Minocycline and the Treatment of Multidrug-Resistant Acinetobacter baumannii

December 15th, 2014 by Warren S. Joseph DPM FIDSA
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When most of us think about minocycline it is for the oral treatment of gram positive infection, in particular MRSA.  In fact, the drug is effective against multidrug resistant gram negative organisms, including Acinetobacter baumannii (AB). This point was driven home to me recently when I saw that my favorite ID journal Clinical Infectious Diseases just published a supplement on the topic.  Here is the link to the Table of Contents.  All of the articles are available as free full text and can be downloaded from this link:

http://cid.oxfordjournals.org/content/59/suppl_6.toc#MINOCYCLINEFORTHETREATMENTOFMULTIDRUG-RESISTANTACINETOBACTERBAUMANNII

This supplement was sponsored by The Medicines Company www.themedicinescompany.com who are now marketing an IV formulation of minocycline for this purpose so take that into account while reading the papers. That being said, both of the Guest Editors, Debra Goff, PharmD and Keith Kaye MD, MPH are top quality, fair balanced researchers and authors. (Disclosure: I have NO financial relationship with this company)

The efficacy of minocycline against AB should not come as a huge surprise.  Tigecycline, a minocycline derivative, is often considered one of the drugs of choice for both ESBL and CRE producing gram negatives including MDR-AB.

Also of interest in this Supplement is a brief obituary for one of the true giants in the field of Infectious Diseases, Robert Moellering, Jr, MD.  I had the opportunity to meet Bob on a few occasions at various meetings and advisory boards.  He was a true gentleman who worked closely with the podiatrists at The Beth Israel Deaconess in Boston.  Over the years I have read his work and marveled at his brilliance.  He will be missed.

Posted in Antibiotics, Infection control, Infections, MRSA | No Comments »

The Press Reporting of ID and Antibiotics

December 12th, 2014 by Warren S. Joseph DPM FIDSA
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USA Today ran an interesting story yesterday about a 19 year old woman given an antibiotic by a friend for a “sore throat” who developed Stevens Johnson Syndrome.  This is a terrible incident and my thoughts and prayers go out to the young woman and her family.  What bothered me however was the way in which USA Today reported it.  Here is the link:

http://www.usatoday.com/story/news/nation/2014/12/11/teen-antibiotic-burn-inside-out/20249585/

Yes, it was reported that there was a teen who took an antibiotic making her “Burn From the Inside Out”.  Talk about sensationalism!  It appears that they got that phrase from a physician they contacted.  Now, I’m not questioning the accuracy of that description but it is the use of it in the headline that makes me shake my head.  CNN reported the same story with a more sedate headline: “A friend gave her an antibiotic; now she’s fighting for her life”

http://www.cnn.com/2014/12/10/health/california-antibiotic-allergic-reaction/index.html?hpt=hp_t2

This just got me thinking about other ways in which the lay press reports on infectious diseases and antibiotics.  How many articles have been written on “Super Bugs”?  What ARE “super bugs” anyway?  In one story they may be MRSA, in another CREs.  What about “flesh eating bacteria”?  Some of us remember back about 15 years ago when this term first became popularly used in the press.  It referred to a series of cases of Group A Streptococcal necrotizing fasciitis.  This was hardly a new infection, even back then.  It has probably been around since the beginning of time but boy did they run with it.  Then, within the past few years “flesh eating bacteria” somehow morphed from Group A Strep to MRSA.  Which is it?  Is it both?  I guess.

Finally, since I have been asked frequently, let’s look at Ebola.  Now I am not, and have never claimed to be an expert on viral diseases in general and Ebola in specific.  I have never seen or treated a case and hope to never come across it.  However, just a few weeks ago you could not turn on the TV, pick up a newspaper or magazine and not read about this terrible disease.  In fact, Time Magazine, rightly IMHO, just named those who fight Ebola as their “People of the Year”.  However, let’s put this into perspective.  To the best of my knowledge there were only TWO cases actually contracted in the US and both of those were health care workers directly treating the first unfortunate patient in Dallas.  That did not stop the news sources from rolling out expert after expert about how this disease could potentially spread here in the States, or maybe not.  People were freaking out.   For the first time in all my years of travel I was seeing folks wearing surgical masks on airplanes and taking out sanitizing wipes to treat the airplane seats and trays before sitting down (actually, probably not a bad idea!).  But, as the old saying goes, “today’s news is tomorrow’s fish wrapper”. Other than the Time story, I don’t think I have seen anything about the disease in a few weeks.

