Predicting lower limb periprosthetic joint infections: A review of risk factors and their classification

Table 1 Study characteristics including number of patients, statistical method used, site (hip, knee or both), and duration of patient follow-up

Ref.	Year	Patients (n)			Statistical method used	Site	Follow-up (mo)
		Infected (cases)	Non-infected (controls)	Total			Min	Max	Mean
Berbari et al[9]	1998	462	462	924	OR, CI, P	Both	-	-	-
Lai et al[10]	2007	51	-	-	OR, CI, P	Both	-	84	-
Parvizi et al[11]	2007	78	156	234	OR, CI, P	Both	-	-	-
Pulido et al[12]	2008	63	9182	9245	HR, CI, P	Both	12	72	43
Malinzak et al[13]	2009	43	8451	8494	OR, P	Both	24	192	74.4
Ong et al[14]	2009	887	39042	39929	OR, P	Hip	-	108	-
Berbari et al[5]	2010	339	339	678	OR, CI, P	Both	-	-	-
Peel et al[15]	2011	63	126	189	OR, CI, P	Both	-	-	-
Bozic et al[16]	2012	-	-	40919	HR, CI, P	Hip	12	-	-
Jämsen et al[17]	2012	52	7129	7181	HR, CI, P	Both	0	12	12
Bozic et al[4]	2012	-	-	83011	OR, CI, P	Knee	12	-	-
Dale et al[18]	2012	2778	429390	432168	RR, CI, P	Hip	0	60	60
Greenky et al[19]	2012	389	15333	15722	OR, CI, P	Both	36	108	62.4
Namba et al[20]	2013	404	55812	56216	HR, CI, P	Knee	-	-	-
Somayaji et al[21]	2013	5	254	259	OR, CI, P	Both	12	124	24
Coelho-Prabhu et al[22]	2013	339	339	678	OR, CI, P	Both	2	24	-
Maoz et al[23]	2014	47	3625	3672	OR, CI, P	Hip	12	48	24
Gómez-Lesmes et al[24]	2014	32	1299	1331	OR, CI, P	Knee	-	3	-
Yi et al[25]	2014	126	375	501	OR, CI, P	Both	3	-	-
Wu et al[26]	2014	45	252	297	OR, CI, P	Both	12	144	28
Sousa et al[27]	2014	43	2454	2497	OR, CI, P	Both	1	12	12
Jiang et al[28]	2014	-	-	306946	HR, P	Hip	6	-	-
	2014	-	-	573840	HR, P	Knee	6	-	-
Duchman et al[29]	2015	8062+	70129+	78191	OR, CI, P	Both	-	-	-
Chrastil et al[30]	2015	-	-	13272	HR, CI, P	Both	24	120	-
Crowe et al[31]	2015	26	3393	3419	OR, CI, P	Both	-	12	-
Debreuve-Theresette et al[32]	2015	45	90		OR, CI, P	Both	-	-	-
Bohl et al[33]	2015	-	-	49603	RR, CI, P	Both	-	1	-

RR: Relative risk; HR: Hazard ratio; OR: Odds ratio.

