Excess Costs and Utilization Associated with Methicillin Resistance for Patients with Staphylococcus aureus Infection

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1 infection control nd hospitl epidemiology pril 2010, vol. 31, no. 4 originl rticle Excess Costs nd Utiliztion Associted with Methicillin Resistnce for Ptients with Stphylococcus ureus Infection Gregory A. Filice, MD; John A. Nymn, PhD; Ctherine Lexu, PhD; Christine H. Lees, MPH; Lindsy A. Bockstedt, MS; Kthryn Como-Sbetti, MPH; Lindsey J. Lesher, MPH; Ruth Lynfield, MD objective. To determine differences in helthcre costs between cses of methicillin-susceptible Stphylococcus ureus (MSSA) infection nd methicillin-resistnt S. ureus (MRSA) infection in dults. design. Retrospective study of ll cses of S. ureus infection. setting. Deprtment of Veterns Affirs hospitl nd ssocited clinics. ptients. There were 390 ptients with MSSA infections nd 335 ptients with MRSA infections. methods. We used medicl records, ccounting systems, nd interviews to identify services rendered nd costs for Minnepolis Veterns Affirs Medicl Center ptients with S. ureus infection with onset during the period from Jnury 1, 2004, through June 30, We used regression nlysis to djust for ptient chrcteristics. results. Medin 6-month undjusted costs for ptients infected with MRSA were $34,657, compred with $15,923 for ptients infected with MSSA. Ptients with MRSA infection hd more comorbidities thn ptients with MSSA infection (men Chrlson index 4.3 vs 3.2; P!.001). For ptients with Chrlson indices of 3 or less, men djusted 6-month costs derived from multivrite nlysis were $51,252 (95% CI, $46,041 $56,464) for MRSA infection nd $30,158 (95% CI, $27,092 $33,225) for MSSA infection. For ptients with Chrlson indices of 4 or more, men djusted costs were $84,436 (95% CI, $79,843 $89,029) for MRSA infection nd $59,245 (95% CI, $56,016 $62,473) for MSSA infection. Ptients with MRSA infection were lso more likely to die thn were ptients with MSSA infection (23.6% vs 11.5%; P!.001). MRSA infection ws more likely to involve the lungs, bloodstrem, nd urinry trct, while MSSA infection ws more likely to involve bones or joints; eyes, ers, nose, or throt; surgicl sites; nd skin or soft tissue ( P!.001). conclusions. Resistnce to methicillin in S. ureus ws independently ssocited with incresed costs. Effective ntimicrobil stewrdship nd infection prevention progrms re needed to prevent these costly infections. Infect Control Hosp Epidemiol 2010; 31: Methicillin nd other semisynthetic penicillins represented importnt dvnces in the tretment of Stphylococcus ureus infections, but within 2 yers of their introduction the first clinicl isoltes of methicillin-resistnt S. ureus (MRSA) ppered. 1 Since then, the incidence of MRSA infection hs incresed relentlessly. Until the lte 1990s, MRSA infection occurred mostly in helthcre settings. 2 During the pst decde, helthy people within community settings hve developed infections with new MRSA strins (community-ssocited MRSA), representing new burden of disese. 3-6 Ntionl dt indicte tht hospitliztions for MRSA infection hve incresed 119% from 1999 through S. ureus infections re costly, nd studies hve suggested tht MRSA infections re more costly thn MSSA infections, but these studies hve limittions. Some studies hve investigted only one type of S. ureus infection, others hve quntified costs for only short periods fter onset, nd still others hve used hospitl chrges, which my not reflect utiliztion nd costs ccurtely To contribute towrd more comprehensive ssessment of costs to society, we quntified resources used for ptients with MRSA infections nd for ptients with MSSA infections nd the costs of these resources t tertiry cre Deprtment of Veterns Affirs (VA) hospitl using the VA decision support system (DSS) to determine utiliztion nd costs. DSS is n ctivity-bsed costing system tht mesures costs of VA deprtments, intermedite helthcre products, hospitl stys, nd outptient encounters. 16,17 Others 17 hve found tht DSS is ccurte, complete, nd consistent, nd becuse of the VA s fixed nnul budgets, VA unit costs re less likely to be distorted by the use of reimburse- From the Division of Infectious Diseses, Deprtment of Medicine, University of Minnesot Medicl School (G.A.F.), the Infectious Disese Section, Medicl Service, Veterns Affirs Medicl Center (G.A.F.), nd the Division of Helth Services Reserch nd Policy, University of Minnesot School of Public Helth (J.A.N., L.A.B.), Minnepolis, nd the Minnesot Deprtment of Helth, Sint Pul (C.L., C.H.L., K.C.-S., L.J.L., R.L.), Minnesot. Received June 21, 2009; ccepted September 10, 2009; electroniclly published Februry 24, by The Society for Helthcre Epidemiology of Americ. All rights reserved X/2010/ $ DOI: /651094