I guess the upside to all of this reporting is that it DOES make people more aware of infectious diseases and the potential dangers of inappropriately used antibiotics.  If just one person thinks twice and refuses an antibiotic proffered by a friend for a probable viral infection and remembers this poor woman and her fight with SJS, I guess the Press did their job.

 

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Medscape Interview about Diabetic Foot Osteomyelitis

December 8th, 2014 by Warren S. Joseph DPM FIDSA
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Just over a week ago my good friend and colleague in lower extremity ID, Mark Kosinski, DPM, FIDSA and I were interviewed by Miriam Tucker, a reporter for Medscape, about a recent paper that compared 6 weeks vs 12 weeks of antibiotic therapy for DFO that did not undergo surgical debridement.  The impetus for this interview was a study published in Diabetes Care by Tone, et.al.  Here are links to the PubMed abstract for that paper, and the original interview on Medscape along with a link to David Armstrong’s excellent “diabeticfootonline” blog where, with his permission and my thanks to him, I am cutting and pasting his reporting of this below. Although the article is a bit longer than my usual posting, I think it is worth reading as both Mark and I discuss what is unique and interesting about this excellent study.

http://www.ncbi.nlm.nih.gov/pubmed/25414157

http://diabeticfootonline.blogspot.com/2014/11/short-course-oral-antibiotics-as-good.html

http://www.medscape.com/viewarticle/835503

Dr. Armstrong’s Report:

Here’s a great summary and commentary regarding the work by Tone, et al that we previously posted featuring our SALSAmigos Warren S. Joseph and Mark Kosinski.  By Miriam E. Tucker (Medscape)

UPDATED November 27, 2014 // Six weeks of antibiotics may be sufficient for treating patients with diabetic foot osteomyelitis even in the absence of surgery, a new randomized prospective trial finds.

The results from 40 patients seen at five French general hospitals between 2007 and 2009 were  published onlineNovember 20 in Diabetes Care by infectious disease specialist Dr Alina Tone (Gustave Dron Hospital, Tourcoing, France) and colleagues.

Current guidelines by the Infectious Diseases Society of America (IDSA) call for 3 months or more of antibiotic therapy when diabetic foot osteomyelitis is not treated surgically or when residual dead bone remains after surgery. But in the new study, remission was achieved in about two-thirds of patients following either protocol (6 or 12 weeks of treatment).

The main finding of the study shows that “one can treat patients with diabetic foot osteomyelitis with only 6 weeks of treatment, despite infected bone [not being] removed,” principal investigator Dr Eric Senneville (Gustave Dron Hospital) told Medscape Medical News.

The primary aim of reducing the duration of antibiotic therapy “is to limit the pressure on bacteria and therefore to decrease the emergence of bacterial résistance,” he added, although he noted that the design of the current study did not allow this issue to be examined.

Also important and demonstrated in the trial, Dr Senneville said, was to reduce the number of adverse events related to antibiotics and risk of drug–drug interactions “because these patients usually have a lot of medications due to the frequent comorbidities reported in this population.”

Accumulating Evidence Addresses Several Important Issues 

This is a “good, well-done, high level of evidence study. It’s what we need in these patients,” said Dr Warren S Joseph, consultant in lower-extremity infectious diseases (Roxborough Memorial Hospital, Philadelphia, Pennsylvania) and coauthor of the IDSA guidelines along with Dr Senneville, when asked for comment.

Dr Joseph pointed out that the results address several areas of debate in the field. Not only did the study authors find 6 weeks of treatment to be as good as 12 weeks, but antibiotics were primarily given orally rather than intravenously, and in half of patients they were not given empirically but started once culture results were obtained, with no difference in outcomes.

And, the study also reinforces the overall idea—still under debate—that nonsurgical treatment is acceptable for selected patients with osteomyelitis.

“The evidence is getting stronger and stronger that there are alternative methods for treating osteomyelitis—some without surgery, some without intravenous antibiotics, for varying lengths of time—that work every bit as well as that old standby of 6 weeks of intravenous therapy,” Dr Joseph told Medscape Medical News.

