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Outcomes following debridement, antibiotics and implant retention in the management of periprosthetic hip joint infections: a review of cohort studies. Abstract Aims The aims of the study were to review and analyse the reported series of debridement, antibiotics and implant retention (DAIR) in the management of infected total hip replacements (THRs) to establish the overall success and the influencing factors. Patients and methods Using a standardised and recognised study protocol (“Meta- analysis of observational studies in epidemiology (MOOSE) guidelines) a comprehensive review and analysis of the literature was performed. The primary outcome measure of interest was treatment success. The search strategy and inclusion criteria plus quality assessment yielded 39 articles eligible for analysis, which included 1296 patients. Results The proportion of success from the literature following DAIR in the management of infected THRs appeared to have improved since 2004 with a pooled mean proportion of success of 72.2%. For all reported series, from 1977 onwards, there was improved success with early debridement (< seven days) (75.7%) and exchange of modular components (77.5%). There was a

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Page 1:  · Web viewOutcomes following debridement, antibiotics and implant retention in the management of periprosthetic hip joint infections: a review of cohort studies. Abstract. Aims

Outcomes following debridement, antibiotics and implant retention in the management of periprosthetic hip joint infections: a review of cohort studies.

Abstract

Aims

The aims of the study were to review and analyse the reported series of debridement,

antibiotics and implant retention (DAIR) in the management of infected total hip

replacements (THRs) to establish the overall success and the influencing factors.

Patients and methods

Using a standardised and recognised study protocol (“Meta-analysis of observational studies

in epidemiology (MOOSE) guidelines) a comprehensive review and analysis of the literature

was performed. The primary outcome measure of interest was treatment success. The search

strategy and inclusion criteria plus quality assessment yielded 39 articles eligible for analysis,

which included 1296 patients.

Results

The proportion of success from the literature following DAIR in the management of infected

THRs appeared to have improved since 2004 with a pooled mean proportion of success of

72.2%. For all reported series, from 1977 onwards, there was improved success with early

debridement (< seven days) (75.7%) and exchange of modular components (77.5%). There

was a statistically non-significant improvement if debridement was performed within four

weeks of the original surgery (73.0%).

Conclusion

The reported success following DAIR has improved since 2004. The only determinants of

outcome found by this review were the timing of debridement from onset of symptoms and

the exchange of modular components.

Take home message

A DAIR procedure, with exchange of modular components should be considered for acutely

infected THR when presenting within seven days from the onset of symptoms. Future cohorts

should include a core outcome set of relevant data for future meta-analyses.

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Introduction

In the UK over 100,000 primary total hip replacements (THRs) are performed

annually1,2. The numbers, both in the NHS and private health-care sector, have soared over

the last decade. They are expected to continue rising over the next 25 years. While all

complications are undesirable, the most feared complication of THR is infection, due to its

resistance to conservative treatment with standard antibiotic therapy3. The choice of treatment

for periprosthetic joint infections (PJIs) generally depends on a number of factors, including

local factors referring to the bone and tissue condition, fixation and stability of the prosthesis,

the chronicity of infection, the type of organism, and the host’s condition3–5. In the case of

early infection, within four 4-twelve 3 weeks of the original surgery, onset debridement,

antibiotics and implant retention (DAIR) can be a first-line option 3,4. However there is a very

wide range of reported proportions of success for DAIR in the management periprosthetic hip

infections ranging from 14%6-100%7–9. Treatment of acute THR infections with debridement

and implant retention was first reported in the 1974 by Müller 10 and then Coventry 11 in 1975

with an 80% and 20% success, respectively. Burton and Schurman 12 reported their experience

with the technique in 1977 with 75% remaining infection. The approach by Burton and

Schurman was “radical debridement of all necrotic debris and removal of the prosthesis,

where the prosthetic components were loose or bone involvement was present. The patients

were treated with wound irrigation with an appropriate antibiotic and were maintained on

high doses of parenteral antibiotics for as long as possible 12 .” Muller and Coventry described

similar techniques with Coventry advocating “closure over tubes” to encourage drainage of

purulent material 11 . With further reports of experience with the technique factors thought to

improve treatment success included onset of PJI within the first four weeks following

implantation 13 ; debridement initiated early after the onset of symptoms of infection 14 ; the

absence of a sinus tract or radiographic signs implant loosening at the time of debridement 15 ;

and the type, duration, and route of antimicrobial therapy 16–19 .

Aims

The aims of the study were to analyse and summarise the reported series to establish

the overall proportions of success following DAIR in the management of periprosthetic hip

infections and secondarily to identify risk factors for failure.

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Methodology

Search strategy.

A computerized literature search was conducted in the MEDLINE, and Science

Citation Index Expanded (ISI Web of Science) databases for relevant reports from their

inception to May 2016. The following algorithm was applied to both the Medical Subject

Heading (MeSH) and the full text: (1) “total hip replacement” OR “total hip arthroplasty” OR

“arthroplasty” OR “hip joint” OR “joint prosthesis” OR “hip prosthesis” AND “infection” (2)

“debridement” OR “implant retention” or “treatment outcome” (MeSH terms). The

bibliographies of the retrieved studies and other relevant publications, including reviews and

meta-analyses, were examined for additional articles. No language restrictions were imposed.

Study selection criteria.

Articles were included if 1) they contained raw outcome data from a group

undergoing DAIR for the management of infected THRs; 2) infection was defined as per

established criteria4,14,20; 3) reported the primary outcome of interest; and 4) were

observational studies (either prospective or retrospective in design). No distinction was made

of type or size of implant used or whether the prosthesis was cemented or uncemented.

The primary outcome measure of interest was treatment success. Successful treatment

was defined as per international multidisciplinary consensus 21 1) absence of

recurrent/persistent periprosthetic infection; 2) no requirement for long-term antibiotic

suppression; 3) no requirement for revision surgery; 4) no excision of prosthesis, and 5) no

mortality due to periprosthetic infection-related sepsis.

