Chronic infections in hip arthroplasties: comparing risk of reinfection following one-stage and two-stage revision: a systematic review and meta-analysis

Figures & data

Table 1 Search strategy

Search performed in the following numerical order (Pubmed/Embase) #1 Hip arthroplasties #2 Hip replacement #3 Hip replacements #4 Replaced hip #5 Hip implant #6 Hip implants #7 Hip joint replacement #8 Hip joint replacements #9 Total hip prosthesis #10 Hip prostheses #11 Infection OR infections #12 One stage OR 1 stage #13 Two stage OR 2 stage #14 Delayed reimplantation OR stage reimplantation OR staged reimplantation #15 #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 #16 #12 OR #13 OR #14 #15 #11 AND #15 AND #16

Notes: The search strategy was applied as key concepts. No limits applied. The Cochrane Library was searched using: infection AND hip/infection AND arthroplasty/infection AND hip replacement. The World Health Organization platform for international clinical trials registries (http://www.who.int/ictrp) was searched for ongoing, terminated, or completed trials using: infection AND hip/infection AND arthroplasty/infection AND hip replacement. Keywords used to assess relevancy in the electronic database search: hip, infected, infection, bacteria (or specific species), septic, one-stage, two-stage, direct exchange, exchange, stage, staged, revision, arthroplasty, replacement, prosthesis, treatment, spacer, beads, outcome.

Figure 1 PRISMA flow diagram.

Abbreviation: PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analysis.

Table 2 Characteristics of studies with patients in the one-stage revision cohort

Authors	Reimplantation performed	Patients with performed reimplantation	Years of inclusion	Gender, % male	Age, years (range)	Time with infection/infected prosthesis	Antibiotic treatment regime (study level)	Non-septic revisions after reimplantation, n (%)	Follow-up, month (range)	Definition of infection (study level)
Yoo et al^Citation47	Cementless	12	1991–2005	67	50 (29–72)	3.6 years (1.2–9.8)	iv or iv/po combined for 3–24 weeks	1 (8)	86,4 (39,6–135,6)	Chronic hip pain + purulent fluid/pus on op + elevated crp or SR (a positive culture to be included in study)
Lai et al^Citation48	Cementless	7	1991–1993	71	62 (52–68)	“Late or delayed”	iv 2–6 weeks then po min 2 months	n/a	42 (33–54)	Positive culture
Rudelli et al^Citation49	Cementless	6	1989–1994	50	60 (39–71)	Minimum 4 months	iv min 4 weeks then po, total 6 months	0	138.7 (101–173)	A positive culture from min 6 samples (2 pt only fistula, 1 pt. Only pos culture from pre-op aspiration)
Mulcahy et al^Citation50	Cemented	15	n/a	87	64 (49–82)	2.2 years (6 months–16 years)	iv 3 weeks	0	48 (24–84)	Positive culture
Callaghan et al^Citation51	Cemented	24	1977–1983	50	65 (37–86)	4.9 years (1–11)	iv 10 days then po 3–6 months	1 (4)	109,2 (12–168)	Positive culture + purulence/inflammation during opertion
Hope et al^Citation52	Cemented	72	1976–1987	44	64 (30–85)	n/a (>3 weeks after pre-op aspiration)	n/a	2 (3)	45 (5–121)	“Clinical, hematological and radiological criteria” (in study only CNS proven infections)
Ure et al^Citation53	Cemented	20	1979–1990	80	61 (32–85)	53 months (6.6–148)	iv 2–18 weeks then po 3–6 months	2 (10)	123,6 (66–205,2)	A positive culture + >5 polymorph leukocytes per field
Raut et al^Citation54	Cemented	183	1979–1990	52	65 (17–84)	n/a (referalls)	iv 1–4 weeks then po 6 weeks–3 months	4 (2)	83 (24–164)	Pyogenic granulation tissue or pus or sinus + radiologic evidence + bacteriology
Drancourt et al^Citation55	Cemented	10	1987–1991	n/a	n/a	32.6 months (1–130)	po 5 months before and 1 month after revision	n/a	27,6 (9–61)	Fistula or pain and elevated crp and SR > 50 or radiological loosening and elevated crp and SR > 50 AND 2 positive cultures
Rudelli et al^Citation49	Cemented	26	1991–2000	38	62 (37–83)	minimum 4 months	iv min 4 weeks then po, total 6 months	0	84,1 (42–175)	A positive cultures from min 6 samples (2 pt only fistula, 1 pt. Only pos culture from pre-op aspiration)

Abbreviations: n/a, not available; iv, intraveneous; po, per os; crp, c-reactive protein; SR, sedimentation rate.