“That’s why this study is important. It’s adding to the accumulated evidence out there that we have newer ways to treat osteomyelitis than just about everybody in the world thinks is the right way to do it.”

Dr Mark Kosinski (New York College of Podiatric Medicine, NY) agrees: “This is a well-designed, multicenter, prospective randomized study that significantly adds to our knowledge about treating diabetic foot osteomyelitis.”

“It is heartening to see that this study utilized oral meds as its primary treatment regimen,” Dr Kosinski told Medscape Medical News. “Over the years, IV antibiotics have remained for many (for better or worse) the perceived gold standard for treatment of diabetic foot osteomyelitis. Despite emerging evidence to the contrary, many clinicians still doggedly cling to the notion that IV is superior to oral for treating chronic bone infection.”

But “adherence to such dogma leads to overutilization of parenteral meds (which should be best reserved for treating acute infection), increases healthcare costs (increases length of hospital stay, placement of peripherally inserted central catheter lines, infusion nurses, materials associated with IV meds, etc), and presents the possibility of infection of the IV line itself,” he added.

Reducing Antimicrobial Use

In the French study, participants all had osteomyelitis complicating a neuropathic foot without peripheral arterial disease. Empirical antibiotics were prescribed while waiting for culture results only if the treating physician considered it necessary.

Antibiotics were selected based on the culture results and patient comorbidities, and were given orally for the entire time or intravenously for 5 to 7 days followed by oral administration for the rest of the time.

Staphylococcus aureus was the most common organism cultured from bone samples, followed by coagulase-negative staphylococci and gram-negative bacilli. Most of the infections (45%) were polymicrobial.

Oral coamoxiclav was prescribed empirically while waiting for culture results in 45% of patients, and in four of those 18 patients the pathogen turned out to be resistant to the antibiotic.

Empiric use of rifampin was discouraged, with good reason, Dr Senneville told Medscape Medical News. “Rifampin should never be used as an empirical therapy because of the risk of selection of rifampin-resistant bacteria.”

However, rifampin was the most frequently used antibiotic based on culture results (in 76%), followed by a fluoroquinolone (70%). A combination of the two was used in 47%.

Antibiotic-related adverse events occurred in 6 (30%) of the 20 patients randomized to 6-week treatment and 10 (50%) of the 20 patients in the 12-week group. Gastrointestinal symptoms related to rifampin were the most common adverse event (three vs nine episodes in the 6- and 12-week groups, respectively). Other adverse events did not differ between the groups.

Remission, defined as (1) the absence of local or systemic signs of infection, (2) stabilized or improved radiographic abnormalities on plain X-rays assessed at the end of treatment and 1 year, and (3) complete, sustained healing of the wound responsible for the underlying osteomyelitis, occurred in 26 patients (65%).

There was no significant difference in remission rates between the groups, with remission rates achieved in 12 patients (60%) in the 6-week group and 14 patients (70%) in the 12-week group.

The authors couldn’t identify any specific parameter that appeared to be associated with patient outcome, including methicillin-resistant S aureus; five of seven patients with methicillin-resistant S aureus still achieved remission.

The median delay of 14 days between bone biopsy and beginning of documented antibiotic therapy may appear surprising, they note, “but we think that diabetic foot osteomyelitis is not an indication for urgent antibiotic therapy, especially in patients with no signs of inflammation of the foot, which was the case in 22 (55%) of our patients.”

Indeed, there was no difference in outcome between patients treated with antibiotics immediately after bone biopsy compared with those given them after microbiological results were available (= .84).

They conclude that a further larger-scale study is warranted to assess other beneficial effects of a reduction in duration of antimicrobial therapy for diabetic foot osteomyelitis, especially with respect to the emergence of bacterial resistance and antibiotic-related adverse effects.

Evolving Views Regarding Antibiotic Therapy 

Dr Kosinski said he is impressed with the study methodology, particularly the inclusion of a bone-biopsy-recovered pathogen after a 2-week antibiotic-free period. “Bone biopsies are underutilized as a diagnostic modality, yet transcutaneous bone biopsies are easy to do, have a low complication rate, and yield valuable information as to the infecting organism toward which to direct antibiotic therapy.”

