Outcome of hip and knee periprosthetic joint infections caused by pathogens resistant to biofilm-active antibiotics: results from a prospective cohort study

Abstract

Background
Periprosthetic joint infections (PJI) caused by pathogens, for which no biofilm-active antibiotics are available, are often referred to as difficult-to-treat (DTT). However, it is unclear whether the outcome of DTT PJI is worse than those of non-DTT PJI. We evaluated the outcome of DTT and non-DTT PJI in a prospective cohort treated with a two-stage exchange according to a standardized algorithm. Methods
Patients with hip and knee PJI from 2013 to 2015 were prospectively included and followed up for ≥ 2 years. DTT PJI was defined as growth of microorganism(s) resistant to all available biofilm-active antibiotics. The Kaplan–Meier survival analysis was used to compare the probability of infection-free survival between DTT and non-DTT PJI and the 95% confidence interval (95% CI) was calculated. ResultsAmong 163 PJI, 30 (18.4%) were classified as DTT and 133 (81.6%) as non-DTT. At a mean follow-up of 33 months (range 24–48 months), the overall treatment success was 82.8%. The infection-free survival rate at 2 years was 80% (95% CI 61–90%) for DTT PJI and 84% (95% CI 76–89%) for non-DTT PJI (p = 0.61). The following mean values were longer in DTT PJI than in non-DTT PJI: hospital stay (45 vs. 28 days; p < 0.001), prosthesis-free interval (89 vs. 58 days; p < 0.001) and duration of antimicrobial treatment (151 vs. 117 days; p = 0.003). Conclusions
The outcome of DTT and non-DTT PJI was similar (80–84%), however, at the cost of longer hospital stay, longer prosthesis-free interval and longer antimicrobial treatment. It remains unclear whether patients undergoing two-stage exchange with a long interval need biofilm-active antibiotics. Further studies need to evaluate the outcome in patients treated with biofilm-active antibiotics undergoing short vs. long interval.

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Archives of Orthopaedic and Trauma Surgery
https://doi.org/10.1007/s00402-018-2886-0
ORTHOPAEDIC SURGERY
Outcome ofhip andknee periprosthetic joint infections caused
bypathogens resistant tobiofilm-active antibiotics: results
fromaprospective cohort study
DorukAkgün1· CarstenPerka1· AndrejTrampuz1· NoraRenz1
Received: 4 October 2017
© Springer-Verlag GmbH Germany, part of Springer Nature 2018
Abstract
Background Periprosthetic joint infections (PJI) caused by pathogens, for which no biofilm-active antibiotics are available,
are often referred to as difficult-to-treat (DTT). However, it is unclear whether the outcome of DTT PJI is worse than those of
non-DTT PJI. We evaluated the outcome of DTT and non-DTT PJI in a prospective cohort treated with a two-stage exchange
according to a standardized algorithm.
Methods Patients with hip and knee PJI from 2013 to 2015 were prospectively included and followed up for ≥ 2years.
DTT PJI was defined as growth of microorganism(s) resistant to all available biofilm-active antibiotics. The Kaplan–Meier
survival analysis was used to compare the probability of infection-free survival between DTT and non-DTT PJI and the 95%
confidence interval (95% CI) was calculated.
Results Among 163 PJI, 30 (18.4%) were classified as DTT and 133 (81.6%) as non-DTT. At a mean follow-up of 33months
(range 24–48months), the overall treatment success was 82.8%. The infection-free survival rate at 2years was 80% (95%
CI 61–90%) for DTT PJI and 84% (95% CI 76–89%) for non-DTT PJI (p = 0.61). The following mean values were longer in
DTT PJI than in non-DTT PJI: hospital stay (45 vs. 28 days; p < 0.001), prosthesis-free interval (89 vs. 58 days; p < 0.001)
and duration of antimicrobial treatment (151 vs. 117 days; p = 0.003).