Table 3 Characteristics of studies with patients in the two-stage-revision cohort

Authors	Reimplantation performed	Patients with performed reimplantation	Years of inclusion	Time with infection/infected prosthesis	Gender, % male	Age, years (range)	Interval between first revison and reimplantation (range)	Spacer (with antibiotics)/beads/none	Antibiotic treatment regimen (study level)	Non-septic revisions after reimplantation, n (%)	Follow-up, month (range)	Definition of infection (study level)
Lai et al^Citation48	Cementless	19	1991–1993	“late or delayed”	89	49 (29–67)	32,5 weeks (8–66)	Beads only 19 patients	iv 2–6 weeks then po min 2 months	n/a	38 (25–51)	Positive culture
Buttaro et al^Citation56	Cementless	29	1997–2000	11.7 months (3–48)	40	59 (32–78)	14.7 weeks (5–96)	None	iv 5–8 weeks then po 4–16 weeks	1 (3)	32.4 (24–60)	A positive culture from five samples
Fehring et al^Citation57	Cementless	22	n/a	“Chronic infections”	n/a	n/a	4,7 months	Beads only 16 patients	iv 6 weeks	1 (5)	37,5 (24–98)	A positive culture or positive histology for infection
Fink et al^Citation58	Cementless	36	2002–2006	4,4 years (±4 years)	44	69 (sd ±10)	6 weeks for all	Spacer (w)	iv 2 weeks then po 4 weeks	0	35 (24–60)	Pre-op hip aspiration and observation of the same microorganism in at least two of five cultures and observation of a microorganism in at least one sample and at least five neutrophilic polymorphonuclear leukocytes per high-power field (×400) in the associated histologic preparation
Hofmann et al^Citation59	Cementless	27	1991–2001	63 months (2–413)	56	64 (38–87)	14 weeks (3–49)	Spacer (w)	iv 6–8 weeks then for 17 pt po for 6 weeks	n/a	76 (28–148)	A positive culture or clinical history + elevated CBS, CRP, ESR + inflammation on frozen section
Koo et al^Citation60	Cementless	12	1993–1997	8.25 months (2–36)	75	56 (37–73)	6 (6–8)		iv 6 weeks	0	45 (24–66)	Positive culture or pus
Yamamoto et al^Citation61	Cementless	10	1998–2002	48 days (32–73)	50	63 (44–76)	125 days (85–245)	Spacer (w)	iv 2–12 months	n/a	42.6 (5–62)	“Infection”
Nestor et al^Citation62	Cementless	34	1984–1989	24 months, (1–108)	n/a	61 (26–70)	7 months (3–19)	None	iv 28 days (9–42) then po 14 days (0–40)	2 (6)	47 (24–72)	Combination of pain, draining sinus, fever, haematolgical markers, scintigraphic scans, pre-op aspiration with positive cultures OR positive intraoperative cultures
McDonald et al^Citation63	Cemented	81	1969–1985	2,5 years (31 days–14,8 years)	53	60 (33–80)	1.5 years (6 days–6.2 years)	None	iv 26 days (4–59) (two pt received oral instead). No antibiotics in cement	7 (9)	66 (24–163, 2)	Histological evidence of infection and positive culture or gross purulence
Cordero-Ampuero et al^Citation64	Cemented	20	1997–2007	>3 months since index surgery	40	67 (46–80)	9,1 months (3–23)	None	iv < 5 days then po 6 months	n/a	55,2 (12–132)	3 or more positive cultures
Evans^Citation65	Cemented	11	1995–2002	MSIS stage III	55	70 (43–90)	98 days (44–192)	Spacer (w)	iv 6 weeks	0	24 (24)	“Infection” (10 culture positive, 1 culture negative)
Magnan et al^Citation66	Cemented	8	1996–1999	2–168 months	75	71 (58–83)	5 months (3–9)	Spacer (w)	n/a	0	36 (24–48)	“Infection” (4 culture positive, 4 culture negative)
