Changes in prescriptive practices in skin and soft tissue infections associated with the increased occurrence of community acquired methicillin resistant Staphylococcus aureus

Changes

in

prescriptive

practices

in

skin

and

soft

tissue

infections

associated

with

the

increased

occurrence

of

community

acquired

methicillin

resistant

Staphylococcus

aureus

Cheryl

Meddles-Torres

,

Shuang

Hu

,

Corrine

Jurgens

a_{BiologyDepartment,QueensboroughCommunityCollege,222-0556thAvenue,M213,Bayside,NY} 11364,USA

b_{StonyBrookUniversity,MathematicsDepartment,StonyBrook,NY11794,USA}

Received8January2013 ;receivedinrevisedform29April2013;accepted30April2013

KEYWORDS MRSA; SSTI; Staphylococcusaureus; Communityacquired; Methicillinresistance Summary

Background: Over30%of theUSpopulationiscolonized withmethicillinresistant Staphylococcusaureus(MRSA).Peoplewithinthecommunity,withoutfactors asso-ciatedwithHospitalAcquired(HA)MRSA,presentwithskinandsofttissueinfections (SSTIs).CommunityAcquiredMRSA(CA-MRSA)isresistanttoantibioticstypically pre-scribedforSSTI.ManySSTIsaretreatedwithantibioticsthatareineffectiveagainst drugresistantstrains.

Studyobjectives: Thisstudy examines theincidenceofSSTIs associatedwith CA-MRSA,todetermineifanincreaseinSSTI’sisassociatedwithchangesinprescribing patternsforMRSA.

Methods: A secondary analysis of the National Ambulatory Medical Care Survey (NAMCS) and National Hospital Ambulatory Medical Care Survey (NHAMCS) data wasusedtodetectincidenceofSSTIsbasedonICD-9coding betweentheperiods of 1997—2002 and2003—2008. Antibioticprescribingpatternswereexamined for treatment.

Results:IncidenceofSSTIsincreasedby84.7%from1997—2002to2003—2008. Antibi-oticsprescribedformethicillinsensitiveS.aureusdecreasedwhiletreatmentwith MSRAantibioticsincreased.

Abbreviations:CA-MRSA,CommunityAcquiredMRSA;SSTI,skinandsofttissueinfections;MRSA,methicillinresistant Staphylococ-cusaureus;MSSA,methicillinsensitiveStaphylococcusaureus;NAMCS,NationalAmbulatoryMedicalCareSurvey;NHAMCS,National HospitalAmbulatoryMedicalCareSurvey.

∗_{Correspondingauthorat:2241ArthurStreet,Merrick,NY11566,USA.Tel.:+15169937595/7186316056;fax:+17186316678.}

E-mailaddresses:[email protected],[email protected](C.Meddles-Torres),[email protected] (S.Hu),[email protected](C.Jurgens).

1 _{Tel.:+16314443236.}

1876-0341/$—seefrontmatter.PublishedbyElsevierLimitedonbehalfofKingSaudBinAbdulazizUniversityforHealthSciences.

Conclusion:ThereisanincreasedincidenceofSSTIwithinthecommunity,suggesting thatCA-MRSAmaybeacontributingfactor.Healthcareprovidersarerecognizingthe increasedincidenceofCAMRSA,andaretreatingSSTIwithappropriateantibiotics. Published by Elsevier Limited on behalf of King Saud Bin Abdulaziz University for HealthSciences.

Introduction

Staphylococcus aureus is a bacterium commonly found on normal skin and in the nasal flora of healthy individuals in the community. It is esti-mated that at least 30%of the US population are permanentlycolonized oraretransientcarriers of

S. aureus[1—3]. Since thedevelopment of antibi-otics, S. aureus has quickly become resistant to many antibiotics thatarecommonly usedto treat staphylococcal infections, such as beta-lactams and macrolides [1,2,4,5]. Currently, methicillin-resistant S. aureus(MRSA) infections areendemic inmanyhealthcareinstitutions.Furthermore,new strainsofMRSAaredevelopingwithincommunities, affectingpeoplewithoutrecognizedriskfactorsfor hospital-acquiredMRSA(HA-MRSA)[6—10].

Background

and

significance

Beginningin the1990s,community-acquiredMRSA (CA-MRSA) infections emerged in persons with-out recognized risk factorsassociated with MRSA, such as a prior history of healthcare exposure, hospitalization, surgery, permanent intravenous linesandotherindwellingdevices,orhemodialysis

[3,10—13]. Comparedwith theantibiotic-resistant nature of HA-MRSA, CA-MRSA is more susceptible to antibiotic treatment, and uncomplicated cases can be treated successfullyin anambulatory care setting [11]. Themajority ofinfections causedby CA-MRSAareskinand softtissueinfections(SSTIs) thattypicallypresentasboils,abscesses,or celluli-tis[10,14—16].

