Cost-analysis of inpatient and outpatient parenteral antimicrobial therapy in orthopaedics: A systematic literature review

Table 1 Exclusion criteria for systematic literature review

Exclusion criteria
No relation to OPAT
No bacterial infections
Only prophylactic antibiotic therapy
No distinction between oral and parenteral outpatient antibiotic therapy
Parenteral therapy with orally available antibiotics
Non-English language publication
No original study (e.g., comments, letters, etc.)
Combination of IPAT and OPAT
Only patients < 18 yr
Case reports and case series with < 15 cases
Poster-publications/Congress abstracts etc.
“Specific infections” or tropical diseases
Study protocols (without original clinical data)
Simulations (without original clinical data)
CME publications (without original clinical data)
Non-peer-reviewed journals
No full text available

OPAT: Outpatient parenteral antibiotic therapy.

Table 2 Classification of publications

A	Original research with health economic data on OPAT (costs)
B	Secondary literature with health economic data on OPAT in PPJI
C	Pro-/Retrospective study on OPAT (PPJI of hip or knee)
D	Pro-/Retrospective study on OPAT (other infections)
E	Guidelines, reviews on OPAT with health economic data
F	Exclusion of publication

OPAT: Outpatient parenteral antibiotic therapy; PPJI: Periprosthetic joint infections.

Table 3 Details of included studies

ID	First author	Ref.	Year	Country	Design	Diagnosis	Cases/Patients (n)	Antibiotic agent
1	Al Alawi	[8]	2015	Bahrain	Retrospective	Bacterial tonsillitis	97	Ceftriaxon
2	Antoniskis	[9]	1978	United States	Retrospective	Endocarditis + Osteomyelitis	13/7 (Controls)	Multiple
3	Bernard	[10]	2001	Switzerland	Prospective	Osteomyelitis (incl. 10 PPJI)	39	Multiple
4	Chapman	[11]	2009	United Kingdom	Retrospective	multiple	334/296	Multiple
5	Connors	[12]	2017	Canada	Prospective	Dental	110/.	Multiple
6	Gonzales	[13]	2017	Spain	Retrospective	Multiple	1324/1190	Multiple
7	Gray	[14]	2012	United Kingdom	Retrospective	Multiple	291/.	Multiple
8	Grizzard	[15]	1991	United States	Retrospective	Multiple	46/.	Multiple
9	Harrison	[16]	2015	United Kingdom	Retrospective	Kidney transplant	12/9	n. a.
10	Heintz	[17]	2011	United States	Prospective	Multiple	569/536	Multiple
11	Kieran	[18]	2009	Ireland	Retrospective	Multiple	60/56	Multiple
12	Lacroix	[19]	2014	France	Retrospective	Endocarditis	18/.	Multiple
13	Malone	[20]	2015	Australia	Retrospective	Diabetic foot	59/.	n. a.
14	Nathwani	[21]	2003	United Kingdom	Retrospective	Bone and joint	55/.	Teicoplanin
15	Nguyen	[22]	2010	United States	NA	Cellulitis	80/.	Multiple
16	Ruh	[23]	2015	United States	Retrospective	Multiple	96/85	Multiple
17	Seaton	[24]	2014	United Kingdom	Retrospective	MRSA skin and soft tissue	173/.	Multiple
18	Sims	[25]	2013	United Kingdom	Retrospective	PPJI	96/85	Multiple
19	Theocharis	[26]	2012	Greece	Retrospective	Multiple	173/.	Multiple
20	Wai	[27]	2000	Canada	Retrospective	Multiple	80/.	Multiple
21	Yong	[28]	2009	Singapore	Retrospective	Multiple	96/85	Multiple

OPAT: Outpatient parenteral antibiotic therapy; PPJI: Periprosthetic joint infections.

Table 4 Detailed description of costs of outpatient parenteral antibiotic therapy and inpatient parenteral antibiotic therapy depending on available information