Dairaku et al^Citation67	Cemented	7	n/a	50 months (2–103) (duration of infection before revision 1–12 months)	29	65 (55–81)	15 weeks (12–22)	Spacer (w)	n/a	1 (14)	18 (6–68)	Culture postitive (1 pt elevated crp + osteolysis)
Nusem and Morgan^Citation68	Cemented	18	1990–1999	6 years (2–10)	n/a	66 (45–86)	5 months (1–8)	Spacer (w)	iv 3–4 weeks then po 1–31 weeks	2 (11)	108 (60–168)	“Infection” (all patients seemingly culture positive)
Lieberman et al^Citation69	Cemented	32	1985–1988	41 months (1–186)	n/a	67 (32–89)	62 days (20 days–32 months)	Beads 4 patients	iv 41 days (20–49). Antibiotics in cement in only 17 pt	0	40 (24–75)	Culture positive
Sanchez-Sotelo et al^Citation70	Unknown	168	1988–1998	5,1 year (4 months–20 years)	65	67 (32–89)	9,4 months (3–18)	Spacer (w) 31 patients	iv 6 weeks (3–18)	34 (20)	24 (n/a–192)	Two or more positive cultures (n = 146) OR culture from pre-op aspiration with preoperative signs of infection: “frank pus”, histopathologic exam, sinus
Stockley et al^Citation71	Unknown	114	1991–2004	“Chronic infections”	55	64 (28–83)	6,4 months (2–22)	Beads	iv only 1. Postoperative day	n/a	74 (2–175)	Culture positive
Hanssen and Osmon^Citation13	Unknown	17	1996–1997	26 months (1.4–28) (duration of infection MCPherson stage III)	47	64 (31–82)	159 days (90–780)	None	n/a	n/a	n/a	Culture positive
Incavo et al^Citation72	Unknown	11	n/a	47 months (3–240)	n/a	n/a	n/a (6–24weeks)	Spacer (w)	iv 4–6 weeks (then “some” patients po)	n/a	n/a	Culture positive
Takigami et al^Citation78	Unknown	8	1999–2006	18,6 months (1–56)	75	65 (49–79)	16,8 weeks (12–27)	Ceramics blocks (w)	iv 4.2 weeks (2–8)	0	49 (24–81)	“… based on clinical, radiological and histological evidence …” – 6 pt culture positive
Lim et al^Citation73	Unknown	34	1995–2006	41 months (2–144)	n/a	59 (35–79)	20 weeks (6–88)	Spacer (w) or beads	iv 9.6 weeks (4–24)	2 (6)	52,8 (24–120)	2 or more positive culture OR histopathological exam OR sinus
Tsukayama et al^Citation11	Unknown	34	1980–1991	“>one month after index op and had an insidious course”	n/a	n/a	110 days (34–720)	Beads (w)	iv 6 weeks	n/a	50,4 (15,6–132)	Min 2 of 5 positive cultures OR pus preoperatively
Wang et al^Citation74	Unknown	22	1988–1993	4,6 years (4 months – 11 years)	82	48 (28–75)	6,6 months (1,5–24)	Beads 13 patients	iv 16 days (7–42)	3 (9)	48 (24–84)	Preoperative pus or histopathological exam (all patients culture positive)
Whittaker et al^Citation75	Unknown	43	1998–2003	12 months (3–36)	49	69 (33–90)	21 weeks (8 weeks–23 months)	Spacer (w)	iv 2 weeks	0	49 (25–83)	2 or more positive cultures or histopathological exam
Cabrita et al^Citation16	Unknown	55	1996–2003	>4 weeks	n/a	n/a	n/a (60–610 days)	Spacer (w) 33 patients	iv 3 weeks then po 6 months	6 (11)	48 (24–102)	Culture positive
Isiklar et al^Citation79	Unknown	9	1996–1998	28 months (3–96) (duration of infection > 6 weeks)	33	63 (38–78)	7 weeks (3–14)	Spacer (w)	iv 3–14 weeks then po 12–24 weeks	0	24 (160–36)	S. Epidermidis proven infection
Scharfenberger et al^Citation80	Unknown	8	1998–2003	>2 months	n/a	n/a	n/a	Spacer (w)	iv 6 weeks	1 (13)	n/a (24–n/a)	Culture positive
Walter et al^Citation77	Unknown	40	2001–2005	> 4 weeks	55	66 (48–86)	n/a	Beads or spacer (w)	Min 6 weeks, of iv + po	4 (10)	7 (3–48)	Culture positive

