Hospitalist Perspective on the Treatment of Skin and Soft Tissue Infections

17 Pages·2014·0.34 MB·English

UC Irvine
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Title
Hospitalist perspective on the treatment of skin and soft tissue infections.
Permalink
https://escholarship.org/uc/item/9fc8m6db
Journal
Mayo Clinic proceedings, 89(10)
ISSN
0025-6196
Authors
Amin, Alpesh N
Cerceo, Elizabeth A
Deitelzweig, Steven B
et al.
Publication Date
2014-10-01
DOI
10.1016/j.mayocp.2014.04.018
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License, availalbe at https://creativecommons.org/licenses/by/4.0/

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REVIEW
Hospitalist Perspective on the Treatment of Skin
and Soft Tissue Infections
Alpesh N. Amin, MD, MBA; Elizabeth A. Cerceo, MD; Steven B. Deitelzweig, MD;
James C. Pile, MD; David J. Rosenberg, MD; and Bradley M. Sherman, MD
Abstract
The prevalence of skin and soft tissue infections (SSTIs) has been increasing in the United States. These
infectionsareassociatedwithanincreaseinhospitaladmissions.Hospitalistsplayanincreasinglyimportant
role in the management of these infections and need to use hospital resources efficiently and effectively.
When available, observation units are useful for treating low-risk patients who do not require hospital
admission. Imaging tools may help to exclude abscesses and necrotizing soft tissue infections; however,
surgical exploration remains the principal means of diagnosing necrotizing soft tissue infections. The most
commonpathogensthatcauseSSTIsarestreptococciandStaphylococcusaureus.Methicillin-resistantSaureus
(MRSA) is a prevalent pathogen, and concerns are increasing regarding the unclear distinctions between
community-acquired and hospital-acquired MRSA. Other less frequent pathogens that cause SSTIs include
Enterococcus species, Escherichia coli, Klebsiella species, Enterobacter species, and Pseudomonas aeruginosa.
Cephalexin and clindamycin are suitable options for infections caused by streptococcal species and
methicillin-susceptible S aureus. The increasing resistance of S aureus and Streptococcus pyogenes to eryth-
romycinlimitsitsuseintheseinfections,andbetteralternativesareavailable.Parenteralcefazolin,nafcillin,
or oxacillin can be used in hospitalized patients with nonpurulent cellulitis caused by streptococci and
methicillin-susceptible S aureus. When oral MRSA therapy is indicated, clindamycin, doxycycline,
trimethoprim-sulfamethoxazole,orlinezolidisappropriate.Vancomycin,linezolid,daptomycin,tigecycline,
telavancin, and ceftaroline fosamil are intravenous options that should be used in MRSA infections that
require patient hospitalization. In the treatment of patients with SSTIs, hospitalists are at the forefront of
providingproperpatientcarethatreduceshospitalcosts,durationoftherapy,andtherapeuticfailures.This
review updates guidelines on the management of SSTIs with a focus on infections caused by S aureus,
particularly MRSA, and outlines the role of the hospitalist in the effective management of SSTIs.
ª2014MayoFoundationforMedicalEducationandResearch n MayoClinProc.2014;89(10):1436-1451
S
FromtheDepartmentof kin andsofttissueinfections(SSTIs)are commonorganismsthatcauseSSTIsareStaphy-
Medicine,Universityof common,encompassingawiderangeof lococcus aureus and Streptococcus species.5,6
CaliforniaatIrvine,Irvine
(A.N.A.);Departmentof clinical presentations and definitions, Methicillin-resistant S aureus (MRSA) is a pre-
HospitalMedicine,Cooper and have increased significantly since the mid- dominantpathogenthatcausesSSTIs,isassoci-
UniversityHealthCare,
1990s. Ambulatory visits for abscess and cellu- ated with increased length of hospitalization,
Camden,NJ(E.A.C.);
OchsnerClinicFoundation, litishavetripledfrom1993to2005,withvisits and is an independent risk factor for increased
NewOrleans,LA(S.B.D.); for all SSTIs reaching 14.2 million in 2005.1,2 mortality and hospital charges compared with
DepartmentofHospital UsingdatafromtheHealthcareCostandUtiliza- methicillin-susceptible S aureus(MSSA).7,8The
Medicine,MedicineInstitute,
ClevelandClinic,Cleveland, tion Project National Inpatient sample, Edels- increasing incidence of SSTIs in both ambula-
OH(J.C.P.);Departmentof berg et al3 found a 29% increase in hospital tory and hospital settings, coupled with the
Medicine,HofstraNorth
admissions for SSTIs during a 5-year period increase of MRSA as a causative pathogen, de-
ShoreeLIJSchoolof
Medicine,Manhasset,NY (2000-2004).Inastudythatassessedtheincre- mandsoptimalmanagementoftheseinfections
(D.J.R.);andDepartmentof mentalclinicalandeconomicburden ofhospi- toimproveoutcomes.