Table 2 Paper quality, defined by presence of record and reporting bias

Ref.	Design	Record bias	Reporting bias (outcome measure); definition of infection
Berbari et al[9]	Retrospective	No	2 or more cultural examination positive for the same microorganism; sinus tract; purulence around the prosthesis/joint
Lai et al[10]	Retrospective	No	2 or more cultural examination positive for the same microorganism; clinical diagnosis
Parvizi et al[11]	Prospective	No	Criteria based upon 3 of 5 features1
Pulido et al[12]	Retrospective	Yes	Criteria based upon 3 of 5 features1
Malinzak et al[13]	Retrospective	No	Unknown
Ong et al[14]	Retrospective	Yes	Diagnostic code in Medicare database
Berbari et al[5]	Prospective	Yes	2 or more cultural examination positive for the same microorganism; acute inflammation on histopathological examination; sinus tract; purulence around the prosthesis/joint
Peel et al[15]	Prospective	Yes	Criteria based upon 3 of 5 features1
Bozic et al[16]	Retrospective	Yes	Diagnostic code in Medicare database
Jämsen et al[17]	Prospective	Yes	CDC definition of surgical site infection3
1Bozic et al[4]	Retrospective	Yes	Diagnostic code in Medicare database
Dale et al[18]	Retrospective	Yes	Clinical as reported by the surgeon after surgery
Greenky et al[19]	Retrospective	No	Criteria based upon 3 of 5 features1
Namba et al[20]	Retrospective	Yes	CDC definition of surgical site infection3
Somayaji et al[21]	Retrospective	No	Criteria based upon 3 of 5 features1
Coelho-Prabhu et al[22]	Retrospective	Yes	2 or more cultural examination positive for the same microorganism; sinus tract; purulence around the prosthesis/joint
Maoz et al[23]	Retrospective	Yes	CDC definition of surgical site infection3
Gómez-Lesmes et al[24]	Prospective	Yes	Criteria based upon 3 of 5 features1
Yi et al[25]	Retrospective	No	Criteria based upon 3 of 5 features1
Wu et al[26]	Retrospective	Yes	MSIS definition2
Sousa et al[27]	Retrospective	No	Criteria based upon 3 of 5 features1
Jiang et al[28]	Prospective	Yes	Diagnostic code in Medicare database
Duchman et al[29]	Prospective	Yes	Criteria based upon 3 of 5 features1
Chrastil et al[30]	Retrospective	Yes	Diagnostic code in Medicare database
Crowe et al[31]	Retrospective	Yes	CDC definition of surgical site infection3
Debreuve-Theresette et al[32]	Retrospective	No	CDC definition of surgical site infection3
Bohl et al[33]	Prospective	Yes	American College of Surgeons National Surgical Quality Improvement Program definition

¹Refers to 3 of 5 of the following criteria: (1) abnormal serology (ESR > 30 mm/h; CRP > 1 mg/dL); (2) strong clinical and radiographic suspicion for infection; (3) positive joint aspiration culture for infection; (4) evidence of purulence during the subsequent surgical intervention; and (5) positive intraoperative culture;

²Musculoskeletal Infection Society (MSIS) definition;

³Defined as (1) deep infection; (2) purulent drainage; (3) dehiscence; (4) fever; and (5) localized pain. CRP: C-reactive protein; ESR: Erythrocyte sedimentation rate.