2 366 infection control nd hospitl epidemiology pril 2010, vol. 31, no. 4 figure 1. Flowchrt depicting ptient prticiption nd exclusion from the study. ment-mximizing strtegies thn re privte systems pid on per unit bsis. methods S. ureus Illness We extrcted informtion from the Minnepolis VA Medicl Center microbiology lbortory dtbse on ll S. ureus isoltions during the study period, Jnury 1, 2004, through June 30, We reviewed medicl records for ll ptients with S. ureus isoltes to find cses of S. ureus disese. Diseses were ctegorized ccording to Ntionl Nosocomil Infections Surveillnce system definitions. 18 Ptients with more thn one mnifesttion during the first episode of disese (eg, cystitis nd pyelonephritis) were ctegorized ccording to the most severe disese on the bsis of criteri tht included (1) whether infection ws deep or superficil, (2) the severity of signs nd symptoms, nd (3) the sequence of onset nd resolution of seprte mnifesttions. Ptients with multiple episodes of S. ureus disese were enrolled only for the first one. We chrcterized these illnesses, other medicl problems, nd complictions of illness or therpy during the 6 months fter onset of signs or symptoms of the index S. ureus infection. Methicillin resistnce ws determined by use of stndrd methods. 19 Two ptients who hd both MSSA isoltes nd MRSA isoltes were included s MRSA ptients. Dt Sources nd Costs Clinicl dt were collected from the VA electronic clinicl ptient record system, 20 nd utiliztion nd cost dt were collected from the DSS. 16,17 The DSS detils ll direct nd indirect costs of cre, including services provided by contrcted non-va providers (on fee bsis); bundles costs ccording to user specifictions; nd stores dt on every service received by ech ptient. Services included clinic visits, hospitl bed dys djusted for type of unit nd cuity, procedures, contrcted services, medictions, nd supplies. We quntified services nd costs for ech dy during the 6 months fter onset of S. ureus illness. VA cre is provided to veterns of United Sttes uniformed services. Veterns re chrged only copyments for medictions nd certin services, nd lower income veterns py mens-djusted rte. Clinicl dt, including demogrphic informtion nd clinicl detils on infections, tests, tretments, complictions, underlying comorbidities, nd outcomes, were extrcted with stndrdized cse report forms. The cses of 40 (5.5%) ptients rndomly selected mong the 725 prticipnts were reviewed independently by study personnel to ensure ccurcy, consistency, nd completeness. The cses of n dditionl 108 (15%) ptients were discussed by 2 or more reviewers becuse the clssifiction decisions were complex or difficult. Finl clssifictions were decided by mens of consensus. Beginning in Jnury 2005, we conducted interviews to estimte costs incurred by ptients or third-prty pyers for cre received from sources outside the Minnepolis VA Medicl Center. To minimize recll problems, we interviewed ptients with recent cses (onset fter December 31, 2004). Ptients or uthorized fmily members or friends were sked bout helth cre received in non-va settings nd out-ofpocket costs for helth cre nd ssocited expenses (eg, trnsporttion) on 2 occsions, 4 16 weeks nd weeks fter onset. For those who received cre in non-va settings, we sought permission to vlidte with other providers the numbers nd types of clinic visits nd/or length of sty in community hospitls or nursing homes. Sttisticl Anlysis The primry nd secondry outcomes were differences in helthcre costs nd utiliztion, respectively, between the MRSA group nd the MSSA group. Costs were djusted to 2007 US dollr mounts with the Consumer Price Index s recommended by the VA. 21 We used the Student t nd x 2 tests to determine the significnce of differences in bseline chrcteristics. Becuse helthcre cost distributions were skewed, we tested differences between groups in univrite cost nlyses with the nonprmetric Mnn-Whitney U test. We used semilogrithmic ordinry lest-squres model for multivrite cost nlyses, with the nturl log of totl helthcre costs s the dependent vrible. 22 We did not use generlized liner model, becuse substntil kurtosis of the log helthcre costs indicted tht precision would hve been indequte. 22 The regression eqution for log-costs included vribles for infection site, ge, Chrlson index, 23 urbn residency, deth, nd methicillin resistnce. The Chrlson index is used to quntify the effect of comorbidity on helth nd