Medicine,GlenCove
talized patients with a secondary diagnosis of Thisreviewoutlinestheroleofthehospital-
Hospital,NorthShoreeLIJ
UniversityHealthSystem, SSTIscomparedwithmatchedcontrolswithout istintheeffectivemanagementofSSTIs,witha
OysterBay,NY(B.M.S.). SSTIs, patients with SSTIs had a mean of 3.8 focusoninfectionscausedbySaureus,particu-
additional days of hospitalization, $14,794 larly MRSA. A PubMed search was performed
excess hospital charges, and an increased risk from2000tothepresentusingthesearchterms
of mortality (odds ratio, 1.32).4 The most SSTI, MRSA, surveillance, resistance, clinical
1436 MayoClinProc. n October2014;89(10):1436-1451 n http://dx.doi.org/10.1016/j.mayocp.2014.04.018
www.mayoclinicproceedings.org n ª2014MayoFoundationforMedicalEducationandResearch
HOSPITALIST PERSPECTIVE ON SSTI TREATMENT
guidelines, antimicrobials, and hospitalists and
supplementedwitharticlesunder“Relatedcita- ARTICLEHIGHLIGHTS
tionsinPubMed.”Studieswereselectedonthe
n Skin and soft tissue infections (SSTIs) caused by methicillin-
basis of clinical relevance, date published,
resistant Staphylococcus aureus are increasing in prevalence in
comparative trials, and standards of practice.
The term SSTIs is used throughout to refer to hospitals in the United States. Hospitalists should carefully
skin infections; however, terms specified in determine appropriate antimicrobial therapy for SSTIs on the
published studies or approved indications are basis of severity of illness, bacterial susceptibilities, risk of
retainedwhenappropriate.
adverse effects, and local resistance patterns.
n Ultrasonography can be used as initial diagnostic imaging for
DIAGNOSIS AND MANAGEMENT
suspected abscesses. Computed tomography can help to
There are a variety of SSTIs, and differentiating
infection type is important in selecting appro- exclude necrotizing infections to avoid unnecessary surgical
priatetreatment(Table1).9-16Abscessesarecol- incisionanddebridement;however,surgicalexplorationmaybe
lections of pus within the dermis or deeper necessary to confirm or exclude suspected necrotizing soft
tissues, commonly treated with incision and
tissue infections.
drainage alone.14 Systemic antibiotics may be
n When available, observation units can be used for certain
required for abscesses accompanied by fever or
extensive surrounding cellulitis. Cellulitis and patients with SSTIs to identify patients suitable for hospital
erysipelas are diffuse spreading skin infections admission. Good candidates for observation therapy are those
notassociatedwithunderlyingsuppurativefoci. who are likely to respond to empiric therapy, are expected to
Erysipelas is differentiated from cellulitis by the
requireashortstay,andhavealowprobabilityofinfectionwith
depthofinflammation;erysipelasaffectstheup-
resistant organisms.
perdermis,includingthesuperficiallymphatics,
whereas cellulitis affects the deeper dermis and n Hospitalized patients with complicated SSTIs should receive
subcutaneous fat. Antibiotics with coverage for empiric therapy for methicillin-resistant S aureus with intrave-
streptococci typically provide effective therapy nous agents, such as vancomycin, linezolid, and daptomycin.
forerysipelas.AntibioticswithSaureuscoverage Other options include clindamycin, tigecycline, and newer
areappropriatewhencellulitisisassociatedwith
agents, such as ceftaroline fosamil and telavancin.
an underlying abscess or penetrating trauma.14
n Oralantimicrobialagentsshouldbeconsideredasinitialtherapy
Surgicalsiteinfectionsshouldbesuspectedinpa-
tientswithpostoperativefever,particularlywith in less severe infections. Patients should be switched from
onset more than 48 hours after surgery. The intravenoustooralantimicrobialtherapywhentheyareafebrile
mainstay of therapy for surgical site infections for24hoursorlonger,improvingclinically,andabletotakeoral
is changing of wound dressings and surgical
medications.
debridement. Adjunctive antibiotic therapy
shouldnotlastlongifadequatesourcecontrol
has been achieved. Necrotizing soft tissue in-
fections (NSTIs) are rare (500-1500 cases in complete surgical debridement, combined
the United States each year) but lethal, with antimicrobial therapy, close monitoring,
involvinganylayerofthesofttissuecompart- andphysiologicsupport.17,18
ment(eg,dermis,subcutaneoustissue,super- Hospitalizationshouldbeconsideredforpa-
ficialfascia,deepfascia,ormuscle).14,17When tientswithcellulitiswhopresentwithfever,pain,
there is tense edema outside the area of advancing erythema, hemodynamic instability,