Conclusions The outcome of DTT and non-DTT PJI was similar (80–84%), however, at the cost of longer hospital stay,
longer prosthesis-free interval and longer antimicrobial treatment. It remains unclear whether patients undergoing two-stage
exchange with a long interval need biofilm-active antibiotics. Further studies need to evaluate the outcome in patients treated
with biofilm-active antibiotics undergoing short vs. long interval.
Keywords Periprosthetic joint infection· Difficult-to-treat· Outcome· Biofilm-active antibiotics
Introduction
Periprosthetic joint infection (PJI) is a rare but severe com-
plication after joint arthroplasty [1]. The reported incidence
in hip and knee arthroplasty ranges from 0.3 to 2.2% after
primary and up to 5.9% after revision surgery [2–4]. Numer-
ous studies reported high cure rates of PJI (72–100%) using
a two-stage prosthesis exchange [5–12]. Although the main
surgical procedures are well described (i.e., prosthesis reten-
tion, one-stage or two-stage exchange), the type and duration
of antimicrobial treatment are still discussed controversially
and are often not mentioned in published reports.
While the role of microbial biofilms in the pathogenesis
of PJI is well studied [13, 14], the impact of the type of
pathogen and its antimicrobial susceptibility on the treat-
ment outcome is not well investigated. This topic is gaining
* Doruk Akgün
doruk.akguen@charite.de
Carsten Perka
carsten.perka@charite.de
Andrej Trampuz
andrej.trampuz@charite.de
Nora Renz
nora.renz@charite.de
1 Corporate member ofFreie Universität Berlin,
Humboldt-Universität zu Berlin, andBerlin Institute
ofHealth, Center forMusculoskeletal Surgery, Charité,
Universitätsmedizin Berlin, Charitéplatz 1, 10117Berlin,
Germany

Archives of Orthopaedic and Trauma Surgery
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importance in the era of rising antimicrobial resistance, tak-
ing into account that only few antimicrobial agents exhibit
anti-biofilm activity such as rifampin against staphylococcal
biofilms [15–20] and ciprofloxacin, against Gram-negative
biofilms [21–23]. Several clinical studies demonstrated
higher cure rates of staphylococcal PJI with rifampin-
containing regimens compared to regimens containing no
biofilm-active antimicrobials, if the prosthesis was retained
[24, 25].
Therefore, PJI caused by pathogens, for which no bio-
film-active antibiotics are available, are often referred to
as difficult-to-treat (DTT), including rifampin-resistant
staphylococci, fluoroquinolone-resistant Gram-negative
bacteria, enterococci and fungi (mainly Candida spp.) [26].
PJI caused by enterococci and fungi are defined as DTT
independent of the pathogen susceptibility, as anti-biofilm
antimicrobials against these pathogens are lacking, as also
shown by high failure rates in PJI due to these microorgan-
isms [27–29].
In the literature, two-stage exchange with a long interval
(> 6 weeks) is recommended in case of a DTT PJI but it is
unclear whether the unavailability of biofilm-active antibi-
otics adversely influences the treatment outcome compared
to non-DTT PJI if a two-stage exchange is used. In this pro-
spective cohort study, we compared the outcome of DTT and
non-DTT PJI managed with a two-stage exchange arthro-
plasty and standardized antimicrobial treatment regimen.
Methods
Study design
This retrospective analysis of prospectively collected data
was conducted in a tertiary healthcare center, providing
advanced specialty care to a population of about four mil-
lion inhabitants and including a specialized referral center
for septic surgery. A standardized diagnostic and therapeutic
algorithm was applied, including the surgical and antimi-
crobial treatment (see details below). The study protocol
was reviewed and approved by the institutional ethics com-
mittee and was done in accordance with the Declaration of
Helsinki.
Study population
Consecutive patients with hip and knee PJI treated with
a two-stage exchange at our institution from April 2013
through December 2015 were included. Patients with native
septic arthritis, with incomplete data sets and those with
follow-up less than 24 months were excluded.