ID	First author	Ref.	Cost IPAT	Cost OPAT	Cost-difference	Comment
1	Al Alawi1	[8]	€43152.41 / €50343.67 €143.37/d2	€17261.45 €57.35/d2	€25890.96 €86.02/d2	301 bed days were saved by OPAT. Exact cost reduction not clear in text
2	Antoniskis	[9]	US $234.22/d US $10022.23 /pat	US $69.35/d US $6357.52/pat	US $229.70/d US $3664.71/pat	Historical data/prices from 1977/78. Average day costs calculated
3	Bernard	[10]	US $710/d US $2233945	US $129/d US $360060	US $581/d US $1873885	2.147 patient-days of 39 patients
4	Chapman	[11]	£372.53/d £1502769	£151.79/d £612306	£220.74/d £890,463	Calculation based on 4034 bed-days
5	Connors1	[12]	CAN $1720.70 / d CAN $717530 €1063451.21	CAN $1094/d CAN $120096 €177994.28	CAN $288/d CAN $597434 €884919.24	110 patients with 417 bed-days. Average: 3.8 d with CAN $1094 / case
6	Gonzales	[13]	€4357/pat €518.70/d	€2350/pat €98.30/d	€420.40/d	Very detailed calculation. Methods presented. IPAT for an average of 8.4 days. OPAT included IPAT for readmission within 30 d
7	Gray	[14]			£192635 £662/patient	Simulation of cost analysis based on potentially saved bed days. Calculation include OPAT as well as other treatment changes. 18/429 patients in the calculation would have been eligible for OPAT
8	Grizzard	[15]	US $159.54/d US $101314	US $112.68/d US $29763	US $112.68/d US $71551	Historical data (1988). Cost-Charge Ratio. Additional Homecare-treatment (OPHAT) of center based OPAT and IPAT differentiated. 635 bed days
9	Harrison	[16]	£264 / d £84480	£109.59 / d £35070	£154.41 / d £49,410	Simplified calculation. 320 bed days
10	Heintz	[17]	US $424080 US $658.50/visit			Simplified calculation with relevant limitations. 228 bed days were saved by OPAT
11	Kieran	[18]	€342862	€167.60/d €558912	€-216.050	Prospective study on 60 cases. 1289 bed days saved. Community nurses included in OPAT calculation
12	Lacroix	[19]	€1125/d €335250	€228/d €67943	€897/d €14850/pat €267307	Simulated cost analysis. 298 bed days saved
13	Malone	[20]	US $829/d US $1143.957	US $278848	US $14661/pat US $864997	IPAT costs based on Council of Australian Governments. 1,569 bed days saved
14	Nathwani	[21]	£300 / d £11400 / pat £627000	£1,749.15/pat £96,203.25	£9650.85/pat £530796.75	Three groups: IPAT, OPAT (Teicoplanin) and outpatient oral therapy (Linezolid). Oral group not included
15	Nguyen	[22]	US $1180/d US $556960	US $385/d US $181720	US $795/d US $375240	472 OPAT visits
16	Ruh	[23]	US $7540135.35	US $607583.32	US $6932552.03	Complex cost calculation with multiple factors
17	Seaton	[24]	£13019.57/pat £455685	£6,532.89/pat £228651	£6,487/pat £227034	Three groups: IPAT, OPAT (Teicoplanin) and outpatient oral therapy (Linezolid). Oral group not included. Calculation based on 37 cases
18	Sims	[25]	£250/d £14500/pat	£24/d 1392/pat	£24/d £13108/pat	For two weeks OPAT cost reduction of 2108 £/Pat
19	Theocharis	[26]	€167.50-195.50/d	€164/d €637/pat		Re-admission rates (14.2%) and costs not included in OPAT calculation
20	Wai	[27]	€20728/pat €2901983	€2774/pat €388402	€17954/pat €2513580	Very detailed cost analysis for IPAT and OPAT. Perspectives of payer and hospitals were presented
21	Yong	[28]	US $457/d US $12403/pat	US $278/d US $12736/pat		Includes calculation for opportunity-costs

¹Currency converted to Euro using exchange rates based on the middle of the publication year;

²Calculation simplified based on limited data. IPAT: Inpatient parenteral antibiotic therapy; OPAT: Outpatient parenteral antibiotic therapy.

Table 5 Daily costs calculated in Euro for inpatient parenteral antibiotic therapy and outpatient parenteral antibiotic therapy (exchange rate based on mid of publication year)

ID	First author	Year	Ref.	IPAT		OPAT
				€ per case	€ per day	€ per case	€ per day
1	Al Alawi	2015	[8]		143.361		57.351
2	Antoniskis	1978	[9]		251.26		74.09
3	Bernand	2001	[10]		755.88		137.34
4	Chapman	2009	[11]	-	418.92		170.71
5	Connors	2017	[12]	2550.69		1621.42
6	Gonzales	2017	[13]	4357	519	2350	98
7	Gray	2012	[14]
8	Grizzard	1991	[15]		110.29		77.89
9	Harrison	2015	[16]		337.26		140.53
10	Heintz	2011	[17]		492.12		28.38
11	Kieran	2009	[18]				168
12	Lacroix	2014	[19]		1125		228
13	Malone	2015	[20]		68524
14	Nathwani	2003	[21]	17502.42	460.59	2685.24
15	Nguyen	2010	[22]		823.73		268.76
16	Ruh	2015	[23]
17	Seaton	2014	[24]	15670.97		7863.77
18	Sims	2013	[25]	17881.4	308.3	1716.61	29.6
19	Theocharis	2012	[26]		180	637	164
20	Wai	2000	[27]	20278		9188
21	Yong	2009	[28]	8873.23	326.94	9111.46	198.88

¹Calculation simplified based on limited data. Calculations not applicable for two studies. IPAT: Inpatient parenteral antibiotic therapy; OPAT: Outpatient parenteral antibiotic therapy.