compromised skin, pain disproportionate to and failure to respond to outpatient therapy.18
appearance, ecchymosis, bullae, significant Additional factors include a compromised im-
systemic toxic effects, or presence of crepitus munesystem;comorbidities,suchasperipheral
and/or subcutaneous gas, NSTIs should be vascular disease, diabetes mellitus, or chronic
suspected.17 Prompt diagnosis is needed to venous insufficiency; and abnormal laboratory
achievesuccessfuloutcomes;thus,hospitalists values, including elevated creatinine orcreatine
should seek surgical and infectious disease kinase (CK) level, low serum bicarbonate level,
consultation when NSTIs are suspected. The ormarkedleftshift.14,18Gramstain,antimicro-
mainstay of therapy for NSTIs is early and bialsusceptibilitytesting,andculturesforblood,
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MAYO CLINIC PROCEEDINGS
TABLE1. SSTITypesandManagementRecommendationsWithMRSAConsiderationsinHospitalizedPatientsa,9-16
TypeofSSTI ManagementRecommendation
Abscess
Cutaneousabscess Incisionanddrainage
Abscessassociatedwithsevereorextensivedisease,rapidprogression Incisionanddrainageand/orantibiotictherapy
withassociatedcellulitis,systemicsignsandsymptoms,comorbidities
orimmunosuppression,extremesofage,areathatisdifficulttodrain,
septicphlebitis,lackofresponsetoincisionanddrainage
Nonpurulent(nodrainageorexudate)cellulitisinhospitalsetting b-Lactamantibioticmaybeconsideredwithmodificationforagents
againstMRSAifnoclinicalresponse:IVpenicillinase-resistantpenicillins,
includingnafcillinoroxacillin1-2gevery4hours;first-generation
cephalosporins,includingcefazolin1gIVevery8hours
ComplicatedSSTIinhospitalsetting,includingdeepersofttissueinfections, Broad-spectrumantibioticswithcoverageforMRSApendingculturedata:
surgicalortraumaticwoundinfections,majorabscesses,cellulitis,or vancomycin,15-20mg/kgevery8-12hoursb;linezolid,600mgtwice
infectedulcersandburns daily(oralorIV);daptomycin,4mg/kgperdoseIVoncedailyb;
telavancin,10mg/kgperdoseIVoncedailyb;clindamycin,600mg
3timesdaily(oralorIV)c;tigecycline,initialdoseof100mgIVfollowed
by50mgevery12hoursIVd;ceftarolinefosamil,600mgIVevery
12hoursb,d;surgicaldebridement;7-14daysoftherapy
aIV¼intravenous;MRSA¼methicillin-resistantStaphylococcusaureus;SSTI¼skinandsofttissueinfection.
bRequiresdoseadjustmentinrenallyimpairedpatients.
cPerprescribinginformation,clindamycincanbedosedupto2700mg/dIVindivideddosesforsevereinfections.Fororaldosing,although300to450mgevery6hoursis
recommendedforsevereinfections,higherdosesmaybeneededforhospitalizedpatients.
dNotincludedinInfectiousDiseasesSocietyofAmericaguidelines.TigecyclineisapprovedforMRSAcomplicatedskinandskinstructureinfections.Ceftarolinefosamilis
approvedforMRSAacutebacterialskinandskinstructureinfections.Dosingisrecommendedfromprescribinginformation.
needle aspirate, or punch biopsy specimens Bedside ultrasonography can be performed in
shouldbeperformedwhenfeasible.14However, theemergencydepartmenttoimprovediagnostic
forcellulitis,aspirationoftheskinisnothelpful accuracy during clinical examination,23,24 with
in75%to80%ofcases,14lessthan5%ofblood the advantages of portability, immediate avail-
cultureresultsarepositive,19andapproximately ability,lowcosts,andincreasedpatientcomfort
20%ofculturesfrombiopsyspecimensyieldan comparedwithformalultrasonography.24Com-
organism.20Positiveneedleaspirationresultscan puted tomography should be reserved for pa-
vary, depending on the patient population, in- tientsinwhom theultrasonographicimagesare
clusion criteria, and identification of organisms unclearortheabscessextendsintodeepertissue.
aspathogensorcontaminants,limitingitsdiag- Studies with 16- and 64-section CT in patients
nosticvalue.14InasystematicMEDLINEreview withsuspectedNSTIrevealthatCTsmaybesuf-
publishedin2010,15.7%to16.0%of808pa- ficiently sensitivetoexcludeNSTIs andprevent
tients with cellulitis had positive needle aspira- unnecessary surgery; however, surgical explora-
tion and/or punch biopsy culture results from tion with small incisions remains the principal
intact skin.21 Infectious disease consultation meansofconfirmingorexcludingNSTIswhen-
should be considered for patients who have everthereisalikelihoodoftheseinfections.14,25
immunodeficiency or severe cellulitis or who Althoughmagneticresonanceimaginghasbeen
donotrespondtoinitialantibioticregimens.18 proposed to differentiate NSTIs from non-
NSTIs, its high sensitivity and low specificity
Imaging can result in overdiagnoses of NSTIs that may
Diagnosisofanabscessismadeonthebasisof leadtounnecessarysurgery.26,27
history, physical examination, and imaging.
