The Open Orthopaedics Journal




ISSN: 1874-3250 ― Volume 13, 2019
RESEARCH ARTICLE

Intraoperative Cultures in Reimplantation of a Two-Stage Protocol: Only 1 vs. At Least 2 Positive Microbiological Results



José Cordero-Ampuero1, 2, Ana Ortega-Columbrans1, Eduardo Garcia-Rey2, 3, Eduardo Garcia-Cimbrelo3, *
1 Department of Orthopaedic Surgery and Traumatology, University Hospital La Princesa, Madrid, Spain
2 Medicine School, Universidad Autónoma de Madrid, Madrid, Spain
3 Department of Orthopaedic Surgery and Traumatology, University Hospital La Paz-IDIPaz, Madrid, Spain

Abstract

Background:

The main reason for using a two-stage exchange in Prosthetic Joint Infection (PJI) is that bacteria are completely eradicated in reimplantation surgery. However, reports of a positive culture in the second surgery are growing. The number of positive intraoperative cultures and their influence on final results is not well-established.

Objectives:

To compare epidemiological characteristics, infection recurrence and clinical evolution of patients with only one vs. at least two positive cultures based on our series of cases with positive cultures in reimplantation surgery.

Material and Methods:

Retrospective study of 55 patients was conducted prospectively. They were diagnosed with chronic PJI, treated with a two-stage protocol and at least three intraoperative cultures were obtained in the second stage. These cultures were negative in 28 patients. Fourteen patients showed two or more cultures with the same microorganism and they were denominated patients with positive cultures. Thirteen patients showed only one positive culture, and they were considered contaminated. Both groups of patients (positive cultures and contaminated ones) received the second cycle of oral antibiotics for 6 months. Functional results were evaluated with the Harris Hip Score (hips) or Knee Society Clinical Rating Score (KSCRS) (knees).

Results:

There were no significant differences between patients with positive or contaminated cultures for age (p=0.420) and sex (p=0.385). The knee was involved in 13/14 positive and in only 6/13 contaminated patients (p=0.013). Staphylococcus epidermidis was the predominant isolate, but there were differences between positive (methicillin-resistant in 7/14 patients) and contaminated cultures (methicillin-sensitive in 6/13). There were no differences in the prevalence of polymicrobial cultures (p=0.785) or coincidence with cultures from the first stage (p=0.257). Three infection recurrences have appeared in patients with positive cultures (3/13, 21%) and none in patients with contaminated cultures. There are no differences in HSS or KSCRS when comparing final functional results between groups (p=0.411).

Conclusion:

The prevalence of positive cultures in reimplantation surgery is higher than expected (25%), and more frequent in women and in knee arthroplasties. The most frequently involved microorganism is Staphylococcus epidermidis, but antibiotic sensitivity varies between patients with positive cultures (methicillin-resistant) and those with contaminated cultures (methicillin-sensitive). There were no infection recurrences in patients with contaminated cultures, but those with positive cultures present a risk of over 20%.

Keywords: Prosthetic joint infection, Two-stage exchange arthroplasty, Reimplantation culture, Clinical evolution, Staphylococcus epidermidis, predominant isolate.


Article Information


Identifiers and Pagination:

Year: 2019
Volume: 13
First Page: 159
Last Page: 165
Publisher Id: TOORTHJ-13-159
DOI: 10.2174/1874325001913010159

Article History:

Received Date: 23/12/2018
Revision Received Date: 25/03/2019
Acceptance Date: 20/05/2019
Electronic publication date: 30/06/2019
Collection year: 2019

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© 2019 Cordero-Ampuero et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


* Address correspondence to this author at the Department of Orthopaedic Surgery and Traumatology, University Hospital La Paz-IDIPaz, Madrid, Spain; E-mail: gcimbrelo@yahoo.es





