One of our readers recently sent the blog the following comment:

“Anything new to add to comments in book about laser treatment of fungal nails?  In my area there are ads for DPMs offering this $1000 per treatment!  My question is; does it work?”

Up to this point I have been tacitly avoiding this topic waiting for all of the chips to fall into place.  I guess it is time to, at least give my initial thoughts.  I will start by disclosing that I was a member of the original Patholase/PinPointe Advisory Board although I am currently not working with that company and I am a current Advisory Board member for Nomir. Being under a non-disclosure agreement with both I must therefore be very careful to only give background information that is in the public domain and give only MY OPINION based on the information in the public domain so as not to let slip any confidential information that I may have picked up along the way.  This is another reason I have not written about this topic.     

Although there may be more than two commercial products to mention, I will limit my discussion to the two best known, the PinPointe Laser from Patholase and the Noveon Laser from Nomir.  These are totally different devices that use different forms of laser energy. As I write this NEITHER is FDA approved specifically for the treatment of onychomycosis although both have a device clearance for general podiatric and dermatologic use.  Interestingly, if you actually look for the specifics of that general definition, onychomycosis is not included.

To this point each company has taken very different marketing approaches.  PinPointe, despite not having the FDA approval, has been aggressively marketing the device to podiatrists based on their general usage clearance.  Up to this point, their publically available data supporting the use of the device for onychomycosis has been limited to a small number of patients originally treated pre-marketing and by early adapters of the device.  This data is not from a prospective, IRB approved, randomized controlled trial. To their credit, a quick search on www.clinicaltrials.gov under the term “onychomycosis” does reveal that they are currently engaged in such a clinical trial.  They also continue to collect retrospective data from current users.  To the best of my knowledge they have published no studies based on their clinical data or their technology. 

Nomir has taken the path of performing an initial three IRB approved, prospective clinical trials and has submitted their pivotal trial to the FDA in an attempt to receive an onychomycosis indication.  Their technology, using a dual wavelength (870 & 930 nm) near infrared (IR) laser light to cause photoinactivation of  both fungus and bacteria, including T. rubrum and MRSA, at physiologic temperatures, has been shown to be successful in vitro and in vivo, and was recently published by its developer Dr. Eric Bornstein http://www.nomirmedical.com/products/publications.htm in the Nov/Dec 2009 issue of Photochemistry and Photobiology.  They have also submitted the preliminary results of their pivotal clinical data for the treatment of onychomycosis which has been accepted for publication in a peer reviewed, indexed journal.  Although they have signed up podiatrists to be trained on the device, it has not yet been made commercially available. 

Enough background…to answer the question that initiated this discourse, I guess I would have to say that, yes, given the data I have seen, these two laser therapies do, in fact, show positive results in the treatment of onychomycosis.  Will they work in every patient with nail fungus?  Of course not!  Even oral terbinafine only had a 38% total cure rate in its clinical trials.  Which brings up another question…do they work even as well as the oral agents?  Frankly, no one can say at this point without seeing the results of the same type of well designed, controlled trials that those drugs went through.  I will say this much for certain, there is no risk of systemic toxicity with the lasers as there is with the oral drugs, no matter how rare.  Is the treatment worth $1000?  That is something that only an individual patient can answer.  I hear through the proverbial grapevine that there has been no shortage of folks willing to pay that or similar amounts for the treatment.  Heck, there are scores of physicians specializing in cosmetic treatments, some without rigidly controlled and studied FDA approved data, that have done quite well promoting their services.

Until more information is available on which definitive statements can be made, I would have to advise each of my readers to use their own moral and ethical compass in determining what is appropriate for their patients and their practice.   I would really appreciate any comments you may have if you are currently using a laser on either your own patient experience or if you have seen patients treated by other docs and their satisfaction level.

To any of my readers planning on attending the NY Clinical Conference this coming weekend, I will be in the exhibit hall at the DataTrace booth on Saturday January 30th.  I will be there to discuss this blog, sign copies of the 3rd Edition (not that it will increase the value of it…heck, it may diminish it!) and just generally hang out and meet anyone interested in discussing lower extremity infectious diseases.  Please come by and say “Hi”.

Two studies published in the January 7, 2010 issue of the New England Journal of Medicine have received a tremendous amount of play in the popular press.  One paper out of Baylor in Houston looked at comparing chlorhexidine + alcohol vs. povidone iodine as a preoperative surgical prep.  In a total of 849 subjects in the ITT analysis they found that the surgical site infection rate was significantly lower with the chlorhexidine + alcohol than it was with the old “standby” povidone iodine (9.5% v. 16.1% P=0.004) Here is a link to that abstract http://content.nejm.org/cgi/content/short/362/1/18.

