There is a small group of us that, when we find an interesting article dealing with infections, we pass them on so we can all be stay up to date.  Some of the journals are fairly obscure and are not in my usual monthly reading so I find this a great way to read articles I wouldn’t normally come across.  Below are three such recent papers, all either still ePub ahead of print or recently published about which I find interesting enough to say a few words.

McCarthy NL, et al.  Health care-associated and community associated MRSA infections: A comparison of Definitions.  American Journal of Infection Control, 2010:  This retrospective chart review attempts to determine risk factors for CA-MRSA and HA-MRSA based on two commonly used definitions; the epidemiology of the infection and the phenotypic antibiotic sensitivity without looking at the genotype (i.e. looking for the SCCmecIV gene to determine a USA300 strain).  Not surprisingly, to quote their Conclusion from the Abstract “We found few differences between CA- and HA-MRSA infections regardless of how health care association was found. We believe that the migration of CA-MRSA into health care settings and the recent increasing antibiotic resistance of CA-MRSA strains contribute to the lack of factors associated with HA (vs CA) MRSA.”  One finding I did think was particularly relevant was that CA-MRSA accounted for the overwhelming majority of skin and soft tissue infections (p <.0001).

For the past year or two I have been lecturing and writing that the use of classic “risk factors” to determine HA vs CA was a technique of the past. This was recently driven home to me when I saw 3 patients in the hospital with MSSA, 2 of whom were 80+ years old and lived in long term care facilities while I had a perfectly healthy 30 something with no pertinent medical history whatsoever present with a CA-MRSA.  I still continue to use the phenotypic method of looking at antibiotic susceptibilities, particularly toward Bactrim and tetracyclines since we have not seen much CA-MRSA resistance to these drugs at our facility.  It is becoming clearer that perhaps we will need to do the genetic typing, such as the TEM-PCR I discussed in a recent post to really know what we have.  Of course, it may be a moot point in skin and skin structure infections since, as validated by this report, I don’t remember seeing an HA-MRSA in over 2 years.

Nagoba BS et al. A Simple and effective approach for the treatment of diabetic foot ulcers with different Wagner grades.  International Wound Journal, April 23, 2010:  This is a retrospective case series from India that collected data from 1998 into 2009.  They looked at the application of a 3% citric acid gel preparation onto 115 diabetic foot ulcerations of various Wagner classification severities up to, and not including grades IV and V.  Of interest to me was that they took cultures of all of the wounds and performed broth dilution sensitivities of all the organisms against the citric acid.  They found that in grade I-II ulcerations they had 94%+ healing in 5-34 applications.  They also found that in deeper wounds there was marked decrease in slough and drainage with increases in healthy granulation.  They concluded that citric acid was safe and maybe even promoted granulation tissue while killing the bacteria found on the wounds.   

I find various problems with the design of this study and am not reporting it because I consider it an earth shattering breakthrough.  Rather, I bring it to your attention because, currently, one of the “Holy Grails” of wound healing is to find an safe, effective, affordable topical antimicrobial to, perhaps, assist in wound healing.  Heck, I am still not even convinced that bioburden reduction is all that many claim it is, as I have blogged before, however, we are all programmed to kill bacteria on a wound and maybe this is an option.  It should probably at least be looked at in more detail.

Traunmuller F, et al. Linezolid concentrations in infected soft tissue and bone following repetitive doses in diabetic patients with bacterial foot infections.  International Journal of Antimicrobial Agents, 2010:  This study assayed fluid from interstitial spaced, inflamed subcutaneous adipose tissue and metatarsal bone from patients with inflamed diabetic foot infections who were at steady state condition after 600 mg twice daily dosing of linezolid.  What they found was not particularly surprising; in all tissues linezolid penetrated to a level that was similar, if not slightly higher than what was found in plasma.  To quote their Abstract “We conclude that linezolid administered at 600 mg twice daily may be considered an effective treatment in diabetic patients suffering from bacterial foot infections complicated by osteomyelitis”. 

