Economic burden of inpatient and outpatient antibiotic treatment for methicillin-resistant Staphylococcus aureus complicated skin and soft-tissue infections: a comparison of linezolid, vancomycin, and daptomycin

Figures & data

Figure 1 Model structure.

Abbreviations: cSSTI, complicated skin and soft tissue infection; AE, adverse events; MRSA, methicillin-resistant Staphylococcus aureus.

Table 1 Model input data

	Linezolid	Vancomycin	Daptomycin	Data source
Clinical inputs
First-line treatment
Success, %	89.5	89.5	89.5a	Itani et al^Citation7,Citation28
Failure or discontinuation, %b	10.5	10.5	10.5	(Calculated from above)
Second-line treatment
Success, %	100	100	100	Assumption
Resource inputs
Hospital stay, days	4.5	4.5	4.5	Barrett et al^Citation16
Hospital stay due to failure or discontinuation, additional daysb	5	5	5	Edelsberg et al^Citation27
Empiric antibiotic therapy, days	2	2	2	De Cock et al,^Citation21 Schurmann et al^Citation23
Definitive antibiotic therapy, days	12	12	12	Weigelt et al,^Citation10 Liu et al^Citation1
IV therapy, days	2.5	12	12
Oral therapy, days	9.5	0	0
Intravenous doses per day	2	2	1	Product label,^Citation2 Tice^Citation46
Oral doses per day	2	0	0	Product label^Citation2
ID physician inpatient visits	1	1	1	Tice et al,^Citation43 assumption
ID physician office visits	1	1	1	Tice et al,^Citation43 assumption
Outpatient laboratory work	1	1	1	Tice^Citation46
Outpatient parenteral antibiotic days	0	9.5	9.5	Calculated from above, also consistent with Itani et al^Citation7
PICC placement	0	1	1	Tice^Citation46
PICC complications	0	1c	1c	Tice et al,^Citation31 Moureau et al^Citation30

Notes:

a Assumed to be same as linezolid/vancomycin for the base-case analysis; no direct trial comparison with linezolid and daptomycin;

b discontinuation due to adverse event;

c PICC complication costs will be added to all patients undergoing PICC placement. These costs are further detailed in Table 2.

Abbreviations: ID, infectious disease; IV, intravenous; PICC, peripherally inserted central catheter.

Table 2 Cost inputs

Cost inputs	Cost adjusted to 2011 (US$)a	Data source
Drug costs (wholesale acquisition cost per dose)
Linezolid IV 600 mg	$107.10	First DataBank, Inc^Citation34
Linezolid oral 600 mg	$89.39	First DataBank, Inc^Citation34
Vancomycin IV 1 g	$5.79	First DataBank, Inc^Citation34
Cefazolin IV 1 g	$2.19	First DataBank, Inc^Citation34
Daptomycin IV 300 mg (500 mg vial used)	$256.29	First DataBank, Inc^Citation34
Injection costs per dose	$7.21	Tice et al^Citation33
Medical costs
General ward, per day	$1,348.50	Candrilli and Mauskopf^Citation35
ID specialist, inpatient visit	$231.95	CPT 99253, inpatient consult, 50th percentile, Ingenix^Citation36
Physician outpatient visit	$222.40	CPT 99215, office visit, 50th percentile, Ingenix^Citation36
Laboratory tests, vancomycin	$101.06	CPT 80069 renal function $64.92 + CPT 80202 vancomycin level $36.14, Ingenix^Citation36
Laboratory tests, linezolid	$34.34	CPT 85025 – complete blood count, Ingenix^Citation36
OPAT daily cost	$193.67	Tice et al^Citation32 (fee-for-service with medication related costs removed)
PICC placement	$656.80	CPT 36569 for placement $561.58 + CPT 71010 for X-ray $95.22, 50th percentile, Ingenix^Citation36
PICC complication cost per patient	$153.81
• Physician visit		• 17% (Tice et al^Citation31) @ CPT 99215, $222.40 (Ingenix^Citation36)
• Declotting procedure with CathFlo		• 7% (Tice et al^Citation31) @ CPT 36593 $199.66 (Ingenix^Citation36) and drug cost $106.33 (First DataBank^Citation34)
• Emergency room visit		• 2% (Moureau et al^Citation30) @ CPT 99284 $380.40 (Ingenix^Citation36) + facility fees of $222.58
• Rehospitalization		• 1% (Moureau et al^Citation30) @ DRG 920 $5,114.60 (2008 Median cost from HCUP adjusted to US$ 2011)
• PICC replacement including chest X-ray		• 5% (Moureau et al^Citation30) @ CPT 36584 $532.42 + CPT 71010 $95.22 (Ingenix^Citation36)