The second study, out of the Netherlands, explored the issue of decolonization in nasal carriers of S. aureus.  http://content.nejm.org/cgi/content/short/362/1/9.  A total of 6771 patients were screened on admission using PCR for rapid identification of the Staph.  1270 swabs were positive, 808 underwent a surgical procedure.  The patients were all treated with mupirocin nasal ointment and chlorhexidine soap vs. a placebo.  The rate of S. aureus infection was 3.4% in the treated group vs. 7.7% in the placebo group.    Interestingly, ALL were methicillin susceptible (MSSA) so the study may, or may not be able to be extrapolated to MRSA carriage.

Hospital acquired infections, particularly surgical site infections cause a tremendous amount of morbidity and mortality not to mention costing billions of dollars to treat.  The monetary situation is complicated by CMS guidelines that may not pay a hospital for treatment of any nosocomial infection.  Therefore, new and improved techniques for minimizing these infections are being studied.  Some of what is done today for infection prevention in the surgical suite has not changed much in decades i.e. the use of the povidone iodine prep.  I remember doing those back when I was a surgical resident in the early 1980s!  Chlorhexidine is by no means a new product.  In fact, it may be older than povidone iodine.  A quick PubMed search finds papers going back to the 1960s.  More recently, the combination of chlorhexidine with alcohol has shown to be a better antiseptic with longer activity than chlorhexidine alone.  This is true not only for prepping the patient but also as a hand prep for the physician.  This recent study just shows us that as new high level evidence becomes available, we may have to change some very ingrained thoughts and practices.

As for the nasal carriage paper, I find that interesting and not unexpected.  What needs to be looked at is carriage of MRSA and surgical site infections.  There are some papers out there and I do discuss them in the book.  This is a more involved topic for another post. 

Telavancin (Vibativ – Theravance/Astellas) is a novel lipoglycopeptide, related to vancomycin, that has been recently approved by the FDA for the treatment of complicated skin and skin structure infections (cSSSI) caused by MRSA.  Telavancin now joins the ranks of vancomycin, linezolid, daptomycin and tigecycline as being the only 5 antibiotics with this approval.  An excellent review of this drug was published by Saravolatz, Stein and Johnson in the December 15, 2009 issue of Clinical Infectious Diseases.  Here is a link to the Abstract: http://www.journals.uchicago.edu/doi/abs/10.1086/648438 .  I highly recommend anyone interested in this drug to search out this complete article and familiarize yourself with it.

Without going into too much detail (which may infringe on copyright?), I would like to point out a few important take home messages that I got out of this paper and from my review of other literature on the subject. First some of the positives:

1.  The usual dose is 10mg/kg q24h.  Thus, we have the ease of a once daily dosing

2.  The drug is consistently bactericidal against most S. aureus.   Various reviews have shown that this probably has little impact in the treatment of cSSSI and may be more important in blood stream infections for which this drug is not approved.

3.  It is effective against MSSA, MRSA, VISA and hVISA.  It is also effective against daptomycin and linezolid resistant strains.  It does not have activity against the most common strains of VRE.

4.  Unlike vancomycin, there is no call to monitor serum trough levels

5.  In two pivotal cSSSI clinical trials it was found to be “non inferior” (FDA speak) to vancomycin. 63% of the S. aureus strains were MRSA making it the largest number of MRSA patients in a cSSSI study to date.

Now some downsides:

 1.  It is primarily excreted through the kidneys so significant dosage modification must be made in cases of renal insufficiency. The recommendations are the full 10 mg/kg q24h if the creatinine clearance is >50 mL/min, 7.5 mg/kg if 30-50 and 10 mg/kg q48h if the clearance is <30.

2.  Chronic, infected diabetic foot ulcerations were specifically excluded from the two pivotal trials!  I don’t see this drug receiving the coveted “…including diabetic foot infections” approval anytime soon.

3.  Although the overall safety looked comparable to vancomycin there were higher rates of some significant adverse events including altered taste, nausea and vomiting along with an increase in renal events.  On the other hand, vancomycin had higher rates of infusion reactions

4.  The drug has received a black box warning for fetal risk.

So what is the bottom line?  I agree with the authors of this review that we need new novel antibiotics to combat MRSA especially given all of the increasing reports of vancomycin MIC creep and treatment failures.  Many of the drugs that looked promising earlier in their development have either been slowed considerably (ceftobiprole) or stopped totally (oritavancin, iclaprim) so the once fertile pipeline is looking a bit thin.  Telavancin gives us one more drug to add to that relatively short list of alternatives to vanco especially with organisms that have developed resistance (although extremely rare) to those other antibiotics.  At this early point in its history, I am somewhat concerned about its lack of diabetic foot infection data and its increase in adverse events compared to vanco.  The black box may also impact some potential patients.  Given that we have other vanco alternatives with years of clinical experience, including diabetic foot data, and well known safety profiles I may feel more comfortable seeing more clinical data and published AE experiences before jumping in with both feet.