January 2005 Practical Dermatology 33

Infections caused by Methicillin-Resistant Staphylococcusaureus (MRSA), S. aureus resistant to all beta-lactamantibiotics, had been a disease limited primarily to hospi-tals and nursing homes for the last several decades. MostS. aureus isolated from community-acquired

infections were susceptible to nafcillin, oxacillin,dicloxacillin, methicillin (beta-lactamase stable peni-cillins), and cephalexin or cefadroxil (first generationcephalosporins). Today, however, we are hearingmore frequent reports of this highly resistant organ-ism in communities where individuals have had nosignificant exposure to hospitals or nursing homes,and as dermatologists know from experience in thetreatment of acne, antibiotic resistant bacteria havebecome a worldwide problem with limited solutions(Table 1).

Know the Risk Factors MRSA was first identified in the 1960’s, shortly afterthe introduction of methicillin. Infections thatresulted from this organism were generally acquiredin the hospital or in a nursing home. Established riskfactors for hospital acquired MRSA (HA-MRSA) infectionsinclude recent hospitalization, surgery, residence in a long-termcare facility, dialysis, and indwelling percutaneous medicaldevices and catheters. These infections are difficult to treat andhave typically required the use of intravenous vancomycin.

In the recent past, cases of MRSA infection in healthy com-munity dwelling, persons without established risk factors havebeen documented. These infections, which have been acquiredin the community, have been referred to as community-

acquired orc o m m u n i t y -a s s o c i a t e dMRSA (CA-MRSA). Reportsof CA-MRSAhave come froma variety of set-tings andgroups, includ-ing athletes,inmates, mili-tary recruits,men who havesex with men,injection drugusers, homelessindividuals, and

pacific islanders.1-7 Day care attendance has also been men-tioned in the literature as a risk for CA-MRSA.

Humans are a natural reservoir for S. aureuss, and asympto-matic colonization is far more common than infection. Thenasopharynx, perineum, and sometimes the hands and skin are

MRSA infections are no longer limited to hospitals.

An infectious disease specialist offers insight on what this means for dermatologists.

By Robert S. Jones, DO, Reading, PA

“Physicians should also be aware that the

more resistant HA-MRSAinfections could be

present in the outpatientsetting months after discharge from the

hospital or long-term care facility.”

34 Practical Dermatology January 2005

frequent sites of colonization. Transmission occurs by direct,person-to-person contact with another individual who is col-onized or infected with community-associated MRSA or hos-

pital-associated MRSA (HA-MRSA). Significantly higher car-riage rates are seen in injection drug users, persons withinsulin-dependent diabetes mellitus, patients with dermato-logic conditions, patients with long term indwelling vascularaccess, and healthcare workers compared to the general pop-ulation. Young children tend to have higher colonizationrates, probably due to their frequent contact with respiratorysecretions. Colonization with S. aureus may be transient orpersistent and can last for years; the same is true for MRSA.

The origins of CA-MRSA remain uncertain. The emer-gence is due to the insertion of a mecA gene into methicillin-susceptible S. aureus strains. Unlike plasmid encoded beta-lac-tamase production, the methicillin resistant determinant mecis chromosomally encoded. All methicillin resistance is due tothe mecA gene, which has been renamed staphylococcal cas-sette chromosome mec (SCCmec). The mecA elements aredesignated I-IV. The element associated with CA-MRSA is

mecA IV, and I-III are associated with HA-MRSA. Regardlessof the origins, emergence of MRSA within the community isa major threat with significant implications for management

and treatment.

Recognize the SignsCommunity-acquired MRSA cases have beendefined as:1.) a MRSA infection identified within 48 hours ofhospital admission; 2.) no previous history of hospitalization, surgery,dialysis, or residence in a long-term care facilitywithin one year of the MRSA culture date; 3.) no permanent indwelling catheter or percuta-neous medical device at time of culture, and no pre-viously positive culture for MRSA.8

Patients with CA-MRSA may present with skin andsoft tissue infections characterized by swelling,pain, purulent drainage, or erythema. Infectionscan include furuncles, deep-seated folliculitis,impetigo, abscesses, or cellulites, and it is notuncommon for a patient to present for medicalattention for a “spider bite” or a “sore.” Infectionscan be severe and can lead to systemic infectionsincluding pneumonia, osteomyelitis, septic arthri-tis, endocarditis, and sepsis. There appear to be nodifferences in overall disease severity between CA-MRSA and nosocomial MRSA infections.