Notes:

a Drug prices reported as wholesale acquisition costs 2011, all other costs adjusted to 2011 US$.

Abbreviations: IV, intravenous; ID, infectious disease; OPAT, outpatient therapy; PICC, peripherally inserted central catheter; CPT, current procedural terminology; DRG, diagnosis-related group; HCUP, Healthcare Cost and Utilization Project.

Table 3 Base-case analysis results

Costs per patient (US$)	Linezolid (US$)	Vancomycin (US$)	Daptomycin (US$)
Total inpatient costs	$7,835	$7,095	$7,922
Inpatient drug costs	$626	$119	$713
Drug treatment	$554	$47	$659
Drug administration	$72	$72	$54
Inpatient medical costs	$7,209	$6,976	$7,209
Hospital days	$6,068	$6,068	$6,068
ID specialist	$232	$232	$232
Adverse event costsa	$435	$201	$435
Failure costs	$474	$474	$474
Total outpatient costs	$2,736	$4,001	$5,690
Outpatient drug costs	$2,086	$634	$2,766
Drug treatment	$2,075	$487	$2,698
Drug administration	$11	$148	$68
Outpatient medical costs	$650	$3,367	$2,924
Physician visit	$246	$246	$246
Laboratory work	$34	$101	$28
OPAT costb	$285	$2,125	$1,840
PICC line and complicationsb	$85	$896	$811
Total cost of treatment	$10,571	$11,096	$13,612
Total drug costs	$2,712	$754	$3,479
Total medical costs	$7,859	$10,343	$10,133

Notes: Costs may not tally due to rounding.

a Adverse event costs are higher for linezolid and daptomycin arm because they are assigned the vancomycin adverse event costs from empiric treatment plus any linezolid/daptomycin adverse event costs. Vancomycin is only assigned adverse event costs once;

b OPAT and PICC line costs are incurred in the linezolid arm through treatment failures and switching to other IV antibiotics.

Abbreviations: ID, infectious disease; OPAT, outpatient parenteral antibiotic therapy; PICC, peripherally inserted central catheter; IV, intravenous.

Table 4 Scenario-based sensitivity analyses

Scenarios	Linezolid total cost (US$)	Vancomycin total cost (US$)	Daptomycin total cost (US$)
Scenario 1, trial-based length of stay^Citation7	$14,906	$16,178	$18,694
Linezolid, 7.6 days
Vancomycin and daptomycin, 8.9 days
Scenario 2, no PICC line costs	$10,486	$10,201	$12,802
Scenario 3, meta analysis efficacy rates^Citation8	$11,458	$13,030	$14,856
Linezolid, 84.4% (credible interval: 76.6%–90.6%)	QALY = 0.063	QALY = 0.060	QALY = 0.061
Vancomycin, 74.7% (credible interval: 64.1%–83.5%)		ICER = dominated by Linezolid	ICER = dominated by Linezolid
Daptomycin, 78.1% (credible interval: 54.6%–93.2%)

Abbreviations: ICER, incremental cost effectiveness ratio; PICC, peripherally inserted central catheter; QALY, quality-adjusted life years.

