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  <front>
    <journal-meta><journal-id journal-id-type="publisher">JBJI</journal-id><journal-title-group>
    <journal-title>Journal of Bone and Joint Infection</journal-title>
    <abbrev-journal-title abbrev-type="publisher">JBJI</abbrev-journal-title><abbrev-journal-title abbrev-type="nlm-ta">J. Bone Joint Infect.</abbrev-journal-title>
  </journal-title-group><issn pub-type="epub">2206-3552</issn><publisher>
    <publisher-name>Copernicus Publications</publisher-name>
    <publisher-loc>Göttingen, Germany</publisher-loc>
  </publisher></journal-meta>
    <article-meta>
      <article-id pub-id-type="doi">10.5194/jbji-6-219-2021</article-id><title-group><article-title>Periprosthetic hip infections in a Swedish regional hospital between 2012 and 2018: is there a relationship between <italic>Cutibacterium acnes</italic> infections and uncemented prostheses?</article-title><alt-title>Periprosthetic hip infections in a Swedish regional hospital between 2012 and 2018</alt-title>
      </title-group><?xmltex \runningtitle{Periprosthetic hip infections in a Swedish regional hospital between 2012 and 2018}?><?xmltex \runningauthor{U. Hedlundh et al.}?>
      <contrib-group>
        <contrib contrib-type="author" corresp="yes" rid="aff1">
          <name><surname>Hedlundh</surname><given-names>Urban</given-names></name>
          <email>urban.hedlundh@vgregion.se</email>
        <ext-link>https://orcid.org/0000-0002-9753-8426</ext-link></contrib>
        <contrib contrib-type="author" corresp="no" rid="aff1">
          <name><surname>Zacharatos</surname><given-names>Michail</given-names></name>
          
        </contrib>
        <contrib contrib-type="author" corresp="no" rid="aff1">
          <name><surname>Magnusson</surname><given-names>Jonas</given-names></name>
          
        </contrib>
        <contrib contrib-type="author" corresp="no" rid="aff1">
          <name><surname>Gottlander</surname><given-names>Magnus</given-names></name>
          
        </contrib>
        <contrib contrib-type="author" corresp="no" rid="aff2 aff3">
          <name><surname>Karlsson</surname><given-names>Johanna</given-names></name>
          
        </contrib>
        <aff id="aff1"><label>1</label><institution>Department of Orthopedic Surgery, Uddevalla Hospital, SE 451 80, Uddevalla,
Sweden</institution>
        </aff>
        <aff id="aff2"><label>2</label><institution>Department of Infectious Diseases, NU Hospital Group, Trollhättan/Uddevalla,
Sweden</institution>
        </aff>
        <aff id="aff3"><label>3</label><institution>Department of Infectious Diseases, Institute of
Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg,
Sweden</institution>
        </aff>
      </contrib-group>
      <author-notes><corresp id="corr1">Urban Hedlundh (urban.hedlundh@vgregion.se)</corresp></author-notes><pub-date><day>4</day><month>June</month><year>2021</year></pub-date>
      
      <volume>6</volume>
      <issue>6</issue>
      <fpage>219</fpage><lpage>228</lpage>
      <history>
        <date date-type="received"><day>19</day><month>January</month><year>2021</year></date>
           <date date-type="rev-recd"><day>18</day><month>May</month><year>2021</year></date>
           <date date-type="accepted"><day>24</day><month>May</month><year>2021</year></date>
      </history>
      <permissions>
        <copyright-statement>Copyright: © 2021 Urban Hedlundh et al.</copyright-statement>
        <copyright-year>2021</copyright-year>
      <license license-type="open-access"><license-p>This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this licence, visit <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">https://creativecommons.org/licenses/by/4.0/</ext-link></license-p></license></permissions><self-uri xlink:href="https://jbji.copernicus.org/articles/6/219/2021/jbji-6-219-2021.html">This article is available from https://jbji.copernicus.org/articles/6/219/2021/jbji-6-219-2021.html</self-uri><self-uri xlink:href="https://jbji.copernicus.org/articles/6/219/2021/jbji-6-219-2021.pdf">The full text article is available as a PDF file from https://jbji.copernicus.org/articles/6/219/2021/jbji-6-219-2021.pdf</self-uri>
      <abstract><title>Abstract</title>
    <p id="d1e132">The purpose of this study was to evaluate patients requiring in-patient care
due to a periprosthetic joint infection (PJI), with respect to bacterial
agents, surgical treatment, antibiotics, and outcome. We retrospectively identified all infected total hip arthroplasties (THAs) in
a Swedish regional hospital during a 7-year period (2012–2018) and reviewed
medical records and microbiological data. A total of 89 infected THAs in 87 patients were identified. Standardized
treatment with debridement with retention of the implant and antibiotics
(DAIR) was initially performed in 53 cases (60 %), one or two stage
revisions in 33 cases (37 %), and an immediate Girdlestone in 3 cases (3 %). Infection eradication was seen in 77 PJIs (87 %) in addition to
six patients (7 %) ending up with a permanent but uninfected Girdlestone.
All six patients with manifest failures were infected with <italic>Staphylococcus aureus</italic>, two of which
were also polymicrobial. <italic>Cutibacterium acnes</italic> was found in 18 of 89 patients (16 %) distributed
in 15 uncemented implants but only in 3 hybrids and cemented arthroplasties,
while remaining pathogens were equally distributed in uncemented THAs (<inline-formula><mml:math id="M1" display="inline"><mml:mrow><mml:mi>n</mml:mi><mml:mo>=</mml:mo><mml:mn mathvariant="normal">31</mml:mn></mml:mrow></mml:math></inline-formula>) and THAs with at least one cemented component (<inline-formula><mml:math id="M2" display="inline"><mml:mrow><mml:mi>n</mml:mi><mml:mo>=</mml:mo><mml:mn mathvariant="normal">40</mml:mn></mml:mrow></mml:math></inline-formula>; <inline-formula><mml:math id="M3" display="inline"><mml:mrow><mml:mi>p</mml:mi><mml:mo>=</mml:mo><mml:mn mathvariant="normal">0.003</mml:mn></mml:mrow></mml:math></inline-formula>).
Eradication was achieved in all 18 patients when <italic>Cutibacterium acnes</italic> was the only culture (<inline-formula><mml:math id="M4" display="inline"><mml:mrow><mml:mi>n</mml:mi><mml:mo>=</mml:mo><mml:mn mathvariant="normal">14</mml:mn></mml:mrow></mml:math></inline-formula>) or
clearly dominant among positive cultures (<inline-formula><mml:math id="M5" display="inline"><mml:mrow><mml:mi>n</mml:mi><mml:mo>=</mml:mo><mml:mn mathvariant="normal">4</mml:mn></mml:mrow></mml:math></inline-formula>). DAIR was successful in
selected postoperative infections up to 6 months after hip replacement.
<italic>Cutibacterium acnes</italic> infections in hip arthroplasty may be underdiagnosed. Cemented components
in THAs seem to protect from colonization with <italic>Cutibacterium acnes</italic>.</p>
  </abstract>
    </article-meta>
  </front>
<body>
      