For diagnosing abscesses, ultrasonography is Causative Pathogens
more sensitive (sensitivity, 96.7%; specificity, Certain pathogens are associated with specific
85.7%) than computed tomography (CT) types of infections and should be considered
(sensitivity, 76.7%; specificity, 91.4%) and is alongwithpatientcharacteristicsandpredispos-
favored as the initial diagnostic imaging test.22 ingriskfactors.StreptococcusspeciesandSaureus
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HOSPITALIST PERSPECTIVE ON SSTI TREATMENT
arethemostcommonpathogensinSSTIs.Strep- of gram-positive, gram-negative, and anaerobic
tococcusspeciestypicallycausediffuse,nonpuru- organisms,includingClostridiumspecies.15The
lent cellulitis and erysipelas.14 In a study of NSTIs that are monomicrobial can be caused
hospitalized patients with nonculturable cellu- byStreptococcuspyogenes,Vibriovulnificus,Aero-
litis, acute and convalescent serologic tests for monas hydrophilia, anaerobic streptococci, or,
antiestreptolysin-O and antieDNase-B anti- occasionally, community-acquired MRSA (CA-
bodies along with blood cultures were used in MRSA).14,32 Surgical site infections are usually
determining b-hemolytic streptococci as the caused by S aureus and streptococcal species,
causative pathogen in 73% of this population.5 but those that involve colonic, vaginal, biliary,
Saureusisoneofthemostpredominantorgan- orrespiratorymucosaltissuescanhaveacombi-
isms, causing 44.6% to 46.9% of SSTIs,6,28 nationofaerobicandanaerobicpathogens.14
particularlycellulitisthatispurulentandassoci-
atedwithabscesses.9,14AmongSaureusisolated Health CareeAssociated Infections
from SSTIs, MRSA prevalence is high (35.9%- Health careeassociated infections are usually
56.8%).6,28Ina10-yearstudy(1998-2007),ab- complicated skin and soft tissue infections
scess and wound isolates caused by MRSA (cSSTIs) and may increase the hospital
increased nearly 8-fold (70.4%) and 4-fold length of stay and mortality compared with
(55.2%), respectively.29 Ray et al30 reported community-acquiredinfections.33Healthcaree
that the rate of MRSA stabilized or decreased associated risk factors include hospitalization
slightlybetween2005and2009;however,80% within the previous year, antibiotic use within
of culture-positive skin infections were caused the previous 90 days, dialysis dependence, or
bySaureus,andhalfwereduetoMRSA.Findings transfer from a nursing home. Community-
oftheSentryAntimicrobialMonitoringprogram acquired cSSTIs are commonly caused by
providesomeinsightintotheoccurrencerateof S aureus, and health careeassociated cSSTIs
lesscommonpathogensisolatedfromSSTIsdur- arelikelytobemixedinfectionsthatalsoinclude
ing a 7-year period (1998-2004).6 Occurrence Enterococcus species and gram-negative organ-
rates of these pathogens include Enterococcus isms.33Mixedinfectionscanincreasemortality,
species (9.8%), Pseudomonas aeruginosa (8.2%), length of stay, and hospital charges compared
Escherichia coli (6.9%), Enterobacter species with gram-positive or gram-negative infections
(4.1%),andKlebsiellaspecies(4.0%).6 alone.8
Most SSTIs are caused by gram-positive
pathogens. Gram-negative organisms are more Methicillin-ResistantSaureus
likelytobefoundinpatientswithcompromised Initially,CA-MRSAwasreportedinspecificpop-
immunesystems,diabeticfootinfections(DFIs), ulations (eg, intravenous [IV] drug users and
NSTIs, or surgical site infections. Infected im- athletes)34,35 but currently is so common in
munocompromised patients require broad- thecommunitythathistoricallyhigh-riskgroups
spectrum empiric coverage against resistant are no longer clinically useful. Epidemiologi-
gram-positive organisms (eg, MRSA) and cally, CA-MRSA infections occur in individuals
gram-negativeorganisms(eg,Pseudomonasspe- intheoutpatientsettingorwithin2daysofhos-
cies).14ManyDFIsarepolymicrobial,although pitalization and without the presence of health
when presenting acutely, most are caused by careeassociated risk factors, whereas hospital-
gram-positive cocci.31 In diabetic patients with acquired MRSA is traditionally associated with
chronic infections or prior antibiotic therapy, recenthospitalization.36,37Typically,CA-MRSA
aerobicgram-negativebacilliareoftencopatho- is resistant to fewer classes of antibiotics and
gens, and obligate anaerobes should be sus- carries Panton-Valentine leukocidin genes,
pected in ischemic or necrotic wounds. In whichleadtoproductionofcytotoxins,causing
addition,NSTIs should alwaysbe suspected to necrosisandleukocytedestruction.38,39Despite
bepolymicrobialuntilprovenotherwiseinpost- these differences, the distinction between CA-
surgical patients and in patients with diabetes, MRSAandhospital-acquiredMRSAisbeginning
peripheral vascular disease, decubitus ulcers, toblur40asCA-MRSAisbeingtransmittedinthe
orspontaneousmucosaltearsofthegastrointes- health care setting.41 In studies of bloodstream
tinalorgastrourinarytract.14Treatmentshould infections, the CA-MRSA USA300 genotype is
includebroad-spectrum antimicrobial coverage a significant cause of nosocomial infections,42
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MAYO CLINIC PROCEEDINGS
resultinginsimilarriskfactorsandoutcomesfor services under Medicare Part A.51 A physician
these patients.37 Current recommendations for order is required for inpatient admission on
the decision to treat empirically for MRSA in thebasisoffactorsthatincludepatientmedical
hospitalized patients are typically made on the historyandcomorbidities,severityofsignsand
basis of infection severity and progression.9 symptoms, and risk of adverse effects. As a
Becauseempiricbroad-spectrumantibioticsfol- guidelineforwhentoadmitpatients,aproposal
lowedbydeescalationisthestandardofcarefor has been made that beneficiaries who require
suspected serious MRSA infections,9 there is a hospital services, including OU services,52 for
need for more accurate MRSA risk assessment more than 1 Medicare utilization day (defined
modelstotailortreatmentappropriately.Zilber- ascarethatspans2midnights)areappropriate
bergetal43developedabedsideriskprediction for hospital admission with Medicare Part A
scoremodelthatusedage,ethnicity,andcomor- payment.51 Patient hospital services that span
bidities that more accurately identified patients fewer than 2 midnights should be provided in
with MRSA than screening with health caree the outpatient setting, unless the physician
associated risk factors, although both methods clearlydocumentsexpectationsthatthepatient
needimprovement. will require care that spans 2 midnights. With
the implementation of this guidance, patients
Where Should Patients Be Treated? with SSTIs who improve quickly and do not
Observationunits(OUs)arepreferredplacesto requirecare that spans 2 midnights inthe OU
assess and treat many patients with SSTIs.44 can continue treatment in the outpatient
Hospitalists can identify good candidates for setting, whereas those who require care that
OUs,suchasthoselikelytorespondtoempiric spans more than 2 midnights may need to be
therapy,thosewhorequireashortstay,orthose admitted.