3 methicillin-resistnt s. ureus nd costs 367 tble 1. Chrcteristic Bseline Chrcteristics of Ptients Infected with Stphylococcus ureus All prticipnts (N p 725) with MRSA (n p 335) with MSSA (n p 390) Odds rtio, MRSA : MSSA Age.07 Men SD, yers yers 15 (2) 7 (2) 8 (2) yers 73 (10) 31 (9) 42 (11) yers 270 (37) 116 (35) 154 (39) yers 226 (31) 107 (32) 119 (31) x80 yers 141 (19) 74 (22) 67 (17) Mle sex 704 (97) 324 (97) 380 (97).56 b Rurl residence 226 (31) 101 (30) 125 (32).58 b Chrlson index, men SD !.001 Infection site or disese Bone nd/or joint c 74 (10) 27 (8) 47 (12) 0.64 Bronchitis 22 (3) 10 (3) 12 (3) 0.97 Bcteremi 85 (12) 44 (13) 41 (11) 1.29 Crdiovsculr system d 7 (1) 2 (1) 5 (1) 0.46 Eyes, er, nose, throt 40 (6) 7 (2) 33 (8) 0.23 Gstrointestinl 1 (0.1) 0 (0.0) 1 (0.3) Pneumoni 76 (10) 59 (18) 17 (4) 4.69 Surgicl site 90 (12) 31 (9) 59 (15) 0.57 Skin, soft tissue 221 (30) 87 (26) 134 (34) 0.67 Urinry trct 109 (15) 68 (20) 41 (11) 2.17 Died within 6 months 124 (17) 79 (24) 45 (12).002 b note. Dt re no. (%) unless otherwise indicted. MRSA, methicillin-resistnt Stphylococcus ureus; MSSA, methicillin-susceptible S. ureus. Clculted with use of the Student t test. b Clculted with use of the x 2 test. c Includes infections involving prosthetic devices in bone or joint. d Includes endocrditis. P is bsed on the presence of diseses nd in some cses on severity in the ctegories of humn immunodeficiency virus/ AIDS, circultory, therosclerotic crdiovsculr, chronic pulmonry, connective tissue, peptic ulcer, mlignnt, liver, or kidney diseses; dibetes mellitus; dementi; or hemiplegi. We tested for possible interctions between methicillin resistnce, deth, nd Chrlson index. To simplify nlysis, we collpsed infection sites into 4 brod ctegories: (1) respirtory included pneumoni nd bronchitis; (2) skeletl included bone nd joint infections, including infected bone or joint prostheses; (3) blood nd crdiovsculr included bloodstrem nd crdiovsculr system infections; nd (4) skin, mucosl, nd soft tissue included eye, er, nose, throt, skin nd soft tissue, urinry trct, nd gstrointestinl infections nd ws designted the reference group. An nlysis performed with initil infection sites before we collpsed them into ctegories produced similr results. To estimte ctul dollr mounts, we trnsformed the results from nturl logrithm scle costs bck to dollr mounts. There ws no evidence of heteroscedsticity with the Breusch-Pgn test, which llowed for single smering estimte for trnsformtion To isolte the effect of MRSA sttus on helthcre costs while controlling for ll covrites, we used the method of recycled prediction. 26 We predicted totl helthcre costs s if ll study prticipnts hd MRSA infection or s if ll study prticipnts hd MSSA infection. All estimtes were 2 tiled, nd P vlues of less thn.05 were considered to show sttisticlly significnt difference. Sttisticl nlyses were performed using Stt, version 9.1 (SttCorp). The institutionl review bords of the Minnepolis VA Medicl Center, the University of Minnesot, nd the Minnesot Deprtment of Helth pproved the study. results S. ureus ws isolted 2,614 times from 1,291 ptients during the study period. Of these 1,291 ptients, 948 (73%) hd S. ureus illnesses tht met inclusion criteri (Figure 1). All 390 ptients with onset in 2004 were enrolled, comprising 184 ptients with MRSA infection nd 206 ptients with MSSA infection. For ptients with onset fter December 31, 2004, we sked for consent to conduct interviews. Of the 558 ptients or uthorized fmily members or friends whom we ttempted to contct, 113 (20%) refused to prticipte, 44 (8%) were not cpble of giving informed consent, nd 66 (12%) could not be reched. This left 335 ptients with onset