1. INTRODUCTION

Two-stage exchange is the most used treatment for chronic Prosthetic Joint Infection (PJI). The main advantage of a two-stage protocol is that infection is supposedly cured when reimplantation is done. Infection eradication can be evaluated by different diagnostic methods: serological markers [1Cordero-Ampuero J, Esteban J, García-Cimbrelo E. Oral antibiotics are effective for highly resistant hip arthroplasty infections. Clin Orthop Relat Res 2009; 467(9): 2335-42.
[http://dx.doi.org/10.1007/s11999-009-0808-8] [PMID: 19333670]
-6Stockley I, Mockford BJ, Hoad-Reddick A, Norman P. The use of two-stage exchange arthroplasty with depot antibiotics in the absence of long-term antibiotic therapy in infected total hip replacement. J Bone Joint Surg Br 2008; 90(2): 145-8.
[http://dx.doi.org/10.1302/0301-620X.90B2.19855] [PMID: 18256078]
], scintigraphy [4Piriou P, de Loynes B, Garreau de Loubresse C, Judet T. [Use of combined gallium-technetium scintigraphy to determine the interval before second-stage prosthetic reimplantation in hip arthroplasty infection: a consecutive series of 30 cases]. Rev Chir Orthop Repar Appar Mot 2003; 89(4): 287-96.
[PMID: 12844031]
], preoperative aspiration [5Schindler M, Christofilopoulos P, Wyssa B, et al. Poor performance of microbiological sampling in the prediction of recurrent arthroplasty infection. Int Orthop 2011; 35(5): 647-54.
[http://dx.doi.org/10.1007/s00264-010-1014-8] [PMID: 20419507]
, 7Mont MA, Waldman BJ, Hungerford DS. Evaluation of preoperative cultures before second-stage reimplantation of a total knee prosthesis complicated by infection. A comparison-group study. J Bone Joint Surg Am 2000; 82(11): 1552-7.
[http://dx.doi.org/10.2106/00004623-200011000-00006] [PMID: 11097443]
], or intraoperative histology of frozen samples [8Burnett RS, Kelly MA, Hanssen AD, Barrack RL. Technique and timing of two-stage exchange for infection in TKA. Clin Orthop Relat Res 2007; 464(464): 164-78.
[PMID: 17975376]
]. Despite these tests, some patients present positive intraoperative cultures in their second surgery for reimplantation.

Few authors have studied the prevalence of positive cultures in the second surgery, or the epidemiology and final clinical result in these patients [9Cabo J, Euba G, Saborido A, et al. Clinical outcome and microbiological findings using antibiotic-loaded spacers in two-stage revision of prosthetic joint infections. J Infect 2011; 63(1): 23-31.
[http://dx.doi.org/10.1016/j.jinf.2011.04.014] [PMID: 21596440]
-13Sorlí L, Puig L, Torres-Claramunt R, et al. The relationship between microbiology results in the second of a two-stage exchange procedure using cement spacers and the outcome after revision total joint replacement for infection: the use of sonication to aid bacteriological analysis. J Bone Joint Surg Br 2012; 94(2): 249-53.
[http://dx.doi.org/10.1302/0301-620X.94B2.27779] [PMID: 22323695]
]. Moreover, antibiotic-loaded cement spacer is a foreign body and may increase the risk of infection persistence [9Cabo J, Euba G, Saborido A, et al. Clinical outcome and microbiological findings using antibiotic-loaded spacers in two-stage revision of prosthetic joint infections. J Infect 2011; 63(1): 23-31.
[http://dx.doi.org/10.1016/j.jinf.2011.04.014] [PMID: 21596440]
, 11Mariconda M, Ascione T, Balato G, et al. Sonication of antibiotic-loaded cement spacers in a two-stage revision protocol for infected joint arthroplasty. BMC Musculoskelet Disord 2013; 14: 193.
[http://dx.doi.org/10.1186/1471-2474-14-193] [PMID: 24192225]
-13Sorlí L, Puig L, Torres-Claramunt R, et al. The relationship between microbiology results in the second of a two-stage exchange procedure using cement spacers and the outcome after revision total joint replacement for infection: the use of sonication to aid bacteriological analysis. J Bone Joint Surg Br 2012; 94(2): 249-53.
[http://dx.doi.org/10.1302/0301-620X.94B2.27779] [PMID: 22323695]
].

The aims of this study are: 1) To analyze epidemiological characteristics of patients with positive intraoperative cultures in reimplantation surgery; and 2) To compare infective, functional and radiographic results in patients with positive intraoperative cultures vs. those with a single contaminated culture.

2. MATERIALS AND METHODS

2.1. Design

Retrospective study of a case series followed prospectively in the outpatient clinic.