<sec id="Ch1.S1" sec-type="intro">
  <label>1</label><title>Introduction</title>
      <p id="d1e220">Periprosthetic joint infection (PJI) is a feared and serious complication of
prosthetic surgery, which causes great suffering for the individual and
requires major healthcare resources. The incidence in primary interventions
is 0.5 %–2 %, higher for revision procedures (Engesaeter et al., 2011), and seems to be
increasing both worldwide (Kurtz et al., 2012) and
in Scandinavia (Dale et al., 2012). Antibiotic treatment alone is
insufficient to eradicate and cure infection (Sendi et al., 2017; Zimmerli
et al., 2004). Complete exchange of implants, particularly when performed as
a two-stage procedure, results in substantial morbidity, loss of ambulation,
and decreased quality of life (Leonard et al., 2014).
Debridement, antibiotics, and implant retention (DAIR) of well fixated
implants has gained increased popularity in an international context
due to both increased cure rates and patient preference. Diverse selection
criteria, various treatment protocols, insufficient detection of causative
bacterial agents, limited surgical accuracy, and inconsistent<?pagebreak page220?> follow-up
significantly limits comparisons between studies (Tsang et al., 2017).</p>
      <p id="d1e223">The most common contaminating organism in PJI is <italic>Staphylococcus aureus</italic> followed by coagulase
negative staphylococci (CoNS), streptococci, <italic>Escherichia coli</italic>, <italic>Enterococcus</italic> species, and in
recent years <italic>Cutibacterium acnes</italic> (formerly <italic>Propionibacterium acnes</italic>). Colonization and antibiotic resistance vary in
different parts of the world; however, the <italic>Staphylococcus aureus</italic> and coliform strains have been
considered more difficult to treat (Zimmerli et al., 2004; Grammatopoulos
et al., 2017).</p>
      <p id="d1e245">This study originally started as a part of our department's quality follow-up that evaluates all patients with an infected total hip arthroplasty (THA)
treated within the NU Hospital Group in western Sweden (Norra Älvsborgs
Community Hospital, which has an orthopedic emergency department, and Uddevalla
Hospital, which has an elective care unit). This was in accordance with a
national, interdisciplinary collaboration for safer prosthetic knee and hip
operations (PRISS) that was presented in 2013 and suggested continuous local
follow-up of routines and results (Lindgren et al., 2014). The purpose of
our retrospective investigation was to evaluate all PJIs at a medium-sized
Swedish hospital during a 7-year period with respect to infecting
microorganisms, surgical treatment, antibiotics, and outcome.</p>
</sec>
<sec id="Ch1.S2">
  <label>2</label><title>Patients and methods</title>
<sec id="Ch1.S2.SS1">
  <label>2.1</label><title>Design and data collection</title>
      <p id="d1e263">Adult patients in the NU Hospital Group diagnosed with a PJI between 1 January 2012 and 31 December 2018 were included in the
study. Information from three official database registers were collected.
First the operative record's database of performed surgical interventions as
well as the in-patient database in the NU Hospital Group were both searched
for the ICD-10 code “T84.5”, indicating a deep periprosthetic joint
infection. All discovered procedures were then controlled against our
surgical data reported to and collected in the Swedish National Hip
Registry. Our primary THAs between 2012 and 2014 were additionally matched
with the Swedish Prescription Drug register in a follow-up study of
infection registration based on the National Registry (Lindgren et al.,
2014). The patient files for all registered infections were then collected
and scrutinized by the authors to both confirm the diagnosis and match it
according to the guidelines published by Musculoskeletal Infection Society (Parvizi et al., 2011) and the Infectious
Diseases Society of America (Osmon et al.,
2013) to ensure conformity. Patients with semi-total arthroplasties without
an acetabular component were excluded, since these implants were only used
in treatment of cervical hip fractures in old and fragile patients. As
previously described these patients have considerable comorbidity, are often
institutionalized, and both treatment and follow-up is unreliable (Guren
et al., 2017).<?xmltex \hack{\newpage}?></p>
</sec>
<sec id="Ch1.S2.SS2">
  <label>2.2</label><title>Definitions</title>
      <p id="d1e275">A PJI was considered present with the major criterium of two or more
positive cultures with growth of the same microbiological organism in joint
fluid or collected tissue samples. Additionally, at least two of the
following criteria were present: wound discharge, sinuses, fever, local
inflammation signs, raised CRP  (<inline-formula><mml:math id="M6" display="inline"><mml:mo lspace="0mm">&gt;</mml:mo></mml:math></inline-formula> 10), or clinical findings of
joint distress and particularly load pain.</p>
      <p id="d1e285">Routinely, five tissue cultures were collected at implant exchange surgery
from the interface between both the cup and the stem implant as well as
cancellous bone when available, or otherwise including at least five samples
from the joint capsule. The samples were harvested before perioperative
intravenous antibiotic treatment was administrated. Antibiotic treatment was
given according to established protocols (Osmon et al., 2013; Zimmerli et
al., 2004) and national guidelines (Tevell et al., 2019) depending on
antibiotic susceptibility and started with intravenous antibiotic therapy
that was continued for 7–10 d followed by oral medication that was
scheduled to terminate after 3 months.</p>
      <p id="d1e288">The laboratory handling of microbiological tissues was changed in early
2015. Before, 10 samples were collected in broth and transported to the
laboratory, where the material was plated on agar plates. From 2015, at
least five tissue samples are routinely harvested at surgery and collected
in empty sterile test tubes. Any further treatment of samples is performed
in the laboratory. Transportation time is thereby considered less crucial,
and the laboratory cultivates a fresh tissue section with imprint on agar
substrate primarily. Afterwards, residual tissue pieces are continuously
chopped for prolonged enrichment, which is routinely performed in all
samples labeled “prosthesis”. This reduces the risk of rapidly and strongly
growing species taking over and hiding slow-growing pathogens such as
<italic>Cutibacterium acnes</italic>.</p>
      <?pagebreak page221?><p id="d1e294">An infection was classified as either postoperative or hematogenous. Cases
with a sudden onset of inflammatory symptoms well beyond the postoperative
period with a previously well-functioning arthroplasty were considered
hematogenous (here ranging from 5 months to 25 years; median 6 years). In
postoperative infections, we have refrained from distinguishing between
acute and chronic PJI in accordance with the recommendation at the Second
International Consensus Meeting on Musculoskeletal Infections (Elkins et
al., 2019). In most of our postoperative PJIs there had been wound
complications and a superficial site infection following the insertion of
the implant without a continuous period with an optimally functioning joint.
However, there were also infections with a probable origin in the prosthetic
procedure with well healed surgical wounds and no septic episodes but a
rehabilitation phase with continuous discomfort and loading pain. These
infections were first evident after repeated visits, laboratory
investigations, and finally progressive radiographic changes (Fig. 1).<?xmltex \hack{\newpage}?></p>

      <?xmltex \floatpos{t}?><fig id="Ch1.F1"><?xmltex \currentcnt{1}?><?xmltex \def\figurename{Figure}?><label>Figure 1</label><caption><p id="d1e301">Radiograph of 4-year-old infection with coagulase negative staphylococci
(CoNS) in uncemented THAs. Radiolucent lines are evident around the cup in
Charnley zone 3 and around the stem in Gruen zones 1 and 7. © 2021 Urban Hedlundh.</p></caption>
          <?xmltex \igopts{width=142.26378pt}?><graphic xlink:href="https://jbji.copernicus.org/articles/6/219/2021/jbji-6-219-2021-f01.jpg"/>

        </fig>

      <p id="d1e310">A PJI was considered eradicated when there were no inflammatory signs
including normalized ESR and/or CRP or symptoms from the hip joint for a
minimum of 2 years after termination of antibiotic treatment, which is
considered the shortest time in published literature to establish infection
eradication (Sendi et al., 2017). Unrelated death (<inline-formula><mml:math id="M7" display="inline"><mml:mrow><mml:mi>n</mml:mi><mml:mo>=</mml:mo><mml:mn mathvariant="normal">2</mml:mn></mml:mrow></mml:math></inline-formula>) or hip
revisions for other reasons than infection with negative perioperative
cultures (<inline-formula><mml:math id="M8" display="inline"><mml:mrow><mml:mi>n</mml:mi><mml:mo>=</mml:mo><mml:mn mathvariant="normal">3</mml:mn></mml:mrow></mml:math></inline-formula>) occurring during follow-up within 2 years were labeled
eradicated. Final failure was defined as an ongoing PJI with no planned
future surgery but suppressive life-long antibiotic treatment. Girdlestone
resection arthroplasties were reported separately since they were successful
regarding infection eradication, but not from a prosthetic point of view.</p>