4 368 infection control nd hospitl epidemiology pril 2010, vol. 31, no. 4 tble 2. Compliction type Complictions Associted with Stphylococcus ureus Infection with MRSA (n p 335) with MSSA (n p 390) Odds rtio, MRSA : MSSA Any type, t lest 1 compliction 88 (26.3) 46 (11.8) 2.66 Adverse drug effect 17 (5.1) 12 (3.1) 1.68 Crdiovsculr 4 (1.2) 4 (1.0) 1.17 Centrl nervous system 15 (4.5) 7 (1.8) 2.56 Genitourinry 14 (4.2) 11 (2.8) 1.50 Hemtologicl 5 (1.5) 5 (1.3) 1.17 Limb loss 11 (3.3) 10 (2.6) 1.29 Locl progression of infection 5 (1.5) 1 (0.3) 5.89 Respirtory 37 (11.0) 12 (3.1) 3.91 Shock 14 (4.2) 13 (3.3) 1.26 Other 5 (1.5) 8 (2.1) 0.72 note. Dt re no. (%) of ptients. MRSA, methicillin-resistnt Stphylococcus ureus; MSSA, methicillin-susceptible S. ureus. Some ptients experienced more thn 1 type of compliction. Occurrence of 1 or more complictions ws significntly more common mong ptients with MRSA infection ( P!.001, x 2 test). fter Jnury 1, 2005, 151 with MRSA infection nd 184 with MSSA infection. Overll, there were 335 ptients with MRSA infection nd 390 ptients with MSSA infection (Tble 1), which represented 73% (335 of 456) nd 79% (390 of 492) of the totl number of ptients with illnesses in these ctegories, respectively. Medin ge, medin Chrlson index, proportions with MRSA infection or MSSA infection, nd mortlity rtes were similr for ptients with onset before or fter Jnury 1, We completed 2 interviews with 266 ptients with onset in 2005 or Medin reported out-of-pocket costs were $5 for cses of MRSA infection nd $7 for cses of MSSA infection, nd the distributions were skewed. Fifty-three of the 266 interviewed ptients reported receiving non-va helthcre services, but recll ws difficult nd inconsistent. We were ble to estimte costs from utiliztion records from non-va providers for only 29 of these ptients, nd these costs totled $86,497. Becuse reported out-of-pocket nd non-va expenses were less ccurte nd mrginl, compred with totl DSS nd fee-bsis costs ($37,053,893), out-of-pocket nd non-va costs were excluded from further nlyses. Age nd sex distributions were similr for ptients with MRSA infection nd ptients with MSSA infection (Tble 1). Seven hundred four (97%) of 725 ptients were mle, nd 226 (31%) ptients lived in rurl res. with MRSA hd higher men Chrlson indices thn did ptients infected with MSSA (4.3 vs 3.2; P!.001). Deth within 6 months of onset occurred more often mong ptients infected with MRSA (79 ptients [23.6%]) thn mong ptients infected with MSSA (45 ptients [11.5%]; P!.001). Sites of S. ureus disese differed significntly between the 2 groups ( P!.001). with MRSA were more likely to hve pneumoni, urinry trct infections, or bcteremi. Ptients infected with MSSA were more likely to hve bone or joint infections; infections of eyes, ers, nose, or throt; surgicl site infections; or infections of skin or soft tissue. One hundred thirty-four (18%) of 725 ptients hd complictions of S. ureus infection or its tretment (Tble 2). Complictions were significntly more common mong ptients with MRSA. Costs Undjusted medin costs were more thn twice s lrge for ptients with MRSA infection s for ptients with MSSA infection ( P!.001; Tble 3). The excess ws ttributble to greter inptient hospitl costs. The undjusted medin outptient costs of ntimicrobil gents, lbortory tests, nd imging tests were significntly greter for ptients infected with MSSA thn for ptients infected with MRSA, but overll medin outptient costs were not significntly different. We isolted the influence of methicillin resistnce on totl costs with the use of multivrite regression nlysis (Tble 4). In the min model, we found single significnt interction, between MRSA nd Chrlson index ( P p.02). The nlysis ws run gin seprtely for ptients with lower Chrlson indices (0 3) nd for ptients with higher Chrlson indices (4 or more). Methicillin resistnce ws significnt predictor of incresed helthcre costs within ech strtum fter djustment for ge, Chrlson index, deth, initil infection site, nd urbn residency. In the strtum with lower Chrlson indices, costs were 70% greter for ptients infected with MRSA thn for ptients infected with MSSA. In the strtum with higher Chrlson indices, costs were 43% greter for ptients infected with MRSA. Among ptients in the lower strtum, Chrlson index ccounted for 27% of excess costs, independent of other vribles. Among ptients in both strt, infections of the blood nd crdiovsculr, skeletl, or respirtory systems were ssocited with significntly greter costs thn were infections of the skin, mucos, or soft tissues.

