ARTHROPLASTY
High failure rates in treatment of
D. Akgn,
A. Trampuz,
C. Perka,
N. Renz
From Charit
Universittsmedizin
Berlin, Center for
Musculoskeletal
Surgery, Berlin,
Germany
D. Akgn, MD, Orthopaedic
Surgeon
A. Trampuz, MD, Infectious
Disease Specialist
C. Perka, MD, Orthopaedic
Surgeon
N. Renz, MD, Internal
Medicine Specialist
Charit Universittsmedizin
Berlin, Center for
Musculoskeletal Surgery,
Berlin, Germany.
Correspondence should be sent
to D. Akgn; email:
doruk.akguen@charite.de
2017 The British Editorial
Society of Bone & Joint
Surgery
doi:10.1302/0301-620X.99B5.
BJJ-2016-0851.R1 $2.00
Bone Joint J
2017;99-B:6539.
Received 24 August 2016;
Accepted after revision 29
December 2016
VOL. 99-B, No. 5, MAY 2017
streptococcal periprosthetic joint infection
RESULTS FROM A SEVEN-YEAR RETROSPECTIVE COHORT STUDY
Aims
To investigate the outcomes of treatment of streptococcal periprosthetic joint infection (PJI)
involving total knee and hip arthroplasties.
Patients and Methods
Streptococcal PJI episodes which occurred between January 2009 and December 2015 were
identified from clinical databases. Presentation and clinical outcomes for 30 streptococcal
PJIs in 30 patients (12 hip and 18 knee arthroplasties) following treatment were evaluated
from the medical notes and at review. The Kaplan-Meier survival method was used to
estimate the probability of infection-free survival. The influence of the biofilm active
antibiotic rifampin was also assessed.
Results
The infection was thought to have been acquired haematogenously in 16 patients and peri-
operatively in 14. The median follow-up time for successfully treated cases was 39.2 months
(12 to 75), whereas failure of the treatment occurred within the first year following
treatment on every occasion. The infection-free survival at three years with 12 patients at
risk was 59% (95% confidence interval 39% to 75%). Failure of the treatment was observed
in ten of 22 PJIs (45%) treated with a two-stage revision arthroplasty, two of six (33%)
treated by debridement and prosthesis retention, and in neither of the two PJIs treated with
one-stage revision arthroplasty. Streptococcal PJI treated with or without rifampin included
in the antibiotic regime showed no difference in treatment outcome (p = 0.175).
Conclusion
The success of treatment of streptococcal PJI in our patient cohort was poor (18 of 30 cases,
59%). New therapeutic approaches for treating streptococcal PJI are needed.
Cite this article: Bone Joint J 2017;99-B:6539.
It is estimated that streptococci account for such as rifampin is also unclear. Playing a key
10% of periprosthetic joint infections (PJI).1 role in eradication of staphylococcal biofilms, the
Haematogenous spread from a distant primary activity of rifampin on streptococcal biofilm is
focus of infection represents the predominant unknown. While in vitro studies suggest no activ-
route of infection.2 In the last two decades there ity of rifampin on streptococcal biofilms, a recent
has been an increase in invasive streptococcal clinical study demonstrated better results for
infections in adults.3 Therefore it would not be patients with streptococcal infection, treated
unexpected for frequency of streptococcal PJI to with the addition of rifampin.11
have increased. However, little is known about We have conducted a retrospective cohort
the clinical presentation, management and study of all patients with streptococcal PJI
treatment outcomes of streptococcal PJI. Previ- treated at our institution to evaluate the patho-
ously, infections due to group B streptococci genesis, clinical characteristics, and outcomes of
have been reported.1,4-7 Data on other types of treatment. We have also analysed the influence of
streptococcal infection are limited. rifampin in combination with standard antibiotic
Streptococcal infections were thought to be treatment on the outcome of streptococcal PJI.
readily responsive to treatment due to their broad
antimicrobial sensitivity (including penicillin). Patients and Methods
However, conflicting data exist about the out- This cohort study was conducted at a tertiary
comes of treatment for streptococcal PJI.1,6,8-10 healthcare centre, providing specialty care, to a
The role and influence of anti-biofilm antibiotics, population of about four million. Cases were
653
654 D. AKGN, A. TRAMPUZ, C. PERKA, N. RENZ
identified from our PJI database and data were obtained by
reviewing and collating the electronic medical records of
patients with streptococcal PJI. The antimicrobial and sur-
gical treatment undertaken were performed at the discre-
tion of the treating physicians and surgeons, guided by an
established treatment algorithm for PJI.12 The study proto-
col was reviewed and approved by our institutional ethics
committee.
Patients with hip and knee PJI caused by streptococci and
treated at our institution between January 2009 and
December 2015, were identified. A total of 13 patients with
polymicrobial infections (n = 11) or with incomplete data
(n = 2) were excluded. In total 30 patients with streptococ-
cal PJIs were considered eligible and included in the study,
involving 12 hip and 18 knee arthroplasties. The median
patient age was 71 years (47 to 90).
PJI was defined when at least one of the following crite-
ria were present:12,13 macroscopic purulence around the