We all know that linezolid is not FDA indicated for the treatment of osteomyelitis.  In fact, NO antibiotic marketed in the past 10-12 years has been indicated for osteo, not because they don’t work but because the FDA has not developed “Guidance for Industry” on how to perform an osteomyelitis study.  I have also never been a believer in the concept of “bone penetration” as being an important indicator of osteo efficacy.  They techniques have never been standardized and really, to my mind, penetration numbers mean nothing. That all being said, at least this paper gives those of you who remain stuck on the concept of bone penetration evidence that linezolid does get into, not only bone but also frankly infected diabetic foot tissues.  This is not unlike data published by Gary Stein, PharmD and recently reviewed in the Jan/Feb 2010 issue of the Journal of the American Podiatric Medical Association (Nicolau DP, Stein GE. Therapeutic options for diabetic foot infections: A review with an emphasis on tissue penetration characteristics)

I will be in Columbus, OH for the Region IV (Ohio) meeting to lecture on June 3, 2010.  I have been given the “Learning Lunch” spot from 12:00 to 1:30 and plan on covering a broad range of lower extremity infectious diseases topics including MRSA, antibiotic therapy for osteomyelitis and diabetic foot infections.

Prior to my session, I will be in the Exhibit Hall from 9:30 – 11:30 at the Data Trace Booth to sign copies of the Handbook, talk about this blog and just answer questions anyone might have about treating infections.

I hope to see folks there!

The following is from the text I sent to Podiatry Today Magazine for an upcoming feature they are planning on Innovations in Podiatry.  I really feel that molecular diagnosis of infection has the potential to change the way we diagnose and ultimately treat lower extremity infections.  The company I discuss in the article below, Diatherix, has a unique technology that allows the identification of up to 25 organisms from a single specimen and a single run of the test yielding results in just a few hours.  Just for full disclosure, although I have met with the CEO of the company to discuss the technology I have no financial interest or other conflicts at this time:

The current standard for making a bacteriologic diagnosis of a lower extremity infection is the use of a culture and sensitivity.   The problem with this test is that it may take several days to obtain a result while the patient has been placed on empiric antibiotic therapy that may be either too broad or too narrow spectrum.  Although Polymerase Chain Reaction (PCR), to look at the DNA of the organisms found on a specimen, has been used for a number of years to rapidly identify the bacteria, it has been limited mostly to reference laboratories and is hindered by usually only being able to identify one organism at a time.  This is changing with the use of Target Enriched Multiplex-PCR (Tem-PCR) which has the ability to identify up to 25 or more organisms with a single sample and to do it within just a few hours. A company based out of Huntsville, AL, Diatherix, is now commercializing this technology so that any physician in an office or wound center can order this test.  The clinician receives swabs and transfer materials, including overnight mailers from the company.  They take a specimen, as they would a standard C&S; place it in the mailer to Diatherix which receives it the next morning.  By that afternoon a result is communicated to the clinician including the identity of the organism, its relative frequency compared to other bacteria found in the specimen and any genetic markers for resistance, such as the presence of the mecA gene indicating MRSA.

By accurately identifying disease-producing pathogens early, Tem-PCR results can assist physicians in forming a more accurate diagnosis. This provides them the opportunity to accurately diagnosis the condition which leads to the appropriate treatment rather than treating empirically. By enabling physicians to link diagnostics to therapeutics, Tem-PCR results can assist by eliminating the inappropriate use of antibiotics eliminating unnecessary treatments, reducing the development of genetic drug resistance, potentially reducing cost of therapy and providing a better patient outcome.

The Tem-PCR technology provides multiplex amplification of genomic material from multiple pathogens with greatly increased sensitivity compared to standard multiplex PCR.  Standard multiplex PCR in general cannot amplify multiple pathogens in a single analysis due to each set of primers requiring differing optimum conditions for best amplification.  Tem-PCR works around this by essentially turning the multiplex into a singleplex reaction needing one primer set and one set of optimum conditions so that the best amplification can be obtained.  This allows more results from a single sample as a benefit of Tem-PCR over both singleplex PCR and qPCR (real time PCR).

Three significant benefits of producing multiple results from a single sample are being able to accurately identify pathogens causing infection in a rapid fashion, the identification of co-infections and the identification of genetic drug resistance. If a patient presents with a wound that is not healing a physician will perform a culture in order to identify the pathogen or pathogens present. At this point the physician will often treat the symptoms empirically due to the multitude of pathogens that could be causing the infection.  If the patient is on antibiotics at the time the sample is taken for culture there is a very good chance the culture will be negative which leaves the physician to continue empiric treatment. If on the other hand the physician had obtained a sample to be performed by Tem-PCR up to 25 pathogens would be tested including genetic drug resistance providing the physician with definitive information leading to proper treatment.

Diatherix claims that the test is covered by most insurance companies.