However, he noted a limitation of the work: the exclusion of patients with peripheral arterial disease. “It will be interesting to see if future studies will support similar conclusions in patients with compromised arterial supply, which so many of our patients with diabetes suffer from.”

Dr Joseph praised the investigators’ three-pronged definition of remission, noting it has been a matter of debate and is also an issue for the US Food and Drug Administration, which hasn’t approved a new antibiotic for diabetic osteomyelitis in over 20 years.

“FDA doesn’t have good guidance for industry on how to do an osteomyelitis study. No one has ever come up with a good definition on what constitutes a cure of osteomyelitis. [The authors] have done a decent job here—though not perfect—of trying to define it.”

Dr Joseph also pointed out that the guideline recommendations of 6 or 12 weeks of antibiotic therapy for various clinical scenarios does not have good supporting evidence. Moreover, recent studies suggest that in some cases in which surgery is performed, just 3 to 4 weeks therapy, or even no antibiotics, is sufficient.

“What excites me about this paper is it’s just one more piece of the puzzle…here they’re using 6 weeks, but it’s primarily oral [and there was no surgery]. Other studies have used less than 6 weeks when they’ve surgically removed bone. Frankly, [the authors] might have been able to go 4 weeks and get just as good a result as at 6 weeks. They just didn’t test that. That might be a next step.”

Dr Kosinski concurs: “I am also pleasantly surprised to see that the length of treatment may be significantly shorter than once thought,” and that the notion that diabetic foot osteomyelitis is always a surgical disease “is changing.”

“Likewise for the route of administration,” he added. “We now have at our disposal, antibiotics with high bioavailability after oral administration, antibiotics that may help change the widely held notion that parenteral is always better.”

“I have no doubt that by the time of the next incarnation of the IDSA guidelines, studies such as this one will play a role in their revision,” he concluded.

The study authors have reported no relevant financial relationships. Dr Joseph is a consultant to Dipexium Pharmaceuticals and consultant/speaker for Merck. Dr Kosinski had no disclosures.

Diabetes Care. Published online November 20, 2014. Abstract

 

 

Posted in Antibiotics, Diabetic Foot, Infections, Onychomycosis | No Comments »

Dalbavancin & Oritavancin – PART 2

November 17th, 2014 by Warren S. Joseph DPM FIDSA
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In my post last week I mentioned I would write a follow up to discuss my opinions on the use of these drugs for lower extremity infections.  I have not yet had the opportunity to try either so these are really “top line” thoughts taken what I know, have read or heard from others, into consideration.

– These drugs are expensive and I wonder who will cover the cost. The two doses of dalbavancin reportedly cost somewhere in the neighborhood of $4500 while the single dose of oritavancin is considerable less at around $2600 for the required single dose. Given hospital pharmacies are always worried about their budgets (they complained about the cost of linezolid when it was originally only about $1500!) can they be convinced to stock these drugs? What about insurance companies when they can demand patients receive generic vancomycin for next to no cost at all?

– The argument is made by the companies that these drugs will keep patients out of the hospital thus saving costs. That does make a lot of sense…on the surface. If you don’t admit the patient you don’t run up costs for the actual stay and only the outpatient treatment. The problem with this line of thinking is that many, especially for profit, hospitals make money by having “heads in beds”. The last thing they would want to do is decrease the number of admissions from the E.D. I make this statement with the disclosure that I am far from expert in hospital reimbursement economics, it’s just what I have been told by some hospital administrators.

– Who will make the decision to administer these drugs? The Emergency Physician? I doubt most would feel comfortable with these antibiotics. Furthermore, would they just stock it in the E.D? Who’s budget does it go under? The Pharmacy or the E.D.? What about the out-patient infusion center. This is probably the most likely scenario, especially if run/owned by an ID specialist, depending or reimbursement considerations.

– If the patient did receive a dose in the E.D. and the decision was made to admit the patient, the patient no longer needs IV antibiotics. Would the admission be denied as not meeting hospital level care?

– What if the patient developed an adverse event (“AE”). Neither of these drugs is dialyzed out of the blood. Will the AE be present for the entire length of the half life? That being said the clinical trials showed that AEs were rare and those that did occur were self limiting. Of course, with widespread use of any new drug previously untoward reactions can be discovered.