<?xmltex \floatpos{t}?><table-wrap id="Ch1.T1" specific-use="star"><?xmltex \currentcnt{1}?><label>Table 1</label><caption><p id="d1e340">Surgical data on patients undergoing THA (primary and revision) at our
institution between 2012 and 2018 compared with the infected THA patients
operated on during the same period and included in the study. Please note that 18
of the study patients were primarily operated on elsewhere and 20 additional
patients were operated on prior to 2012. Surgical risk was defined according to
the American Society of Anesthesiologists physical status classification
(ASA).</p></caption><oasis:table frame="topbot"><oasis:tgroup cols="3">
     <oasis:colspec colnum="1" colname="col1" align="left"/>
     <oasis:colspec colnum="2" colname="col2" align="right"/>
     <oasis:colspec colnum="3" colname="col3" align="right"/>
     <oasis:thead>
       <oasis:row>
         <oasis:entry colname="col1"/>
         <oasis:entry colname="col2">THA</oasis:entry>
         <oasis:entry colname="col3">Infected THAs in study</oasis:entry>
       </oasis:row>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1"/>
         <oasis:entry colname="col2"><inline-formula><mml:math id="M9" display="inline"><mml:mrow><mml:mi>n</mml:mi><mml:mo>=</mml:mo><mml:mn mathvariant="normal">2975</mml:mn></mml:mrow></mml:math></inline-formula></oasis:entry>
         <oasis:entry colname="col3"><inline-formula><mml:math id="M10" display="inline"><mml:mrow><mml:mi>n</mml:mi><mml:mo>=</mml:mo><mml:mn mathvariant="normal">51</mml:mn></mml:mrow></mml:math></inline-formula></oasis:entry>
       </oasis:row>
     </oasis:thead>
     <oasis:tbody>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1">Number of THAs</oasis:entry>
         <oasis:entry colname="col2"/>
         <oasis:entry colname="col3"/>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Primary</oasis:entry>
         <oasis:entry colname="col2">2646</oasis:entry>
         <oasis:entry colname="col3">43</oasis:entry>
       </oasis:row>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1">Revision</oasis:entry>
         <oasis:entry colname="col2">329</oasis:entry>
         <oasis:entry colname="col3">8</oasis:entry>
       </oasis:row>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1">Gender</oasis:entry>
         <oasis:entry colname="col2"/>
         <oasis:entry colname="col3"/>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Male</oasis:entry>
         <oasis:entry colname="col2">1270</oasis:entry>
         <oasis:entry colname="col3">32</oasis:entry>
       </oasis:row>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1">Female</oasis:entry>
         <oasis:entry colname="col2">1705</oasis:entry>
         <oasis:entry colname="col3">19</oasis:entry>
       </oasis:row>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1">Mean age (years <inline-formula><mml:math id="M11" display="inline"><mml:mo>±</mml:mo></mml:math></inline-formula> SD)</oasis:entry>
         <oasis:entry colname="col2">69 <inline-formula><mml:math id="M12" display="inline"><mml:mo>±</mml:mo></mml:math></inline-formula> 10</oasis:entry>
         <oasis:entry colname="col3">67 <inline-formula><mml:math id="M13" display="inline"><mml:mo>±</mml:mo></mml:math></inline-formula> 14</oasis:entry>
       </oasis:row>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1">Implant fixation</oasis:entry>
         <oasis:entry colname="col2"/>
         <oasis:entry colname="col3"/>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Uncemented</oasis:entry>
         <oasis:entry colname="col2">1079</oasis:entry>
         <oasis:entry colname="col3">30</oasis:entry>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Cemented</oasis:entry>
         <oasis:entry colname="col2">1547</oasis:entry>
         <oasis:entry colname="col3">17</oasis:entry>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Hybrid</oasis:entry>
         <oasis:entry colname="col2">273</oasis:entry>
         <oasis:entry colname="col3">4</oasis:entry>
       </oasis:row>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1">Missing</oasis:entry>
         <oasis:entry colname="col2">76</oasis:entry>
         <oasis:entry colname="col3">0</oasis:entry>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Mean body mass index (kg m<inline-formula><mml:math id="M14" display="inline"><mml:msup><mml:mi/><mml:mrow><mml:mo>-</mml:mo><mml:mn mathvariant="normal">2</mml:mn></mml:mrow></mml:msup></mml:math></inline-formula>, <inline-formula><mml:math id="M15" display="inline"><mml:mo>±</mml:mo></mml:math></inline-formula> SD)</oasis:entry>
         <oasis:entry colname="col2">27.8 <inline-formula><mml:math id="M16" display="inline"><mml:mo>±</mml:mo></mml:math></inline-formula> 4.9</oasis:entry>
         <oasis:entry colname="col3">30.0 <inline-formula><mml:math id="M17" display="inline"><mml:mo>±</mml:mo></mml:math></inline-formula> 7.5</oasis:entry>
       </oasis:row>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1">Missing data</oasis:entry>
         <oasis:entry colname="col2">265</oasis:entry>
         <oasis:entry colname="col3">4</oasis:entry>
       </oasis:row>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1">Patient surgical risk</oasis:entry>
         <oasis:entry colname="col2"/>
         <oasis:entry colname="col3"/>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">ASA 1</oasis:entry>
         <oasis:entry colname="col2">488</oasis:entry>
         <oasis:entry colname="col3">8</oasis:entry>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">ASA 2</oasis:entry>
         <oasis:entry colname="col2">1712</oasis:entry>
         <oasis:entry colname="col3">23</oasis:entry>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">ASA 3</oasis:entry>
         <oasis:entry colname="col2">700</oasis:entry>
         <oasis:entry colname="col3">19</oasis:entry>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">ASA 4</oasis:entry>
         <oasis:entry colname="col2">6</oasis:entry>
         <oasis:entry colname="col3">0</oasis:entry>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Missing data</oasis:entry>
         <oasis:entry colname="col2">69</oasis:entry>
         <oasis:entry colname="col3">1</oasis:entry>
       </oasis:row>
     </oasis:tbody>
   </oasis:tgroup></oasis:table></table-wrap>

</sec>
<sec id="Ch1.S2.SS3">
  <label>2.3</label><title>Primary hip arthroplasty surgery</title>
      <p id="d1e699">In all primary surgery from 2016, the patient arrived at the hospital on the
day of the operation. Preoperative cleansing at home with sponges containing
chlorhexidine gluconate (CHG) were advocated twice on the day before surgery
as well as in the morning before leaving home. Prior to surgery the affected
leg and groin was cleaned once more with CHG in the theater and then with
chlorhexidine alcohol 50 % before draping. Between 15 and 30 min before skin
incision, 2 g of flucloxacillin was administered intravenously
followed by two additional doses 2 and 6 h after the first dose
according to Swedish tradition and guidelines (Tevell et al., 2019). In 5
to 10 % of the patients another antibiotic was chosen due to allergy.
The theater had laminar air flow and all persons in the room were dressed in
reusable non-permeable polyester coveralls including helmets. The surgical
staff used an additional reusable impenetrable gown and two pair of gloves.</p>
</sec>
<sec id="Ch1.S2.SS4">
  <label>2.4</label><title>Surgical grouping</title>
      <p id="d1e710">All patients with at least two culture-positive tissue samples and/or joint
aspiration with growth of the same microorganism were included in the study
(Fig. 2). Four patients undergoing an outdated treatment with only
drainage and limited irrigation due to high age and poor health status were
excluded. In accordance with inclusion criteria, four patients who were
diagnosed with a suspect joint infection by only one joint aspiration
culture or a wound cultivation were excluded as well as one patient with a
suspected but culture-negative PJI. The remaining 89 PJIs were divided in three
groups according to surgical treatment (Fig. 2).</p>

      <?xmltex \floatpos{t}?><fig id="Ch1.F2"><?xmltex \currentcnt{2}?><?xmltex \def\figurename{Figure}?><label>Figure 2</label><caption><p id="d1e715">Presentation of all 89 total hip arthroplasties labeled periprosthetic
joint infections (PJIs). Outcome of standardized treatment has been
classified as “eradication” and “failure”.</p></caption>
          <?xmltex \igopts{width=236.157874pt}?><graphic xlink:href="https://jbji.copernicus.org/articles/6/219/2021/jbji-6-219-2021-f02.png"/>

        </fig>

      <p id="d1e724"><list list-type="bullet">
            <list-item>

      <p id="d1e729"><italic>Debridement, antibiotics, and implant retention in accordance with published DAIR protocols (Tsang et al., 2017).</italic> The joint was dislocated, and
aggressive surgical debridement was performed by experienced revision
surgeons followed by irrigation with 1–3 L of sterile sodium
chloride before exchangeable modular heads and liners were changed.
Resorbable, equine collagen fleeces containing between 70 and 280 mg of
gentamicin were implanted in the joint before wound closure. The size of the
fleece was usually not listed in the operative records. The procedure was
planned to be performed within 6 weeks postoperatively but sometimes
occurred later. Time from onset of symptoms was usually not specified in
files since initial surgical wound care and agraffe removal was performed by
district<?pagebreak page222?> nurses and general practitioners. Hematogenous PJI was treated with
DAIR within 2 weeks of presumed acute onset of symptoms.</p>
            </list-item>
            <list-item>

      <p id="d1e737"><italic>One- or two-stage implant exchange (revision).</italic> This was the preferred
treatment in long-standing infections exceeding 6 months, less when
radiographic zones were evident (Fig. 1), as well as when any loose
implants were discovered during planned DAIR surgery. In 15 patients with
loose stems but well-integrated cups in porous metal, there was only an
exchange of liner, removal of cup screws, and implantation of gentamicin
fleece in existing screw holes in addition to the stem exchange. Well
integrated anchored titanium stems were left in four cases, and here only the
cup and modular head was changed. All cemented components were revised, and
adjacent detectable bone cement removed.</p>
            </list-item>
            <list-item>

      <p id="d1e745"><italic>Complete and permanent removal of implants in a Girdlestone-like procedure (Vincenten et al., 2019).</italic></p>
            </list-item>
          </list><?xmltex \hack{\newpage}?></p>
</sec>
<sec id="Ch1.S2.SS5">
  <label>2.5</label><title>Statistics</title>
      <p id="d1e761">Descriptive statistics were used to summarize demographic data, time,
antibiotic treatment, and involved microorganisms. Calculations of group
comparisons using <inline-formula><mml:math id="M18" display="inline"><mml:mrow><mml:mn mathvariant="normal">2</mml:mn><mml:mo>×</mml:mo><mml:mn mathvariant="normal">2</mml:mn></mml:mrow></mml:math></inline-formula> contingency tables were performed by
Fisher's exact test. Non-parametric group comparisons used
the Mann–Whitney <inline-formula><mml:math id="M19" display="inline"><mml:mi>U</mml:mi></mml:math></inline-formula> test. A <inline-formula><mml:math id="M20" display="inline"><mml:mi>p</mml:mi></mml:math></inline-formula> value of <inline-formula><mml:math id="M21" display="inline"><mml:mo>&lt;</mml:mo></mml:math></inline-formula> 0.05 was considered
statistically significant.</p>