2.2. Inclusion Criteria

  1. Patients diagnosed with PJI according to the Musculoskeletal Infection Society criteria [14Parvizi J, Zmistowski B, Berbari EF, et al. New definition for periprosthetic joint infection: From the Workgroup of the Musculoskeletal Infection Society. Clin Orthop Relat Res 2011; 469(11): 2992-4.
    [http://dx.doi.org/10.1007/s11999-011-2102-9] [PMID: 21938532]
    ].
  2. Late/chronic PJI (more than 3 months after the index surgery) [15Tsukayama 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; 78(4): 512-23.
    [http://dx.doi.org/10.2106/00004623-199604000-00005] [PMID: 8609130]
    ].
  3. Treatment with a two-stage protocol.
  4. At least 3 intraoperative cultures obtained during the second surgery (reimplantation).

2.3. Exclusion Criteria

Patient non-compliance with antibiotic treatment; second stage not performed (patient rejection, worsening of medical condition, and/or unacceptable anesthetic or surgical risks); inadequate follow-up.

2.4. Ethics

All patients included gave written and oral informed consent for the inclusion of their clinical data (not personal ones) for the study. Confidentiality for personal data has been maintained during the entire study. This study was approved by the Local Ethics Committee with the number 3261 on December 14th, 2017.

2.5. First Surgery

All patients received a first stage surgery with removal of all implants and cement, aggressive debridement and irrigation with 12 liters of saline supplemented with 120 ml of iodine (Betadine, Viatris Manufacturing, Mundipharma AG, CH). No spacer was used in any hip, so patients remained in a temporary Girdlestone resection-arthroplasty. Knees were implanted with a static hand-made spacer manufactured with Copal cement (polymethylmetacrylate with gentamicin 1g and clindamycin 1 g, Biomet Merck GmbH, Ried b Kerzers, CH).

2.6. Antibiotic Treatment

After the first stage (removal surgery) patients were treated with a combination of two oral antibiotics for six months [2Cordero-Ampuero J, Esteban J, García-Cimbrelo E, Munuera L, Escobar R. Low relapse with oral antibiotics and two-stage exchange for late arthroplasty infections in 40 patients after 2-9 years. Acta Orthop 2007; 78(4): 511-9.
[http://dx.doi.org/10.1080/17453670710014167] [PMID: 17966006]
]. Antibiotics were selected taking into account the sensitivity in antibiograms, as well as their activity inside biofilm and against intracellular bacteria. Those used were: linezolid, rifampin, ciprofloxacin, levofloxacin, fosfomicin, doxycycline and amoxicillin-clavulanic acid. Prescribed doses were the maximum recommended, but not adjusted to individual weight (Table 1). Hematopoietic, renal and hepatic function, as well as CRP and ESR, were monitored monthly with blood analysis.

Table 1
Antibiotics and doses used for oral treatment.


2.7. Second Stage (Reimplantation)

This was delayed until clinical and serological normalization (healing of wound, no inflammatory signs, ESR<30 mm/h and CRP<0.8 mg/L). At the beginning of this surgery, three to eight tissue samples were obtained for microbiological culture from those areas with the worst macroscopic aspect (including at least one synovial sample and one sample from each interphase). A second debridement was performed, and a new prosthesis was implanted with Copal cement [2Cordero-Ampuero J, Esteban J, García-Cimbrelo E, Munuera L, Escobar R. Low relapse with oral antibiotics and two-stage exchange for late arthroplasty infections in 40 patients after 2-9 years. Acta Orthop 2007; 78(4): 511-9.
[http://dx.doi.org/10.1080/17453670710014167] [PMID: 17966006]
].

2.8. Cultures in Reimplantation Surgery

The cases were divided into two groups. Patients with positive cultures are those who presented the same microorganism isolate in at least two intraoperative cultures from the reimplantation surgery (even if it grew in enrichment media or if it is considered habitual contaminant); patients with contaminated cultures were those with any microorganism growing in only one of the intraoperative cultures. All these micro-organism patients (those with positive cultures and those with contaminated ones) were treated with the second cycle of combined oral antibiotics, selected according to the new antibiogram, for six months, following the same criteria described above [2Cordero-Ampuero J, Esteban J, García-Cimbrelo E, Munuera L, Escobar R. Low relapse with oral antibiotics and two-stage exchange for late arthroplasty infections in 40 patients after 2-9 years. Acta Orthop 2007; 78(4): 511-9.
[http://dx.doi.org/10.1080/17453670710014167] [PMID: 17966006]
].

