in many ways to the one tested in the STEP trial — which showed that the vaccine not only didn’t work in protecting from HIV infection or lowering HIV RNA levels, but led to an increase in the risk of HIV acquisition for those persons vaccinated who had pre-existing adenovirus immunity. The challenges of developing an effective AIDS vaccine are legion, but here’s a particular tough one: can you imagine trying to write the informed consent for the next major efficacy trial? Yikes.
July 19th, 2008
“Floxins” and the black-box warning: Anyone notice? Anyone care?
Fluoroquinolones — the “floxins”, every medical house officer’s favorite antibiotic class — will carry a black-box warning about the risk of tendinitis and tendon rupture. We’ve known about this side effect for years, why now the change? In FDA speak:
FDA’s recent evaluation of the medical literature and the post-marketing adverse event reports submitted to the Adverse Events Reporting System (AERS) confirmed that serious reports of tendinitis and tendon rupture with the fluoroquinolones continue to be reported in similar or increased numbers.
In other words, the rate of this side effect hasn’t increased. Or it has.
Regardless, it’s a good idea to get this information out to practitioners. The use of these drugs is so pervasive I suspect some clinicians believe that patients suffer from levofloxacin deficiency. (Cure: give levofloxacin.) Since they’re used so commonly, even rare severe side effects are important.
And when Achilles tendon rupture occurs, it’s pretty devastating. Pain, then surgery, then immobility for months. I’ve seen 3 cases, one of which ironically occurred in a pediatrician — who I bet won’t prescribe a quinolone to kids even if the drugs ultimately get approved for pediatric use. One hopes that telling a patient to stop the drug and avoid exercise if pain or swelling occurs while on a quinolone might prevent the tendon from rupturing.
Will this change prescribing practices, either in the hospital or office setting? Doubtful — the side effect is pretty darn rare, and it seems to be a local ordinance in some hospitals that every patient must receive at least one dose of levofloxacin before discharge. Nonetheless, it’s a good reminder that even our best drugs have some warts.
Paul E. Sax, MD
Contributing Editor
NEJM Journal Watch
Infectious Diseases
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