<?xmltex \floatpos{t}?><table-wrap id="Ch1.T2" specific-use="star"><?xmltex \currentcnt{2}?><label>Table 2</label><caption><p id="d1e800">Isolated microorganisms in 89 revised periprosthetic hip joint infections.
The number of cultures was 110 since significant growth (<inline-formula><mml:math id="M22" display="inline"><mml:mo lspace="0mm">≥</mml:mo></mml:math></inline-formula> two tissue
samples) of more than one bacterium was noted in 21 patients. Cultures in
patients with repeated surgery and the same bacterial strains have only been
counted once.</p></caption><oasis:table frame="topbot"><oasis:tgroup cols="7">
     <oasis:colspec colnum="1" colname="col1" align="left"/>
     <oasis:colspec colnum="2" colname="col2" align="right"/>
     <oasis:colspec colnum="3" colname="col3" align="right"/>
     <oasis:colspec colnum="4" colname="col4" align="right"/>
     <oasis:colspec colnum="5" colname="col5" align="right"/>
     <oasis:colspec colnum="6" colname="col6" align="right"/>
     <oasis:colspec colnum="7" colname="col7" align="right"/>
     <oasis:thead>
       <oasis:row>
         <oasis:entry colname="col1"/>
         <oasis:entry colname="col2"/>
         <oasis:entry colname="col3">Monomicrobial</oasis:entry>
         <oasis:entry colname="col4">Eradication</oasis:entry>
         <oasis:entry colname="col5"/>
         <oasis:entry colname="col6"/>
         <oasis:entry colname="col7"/>
       </oasis:row>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1">Organism</oasis:entry>
         <oasis:entry colname="col2"><inline-formula><mml:math id="M27" display="inline"><mml:mi>n</mml:mi></mml:math></inline-formula> (%)</oasis:entry>
         <oasis:entry colname="col3">infection</oasis:entry>
         <oasis:entry colname="col4"><inline-formula><mml:math id="M28" display="inline"><mml:mi>n</mml:mi></mml:math></inline-formula> ( %)</oasis:entry>
         <oasis:entry colname="col5">Failure</oasis:entry>
         <oasis:entry colname="col6">Girdlestone</oasis:entry>
         <oasis:entry colname="col7"><inline-formula><mml:math id="M29" display="inline"><mml:mrow><mml:msup><mml:mi>p</mml:mi><mml:mtext>c</mml:mtext></mml:msup></mml:mrow></mml:math></inline-formula></oasis:entry>
       </oasis:row>
     </oasis:thead>
     <oasis:tbody>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1">Gram-positive bacteria</oasis:entry>
         <oasis:entry colname="col2"/>
         <oasis:entry colname="col3"/>
         <oasis:entry colname="col4"/>
         <oasis:entry colname="col5"/>
         <oasis:entry colname="col6"/>
         <oasis:entry colname="col7"/>
       </oasis:row>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1">CoNS<inline-formula><mml:math id="M30" display="inline"><mml:msup><mml:mi/><mml:mtext>a</mml:mtext></mml:msup></mml:math></inline-formula></oasis:entry>
         <oasis:entry colname="col2">33 (30)</oasis:entry>
         <oasis:entry colname="col3">23</oasis:entry>
         <oasis:entry colname="col4">30 (91)</oasis:entry>
         <oasis:entry colname="col5">2</oasis:entry>
         <oasis:entry colname="col6">1</oasis:entry>
         <oasis:entry colname="col7">0.27</oasis:entry>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1"><italic>Staphylococcus aureus</italic></oasis:entry>
         <oasis:entry colname="col2">22 (20)</oasis:entry>
         <oasis:entry colname="col3">16</oasis:entry>
         <oasis:entry colname="col4">12 (55)</oasis:entry>
         <oasis:entry colname="col5">6</oasis:entry>
         <oasis:entry colname="col6">4</oasis:entry>
         <oasis:entry colname="col7">0.0001</oasis:entry>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1"><italic>Cutibacterium acnes</italic></oasis:entry>
         <oasis:entry colname="col2">18 (16)</oasis:entry>
         <oasis:entry colname="col3">14</oasis:entry>
         <oasis:entry colname="col4">18 (100)</oasis:entry>
         <oasis:entry colname="col5">0</oasis:entry>
         <oasis:entry colname="col6"/>
         <oasis:entry colname="col7">0.07</oasis:entry>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1"><italic>Streptococcus</italic> spp.</oasis:entry>
         <oasis:entry colname="col2">15 (14)</oasis:entry>
         <oasis:entry colname="col3">8</oasis:entry>
         <oasis:entry colname="col4">14 (93)</oasis:entry>
         <oasis:entry colname="col5">1</oasis:entry>
         <oasis:entry colname="col6"/>
         <oasis:entry colname="col7">0.46</oasis:entry>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1"><italic>Enterococcus</italic> spp.</oasis:entry>
         <oasis:entry colname="col2">8 (7)</oasis:entry>
         <oasis:entry colname="col3">2</oasis:entry>
         <oasis:entry colname="col4">7 (88)</oasis:entry>
         <oasis:entry colname="col5">1</oasis:entry>
         <oasis:entry colname="col6"/>
         <oasis:entry colname="col7">1.0</oasis:entry>
       </oasis:row>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1"><italic>Corynebacterium</italic> spp.</oasis:entry>
         <oasis:entry colname="col2">2 (2)</oasis:entry>
         <oasis:entry colname="col3">0</oasis:entry>
         <oasis:entry colname="col4">2 (100)</oasis:entry>
         <oasis:entry colname="col5">0</oasis:entry>
         <oasis:entry colname="col6"/>
         <oasis:entry colname="col7">1.0</oasis:entry>
       </oasis:row>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1">Gram-negative bacteria</oasis:entry>
         <oasis:entry colname="col2"/>
         <oasis:entry colname="col3"/>
         <oasis:entry colname="col4"/>
         <oasis:entry colname="col5"/>
         <oasis:entry colname="col6"/>
         <oasis:entry colname="col7"/>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1"><italic>Escherichia coli</italic></oasis:entry>
         <oasis:entry colname="col2">5 (5)</oasis:entry>
         <oasis:entry colname="col3">4</oasis:entry>
         <oasis:entry colname="col4">4 (80)</oasis:entry>
         <oasis:entry colname="col5">0</oasis:entry>
         <oasis:entry colname="col6">1</oasis:entry>
         <oasis:entry colname="col7">0.58</oasis:entry>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1"><italic>Enterobacter</italic> spp.</oasis:entry>
         <oasis:entry colname="col2">2 (2)</oasis:entry>
         <oasis:entry colname="col3">1</oasis:entry>
         <oasis:entry colname="col4">2 (100)</oasis:entry>
         <oasis:entry colname="col5">0</oasis:entry>
         <oasis:entry colname="col6"/>
         <oasis:entry colname="col7">1.0</oasis:entry>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Other<inline-formula><mml:math id="M31" display="inline"><mml:msup><mml:mi/><mml:mtext>b</mml:mtext></mml:msup></mml:math></inline-formula></oasis:entry>
         <oasis:entry colname="col2">5 (5)</oasis:entry>
         <oasis:entry colname="col3">0</oasis:entry>
         <oasis:entry colname="col4">4 (80)</oasis:entry>
         <oasis:entry colname="col5">1</oasis:entry>
         <oasis:entry colname="col6"/>
         <oasis:entry colname="col7">0.58</oasis:entry>
       </oasis:row>
     </oasis:tbody>
   </oasis:tgroup></oasis:table><table-wrap-foot><p id="d1e810"><inline-formula><mml:math id="M23" display="inline"><mml:msup><mml:mi/><mml:mtext>a</mml:mtext></mml:msup></mml:math></inline-formula> CoNS <inline-formula><mml:math id="M24" display="inline"><mml:mo>=</mml:mo></mml:math></inline-formula> coagulase negative staphylococci.
<inline-formula><mml:math id="M25" display="inline"><mml:msup><mml:mi/><mml:mtext>b</mml:mtext></mml:msup></mml:math></inline-formula> <italic>Hemophilus influenzae, Klebsiella oxytoca, Serratia</italic> sp., <italic>Acinetobacter</italic> sp., <italic>Eikenella corrodens</italic>.
<inline-formula><mml:math id="M26" display="inline"><mml:msup><mml:mi/><mml:mtext>c</mml:mtext></mml:msup></mml:math></inline-formula> Calculated on treatment failure including Girdlestone vs. eradication
in the specific bacterium/group of bacteria vs. all other.</p></table-wrap-foot></table-wrap>