Data collection

Data was extracted by a single reviewer (S-TJT) and checked by the project

supervisors (PG and AHRW). Any discrepancies were discussed, if a consensus was not

reached, the study was excluded. Data was extracted for: first author’s last name; study

design; study characteristics (including year and country of study); sample size; proportion

completing follow-up; duration of follow-up; subject characteristics (sex distribution and

mean age at time of surgery); timing of debridement surgery (median duration from primary

surgery and from symptom onset); number of DAIR procedures performed; modular

component exchange at time of debridement; and proportion of success. Study quality was

assessed independently and scored by a single reviewer using the Newcastle–Ottawa Scale22

(NOS). The NOS is a validated tool for assessing the quality of non-randomized studies,

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including cohort and case–control studies. The maximum score a study can achieve is nine 22.

Only those considered of adequate quality (≥7) were included in the analyses. The

Newcastle-Ottawa scores for each included study are presented in Table 1. The mean score

was 7.90 (±0.55).

Meta-analysis

Meta-analysis of observational studies carries many inherent potential challenges

related to biases and diversity in the original studies, performing such analyses is an accepted

technique provided it is conducted according to well established guidelines. This review of

observational studies was conducted in accordance to the meta-analysis of observational

studies in epidemiology (MOOSE) guidelines 34 . Data were analysed using SPSS statistical

software version 21.0 (SPSS Inc., Chicago, Illinois) and Microsoft Excel 2016 (Microsoft,

Redmond, Washington, USA). For continuous outcomes the weighted mean difference was

calculated along with the 95% confidence intervals (CI). Subsequent comparisons were

performed using Student’s T-test and univariate analysis of variance (ANOVA) for

parametric data and Mann-Whitney U test for non-parametric data.

Results

The search strategy revealed 1370 clinical trials. Thirty-nine case-control and cohort

trials, reporting on the outcome of 1296 patients, were suitable for inclusion. Table 1 . details

the study characteristics for each included trial. Review and observational studies were

excluded due to ‘no raw data reported’ (n=9) and ‘mixed cohort (prosthesis or treatment)’

(n=33) (Fig.1).

Overall proportion of success following DAIR

The overall proportion of success following DAIR in the management of infected

THRs was 64.7% (836/1296 patients) (Table. 1).

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Author Year Country Study period (start)

Study period (end)

Average time from primary

surgery to debridement

Average time from onset of symptoms to debridement

Infection criteria

Sample size (n)

Mean age

(years)

Average follow-up (months)

Success (n)

Success (%)

Culture results

Total duration of antibi-otic ther-

apy (weeks)

Removable components exchanged at debridement

More than 75% had >1 debridement

NOS* Selection

score

NOS* Com-parability

score

NOS* Ex-posure score

NOS (total)

Burton et al12 1977 US 1971 1975 >4weeks >7days Positive culture specimens

4 35 14 2 50 Mixed Not re-ported

No No 3 2 2 7

Morscher et al23 1990 Switzerland 1980 1986 Not reported Not reported Positive culture specimens

6 72 37 4 67 Mixed Not re-ported

No No 3 2 3 8

Collins et al24 1991 US 1972 1987 Not reported Not reported Positive culture specimens

34 59 48 15 44 Mixed Not re-ported

No Yes 2 2 2 6

Tsukayama et al13 1996 US 1980 1991 <4weeks >7days Tsukayama criteria

41 63 46 28 68 Mixed 6 Yes No 3 2 3 8

Crockarell et al25 1998 US 1975 1991 Not reported >7days Tsukayama criteria

42 58 72 9 21 Not re-ported

Not re-ported

No Not reported 3 2 3 8

Krasin et al26 2001 Israel 1995 1997 >4weeks >7days Positive culture specimens

7 68 30 2 29 Gram +ve

6 No No 3 2 3 8

Kilgus et al6 2002 US 1997 2001 Not reported Not reported Tsukayama criteria

35 65 27 5 14 Mixed Not re-ported

Yes Yes 2 2 3 7

Meehan et al27 2003 US 1969 1998 >4weeks <7days Mayo cri-teria

6 67 60 4 67 Gram +ve

Not re-ported

Yes Yes 3 2 3 8

Soriano et al28 2003 Spain 1997 2000 >4weeks Not reported Positive culture specimens

10 69 22 9 90 Mixed 6 No No 3 2 3 8

Giulieri et al29 2004 Switzerland 1984 2001 >4weeks Not reported Positive culture specimens

11 72 28 7 64 Mixed 100 No Not reported 3 3 3 9

Theis et al30 2007 NZ 1990 2000 >4weeks <7days Tsukayama criteria

36 74 56 19 53 Gram +ve

Not re-ported

No No 3 2 3 8

Aboltins et al31 2007 Australia 1998 2003 >4weeks >7days US CDC criteria

13 70 44 12 92 Gram +ve

72 Yes Not reported 3 2 3 8

Parvizi et al32 2009 USA 1999 2006 Not reported >7days Parvizi cri-teria

24 65 Minimum 24 months

8 33 Gram +ve

Not re-ported

No Not reported 4 2 3 9

Byren et al33 2009 UK 1998 2003 >4weeks <7days Positive culture specimens

52 70 28 45 87 Mixed 52 Yes No 3 2 3 8

Tintle et al8 2009 USA 2002 2004 <4weeks <7days US CDC criteria

3 56 39 3 100 Mixed 6 Yes Yes 3 2 3 8

Azzam et al34 2010 USA 1997 2005 >4weeks >7days Parvizi cri-teria

53 65 68 24 45 Mixed Not re-ported

Yes Not reported 3 2 3 8

Estes et al7 2010 USA 2002 2009 >4weeks <7days Parvizi cri-teria

4 65 58 4 0 Mixed Not re-ported

Yes Yes 3 2 3 8

Aboltins et al35 2011 Australia 1998 2007 <4weeks <7days Mayo cri-teria

15 75 28 13 87 Gram -ve

75 Yes Yes 3 2 3 8

Koyonos et al36 2011 USA 1996 2007 Not reported Not reported Parvizi cri-teria

60 64 54 18 30 Mixed Not re-ported

Not reported Not reported 3 2 3 8

Vilchez et al37 2011 Spain 2000 2007 <4weeks <7days Positive culture specimens

18 70 25 16 89 Gram +ve

14 Yes No 3 2 3 8

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Engesæter et al38 2011 Norway 1987 2009 >4weeks Not reported Registry coding