In one study that compared CA-MRSA andHA-MRSA infections, CA-MRSA infected patientswere younger (23 years old vs. 68 years old), morefrequently non-white, and had a lower householdincome.7 Among pediatric patients with CA-

MRSA, dermatologic conditions were the most commonunderlying medical condition. In adult cases, tobacco use anddiabetes were the most common underlying medical illnessesfollowed by dermatologic conditions.7

Multiple factors may contribute to the pathogenicity ofthe CA-MRSA, and these separate it from its nosocomialcounterpart. The Panton-Valentine leukocidin gene codes forone of these factors; it codes for the production of cytotoxinsthat cause tissue necrosis by forming pores in cellular mem-branes. This gene has been found more commonly in CA-MRSA and is responsible for severe cases of necrotizing infec-tion. Other exotoxin genes or combinations of genes couldalso be important pathogenic factors as well (Table 2).

The emergence of CA-MRSA infections complicates themanagement of outpatients presenting with skin and soft tis-sue infections. Upon presentation, there is no visible orimmediately identifiable way to recognize which infections

Erasing the MRSA Threat

TABLE 1

What can be done about Antibiotic Resistance?n Use antibiotics only when necessaryn Use the shortest course necessary to cure the infectionn Use the agent with the narrowest spectrum to decrease pressure on further development of resistance

TABLE 3

Outpatient Evaluation of MRSA Skin and Soft Tissue Infectionsn Assess risk factors for MRSA (e.g. recent hospitalization, nursinghome residence, etc.)n Examine skin lesion for cellulites crepitus, fluctuance, sinusdrainagen Drain or aspirate infection if possible (minor infections may resolvewith antibiotics alone)n Send cultures when possible

TABLE 2

Comparison of Hospital and Community-Acquired MRSAFeature HA-MRSA CA-MRSASCC mec Type I-III Type IVToxins Fewer More commonPanton-Valentine leukocidin Rare CommonAntibiotic resistance Multiply resistant Sensitive, except

for beta-lactamsTransmission route Person-person Person-person

January 2005 Practical Dermatology 35

are caused by CA-MRSA versus any other microor-ganism. Skin infections should be carefully exam-ined, looking for signs of cellulites, crepitus, fluctu-ance, or sinus drainage (Table 3); incision anddrainage should be performed whenever feasible.Furuncles and small abscesses can be drained underlocal anesthesia, while larger wounds, abscesses,infections of the face, hands, or deeper compart-ments may require surgical consultation. Anywound drainage should be promptly sent to themicrobiology laboratory for routine bacterial cul-tures and antibiotic susceptibilities. Gram stain willprovide a quick reference as to whether the organ-isms seen are gram positive or gram negative.Cultures should be sent in a timely manner toensure best results. Since the microbial etiology ofthe infection cannot be ascertained by visualinspection and cannot be differentiated clinicallybetween S. aureus, CA-MRSA, HA-MRSA, or anyother microorganism, cul-tures should be done at thetime of initial evaluation.

Understand YourTreatment OptionsIn some cases, incision anddrainage alone will ade-quately treat minor infec-tions without the need forantibiotic therapy. Empiricantibiotic therapy is indi-cated for patients withlarge or multiple furun-cles, soft tissue abscesses,cellulitis, deep-seated folli-culitis, impetigo, ecthyma,systemic disease or symp-toms or for those who areotherwise at high risk forserious complications,such as patients with pros-thetic heart valves or previ-ously diagnosed endo-carditis. Treatment shouldbe based upon culture andsusceptibility data; howev-er, the optimal treatmentfor CA-MRSA is notknown since no controlledtrials have assessed

TABLE 5

Management of CA-MRSA Infections in the Outpatient Setting

Drug Oral Dose Comments

TABLE 4

Antimicrobial Susceptibility Profile of Community-Associated (n=106) and Health Care-Associated (n=211)MRSA Isolates in Minnesota in 20008

Drug CA-MRSA n (%) HA-MRSA n (%) P valueOxacillin 0 0

Ciprofloxacin 84 (79) 33 (16) P<0.001

Clindamycin 88 (83) 44 (21) P<0.001

Erythromycin 47 (44) 18 (9) P<0.001

Gentamicin 100 (94) 168 (80) P=0.001

Rifampin 102 (96) 199 (94)

Tetracycline 98 (92) 194 (92)