Table 3 Host-related risk factors

	Ref.	Statistical parameter					Site
		HR	OR	RR	95%CI	P value
General
Age: 65-75 yr (compared to 45-65)	[26]		3.36		1.30-8.69	0.013	Hip/knee
Comorbidities (total number)	[10]		1.35		1.10-1.66	0.005	Hip/knee
Charlson index + 5 (compared to 0)	[14]		2.57		1.96-3.37	< 0.001	Hip
Place of residence (rural)	[26]		2.63		1.13-6.10	0.025	Hip/knee
Hispanic race (compared to White)	[20]	0.69			0.49-0.98	0.038	Knee
Alcohol abuse	[26]		2.95		1.06-8.23	0.039	Hip/knee
Tobacco use	[29]		1.47		1.21-1.78	0.001	Hip/knee
	[31]		3.4		1.23-9.44	0.029	Hip/knee
	[32]	3.91	3.4		1.19-12.84	0.032	Hip/knee
Tobacco use (S aureus colonization)	[23]		12.76		2.47-66.16	0.017	Hip
Gender
Female	[14]		0.83			0.009	Hip
Male	[18]			1.9	1.80-2.10	< 0.001	Hip
	[20]	1.89			1.54-2.32	< 0.001	Knee
	[31]		3.55		1.60-7.84	0.002
Endocrine disorders
Diabetes mellitus	[4]		1.19		1.06-1.34	0.0025	Knee
	[26]		5.47		1.77-16.97	0.003	Hip/knee
	[22]	1.46			1.27-1.68	0.0007	Hip
	[9]		4		1.13-14.18	0.032	Hip/knee
	[20]	1.28			1.03-1.60	0.025	Knee
	[17]	2.31			1.12-4.72	< 0.001	Hip/knee
	[15]		1.4		0.90-2.10	0.06	Hip/knee
	[5]		1.8		1.20-2.80	0.006	Hip/knee
	[13]		3.1			0.02	Hip/knee
	[44]		2.21		1.34-3.64	0.001	Knee
Pre-op BM > 6.9 mmol/L	[17]	2.25			0.60-8.50	0.073	Hip/knee
Pre-operative hyperglycemia	[30]	1.44			1.09-1.89	0.008	Hip/knee
Psychiatric disorders
Depression	[4]		1.28		1.08-1.51	0.0035	Knee
	[16]	1.6			1.32-1.93	0.0039	Hip
Psychosis	[16]	1.74			1.38-2.20	0.0044	Hip
	[4]		1.26		1.02-1.57	0.0331	Knee
Haematological disorders
Preoperative anaemia	[16]	1.36			1.15-1.62	0.0005	Hip
	[19]		1.95		1.41-2.69	< 0.001	Hip/knee
	[4]		1.26		1.09-1.45	0.0014	Knee
Coagulopathy	[16]	1.58			1.24-2.01	0.0002	Hip
Malignancy
Metastatic malignancy	[4]		1.59		1.03-2.47	0.0369	Knee
Tumour 5 yr before implant	[5]		3.1		1.30-7.20	< 0.01	Hip/knee
Cardiovascular disorders
Congestive heart failure	[4]		1.28		1.13-1.46	< 0.0001	Knee
	[16]	1.57			1.33-1.84	0.0409	Hip
Cardiac arrhythmia	[16]	1.48			1.30-1.70	0.0012	Hip
Coronary artery disease	[21]		5.10		1.30-19.8	0.017	Hip/knee
Valvular disease	[4]		1.15		1.01-1.31	0.039	Knee
Peripheral vascular disease	[4]		1.13		1.01-1.27	0.0381	Knee
	[16]	1.44			1.24-1.68	0.0032	Hip
Gastroenterology disorders
Liver cirrhosis	[28]	5.4				< 0.001	Hip
	[28]	3.4				< 0.001	Knee
Hepatitis B virus (amongst males)	[44]		4.32		1.85-10.09	< 0.001	Knee
OGD with biopsy	[22]		2.8		1.10-7.10	0.03	Hip/knee
Respiratory disorders
Chronic pulmonary disease	[4]		1.22		1.10-1.36	< 0.0001	Knee
	[31]		4.34		1.28-14.70	0.041	Both
Pulmonary circulation disorders	[4]		1.42		1.06-1.91	0.0205	Knee
Renal disorders
Renal disease	[4]		1.38		1.11-1.71	0.0038	Knee
Renal function (mL/min)	[15]		1		0.90-1.00	0.05	Hip
Rheumatoid arthritis
Rheumatoid arthritis	[15]		3.3		0.80-13.90	0.09	Hip/knee
	[4]		1.18		1.02-1.37	0.0277	Knee
	[16]	1.71			1.42-2.06	< 0.0001	Hip
ASA grade
ASA score	[15]		2.2		1.30-4.00	0.006	Hip/knee
Mean score	[11]		2.07		1.08-1.97	0.03	Hip/knee
3 (compared to 1 or 2)	[20]	1.65			1.33-2.00	< 0.001	Knee
> 4	[12]	1.95			1.00-3.70	0.04	Hip/knee
Body mass index
Obesity	[4]		1.22		1.03-1.44	0.0219	Knee
	[16]	1.73			1.35-2.22	< 0.0001	Hip
BMI (kg/m2)	[15]		1.1		1.00-1.10	0.05	Hip
	[12]	3.23			1.60-6.50	0.001	Hip/knee
< 20	[21]		6		1.20-30.9	0.033	Hip/knee
25-30	[5]		0.4		0.30-0.70	< 0.001	Hip/knee
≥ 28 (compared to 18.5-28)	[26]		2.77		1.20-6.40	0.017	Hip/knee
31-39	[5]		0.5		0.30-0.70	< 0.001	Hip/knee
35 (compared to < 35)	[20]	1.47			1.17-1.85	0.001	Knee
	[32]	1.84			1.11-3.05	0.007	Both
> 40	[23]		4.13		1.30-12.88	0.01	Hip
	[13]		3.3			0.045	Knee
	[17]	6.41			1.67-24.59	< 0.001	Hip/knee
> 50	[13]		18.3			< 0.001	Hip/knee
Malnutrition	[25]		2.3		1.50-3.50	< 0.001	Hip/knee
Serum albumin < 3.5 g/dL	[33]		2		1.50-2.80	< 0.001	Hip/knee
Immunocompromise
Immunocompromise	[5]		2.2		1.60-3.00	< 0.001	Hip/knee
Inflammatory disease	[18]			1.4	1.10-1.70	0.001	Hip
Prednisone dose exceeds 15 mg/d	[21]		21		3.50-127.2	< 0.001	Hip/knee
Systemic steroid therapy	[15]		3.3		0.80-13.90	0.09	Hip/knee
Infection
Distant organ infection	[5]		2.2		1.50-3.25	< 0.001	Hip/knee
Nasal S. Aureus Infection	[31]		3.95		1.80-8.71	< 0.001	Hip/knee
Nasal MRSA Infection	[31]		8.24		3.23-21.02	< 0.001	Hip/knee
Asymptomatic bacteriuria	[27]		3.23		1.67-6.27	0.001	Hip/knee
Genitourinary infection	[10]		2.8		1.01-7.77	0.048	Hip/knee
Operative indication
Hip fracture	[18]			2.1	1.90-2.40	< 0.001	Hip
Post-traumatic osteoarthritis	[20]	3.23			1.68-6.23	< 0.001	Knee
Prior operation on the index joint	[5]		1.9		1.30-2.60	< 0.001	Hip/knee
Per additional surgery	[32]		2.88		1.45-5.80	0.018	Hip/knee
Avascular necrosis	[18]			1.7	1.40-2.10	< 0.001	Hip