5 methicillin-resistnt s. ureus nd costs 369 tble 3. Cost ctegory Undjusted Medin Helthcre Costs of Stphylococcus ureus Infections with MRSA (n p 335) with MSSA (n p 390) P Totl cost $34,657 ($11,517 $98,287) $15,923 ($5,270 $45,684)!.001 Inptient tretment b Overll inptient costs $26,274 ($4,531 $86,974) $6,748 ($0 $35,089)!.001 Bsic inptient costs $16,416 ($2,661 $54,180) $3,820 ($0 $21,913)!.001 Antimicrobil gents $142 ($6 $508) $21 ($0 $337)!.001 Other drugs $1,530 ($242 $5,502) $406 ($0 $2,394)!.001 Lbortory tests $1,002 ($179 $2,749) $362 ($0 $1,249)!.001 Imging $1,048 ($0 $5,453) $227 ($0 $1,597)!.001 Surgicl procedures $0 ($0 $3,432) $0 ($0 $378).02 PMR $0 ($0 $731) $0 ($0 $98)!.001 Mentl, socil, nd spiritul $459 ($33 $1,280) $80 ($0 $750)!.001 Hemodilysis $0 ($0 $0) $0 ($0 $0).42 Other d $1,307 ($9 $5,818) $100 ($0 $1,980)!.001 Outptient tretment Overll outptient costs $4,322 ($1,395 $9,438) $4,495 ($2,076 $8,979).30 Bsic clinic costs $1,169 ($345 $2,494) $1,344 ($626 $2,571).05 Antimicrobil gents $2 ($0 $28) $7 ($0 $32).01 Other drugs $766 ($41 $1,979) $793 ($173 $1,678).72 Lbortory tests $171 ($0 $450) $232 ($95 $484).005 Imging $95 ($0 $446) $146 ($0 $506).04 Surgicl procedures $0 ($0 $374) $44 ($0 $451).13 PMR $0 ($0 $0) $0 ($0 $0).75 Mentl, socil, nd spiritul $0 ($0 $108) $0 ($0 $83).09 Hemodilysis $0 ($0 $0) $0 ($0 $0).63 Other e $661 ($51 $2,106) $652 ($158 $1,976).37 note. Dt re medin (rnge). MRSA, methicillin-resistnt Stphylococcus ureus; MSSA, methicillin-susceptible S. ureus; PMR, physicl medicine nd rehbilittion. Clculted with the Wilcoxon-Mnn-Whitney test. b Includes room nd bord, ptient cuity costs, nutrition, nd some identified in-hospitl medicl cre costs. d Includes home cre costs while the ptient ws hospitlized, inptient fee-bsis costs, nd other nonctegorized costs. e Includes costs for outptient observtion (room nd bord, cuity, nutrition, nd some costs incurred while ptient ws under observtion sttus), outptient fee-bsis costs, nd other nonctegorized costs. Neither urbn residency nor deth ws significnt predictor of excess costs. For the strtum with lower Chrlson indices, the djusted men cost of medicl services received by ptients infected with MRSA ws $51,252 (95% CI, $46,041 $56,464), compred with $30,158 (95% CI, $27,092 $33,225) for those infected with MSSA. For the strtum with higher Chrlson indices, the djusted men cost of medicl services received by ptients infected with MRSA ws $84,436 (95% CI, $79,843 $89,029), compred with $59,245 (95% CI, $56,016 $62,473) for ptients infected with MSSA. Utiliztion with MRSA spent more dys hospitlized on wrds nd in intensive cre units, nd while hospitlized, they received more lbortory tests, imging tests, nd physicl medicine nd rehbilittion services thn did ptients infected with MSSA (Tble 5). Outptient utiliztion ws similr for the 2 groups, except tht ptients infected with MSSA received more lbortory tests. discussion Costs ssocited with MRSA infection were significntly greter thn those ssocited with MSSA infection. The reltive disprity ws greter for ptients with lower Chrlson indices, but the bsolute disprity ws greter for ptients with higher Chrlson indices. For 6 months fter onset, men djusted costs ssocited with methicillin resistnce verged $21,094 more for ptients with Chrlson indices of 3 or lower nd $25,191 more for ptients with higher Chrlson indices. This study included ll cliniclly importnt S. ureus infections rther thn infections of single orgn or single type of infection. Becuse VA ptients hve nerly complete coverge for medicl expenses nd strong loylty to the VA helthcre system, nerly ll costs for the 6 months fter onset were cptured for ech ptient. Informtion glened from