Data collection
Cases were identified from the institutional patient-based PJI
database and data obtained by reviewing electronic medical
charts of consecutive patients with hip and knee PJI (see def-
inition below) and completing a case report form. At admis-
sion, comorbidities, the Charlson Comorbidity Index score
(CCI) [30], surgical history of the infected joint, clinical
manifestation, laboratory values such as serum C-reactive
protein (CRP) and blood leukocytes and presumed route of
infection (intraoperative vs. hematogenous) were recorded.
In addition, the following data were extracted: number of
revision surgeries between stages, length of hospital stay,
total duration of antimicrobial therapy, serum CRP value at
the time of reimplantation, microbiological and pathological
results of revisions and reimplantation.
Definition ofperiprosthetic joint infection
In this cohort, PJI was diagnosed according to the proposed
European Bone and Joint Infection Society (EBJIS) crite-
ria [31], since these criteria were used in several outcome
studies [32, 33] and are increasingly applied due to their
high sensitivity in low-grade infections. According to this
classification system, PJI was confirmed when at least one
of the following criteria was fulfilled: (1) macroscopic puru-
lence around the prosthesis; (2) presence of sinus tract; (3)
increased synovial fluid leukocyte count and differential
(> 2000 leukocytes/µl or > 70% granulocytes); (4) signifi-
cant microbial growth in synovial fluid, periprosthetic tissue
or sonication culture of retrieved prosthesis components; (5)
positive histopathology, defined as ≥ 23 granulocytes per
10 high-power field, corresponding to the type II or type III
classification of the periprosthetic membrane [34]. DTT PJI
was diagnosed when at least one of the causing microorgan-
isms was resistant to biofilm-active antibiotics, including
rifampin-resistant staphylococci, enterococci, fluoroqui-
nolone-resistant Gram-negative bacteria and fungi [26].
Sonication was performed for 1min at 40kHz (BactoSonic,
Bandelin electronic, Berlin, Germany), the resulting sonica-
tion fluid was plated onto aerobic and anaerobic sheep blood
agar plates and incubated for 14 days.
Standardized surgical andantimicrobial treatment
algorithm
Surgical treatment
During the first stage of the two-stage prosthesis exchange,
all implant parts, necrotic tissue, bone cement and other
foreign material were removed, followed by debridement

Archives of Orthopaedic and Trauma Surgery
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of the surrounding tissue. In hip joints, resection arthro-
plasty without cement spacer was performed, according to
the institutional standard practice, whereas in knee joints an
antibiotic-loaded static cement spacer was inserted. Cement
spacers were loaded with 4g of antibiotics per 40g PMMA,
typically gentamicin in combination with either clindamycin
or vancomycin. The time of reimplantation was determined
by the following criteria: the local status was satisfactory
(no discharge from the incision site, surgical wound healed,
soft tissues not compromised) and absence of laboratory
signs of persisting infection (increased CRP without other
known reason). In DTT PJI, a longer interval (> 6 weeks)
was preferred [26]. In case of suspected persistent infec-
tion, an additional revision surgery with debridement was
performed (and spacer exchange, if present).
Antimicrobial treatment
Antibiotics were routinely administered intravenously for the
first 2 weeks, followed by oral antimicrobials until reimplan-
tation. If no appropriate oral antibiotics were available, an
outpatient intravenous antimicrobial therapy was adminis-
tered. Antibiotics were continued until reimplantation with-
out an antibiotic-free interval and without a pre-implantation
diagnostic joint aspiration. After reimplantation, antibiotics
were initially administered intravenously until the wound
was healed, followed by an oral biofilm-active (in non-DTT
PJI) or biofilm-non-active antimicrobials (in DTT PJI) for a
total treatment duration of at least 12 weeks, with a mini-
mum of 6 weeks antimicrobial course after reimplantation.