2.9. Clinical Series

From 2002 to 2017, 64 patients were treated with a two-stage protocol in our hospital. Of these 64, nine were excluded because the reimplantation culture results were lost (change from paper to digital history). Among the 55 included patients (Table 2), 28 showed all cultures as negative in their reimplantation surgery and were not considered for this study. On the contrary, 14 were considered as patients with positive cultures (at least two similar microbiological isolations), and 13 as patients with contaminated cultures (only one positive culture). Patients were followed in the outpatient clinic for clinical, radiographic and serological (CRP and ESR) monitoring at 4, 8, 12, 16, 20 and 24 weeks post-second surgery. Afterward they continued clinical, radiographic and serological controls every six months until the time of writing or their death. No patient has been lost to follow-up.

2.10. Infection Eradication

This was defined as the absence of any clinical, radiographic or serological signs of infection during the entire follow-up. Clinical signs and symptoms taken as suggestive of infection were chronic severe pain, persistent This was defined as the absence of any clinical, radiographic or serological signs of infection during the entire follow-up. Clinical signs and symptoms taken as suggestive of infection were chronic severe pain, persistent

Table 2
Epidemiological characteristics of patients.


2.11. Statistical Analysis

A prior calculation of sample size was not performed so as to include as many patients as possible. Independent variables were age, sex, joint, cultures in the first stage surgery, and cultures in the second stage surgery. Dependent variables were infection recurrence by original bacteria, new infection by different bacteria, functional orthopaedic result evaluated by Harris Hip score (HHS) [16Harris WH. Traumatic arthritis of the hip after dislocation and acetabular fractures: Treatment by mold arthroplasty. An end-result study using a new method of result evaluation. J Bone Joint Surg Am 1969; 51(4): 737-55.
[http://dx.doi.org/10.2106/00004623-196951040-00012] [PMID: 5783851]
] or Knee Society Clinical Rating Score (KSCRS) [17Insall JN, Dorr LD, Scott RD, Scott WN. Rationale of the knee society clinical rating system. Clin Orthop Relat Res 1989; (248): 13-4.
[http://dx.doi.org/10.1097/00003086-198911000-00004] [PMID: 2805470]
], and radiographic loosening. Pearson and Fisher's tests were applied for qualitative variables and Student’s t-test for quantitative variables. Calculations were done using IBM-SPSS Statistics v.24 software. Significance was established at 0.05% (p ≤0.05), and the odds ratios were calculated.

3. RESULTS

The average age of patients with positive cultures (those with at least two positive cultures of the same microorganism in reimplantation surgery) was 69.7 +/- 8.6 years, while that of patients with contaminated cultures (those with only one positive culture) was 66.8 +/- 9.5. This difference was not significant (p= 0.420). The group of patients with positive cultures was formed by 12 females and two males, while those with contaminated cultures were nine females and four males. Again the difference was not statistically significant (p=0.385). On the contrary, PJI was located in the knee in 13/14 positive cultures, but in only 6/13 contaminated cultures; this difference was statistically significant (p= 0.013).

Methicillin-resistant Staphylococcus Epidermidis (MRSE) was the predominant microorganism in patients with positive cultures, being isolated in 7/14 (50%) cases (Table 3). Meanwhile, the predominant bacteria in patients with contaminated cultures were Methicillin-Sensitive Staphylococcus Epidermidis (MSSE), cultured in 6/13 (46.2%) (Table 3). This difference is also statistically significant (p=0.019). On the contrary, there were no significant differences in the prevalence of polymicrobial cultures between patients with positive cultures (5/14) and those with contaminated ones (4/13) (p=0.785).

The bacteria isolated in reimplantation surgery were the same as those identified in the first surgery (persistence of infection) in 9/14 (64.3%) patients with positive cultures and in only 5/13 (38.5%) with contaminated cultures, but this difference was not significant (p=0.257).

There have been three infection recurrences in the entire series. All of them appeared in patients with positive cultures in reimplantation surgery, all developed in knee infections, two were in females and one in a male. No infection recurrence has presented during follow-up in patients with contaminated cultures. This difference is statistically significant (p=0.013).

Table 3
Results of intraoperative cultures in reimplantation surgery.


There have been no radiological loosenings in any of the groups over the course of the whole follow-up.