Patients present to primary care with lesions thatarepustularandmayhavecentralnecrosisor purulent drainage. The lesions may be reddened and demonstratetender and palpable fluctuance. Healthcareproviderscommonlytreatpatients pre-senting with SSTIs with antibiotics used to treat methicillin-sensitive S. aureus (MSSA) [4,5]. How-ever, these antibiotics are not therapeutic for CA-MRSA, leading totreatment failure, increasing a patient’s exposureto more antibiotics,allowing possiblecontactwithdrainagefromlesionstomore people inthe community,and increasingthe asso-ciatedhealthcarecostswithrepeatedvisitstothe primarycareoffice.

The purpose of this study was to determine if there is a relationship between the increased prevalence of SSTIs and CA-MRSA by comparing theoccurrencesin1997—2002and2003—2008and changes in prescribing patterns for antibiotics for patientspresentingwithSSTIs.Wehypothesizethat byidentifyinganincreaseinCA-MRSAwithina pop-ulation,practitionerswillmorelikelyscreenforthe presence of MRSA and treat with the appropriate antibiotics.

Review

of

the

literature

CA-MRSA is described as a leading cause of SSTIs in the United States [10,17]. Approximately 80% of CA-MRSAinfections are SSTIs [10]. In addition, CA-MRSA infections have emerged among patient groupswithriskfactorsnotassociatedwith health-care,whichincludespatientswithsportsexposure, incarceration, intravenous druguse, overcrowded housing,andpoorhygiene[11,16,18—20].However, theepidemiologyofCA-MRSAis becoming increas-inglycomplex,andinprimarycare,patientsfound to be working in a healthcare setting are also at increasedrisk[21,22].Nonetheless,theprevalence of CA-MRSA is increasing, and notably, patients presenting with SSTIs are being treated without considerationofthedrug-resistantnatureofMRSA

[23].

Often, treatmentofabscesseswithincisionand drainageisanadequatetreatmentforSSTIscaused byStaphylococcalinfections[23—25].Studies sug-gestthattreatmentofSSTIsaftersurgicaldrainage and treatmentwith prescription ofantibiotics not effectiveagainstMRSAinfectionshavehighsuccess rates[23,25]. However, in aninternational survey conductedbytheNewEnglandJournalofMedicine, the majority of the respondents indicated that antibiotictreatmentwouldbeprescribedfollowing incisionanddrainage[26].

Antibiotics classes commonly prescribed for MSSA infections are the beta-lactams and cephalosporins. However, they have no thera-peuticeffectonMRSA.Ifthereisclinicalsuspicion of CA-MRSA in SSTIs and the patient is described as high risk, it is important to culture SSTIs and prescribe antibiotics based on culture and

sensitivities of the sample [3,17,27]. Antibiotic classesshowntohavetherapeuticeffectsonMRSA are fluoroquinolones, tetracyclines, clindamycin, andtrimethoprim/sulfamethoxazole[20,23,28].

In an outpatient setting, trimetho-prim/sulfamethoxazole, fluoroquinolones, tetracyclines, and clindamycin have demon-strated therapeutic effects on CA-MRSA with monotherapy [20,23,25,28]. Linezolid is also a feasible treatment option for CA-MRSA; however, it is very expensive compared with other drugs with similar efficacies and should be reserved for the more resistant strains associated with HA-MRSA [14,18,27]. Rifampicin is not prescribed for monotherapy but is prescribed in combination with other antibiotics for active infections for a synergisticeffect.

Methods

Asecondaryanalysisofapubliclyavailabledataset wasused toexamine occurrencesofpatients pre-sentingwithSSTIsandtheantibioticsprescribedfor treatment.

Data

source

PublicusedatafromtheNationalAmbulatory Med-icalCareSurvey(NAMCS)andtheNationalHospital Ambulatory Medical Care Survey (NHAMCS) were used for this analysis. The NAMCS is a probabil-itysamplesurveyofoffice-basedphysiciansinthe UnitedStates.TheNHAMCSisanannualprobability sample surveyof hospitaloutpatient departments andemergencydepartmentsintheUS.TheUS Cen-sus Bureauis responsible for fieldoperations and datacollection.