Evaluation offollow‑up
Patients were evaluated in our outpatient clinic 3, 6, 12
months after septic revision surgery and annually afterwards.
A standardized questionnaire evaluating the general health,
joint and skin status, any additional surgical interventions,
clinical complaints, and antibiotic use was used. Clinical,
laboratory and radiological evaluations were performed and
evaluated by an orthopedic surgeon and an infectious dis-
ease specialist. Further follow-up was performed contacting
the patients by phone or during the visit in the outpatient
clinic. Treatment outcome of PJI was evaluated accord-
ing to the modified Delphi international multidisciplinary
consensus criteria [35]. Infection-free outcome was defined
when all of the following criteria were fulfilled: (1) infec-
tion eradication, characterized by a healed wound without
sinus tract, drainage, and no recurrence of the infection at
last follow-up, (2) no subsequent surgical intervention after
reimplantation for persistent or perioperative infection, (3)
no PJI-related death, and (4) no long-term antimicrobial sup-
pression therapy (duration > 6 months) after reimplantation.
Due to poor sensitivity and specificity, laboratory parameters
such as CRP were not used for determination of infection
eradication [36].
Statistical analysis
Chi-square and Fisher’s exact tests were employed to com-
pare differences between categorical variables. The two-
sample t test (for parametric distribution) or Mann–Whitney
U test (for non-parametric distribution) was used to compare
continuous variables between groups. A multiple logistic
regression model in forward stepwise was used to determine
factors associated with DTT PJI evaluating the following
variables: (1) age-adjusted Charlson comorbidity index; (2)
age; (3) joint; (4) sex; (5) number of previous septic revision;
(6) sinus tract. The probability of infection-free survival and
the 95% confidence interval (95% CI) was estimated using
the Kaplan–Meier survival method. Survival curves between
groups were compared by the log-rank (Mantel–Cox) test. A
p value < 0.05 was considered significant. Statistical analysis
was performed using SPSS version 20 software (SPSS Inc.,
Chicago, IL, USA) and the software Prism (Version 7.03;
GraphPad, La Jolla, CA, USA).
Results
Patient demographics andinfection characteristics
Demographic data, clinical and laboratory findings of PJI
are summarized in Table1. During the study period, 182
patients undergoing two-stage exchange were identified.
After exclusion of 19 PJI due to a follow-up shorter than
24 months, 163 patients were included, 84 with hip and 79
with knee prostheses. Data of this patient cohort analyzing
the effect of positive microbiology at reimplantation on sub-
sequent treatment failure were recently published [37]. In 30
PJI (18 hip and 12 knee prostheses), PJI was categorized as
DTT, caused by enterococci in 18 patients, rifampin-resist-
ant Staphylococcus epidermidis in 10 patients and fungi in
3 patients. One patient had a polymicrobial infection with
Enterococcus faecalis and Candida albicans. No infection
caused by fluoroquinolone-resistant Gram-negative bacteria
was found. History of a previous septic revision was reported
in 70% (21 of 30) of patients in DTT group compared to 46%
(61 of 133) of patients in non-DTT group (p = 0.025). Mixed
infection was documented more frequently in DTT group
than non-DTT group (Table1).
Treatment
Table2 summarizes data on treatment characteristics. The
hospital stay (45 vs. 28 days, p < 0.001) and the prosthesis-
free interval (89 vs. 58 days; p < 0.001) were significantly

Archives of Orthopaedic and Trauma Surgery
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longer in the DTT PJI group. The total duration of antimicro-
bial treatment was longer in the DTT PJI group than in the
non-DTT PJI group (151 vs. 117 days; p = 0.003).
Outcome analysis
At a mean follow-up of 33months (range 24–48months),
the overall treatment success was 82.8%. Figure1 shows the
Kaplan–Meier-estimated infection-free survival of DTT PJI
and non-DTT PJI group. The infection-free survival rate at
2years was 80% (95% CI 61–90%) for DTT PJI group and
84% for non-DTT PJI group (95% CI 76–89%) (p = 0.614).