prosthesis; presence of sinus tract; abnormal synovial fluid
leucocyte count and differential (> 2000 leucocytes/l or
> 70% granulocytes); growth of Streptococcus species from
synovial fluid, periprosthetic tissue or sonication culture of
retrieved prosthetic components; positive histopathology,
defined as a mean of 23 granulocytes per ten high-
powered fields, corresponding to type 2 or type 3 peripros-
thetic membrane.14
Infections were classified into three groups according to
the time of onset following hip or knee arthroplasty, as
early (less than three months), delayed (three to 24 months)
and late PJI (> 24 months).15 Haematogenous infection was
defined when the onset of the symptoms was more than
three months after the index arthroplasty surgery and the
infection was of acute onset, or the same Streptococcus spe-
cies was isolated from blood cultures respectively from a
distant focus of infection. Acute infection was defined when
new joint symptoms commenced less than or equal to three
weeks post-operatively, in cases of early peri-operative PJI
or after an initial uneventful clinical course following the
index surgery, and without signs of prosthetic loosening at
the onset of symptoms in the case of haematogenous PJI. In
addition to these criteria, each case was evaluated and clas-
sified by an interdisciplinary team of an orthopaedic sur-
geon (DA or CP) and an infectious disease specialist (NR or
AT). The interval from the primary arthroplasty or last
revision surgery to diagnosis of streptococcal infection was
identified.
Success of treatment of the PJI was judged according to
the Delphi international multidisciplinary consensus.16
Presence of all the following criteria were required at the
latest follow-up: infection eradication, characterised by a
well healed wound and no clinical evidence of recurrent
infection (e. g., no persisting wound drainage or sinus for-
mation); no further surgical intervention for persistent
signs of infection after re-implantation; no PJI-related
death; no long-term antimicrobial suppression therapy
(duration more than six months). Treatment failure was
classified as clinical recurrence of PJI during antimicrobial
therapy or recurrence of PJI more than two weeks after
completion of antimicrobial therapy with isolation of same
streptococcal species in the joint. A re-infection was defined
as a new infection after completion of antimicrobial ther-
apy with a different pathogen than initially identified.
All patients with PJI underwent revision surgery. Acute
infections were typically treated with retention of the pros-
thesis, change of the mobile parts, irrigation, and surgical
debridement, except when symptoms persisted for more
than three weeks, there were radiographically loose
implants or if sinus tract, compromised soft-tissue condi-
tions or major abscess formation were present. These
patients underwent either a one-stage or two-stage revision
arthroplasty, determined by the preference of the surgeon.
Intravenous antibiotics were started after tissue sampling
and administered for two weeks followed by an oral regi-
men, for a total of 12 weeks. Oral antibiotics with high oral
bioavailability and bone penetration, were prescribed
according to susceptibility testing of the causetive organ-
ism. From January 2015 rifampin was routinely added to
the treatment regimen for all streptococcal PJI being com-
menced after the definitive surgical procedure.
Patients were assessed at three, six and 12 months, fol-
lowing their revision surgery, by an orthopaedic surgeon
(DA or CP) and an infectious disease specialist (NR or AT).
Review and evaluation were performed, contacting the
patients by telephone or during out-patient consultation
using a standardised questionnaire, to evaluate general
health, joint and skin status, any additional surgical inter-
ventions, clinical complaints and any antibiotic use.
Statistical analysis. For comparison of categorical variables
Fishers exact test was applied. The probability of infection-
free survival and the respective 95% confidence interval
(CI) was estimated using the Kaplan-Meier survival
method. Survival curves between groups were compared
with the log-rank (Mantel-Cox) test. A two-sided p-value
< 0.05 was considered significant. For statistical analyses
the R Statistical Package version 3.1.3. (R Foundation,
Vienna, Austria) and Prism version 7.01 software (Graph-
Pad, La Jolla, Califoria) were used.
Results
Demographic, clinical and laboratory characteristics of the
patients with PJI identified in our study are summarised in
Table I. In all, 24 of 30 patients (80%) presented with acute
clinical symptoms. Eight PJIs (27%) were classified as early
infection, eight (27%) were considered delayed infections
and 14 (47%) were late infections. The median interval
from the index surgery until the diagnosis of streptococcal
PJI was 58 months (0.7 to 145). In 15 patients (50%), pre-
vious revision surgery had been performed; in nine patients
for reasons other than infection and in six patients for
infection.
The presumed route of infection was haematogenous in
16 cases and peri-operative in 14. In two haematogenous
THE BONE & JOINT JOURNAL
 HIGH FAILURE RATES IN TREATMENT OF STREPTOCOCCAL PERIPROSTHETIC JOINT INFECTION 655