Trimethoprim/

sulfamethoxazole 101 (95) 189 (90)

Vancomycin 106 (100) 211 (100)

Trimethoprim-Sulfamethoxazole

+/- rifampin

Clindamycin+/- rifampin

Fluoroquinolones• Ciprofloxacin• Levofloxacin• Gatifloxacin• Moxifloxacin• +/- rifampin

TetracyclineMinocyclineDoxycycline

+/-rifampin

Linezolid

1 DS tablet every 8-12 hrs.

300 mg BID

150-300 mg Q 6hrs

300 mg BID

500 mg Q 12500-750 mg Q 24400 mg Q24400 mg Q24300 mg BID

500 mg QID100 mg Q24100 mg BID300 mg BID

600 mg BID

• Check for sulfa allergy• Check for drug interactions• Do not use for empiric therapy in

suspected streptococcal infections

• Potential for inducible resistance• Good bone penetration• Check for rifampin drug interactions

• Efficacy of fluoroquinolones may beaffected by rapid resistance; additionof rifampin should be considered

• Check for rifampin drug interactions• Absorption of quinolones is impaired

by antacids

• Check for drug interactions• Potential for secondary yeast

infections• Do not administer with dairy

products

• Reserve for highly resistant infections• Avoid in patients on SSRIs• May cause bone marrow suppression• Expensive

36 Practical Dermatology January 2005

whether in vitro antibiotic sus-ceptibilities correlate with clinicalresponse.

CA-MRSA infections areresistant to beta-lactam antibi-otics (penicillins andcephalosporins) but may be sus-ceptible to other available oralantibiotics, such as trimetho-prim-sulfamethoxazole and clin-damycin (Table 4). Review ofmicrobiology susceptibilities maybe necessary with the microbiolo-gy laboratory for isolates that aresusceptible to clindamycin but resistant to erythromycin,because organisms that are erythromycin resistant and clin-damycin susceptible may have inducible clindamycin resist-ance. The laboratory can confirm this through the use of invitro testing (D-test). The frequency of inducible clindamycinresistance in erythromycin susceptible strains varies fromcommunity to community and by species. In these strains,clindamycin would not be a suitable antibiotic selection, asresistance would develop in a matter of days. Physiciansshould also be aware that the more resistant HA-MRSA infec-

tions could be present in the out-patient setting months after dis-charge from the hospital or long-term care facility. Once an indi-vidual is colonized or has an infec-tion with MRSA, it is likely that arepeat or new infection will bewith the same organism.

The duration of antibiotictherapy should be based uponseverity of illness, immune statusof the host, and the clinicalresponse. Adequately drained,uncomplicated skin and soft tissue

CA-MRSA infections usually resolve with 10 to 14 days oftherapy. Systemic infections, such as sepsis and osteomyelitis,require hospitalization, intravenous antibiotics, and possibly alonger duration of therapy. Patients should be monitoredcarefully even after the completion of their antibiotic coursesince recurrent infections at the same or different site arecommon. Topical mupirocin and/or washing with a bacterici-dal soap has not been proven beneficial in the decolonizationof the nares and other body sites including the ears, navel,axillae, groin, and interdigital web spaces.

Vancomycin remains the drug of choice for thetreatment of infections caused by MRSA, particu-larly for hospitalized patients. Unfortunately theoral form of vancomycin is not absorbed ade-quately to achieve necessary serum or tissue levelsand must be administered as an intravenouspreparation to be effective. This is time consum-ing to set up, generally requiring a percutaneousintravenous central catheter (PICC) and drugmonitoring, and may not be convenient for theambulatory patient. Therefore, it may be awkwardto offer patients this option in the out-of-hospitalsetting. HA-MRSA is often resistant to multipledrugs, whereas CA-MRSA often retains suscepti-bility to tetracycline, rifampin, quinolones,trimethoprim-sulfamethoxazole, and clin-damycin; however, the latter needs to be usedwith caution because of the possibility ofinducible resistance in erythromycin–resistantstrains (Table 5). Rifampin should never be usedalone due to the rapid development of resistanceand therefore should only be used in combinationwith other drugs. Combinations such as tetracy-cline and rifampin, trimethoprim-sulfamethoxa-zole and rifampin, a quinolones plus rifampin, orclindamycin plus rifampin may be reasonable