Human

subjects’

protection

Before 2003, NAMCS and NHAMCS were exempt fromInstitutionalReviewBoardReview.InFebruary 2003,NAMCSandNHAMCSprotocolswereapproved by the CDC’s National Center for Health Statis-tics Research Ethics Review Board. Waivers were granted for the requirements to obtain informed consent of patients and patient authorization for releaseofpatient medicalrecord databy health-careproviders.

Sample

Allpatientspresentingforambulatorymedicalcare wereidentifiedfrom1997to2002and2003to2008

from the NAMCS and NHAMCS public data based uponInternational ClassificationofDisease, Ninth Revision, Clinical Modification (ICD-9-CM) codes thatare representativeof SSTIs and the prescrib-ing patterns of antibiotics, which were compared withSSTIprevalence.

Data

collection

procedures

Patientsurveysfrom1997to2002and2003to2008 wereanalyzed. Each datarecordcontains patient demographicdataandinformationaboutthevisit, includingcauseofinjury,diagnosis,ambulatory sur-gical procedures, NAMCS and NHAMCS outpatient department,medications,anddisposition.Upto3 diagnosesarecodedaccordingtotheICD-9-CM,and upto8medicationswererecordedpervisit.

Drugs are coded in terms of their generic components and therapeutic classes using Lex-icon Plus. The Lexicon Plus is a compre-hensive database of all prescription and non-prescription drugs available in the US market (http://www.multum.com/Lexicon.htm).

Analysis

Toestimatethe numberofvisitsinallambulatory settings,NAMCSand NHAMCSdatawerecombined toproduce nationalestimates,and the datawere separatedinto2groupsof5yearseach(1997—2002 and2003—2008).Thefrequencieswerecalculated, aswerethepercentagesofvisitsofselectedICD-9 codes,patientcharacteristics,andantibioticdrugs with95%CIandstandarderrorusingtheestimates of the US population provided by the US Census Bureauand with SAS statisticalanalysis software. Tofurtherdetermine whichfactorswere indepen-dently associated with SSTIs,a logistic regression analysis of all visits was performed. The depend-ent variable was defined as a diagnosis of one of theSSTIs. The modelcontains the following inde-pendent variables: age, sex, race, ethnicity, and expectedsourceofpayment.

Results

Based upon comparison of Tables 1 and 2, dur-ing 1997—2002, a total of 4.8 million visits were madetoUSambulatorycareprovidersforselected skin and soft tissue infections, which represents 0.6%(95%CI0.59—0.68)ofallvisits.Theincidence increasedduring2003—2008:atotalof7.3million visitswere madetoUS ambulatorycare providers for SSTS, representing 0.83% (95% CI 0.78—0.88)

Table1 FrequencyandpercentageofambulatorycarevisitsforselectedSSTI1997—2002. Diagnosis ICD-9-CMcode No.visits/1000

persons

%Visits Stderrof% 95%CIofpercentage

Allvisits 478,210 NA NA NA

SelectedSSTI 3977 0.6345 0.0203 0.0593—0.6756

Carbuncleandfuruncle 680 123 0.0251 0.0034 0.0181—0.0320

Cellulitis/abscess 681/682 3146 0.4719 0.0181 0.4353—0.5085 Skin/subcutaneousinfection 686 436 0.0735 0.0062 0.0610—0.0860

Folliculitis 704.8 272 0.0640 0.0042 0.0554—0.0726

Unspecifiedlocalinfection andsubcutaneoustissue

686.9 352 0.0432—0.0667

Table2 FrequencyandpercentageofambulatorycarevisitsforselectedSSTI2003—2008. Diagnosis ICD-9-CMcode No.visits/1000

persons

%Visits Stderrof% 95%CIofpercentage

Allvisits 582,806 NA NA NA

SelectedSSTI 7345 0.8283 0.0258 0.7777—0.8790

Carbuncleandfuruncle 680 213 0.0379 0.0057 0.0268—0.0491

Cellulitis/abscess 681/682 6239 0.6562 0.0229 0.06112—0.7012 Skin/subcutaneousinfection 686 516 0.0659 0.0065 0.0532—0.0785

Folliculitis 704.8 377 0.0684 0.0070 0.0547—0.0821

Unspecifiedlocalinfection andsubcutaneoustissue

686.9 420 0.0534 0.0057 0.0422—0.0645

Table3a Frequencyandpercentagedistributionofambulatorycarevisitsforselectedskinandsofttissue infec-tionsbyselectedpatientandtheirvisitcharacteristicsfrom1997to2002.