Two of six failures in DTT PJI group were suppressed
with long-term antibiotics and the remaining four needed
a revision surgery due to a persistent infection, two cases
with isolation of the same microorganism and two cases with
other microorganisms. Two cases in the non-DTT PJI group
failed due to implemented long-term suppression antibiotic
therapy and 20 cases relapsed requiring another surgical
revision. None of the patients with suppression therapy (in
both groups) needed further surgical treatment.
Analyzing affected hip and knee prosthesis with differ-
ent surgical approach (i.e., use of cement spacers in knee
and resection arthroplasty in hip joints), the treatment suc-
cess was significantly better in hip than knee prosthesis. In
hip prosthesis cure of PJI was achieved in 75 of 84 patients
(89%) [including 15 of 18 patients (83%) in DTT group
and 60 of 66 patients (91%) for non-DTT], whereas in knee
Table 1 Patient demographics, clinical and laboratory findings
* The values are given as the mean and the standard deviation
a The values are given as the number with the percentage of the group in parentheses
Variable All patients (n = 163) DTT PJI group (n = 30) Non-DTT PJI group
(n = 133)
p value
Patient age at the time of explantation (years)* 70 ± 10 69.5 ± 12.5 69.6 ± 9.8 0.965
Sexa0.978
Male 71 (43.6) 13 (43.3) 58 (43.6)
Female 92 (56.4) 17 (56.7) 75 (56.4)
Jointa0.304
Hip 84 (51.5) 18 (60) 66 (49.6)
Knee 79 (48.5) 12 (40) 67 (50.4)
Charlson comorbidity index (age adjusted)*4 ± 2.1 4.5 ± 2.6 3.9 ± 2 0.122
CRP at admission (mg/l)*39.2 ± 67 41 ± 49.9 38.8 ± 70.5 0.053
Microbiologya
Monomicrobial 79 (48.5) 14 (46.7) 65 (48.9) 0.827
Polymicrobial 61 (37.4) 16 (53.3) 45 (33.8) 0.046
Negative cultures 23 (14.1) – 23 (17.3) –
No. of patients with previous septic revisionsa82 (50.3) 21 (70) 61 (45.9) 0.025
No. of previous septic revisions* 2.5 ± 1.6 1.8 ± 1.7 1.1 ± 1.7 0.015
Table 2 Treatment and outcome characteristics of all patients
The values are given as the mean and the standard deviation
a The four patients who were suppressed with long-term antimicrobial therapy are excluded
Variable All patients (n = 163) DTT PJI group (n = 30) Non-DTT PJI group
(n = 133)
p value
Treatment
Time until reimplantation (days) 63.9 ± 34.5 89.4 ± 50.5 58.1 ± 26.9 < 0.001
CRP prior to reimplantation (mg/l) 11.9 ± 13.1 10 ± 11.8 12.3 ± 13.4 0.164
Total duration of antimicrobial therapy (days) 123.3 ± 57.7 150.8 ± 74.7 117.4 ± 51.7 0.003
Duration of i.v. antimicrobial therapy (days)a32.8 ± 20.2 50.4 ± 31 29 ± 14.7 < 0.001
Duration of oral antimicrobial therapy (days)a84.1 ± 32.2 90.1 ± 47.3 82.8 ± 28.2 0.553
No. of revisions during interval 1.7 ± 1.3 2 ± 1.6 1.5 ± 1 0.324
Duration of hospital stay (days) 31.2 ± 15.9 44.5 ± 26.5 28.2 ± 10.4 < 0.001

Archives of Orthopaedic and Trauma Surgery
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prosthesis PJI was cured in 59 of 79 patients (75%) [includ-
ing 8 of 12 patients (75%) in DTT group and 51 of 67 (76%)
in non-DTT group] (p = 0.023).