6 370 infection control nd hospitl epidemiology pril 2010, vol. 31, no. 4 tble 4. Vrible Multivrite Anlysis of Log Totl Cost Estimte (95% CI) Stndrd error P Effect on cost, % Chrlson index 0 3 MRSA infection 0.53 ( ) 0.13! Chrlson index 0.24 ( ) 0.06! Deth 0.19 ( 0.69 to 0.30) Age 0.01 ( 0.01 to 0.00) Infection site b 0.0 Skeletl 0.82 ( ) 0.20! Respirtory system 1.70 ( ) 0.22! Blood nd crdiovsculr system 1.91 ( ) 0.24! Urbn residency 0.16 ( 0.43 to 0.12) Chrlson index x4 MRSA infection 0.35 ( ) Chrlson index 0.05 ( 0.01 to 0.12) Deth 0.03 ( 0.28 to 0.35) Age 0.02 ( 0.03 to 0.00) Infection site b 0.0 Skeletl 0.96 ( ) 0.23! Respirtory system 0.97 ( ) 0.19! Blood nd crdiovsculr system 0.96 ( ) 0.18! Urbn residency 0.13 ( 0.15 to 0.42) note. R 2 for the Chrlson comorbidity index 0 3 multivrite model ws R 2 for the Chrlson comorbidity index x4 multivrite model ws CI, confidence intervl; MRSA, methicillin-resistnt Stphylococcus ureus. Effect on cost ws clculted by exponentiting the estimte nd subtrcting 1, tht is, exp (estimte) 1. b Skin, mucosl, nd soft tissue ws the reference infection site ctegory. ptient interviews nd from providers outside the VA system ws less ccurte thn VA dt, but it showed tht non-va costs were insubstntil. Severl fetures of our study popultion nd design mximized our bility to cpture costs ssocited with recurrences, complictions, nd long-term morbidity, which re common fter S. ureus infections. 27,28 Like others, 9,11,13,28 we found tht it ws not possible to seprte clenly services provided to dignose nd tret S. ureus infection from services for concurrent conditions, so the costs of these conditions were included in our nlysis. Multivrite nlysis showed tht much of the excess cost ssocited with methicillin resistnce ws independent of conditions reflected in the Chrlson index. The pproch tht we used to quntify costs cn be esily replicted or compred with future studies or used to predict costs in other popultions. with MRSA spent more dys in intensive cre units nd other wrds thn did ptients infected with MSSA, s reported previously. 29 with MRSA received more lbortory tests, imging tests, nd rehbilittion during hospitliztion. Inptient costs for ntimicrobil gents were greter for ptients infected with MRSA, nd outptient costs for ntimicrobil gents were greter for ptients infected with MSSA, but totl costs for ntimicrobil gents were less thn 1% of overll helthcre costs nd contributed only mrginlly to differences between the 2 groups. Mentl, socil, nd spiritul costs were greter for ptients infected with MRSA, which probbly reflected their more numerous comorbidities nd the frilties tht ccompnied these comorbidities. Overll outptient costs nd utiliztion were similr between the 2 groups. Excess costs ssocited with methicillin resistnce dd to the substntil costs of S. ureus infections in generl. In one study of S. ureus bcteremi ssocited with prosthetic devices from 1994 through 2002, men hospitl nd outptient services for the 12-week period fter onset cost $67,439 for nosocomil infections nd $37,868 for community-cquired infections in 2002 US dollrs. 28 Tht study emphsized tht recurrence is common with S. ureus infection: 15% of ptients with device-relted S. ureus infections were dischrged nd then rehospitlized to tret recurrent infection. 