RR: Relative risk; HR: Hazard ratio; OR: Odds ratio.

Table 4 Provider-related risk factors

	Ref.	Statistical parameter					Site
		HR	OR	RR	95%CI	P value
Antibiotic use
Antibiotic surgical prophylaxis	[5]		0.5		0.30-0.80	0.003	Hip/knee
Antibiotic irrigation	[20]	0.67			0.48-0.92	0.014	Knee
Surgical technique
Exposure requiring quadriceps release	[20]	4.76			1.18-19.21	0.029	Knee
Use of wound drain tube	[15]		0.09		0.01-0.80	0.03	Knee
Side of surgery
Simultaneous bilateral surgery	[12]	5.85			2.50-13.90	< 0.0001	Hip/knee
	[20]	0.51			0.31-0.83	0.007	Knee
Single side (compared to bilateral)	[13]		3.1			0.0024	Hip/knee
	[13]		4			0.009	Knee
Cement
Antibiotic-laden cement	[20]	1.53			1.18-1.98	< 0.001	Knee
Non-antibiotic cement	[8]			1.5	1.30-1.80	< 0.001	Hip
Hybrid (compared to uncemented)	[8]			1.6	1.40-1.80	< 0.001	Hip
Operative duration
Length of operation (> 115 min)	[23]		3.38		1.23-9.28	0.018	Hip
(> 210 min)	[14]		1.78		1.40-2.26	< 0.0001	Hip
(≥ 240 min)	[5]		2.7		1.50- 5.00	0.002	Hip/knee
Hospital factors
Hospital volume < 100 (vs > 200/yr)	[20]	0.33			0.12-0.90	0.03	Knee
Medicare buy-in	[14]		1.34			0.005	Hip

RR: Relative risk; HR: Hazard ratio; OR: Odds ratio.