who have a low probability of being infected
withresistantorganisms,45andreservehospital
ANTIMICROBIAL THERAPY
resources for patients with cellulitis and tissue
necrosis, severe pain, neck abscesses, or infec- Guideline Recommendations
tionsinspecificlocations(eg,periorbital,facial, Appropriateinitialantibiotictherapyisessential
andhand).46,47PatientsinOUswhorespondto inthetreatmentofSSTIstoimproveoutcomes
therapy can be switched to home therapy (Table 1).9,14,31,53 Inappropriate initial therapy
within24hours.Thoseslowtorespondshould increases patient morbidity, mortality, hospital
be evaluated for resistant pathogens or wors- length of stay, and total treatment costs.54
ening infection and should be hospitalized if Empiric therapy should be directed against
alternative therapy does not result in clinical likely pathogens.53 Penicillin is the treatment
improvement.47 However, in some patients, of choice for erysipelas, and first-generation
cutaneousinflammationmayworsenafteriniti- cephalosporins or penicillinase-resistant semi-
ationofeffectivetherapy,mostlikelybecauseof synthetic penicillins, such as dicloxacillin, can
thereleaseofpotentenzymescausedbysudden be used when MSSA is suspected.14 Agents
pathogendestruction.14Inretrospectivestudies that target streptococci are suggested for non-
of SSTIs, females and patients with fever, purulent cellulitis. If the cellulitis is purulent
elevated lactate level, cellulitis of the hand, or orresultsfrompenetratingtrauma,agentswith
leukocytosis (whitebloodcellcount>15,000/ additional antistaphylococcal activity, such as
mL[to convert to (cid:2)109/L, multiply by 0.001]) cephalexin, the combination of trimethoprim
were more likely to be hospitalizedafter being and sulfamethoxazole, minocycline, doxycy-
in an OU.48,49 In these studies, 29% to 38% cline, clindamycin, or dicloxacillin, should be
ofpatientswereadmittedtoinpatientunitsafter used. If anaerobes are suspected (eg, cellulitis
beinginOUs.Inaddition,evidence-baseddeci- due to deep penetrating trauma), the use of
sion support criteria, such as InterQual,50 can thecombinationofamoxicillinandclavulanate
helpdeterminewhetherpatientsshouldremain or other agents with anaerobic activity may be
inOUsorbehospitalized. beneficial.IncreasingresistanceofSaureusand
OnOctober1,2013,theCentersforMedi- Spyogenestoerythromycinlimitsitsuseinthese
care and Medicaid Services implemented re- infections, and better alternatives are avail-
quirements for hospital payment of inpatient able.55,56 Although empiric therapy for MRSA
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HOSPITALIST PERSPECTIVE ON SSTI TREATMENT
hasbecomestandardinhospitalizedpatientsfor 2009.58Inparticular,MRSAshouldbesuspected
whomSaureusisasignificantconcern,MRSAis in abscesses that do not respond to oral b-lac-
probably not a common cause of nonpurulent tamsafteradequatedrainage.14Oralanti-MRSA
cellulitis. Therefore, in circumstances in which agents should be used as initial therapy in pa-
patients are hospitalized with nonpurulent tients who do not require hospitalization. The
cellulitis, IV penicillinase-resistant penicillins CA-MRSAcanbetreatedwithnoneb-lactaman-
(eg, nafcillin and oxacillin) or first-generation tibiotics, such as doxycycline or minocycline.14
cephalosporins (eg, cefazolin) may be consid- Trimethoprim-sulfamethoxazole can also be
ered, with modification for therapy against used to treat serious staphylococcal infections,
MRSAifthereisnoclinicalresponse.9,14Clinda- including MRSA infections, although a single
mycinorvancomycincanbeusedasasubstitute trialfounditslightlylesseffectivethanvancomy-
in the presence of life-threatening penicillin cin in this setting.59 Because trimethoprim-
allergy.14 Uncomplicated cutaneous abscesses sulfamethoxazoleisnotactiveagainstSpyogenes,
can often be managed with incision and additionalagentsmaybeneededifSpyogenesis
drainage alone.9,53 Antibiotics are recommen- suspected.ClindamycinisavailableIVandorally
ded for abscesses in patients with severe or and has anti-MRSA activity but shouldbe used
extensive disease, signs and symptoms of sys- withcautionbecauseofinducibleorconstitutive
temic illness, extremes ofage, associated septic clindamycin resistance.9 Patients hospitalized
phlebitis,comorbidities,orimmunosuppression with cSSTIs should receive empiric therapy