28 Recurrences were common for our ptients nd dded to overll costs. In popultion-bsed study, the totl cost of ll nonobstetricl S. ureus infections in hospitls in New York, New York, for 1995 ws estimted to be $435.5 million, with per-ptient verge cost of $32, In the United Sttes, hospitliztions during which S. ureus infection ws dignosed nd treted incresed 62% from 294,570 during 1999 to 477,927 during ,30 In severl studies, medicl costs ssocited with MRSA infection hve been greter thn for MSSA infection, but methods nd results hve been vrible nd difficult to generlize In one study, the verge dily inptient costs for MRSA bcteremi during the period from 1997 through 1999 were 2.8 times the costs for MSSA bcteremi. Excess costs

7 methicillin-resistnt s. ureus nd costs 371 tble 5. Undjusted Medin Helthcre Utiliztion Utiliztion ctegory with MRSA (n p 335) with MSSA (n p 390) Medin (rnge) No. (%) Medin (rnge) No. (%) Inptient utiliztion Inptient dys 15 (4 54) 268 (80) 5 (0 20) 245 (63)!.001 Intensive cre unit dys 0 (0 2) 104 (31) 0 (0 0) 77 (20)!.001 Other hospitl wrd dys 11 (2 42) 257 (77) 4 (0 18) 239 (61)!.001 Lbortory tests 104 (22 288) 267 (80) 32 (0 128) 243 (62)!.001 Imging tests 5 (0 19) 242 (72) 1 (0 8) 208 (53)!.001 Surgicl procedures 0 (0 1) 87 (26) 0 (0 0) 105 (27).07 PMR 0 (0 9) 153 (46) 0 (0 1) 105 (27)!.001 Outptient utiliztion Clinic visits 6 (2 12) 287 (86) 7 (3 12) 363 (93).03 Lbortory tests 19 (0 46) 246 (73) 26 (9 52) 339 (87).006 Imging tests 1 (0 3) 172 (51) 1 (0 3) 236 (61).05 Surgicl procedures 0 (0 0) 26 (8) 0 (0 0) 35 (9).56 PMR 0 (0 0) 53 (16) 0 (0 0) 59 (15).77 note. MRSA, methicillin-resistnt Stphylococcus ureus; MSSA, methicillin-susceptible S. ureus; PMR, Physicl Medicine nd Rehbilittion. No. (%) refers to the number nd percentge of ptients with t lest 1 utiliztion for the given ctegory. b Clculted with use of the Wilcoxon-Mnn-Whitney test. P b for MRSA infection occurred in ptients with more severe underlying illnesses. 11 In second study, medin costs for tretment of ptients with MRSA bcteremi were $14,655, compred with $10,655 for ptients with MSSA bcteremi. 13 In third study, the djusted men cost ssocited with MRSA bcteremi ws $21,577, compred with $11,688 for MSSA bcteremi. 14 In ptients with end-stge kidney disese who were dependent on hemodilysis nd who developed MRSA bcteremi, men djusted costs were $25,518, compred with $17,354 for ptients with end-stge kidney disese who were dependent on hemodilysis nd who developed MSSA bcteremi. 15 In study of S. ureus surgicl-site infections, medin chrges were $92,363 for MRSA infections, compred with $52,791 for MSSA infections, nd fter djustment for other vribles, estimted costs for MRSA infection were 19% greter. 9 Our study hd some limittions. It ws performed t single hospitl; ll VA ptients were dults, nd most were mle. Becuse out-of-pocket expenses were excluded, this nlysis presents costs from the VA perspective, but out-ofpocket expenses were smll compred with VA costs. During the study period, ptients infected with MRSA were plced in isoltion, which incurred extr costs for privte rooms, gowns, gloves, nd lbor. These costs were not ssigned to individul ptients in the DSS nd could not be included in costs ttributed to MRSA infection. Ptients were not screened systemticlly during the study period for MRSA crrige. Other reserchers hve documented tht costs of screening, isoltion, nd in some cses erdiction in response to outbrek or endemic MRSA infection re substntil. During n MRSA outbrek in Finlnd in 2003, control mesures, infection-relted tretment costs for 168 cses, nd lost revenue from closed hospitl beds were estimted to cost i1,569,830 (US $1,899,871). 