MARCH 2011 • PODIATRY MANAGEMENTwww.podiatrym.com 1

Editor’s Note: This is the first inan occasional series in which newData Trace books are introduced to po-diatrym.com visitors via selected ex-cerpts. Data Trace Publishing Compa-ny has been a leading publisher in thepodiatry field since 1989.

The following is an excerpt fromthe MRSA section in Dr. Joseph’s book:

Methicillin ResistantStaphylococcus Aureus

Prior to this third edition of theHandbook, methicillin resistantStaphylococcus aureus, or MRSA, was

covered in the chapter on bacterialmicroorganisms. When the firstedition was published in 1990,MRSA was still a primarily nosoco-mial organism which rarely wasfound in lower extremity infec-tions. By the time the second edi-tion was published in 2003 (writtenduring 2002), the current “epidem-ic” of MRSA including the differen-tiation of then titled “communityacquired” or CA, and “hospital ac-quired” or HA strains, was becom-ing better appreciated. MRSA wasbeing found in patients with none

of the traditional risk factors, but itwas still a bit of a novelty. Now, theepidemic is in full swing. Some hos-pital’s antibiograms show over 70

percent of their Staph isolatesMRSA. Nomenclature has evolved.Numerous new drugs have been re-

Continued on page 2

Handbook of LowerExtremity Infections,3rd EditionDr. Joseph’s new book provides the most updated information available.

T H E D A T A T R A C E A U T H O R S ’ S E R I E S

Handbook of LowerExtremity Infections,

3rd Edition

Warren S. Joseph, DPM, FIDSA, author ofthis and the two previous editions, has

updated Handbook of Lower Extremity Infec-tions to include a new chapter on MRSA, anupdated antibiotic agents section, and infor-mation discussing the latest diagnostic testingand evidence-based treatments. In addition, you can follow Dr.Joseph as he posts regular updates about the book as well as evolv-ing literature pertinent to lower extremity infections on A Handbookof Lower Extremity Infections Companion Blog.

Dr. Joseph is an attending specializing in podiatric medicine andinfectious diseases at RoxboroughMemorial Hospital in Philadelphia,PA and serves as a podiatric consul-tant at the Coatesville VA MedicalCenter in Coatesville, PA. A national-ly recognized specialist in the treat-ment of lower extremity infectiousdiseases, Dr. Joseph is a fellow of theInfectious Diseases Society of Ameri-ca and sits on the IDSA Diabetic FootInfections Guidelines Committee.

For more information about theHandbook of Lower Extremity Infec-tions, 3rd edition or to order yourcopy today, please call 1-800-342-0454 or visit DataTrace.com �

Warren S. Joseph,DPM, FIDSA

Some hospitals’

antibiograms show

over 70 percent of

their Staph isolates

MRSA.

to become the pathogen it is today.Eady and Cove postulated in 2003that MRSA probably arose from co-agulase negative staph (CNS), ex-plaining that:

1) True infecting strains are usu-ally fairly susceptible, and easilykilled by antibiotics.

2) Commen-sal, or communi-ty-resident strains(such as CNS), areexposed anytimea patient takes anantibiotic, even-tually leading toresistance inthose commen-sals.

3) β-lactamdrugs can be de-livered to the skinvia sweat, thusc o n t i n u a l l ybathing these res-ident strains inlow levels of an-

tibiotic also leading to resistance.4) Of particular interest in the

lower extremity is that fungal toeweb infections may produce lowlevels of β-lactam antibiotics thatmay select out resistant organ-isms…leading to another reason toaggressively treat fungal infectionsof the foot!