We have not found significant differences between patients with positive cultures when compared with those with contaminated cultures when functional orthopaedic results are analyzed at the end of follow-up (as evaluated by HHS and KSCRS scores) (p=0.411). Interestingly, patients with polymicrobial cultures presented lower HHS and KSCRS scores than those infected by only one bacteria and this result appeared in patients with positive cultures as well as in those with contaminated ones, but the differences were not significant for either groups (p=0.094 and p=0.186).

4. DISCUSSION

This study has some limitations. The first comes from its retrospective design resulting in the loss of some data (culture results records), but no patient has been lost during the entire follow-up. The second limitation derives from the small number of cases, so the statistical significance is sometimes not reached when data are compared. PJI is a low-frequency complication (0.3% to 2.22% in primary arthroplasties and 5.9% in revision surgery) [18Akgün D, Perka C, Trampuz A, Renz N. Outcome of hip and knee periprosthetic joint infections caused by pathogens resistant to biofilm-active antibiotics: results from a prospective cohort study. Arch Orthop Trauma Surg 2018; 138(5): 635-42.
[http://dx.doi.org/10.1007/s00402-018-2886-0] [PMID: 29352435]
] and is treated with different protocols, so the number of PJI treated with a two-stage protocol is very small. Moreover, even nowadays multiple microbiological sampling in reimplantation surgery is not a frequent practice.

The definition of the infected patient when reimplantation surgery is performed (persistence of previous infection or a new infection) is highly controversial in the literature. We have found 14/55 patients with positive cultures and 13/55 with contaminated cultures (Table 2), which is a high rate. Published figures are highly variable, ranging from 0% in old papers [10Kendall RW, Duncan CP, Beauchamp CP. Bacterial growth on antibiotic-loaded acrylic cement. A prospective in vivo retrieval study. J Arthroplasty 1995; 10(6): 817-22.
[http://dx.doi.org/10.1016/S0883-5403(05)80081-6] [PMID: 8749767]
] to 50% in some recent ones [9Cabo J, Euba G, Saborido A, et al. Clinical outcome and microbiological findings using antibiotic-loaded spacers in two-stage revision of prosthetic joint infections. J Infect 2011; 63(1): 23-31.
[http://dx.doi.org/10.1016/j.jinf.2011.04.014] [PMID: 21596440]
, 12Nelson CL, Jones RB, Wingert NC, Foltzer M, Bowen TR. Sonication of antibiotic spacers predicts failure during two-stage revision for prosthetic knee and hip infections. Clin Orthop Relat Res 2014; 472(7): 2208-14.
[http://dx.doi.org/10.1007/s11999-014-3571-4] [PMID: 24658903]
]. All these results must be analyzed cautiously because of four great differences between published studies. The first is the different definition of the positive vs. contaminated case: this has evolved over the years [19Parvizi J, Tan TL, Goswami K, et al. The 2018 definition of periprosthetic hip and knee infection: An evidence-based and validated criteria. J Arthroplasty 2018; 33(5): 1309-1314.e2.
[http://dx.doi.org/10.1016/j.arth.2018.02.078] [PMID: 29551303]
], especially after the development of new microbiological techniques such as sonication [12Nelson CL, Jones RB, Wingert NC, Foltzer M, Bowen TR. Sonication of antibiotic spacers predicts failure during two-stage revision for prosthetic knee and hip infections. Clin Orthop Relat Res 2014; 472(7): 2208-14.
[http://dx.doi.org/10.1007/s11999-014-3571-4] [PMID: 24658903]
, 20Esteban J, Gadea I, Pérez-Jorge C, et al. Diagnosis of spacer-associated infection using quantitative cultures from sonicated antibiotics-loaded spacers: implications for the clinical outcome. Eur J Clin Microbiol Infect Dis 2016; 35(2): 207-13.
[http://dx.doi.org/10.1007/s10096-015-2531-6] [PMID: 26610339]
], as well as methods of data interpretations [9Cabo J, Euba G, Saborido A, et al. Clinical outcome and microbiological findings using antibiotic-loaded spacers in two-stage revision of prosthetic joint infections. J Infect 2011; 63(1): 23-31.
[http://dx.doi.org/10.1016/j.jinf.2011.04.014] [PMID: 21596440]
]. The second difference between studies is the type of spacer used, or even not used as is the case for the hips in our series. The third difference is derived from the different techniques employed in each local Microbiology Department (for example, use or not of enrichment media). The fourth, and possibly the most important, arises from the number and type of microbiological samples obtained and the location from which they are obtained. The patients analyzed in the present series present a high number of samples (up to eight in the most recent cases) and always have bone and synovium samples, as well as sonication results. Other studies include articular fluid and synovial membrane [9Cabo J, Euba G, Saborido A, et al. Clinical outcome and microbiological findings using antibiotic-loaded spacers in two-stage revision of prosthetic joint infections. J Infect 2011; 63(1): 23-31.
[http://dx.doi.org/10.1016/j.jinf.2011.04.014] [PMID: 21596440]
], tissue and sonication [11Mariconda M, Ascione T, Balato G, et al. Sonication of antibiotic-loaded cement spacers in a two-stage revision protocol for infected joint arthroplasty. BMC Musculoskelet Disord 2013; 14: 193.
[http://dx.doi.org/10.1186/1471-2474-14-193] [PMID: 24192225]
, 12Nelson CL, Jones RB, Wingert NC, Foltzer M, Bowen TR. Sonication of antibiotic spacers predicts failure during two-stage revision for prosthetic knee and hip infections. Clin Orthop Relat Res 2014; 472(7): 2208-14.
[http://dx.doi.org/10.1007/s11999-014-3571-4] [PMID: 24658903]
], only sonication [13Sorlí L, Puig L, Torres-Claramunt R, et al. The relationship between microbiology results in the second of a two-stage exchange procedure using cement spacers and the outcome after revision total joint replacement for infection: the use of sonication to aid bacteriological analysis. J Bone Joint Surg Br 2012; 94(2): 249-53.
[http://dx.doi.org/10.1302/0301-620X.94B2.27779] [PMID: 22323695]
], swabs from tissues [5Schindler M, Christofilopoulos P, Wyssa B, et al. Poor performance of microbiological sampling in the prediction of recurrent arthroplasty infection. Int Orthop 2011; 35(5): 647-54.
[http://dx.doi.org/10.1007/s00264-010-1014-8] [PMID: 20419507]
] or cement [10Kendall RW, Duncan CP, Beauchamp CP. Bacterial growth on antibiotic-loaded acrylic cement. A prospective in vivo retrieval study. J Arthroplasty 1995; 10(6): 817-22.
[http://dx.doi.org/10.1016/S0883-5403(05)80081-6] [PMID: 8749767]
]. Perhaps in the future bacterial 16s RNA detection [21Bereza P, Ekiel A, Auguściak-Duma A, et al. Comparison of cultures and 16S rRNA sequencing for identification of bacteria in two-stage revision arthroplasties: preliminary report. BMC Musculoskelet Disord 2016; 17: 138.
[http://dx.doi.org/10.1186/s12891-016-0991-1] [PMID: 27015812]
] may become standard. Other confounding factors could also influence culture results in reimplantation: aseptic preparation of the surgical field, plastic drapes, double gloves, or the duration and difficulty of the surgery [22Shahi A, Parvizi J. Prevention of periprosthetic joint infection: Pre-, intra-, and post-operative strategies. SA Orthop J 2015; 14: 52-60.].