180 72 Not repor-ted (Re-

gistry data)

146 81 Not re-ported

Not re-ported

Yes No 3 2 3 8

Cobo et al39 2011 Spain 2004 2006 <4weeks >7days Tsukayama criteria

57 77 26 30 53 Mixed 12 Yes No 2 2 3 7

Klouche et al40 2011 France 2002 2008 Not reported <7days Tsukayama criteria

12 69 30 3 25 Mixed 12 Yes No 3 2 3 8

Buller et al41 2012 USA 1996 2010 >4weeks >7days Mayo cri-teria

62 65 34 35 56 Mixed 6 Yes Not reported 3 2 3 8

Sukeik et al42 2012 United King-dom

1999 2006 <4weeks >7days Sukeik cri-teria

26 70 79 20 77 Gram +ve

6 Yes No 3 2 3 8

Choi et al43 2012 USA/Switzerland

1999 2007 <4weeks Not reported Tsukayama criteria

28 65 Not repor-ted

19 68 Gram +ve

6 Yes No 3 2 2 7

Perez-Cardona et al9

2012 Spain 2008 2010 <4weeks Not reported Tsukayama criteria

5 84 14.6 5 100 Not re-ported

11 No No 3 2 3 8

Westberg et al44 2012 Sweden 1998 2005 <4weeks Not reported Tsukayama criteria

38 75 48 27 71 Mixed 7 Yes No 3 2 3 8

Kuiper et al45 2013 Netherlands 2004 2009 >4weeks Not reported Crockarell criteria

34 73 35 25 74 Mixed 18 No Yes 3 2 3 8

Kuiper et al46 2013 Netherlands 2004 2009 <4weeks <7days Crockarell criteria

62 70 35 38 71 Mixed Not re-ported

Yes Not reported 3 2 2 7

Geurts et al47 2013 Netherlands 1982 2010 <4weeks Not reported Mayo cri-teria

69 69 27 57 83 Gram +ve

13 No Yes 3 2 3 8

Peel et al48 2013 Australia 2000 2010 <4weeks <7days Mayo cri-teria

28 73 34 20 71 Gram +ve

Not re-ported

Yes Yes 3 2 3 8

Merollini et al49 2013 Australia 2006 2009 >4weeks Not reported US CDC criteria

68 72 Not repor-ted

41 60 Not re-ported

Not re-ported

No Not reported 4 2 3 9

Aboltins et al50 2013 Australia 2006 2009 <4weeks <7days US CDC criteria

19 69 24 17 89 Mixed 52 No Yes 3 2 3 8

Konigsberg et al51 2014 USA 1995 2006 Not reported <7days Mayo cri-teria

20 60 56 16 80 Mixed 42 Yes No 3 2 3 8

Betz et al52 2014 Switzerland 1996 2012 Not reported Not reported Positive culture specimens

38 78 42 31 82 Gram +ve

12 Yes Yes 2 2 3 7

Moojen et al53 2014 Netherlands 2001 2008 <4weeks Not reported Positive culture specimens

33 74 48 29 88 Gram +ve

12 Yes No 3 2 3 8

Moojen et al54 2015 Netherlands 2001 2008 <4weeks Not reported Positive culture specimens

35 67 Not repor-ted

25 71 Mixed 12 No Yes 3 2 3 8

Veltman et al55 2015 Netherlands 2008 2013 <4weeks Not reported Positive culture specimens

8 80 36 7 88 Gram -ve

12 Yes Yes 3 2 3 8

*Newcastle-Ottawa score22

Table 1. Comparison of studies evaluating the outcomes following debridement, antibiotics, and implant retention (DAIR) in the management of peripros-thetic hip joint infections

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Statistical analysis of influencing factors following DAIR

Studies published before 2004 6,12,13,23–29 were found to have a lower proportion of

success with a mean success of 43.3% (85/196 patients) (95% CI 36.3-50.6). Studies

published after 2004 7,9,30,32,34–55 had a mean proportion of success of 67.2% (693/1032 patients)

(95% CI 64.2-70.0). This difference was found to reach statistical significance (p<0.0001).

Studies published after 2004 but had treatment periods that ended prior to and including 2004

were excluded 8,31,33 from this analysis. A similar pattern was seen if studies were grouped by

treatment period. For studies where all patients were treated prior to 2004 6,12,13,23–31,33 the mean

proportion of success was 54.2% (161/297) (95% CI 48.3-60.0) compared with 67.7%

(674/996 patients) (95% CI 64.7-70.6) in studies which included patients treated after

2004 7,9,32,34–55. Again this difference was found to be statistically significant (p<0.0001). One

study 8 which had a treatment period from 2002-2004 was excluded from this analysis.

Overall there was a non-statistically significant trend of increasing proportions of success in

last fifteen years ( Fig. 2 ).

The time from onset of symptoms to surgical debridement was also found to be

associated with a difference in the proportion of success. A bubble plot demonstrated a non-

linear relationship between time from onset of symptoms to surgical debridement and

treatment success. A decline in treatment success was noted in studies that had a median time

from symptom onset to surgical debridement of greater than seven days (Fig.3). In the

studies where the median time from onset of symptoms to surgical debridement was more

than seven days 12,25,26,32,34,39,41,42 the pooled proportion of success was 51.8% (170/329 patients)

(95% CI 46.1-57.2). In studies where the median time from onset of symptoms to surgical

debridement was less than seven days 7,8,27,30,33,35,40,46,48,50,51,56 the pooled proportion of success

was 72.0% (198/275 patients) (95% CI 66.3-77.2), which was found to be significantly

different (p<0.0001).