Abbreviations: n/a, not available; iv, intraveneous; po, per os; crp, c-reactive protein; SR, sedimentation rate.

Table 4 Methodological characteristics of included studies

Authors	Study design	Comparing cohorts of 1- vs 2-stage revision	Data colletion	In-/exclusion clearly defined	Co-morbidity defined or includeded patients (study or patient level)	Follow-up more than 2 years for all patients	Patient level information regarding microbial diagNosis and antibiotic treatment regimen	Number of urgeons performing there visions	Information on nature of infected index prosthesis
Yoo et al^Citation47	Cohort	No	Retrospective	Yes	No	Yes	No	Yes	Yes
Lai et al^Citation48	Cohort	No	Retrospective	No	Yes	Yes	No	Yes	Yes
Rudelli et al^Citation49	Cohort	No	Retrospective	No	No	Yes	No	No	No
Mulcahy et al^Citation50	Cohort	No	Retrospective	No	No	Yes	No	Yes	No
Callaghan et al^Citation51	Cohort	No	Retrospective	Yes	No	No	No	No	Yes
Hope et al^Citation52	Cohort	No	Retrospective	Yes	No	No	No	Yes	Yes
Ure et al^Citation53	Cohort	No	Prospective	No	No	Yes	Yes	No	No
Raut et al^Citation54	Cohort	No	Prospective	No	No	Yes	No	Yes	Yes
Drancourt et al^Citation55	Cohort	No	Prospective	Yes	No	Not	Yes	No	No
Buttaro et al^Citation56	Cohort	No	Retrospective	Yes	No	Yes	No	No	Yes
Fehring et al^Citation57	Cohort	No	Retrospective	No	No	Yes	No	No	No
Fink et al^Citation58	Cohort	No	Prospective	Yes	Yes	Yes	No	No	Yes
Hofmann et al^Citation59	Cohort	No	Retrospective	No	No	Yes	No	Yes	Yes
Koo et al^Citation60	Cohort	No	Retrospective	No	No	Yes	Yes	No	Yes
Yamamoto et al^Citation61	Cohort	No	Retrospective	No	Yes	No	No	No	Yes
Nestor et al^Citation62	Cohort	No	Retrospective	No	No	Yes	Yes	Yes	Yes
McDonald et al^Citation63	Cohort	No	Retrospective	No	No	Yes	No	No	Yes
Cordero-Ampureo et al^Citation64	Cohort	No	Prospective	Yes	No	No	Yes	No	No
Evans^Citation65	Cohort	No	Retrospective	No	Yes	Yes	Yes	No	No
Magnan et al^Citation66	Cohort	No	Retrospective	No	No	Yes	No	No	No
Dairaku et al^Citation67	Cohort	No	Retrospective	No	No	No	Yes	No	Yes
Nusem and Morgan^Citation68	Cohort	No	Retrospective	No	No	Yes	No	No	No
Lieberman et al^Citation69	Cohort	No	Retrospective	Yes	No	Yes	No	No	No
Sanchez-Sotelo et al^Citation70	Cohort	No	Retrospective	Yes	Yes	Yes	No	No	Yes
Stockly et al^Citation71	Cohort	No	Prospective	No	No	No	No	Yes	No
Hanssen and Osmon^Citation13	Cohort	No	Retrospective	No	Yes	No	No	Yes	Yes
Incavo et al^Citation72	Cohort	No	Retrospective	No	Yes	No	No	No	Yes
Takigami et al^Citation78	Cohort	No	Retrospective	No	No	Yes	Yes	No	No
Lim et al^Citation73	case-control(-on sensitivity pattern)	No	Retrospective	Yes	Yes	Yes	No	Yes	No
Tsukayama et al^Citation11	Cohort	No	Retrospective	No	No	No	No	No	Yes
Wang and Chen^Citation74	Cohort	No	Retrospective	No	Yes	Yes	No	No	Yes
Whittaker et al^Citation75	Cohort	No	Prospective	Yes	Yes	Yes	No	No	No
Cabrita et al^Citation16	RCT (spacer vs no spacer)	No	Prospective	Yes	Yes	Yes	No	No	No
Isiklar et al^Citation79	Cohort	No	Prospective	Yes	Yes	No	Yes	No	No
Scharfenberger et al^Citation80	Cohort	No	Retrospective	Yes	Yes	Yes	No	No	No
Walter et al^Citation77	Cohort	No	Prospective	No	Yes	No	No	No	No

Figure 2 Forest plot illustrating absolute risk of reinfection in ascending order with relative weight of individual studies.

Notes: Event rate, absolute risk of reinfection; lower/upper limits, 95% confidence interval; total, number reinfected/number reimplanted.

Figure 3 Forest plot illustrating stratified analysis by type of revision performed with relative weight of individual studies.

Notes: Event rate, absolute risk of reinfection; lower/upper limits, 95% confidence interval; total, number reinfected/number reimplanted.

Figure 4 Forest plot illustrating two-stage revision stratified by implant used in reimplantation.

Notes: Event rate, absolute risk of reinfection; lower/upper limits, 95% confidence interval; total, number reinfected/number reimplanted.
Abbreviation: CI, confidence interval.

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