</sec>
</sec>
<sec id="Ch1.S3">
  <label>3</label><title>Results</title>
<sec id="Ch1.S3.SS1">
  <label>3.1</label><title>Study population, patient characteristics, and survival</title>
      <p id="d1e1249">A total of 87 patients with 89 PJI episodes were included in the study. One
patient with bilateral arthroplasties had a simultaneous bacterial
precipitation in both hips and bilateral DAIR treatment, while another was
initially successfully treated but infected with a new pathogen after
further revision surgery. A total of 18 primary arthroplasties had been performed
in other hospitals at a median of 2 years (23 d–24 years) before the
patients attended care at our institution.<?pagebreak page223?> Median age at the time of
diagnosis was 68 years (40–92); 31 of the patients were female (34 %), and 12 patients died from causes not related to the PJI at an average
of 59 months (16–90) after revision surgery and excision arthroplasties.
No deaths directly attributable to the PJI were identified.</p>
</sec>
<sec id="Ch1.S3.SS2">
  <label>3.2</label><title>Microbiology</title>
      <p id="d1e1260">Distribution of bacteria in collected tissue samples is presented in Table 2.</p>
      <p id="d1e1263">Coagulase negative staphylococci (CoNS), <italic>Staphylococcus aureus</italic>, and <italic>Cutibacterium acnes</italic> were the three most prevalent
bacteria and were detected in 30 %, 20 %, and 16 % of the cultures, respectively. Multiple organisms were found in 24 % of the cases while 76 % of the infections were monomicrobial with no difference in failure rate
(2 out of 19 vs. 10 out of 58; <inline-formula><mml:math id="M32" display="inline"><mml:mrow><mml:mi>p</mml:mi><mml:mo>=</mml:mo><mml:mn mathvariant="normal">0</mml:mn></mml:mrow></mml:math></inline-formula>.7). Final surgical failure resulting in life-long
antibiotic suppression (<inline-formula><mml:math id="M33" display="inline"><mml:mrow><mml:mi>n</mml:mi><mml:mo>=</mml:mo><mml:mn mathvariant="normal">6</mml:mn></mml:mrow></mml:math></inline-formula>) or Girdlestone (<inline-formula><mml:math id="M34" display="inline"><mml:mrow><mml:mi>n</mml:mi><mml:mo>=</mml:mo><mml:mn mathvariant="normal">6</mml:mn></mml:mrow></mml:math></inline-formula>) was highly associated with <italic>Staphylococcus aureus</italic> infection (10 out of 12; 83 %; <inline-formula><mml:math id="M35" display="inline"><mml:mrow><mml:mi>p</mml:mi><mml:mo>=</mml:mo><mml:mn mathvariant="normal">0.0001</mml:mn></mml:mrow></mml:math></inline-formula>) (Table 2).</p>
      <p id="d1e1324"><italic>Cutibacterium acnes</italic> was isolated in 18 of 89 PJIs (20 %), in 14 out of 18 cases (78 %) as the
single growing pathogen. A total of 15 cases (83 %) were diagnosed after 2015.
Patient characteristics in <italic>Cutibacterium</italic> infections compared with other
infectious agents are presented in Table 3. DAIR (<inline-formula><mml:math id="M36" display="inline"><mml:mrow><mml:mi>n</mml:mi><mml:mo>=</mml:mo><mml:mn mathvariant="normal">11</mml:mn></mml:mrow></mml:math></inline-formula>) or revision
implant exchange (<inline-formula><mml:math id="M37" display="inline"><mml:mrow><mml:mi>n</mml:mi><mml:mo>=</mml:mo><mml:mn mathvariant="normal">7</mml:mn></mml:mrow></mml:math></inline-formula>) was successful in all cases. <italic>Cutibacterium acnes</italic> infections were seen
in 15 out of 18 of the uncemented implants (83 %) as compared to 30 out of 71 (42 %)
of all other PJIs (<inline-formula><mml:math id="M38" display="inline"><mml:mrow><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn mathvariant="normal">0.003</mml:mn></mml:mrow></mml:math></inline-formula>) (Table 3).<?xmltex \hack{\newpage}?></p>

<?xmltex \floatpos{t}?><table-wrap id="Ch1.T3" specific-use="star"><?xmltex \currentcnt{3}?><label>Table 3</label><caption><p id="d1e1376">Differences between periprosthetic joint infections with growth of
<italic>Cutibacterium acnes</italic> in tissue samples and other bacteria in 89 patients with total hip
arthroplasty.</p></caption><oasis:table frame="topbot"><oasis:tgroup cols="4">
     <oasis:colspec colnum="1" colname="col1" align="left"/>
     <oasis:colspec colnum="2" colname="col2" align="right"/>
     <oasis:colspec colnum="3" colname="col3" align="right"/>
     <oasis:colspec colnum="4" colname="col4" align="right"/>
     <oasis:thead>
       <oasis:row>
         <oasis:entry colname="col1"/>
         <oasis:entry colname="col2"><italic>Cutibacterium acnes</italic></oasis:entry>
         <oasis:entry colname="col3">Other bacteria</oasis:entry>
         <oasis:entry colname="col4"/>
       </oasis:row>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1"/>
         <oasis:entry colname="col2"><inline-formula><mml:math id="M43" display="inline"><mml:mrow><mml:mi>n</mml:mi><mml:mo>=</mml:mo><mml:mn mathvariant="normal">18</mml:mn></mml:mrow></mml:math></inline-formula></oasis:entry>
         <oasis:entry colname="col3"><inline-formula><mml:math id="M44" display="inline"><mml:mrow><mml:mi>n</mml:mi><mml:mo>=</mml:mo><mml:mn mathvariant="normal">71</mml:mn></mml:mrow></mml:math></inline-formula></oasis:entry>
         <oasis:entry colname="col4"><inline-formula><mml:math id="M45" display="inline"><mml:mi>p</mml:mi></mml:math></inline-formula></oasis:entry>
       </oasis:row>
     </oasis:thead>
     <oasis:tbody>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1">Gender</oasis:entry>
         <oasis:entry colname="col2"/>
         <oasis:entry colname="col3"/>
         <oasis:entry colname="col4"/>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Male</oasis:entry>
         <oasis:entry colname="col2">13</oasis:entry>
         <oasis:entry colname="col3">45</oasis:entry>
         <oasis:entry colname="col4"/>
       </oasis:row>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1">Female</oasis:entry>
         <oasis:entry colname="col2">5</oasis:entry>
         <oasis:entry colname="col3">26</oasis:entry>
         <oasis:entry colname="col4">0.59</oasis:entry>
       </oasis:row>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1">Median age, years (range)</oasis:entry>
         <oasis:entry colname="col2">65 (40–75)</oasis:entry>
         <oasis:entry colname="col3">70 (46–92)</oasis:entry>
         <oasis:entry colname="col4">0.20</oasis:entry>
       </oasis:row>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1">Body mass index</oasis:entry>
         <oasis:entry colname="col2"/>
         <oasis:entry colname="col3"/>
         <oasis:entry colname="col4"/>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Median BMI, kg m<inline-formula><mml:math id="M46" display="inline"><mml:msup><mml:mi/><mml:mrow><mml:mo>-</mml:mo><mml:mn mathvariant="normal">2</mml:mn></mml:mrow></mml:msup></mml:math></inline-formula> (range)</oasis:entry>
         <oasis:entry colname="col2">33.8 (24.1–45.0)</oasis:entry>
         <oasis:entry colname="col3">28.3 (20.1–48.4)</oasis:entry>
         <oasis:entry colname="col4">0.16</oasis:entry>
       </oasis:row>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1">Missing data</oasis:entry>
         <oasis:entry colname="col2">0</oasis:entry>
         <oasis:entry colname="col3">15</oasis:entry>
         <oasis:entry colname="col4"/>
       </oasis:row>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1">Surgical risk</oasis:entry>
         <oasis:entry colname="col2"/>
         <oasis:entry colname="col3"/>
         <oasis:entry colname="col4"/>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">ASA 1</oasis:entry>
         <oasis:entry colname="col2">3</oasis:entry>
         <oasis:entry colname="col3">8</oasis:entry>
         <oasis:entry colname="col4"/>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">ASA 2</oasis:entry>
         <oasis:entry colname="col2">10</oasis:entry>
         <oasis:entry colname="col3">31</oasis:entry>
         <oasis:entry colname="col4"/>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">ASA 3</oasis:entry>
         <oasis:entry colname="col2">5</oasis:entry>
         <oasis:entry colname="col3">26</oasis:entry>
         <oasis:entry colname="col4"/>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">ASA 4</oasis:entry>
         <oasis:entry colname="col2">0</oasis:entry>
         <oasis:entry colname="col3">1</oasis:entry>
         <oasis:entry colname="col4">0.35<inline-formula><mml:math id="M47" display="inline"><mml:msup><mml:mi/><mml:mtext>a</mml:mtext></mml:msup></mml:math></inline-formula></oasis:entry>
       </oasis:row>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1">Missing data</oasis:entry>
         <oasis:entry colname="col2">0</oasis:entry>
         <oasis:entry colname="col3">5</oasis:entry>
         <oasis:entry colname="col4"/>
       </oasis:row>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1">Primary implant fixation</oasis:entry>
         <oasis:entry colname="col2"/>
         <oasis:entry colname="col3"/>
         <oasis:entry colname="col4"/>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Uncemented</oasis:entry>
         <oasis:entry colname="col2">15</oasis:entry>
         <oasis:entry colname="col3">30</oasis:entry>
         <oasis:entry colname="col4"/>
       </oasis:row>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1">Cemented/hybrid</oasis:entry>
         <oasis:entry colname="col2">3</oasis:entry>
         <oasis:entry colname="col3">41</oasis:entry>
         <oasis:entry colname="col4">0.003</oasis:entry>
       </oasis:row>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1">Polymicrobial influence</oasis:entry>
         <oasis:entry colname="col2"/>
         <oasis:entry colname="col3"/>
         <oasis:entry colname="col4"/>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Single microbe</oasis:entry>
         <oasis:entry colname="col2">14</oasis:entry>
         <oasis:entry colname="col3">54</oasis:entry>
         <oasis:entry colname="col4"/>
       </oasis:row>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1">Polymicrobial</oasis:entry>
         <oasis:entry colname="col2">4</oasis:entry>
         <oasis:entry colname="col3">17</oasis:entry>
         <oasis:entry colname="col4">1.00</oasis:entry>
       </oasis:row>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1">Result surgical treatment</oasis:entry>
         <oasis:entry colname="col2"/>
         <oasis:entry colname="col3"/>
         <oasis:entry colname="col4"/>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Eradication</oasis:entry>
         <oasis:entry colname="col2">18</oasis:entry>
         <oasis:entry colname="col3">59</oasis:entry>
         <oasis:entry colname="col4"/>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Failure</oasis:entry>
         <oasis:entry colname="col2">0</oasis:entry>
         <oasis:entry colname="col3">6</oasis:entry>
         <oasis:entry colname="col4"/>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Girdlestone</oasis:entry>
         <oasis:entry colname="col2">0</oasis:entry>
         <oasis:entry colname="col3">6</oasis:entry>
         <oasis:entry colname="col4">0.12<inline-formula><mml:math id="M48" display="inline"><mml:msup><mml:mi/><mml:mtext>b</mml:mtext></mml:msup></mml:math></inline-formula></oasis:entry>
       </oasis:row>
     </oasis:tbody>
   </oasis:tgroup></oasis:table><table-wrap-foot><p id="d1e1382">ASA: American Society of Anesthesiologists physical status classification.
<inline-formula><mml:math id="M39" display="inline"><mml:msup><mml:mi/><mml:mtext>a</mml:mtext></mml:msup></mml:math></inline-formula> Calculated on ASA 1 <inline-formula><mml:math id="M40" display="inline"><mml:mo>+</mml:mo></mml:math></inline-formula> ASA 2 vs. ASA 3 <inline-formula><mml:math id="M41" display="inline"><mml:mo>+</mml:mo></mml:math></inline-formula> ASA 4.
<inline-formula><mml:math id="M42" display="inline"><mml:msup><mml:mi/><mml:mtext>b</mml:mtext></mml:msup></mml:math></inline-formula> Calculated on treatment failure including Girdlestone vs. eradication
in patients with growth of <italic>Cutibacterium acnes</italic> vs. all other.</p></table-wrap-foot></table-wrap>