orabscessesinanareawheredrainageisdifficult with IV broad-spectrum antibiotics with MRSA
orineffective.9 coverageandappropriatesurgicaldebridement.9
Treatmentchoiceforsurgicalsiteinfections EmpiricIVagentsagainstMRSAincludevanco-
depends on the infection location.14 Clean mycin, linezolid, daptomycin, and ceftaroline
woundsonthetrunk,head,neck,orextremities fosamil.Stepdowntooraltherapy,suchastetra-
usuallyrespond to cefazolin, oxacillin, or clin- cycline,linezolid,clindamycin,ortrimethoprim-
damycin. Infections that result from surgery sulfamethoxazole, should be considered on the
on the perineum, gastrointestinal tract, or basisofsusceptibilityresultsandafterinitialclin-
female genital tract require a regimen that icalresponse.14
includes antianaerobic activity. The DFIs that General guidelines for duration of therapy
present acutely generally respond to narrow- arerecommended;however,giventheconsid-
spectrum agents that cover aerobic gram- erablepatient-to-patientvariabilityinlengthof
positive cocci.31 Gram-negative coverage is therapy for SSTIs, duration should be deter-
neededfordiabeticpatientswhoreceivedanti- mined on the basis of clinical response. Pa-
biotics within the past month or have severe tients treated for cellulitis in the outpatient
or chronic infections.31 Anaerobic coverage settingshouldreceive5to10daysoftherapy.9
shouldbeaddedinthesettingofischemictissue For hospitalized patients with cSSTIs, appro-
and/orsystemictoxiceffects.TheNSTIsrequire priate antimicrobial therapy of 7 to 14 days
empiric gram-positive and gram-negative cov- is suggested.9 More complex infections, such
eragewithagentsactiveagainstanaerobicpath- as infections from hand wounds, can be
ogens(eg,piperacillin-tazobactamcombination complicated by nerve injury or fracture and
or a carbapenem).17 Parenteral clindamycin often require prolonged courses of antimicro-
should be added to inhibit toxin production bial therapy for osteomyelitis (4-6 weeks) or
and control inflammatory responses in severe synovitis (3-4 weeks).14 For patients with un-
group A streptococcal and clostridial infec- complicated orbital cellulitis, antibiotic ther-
tions.14,17 Vancomycin, daptomycin, or line- apy should be continued until all signs of
zolid should be included in these regimens orbital cellulitis have resolved and for a total
untilMRSAisruledout.15 of 2 or more to 3 weeks,60 with a shorter
Consistent with epidemiologic data indi- course of therapy appropriate for preseptal
cating a significantly increased incidence of cellulitis. In NSTIs, antimicrobial therapy
MRSA in SSTIs from 2000 (34%) to 2006 must be continued until the patient is afebrile
(77%, P<.001),57 use of initial antibiotics with for 48 to 72hours, hasclear clinical improve-
MRSAactivityhasincreasedforhospitalizedpa- ment, and no longer requires repeated opera-
tientswithcSSTIsfrom30%in2000to71%in tive procedures.14
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MAYO CLINIC PROCEEDINGS
Treatment Failure aureus.75 Heteroresistant VISA has minimum
Therateofinitialtreatmentfailureisconsider- inhibitoryconcentrations(MICs)withinthein-
able for cSSTIs. In a study that reviewed data termediate range but reduced susceptibility.76
from more than 100 US hospitals, 16.6% of Heteroresistant VISA can be inducible, poten-
acute infections, 34.1% of chronic or ulcera- tially resulting in therapeutic failurewith stan-
tive infections, and 26.7% of surgical site dard doses against strains with MICs of 0.5 to
infections had initial treatment failure.54 Fail- 2mg/mL.13,77In2006,afterevaluatingmicrobi-
ure to initiate antimicrobial therapy active ologicalandclinicaldataindicatingthatSaureus
against the causative pathogen within 48 isolates are less likely to respond when vanco-
hours of presentation is an independent risk mycinMICsare4mg/mLorgreater,theClinical
factor for treatment failure.61 Recently, the and Laboratory Standards Institute lowered
US Food and Drug Administration (FDA) susceptibility breakpoints from 4 to 2 mg/
revised its guidance for the evaluation of clin- mL.78 The clinical implications of a possible
ical response in skin infections to earlier time gradualincreaseinMICswithinthesusceptible
points of 48 to 72 hours after initiation of range,alsoknownasMICcreep,arenotclear.