As far as is known to authors, no previous study has compared the epidemiological characteristics of reimplantation patients with positive cultures vs. those with contaminated cultures. Our positive culture cases were most frequent in knee surgeries, and this was statistically significant, while another study [13Sorlí L, Puig L, Torres-Claramunt R, et al. The relationship between microbiology results in the second of a two-stage exchange procedure using cement spacers and the outcome after revision total joint replacement for infection: the use of sonication to aid bacteriological analysis. J Bone Joint Surg Br 2012; 94(2): 249-53.
[http://dx.doi.org/10.1302/0301-620X.94B2.27779] [PMID: 22323695]
] reports a greater incidence in hips (70% vs. 62%) but without statistical difference. Similarly, our cases with contaminated cultures appear with more frequency in hips (7/13), and again this was significant. A plausible explanation for this difference may come from the use of spacer, a foreign body that liberates high doses of antibiotics over the first days, but afterward may be colonized by a new biofilm composed of resistant organisms [23Anagnostakos K, Hitzler P, Pape D, Kohn D, Kelm J. Persistence of bacterial growth on antibiotic-loaded beads: is it actually a problem? Acta Orthop 2008; 79(2): 302-7.
[http://dx.doi.org/10.1080/17453670710015120] [PMID: 18484259]
]. With this hypothesis, not using a spacer (as done in our hips) may actually be a protective factor.