Characteristics No.visits/1000persons %Distribution 95%CIofpercentage Patientsex Female 1892 50.1706 47.8595—52.4818 Male 2085 49.8294 47.5182—52.1405 Patientage Under15years 453 15.0232 13.1032—16.9433 15—24years 525 9.7090 8.1442—11.2737 25—44years 1341 29.3982 27.0483—31.7480 45—64years 1054 26.0881 24.0824—28.0939 65—74years 292 8.9170 7.2548—10.5792

75yearsandover 312 10.8645 9.0839—12.6452

Patientrace

White 3045 84.5600 82.1030—87.0169

Black 797 11.8553 9.5511—14.1595

Other 135 3.5847 2.3527—4.8168

Patientethnic(selected)

HispanicorLatino 619 11.0596 9.0556—13.0636

Non-HispanicorLatino 2673 69.1289 65.2427—73.0150

Patientpaytype(selected)

Privateinsurance 1612 53.5738 51.3031—55.8445

Medicare 625 17.2859 15.3741—19.1977

Medicaid 754 12.9390 10.6459—15.2322

Self-pay 521 7.8414 6.6409—9.0419

Table3b Oddsratioestimates1997—2002.

Effect Pointestimate 95%Waldconfidence limits Age 1.003 0.975 1.032 Sex 1.418 1.296 1.552 Race 0.962 0.862 1.074 Ethnic 1.052 0.983 1.127 Paytype 1.003 0.984 1.023

of all visits. This is an increase of 84.7% when comparedto1997—2002period. Thisincreasewas predominately influenced by diagnoses of celluli-tis/abscess(ICD-code681/682),whichincreasedby 98.3%from1997—2002to2003—2008.

AcomparisonofTables3aand4ashowsthevisit frequency and percentage distributions for SSTIs according to the patient characteristics of sex, age, ethnic,race, and payment type. When com-paring these two tables, the distributions of the characteristics for both periods reveal no signifi-cant differences in patient demographics. In the two periods, the factor of sex had no impact on the number and percentage distribution ofvisits. As for age, the frequency of visits in the two periods was higher for persons aged 25—64 than

Table4b Oddsratioestimates2003—2008.

Effect Pointestimate 95%Waldconfidence limits Age — — Sex 1.424 1.283 1.581 Race 1.108 1.005 1.222 Ethnic 1.009 0.992 1.026 Paytype 1.052 1.023 1.081

for persons in other age groups. White patients made a greater proportion of visits compared with patients from non-Hispanic or Latino back-grounds.Privateinsurancewasthemostfrequently recordedexpectedsourceofpayment,accounting for approximatelyhalf ofthe visits. Medicareand Medicaidwerethesecondarymainpaymentsources and accounted for approximately 30% of allvisits (seeTables3band4b).

Comparing the antibiotics prescribed in

Tables 5 and 6, the prescription of penicillins decreased by 21.2%, and cephalosporin pre-scriptions decreased by 24%. Both of these antibiotics are not effective against MRSA. Tetracycline prescriptions increased by 471%, quinolones/derivatives increased by 94%, and

Table4a Frequencyandpercentagedistributionofambulatorycarevisitsforselectedskinandsofttissue infec-tionsbyselectedpatientandtheirvisitcharacteristicsfrom2003to2008.

Characteristics No.visits/1000persons %Distribution 95%CIofpercentage Patientsex Female 3567 49.9280 47.6646—52.1915 Male 3778 50.0720 47.8085—52.3354 Patientage Under15years 945 16.9828 14.9663—18.9993 15—24years 1199 12.7207 11.0256—14.4157 25—44years 1449 25.8729 23.9326—27.8133 45—64years 1889 29.7233 27.4093—32.0373 65—74years 414 6.4361 5.3118—7.5605

75yearsandover 449 8.2641 6.9493—9.5790

Patientrace

White 5273 79.4950 77.0926—81.8975

Black 1752 15.7377 13.6140—17.8615

Other 320 4.7672 3.3285—6.2059

Patientethnic(selected)

HispanicorLatino 920 11.1993 8.4747—13.9239

Non-HispanicorLatino 5773 78.4539 74.9204—81.9874

Patientpaytype(selected)

Privateinsurance 2535 48.8826 46.4834—51.2818

Medicare 945 15.4835 13.8097—17.1572

Medicaid 1715 15.0395 13.3532—16.7257

Self-pay 1362 11.9660 10.5252—13.4068

Table5 FrequencyandpercentageofantibioticdrugsatambulatorycarevisitsforselectedSSTI1997—2002. Antibioticclasses No.prescriptions/1000 Percentage 95%CIforpercentage

Allvisits 3977 NA NA MSSAantibiotics Penicillins 451 11.9442 10.2671—13.6213 Cephalosporins 1711 36.6708 34.3055—39.0361 MRSAantibiotics Tetracyclines 45 1.9362 1.0442—2.8282 Fluoroquinolones(quinolones/derivatives) 190 7.2426 5.8183—8.6669 Trimethoprim/sulfamethoxazole 30 1.0463 0.4846—1.6080