I guess my bottom line is that I am totally fascinated by these drugs and their unique pharmacokinetics.  I can see weekly doses to treat osteomyelitis (although neither are FDA approved for this nor even tested).  I can see taking a patient with an infection who is not doing well on an oral MRSA drugs, such as doxycycline or TMP/SMX, and just treating them with an IV dose or two.  Perhaps, treating a patient who, for whatever reason, can’t take oral linezolid or tedizolid but does not require hospitalization for their infection is another potential use. I will continue to watch and learn about these two new drugs whenever I can and pass along any information I can.

Posted in Antibiotics, Infections, MRSA, Osteomyelitis | No Comments »

New Antibiotics – Dalbavancin & Oritavancin PART 1

November 10th, 2014 by Warren S. Joseph DPM FIDSA
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In this entry I will continue to explore some of the new antibiotics that have been recently approved for use in acute bacterial skin and skin structure infections (ABSSSI). I will discuss these two together since they are quite similar in a number of important ways and share many of the same properties.

Both dalbavancin (Dalvance™ – Actavis) and oritavancin (Orbactive™ – The Medicines Company) are classified as “semisynthetic lipoglycopeptide” antibiotics. Both are effective against resistant gram positive organisms including MRSA.  They have both been around for quite awhile having been studied and then turned down for approval by the FDA back around 2007-8 citing lack of sufficient data.  Both were then dropped by their original companies and eventually picked up by others who finished the study process to get them FDA approved.  They also both share similar pharmacokinetics with very long half lives allowing weekly dosing.  Dalbavancin is dosed 1 gram IV on day 1 followed by 500mg on day 8, while Oritavancin is given in a single 1200mg IV dose.

In the Phase III clinical trials for dalbavancin, entitled the “Discover 1 & Discover 2 “ trials (http://www.nejm.org/doi/full/10.1056/NEJMoa1310480 ), dalbavancin given in the 2 dose regimen was found to be noninferior to IV vancomycin followed by po linezolid  (clinical success 90.6% for Dalbavancin vs. 93.8% for the comparator) with adverse events being less frequent in the dalbavancin group.

Similarly, in the two Phase III trials of oritavancin (http://www.nejm.org/doi/full/10.1056/NEJMoa1310422) the single dose regimen was compared to twice daily IV vancomycin for 7 to 10 days.  The primary end point (reduction in lesion size by 20% at 48-72 hours – the current FDA standard and probable topic for a future post) was met in 82.3% for oritavancin vs. 78.9% of the time.  Although adverse event rates were similar, nausea was found more commonly in the oritavancin group.

So, where do these drugs fit in terms of our clinical usage in the management of lower extremity infections? As you can imagine, I have my opinions…but you will have to wait for my next post!

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ONYCHOMYCOSIS – What Are We Teaching?

November 3rd, 2014 by Warren S. Joseph DPM FIDSA
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I have been doing LOTS of talks on onychomycosis over the past few months. The vast majority of these have been CME lectures where I spend significantly more time reviewing the background information of onycho than talking about new drug therapies.  What has amazed me since I first started speaking on this topic over 25 years ago is the lack of understanding of the science behind this INFECTION.  Yes, you read that correctly…onychomycosis is an INFECTION and should be treated with anti-INFECTIVES.  We don’t think twice about treating a bacterial infection with an antibiotic, why don’t we feel as strongly about treating a fungal infection with an antifungal?  This has been my introductory statement in every lecture I give about this disease since I first became interested in this topic and my feeling has not waivered about it.

Perhaps I will expand upon that concept in a future post but for this entry, I want to talk about the total lack of understanding/interest in learning about onycho exhibited by our next generation of this profession; our students and residents. Many students and residents have been attending some of these CME lectures. I don’t know that they are necessarily there to hear my talk or rather it is just a diversion between the “more interesting” surgical topics that are being presented at the same meetings.  Their lack of knowledge about onychomycosis, however, was driven home to me recently while I was speaking at the PRESENT Residency Summit in Teaneck, NJ.

