An ongoing dialogue on HIV/AIDS, infectious diseases,
January 10th, 2010
Ceftobiprole’s Long Road to Approval Gets Longer
Cephalosporins with activity against MRSA are out there, but we don’t have them yet. Just recently, the leader of the pack, ceftobiprole, hit another roadblock:
The FDA has indicated in its Complete Response Letter to Johnson & Johnson PRD that it has completed the review of the application and has determined that it cannot approve the application in its present form … The Agency determined that data from Studies BAP00154 and BAP00414 cannot be relied upon because inspections and audits of approximately one-third of the clinical trial sites for these studies found the data from a large proportion of these sites to be unreliable or unverifiable, raising concerns regarding the overall data integrity for both studies
The recommendation from the FDA? Do more studies. (Which means more delay, more $$$.)
One of the great frustrations of antibiotic development is that there’s clearly a need for better drugs for MRSA — unlike, say, a new PPI — yet this pipeline has been pretty dry.
In fact, I bet not a day goes by in medical centers that this need is not readily apparent to ID doctors, surgeons, intensivists, pulmonologists, nephrologists (don’t dialysis patients seem to have the hardest time with MRSA?), endocrinologists (except maybe for people with diabetes), transplant specialists. Pretty much everyone knows this bug is common and hard to treat.
If we start with the premise that vancomycin is the gold standard — and a fairly tarnished one at that — what are our alternatives? Linezolid was a big advance (especially because it can be given orally), but it was approved ten years ago, is bacteriostatic, has certain unavoidable toxicity issues, and is costly, especially compared to other oral antibiotics. Daptomycin was a somewhat smaller step forward, and I confess I still haven’t had the occasion to use telavancin. Trimethoprim-sulfa and tetracyclines are active, but likely less so than vancomycin.
And ceftobiprole? The initial application to the FDA was submitted in 2007; it is already approved in several other countries. And while I have no idea whether the efficacy and safety of the drug will be preferable to what we have now — perhaps someone from Canada or Hong Kong or Europe can clue me in — just having more options for MRSA seems like a very good thing.
Ceftaroline/NXL104, anyone?
January 1st, 2010
Top 10 Stories of the Year
No end-of-year wrap-up is complete without a “Top 10” list, and Journal Watch: AIDS Clinical Care is no exception.
This year we did two lists, one chosen by the Editors, the other a numeric tally of what’s read on line by the Readers.
The “When to start” issue was the top story from the Editors.
The big hit from Readers was the case of occupational exposure from a source patient who refused testing. (I posted it here this past June.)
Not much overlap between the two lists, reflecting I think several issues:
- Editors are choosing from scientific advances; the readers from what they find clinically useful or interesting. They can be the same thing, but they don’t have to be. (Hardly doubt many were counting on IL-2 to enter the clinics this year, for example.)
- What people read on-line may be different from what they consider important. Some on-line stuff is just fun. Or funny. Or controversial.
- The on-line readership is given a big boost from Physician’s First Watch.
Hope you enjoy, and Happy New Year!
December 28th, 2009
Holiday Surprise: Generic Valacyclovir
Last week one of my patients went to refill a Valtrex prescription, and was offered generic valacyclovir for the first time. It made him nervous, so he requested I write a “brand-name only” script.
I confess the existence of a generic formulation of valacyclovir — which according to the PharmD here has been available for several months — was news to me. 
(Generic acylcovir and famciclovir* have been available for years.)
And while there is no reason to suspect generic valacylcovir will have any unusual issues related to efficacy or toxicity compared to the branded version, this Times article reminds us that this is not always the case:
Joe Graedon, who has been writing about pharmaceuticals for three decades and runs a consumer advocacy Web site, the People’s Pharmacy (peoplespharmacy.com), was 100 percent behind generics for many years. “We were the country’s leading generic enthusiasts,” he told me recently. But over the last eight or nine years, Mr. Graedon began hearing about “misadventures” from people who read his syndicated newspaper column.
What follows are some anecdotal experiences and opinions — largely from the psych, neurology, and cardiology fields — about the potential dangers of even slight differences in bioequivalence or excipients between branded and generic drugs. For even more of the same, read the comments section here.
Which brings me back to my patient: Since he’s taking the Valtrex for an unusual reason (recurrent HSV-related meningitis), and since he’s willing to pay extra for the branded version, I went ahead and wrote the “brand name only” script.
My thinking? Let’s see what a year or so of experience with generic valacyclovir brings us when used for more typical indications before making the switch.
(*Why isn’t this spelled “famcyclovir”?)
December 20th, 2009
Infections from Transplant Donors: Rare but Inevitable
Two kidney transplant patients are critically ill due to Balamuthia mandrillaris encephalitis they acquired from the organ donor:
The same infection probably killed the organ donor, but it was not diagnosed; his doctors thought he had an autoimmune disease. Two other patients also received heart and liver transplants from the donor, but neither has become ill.
Infections due to free-living amoeba are extremely rare; those acquired from transplant even more so.
Hence the lesson from these transplant-related cases is not that there’s a new threat to the health of transplant recipients.
But it’s a reminder that the infection risk will never be zero. We cannot test donors for every possible disease, and the shortage of available organs means that some donor-derived infections will inevitably continue.
(These LCMV cases caused quite the stir around here a few years ago.)
Organ transplantation remains one of the great miracles of medicine. With the caveat that I don’t know further details about this donor’s case, it seems that a (small) risk of donor-derived infection is the price of doing business.