therapy,62 which can be used to assess thera- Treatment failures have been reported with
peutic failure. Patients whose conditions dete- vancomycin-susceptible strains that have rela-
riorated despite empiric antibiotic therapy tivelyhighMICs,79anddoseescalationtomain-
shouldbetreatedmoreaggressivelyontheba- tain trough levels of 15 to 20 mg/mL has been
sis of Gram stain, culture, and drug suscepti- proposed to achieve therapeutic efficacy.80
bility.14 Worsening of the SSTI may indicate However, higher-dose regimens can increase
the presence of resistant pathogens, and ther- theriskofnephrotoxicity,81whichisassociated
apy should be reevaluated.14 In hospitalized withincreasingtroughlevels(particularly>20
patients after initial treatment failure, MRSA mg/mL),concomitanttherapywithnephrotoxic
should be considered and choice of agent agents, and longer durations of therapy, espe-
shouldbemadeonthebasisofsusceptibilities. ciallydurationslongerthan2weeks.80Vanco-
The need for source control, such as drainage mycin doses of 15 to 20 mg/kg given every 8
or debridement, should also be carefully to 12 hours are necessary for patients with
consideredforpatientsnotrespondingtoanti- normalrenalfunctiontoachievetargetedserum
biotic treatment. troughlevelswhentheMICis1mg/mLorless.13
Linezolid, an oral and IV oxazolidinone,
Updates on MRSA Agents wasapprovedbytheFDAin2000foruncom-
AsummaryofIVandoralantimicrobialagents plicatedskinandskinstructureinfectionsand
withactivityagainstMRSAinSSTIsisprovided complicatedskinandskinstructureinfections
in Table 2, and updates are discussed on the (cSSSIs).65 Linezolid had comparable efficacy
current and more recently approved agents with vancomycin and oxacillin followed by
sincethereleaseoftheInfectiousDiseasesSoci- dicloxacillininpivotaltrials,andlinezolidcan
etyofAmerica2005guidelinesonthemanage- beusedforthetreatmentofMRSASSTIs.82-84
mentanddiagnosisofSSTIs.9-12,14,63-73 Although generally well tolerated when used
Vancomycin is effective and often used foralimitedduration,linezolid iswellknown
against MRSA cSSTIs in the hospital. Empiric foritsriskofcausingreversiblemyelosuppres-
therapy with vancomycin has increased from sionandserotoninsyndrome.Completeblood
2000(18%)to2006(93%).57However,intrinsic cell counts should be monitored weekly to
characteristics of vancomycin that may limit its reduce the risk of myelosuppression,65 which
activityagainstMRSA,suchasslowratesofbacte- canoftenoccurinpatientstreatedfor2weeks
ricidalactivityandpoorpenetrationintotissues, or longer.65,85 Concurrent administration of
should be considered.74 The emergence of linezolid and an SSRI taken in the preceding
vancomycin-intermediate S aureus (VISA) and 5 weeks can precipitate a potentially life-
vancomycin-resistantSaureushasraisedconcerns threateningserotoninsyndrome.86Inaddition,
regarding the use of vancomycin.13 Although concernsaboutadverseevents(AEs)withpro-
these strains are not common, prolonged ex- longed administration have emerged. In post-
posure to vancomycin can increase the risk of marketing surveillance studies, lactic acidosis
infection with VISA or vancomycin-resistant S and peripheral and optic neuropathy were
1442 MayoClinProc. n October2014;89(10):1436-1451 n http://dx.doi.org/10.1016/j.mayocp.2014.04.018
www.mayoclinicproceedings.org
HOSPITALIST PERSPECTIVE ON SSTI TREATMENT
reported in patients receiving linezolid for Tigecyclineshouldbereservedforclinicalsitua-
durations that exceeded the recommended tions in which alternative therapies are not
maximum of 28 days.87 Because symptoms of available.11
lactic acidosis are nonspecific, monitoring of Telavancin, a lipoglycopeptide approved by
serum bicarbonate levels may be more useful the FDA in 2009 for the treatment of gram-
forsuspectedlacticacidosis.87 positivecSSSIs,hadcureratessimilartovanco-
Daptomycin, a lipopeptide with bacteri- mycin in 2 randomized, double-blind, phase 3
cidal activity, was approved by the FDA in studiestoassessitssafetyandefficacyin928pa-
2003forcSSSIs.63Daptomycincanbeconsid- tients with cSSSIs.72 Cure rates for MRSA were
eredforMRSAskininfections,buthospitalists also similar (telavancin, 91%; vancomycin,
should be aware of potential adverse effects 86%).Inameta-analysispublishedin2012of6
with daptomycin, specifically muscle toxic ef- randomizedcontrolledtrialsthatcomparedtela-
fects.88 Daptomycin has been reported to vancinandvancomycinincSSTIs andhospital-
elevate creatine kinase levels in up to 2.1% of acquired pneumonia,93 telavancin had similar
patients,88 which may be associated with efficacy in treating cSSTIs (odds ratio, 1.10;
myopathy and rhabdomyolysis. There is also 95% CI, 0.82-1.48), better clinical response,
a potential for cross-resistance of daptomycin andhighereradicationratesinMRSAinfections.
with vancomycin, and susceptibility tests Telavancinwasassociatedwithclinicallysignifi-
shouldbeperformedwhenfeasibleintheevent cant increases in serum creatinine levels
of prior glycopeptide exposure.71 Cell wall compared with vancomycin (10% and 5%, re-
thickening in VISA strains is correlated with spectively), higher rates of AEs, and AE-related
reduced susceptibility to both vancomycin withdrawals,withmostwithdrawalsbeingrelated
and daptomycin89; thus, daptomycin may not to nausea, vomiting, and renal AEs.93 The FDA
beidealtouseagainstVISAafterlackofefficacy hasissuedaboxedwarningregardingtheuseof
withvancomycin.In2010,theFDAreleaseda telavancininrenallyimpairedpatientsafterdeter-
safety announcement about daptomycin use mining higher all-cause mortality for telavancin
and eosinophilic pneumonia, which can (39%) compared with vancomycin (30%).12
develop 2 to 4 weeks after initiation of ther- Monitoring of renal function is recommended
apy.63,90Patientsreceivingdaptomycinshould for all patients, and use should be considered
be monitored for new-onset or worsening fe- onlywhenthebenefitsoftherapyoutweighthe
ver, cough, dyspnea with hypoxic respiratory risksinpatientswithabaselinecreatinineclear-
insufficiency,anddiffusepulmonaryinfiltrates. ance of 50 mL/min/1.73 m2 or less (to convert
Ifeosinophilicpneumoniaissuspected,dapto- tomL/s/1.73m2,multiplyby0.0167).