Figure2 shows survival curves of three groups with DTT
PJI caused by different microorganisms, including rifampin-
resistant staphylococci, enterococci and fungi. One patient
with polymicrobial infection involving Enterococcus faeca-
lis and Candida albicans was excluded from this sub-group
analysis. No significant differences were seen between the
DTT and non-DTT PJI sub-groups (p = 0.525).
Multiple regression analysis showed higher Charlson
comorbidity index as the only independent risk factor
predictive of DTT PJI (odds ratio 1.3; 95% confidence inter-
val 1.0–1.6; p = 0.046). The number of previous septic revi-
sions in history (1.8 vs. 1.1; p = 0.02) was also significantly
higher in DTT PJI group, but did not remain significant in
the multiple regression analysis (odds ratio 1.3; 95% CI
1.0–1.6; p = 0.059) (Table3).
Discussion
We report an overall treatment success of 82.8%, which is
rather high taking into consideration that the cohort con-
sisted predominantly of complex PJI cases, often referred
to our specialized septic surgery unit after several previous
treatment attempts have failed. Multiple regression analysis
did not show association of previous septic revisions with
DTT PJI. Nevertheless, the history of prior revisions for
infection, especially when combined with insufficient anti-
microbial therapy, is considered as one of the leading factors
associated with emergence of antimicrobial resistance and
consecutive treatment failure. In particular, rifampin mono-
therapy and repeated prior surgical revisions were associated
with emergence of rifampin resistance [38].
Many authors suggested that treating DTT PJI is more
challenging than in non-DTT PJI, requiring two-stage
exchange and a long prosthesis-free interval (≥ 6 weeks)
[26]. In our cohort, antibiotic-free period before reimplan-
tation was not used since discontinuation of antimicrobi-
als may allow recovery of microbial growth and thereby
increase the risk of treatment failure. In addition, joint
aspiration before reimplantation showed low sensitivity
and specificity for detection of persistent infection and was,
therefore, omitted [39–41].
To our knowledge, this is the first study investigating
the outcome of PJI caused by microorganisms, for which
biofilm-active antibiotics are not available. In our cohort,
the treatment outcome of DTT and non-DTT PJI was similar
(80% and 84%, respectively); however, a longer prosthesis-
free interval, longer hospital stay and longer antimicrobial
treatment were needed to achieve the local and laboratory
01020304
05
0
0
20
40
60
80
100
Time (months)
Probability of infection-free survival (%)
p = 0.61
DTT
Non-DTT
Fig. 1 The probability of infection-free survival of difficult-to-treat
(DTT) and non-DTT PJI group
01020304050
0
20
40
60
80
100
Time (months)
Pr
obabilityofinfection-free survival(%)
p = 0.52
Rifampin resistent Staphylococcus epi.
Enterococcus spp.
Candida spp.
Fig. 2 The probability of infection-free survival of three difficult-to-
treat microorganisms (Candida spp., Enterococcus spp., rifampin-
resistant staphylococci). One patient with polymicrobial infection
including Candida albicans and Enterococcus faecalis was excluded
from the analysis
Table 3 Results of multivariate regression analysis as independent
risk factors predictive of DTT PJI
Variable OR (95% CI) p value
Age-adjusted CCI 1.3 (1.0–1.6) 0.046
Age 1.0 (0.9–1.0) 0.178
Joint 0.8 (0.5–1.2) 0.212
Sex 0.9 (0.6–1.4) 0.677
Number of previous septic
revisions
1.3 (1.0–1.6) 0.059
Sinus tract 1.0 (0.6–1.7) 0.998

Archives of Orthopaedic and Trauma Surgery
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conditions required for reimplantation. This finding was
unexpected, since the unavailability of biofilm-active anti-
biotics was hypothesized to be associated with worse out-
come [42]. Based on findings of this study, the term DTT
PJI may not be appropriate, since the outcome is similar to
that in non-DTT PJI when the described surgical and antimi-
crobial treatment algorithm is followed. As recently stated,
a biofilm-active antibiotic should be used after reimplanta-
tion, if an implant (including spacer) is kept in place or the
new device is implanted before complete healing of infec-
tion [43]. As bacteria may also persist in the bone causing
chronic osteomyelitis, antibiotic treatment after reimplanta-
tion may be rational and may reduce the treatment failure
rate.