We have also observed a significant difference in the bacteria isolated in reimplantation cultures: MRSE is predominant in patients with positive cultures, while MSSE is predominant in those with contaminated cultures. The same bacteria were cultured in the first and the second stages in 9/14 cases with positive cultures and in 5/13 with contaminated ones: this is clearly a persistence of infection. Different microorganisms were isolated in 5/14 positive cultures and 8/13 contaminated ones: this result may be interpreted as a new infection. Few papers have differentiated persistence and new infection, but the rate of persistence is low (25% to 36,4%) [9Cabo J, Euba G, Saborido A, et al. Clinical outcome and microbiological findings using antibiotic-loaded spacers in two-stage revision of prosthetic joint infections. J Infect 2011; 63(1): 23-31.
[http://dx.doi.org/10.1016/j.jinf.2011.04.014] [PMID: 21596440]
, 13Sorlí L, Puig L, Torres-Claramunt R, et al. The relationship between microbiology results in the second of a two-stage exchange procedure using cement spacers and the outcome after revision total joint replacement for infection: the use of sonication to aid bacteriological analysis. J Bone Joint Surg Br 2012; 94(2): 249-53.
[http://dx.doi.org/10.1302/0301-620X.94B2.27779] [PMID: 22323695]
].

We have diagnosed three infection recurrences in patients with positive cultures (3/13, 21%) and not one in those with contaminated cultures. Again, no previous study had compared the clinical evolution of patients with positive vs. contaminated cultures in reimplantation. Published results are limited to reporting recurrence in patients with positive cultures. Some papers report a low risk of infection recurrence, from 0% to 9% [9Cabo J, Euba G, Saborido A, et al. Clinical outcome and microbiological findings using antibiotic-loaded spacers in two-stage revision of prosthetic joint infections. J Infect 2011; 63(1): 23-31.
[http://dx.doi.org/10.1016/j.jinf.2011.04.014] [PMID: 21596440]
-11Mariconda M, Ascione T, Balato G, et al. Sonication of antibiotic-loaded cement spacers in a two-stage revision protocol for infected joint arthroplasty. BMC Musculoskelet Disord 2013; 14: 193.
[http://dx.doi.org/10.1186/1471-2474-14-193] [PMID: 24192225]
, 24Murillo O, Euba G, Calatayud L, et al. The role of intraoperative cultures at the time of reimplantation in the management of infected total joint arthroplasty. Eur J Clin Microbiol Infect Dis 2008; 27(9): 805-11.
[http://dx.doi.org/10.1007/s10096-008-0509-3] [PMID: 18431606]
], while others report a very high risk, 24% [5Schindler M, Christofilopoulos P, Wyssa B, et al. Poor performance of microbiological sampling in the prediction of recurrent arthroplasty infection. Int Orthop 2011; 35(5): 647-54.
[http://dx.doi.org/10.1007/s00264-010-1014-8] [PMID: 20419507]
], 50% [12Nelson CL, Jones RB, Wingert NC, Foltzer M, Bowen TR. Sonication of antibiotic spacers predicts failure during two-stage revision for prosthetic knee and hip infections. Clin Orthop Relat Res 2014; 472(7): 2208-14.
[http://dx.doi.org/10.1007/s11999-014-3571-4] [PMID: 24658903]
], or up to 63% [13Sorlí L, Puig L, Torres-Claramunt R, et al. The relationship between microbiology results in the second of a two-stage exchange procedure using cement spacers and the outcome after revision total joint replacement for infection: the use of sonication to aid bacteriological analysis. J Bone Joint Surg Br 2012; 94(2): 249-53.
[http://dx.doi.org/10.1302/0301-620X.94B2.27779] [PMID: 22323695]
]. This high variability may be explained by the different treatments applied to these patients. Mariconda et al. [11Mariconda M, Ascione T, Balato G, et al. Sonication of antibiotic-loaded cement spacers in a two-stage revision protocol for infected joint arthroplasty. BMC Musculoskelet Disord 2013; 14: 193.
[http://dx.doi.org/10.1186/1471-2474-14-193] [PMID: 24192225]
] performed surgical debridement and antibiotics, Cabo et al. [9Cabo J, Euba G, Saborido A, et al. Clinical outcome and microbiological findings using antibiotic-loaded spacers in two-stage revision of prosthetic joint infections. J Infect 2011; 63(1): 23-31.
[http://dx.doi.org/10.1016/j.jinf.2011.04.014] [PMID: 21596440]
] prescribed six weeks of antibiotics, while Sorlí et al. [13Sorlí L, Puig L, Torres-Claramunt R, et al. The relationship between microbiology results in the second of a two-stage exchange procedure using cement spacers and the outcome after revision total joint replacement for infection: the use of sonication to aid bacteriological analysis. J Bone Joint Surg Br 2012; 94(2): 249-53.
[http://dx.doi.org/10.1302/0301-620X.94B2.27779] [PMID: 22323695]
] did not apply a protocolized therapy and did not put all their patients on antibiotics, while Nelson et al. [12Nelson CL, Jones RB, Wingert NC, Foltzer M, Bowen TR. Sonication of antibiotic spacers predicts failure during two-stage revision for prosthetic knee and hip infections. Clin Orthop Relat Res 2014; 472(7): 2208-14.
[http://dx.doi.org/10.1007/s11999-014-3571-4] [PMID: 24658903]
] did not prescribe any treatment except in cases with obvious symptoms.