By definition,all MRSA containwhat is known asthe “mecA gene”conferring themethicillin resis-tance. This genesits on what isknown as theStaphylococcalC h r o m o s o m a lCassette (SC-Cmec). Currentlythere are thoughtto be about seven different varietiesof this SCCmec numbered Ithrough VII. These can be roughlydivided into two broad classifica-tions by which MRSA is currentlydivided:

1) Healthcare Associated MRSA(HA-MRSA)

a) Usually contains SCCmec I,II, III gene.

b) Previously known as “hospi-

leased with even more in thepipeline. The most remarkable evi-dence of how pervasive MRSA hasbecome is the saturation of thetopic in the popular media. Nomatter where in the United Statesyou live, the localevening news sta-tion has had astory of somelocal high schoolathlete being di-agnosed withMRSA, repletewith video of theschool’s custodi-ans disinfectingall of the surfacesbefore the schoolcould re-open. In-evitably therewould be a localphysician orhealth depart-ment “talkinghead” explaining why MRSA is sodangerous, and what to look for inyou or your child. Much of the in-formation, although technically ac-curate, is presented to have thegreatest broadcast impact. In fact,when one of the oldest, highestrated Sunday evening new pro-grams presented a lead story onMRSA, at one point the reporterlooked directly into the camera,and in a very serious tone, relatedthat “This MRSA is even resistant topenicillin!” Not since the “flesh eat-ing bacteria” media blitz of earlierin this decade has a “superbug” re-ceived so much popular press noto-riety. None of this introduction ismeant to impugn the importanceof MRSA. It is a fact of life, andmust be dealt with appropriately,and aggressively. It has the poten-tial to devastate the patient with alower extremity infection as a re-sult of various toxins, and viru-lence factors that it can express.Furthermore, the organism isevolving, spreading rapidly, andbecoming more challenging totreat.

Classification of MRSAThe MRSA that is being cultured

today from most lower extremityinfections is “not your father’sMRSA.” It has evolved significantly

tal acquired” or “healthcareacquired.”

c) Associated with the tradition-al risk factors listed above, and ispretty much the organism thoughtabout as MRSA before the mid-1990s.

2) Community AssociatedMRSA (CA-MRSA).

a) Contains the SCCmec IV(most common) or V gene.

b) Previously known as “Com-munity Acquired.”

c) Most common synonym isthe “USA300” strain. This nomen-clature is constantly changing. Atthe time of this writing, the aboveterms are the most widely accepted,but that too is bound to change asthe distinction, other than genetic,blurs, and CA-MRSA takes over inclinical importance from HA-MRSA,and is found in both communityand hospital settings regardless ofthe presence, or lack thereof, ofclassic risk factors.

CommunityAssociated-MRSA

Given the prevalence, and clini-cal importance of this particularstrain, it is necessary to examine itin more detail. How is it possible todifferentiate CA from HA-MRSA? Is

it clinically rele-vant to make thedifferentiation?

1) To answerthe second ques-tion first…YES, itis important todifferentiate thesetwo types ofMRSA. They eachhave unique an-tibiotic sensitivitypatterns alongwith varying lev-els of virulence

with CA-MRSA being, by far, themore dangerous organism.

2) On the surface, given thenames of each, it would seem easyenough to determine which organ-ism infects a given patient. Afterall, if the patient is in the health-care setting, the infecting strainmust obviously be HA-MRSA…isn’tthat what the name implies? Unfor-

Handbook...

Continued on page 3

2 www.podiatrym.comPODIATRY MANAGEMENT • MARCH 2011

Not since the

“flesh eating

bacteria” media

blitz of earlier in

this decade has

a “superbug”

received so much

popular press

notoriety

The MRSA

that is being

cultured today from

most lower extremity

infections is

“not your father’s

MRSA.”

b) HA-MRSA tends to be rela-tively resistant to most all antibi-otics other than those designedspecifically to work against resistantgram-positive organisms (i.e. line-zolid, vancomycin, daptomycin).

VirulenceWithin Staph there appears to

be a hierarchy ofvirulence:

1) MRSA maybe more virulentthan MSSA.

2) CA-MRSA ismore virulentthan HA-MRSA.