Table 5 Post-surgical risk factors

	Ref.	Statistical parameter				Site
		HR	OR	95%CI	P value
Anaesthetic factors
Intensive care length of stay (d)	[15]		0.5	0.20-1.00	0.06	Knee
Haematological
Blood transfusion	[12]	2.11		1.10-3.90	0.02	Hip/knee
	[15]		2.1	1.00-4.20	0.04	Hip/knee
	[11]		1.63	1.14-2.33	0.007	Hip/knee
Transfusion if RBCs stored > 14 d	[24]		5.9	2.60-13.20	< 0.001	Knee
Perioperative blood loss (via drain tube)	[15]		1	1.00-1.01	0.008	Hip
Cardiac
Postoperative atrial fibrillation	[12]	6.22		1.40-28.5	0.02	Hip/knee
Postoperative myocardial infarction	[12]	20.4		2.10-199.9	0.009	Hip/knee
Hospital factors
Longer hospital stay	[12]	1.09		1.00-1.10	0.0003	Hip/knee
Non same-day surgery	[23]		4.16	1.44-12.02	0.008	Hip
Wound complications
All wound complications	[11]		27	11.00-91.6	0.0002	Hip/knee
Wound discharge	[5]		18.7	7.40-47.2	< 0.001	Hip/knee
	[15]		6.3	1.30-30.7	0.02	Knee
	[15]		5.4	2.00-15.0	0.001	Hip
	[15]		5.7	2.40-13.3	<0.001	Hip/knee
	[11]		32.2	8.7-119.17	< 0.0001	Hip/knee
Haematoma	[5]		3.5	1.30-9.50	0.01	Hip/knee
Surgical site infection	[1]		35.9	8.30-154.6	< 0.01	Hip/knee
Superficial incisional SSI	[15]		3.7	1.10-11.9	0.03	Knee
	[15]		5	1.60-15.9	0.007	Hip
	[15]		4.3	1.90 - 9.90	0.001	Hip/knee
NNIS risk index 2	[9]		3.9	2.00-7.50	< 0.01	Hip/knee
Urinary
Postoperative urinary infection	[12]	5.45		1.00-8.70	0.04	Hip/Knee
	[5]		2.7	1.04-7.10	0.04	Hip/Knee

RR: Relative risk; HR: Hazard ratio; OR: Odds ratio.

Table 6 Classification of risk factors and probability of infection (main factors)

	Risk factor	Minimum increase	Maximum increase	Statistical parameter	Ref.
Host-related risk factors
Modifiable	Systemic steroids	3.3	21	OR	[15,21]
	Tobacco use	3.4	12.76	OR	[23,32]
	Nasal MRSA infection	-	8.24	OR	[31]
	BMI < 20	-	6	OR	[21]
	Coronary artery disease	-	5.1	OR	[21]
	COPD	1.22	4.34	OR	[4,31]
	BMI > 40	-	4.13	OR	[23]
	Pre-operative BM	-	2.25		[17]
Non-modifiable	Diabetes	1.4	5.47	OR	[15,26]
	Liver cirrhosis	-	5.4	HR	[28]
	Male	1.89	3.55	HR,OR	[20,31]
	Age	-	3.36	OR	[26]
	Rheumatoid arthritis	1.18	3.3	OR	[4,15]
	Malignancy	-	3.1	OR	[5]
Provider-related risk factors
Modifiable	Quadriceps release (TKR)	-	4.76	HR	[20]
	Non-same day procedure	-	4.16	OR	[23]
	Prolonged operation	1.78	3.38	HR	[14,23]
Non-modifiable	Prolonged storage of blood	2.6	13.2	OR	[24]

BMI: Body mass index; RR: Relative risk; HR: Hazard ratio; OR: Odds ratio; COPD: Chronic obstructive pulmonary disease; TKR: Total knee replacement.