</sec>
<sec id="Ch1.S3.SS3">
  <label>3.3</label><title>Treatment and outcome</title>
      <p id="d1e1849">The flow chart for the patients in the study is summarized in Fig. 2.
Treatment with DAIR was performed in 53 out of 89 PJI episodes (60 %). Failure
was noted in 7 (13 %) of these procedures. Two chronic failures ended
up with retained prostheses and lifelong antibiotic suppression; three of
the patients suffered extended implant exchanges (revisions) and two
Girdlestones which all resulted in infection eradication. Two patients with
wound complications after DAIR were treated with vacuum-assisted closure
(VAC) and received antibiotics for an additional 3 and 8 months,
respectively. There was no sign of infection recurrence 2 and 3 years
after antibiotic termination.</p>
      <p id="d1e1852">A total of 36 primary revision implant exchanges were performed, resulting in
28 out of 36 (78 %) one-stage revisions and 8 out of 36 (22 %) two-stage revisions.
The outcome of all implant exchange surgery is presented in Table 4. Peri-
and postoperative antibiotic treatment was given in accordance with
preoperative aspiration and wound cultures when available. Follow-up peroral
antibiotics were given following the results of tissue cultures and in
collaboration with an infectious diseases specialist. Changes of antibiotic
therapy were made in approximately 5 % of patients according to allergy
or other toxic effects.</p>
      <?pagebreak page224?><p id="d1e1855">A total of 34 infections (38 %) were classified as hematogenous while 55
(62 %) were postoperative. The postoperative infections also included
three failed DAIR treatments (5 %) which were later successfully revised with
infection eradication. A statistically inferior final outcome of
hematogenously infected patients was not proven (8 out of 34 vs. 4 out of 55; <inline-formula><mml:math id="M49" display="inline"><mml:mrow><mml:mi>p</mml:mi><mml:mo>=</mml:mo><mml:mn mathvariant="normal">0.052</mml:mn></mml:mrow></mml:math></inline-formula>).<?xmltex \hack{\newpage}?></p>

<?xmltex \floatpos{t}?><table-wrap id="Ch1.T4"><?xmltex \currentcnt{4}?><label>Table 4</label><caption><p id="d1e1875">Summary of revision procedures in hematogenous and postoperative
periprosthetic joint infections.</p></caption><oasis:table frame="topbot"><oasis:tgroup cols="2">
     <oasis:colspec colnum="1" colname="col1" align="left"/>
     <oasis:colspec colnum="2" colname="col2" align="right"/>
     <oasis:thead>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1"/>
         <oasis:entry colname="col2"><inline-formula><mml:math id="M50" display="inline"><mml:mi>n</mml:mi></mml:math></inline-formula> (%)</oasis:entry>
       </oasis:row>
     </oasis:thead>
     <oasis:tbody>
       <oasis:row>
         <oasis:entry colname="col1">Type of revision surgery</oasis:entry>
         <oasis:entry colname="col2"/>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">DAIR</oasis:entry>
         <oasis:entry colname="col2">53</oasis:entry>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Eradication</oasis:entry>
         <oasis:entry colname="col2">46 (87)</oasis:entry>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Revision</oasis:entry>
         <oasis:entry colname="col2">3</oasis:entry>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Failure</oasis:entry>
         <oasis:entry colname="col2">2</oasis:entry>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Girdlestone</oasis:entry>
         <oasis:entry colname="col2">2</oasis:entry>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Revision implant exchange</oasis:entry>
         <oasis:entry colname="col2">36</oasis:entry>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">One-stage</oasis:entry>
         <oasis:entry colname="col2">28 (78)</oasis:entry>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Eradication</oasis:entry>
         <oasis:entry colname="col2">26 (93)</oasis:entry>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Failure</oasis:entry>
         <oasis:entry colname="col2">2</oasis:entry>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Girdlestone</oasis:entry>
         <oasis:entry colname="col2">0</oasis:entry>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Two-stage</oasis:entry>
         <oasis:entry colname="col2">8 (22)</oasis:entry>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Eradication</oasis:entry>
         <oasis:entry colname="col2">5 (63)</oasis:entry>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Failure</oasis:entry>
         <oasis:entry colname="col2">2</oasis:entry>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Girdlestone</oasis:entry>
         <oasis:entry colname="col2">1</oasis:entry>
       </oasis:row>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1">Immediate Girdlestone</oasis:entry>
         <oasis:entry colname="col2">3</oasis:entry>
       </oasis:row>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1">Primary antibiotic treatment</oasis:entry>
         <oasis:entry colname="col2"/>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Dicloxacillin</oasis:entry>
         <oasis:entry colname="col2">20 (24)</oasis:entry>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Clindamycin</oasis:entry>
         <oasis:entry colname="col2">10 (12)</oasis:entry>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Cefotaxime</oasis:entry>
         <oasis:entry colname="col2">10 (12)</oasis:entry>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Vancomycin</oasis:entry>
         <oasis:entry colname="col2">33 (38)</oasis:entry>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Piperacillin/tazobactam</oasis:entry>
         <oasis:entry colname="col2">13 (15)</oasis:entry>
       </oasis:row>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1">Other/missing</oasis:entry>
         <oasis:entry colname="col2">3</oasis:entry>
       </oasis:row>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1">Type of infection</oasis:entry>
         <oasis:entry colname="col2"/>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Hematogenous</oasis:entry>
         <oasis:entry colname="col2">34 (38)</oasis:entry>
       </oasis:row>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1">Post-operative</oasis:entry>
         <oasis:entry colname="col2">55 (62)</oasis:entry>
       </oasis:row>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1">Outcome of hematogenous PJI</oasis:entry>
         <oasis:entry colname="col2"/>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Eradication</oasis:entry>
         <oasis:entry colname="col2">26 (76)</oasis:entry>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Failure</oasis:entry>
         <oasis:entry colname="col2">4</oasis:entry>
       </oasis:row>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1">Girdlestone</oasis:entry>
         <oasis:entry colname="col2">4</oasis:entry>
       </oasis:row>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1">Outcome of post-operative PJI</oasis:entry>
         <oasis:entry colname="col2"/>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Eradication</oasis:entry>
         <oasis:entry colname="col2">51 (93)</oasis:entry>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Failure</oasis:entry>
         <oasis:entry colname="col2">2</oasis:entry>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Girdlestone</oasis:entry>
         <oasis:entry colname="col2">2</oasis:entry>
       </oasis:row>
     </oasis:tbody>
   </oasis:tgroup></oasis:table><table-wrap-foot><p id="d1e1878">DAIR: debridement and retention of implant; PJI: prosthetic joint infection.</p></table-wrap-foot></table-wrap>