(Edit: And now the WSJ has weighed in here. Focus is on those harmed by the infection, understandably, and the need to make the process safer — but the fact remains that transplant will never be 100% safe.)
December 13th, 2009
Infection and the ICU: Outcome Predictable, but Important
If you enrolled over 14,000 ICU patients into a study on a single day, and then did follow-up, what would you find regarding the relationship of infection to the outcomes of ICU stay and mortality?
Just such a study was published in JAMA last week, and here are the not-so-stunning conclusions:
Infections are common in patients in contemporary ICUs, and risk of infection increases with duration of ICU stay. In this large cohort, infection was independently associated with an increased risk of hospital death.
To an ID specialist, this is kind of like reading that someone has done a study linking time spent outside in the rain and the likelihood of becoming wet. Patients in ICUs are susceptible to getting infections for innumerable reasons — so many that it seems to us (from our admittedly biased perspective) almost remarkable when an infection doesn’t occur.
In all seriousness, ICU-related infections are a gargantuan problem, and if this study helps publicize the clinical and research needs, more power to it.
December 8th, 2009
Vancouver, Phishing Phlu Scam, Telavancin, and Cartoon
A few things to ponder as the flu activity (mercifully) declines, at least for now:
- Interested in evidence that HIV treatment has become staggeringly effective? Fully 87% of patients receiving treatment in the large British Columbia cohort have an HIV RNA < 50; not only that, the incidence of HIV drug resistance has declined more than 12-fold since 1997. Wow. I wouldn’t want to be in the business of selling resistance tests.
- Did you read about this scam? The text from the hoax is pretty awkward — “This profile has to be created both for the vaccinated people and the non-vaccinated ones” is a choice bit of prose — but one could easily imagine how it could trap at least somebody. And as an example of the levels to which humans will stoop to make money, using fear of a real virus to spread a computer one has to be way down there.
- Has anyone yet actually used telavancin? Not in a clinical trial, but in a patient in clinical practice? If so, what were the indications? How did it go?
- Related, here is a great cartoon — but there’s an even better one on antibiotics that has not yet appeared on-line at The Cartoon Bank, so stay tuned.
December 2nd, 2009
So Much in Less than a Week!
First the updated WHO Guidelines. Then the following:
- Updated DHHS Guidelines. Agree? Disagree? Sensible or crazy? Practical or ivory-tower academic?
- South Africa does the right thing. Yes, it’s about time, but good news nonetheless.
- 2012 International AIDS Meeting in Washington, D.C. First time in USA in a long, long time — 1990, to be exact — and possible now that entry restrictions on people living with HIV will be dropped in January 2010. So mark your calendars now, and make sure you dress light for the weather.
Why so much at once? World AIDS Day? Phase of the moon? Or just chance?
November 28th, 2009
ICAAC-IDSA — Alone Again (Naturally)
Just received my latest copy of Infectious Disease News, that large glossy review magazine* that arrives approximately monthly in my mailbox.
As usual, I turned right to Dr. Theodore C. Eickhoff’s always-thoughtful editorial, this month entitled “Reflections on the 47th IDSA Meeting.” He writes:
It was a much more “user-friendly” number of attendees, in contrast to the almost 15,000 people that attended the joint meeting last year. I heard absolutely no one express a desire to have another joint IDSA-ICAAC meeting.
I can see his point — the combined meeting in Washington last year drew over 15,000 participants, and at times was just too gargantuan to manage.
But if I could for a moment be the lone voice arguing for a joint meeting, here’s my pitch: Last year, tons of people in ID went to ICAAC-IDSA, even people who rarely go to either meeting. This year, not so much — which might explain the “somewhat muted and subdued” tone Eickhoff found at IDSA this year in Philadelphia.
Either that or what the Yankees were doing against the Phillies.
(*Don’t call it a “throwaway!”)
November 20th, 2009
Ties Tied to Bugs
Are doctors’ neckties causing infections? That’s the implication of this Wall Street Journal piece:
The list of things to avoid during flu season includes crowded buses, hospitals and handshakes. Consider adding this: your doctor’s necktie. … A 2004 analysis of neckties worn by 42 doctors and medical staffers at the New York Hospital Medical Center of Queens found that nearly half carried bacteria that could cause illnesses such as pneumonia and blood infections. That compared with 10% for ties worn by security guards at the hospital.
This is old news, of course (yet somehow it warranted front page coverage in the WSJ, go figure). In fact, the British went so far as to ban neckties for doctors entirely in 2006, stating a tie is an “unnecessary piece of clothing.” (No comments about ascots, however.)
One problem with the cited study in the WSJ is that it does not link the wearing of neckties to actual infections in patients — and I don’t think any study has. Meaning this: do the patients of the necktie-wearing docs get more infections than the patients of MDs who dress more casually?
If not, then it’s just another study of this ilk: “We cultured ________ [fill in the blank of some seemingly innocuous item — computer keyboard, reflex hammer, clock radio], and found evidence of staph and coliform bacteria in XX%. These results suggest that [insert item] should be sterilized prior to patient care.”
My hunch: neckties may carry bacteria — see this company’s antimicrobial neckties for vivid proof — but they are not themselves causing nosocomial infections.
But since I could be wrong on this one, should we get rid of neckties in the hospitals and clinics just in case?
Paul E. Sax, MD
Contributing Editor
NEJM Journal Watch
Infectious Diseases
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