3) CA-MRSA isencoded to pro-duce various tox-ins that cause de-struction of tis-sue, kill white blood cells, andallow more rapid spread of theorganism.

a) Panton Valentine Leuko-cidin (PVL)—Almost exclusivelyassociated with CA-MRSA, and, infact, frequently used as a geneticmarker for this strain, PVL is proba-bly the best known and studied ofthe virulence factors expressed bythe organism. It was originally felt

to be the singlemost importantfactor when itcame to causingdisease, and tissuedestruction. Thishas more recentlybeen shown to bethe case in necro-tizing pneumoniabut its role inskin, and skinstructure infec-tion is less cer-tain, and proba-bly not as critical.

b) CytolyticPeptides—Wang,in late 2007, pub-lished a report ofdiscovering a

novel peptide that had the “abilityto recruit, activate, and subsequent-ly lyse human neutrophils, thuseliminating the main cellular de-fense against S. aureus infection.”These may actually play a more im-

tunately, as discussed above, thatdistinction is fading, and many, ifnot most of the patients with lowerextremity infections in the health-care setting are infected withCA-MRSA.

3) The traditional risk factors list-ed above for HA-MRSA do not seemto apply to CA-MRSA transmission.Rather, some authors talk about the“Five Cs” of CA-MRSA risk:

a) Close Contactb) Crowdingc) Lack of Cleanlinessd) Exposure to Contaminated

itemse) Compromised skin integrity

4) These are genetically distinctorganisms. Diagnostic tests such asPCR and pulse gel field elec-trophoresis (PGFE) do exist to lookspecifically for genes unique toeach type of MRSA. Unfortunately,most hospitals are not currentlyusing these techniques so, until itbecomes a more widely availableand utilized modality of differenti-ating CA from HA-MRSA, it will nothelp the average clinician.

5) Probably the easiest and mostclinically relevant way to determineone from theother is to exam-ine the antibioticsensitivities onthe C&S report.

a) CA-MRSAtends to be rela-tively susceptibleto a wide range ofantibiotics otherthan β-lactamdrugs (this maychange in thenear future withthe developmentof anti-MRSAcephalosporins).The SCCmec IVgene is known asa “short segment”cassette so thereis little room on it for resistancegenes. This is why drugs such astrimethoprim/sulfamethoxazole(TMP/SMX) or doxycycl inecan be effect ive against thisorganism.

portant role in soft tissue infectionsthan PVL.

Clinical PresentationBecause of the virulence factors

formed by CA-MRSA, this organismtends to present in skin and skinstructure infections as an aggres-sively spreading abscess. In fact,

there is a practi-cally pathog-nomonic phrasepatients use to de-scribe the lesion,known particular-ly to emergencyphysicians andfamily medicine:“Doc…I have aspider bite!” Whena patient makesthis statement,the importantfirst questionfrom the treating

doctor should be “Did you see thespider?”

Invariably, the patient will saythat, no, it happened at night, andthey woke up with it, or some suchvariation on this theme. As a ruleof thumb:

Always assume a “spider bite” oran “insect bite” reported to you by apatient is a CA-MRSA abscess untilproven otherwise!

Although an abscess is the mostcommon presentation of a CAMR-SA infection, any clone of MRSAcan cause infection in the lower ex-tremity regardless of the presenceor absence of risk factors.

1) Localized abscess (furunclesand carbuncles)—Just restating theobvious to make a point. This is themost common presentation partic-ularly for CA strains.

2) Surgical site infection.3) Diabetic foot infection.4) Osteomyelitis.5) Infected decubitus ulcera-

tions—particularly in patients resid-ing in long term care facilities.

6) Cellulitis—MRSA may play arole in pure cellulitis but it is morecommonly caused by streptococcus.

7) Impetigo—Again, most com-monly caused by streptococcus butMRSA has been implicated also.

8) Anything else—basically, anytype of infection anywhere in thelower extremity could be caused byone strain or another or MRSA. �

Handbook...

3 www.podiatrym.comPODIATRY MANAGEMENT • MARCH 2011

Always assume a

“spider bite” or

an “insect bite”

reported to you by

a patient is a

CA-MRSA abscess until

proven otherwise!

Because of the

virulence factors

formed by

CA-MRSA, this

organism tends to

present in skin

and skin structure

infections as

an aggressively

spreading abscess.