ItaniKMDrydenMSBhattacharyyaHKunkelMJBaruchAMWeigeltJAEfficacy and safety of linezolid versus vancomycin for the treatment of complicated skin and soft-tissue infections proven to be caused by methicillin-resistant Staphylococcus aureusAm J Surg201019980481620227056

 PubMed Web of Science ®Google Scholar

ItaniKMFWeigeltJStevensMSEfficacy and safety of linezolid versus vancomycin for the treatment of complicated skin and soft-tissue infections proven to be due to methicillin-resistant Staphylococcus aureus (MRSA)Presentation at the 18th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID)Reinach, SwitzerlandApril 2008

 Google Scholar

BarrettMWilsonEWhalenD2007 HCUP Nationwide Inpatient Sample (NIS) comparison reportHCUP Methods Series report # 2010–2003US Agency for Healthcare Research and Quality2010

 Google Scholar

EdelsbergJBergerAWeberDJMallickRKuznikAOsterGClinical and economic consequences of failure of initial antibiotic therapy for hospitalized patients with complicated skin and skin-structure infectionsInfect Control Hosp Epidemiol20082916016918179372

 PubMed Web of Science ®Google Scholar

De CockESorensenSLevratFCost-effectiveness of linezolid versus vancomycin for hospitalized patients with complicated skin and soft-tissue infections in FranceMed Mal Infect20093933034019304423

 PubMed Web of Science ®Google Scholar

SchurmannDSorensenSVDe CockEDuttaguptaSReschACost-effectiveness of linezolid versus vancomycin for hospitalised patients with complicated skin and soft-tissue infections in GermanyEur J Health Econ200910657918437437

 PubMed Web of Science ®Google Scholar

WeigeltJItaniKStevensDLauWDrydenMKnirschCLinezolid versus vancomycin in treatment of complicated skin and soft tissue infectionsAntimicrob Agents Chemother2005492260226615917519

 PubMed Web of Science ®Google Scholar

LiuCBayerACosgroveSEClinical practice guidelines by the infectious diseases society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and childrenClin Infect Dis201152e18e5521208910

 PubMed Web of Science ®Google Scholar

Zyvox® [package insert]New York, NYPharmacia and Upjohn Company2010

 Google Scholar

TiceAHandbook of Outpatient Parenteral Antimicrobial TherapyTarrytown, NYCRG Publishing2006

 Google Scholar

TiceADRehmSJDalovisioJRPractice guidelines for outpatient parenteral antimicrobial therapy. IDSA guidelinesClin Infect Dis2004381651167215227610

 PubMed Web of Science ®Google Scholar

TiceABonstellRMarshPKCravenPCMcEniryDWHardingSPeripherally inserted central venous catheters for outpatient intravenous antibiotic therapyInfect Dis Clin Pract19932186190

 Web of Science ®Google Scholar

MoureauNPooleSMurdockMAGraySMSembaCPCentral venous catheters in home infusion care: outcomes analysis in 50,470 patientsJ Vasc Interv Radiol2002131009101612397122

 PubMed Web of Science ®Google Scholar

First Data Bank, IncAnaly$ource OnlineFirst DataBank, IncSouth San Francisco, CA492011

 Google Scholar

TiceADTurpinRSHoeyCTLipskyBAWuJAbramsonMAComparative costs of ertapenem and piperacillin-tazobactam in the treatment of diabetic foot infectionsAm J Health Syst Pharm2007641080108617494908

 PubMed Web of Science ®Google Scholar

CandrilliSMauskopfJHow much does a hospital day cost?Value Health2006A56

 Google Scholar

IngenixNational Fee AnalyzerEden Prairie, MNIngenix2011

 Google Scholar

TiceADHoaglundPANoletBMcKinnonPSMozaffariECost perspectives for outpatient intravenous antimicrobial therapyPharmacotherapy20022263S70S11837549

 PubMed Web of Science ®Google Scholar

LogmanJFStephensJHeegBComparative effectiveness of antibiotics for the treatment of MRSA complicated skin and soft tissue infectionsCurr Med Res Opin2010261565157820429820

 PubMed Web of Science ®Google Scholar