      <p id="d1e2216">The time of occurrence of the postoperative infections is presented in Table 5. In patients with revision surgery (DAIR or implant exchange, excluding Girdlestones) performed within 30 d after THA, infection eradication was
seen in 88 % (21 out of 24) as compared to 95 % (20 out of 21) in patients revised
between 31 and 180 d after primary surgery. Among patients with a later
time point for revision (<inline-formula><mml:math id="M51" display="inline"><mml:mo lspace="0mm">&gt;</mml:mo></mml:math></inline-formula> 180 d, <inline-formula><mml:math id="M52" display="inline"><mml:mrow><mml:mi>n</mml:mi><mml:mo>=</mml:mo><mml:mn mathvariant="normal">12</mml:mn></mml:mrow></mml:math></inline-formula>) three patients had
previously undergone a DAIR. The causative pathogens in treatment failures
of postoperative infections within 180 d (<inline-formula><mml:math id="M53" display="inline"><mml:mrow><mml:mi>n</mml:mi><mml:mo>=</mml:mo><mml:mn mathvariant="normal">4</mml:mn></mml:mrow></mml:math></inline-formula>) including one primary
Girdlestone were monobacterial CoNS in two cases and <italic>Staphylococcus aureus</italic> and <italic>Enterococci</italic> in one case
each respectively.</p>

<?xmltex \floatpos{t}?><table-wrap id="Ch1.T5" specific-use="star"><?xmltex \currentcnt{5}?><label>Table 5</label><caption><p id="d1e2259">Distribution and outcome of postoperative infections during different time
intervals after total hip arthroplasty (THA). Day 0 <inline-formula><mml:math id="M54" display="inline"><mml:mo>=</mml:mo></mml:math></inline-formula> time point for THA.
Failed DAIR in 3 patients resulted in 58 treatment procedures in 55
patients.</p></caption><oasis:table frame="topbot"><oasis:tgroup cols="8">
     <oasis:colspec colnum="1" colname="col1" align="left"/>
     <oasis:colspec colnum="2" colname="col2" align="right"/>
     <oasis:colspec colnum="3" colname="col3" align="right"/>
     <oasis:colspec colnum="4" colname="col4" align="right"/>
     <oasis:colspec colnum="5" colname="col5" align="right"/>
     <oasis:colspec colnum="6" colname="col6" align="right"/>
     <oasis:colspec colnum="7" colname="col7" align="right"/>
     <oasis:colspec colnum="8" colname="col8" align="right"/>
     <oasis:thead>
       <oasis:row>
         <oasis:entry colname="col1"/>
         <oasis:entry colname="col2">Total</oasis:entry>
         <oasis:entry colname="col3">DAIR</oasis:entry>
         <oasis:entry colname="col4">Implant</oasis:entry>
         <oasis:entry colname="col5">Girdlestone</oasis:entry>
         <oasis:entry colname="col6">Eradication</oasis:entry>
         <oasis:entry colname="col7">Failure</oasis:entry>
         <oasis:entry colname="col8">Median day of</oasis:entry>
       </oasis:row>
       <oasis:row rowsep="1">
         <oasis:entry colname="col1"/>
         <oasis:entry colname="col2"><inline-formula><mml:math id="M56" display="inline"><mml:mi>n</mml:mi></mml:math></inline-formula></oasis:entry>
         <oasis:entry colname="col3"><inline-formula><mml:math id="M57" display="inline"><mml:mi>n</mml:mi></mml:math></inline-formula></oasis:entry>
         <oasis:entry colname="col4">exchange <inline-formula><mml:math id="M58" display="inline"><mml:mi>n</mml:mi></mml:math></inline-formula></oasis:entry>
         <oasis:entry colname="col5"><inline-formula><mml:math id="M59" display="inline"><mml:mi>n</mml:mi></mml:math></inline-formula></oasis:entry>
         <oasis:entry colname="col6"><inline-formula><mml:math id="M60" display="inline"><mml:mi>n</mml:mi></mml:math></inline-formula> (%)</oasis:entry>
         <oasis:entry colname="col7"><inline-formula><mml:math id="M61" display="inline"><mml:mi>n</mml:mi></mml:math></inline-formula></oasis:entry>
         <oasis:entry colname="col8">revision surgery</oasis:entry>
       </oasis:row>
     </oasis:thead>
     <oasis:tbody>
       <oasis:row>
         <oasis:entry colname="col1">Day 1–30</oasis:entry>
         <oasis:entry colname="col2">24</oasis:entry>
         <oasis:entry colname="col3">21</oasis:entry>
         <oasis:entry colname="col4">2</oasis:entry>
         <oasis:entry colname="col5">1</oasis:entry>
         <oasis:entry colname="col6">21 (88)</oasis:entry>
         <oasis:entry colname="col7">2</oasis:entry>
         <oasis:entry colname="col8">24</oasis:entry>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Day 31–180</oasis:entry>
         <oasis:entry colname="col2">21</oasis:entry>
         <oasis:entry colname="col3">18</oasis:entry>
         <oasis:entry colname="col4">3</oasis:entry>
         <oasis:entry colname="col5">0</oasis:entry>
         <oasis:entry colname="col6">20 (95)</oasis:entry>
         <oasis:entry colname="col7">1</oasis:entry>
         <oasis:entry colname="col8">53</oasis:entry>
       </oasis:row>
       <oasis:row>
         <oasis:entry colname="col1">Day 181–</oasis:entry>
         <oasis:entry colname="col2">13</oasis:entry>
         <oasis:entry colname="col3">3</oasis:entry>
         <oasis:entry colname="col4">9</oasis:entry>
         <oasis:entry colname="col5">1</oasis:entry>
         <oasis:entry colname="col6">10 (77)</oasis:entry>
         <oasis:entry colname="col7">2</oasis:entry>
         <oasis:entry colname="col8">554</oasis:entry>
       </oasis:row>
     </oasis:tbody>
   </oasis:tgroup></oasis:table><table-wrap-foot><p id="d1e2269">DAIR <inline-formula><mml:math id="M55" display="inline"><mml:mo>=</mml:mo></mml:math></inline-formula> debridement and implant retention.</p></table-wrap-foot></table-wrap>