Alternatively, in studies where the median time from primary surgery to surgical

debridement was less than four weeks 8,9,13,35,37,39,42–44,46–48,50,53–55 the mean proportion of success

was 73.0% (354/485 patients) (95% CI 68.8-76.9). The pooled proportion of success where

the median time from primary surgery to surgical debridement was more than four

weeks 7,12,26–31,33,34,38,41,45,49 was 69.4% (375/540 patients) (95% CI 65.4-73.3), this difference

was not found to be statistically significant (p=0.215).

In the studies where <25% of patients had multiple debridements 9,12,13,23,26,28,30,33,37–40,42–

44,51,53 the proportion of success was 73.3% (420/573 patients) (95% CI 69.5-76.9). This was a

higher proportion of success than the studies where the majority of patients (>75%) had

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multiple debridements 6–8,24,27,35,45,47,48,50,52,54,55 (68.9% (226/328 patients), 95% CI 63.6-73.9).

However this difference was not found to reach statistical significance (p=0.167).

In studies where all patients underwent exchange of modular components (e.g.

femoral head or acetabular liner) at the time of surgical debridement 6–8,13,31,33,35,37–40,42–

44,48,51,52,54,55 the mean proportion of success was 74.0.7% (471/637) (95% CI 70.3-77.3). This

was higher than in those studies where no component exchange took place 9,12,23–26,28–

30,32,36,45,47,49,50,54 (60.7% (245/404), 95% CI 55.7-65.4), which was found to be statistically

significant (p<0.0001).

Discussion

This review found an overall proportion of success 64.7% associated with DAIR

treatment of infected THRs. An earlier and smaller meta-analysis by Romano et al (2012)

reported a lower proportion of success with DAIR, a pooled average success of 55.9% and

52.0% after a single or multiple debridement and irrigation procedures, respectively57.

However the meta-analysis conducted by Romano et al58 included mixed cohorts of infected

total hip and knee replacements treated with DAIR between 1970 and 2011. Only one study

was included that reported the outcome of infected THRs undergoing DAIR, Klouche et al40,

in which 75% of DAIR were successful. A recent case-control study from Oxford reported a

68% success following initial DAIR 58 with a similar complication rate and ability to eradicate

infection as two-stage revision. Overall there is a wide range, 14%6-100%7–9, of reported

success following DAIR in the management of infected THR. The proportion of success

appeared to improve with time ( p<0.0001 ) . In 2004 Zimmerli et al 3 and Darouiche 59

published two highly influential reviews in the New England Journal of Medicine

summarising the management of periprosthetic joint infections. These two papers are the two

most cited articles on the management of PJI. This was found using the following topic

search terms; “Prosthetic joint infection,” “Periprosthetic joint infection,” “Infection” (with

refinement using subject field “Orthopedics”), and “Prosthetic infection” in the Science

Citation Index Expanded database on the Web of knowledge website. The results were

further cross checked using Google Scholar and a cited reference search of Institute for

Scientific Information (ISI) listed Orthopaedic journals (n=79) as per the methodology

described by Lefaivre et al 60. Within the Zimmerli et al review a treatment algorithm was

proposed. We hypothesise that there may have been a learning effect amongst surgeons after

2004 as the indications for DAIR and the risk factors associated with its failure become better

defined. Equally this trend could be a result of publication bias as only studies reporting

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improved success proportions following DAIR were being submitted to and accepted by

journals.

Factors which have been postulated to influence the outcome of DAIR in the

management of infected joint replacement include the timing of debridement14,27,61, number of

debridements53,54, exchange of removal components4,62, responsible micro-organism33,35,48,63–67,

and duration of antibiotic therapy9,39,40,44,52–55.

In this review, the timing of debridement was found to have an influence on the

proportion of success following DAIR. There was a statistically significantly greater success

when debridement took place at a median time of less than seven days from the onset of

infective symptoms (72.0% vs 51.8%, p<0.0001) compared with debridement being

performed at a median time after one week. This relationship was also demonstrated in

Figure. 4. There was a notable outlier with a treatment success of 77% despite the median

time to surgical debridement being 15 days42. In this series 16/26 infections were caused by

low virulence organisms such as Coagulase-negative Staphylococcus, Acinetobacter,

Propionibacterium spp, and Corynebacterium spp which have been found to be more

common in seronegative infections68. This study is of particular interest as, the high

proportion of low virulence infections may have been a factor in the relatively high treatment

success despite the increased time to surgical debridement, suggesting that late DAIR

procedures may still have a high chance of success in patients infected with these organisms.

However, further data is needed to confirm this. One study was excluded from the analysis as

patients were treated with median time of twelve months of post-debridement antibiotic

therapy31 which differed vastly from the included studies in this analysis. Studies from the

Mayo clinic 14,27 found that duration of symptoms and time from implantation influenced

proportions of success following DAIR. Brandt et al 14 reported that if debridement took place

more than two days after the onset of symptoms there was a four-fold increase in treatment

failure. Other centres have reported similar findings, Tattevin et al 69 reported a 100%

proportion of success when debridement was performed within five days of symptom onset.

A recent case-control study conducted by Grammatopoulos et al also reported an improved

ten-year THR survival (87% vs 65%) with DAIR performed less than one week between

symptoms and onset of surgery 58. The importance of the timing of debridement is thought to

be related to the “race to the surface,” as described by Gristina and Costerton70, and

subsequent maturation of the biofilm. Complete maturation of the biofilm is thought to occur

within two to four days of bacterial attachment71,72. It is thought that once maturation has

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taken place irrigation is largely ineffective with re-establishment of the biofilm on the

retained prosthesis within 24 hours73.

A similar relationship has previously been reported regarding the timing of

debridement from initial implantation. Hartman et al61 found that that proportions of success

following DAIR in the management of infected total knee replacements were statistically

higher if debridement occurred within four weeks of implantation (63.6% vs 27.3%). A cut-

off at four weeks has been incorporated into established treatment protocols4. In this meta-

analysis there was a higher proportion of success when the mean time from primary surgery

to surgical debridement in total hip replacements was less than four weeks (73.0% vs 69.4%)

compared to those when debridement was performed after four weeks. However this

difference was not statistically significant (p=0.215). Fehring et al also found that

debridement within 30 days of implantation was not associated with improved proportion of

success (54% vs 24%, p=0.075)73.