31 Estimted costs of infection prevention prctices in Germny in 2000 for MRSA infections or crrige in surgicl ptients were t lest i9622 (US $9,509) per cse. 32 This study hs importnt strengths. We included ll cses of S. ureus infection insted of just certin infection types. The DSS is well suited for studies of helthcre costs nd utiliztion, becuse the method is more ccurte nd subject to less distortion thn tht used in typicl helthcre orgniztion ccounting systems. 17 Dt from this project cn be used to estimte excess costs ssocited with MRSA infection in other helthcre orgniztions or in popultions with known rtes of MRSA infection. The results of this study demonstrte the substntil costs of MRSA infections, even fter djustment for comorbidities. with MRSA re more likely to suffer complictions of their infection nd re more likely to die thn re ptients infected with MSSA. 27 MRSA infections re mjor, growing public helth thret 2-6 with no esy solution. Most US hospitls isolte known MRSA crriers, nd some screen for MRSA crrige mong high-risk ptients or hospitl-wide to identify nd isolte greter percentge of crriers. Screening nd isoltion, with or without efforts to erdicte crrige, hve been ssocited with decresed MRSA secondry trnsmission nd decresed rte of MRSA bcteremi. 33 Generl infection prevention efforts lso reduce the incidence of MRSA infection. For exmple, centrl line ssocited MRSA bloodstrem infections hve decresed in US intensive cre units during the period from 1997 through

8 372 infection control nd hospitl epidemiology pril 2010, vol. 31, no , but decreses were lso observed for bloodstrem infections cused by MSSA nd other pthogens. 34 The optiml blnce between infection prevention efforts trgeted to prevent MRSA infections nd generl infection prevention efforts hs not been definitively estblished nd should be individulized for ech institution. In ddition to ssiduous infection prevention, creful use of ntibiotics in the helthcre setting is crucil. Antibiotic use drives resistnce to ntimicrobil gents, 35 nd there is substntil evidence tht ntimicrobil stewrdship progrms reduce costs by improving ptient outcomes, reducing length of sty, nd optimizing ntibiotic drug costs. 36 cknowledgments We thnk John Troini, MD, for sttisticl dvice; Abiol Fshnu, MD, Jennifer Kuyv, BS, Kristen Moy, MPH, Kene Ogbogu, MD, Oluyemisi Olubi, MD, nd Afolke Sokeye, MPH, for review of medicl records nd interviews; nd Kthy Suber, BA, for extrction of DSS dt. Finncil support. Contrct RO1CI : Applied Reserch on Antimicrobil Resistnce, from the Centers for Disese Control nd Prevention. Potentil conflicts of interest. All uthors report no conflicts of interest relevnt to this rticle. Address reprint requests to Gregory A. Filice, MD, Infectious Disese Section (111F), Veterns Affirs Medicl Center, 1 Veterns Drive, Minnepolis, MN (filic001@umn.edu). references 1. Brber M. Methicillin-resistnt stphylococci. J Clin Pthol 1961;14: Ntionl Nosocomil Infections Surveillnce System. Ntionl Nosocomil Infections Surveillnce (NNIS) System Report, dt summry from Jnury 1992 through June 2004, issued October Am J Infect Control 2004;32: Hot B, Ellenbogen C, Hyden MK, Aroutchev A, Rice TW, Weinstein RA. Community-ssocited methicillin-resistnt Stphylococcus ureus skin nd soft tissue infections t public hospitl: do public housing nd incrcertion mplify trnsmission? Arch Intern Med 2007;167: Popovich KJ, Weinstein RA, Hot B. 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