At this well attended seminar I was in front of close to 200 podiatric residents. I started my talk by polling the audience asking how many of them could recite for me the Lauge Hansen Classification of ankle fractures.  As you could imagine, every single resident raised their hand.  I then asked how many could recite the Zaias Classification of onychomycosis**…NOT A SINGLE HAND was raised!  My comment to them was: “Let me get this straight.  Everyone one of you can recite a classification system for a condition that 1/3 of  you may see twice a year but NONE of you can recite the classification system used in every scientific paper written about a condition you will see 20-30 times a day!”

I believe that this is an indictment of our educational system. This lack of knowledge is not necessarily the fault of the residents/students.  They are just learning what has been preached to them as being “important” by their school faculty residency directors and attendings.  Onychomycosis is something to be palliated (debrided, trimmed, ground, etc) and then discharged and reappointed for 60+ days, not treated as the potentially important infection that it is.  I am afraid that more is being taught about how to properly code onychomycosis than any science behind it. (There are, of course, notable faculty members who really believe in teaching this information as something critically important)  We need to start concentrating on the cognitive, medical aspects of podiatric medicine as well as, if not even more than surgical technique.  Being as common a condition as it is, I see no better place to start that new paradigm of podiatric education than in teaching about onychomycosis.

**In 1972, Nardo Zaias, MD, one of the “Godfathers” of onychomycosis in the dermatology world, developed the classification system that is still used today (with some minor modifications) identifying 4 types: Distal Subungual (DSO), White Superficial (WSO), Proximal Subungual (PSO) and Candidal onychomycosis

Posted in Infections, Onychomycosis | No Comments »

New Antibiotics – Tedizolid

October 23rd, 2014 by Warren S. Joseph DPM FIDSA
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As I mentioned in my previous post, this has been a pretty exciting time in the area of lower extremity infectious diseases. Not only do we have 2 new drugs for onychomycosis (to be covered in future posts) but we also have 3 new FDA approved antibiotics for the treatment of, in FDA Speak; “acute bacterial skin and skin structure infections” (aBSSSI).  These drugs are tedizolid, dalbavancin and oritavancin.  Of these, the one that I am most interested in, at least at this moment, is tedizolid.

Tedizolid phosphate (Sivextro™, Cubist) is an oxazolidinone antibiotic. This is only the second drug in this class to be approved, the first being linezolid back in 2000.  As with linezolid, its spectrum of activity is essentially gram positive organisms including MRSA and VRE.  The difference between the two drugs is what makes it interesting. Linezolid is dosed 600mg (IV or PO) q12h for 10 days.  Tedizolid is dosed 200mg (IV or PO) once daily for only 6 days. By giving the significantly lower dose for a shorter period of time leading to a much lower total drug exposure, some of the more commonly feared adverse events found with linezolid, in particular myelosuppression and possible serotonin syndrome in patients taking SSRIs, look to be significantly lessened, if not totally eliminated. Furthermore, the cost, always an issue when trying to prescribe linezolid, should also be lower.

The two pivotal clinical trials, titled ESTABLISH -1 (oral only) and ESTABLISH-2 (IV with possible switch to oral;

http://www.ncbi.nlm.nih.gov/pubmed/23403680 http://www.ncbi.nlm.nih.gov/pubmed/24909499

Compared tedizolid 200mg daily for 6 days to linezolid 600mg q12h for 10 days. Both studies found tedizolid to be non-inferior (also FDA speak) to linezolid.

So where does this new drug fit in the treatment of lower extremity infections? Because it was approved under the more recent FDA aBSSSI Guidance as opposed to the previous “complicated skin and skin structure infection” guidance, diabetic foot infections is specifically excluded.  This is a flaw in the current aBSSSI guidance document that some of us have been debating with FDA. That does not mean it won’t work in DFI, just that it was not included in the trials.  Furthermore, just because there were no DFIs does NOT mean that there weren’t any lower extremity infections.  In fact, about 40% of the patients in the trials did, in fact, have infections of the lower extremity including infected ulcers, surgical wounds, abscesses, etc.

Given its narrow spectrum of activity against pathogens we find, shorter duration of therapy and possibly enhanced safety profile, tedizolid seems to fit nicely with current concepts of antimicrobial stewardship. This is one new antibiotic that I feel may have an excellent niche in the treatment of LEIs.