Previously there has been debate as to whether single surgical debridement was

sufficient or whether multiple repeat procedures were necessary for optimal treatment.

Moojen et al reported a retrospective comparative study between two different treatment

protocols. Patients in the first protocol received a single surgical debridement and only

additional surgery if infectious symptoms persisted. Patients adhering to the second protocol

always received multiple surgical debridements. There was no statistical difference in

successful outcomes between the two groups (88% vs 71%, p=0.09)53. In this meta-analysis a

similar result was found when comparing studies where >75% patients had multiple

debridements with those where <25% had multiple debridements (68.9% vs 73.3%, p=0.167).

This may be a reflection that those in studies undergoing multiple debridements were

associated with more virulent organisms or had poor host responses rather than the futility of

multiple debridements.

Exchange of modular components at the time of debridement is recommended in the

most commonly used guidelines and treatment algorithms62,74. In this review we found a

statistical effect on outcome following DAIR with exchange of modular components (60.7%

vs 74.0%, p<0.0001). A similar effect was found in a recent case-control study with exchange

of modular components at debridement associated with a 90% ten year THR survival58.

This study was conducted in accordance with established epidemiological meta-

analyses guidelines (MOOSE)75.All included studies have been shown objectively to be of

sufficient quality through the NOS criteria22. The study was limited by the quality and

quantity of the available data. The heterogeneity of research methodologies, surgical

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techniques and treatment protocols, expertise of the treatment centres, patient populations,

and reported outcomes along with the long study period of the cohorts could produce

confounding factors. These confounding factors would need to be taken into account when

interpreting the results of this review. In the analysis of influencing factors summary data of

study outcomes rather than individual outcomes has been used, as in many studies data at an

individual level was not available. The findings produced may not necessarily hold if the

same analysis was performed using individual patient outcomes for each influencing factor.

There is a need for the global use of harmonised observational research methodologies, such

as The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)

statement: guidelines for reporting observational studies 76 . Another would be the creation of

“core outcome sets 77–79 ” for this particular area of orthopaedic research (Table 2). These have

been established in other medical specialties such as rheumatology80 in an attempt to

standardise research and ease interpretation of the literature. Finally further research into this

area of PJI management using more robust research methodologies and clinically relevant

outcomes, such as a randomised control trial and patient reported-outcome scores

respectively, are also recommended.

Table 2. Suggested core outcome set in the reporting of DAIR procedures.

Host Primary surgery

Surgery Microbiology

Antibiotic therapy

Outcome

Age Prosthesis-type (Cemented vs uncemented vs hybrid)

Time from onset of symptoms to initial debridement

Organism Duration Follow-up duration

Host status (Local and systemic factors. Adpoted from Cierny and DiPasquale81)

Time from primary surgery to initial debridement

Antimicrobial sensitivity

Delivery (local and/or systemic)

Criteria for success1. Absence of

recurrent/persistent periprosthetic infection;

2. No requirement for long-term antibiotic suppression;

3. No requirement for revision surgery;

4. No excision of prosthesis,

5. No mortality due to periprosthetic infection-related sepsis

Surgical approach

Exchange of modular components

Patient-reported outcome scores

234

235

236

237

238

239

240

241

242

243

244

245

246

247

248

249

250

251

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In conclusion, the reported outcomes following DAIR appear to be improving with

time as indications are refined and risk factors identified. The most influential determinants

of outcome are timing of debridement from onset of symptoms and exchange of modular

components at the time of initial debridement, and to a lesser extent the time from the

original primary surgery. Surgeons should consider a DAIR procedure with exchange of

modular components for acutely infected THR when presenting within seven days from the

onset of symptoms.

Word count including bibliography: 5254 (excluding bibliography 2900)

Bibliography

1. No authors. 13th Annual Report National Joint Registry for England, Wales, Northern Ireland and the Isle of Man. 2016.

2. No authors. Scottish Arthroplasty Project Biennial report 2016. 2016. 3. Zimmerli W, Trampuz A, Ochsner PE. Prosthetic-joint infections. N Engl J Med. 2004

Oct 14;351(16):1645–54. 4. Parvizi J, Adeli B, Zmistowski B, Restrepo C, Greenwald AS. Management of

Periprosthetic Joint Infection: The Current Knowledge. J Bone Jt Surg. 2012 Jul 18;94(14):e104 1.

5. Lehner B, Witte D, Suda AJ, Weiss S. [Revision strategy for periprosthetic infection]. Der Orthopade. 2009 Aug;38(8):681–8.

6. Kilgus DJ, Howe DJ, Strang A. Results of periprosthetic hip and knee infections caused by resistant bacteria. Clin Orthop Relat Res. 2002 Nov;(404):116–24.

7. Estes CS, Beauchamp CP, Clarke HD, Spangehl MJ. A two-stage retention débridement protocol for acute periprosthetic joint infections. Clin Orthop Relat Res . 2010 Aug 12;468(8):2029–38.

8. Tintle SM, Forsberg JA, Potter BK, Islinger RB, Andersen RC. Prosthesis retention, serial debridement, and antibiotic bead use for the treatment of infection following total joint arthroplasty. Orthopedics. 2009 Feb;32(2):87.

9. Corona Pérez-Cardona PS, Barro Ojeda V, Rodriguez Pardo D, Pigrau Serrallach C, Guerra Farfán E, Amat Mateu C, et al. Clinical experience with daptomycin for the treatment of patients with knee and hip periprosthetic joint infections. J Antimicrob Chemother. 2012 Jul;67(7):1749–54.

10. Muller ME. Preservation of septic total hip replacement versus girdlestone operation. In: The Hip: Proceedings of the Second Open Scientific Meeting of The Hip Society. CV Mosby, St. Louis; 1974.