Another relevant difference between studies is the follow-up period: from one year in some papers [13Sorlí L, Puig L, Torres-Claramunt R, et al. The relationship between microbiology results in the second of a two-stage exchange procedure using cement spacers and the outcome after revision total joint replacement for infection: the use of sonication to aid bacteriological analysis. J Bone Joint Surg Br 2012; 94(2): 249-53.
[http://dx.doi.org/10.1302/0301-620X.94B2.27779] [PMID: 22323695]
] to ten years in our series. Patients with a polymicrobial infection have a worse clinical evolution. This is not statistically significant in our series, but has been previously noted [25Wimmer MD, Friedrich MJ, Randau TM, et al. Polymicrobial infections reduce the cure rate in prosthetic joint infections: outcome analysis with two-stage exchange and follow-up ≥two years. Int Orthop 2016; 40(7): 1367-73. [SICOT].
[http://dx.doi.org/10.1007/s00264-015-2871-y] [PMID: 26183140]
, 26Akgün D, Müller M, Perka C, Winkler T. A positive bacterial culture during re-implantation is associated with a poor outcome in two-stage exchange arthroplasty for deep infection. Bone Joint J 2017; 99-B(11): 1490-5.
[http://dx.doi.org/10.1302/0301-620X.99B11.BJJ-2017-0243-R1] [PMID: 29092988]
].

CONCLUSION

Two or more positive cultures in reimplantation surgery appeared in 25% of patients treated for a PJI with a two-stage exchange. Additionally, another 25% of patients presented contaminated cultures because they present only one positive culture in reimplantation surgery. Patients with positive cultures were more frequently women and have suffered a knee infection. The most frequent bacteria in cases with positive cultures were methicillin-resistant Staphylococcus epidermidis, while the most frequent in cases with contaminated cultures were methicillin-sensitive Staphylococcus epidermidis. With the treatment protocol applied, there were no infection recurrences in patients with contaminated cultures, but those with positive cultures presented a risk of over 20%.

LIST OF ABBREVIATIONS

CRP = C reactive protein
ESR = Erytrocite sedimentation rate
HHS = Harris Hip Score
KSCRS = Knee Society Clinical Rating Score
MSSE = Methicillin-sensitive Staphylococcus epidermidis
MRSE = Methicillin-resistent Staphylococcus epidermidis
PIJ = Prosthetic joint infection

ETHICS APPROVAL AND CONSENT TO PARTICIPATE

This study has been approved by the Local Ethics Committee with the number 3261 on December 14th, 2017.

HUMAN AND ANIMAL RIGHTS

No Animals were used in this research. All human research procedures followed were in accordance with the ethical standards of the committee responsible for human experimentation (institutional and national), and with the Helsinki Declaration of 1975, as revised in 2013.

CONSENT FOR PUBLICATION

All patients included gave written and oral Informed Consent Term for the inclusion of their clinical data (not personal ones) for the study. Confidentiality for personal data has been maintained along all the study.

AVAILABILITY OF DATA AND MATERIALS

Not applicable.

FUNDING

None.

CONFLICT OF INTEREST

Eduardo Garcia-Cimbrelo is on the editorial board of the Open Orthopaedics Journal.

No more conflict of interest. No Financial disclosure.

ACKNOWLEDGEMENTS

Declared none.

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