</sec>
</sec>
<sec id="Ch1.S4">
  <label>4</label><title>Discussion</title>
      <?pagebreak page225?><p id="d1e2486">We investigated 89 infected THAs in 87 patients during a period of 7 years regarding bacterial findings and treatment outcome with respect to
different surgical methods. The number of PJI episodes was relatively small
and, like in other observational studies, this creates a risk that the
diversity of both the patient populations and the treatment strategies cause
inconsistent recommendations despite our best efforts. Nevertheless, our
results support recently published treatment algorithms regarding PJI
(Born et al., 2016; Grammatopoulos et al., 2017; Sendi et al., 2017) and
are comparable with previously presented meta-analysis data concerning
revisions (Leonard et al., 2014) and DAIR (Tsang et
al., 2017). The data also point at a possible relationship between
infections with <italic>Cutibacterium acnes</italic> and uncemented hip implants.<?xmltex \hack{\newpage}?></p>
      <p id="d1e2493">With the exception of <italic>Cutibacterium acnes</italic>, the isolated bacterial agents in our study cohort
did not differ largely from other reports on prosthetic joint infections
with a majority of infections caused by staphylococci (Zimmerli et al.,
2004; Grammatopoulos et al., 2017). Multiresistant organisms are, however, less
common in Sweden than in many other countries, probably due to a more
restrictive use of broad-spectrum antibiotics, which also justifies the use
of Flucloxacillin as the principal preoperative prophylaxis (Molstad et
al., 2008). A majority of the failures in our study cohort (83 %) were
associated with PJIs caused by <italic>Staphylococcus aureus</italic>, which is known as a potent biofilm producer
and is often difficult to eradicate (Moormeier and Bayles, 2017; Sendi et
al., 2017).</p>
      <p id="d1e2502">We found an unexpectedly high number of <italic>Cutibacterium acnes</italic> infections among our patients. In
fact, this was the third dominating species occurring in 16 % of the
patients. Improved microbiological analyses during the study period may have
contributed to these findings since 15 out of 18 cases (83 %) were diagnosed
after the introduction of a new method of analysis at the local laboratory
in 2015. The role of <italic>Cutibacterium acnes</italic> as a true pathogen and not a commensal in PJIs has been
discussed  (Lavergne et al., 2017). Nevertheless, in all our cases the
bacterium was found in at least two tissue specimens and directed treatment
was successful, which would support its causative role in these infectious
episodes. We did not confirm any significant differences regarding age, sex,
BMI, or ASA class when comparing patients with PJIs caused by <italic>Cutibacterium acnes</italic> and other
pathogens. However, a small-sized study like ours may be underpowered
regarding lower median age and a higher incidence of male patients, which
has previously been described in <italic>Cutibacterium acnes</italic> infections (Levy et al., 2008; Mook et
al., 2015).</p>
      <p id="d1e2517"><italic>Cutibacterium acnes</italic> has mainly been reported in open shoulder surgery and shoulder arthroplasty (Levy et al., 2008; Mook et al., 2015). The vicinity to the upper thorax
with presence of acne vulgaris and to the axilla with lipid-rich sebaceous
hair follicles has been designated as the cause, since the bacterium is 10
times more common in this region compared with lower limb infections (Levy et al., 2008). However, our results indicate
that <italic>Cutibacterium acnes</italic> infections in other joint prostheses may be underdiagnosed. Whether
this should cause changes in the antibiotic prophylaxis of certain patient
groups requires significantly larger studies.</p>
      <p id="d1e2526">The relationship between infections with <italic>Cutibacterium acnes</italic> and uncemented hip implants in our
study is striking, particularly considering that only one-third of the total
implants during the study period were uncemented. Nevertheless, this is
significantly more than the 21 % in Sweden during the corresponding
period reported by the National Register. This might, if the observation of
a relationship between <italic>Cutibacterium acnes</italic> and uncemented hip implants is correct, be a reason
for our unusually high proportion of <italic>Cutibacterium acnes</italic> infections. In cemented THAs we have
been using the Optipac Refobacin Bone Cement R system (ZimmerBiomet,
Dieticon, Switzerland) with the 40 g package for cup fixation and 60 g
mixed for stem fixation. In the 40 g of the cement polymer is 0.5 g of
active gentamicin, which has an established bactericidal effect on
particularly gram-positive organisms like <italic>Staphylococcus aureus</italic> and CoNS
(Kendoff et al., 2016; Khassebaf et al., 2015). <italic>Cutibacterium acnes</italic>
growing in biofilm has proven susceptibility to locally administered
gentamicin (Ramage et al., 2003). It might thus be reasonable to assume
an effect on the bacteria by the release<?pagebreak page226?> of antibiotics from the cement
rather than by the influence of different alloys and coatings of the
implants (Lenguerrand et al., 2018; Braem et al., 2014).</p>
      <p id="d1e2544">The short-term clinical outcome of the <italic>Cutibacterium</italic> infections was
successful. Recommended treatment with benzylpenicillin followed by
amoxicillin or clindamycin perorally in single therapy or in combination for
3 months together with adequate surgery (Boisrenoult, 2018) resulted in infection eradication in
all cases. The Addition of rifampicin with its more serious side effects does
not seem to offer any benefits (Jacobs et al., 2016) and was in this
cohort used only in a few polymicrobial infections.</p>
      <p id="d1e2550">Our high proportion of one-stage revisions (78 %) differs from the Swedish
and international tradition but has not shown any negative impact on
infection eradication with more than 90 % successful one-stage revisions.
This is also in agreement with another recent Swedish study by Svensson et al. (2019)
based on data from the Swedish Hip Arthroplasty Register.</p>
      <p id="d1e2553">Establishment of mature biofilm is undoubtedly related to the length of time during which bacteria
affect the implant. However, the optimal interval between THA and the
performance of DAIR in postoperative cases has not been established. Sendi
and coworkers suggested an interval of <inline-formula><mml:math id="M62" display="inline"><mml:mo>≤</mml:mo></mml:math></inline-formula> 30 d after
primary or revision hip arthroplasty (Sendi et al., 2017). In a large
proportion of our cases the time from apparent infection to surgical
intervention was substantially longer, as seen in Table 5, with an average of
45 d after THA surgery. Apparent reasons for this were that initial
surgical wound care and agraffe removal was performed by district nurses and
general practitioners before the patient attended care in the emergency
unit. Here, joint aspiration was performed by educated ultrasound
radiologists. Referral to a competent hip revision surgeon took place about
a week later, surgery after another 2–8 d. Although the shortest
possible time to surgery in postoperative infections is always desirable, we
prioritized surgical experience and consulting the appropriate specialist in
infectious diseases. Despite the delayed surgical intervention, the
treatment was successful in more than 90 % of the patients that were operated on
between 31 and 180 days after THA.</p>
      <p id="d1e2563">The prognosis regarding eradication of a PJI is certainly affected by a
combination of factors including the causative microorganism, its ability to form
biofilm, type of implant, surgical radicality, and duration of
infection. Our material was too small to allow for comparisons between
different pathogens in this aspect. The failures among our post-operative
infections could also not be related to any specific pathogen. In addition,
the sample size was not large enough to establish a statistical significance
regarding the outcome of hematogenous vs. post-operative infections.</p>
      <p id="d1e2566">A major limitation of this study is its retrospective nature reflecting the
care at one medium-sized regional hospital. The limited number of patients
and the heterogenous series renders difficulties in comparisons and a risk of
type-one error. On the other hand, we have possibly included all infected
THAs during a relatively long time period. All PJIs were verified by two or
more positive tissue cultures with growth of the same pathogen. Surgery was
performed by a few experienced surgeons with similar technique and
antibiotic therapy following established guidelines.</p>
      <p id="d1e2570">Optimal treatment of PJI regarding specific infectious agents when it comes
to combining surgery and antibiotics requires large multicenter studies that
are preferably prospectively randomized. Investigations of the correlation
between certain types of implants and bacterial colonization should be made
possible by cross-checking results from national registers and
bacteriological data banks. Our study might in this aspect serve as a pilot
study with new implications.</p>
</sec>
<sec id="Ch1.S5" sec-type="conclusions">
  <label>5</label><title>Conclusions</title>
      <?pagebreak page227?><p id="d1e2582">We found an unexpectedly high number of <italic>Cutibacterium acnes</italic> infections, which raises questions
as to the choice of antibiotic prophylaxis. Our results indicate that the
use of uncemented implants may be a risk factor for PJIs caused by
<italic>Cutibacterium acnes</italic>. Although post-operative infections are preferably surgically treated with
DAIR within a month after hip replacement, infection eradication may still
not be excluded at an extended time provided there are certain types of
bacteria, assured implants, targeted antibiotic selection, and radical
surgery by experienced surgeons. Further large-scale studies are needed to
confirm our results.<?xmltex \hack{\newpage}?></p>
</sec>

      
      </body>
    <back><notes notes-type="specialsection"><title>Ethical statement</title>
    

      <p id="d1e2598">This work is a retrospective study that complies with institutional
guidelines. The purpose was to contribute to optimized treatment at our
institution by the follow-up of medical records. Individual patients cannot
be identified from the data. Ethical committee approval is therefore not
mandatory.</p>
  </notes><notes notes-type="dataavailability"><title>Data availability</title>

      <p id="d1e2604">Data are presented in the tables and figures. Depersonalized individual
patient data are provided for reviewers, but not publicly publishable for
ethical reasons, since individual patients can be identified.</p>
  </notes><notes notes-type="authorcontribution"><title>Author contributions</title>

      <p id="d1e2610">UH, MZ, JM and MG conceived this follow-up study and performed all major
surgery. UH collected data from patient files. JK supervised on bacteriology
and antibiotic treatment and double-checked data from additional local
bacteriological registers. UH and JK wrote the paper. The final draft
was approved by all authors.</p>
  </notes><notes notes-type="competinginterests"><title>Competing interests</title>

      <p id="d1e2616">The project has been registered in the national Swedish register
for medical research (<uri>https://www.researchweb.org/is/vgr/project/261141</uri>, last access: 31 May 2021). No benefits
in any form have been received or will be received from a commercial party
related to the subject of this article. Urban Hedlundh has received lecturer fees from
Zimmer-Biomet and Smith&amp;Nephew.</p>

      <p id="d1e2622">The contact author has declared that neither they nor their co-authors have any competing interests.</p>
  </notes><notes notes-type="reviewstatement"><title>Review statement</title>

      <p id="d1e2628">This paper was edited by Alex McLaren and reviewed by three anonymous referees.</p>
  </notes><ref-list>
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  </ref-list></back>
    <!--<article-title-html>Periprosthetic hip infections in a Swedish regional hospital between 2012 and 2018: is there a relationship between <i>Cutibacterium acnes</i> infections and uncemented prostheses?</article-title-html>
<abstract-html><p>The purpose of this study was to evaluate patients requiring in-patient care
due to a periprosthetic joint infection (PJI), with respect to bacterial
agents, surgical treatment, antibiotics, and outcome. We retrospectively identified all infected total hip arthroplasties (THAs) in
a Swedish regional hospital during a 7-year period (2012–2018) and reviewed
medical records and microbiological data. A total of 89 infected THAs in 87 patients were identified. Standardized
treatment with debridement with retention of the implant and antibiotics
(DAIR) was initially performed in 53 cases (60&thinsp;%), one or two stage
revisions in 33 cases (37&thinsp;%), and an immediate Girdlestone in 3 cases (3&thinsp;%). Infection eradication was seen in 77 PJIs (87&thinsp;%) in addition to
six patients (7&thinsp;%) ending up with a permanent but uninfected Girdlestone.
All six patients with manifest failures were infected with <i>Staphylococcus aureus</i>, two of which
were also polymicrobial. <i>Cutibacterium acnes</i> was found in 18 of 89 patients (16&thinsp;%) distributed
in 15 uncemented implants but only in 3 hybrids and cemented arthroplasties,
while remaining pathogens were equally distributed in uncemented THAs (<i>n</i> = 31) and THAs with at least one cemented component (<i>n</i> = 40; <i>p</i> = 0.003).
Eradication was achieved in all 18 patients when <i>Cutibacterium acnes</i> was the only culture (<i>n</i> = 14) or
clearly dominant among positive cultures (<i>n</i> = 4). DAIR was successful in
selected postoperative infections up to 6 months after hip replacement.
<i>Cutibacterium acnes</i> infections in hip arthroplasty may be underdiagnosed. Cemented components
in THAs seem to protect from colonization with <i>Cutibacterium acnes</i>.</p></abstract-html>
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