11. Coventry MB. Treatment of infections occurring in total hip surgery. Orthop Clin North Am. 1975 Oct;6(4):991–1003.

12. Burton DS, Schurman DJ. Salvage of infected total joint replacements. Arch Surg. 1977 May;112(5):574–8.

13. Tsukayama DT, Estrada R, Gustilo RB. Infection after total hip arthroplasty. A study of the treatment of one hundred and six infections. J Bone Joint Surg Am. 1996

252

253

254

255

256

257

258

259

260

261

262

263264265266267268269270271272273274275276277278279280281282283284285286287288289290291292293

Page 13:  · Web viewOutcomes following debridement, antibiotics and implant retention in the management of periprosthetic hip joint infections: a review of cohort studies. Abstract. Aims

Apr;78(4):512–23. 14. Brandt CM, Sistrunk WW, Duffy MC, Hanssen AD, Steckelberg JM, Ilstrup DM, et al.

Staphylococcus aureus prosthetic joint infection treated with debridement and prosthesis retention. Clin Infect Dis. 1997 May 1;24(5):914–9.

15. Brandt CM, Sistrunk WW, Duffy MC, Hanssen AD, Steckelberg JM, Ilstrup DM, et al. Staphylococcus aureus Prosthetic Joint Infection Treated with Debridement and Prosthesis. Source Clin Infect Dis. 1997;24(5):914–9.

16. Drancourt M, Stein A, Argenson JN, Zannier A, Curvale G, Raoult D. Oral rifampin plus ofloxacin for treatment of Staphylococcus-infected orthopedic implants. Antimicrob Agents Chemother. 1993 Jun;37(6):1214–8.

17. Perry CR, Hulsey RE, Mann FA, Miller GA, Pearson RL. Treatment of acutely infected arthroplasties with incision, drainage, and local antibiotics delivered via an implantable pump. Clin Orthop Relat Res. 1992 Aug;(281):216–23.

18. Widmer AF, Gaechter A, Ochsner PE, Zimmerli W. Antimicrobial Treatment of Orthopedic Implant-related Infections with Rifampin Combinations. Clin Infect Dis. 1992;

19. Zimmerli W, Widmer AF, Blatter M, Frei R, Ochsner PE. Role of Rifampin for Treatment of Orthopedic Implant–Related Staphylococcal Infections A Randomized Controlled Trial. JAMA (Journal Am Med Assoc. 1998;279(19):1537–41.

20. Marculescu CE, Berbari EF, Hanssen AD, Steckelberg JM, Harmsen SW, Mandrekar JN, et al. Outcome of prosthetic joint infections treated with debridement and retention of components. Clin Infect Dis. 2006 Mar 15;42(4):471–8.

21. Diaz-Ledezma C, Higuera CA, Parvizi J. Success after treatment of periprosthetic joint infection: a Delphi-based international multidisciplinary consensus. Clin Orthop Relat Res. 2013 Jul;471(7):2374–82.

22. Wells G, Shea B, O’Connell D, Peterson J, Welch V, Tugwell P. The Newcastle-Ottawa Scale (NOS) for assessing the quality of non-randomized studies in meta-analyses. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. 2016.

23. Morscher E, Babst R, Jenny H. Treatment of infected joint arthroplasty. Int Orthop. 1990 Jun;14(2):161–5.

24. Collins DN, McKenzie JM. Infections at the site of a hip implant. Successful and unsuccessful management. Clin Orthop Relat Res. 1991 Aug;(269):9–15.

25. Crockarell JR, Hanssen AD, Osmon DR, Morrey BF. Treatment of infection with débridement and retention of the components following hip arthroplasty. J Bone Joint Surg Am. 1998 Sep;80(9):1306–13.

26. Krasin E, Goldwirth M, Hemo Y, Gold A, Herling G, Otremski I. Could irrigation, debridement and antibiotic therapy cure an infection of a total hip arthroplasty? J Hosp Infect. 2001 Mar;47(3):235–8.

27. Meehan AM, Osmon DR, Duffy MCT, Hanssen AD, Keating MR. Outcome of Penicillin‐Susceptible Streptococcal Prosthetic Joint Infection Treated with Debridement and Retention of the Prosthesis. Clin Infect Dis. 2003 Apr 1;36(7):845–9.

28. Soriano A, García S, Ortega M, Almela M, Gallart X, Vila J, et al. [Treatment of acute infection of total or partial hip arthroplasty with debridement and oral chemotherapy]. Med Clin (Barc). 2003 Jun 21;121(3):81–5.

29. Giulieri SG, Graber P, Ochsner PE, Zimmerli W. Management of infection associated with total hip arthroplasty according to a treatment algorithm. Infection. 2004 Aug;32(4):222–8.

30. Theis J-C, Gambhir S, White J. Factors affecting implant retention in infected joint replacements. ANZ J Surg. 2007 Oct;77(10):877–9.

31. Aboltins CA, Page MA, Buising KL, Jenney AWJ, Daffy JR, Choong PFM, et al.

294295296297298299300301302303304305306307308309310311312313314315316317318319320321322323324325326327328329330331332333334335336337338339340341342343

Page 14:  · Web viewOutcomes following debridement, antibiotics and implant retention in the management of periprosthetic hip joint infections: a review of cohort studies. Abstract. Aims

Treatment of staphylococcal prosthetic joint infections with debridement, prosthesis retention and oral rifampicin and fusidic acid. Clin Microbiol Infect. 2007 Jun;13(6):586–91.

32. Parvizi J, Azzam K, Ghanem E, Austin MS, Rothman RH. Periprosthetic infection due to resistant staphylococci: serious problems on the horizon. Clin Orthop Relat Res. 2009 Jul;467(7):1732–9.

33. Byren I, Bejon P, Atkins BL, Angus B, Masters S, McLardy-Smith P, et al. One hundred and twelve infected arthroplasties treated with “DAIR” (debridement, antibiotics and implant retention): antibiotic duration and outcome. J Antimicrob Chemother. 2009 Jun;63(6):1264–71.

34. Azzam KA, Seeley M, Ghanem E, Austin MS, Purtill JJ, Parvizi J. Irrigation and debridement in the management of prosthetic joint infection: traditional indications revisited. J Arthroplasty. 2010 Oct;25(7):1022–7.

35. Aboltins CA, Dowsey MM, Buising KL, Peel TN, Daffy JR, Choong PFM, et al. Gram-negative prosthetic joint infection treated with debridement, prosthesis retention and antibiotic regimens including a fluoroquinolone. Clin Microbiol Infect. 2011 Jun;17(6):862–7.

36. Koyonos L, Zmistowski B, Della Valle CJ, Parvizi J. Infection control rate of irrigation and débridement for periprosthetic joint infection. Clin Orthop Relat Res. 2011 Nov;469(11):3043–8.

37. Vilchez F, Martínez-Pastor JCC, García-Ramiro S, Bori G, Maculé F, Sierra J, et al. Outcome and predictors of treatment failure in early post-surgical prosthetic joint infections due to Staphylococcus aureus treated with debridement. Clin Microbiol Infect. 2011 Mar;17(3):439–44.

38. Engesæter LB, Dale H, Schrama JC, Hallan G, Lie SA. Surgical procedures in the treatment of 784 infected THAs reported to the Norwegian Arthroplasty Register. Acta Orthop. 2011 Oct;82(5):530–7.

39. Cobo J, Miguel LGS, Euba G, Rodríguez D, García-Lechuz JM, Riera M, et al. Early prosthetic joint infection: outcomes with debridement and implant retention followed by antibiotic therapy. Clin Microbiol Infect. 2011 Nov;17(11):1632–7.

40. Klouche S, Lhotellier L, Mamoudy P. Infected total hip arthroplasty treated by an irrigation-debridement/component retention protocol. A prospective study in a 12-case series with minimum 2 years’ follow-up. Orthop Traumatol Surg Res. 2011 Apr;97(2):134–8.

41. Buller LT, Sabry FY, Easton RW, Klika AK, Barsoum WK. The preoperative prediction of success following irrigation and debridement with polyethylene exchange for hip and knee prosthetic joint infections. J Arthroplasty. 2012 Jun;27(6):857-64-4.

42. Sukeik M, Patel S, Haddad FS. Aggressive early débridement for treatment of acutely infected cemented total hip arthroplasty. Clin Orthop Relat Res. 2012 Nov;470(11):3164–70.

43. Choi H-R, von Knoch F, Kandil AO, Zurakowski D, Moore S, Malchau H. Retention treatment after periprosthetic total hip arthroplasty infection. Int Orthop. 2012 Apr;36(4):723–9.

44. Westberg M, Grøgaard B, Snorrason F. Early prosthetic joint infections treated with debridement and implant retention: 38 primary hip arthroplasties prospectively recorded and followed for median 4 years. Acta Orthop. 2012 Jun;83(3):227–32.

45. Kuiper JWP, Brohet RM, Wassink S, van den Bekerom MPJ, Nolte PA, Vergroesen DA. Implantation of resorbable gentamicin sponges in addition to irrigation and debridement in 34 patients with infection complicating total hip arthroplasty. Hip Int. 2013 Jan;23(2):173–80.

344345346347348349350351352353354355356357358359360361362363364365366367368369370371372373374375376377378379380381382383384385386387388389390391392393

Page 15:  · Web viewOutcomes following debridement, antibiotics and implant retention in the management of periprosthetic hip joint infections: a review of cohort studies. Abstract. Aims

46. Kuiper JWP, Vos SJC, Saouti R, Vergroesen DA, Graat HCA, Debets-Ossenkopp YJ, et al. Prosthetic joint-associated infections treated with DAIR (debridement, antibiotics, irrigation, and retention): analysis of risk factors and local antibiotic carriers in 91 patients. Acta Orthop. 2013 Aug;84(4):380–6.

47. Geurts JAP, Janssen DMC, Kessels AGH, Walenkamp GHIM. Good results in postoperative and hematogenous deep infections of 89 stable total hip and knee replacements with retention of prosthesis and local antibiotics. Acta Orthop. 2013 Dec;84(6):509–16.

48. Peel TN, Buising KL, Dowsey MM, Aboltins CA, Daffy JR, Stanley PA, et al. Outcome of debridement and retention in prosthetic joint infections by methicillin-resistant staphylococci, with special reference to rifampin and fusidic acid combination therapy. Antimicrob Agents Chemother. 2013 Jan;57(1):350–5.

49. Merollini KMD, Crawford RW, Graves N. Surgical treatment approaches and reimbursement costs of surgical site infections post hip arthroplasty in Australia: a retrospective analysis. BMC Health Serv Res. 2013 Jan;13:91.

50. Aboltins C, Dowsey MM, Peel T, Lim WK, Parikh S, Stanley P, et al. Early prosthetic hip joint infection treated with debridement, prosthesis retention and biofilm-active antibiotics: functional outcomes, quality of life and complications. Intern Med J. 2013 Jul;43(7):810–5.

51. Konigsberg BS, Della Valle CJ, Ting NT, Qiu F, Sporer SM. Acute hematogenous infection following total hip and knee arthroplasty. J Arthroplasty. 2014 Mar;29(3):469–72.

52. Betz M, Abrassart S, Vaudaux P, Gjika E, Schindler M, Billières J, et al. Increased risk of joint failure in hip prostheses infected with Staphylococcus aureus treated with debridement, antibiotics and implant retention compared to Streptococcus. Int Orthop. 2015 Sep 4;39(3):397–401.

53. Moojen DJF, Zwiers JH, Scholtes VAB, Verheyen CCPM, Poolman RW. Similar success rates for single and multiple debridement surgery for acute hip arthroplasty infection. Acta Orthop. 2014 Aug;85(4):383–8.

54. Moojen DJF. Similar success rates for single and multiple debridement surgery for acute hip arthroplasty infection--reply. Acta Orthop. 2015 Feb;86(1):142.

55. Veltman ES, Vos FJ, Meis JF, Goosen JHM. Debridement, antibiotics and implant retention in early postoperative infection with Pseudomonas aeruginosa. J Infect. 2015 Mar;70(3):307–9.

56. Vilchez F, Martínez-Pastor JC, García-Ramiro S, Bori G, Tornero E, García E, et al. Efficacy of debridement in hematogenous and early post-surgical prosthetic joint infections. Int J Artif Organs. 2011 Sep;34(9):863–9.

57. Romanò CL, Manzi G, Logoluso N, Romanò D. Value of debridement and irrigation for the treatment of peri-prosthetic infections. A systematic review. Hip Int. 2012 Jan;22 Suppl 8:S19-24.

58. Grammatopoulos G, Bolduc M-E, Atkins BL, Kendrick BJL, Mclardy-Smith P, Murray DW, et al. Functional outcome of debridement, antibiotics and implant retention in periprosthetic joint infection involving the hip. A case-control study. Bone Jt J. 2017;99:614–22.

59. Darouiche RO. Treatment of Infections Associated with Surgical Implants. N Engl J Med. 2004 Apr;350(14):1422–9.

60. Lefaivre KA, Shadgan B, O’Brien PJ. 100 Most cited articles in orthopaedic surgery. Clin Orthop Relat Res. 2011;469(5):1487–97.

61. Hartman MB, Fehring TK, Jordan L, Norton HJ. Periprosthetic knee sepsis: The role of irrigation and debridement. Clin Orthop Relat Res. 1991;(273):113–8.

394395396397398399400401402403404405406407408409410411412413414415416417418419420421422423424425426427428429430431432433434435436437438439440441442443

Page 16:  · Web viewOutcomes following debridement, antibiotics and implant retention in the management of periprosthetic hip joint infections: a review of cohort studies. Abstract. Aims

62. Zimmerli W, Ochsner PE. Management of infection associated with prosthetic joints. Infection. 2003 Mar;31(2):99–108.

63. Hsieh P-H, Lee MS, Hsu K-Y, Chang Y-H, Shih H-N, Ueng SW. Gram-negative prosthetic joint infections: risk factors and outcome of treatment. Clin Infect Dis. 2009 Oct 1;49(7):1036–43.

64. Jaén N, Martínez-Pastor JC, Muñoz-Mahamud E, García-Ramiro S, Bosch J, Mensa J, et al. Long-term outcome of acute prosthetic joint infections due to gram-negative bacilli treated with retention of prosthesis. Rev Esp Quimioter. 2012 Sep;25(3):194–8.

65. Martínez-Pastor JC, Muñoz-Mahamud E, Vilchez F, García-Ramiro S, Bori G, Sierra J, et al. Outcome of acute prosthetic joint infections due to gram-negative bacilli treated with open debridement and retention of the prosthesis. Antimicrob Agents Chemother. 2009 Nov;53(11):4772–7.

66. Zmistowski B, Fedorka CJ, Sheehan E, Deirmengian G, Austin MS, Parvizi J. Prosthetic joint infection caused by gram-negative organisms. J Arthroplasty. 2011 Sep;26(6 Suppl):104–8.

67. Lora-Tamayo J, Murillo O, Iribarren JA, Soriano A, Sánchez-Somolinos M, Baraia-Etxaburu JM, et al. A large multicenter study of methicillin-susceptible and methicillin-resistant Staphylococcus aureus prosthetic joint infections managed with implant retention. Clin Infect Dis. 2013 Jan;56(2):182–94.

68. McArthur BA, Abdel MP, Taunton MJ, Osmon DR, Hanssen AD. Seronegative infections in hip and knee arthroplasty: periprosthetic infections with normal erythrocyte sedimentation rate and C-reactive protein level. Bone Joint J. 2015 Jul 1;97–B(7):939–44.

69. Tattevin P, Crémieux AC, Pottier P, Huten D, Carbon C. Prosthetic joint infection: when can prosthesis salvage be considered? Clin Infect Dis. 1999 Aug;29(2):292–5.

70. Gristina AG, Costerton JW. Bacterial adherence and the glycocalyx and their role in musculoskeletal infection. Orthop Clin North Am. 1984 Jul;15(3):517–35.

71. Costerton JW, Stewart PS, Greenberg EP. Bacterial biofilms: a common cause of persistent infections. Science. 1999 May 21;284(5418):1318–22.

72. Donlan RM, Costerton JW. Biofilms: survival mechanisms of clinically relevant microorganisms. Clin Microbiol Rev. 2002 Apr;15(2):167–93.

73. Fehring TK, Odum SM, Berend KR, Jiranek WA, Parvizi J, Bozic KJ, et al. Failure of irrigation and débridement for early postoperative periprosthetic infection. Clin Orthop Relat Res. 2013 Jan;471(1):250–7.

74. Parvizi J, Della Valle CJ. AAOS Clinical Practice Guideline: diagnosis and treatment of periprosthetic joint infections of the hip and knee. J Am Acad Orthop Surg. 2010 Dec;18(12):771–2.

75. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of Observational Studies in Epidemiology. A Proposal for Reporting. JAMA. 2011;283(15):2008–12.

76. von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: Guidelines for reporting of observational studies. Internist. 2008;49:688–93.

77. Koroshetz W. A core set of trial outcomes for every medical discipline? BMJ. 2015;350.

78. Bellamy N, Kirwan J, Boers M, Brooks P, Strand V, Tugwell P, et al. Recommendations for a core set of outcome measures for future phase III clinical trials in knee, hip, and hand osteoarthritis. Consensus development at OMERACT III. J Rheumatol. 1997 Apr;24(4):799–802.

444445446447448449450451452453454455456457458459460461462463464465466467468469470471472473474475476477478479480481482483484485486487488489490491492493

Page 17:  · Web viewOutcomes following debridement, antibiotics and implant retention in the management of periprosthetic hip joint infections: a review of cohort studies. Abstract. Aims

79. Feinstein A. The theory and evaluation on sensibility. In: Clinimetrics. New Haven: Yale University Press; 1987. p. 141–66.

80. No authors. http://www.omeract.org/. 2016. 81. Cierny G, DiPasquale D. Periprosthetic total joint infections: staging, treatment, and

outcomes. Clin Orthop Relat Res. 2002 Oct;(403):23–8.

494495496497498