Erasing the MRSA Threat

TABLE 6

Measures for Preventing Staphylococcal SkinInfections Among Sports Participantsn Cover all wounds. If a wound cannot be covered ade-quately, consider excluding players with potentially infec-tious skin lesions from practice or competitions until thelesions are healed or can be adequately covered.

n Encourage good hygiene, including showering andwashing with soap after all practices and competitions.

n Ensure availability of adequate source of soap and hotwater.

n Discourage sharing of towels and personal items (e.g.clothing or equipment).

n Establish routine cleaning schedule for shared equip-ment.

n Train athletes and coaches in first aid for wounds andrecognition of wounds that are potentially infected.

n Encourage athletes to report skin lesions to coaches andencourage coaches to assess athletes regularly for skinlesions.

“Vancomycin remainsthe drug of choice for

the treatment of infections caused by

MRSA, particularly forhospitalized patients.”

January 2005 Practical Dermatology 37

combinations. Prospective studies are needed tocompare various treatment regimens for thisimportant group of patients. Newer antibioticssuch as linezolid have been proven effectiveagainst MRSA skin and soft tissue infectionsalong with demonstrating good in vitro activity,but associated toxicity and relatively high costmay limit its use. Table 5 outlines dosing rec-ommendations.

Control the ThreatIt appears that CA-MRSA is here to stay and isan additional threat to the growing global pub-lic health crisis of antimicrobial resistance. It isimportant to educate primary care physiciansand surgeons about the increasing prevalence ofthis organism as well as the antibiotic suscepti-bility profiles. Efforts to control MRSA infec-tions can no longer depend solely on surveil-lance, infection control efforts, and judiciousantibiotic prescribing practices within the hos-pital setting.

It is important for clinicians to obtain cul-ture and susceptibility data to optimally treatpatients who may have infections due to CA-MRSA. It is no longer adequate to treat empir-ically with beta-lactam antibiotics and expectthe patient to recover. Additionally, it is impor-tant for physicians to educate their patients onways to prevent the spread of MRSA infections(see Tables 6 and 7). We still have more to learnabout the optimal management of CA-MRSA,and future studies should focus on further iden-tifying risk factors for acquisition of CA-MRSA, eliciting the various roles of various tox-ins, and determining the optimal managementand antibiotic selection for these infections.

1.CDC. Methicillin-Resistant Staphylococcus aureus Infections Among Competitive SportsParticipants Colorado, Indiana, Pennsylvania and Los Angeles, 2000-2003. MMWR2004;52(33): 793-95.2.CDC. Methicillin-Resistant Staphylococcus aureus Infections in Correctional Facilities –Georgia, California and Texas, 2001-2003. MMWR 2003. 52 (41):992-6.3.CDC. Outbreak of Community Associated Methicillin Resistant Staphylococcus aureus skinInfections-Los Angeles County CA, 2002-2003. MMWR 2003;52:88.4.Zindeman C et al. Emerg Inf Dis 2004;10:94.15.Charlebois E et al. Clin Inf Dis 2004;39:47.6.CDC. Community-Associated Methicillin-Resistant Staphylococcus aureus Infections inPacific Islanders-Hawaii 2001-2003. MMWR 2004;53(33);767-70.7.Naimi TS et al. Comparison of Community and Health Care-Associated Methicillin-Resistant Staphylococcus aureus Infection. JAMA 2003;290:2976-84.8.LeDell et al. The Changing epidemiology of MRSA: Emergence of Community-AssociatedMRSA in Minnesota. Contagion 2004;1:77-84.

How to Prevent MRSA Infections Patient Information

n Wash hands thoroughly during the day whenever

they are visibly dirty, after using the bathroom, and

before every meal, using bactericidal soap

n Maintain good personal hygiene by taking regular

baths or showers, keep nails short

n Do not share personal hygiene items with others

including toiletries and towels

n Clean off communal surfaces such as recreational

equipment, sauna or steam room sitting areas

before direct contact with body; use a clean barrier

such as a towel or shirt between communal surfaces

and bare skin

n Shower after participating in close contact recre-

ational activities, or attending public gyms, saunas,

or steam rooms

n Do not touch another person’s wounds, infected

skin, or soiled bandages with bare hands

n Seek medical attention for any boils or new sores

that are red and inflamed, or for skin infections fol-

lowing hospital discharge

n Do not scratch skin rashes

n If being treated for an infection follow doctors

orders so the infection can be cured

Photocopy the table below to post in your practice or distribute to patients.