Antimicrobialagents,unspecified 18 0.3797 0.3073—0.4521

Miscellaneousantibacterialagents 136 2.1117 1.6867—2.5367

Table6 FrequencyandpercentageofantibioticdrugsatambulatorycarevisitsforselectedSSTI2003—2008. Antibioticclasses No.prescriptions/1000 Percentage 95%CIforpercentage

Allvisits 7345 NA NA MSSAantibiotics Penicillins 372 4.9020 3.7508—6.0532 Cephalosporins 1379 17.8713 15.8686—19.8739 MRSAantibiotics Tetracyclines 257 4.2060 3.0056—5.4064 Fluoroquinolones (quinalones/derivatives) 370 6.6936 5.4205—7.9667 Trimetho-prim/sulfamethoxazole 1349 13.3544 11.4070—15.3018 Antimicrobialagents, unspecified/miscellaneous antibacterialagents 1522 16.1383 13.8402—18.4364

sulfonamides and trimethoprim increased by 4396%. Overall, prescriptions for drugs that are effective for MSSAdecreased,whileMRSA-specific antibioticprescriptionsincreased.

Discussion

There was a significant increase in SSTIs from 1997—2002to2003—2008.ItisestimatedthatSSTIs increased over the period of 5 years by 84.7%. Patients present to ambulatory care settings with infectionsassociatedwithCA-MRSAprimarilyinthe formofabscesses,whichincreasedby98.3%overa periodof5years.Healthcare providersresponded to the increases in SSTIs and rates of MRSA by prescribing antibiotics that are successful against these ‘‘superbugs.’’ A significant increase in the prescription of antibiotics effective against MRSA (e.g.,trimethoprim/sulfamethoxazole)occurredin the period of 2003—2005. Inversely, there was a decrease in the prescription of penicillins and

cephalosporins, which were once the first-line antibioticsprescribedforSSTIs.

Demographics of age, sex, race, ethnicity, and paytypedidnotrevealanysignificantchangesfor patients presenting with SSTIs between the two timeperiodsexamined. Thesourceofpaymentor paytypedoesnotreflecton apatient’s incomeor social status. However,due tothe increasingcost offee-for-servicetreatment,theexpensemay dis-courage patients without medical insurance from seekingmedicaltreatment.However,therewasan overall increase in infection rates. This could be duetobothantibioticresistanceoccurringat over-whelming rates and the ease of spread of SSTIs by close personal contact, exposure to draining lesions,andinaccuratediagnosisandtreatment.

Limitations in this study included the inability to separate first-time visits from repeat visits. A personreturning for an unresolvedSSTI mayhave beencountedmorethanonetime,andtheanalysis does not account for patient follow-up. In addi-tion,patientsmayhavebeendiagnosedwithmore

thanone typeofSSTI (e.g.,cellulitis andabscess) and thereforemayhave beenidentified bytwoor moreICD-9codes.Thecategoryofantibiotics pre-scribed does not specify the diagnosis for which the drug was prescribed, and an assumption was made that each antibiotic was recorded for the patientpresentingforanSSTIduringthatvisit.The CDCdatabasedoesnothavecurrentprocedural ter-minology (CPT) coding for incision and drainage, needleaspiration,ordebridementofabscessesand wounds. These interventions are first-line treat-ments for infections that fluctuate or that have pusthatcouldbedrained.Therewasalsono infor-mationtodetermine ifthepatient’sinfectionwas culturedandtestedforantibioticsensitivity.

Further study is needed to determine what percentages of patients experienced incision and drainage,debridement,andneedleaspirationsand the susceptibility patterns of cultured infections. If possible, it would be beneficial to track the patients’ courses of treatment from diagnosis to resolutionto estimatedurationoftreatment.The use of other antibiotics, such as rifampicin as an adjunct therapy and linezolid, should also be analyzedtodeterminechangesinprescription pat-terns.Examinationofreinfectionrateswouldalso prove to be useful to determine which patients are at risk for reinfection and to establish which patientsmaybenefitfromdecolonizationofMRSA. Overall, this study demonstrates that there is an increase in infection rates, and health-careproviders arerecognizingpatientspresenting with SSTIs. Patients are treated according to the increaseinCA-MRSAbybeingprescribedantibiotics thathavebeenproventobesuccessfulagainstthe bacteria.

Conflict

of

interest

Theauthorsdeclarenoconflictofinterest.

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