Table I. The characteristics of the 30 patients streptococcal periprosthetic joint infections (PJI)

Characteristic Patients (n = 30)

Age (median, range) yrs 71 (47 to 90)
Gender, female (%) 15 (50)
Affected joint, n (%)
Hip 12 (40)
Knee 18 (60)
Presumed route of infection, n (%)
Haematogenous 16 (53)
Peri-operative 14 (47)
Previous revision surgery performed, n 15 (50)
Without infection 9
With infection* 6
Laboratory findings at admission (median, range)
Serum C-reactive protein (mg/l) 103 (1 to 330)
White blood count (G/l) 10.5 (5.6 to 31)
Interval from implantation/last revision until diagnosis of streptococcal PJI (median, range) (mths) 58 (0.7 to 145)
Classification of PJI according to onset of infection, n (%)
Early infection (< 3 mths) 8 (27)
Delayed infection (3 to 24 mths) 8 (27)
Late infection (> 24 mths) 14 (47)
Surgical treatment, n (%)
Two-stage revision 22 (73)
Debridement and prosthesis retention 6 (20)
One-stage revision 2 (7)
The percentages have been rounded and therefore may not add up to 100%
*four of six patients with infected revisions had more than one preceding revision surgery
including eight hips and 14 knees; the median interval between prosthetic removal and re-implantation was 84 days (71 to 183) in
hips and 69 days (50 to 122) in knees
including three hips and three knees
including one hip and one knee

Table II. Microbiological findings in 30 streptococcal periprosthetic joint infections (PJI)

Streptococcal species n = 30 (%)

S. agalactiae (group B Streptococcus) 12 (40)
S. mitis/oralis* 9 (30)
S. dysgalactiae (group C Streptococcus) 3 (10)
S. gordonii* 2 (7)
S. parasanguinis* 2 (7)
S. thermophilus 1 (3)
S. gallolyticus (formerly known as S. bovis) 1 (3)
*these streptococci belong to the Streptococcus viridans group, typically originating
from the oral cavity
in this patient, colon carcinoma was diagnosed after the diagnosis of streptococcal PJI
S., Streptococcus

PJIs, the primary focus of infection was identified. In one
patient a dental procedure preceded the onset of clinical
symptoms and in another, bacterial endocarditis was diag-
nosed. The patient with infective endocarditis had acute
onset PJI with Streptococcus agalacticae 118 months after
primary knee arthroplasty and was asymptomatic until sev-
eral days before admission, when fever, and swelling and
pain of the knee occurred. At revision, because of treatment
failure later in the course, the same microorganism grew
and transesophageal echocardiography showed mitral
valve vegetation.
Table II summarises the causative pathogens. The pre-
dominant isolated causative organism was Streptococcus
agalactiae (n = 12), followed by Streptococcus viridans
species (including Streptococcus mitis/oralis, Streptococcus
gordonii and Streptococcus parasanguinis). