Study reference

Study characteristics

Patient characteristics

Intervention (I)

Comparison / control (C)

Follow-up

Outcome measures and effect size

Comments

Parvizi, 2008

SR and meta-analysis of 6 RCTs

Literature search up to December 2004

A: Espehaug, 1997; Norway; supported by grants from the Norwegian Research Council and the Norwegian Medical Association’s Fund for Quality Improvement

B: Josefsson, 1990; Sweden, unknown

C: Josefsson and Kolmert, 1993; Sweden, unknown

D: Havelin et al., 1995, Norway, unknown

E: Lynch, 1987, England, unknown

F: McQueen, 1987

Setting and Country: USA

Source of funding:

unknown

Inclusion criteria SR: primary and revision hip arthroplasty, comparative trials of antibiotic loaded versus non-antibiotic cement, if they included data on 100 or more primary hip replacements or 20 or more revision hip replacements, and if they included outcome data at specified follow-up times. Outcome data required for inclusion were the incidence of deep infection and the overall survival rate at the specified interval after surgery.

Exclusion criteria SR: Studies that related to mechanical properties of cement, in vitro studies, and studies of joints other than the hip were excluded; non-clinical studies and non-outcome clinical studies, historical reports and studies without a control group; hips that had been inserted with low-viscosity “Boneloc” cements in the study by Havelin et al. (1995) were excluded; hips in the study by Espehaug et al. (1997) that had been performed using Simplex cement containing erythromycin and colistin were also excluded

N=24.661 hip-replacements

N=21.445 analysed

Describe intervention:

Antibiotic impregnated cement (gentamicin)

A: 1) patients receiving antibiotic prophylaxis both systemically and locally in the bone cement (combined regime);

3) those receiving antibiotics in the cement only (cement only regime)

B: gentamicin bone cement (GBC)

C: gentamicin bone cement (GBC)

D: antibiotic cement

E: gentamicin-containing acrylic cement

F: cefuroxime in bone cement

Describe control:

Non-antibiotic impregnated cement

A: Espehaug, 1997

2) those receiving antibiotics systemically only (systemic only regime);

4) those receiving no antibiotic prophylaxis (no antibiotic

regime).

B: systemic antibiotics

C: systemic antibiotics

D: cement without antibiotics

E: plain bone cement (CMW)

F: systemic cefuroxime

End-point of follow-up (minimum follow-up of two years):

A: five years

B: five years

C: ten years

D: 3,2 years (range 0 to 6,4)

E: 8,1 for CMW series and 3,6 for Palacos with gentamicin

F: McQueen, 1987

G:

H:

I:

….

For how many participants were no complete outcome data available?

1,081 hips (4.4%) were lost to

follow-up or the patients died and were excluded

Outcome measure-1 Deep wound infection

Pooled effect (random effects model):

RR 0,51 (95%BI 0,34 to 0,75) favoring antibiotic cement

Outcome measure-2 overall survival of the hip prothesis

RR 0,72 (95%BI 0,63 to 0,83) favoring antibiotic cement

Wang, 2012

SR and meta-analysis of RCTs

Literature search up to june 2013

B: Chiu, 2002 Knee

C: Hinarejos, 2013 Knee

D: Josefsson, 1981

E: McQueen, 1987 Hip and knee

F: McQueen, 1990 Hip and knee

G: Pfarr, 1979

H:Wannske, 1979

Study design: All RCTs

Setting and Country:

B: Taiwan, hospital

C: Spain, hospital

D: Sweden, hospital

E: Scotland, hospital

F: Scotland, hospital

G: Germany, hospital

H:

Inclusion criteria SR: patients undergoing a primary THA or TKA; include an AIBC trial group and a control group that involved the use of plain bone cement (PBC) or systemic antibiotic (SA), irrespective of the dose and route of administration; and be a published RCT

Exclusion criteria SR: (1) the outcomes were not reported for antibiotic cement use in primary total hip or knee replacement; (2) it was impossible to extrapolate or calculate the necessary data from the published results; (3) primary study patients had a poor physical condition, such as diabetes, malign nt tumor; and (4) studies were animal experiments, in vitro trials or revision arthroplasty, and the operated joint was not the hip or knee

8 studies included

Important patient characteristics at baseline:

N, mean age

A: N= 23 (25 hips, 73 yrs

B: N=340, 69 yrs

C: N=2948, 75 yrs

D: N=1633, 69 yrs

E: 295, 68 yrs

F: N=401, 67 yrs

G: N=200, 65 yrs

H: N=476, 64 yrs

Describe intervention:

B: 2g cefuroxiume

C: 0,5 g ERY and colistin

D: 0,5 g gentamicin

E: 1,5 g cefuroxime

F: 1,5 g cefuroxime

G: gentamicin

H: gentamicin

Describe control:

B: Simplex P

C: Simplex P

D: Palacos

E: CMV

F: CMV

G: Palacos

H: Palacos

End-point of follow-up:

B: 49 months

C: 12 months

D: 24 months

E: 3 months

F: 24 months

G: 24 months

H: 29 months

For how many participants were no complete outcome data available?

(intervention/control)

A: 5 due to missed examinations and further dropout

B: N

C: yes 52

D: yes 52

E: yes

F: yes 4

G: no

H: no

Outcome measure-1 infection

Defined as

We included the seven RCTs which involved the postoperative infection rate of patient as the data of the metaanalysis in Table S3 in File S1. In the aspect of superficial infection rate, because no significant heterogeneity was observed among the subgroups (P= 0.79; I2= 0%), a fixedeffect model was employed. The overall pooled results of 5 RCTs revealed a significant difference between AIBC and control group (RRs, 1.47; 95% CIs, 1.13 to 1.91; P= 0.004) (Figure 2). Furthermore, we found different results based on the respective analysis of two subgroups. In the subgroup of AIBC versus SA, SA had a lower superficial infection rate than AIBC (P= 0.01). However, in the subgroup of AIBC versus PBC, the pooled results showed that there was no statistically significant difference (P= 0.22). For deep infection, heterogeneity between the two subgroups was statistically different (P= 0.06; I2=53%), so we used a random-effect model to evaluate the deep infection rate. The total pooled results exhibited a significant statistical difference between AIBC and control treatments (RRs, 0.41; 95% CIs, 0.17 to 0.97; P= 0.04)

Facultative:

Brief description of author’s

study included both hips and knees.

Hip studies were performed in 1979 and 1981

Study A removed, studied no infection

H: Wannske 1979, not included in reference list

Study reference

Study characteristics

Patient characteristics ²

Intervention (I)

Comparison / control (C) ³

Follow-up

Outcome measures and effect size ⁴

Comments

Colas, 2015

Type of study: cohort

Setting: THA (THR) in hospital, data collected by national health insurance database

Country: France

Source of funding: unclear

Inclusion criteria: + 40 y, THR for osteoarthritis between 04/2010 and 12/2011

Exclusion criteria: THR for trauma or bone cancer, bilateral THR, rosthetic revision before inclusion period, no medical reimbursement after index THR, missing THR characteristics

Describe intervention (treatment/procedure/test):

Antibiotic impregnated cemented THR CoC, ceramic-on-ceramic; CoP, ceramic-on-polyethylene; MoM, metal-on-metal; MoP,metal-on-polyethylene;

Describe control (treatment/procedure/test):

Antibiotic free cemented THR CoC, ceramic-on-ceramic;

CoP, ceramic-on-polyethylene; MoM, metal-on-metal; MoP,metal-on-polyethylene;

Length of follow-up: median 33 months

Loss-to-follow-up:

Not described

Incomplete outcome data:

Not described

Outcome measures and effect size (include 95%CI and p-value if available):

THR revision (including any surgical reintervention in which implant or any of its components was changed or removed.

Antibiotic-impregnated cemented THRs had a better prognosis than uncemented THRs: cumulative revision rates were 2.4% and 3.3%, respectively (P <.001), and the multivariate adjusted hazard ratio was 0.74 (95%CI, 0.67 to 0.84; P <.001).

Revision risk for antibiotic-free cemented THRs was not different compared with uncemented THRs (HR, 0.95; 95% CI, 0.79 to 1.14)

21% used antibiotic loaded bonecement

Engesaeter, 2003

Type of study: registry

Setting: hospital

Country: Norway

Source of funding: unknown

Inclusion criteria: solely prostheses and cements with documented good long-term results in the Register. Only primary prostheses in patients with idiopathic osteoarthritis of the hip were included. We selected prostheses with high-viscosity cement of the brands Palacos with or without gentamicin or Simplex with or without colistin/ erythromycin. Lastly, only those who had received systemic antibiotic prophylaxis with cephalosporin (the first-generation cephalotin or the second-generation cefuroxime) or penicillin (cloxacillin or dicloxacillin, both semisynthetic penicillinase-resistant) were included.

Important patient characteristics at baseline:

N=22170 THA

Mean age: 72 (17-97)

29% males

Describe intervention (treatment/procedure/test):

A combined antibiotic prophylaxis, both systemically and in cement, was used in 71% of the operations, in 1.1% antibiotic solely in the cement and in 1.3% no antibiotic prophylaxis was used at all.

During the study, the prophylaxis regime was switched almost entirely to the combined regime after 1998.

Describe control (treatment/procedure/test):

Only systemic antibiotics

Length of follow-up: median

Loss-to-follow-up:

who died or emigrated during the follow-up were

identified from files provided by Statistics Norway

and the follow-up time for the prostheses in these

patients were censored on the date of death or emigration

Incomplete outcome data:

Not described

Revision:

Systemic and cement:

Systemic only: 50/15676 (0.4% 10-year revision)

Systemic only: 46/5960 (0.7% 10-year revision)

The revision risk for those who received only antibiotic systemically, as compared to a combined, revision was 1.4 times higher with all reasons for revision as endpoint (p <0.001), 1.3 times higher with aseptic loosening (p = 0.02) and 1.8 times higher with infection (p = 0.01)

Study reference

(first author, year of publication)

Bias due to a non-representative or ill-defined sample of patients?¹

(unlikely/likely/unclear)

Bias due to insufficiently long, or incomplete follow-up, or differences in follow-up between treatment groups?²

(unlikely/likely/unclear)

Bias due to ill-defined or inadequately measured outcome ?³

(unlikely/likely/unclear)

Bias due to inadequate adjustment for all important prognostic factors?⁴

(unlikely/likely/unclear)

Colas, 2015

unlikely

Unlikely

unlikely

unlikely

Engesaeter, 2003

unlikely

Unlikely

unlikely

likely

Study

First author, year

Appropriate and clearly focused question?¹

Yes/no/unclear

Comprehensive and systematic literature search?²

Yes/no/unclear

Description of included and excluded studies?³

Yes/no/unclear

Description of relevant characteristics of included studies?⁴

Yes/no/unclear

Appropriate adjustment for potential confounders in observational studies?⁵

Yes/no/unclear/notapplicable

Assessment of scientific quality of included studies?⁶

Yes/no/unclear

Enough similarities between studies to make combining them reasonable?⁷

Yes/no/unclear

Potential risk of publication bias taken into account?⁸

Yes/no/unclear

Potential conflicts of interest reported?⁹

Yes/no/unclear

Parvizi, 2008

yes

yes

Unclear

no

unclear

Described, but not provided

yes

yes

No

Wang,

yes

yes

Yes

yes

unclear

no

yes

yes

no