Antibiotic-impregnated cement spacers may act as a for-
eign body, on which biofilm may form despite initial high
local release of antibiotics [44]. Accordingly, a prosthesis-
free interval without the use of spacer is generally preferred
in difficult-to-treat infections [45]. However, our data are
demonstrating no differences between the DTT and non-
DTT group. Hence, based on these data, spacer may be used
in DTT PJI.
Several authors proposed other types of microorgan-
isms as causing DTT PJI, including methicillin-resistant
staphylococci, Pseudomonas aeruginosa and other resistant
microorganisms, but susceptible to biofilm-active antibiotics
[12, 46–49]. However, the data supporting this conclusion
may represent a bias since most studies were retrospective,
without applying a standardized antimicrobial and surgical
treatment algorithm, including heterogeneous patients, not
reporting the type of antimicrobial treatment and using non-
uniform definitions of treatment failure [50]. In such inho-
mogeneous study population, the findings may be inconclu-
sive. This assumption is supported by several studies which
showed high cure rates (up to 92%) in methicillin-resistant
staphylococcal PJI, when rifampin was administered in com-
bination antimicrobial regimen, compared to low eradica-
tion rates when biofilm non-active agents were administered
alone, such as vancomycin, linezolid, daptomycin and fluo-
roquinolones [20, 51, 52]. Similarly, fluoroquinolones were
also active in the guinea pig foreign-body infection model in
terms of biofilm eradication in Gram-negative bacilli [26].
Therefore, use of biofilm-active antimicrobials and fol-
lowing a standardized therapeutic regime can achieve high
eradication rates in methicillin-resistant staphylococci, simi-
lar to methicillin-susceptible ones without prolonging the
prosthesis-free interval and total duration of antimicrobial
treatment.
We recognize few limitations of this study. First, the
low number of DTT PJI does not permit subgroup analy-
sis regarding the type of microorganism or best surgical
approach and the number of needed revisions. Therefore, it
is unknown whether the same treatment success in DTT PJI
would be achievable with less aggressive surgical regimen.
Second, the contribution of prolonged antimicrobial treat-
ment in DTT PJI on the high success is unknown since no
control group with shorter antimicrobial treatment course
was evaluated. Third, despite the minimum follow-up period
was 24 months, some patients may still develop an infection
relapse. Fourth, as in both groups, the prosthesis-free inter-
val and antibiotic treatment were longer than proposed by
the applied algorithm owing to the complexity of the mainly
secondarily referred patients, the interpretation of the results
is difficult. Fifth, unequal usage of spacers in hip and knee
patients can alter the treatment outcome and mislead our
outcome results.
Conclusion
The treatment outcome of DTT was similar to the one of
non-DTT PJI (80–84%), however, at the cost of longer hos-
pital stay, longer prosthesis-free interval and longer antimi-
crobial treatment in DTT PJI. It remains unclear whether
patients undergoing two-stage exchange with a long inter-
val need biofilm-active antibiotics. Further studies need to
evaluate the outcome in patients treated with biofilm-active
antibiotics undergoing short vs. long interval.
Compliance with ethical standards
Conflict of interest Authors DA, NR and AT declare that they have no
conflict of interest. Author CP reports grants from Aesculap, personal
fees from Zimmer, Smith & Nephew, Depuy/Synthes, Ceramtec and
Link, outside the submitted work.
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