mycintherapyshouldbediscontinuedandsys- Ceftaroline fosamil is the prodrug of
temicsteroidtherapyinitiated.63 ceftaroline, acephalosporinthatexhibits broad-
Tigecycline, a glycylcycline with activity spectrum bactericidal activity against gram-
against anaerobic, gram-negative, and gram- positive pathogens, including MRSA and
positive organisms, including MRSA, was multidrug-resistant Streptococcus pneumoniae,
approvedbytheFDAin2005forthetreatment andgram-negativeorganisms.Itwasapproved
ofcSSSIs.11Ithadefficacysimilartothatofvan- in 2010 for the treatment of acute bacterial
comycin plus aztreonam in2 phase 3, double- skinandskinstructureinfections(ABSSSIs).10
blindpivotalstudiesin1116hospitalizedadults Ceftaroline fosamil therapy resulted in similar
with cSSSIs.91 Tigecycline had a safety profile clinicalcureratescomparedwithvancomycin-
similar to that of vancomycin-aztreonam, but aztreonam in 2 phase 3 clinical trials in pa-
nausea and vomiting were more common tients with cSSSIs.94 Ceftaroline fosamil was
(46%and21%,respectively;P<.001).Recently, also as effective against MRSA cSSSIs (clinical
the FDA issued a boxed warning for increased cure rate, 93.4%) as vancomycin-aztreonam
all-cause mortality with tigecycline treatment (94.3%). In 2012, a retrospective study was
when used in approved indications.92 Analysis publishedontheresultsofananalysisofclin-
of10clinicaltrialsrevealedahigherriskofdeath ical response at earlier time points in a popu-
among patients taking tigecycline (2.5%) com- lation of 400 patients who had ABSSSIs
pared with other antibiotics (1.8%; adjusted consistent with the definition provided by
risk difference, 0.6%; 95% CI, 0.0%-1.2%). the FDA guidance for ABSSSI trials.95 Clinical
MayoClinProc. n October2014;89(10):1436-1451 n http://dx.doi.org/10.1016/j.mayocp.2014.04.018 1443
www.mayoclinicproceedings.org
1
4 TABLE2. SummaryofIVandOralAntibioticsWithActivityAgainstMRSASkinInfectionsa,10-12,63-65
4
4
Agent Advantages Disadvantages DosingforSkinInfections AdverseEvents Resistance
Oralagents
Doxycycline9,14 Activityagainstgram- PregnancycategoryD 100mgorallytwicedailyfor Gastrointestinalintolerance, Tetracyclineresistanceand
positiveandgram- Toothenameldiscolorationin 5-10daysinoutpatient anorexia,rash inducibledoxycycline
negativeorganisms childrenyoungerthan8 purulentcellulitis resistancehavebeen
years reported
DataonuseforMRSA
infectionsarelimited
Notrecommendedfor
streptococcalinfections
Trimethoprim- 95%-100%ofCA-MRSA NotFDAapprovedforany 1-2double-strengthtablets Gastrointestinalintolerance, ResistanceinCA-MRSA
sulfamethoxazole9,66 strainsaresusceptible staphylococcalinfections orallytwicedailyfor5-10days anorexia,rash isolatesislow
invitro PregnancycategoryD inoutpatientpurulentcellulitis
EffectiveforpurulentSSTI Contraindicatedinpatients
inchildren youngerthan2months
M Notrecommendedfor
a
yo streptococcalinfections
Clin Clindamycin9 Excellentpenetrationinto NotFDAapprovedforMRSA 300-450mgorally3timesper Gastrointestinalintolerance Inducibleorconstitutive
Pro abscesses infections dayforoutpatientpurulent (particularly resistancein50%ofMRSA
c. PregnancycategoryB cellulitis Clostridiumdifficileeassociated isolateswithclindamycin
n
O IVformulationavailable diarrhea),rash,pruritus resistance
c
to IVagents
b
er Vancomycin9,67-71 Vastclinicalexperience Activeagainstonlygram- 15-20mg/kgperdoseevery Hypotension,gastrointestinal PossibleMICcreep
2
01 Inexpensive positivepathogens 8-12hours,nottoexceed intolerance,stomatitis,chills, Vancomycin-intermediateand
4
;89 Onlyavailableinparenteral 2gperdose drugfever,rash,eosinophilia, -resistantStaphylococcusaureus
(1
0 form AdjustdosageforCrCL reversibleneutropenia hasbeenseenbutremains
):1
43 Riskofnephrotoxicity uncommon
6
-1 Monitoringofbloodlevels
4
51 required
n
Slowbactericidalactivity
h
ttp Linezolid67,68,70,71 OralandIVformulations Activeagainstonlygram- 600mgIVororalevery12 Gastrointestinalintolerance, Resistanceisuncommonbut
://d available positivepathogens hoursfor10-14daysincSSSIs headache,insomnia,rash, canbeassociatedwithdrug M
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