Table 6 Cost comparison (ratio) per case of outpatient parenteral antibiotic therapy vs inpatient parenteral antibiotic therapy

ID	First author	Year	Ref.	IPAT/OPAT
				Ratio per case	Ratio per day
1	Al Alawi	2015	[8]		2.501
2	Antoniskis	1978	[9]		3.39
3	Bernand	2001	[10]		5.50
4	Chapman	2009	[11]		2.45
5	Connors	2017	[12]	1.57
6	Gonzales	2017	[13]	1.85	5.30
7	Gray	2012	[14]
8	Grizzard	1991	[15]		1.42
9	Harrison	2015	[16]		2.40
10	Heintz	2011	[17]		17.34
11	Kieran	2009	[18]
12	Lacroix	2014	[19]		4.93
13	Malone	2015	[20]
14	Nathwani	2003	[21]	6.52
15	Nguyen	2010	[22]		3.06
16	Ruh	2015	[23]
17	Seaton	2014	[24]	1.99
18	Sims	2013	[25]	10.42	10.42
19	Theocharis	2012	[26]		1.10
20	Wai	2000	[27]	2.21
21	Yong	2009	[28]	0.97	1.64

¹Calculation simplified based on limited data. Calculations not applicable for two studies. A ratio above 1.0 indicates higher cost of inpatient parenteral antibiotic therapy in comparison to outpatient parenteral antibiotic therapy. IPAT: Inpatient parenteral antibiotic therapy; OPAT: Outpatient parenteral antibiotic therapy.

Table 7 Literature details on bone and joint infections

ID	First author	Ref.	Year	Diagnosis
2	Antoniskis	[9]	1978	5 acute OM, 6 chronic OM	No information regarding affected joints
3	Bernard	[10]	2001	39 OM (13 non-union fracture; 16 chronic OM; 10 PPJI)	Sites of OM: femur (n = 11), hip (n = 9); tibia (n = 5), ankle (n = 4), mastoid, calcaneum, vertebra, knee (each n = 2), wrist and phalange (each n = 1). No information on outcome per affected joints
4	Chapman	[11]	2009	Of 334 infections, approx. 20 (6%) were bone and joint associated; bed days saved were approx. 481 of 4034 (12%)	No information regarding affected joints
6	Gonzales	[13]	2017	Underlying diagnosis not mentioned	No information regarding affected joints
7	Gray	[14]	2012	291 cases; 14 in orthopaedics (4.8%)	No information regarding affected joints
8	Grizzard	[15]	1991	OM and septic arthritis most frequent diagnosis in OPAT (30% of patient days)	No information regarding affected joints
10	Heintz	[17]	2011	569 cases; 190 (33.4%) bone and joint associated	No information regarding affected bones or joints
11	Kieran	[18]	2009	60 cases; OM (n = 25, 41.7%), PPJI (n = 2; 3.3%) and septic arthritis (n = 3, 5.1%) accounting for 50%	No information regarding affected bones or joints
13	Malone	[20]	2015	Diabetic foot syndrome. Cellulites with OM (n = 14; 24%) and OM alone (n = 11; 19%) were documented (n = 25; 43%)	No information regarding affected bones or joints
14	Nathwani	[21]	2003	4 septic arthritis; 3 acute and 48 chronic OM (40%/19 = PPJI)	No information regarding affected bones or joints
16	Ruh	[23]	2015	96 cases; bone and joint infection in 14 (39.5%)	No information regarding affected bones or joints
18	Sims	[25]	2013	10 primary total knee replacements and 4 primary total hip replacement	No economic analysis was performed by affected joint
19	Theocharis	[26]	2012	No bone or joint infection mentioned	No information regarding affected bones or joints
20	Wai	[27]	2000	140 cases; 55 bone/joint (39%) infections	No information regarding affected bones or joints
21	Yong	[28]	2009	7/72 cases of OPAT and 9/93 IPAT patient bone and joint associated	No information regarding affected bones or joints

OM: Osteomyelitis; PPJI: Periprosthetic joint infections; IPAT: Inpatient parenteral antibiotic therapy; OPAT: Outpatient parenteral antibiotic