Posted in Antibiotics, Diabetic Foot, Infections, MRSA, Wounds | No Comments »

I’M BAAAACCK

October 20th, 2014 by Warren S. Joseph DPM FIDSA
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Dear Readers,

It’s been awhile. Time really does fly. I realize it has been over a year and a half since my last post. I really don’t have any excuses. Life just seems to happen that way. One day I am posting all sorts of updates on what’s happening in the world of lower extremity infections and then I just stopped. Over these past months, I have had a number of people ask me what ever happened to the blog as they really enjoyed reading it and felt it was valuable. I’ve heard from students, residents, colleagues, my publisher and a surprising number of people I would have never expected to be interested. It made me realize how large my readership and reach really was.

I’ve heard you. I believe that the time is finally right to start things up again. You may have seen the recent ad that DataTrace placed on PM News about the resurrection of the blog. www.podiatrym.com/pmnews.cfm.  There has been quite a bit happening in the world of antibiotics and antifungals for onychomycosis. After having only one FDA approved antibiotic in 5 years, now we have had 3 new drugs released in just a few months. The antifungal situation is even more exciting. It has been 15 years since any new drug has been approved for the treatment of onychomycosis. In just over a month this summer, two new topical agents were approved and are now being marketed. And, that is just the beginning. The literature continues to contain studies on diabetic foot infections, onychomycosis and osteomyelitis at a seemingly increasing rate. I have become a big fan of My NCBI (www.ncbi.nlm.nih.gov/) a free service that allows you to sign up for alerts to newly published literature using any search terms you wish. For example, every Monday morning I receive weekly emails alerting me to papers on the topics of “foot osteomyelitis”, “diabetic foot infections”, and “onychomycosis”.

Over the next few weeks I hope to cover all of these topics and more. I may experiment a bit with format providing some really brief entries to compliment the longer more in-depth posts that really take some time and effort to sit down and write.

I want to thank all of you who have inquired about the blog and asked me to re-start it. Also, thank you to ALL of my readers. The site had quite a nice sized following in the past and I hope to build it back up and surpass that reach in the near future.

Posted in Antibiotics, Diabetic Foot, Osteomyelitis | No Comments »

News Story About Pharma Industry Payments – Response

March 13th, 2013 by Warren S. Joseph DPM FIDSA
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I am sorry that it has been so long since I put up a post.  Things have been slightly hectic. Unfortunately, instead of reporting on new infectious disease information, with this entry I find myself responding to a story about my receiving payments to lecture from the pharmaceutical industry.  The story ran today (3/13/13) in the Philadelphia Inquirer and online at www.philly.com/philly/health/
20130312_Philly_foot_doc_among_highest_paid_by_Big_Pharma.html

When the original print story was run I had not had a chance to respond to the author, reporter Sam Woods.  I give Mr. Woods credit for updating the online story in response to some of my comments, reproduced below, which I emailed to him this morning.

I feel that the Pharma Industry has done an excellent job in disseminating important information that may otherwise not be available to those of us interested in saving limbs of patients with diabetes.  This is done in an unbiased, government approved and monitored way, under strict federal guidance.  My lectures are randomly, and independently audited for compliance with these guidelines and I have never been found to be deficient.

Here is my response to Mr. Wood in its entirety:

Sam

I read your article from today in Philly.com.  Just to respond to a few items:

1.   I did not call you yesterday since my family was at my father’s deathbed.  We lost him last night at 7PM.  You will probably see the obit in the Inquirer in the next day or so.  I had every intention of contacting you this morning (as I am doing now)

2.  As to responding to ProPublica, they phoned me while I was out of the country lecturing at a continuing education (non Pharma sponsored) meeting.

3.  All of my lectures given for the Pharma industry follow strict FDA guidelines and are consistent with the corporate integrity agreements entered into between the companies and the government.  There is full disclosure of this fact at all lectures.

4.  I have not worked at the Coatesville VA in a number of years.  I strictly work out of Roxborough and am a private, self-employed citizen; not an employee of any company, government, hospital, or health care organization.

5.  Thank you for at least quoting the article from last year.  I stand by what I said there.  Some organizations have an agenda to make interactions between Pharma and doctors somehow seem nefarious.  Let me give you some statistics if you want the REAL story:  There are 28 million people in the US with diabetes.  About 350 million worldwide (and yes, I have lectured around the world on this topic).  It used to be said that someone in the world loses a limb to diabetes every 30 seconds.  That is now down to every 20 seconds.  Diabetes is the cause for about 70-80,000 amputations per year in the US alone.  The single greatest cause. The 5 year mortality of people who present to their doctors for the first time with a diabetic foot ulceration is HIGHER than the 5 year mortality for breast cancer, prostate cancer and Hodgkin’s lymphoma.  If you add peripheral arterial disease to that, the 5 year mortality is even higher than colorectal cancer.  Diabetic foot infection accounts for about 33% of the >$100 BILLION spent on patients with diabetes each year and accounts for the greatest number of hospital days YET the NIH only provides <0.2% of all of their diabetes funding to study foot complications (soon to be presented new data).  The vast majority of research in the treatment of diabetic foot infections has been done by the private sector including the Pharma industry.  Yes, I go out and spread this information to my colleagues and it is often paid for by industry. However, by doing so I know I have saved countless limbs and lives.  Frankly, I don’t see anything nefarious about that…only good.

Kind Regards,

Warren Joseph, DPM, FIDSA

Consultant, Lower Extremity Infectious Diseases

Posted in Diabetic Foot, Infections, Uncategorized | No Comments »

Off Label Drug Promotion…Coming Soon?

December 12th, 2012 by Warren S. Joseph DPM FIDSA
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(I want to thank my friend and colleague Jeff Karr, DPM (www.osteomyelitiscenter.com) for alerting me to this news story.)

Just this past week the U.S. Second Circuit Court of Appeals ruled to prohibit criminal prosecution for truthful off label promotion of drugs as a First Amendment right. An excellent analysis of the case can by the law firm of Morgan, Lewis and Bockius can be found at:  http://www.morganlewis.com/pubs/WhiteCollar_LF_CriminalProsecutionTruthfulOff-LabelPromotion_6dec12.pdf and I direct anyone interested to read this summary.  I will not go into details but, rather, discuss how this may affect antibiotics and lower extremity infections (LEIs). 

The case, United States v. Caronia, was against a drug rep who was taped on two occasions discussing off label use of a drug, Xyrem used for narcolepsy, which is a misdemeanor.  From my interpretation of the referenced information, it appears that the Court decided that since the Food, Drug and Cosmetic Act allows physicians to legally prescribe any licensed drug for any indication, promotion of such use, as long as it was not false or misleading, was a “lawful activity” protected by the First Amendment. 

I will start by saying that I don’t believe that this will open the floodgates for armies of drug reps knocking down doors to speak about unapproved uses.  This will probably have to go higher in the court system with the next step being the Supreme Court.  Furthermore, many of the Big Pharma players are running somewhat scared of the Feds right now having sustained multi- BILLION dollar fines and signing “Corporate Integrity Agreements” with the Government that puts very strict rules in place on what they can, and cannot, do in terms of promotion. 

How does this impact antibiotics and LEIs?  Currently we only have 3 antibiotics FDA approved for the treatment of Diabetic Foot Infection; ertapenem, linezolid and piperacillin/tazobactam.  This may not change in the near future.  Under the current “Acute Bacterial Skin and Skin Structure Infection” (aBSSSI) guidance being followed by the FDA for new antibiotic approval, diabetic foot infection has been SPECIFICALLY EXCLUDED.  Although I am hoping that will change in the near future, without a pathway for approval, I don’t see any antibiotics being tested for this until there is a change in policy at the Agency.  A similar situation exists with osteomyelitis.  Because the FDA does not currently have Guidance for Industry on performing a clinical trial for osteo, no antibiotic has been approved for the indication in close to 20 years.  In the meantime, there have been a number of excellent antibiotics with good clinical data for both DFI and osteo that have not been promoted for lack of indication.  If this current ruling stands I don’t see why a rep couldn’t speak to a doc in a truthful and scientific manner, using published literature, to discuss the possible off-label use of a given drug.  I really feel that all would benefit.  The physician would be getting sound information to which they may not have been aware and the patient would receive evidenced based therapies which may currently be withheld from them over fears of unlabeled use.  To me, this is a no-brainer.  Thoughts?  Comments?

Posted in Antibiotics, Diabetic Foot, Infections, Osteomyelitis | 2 Comments »

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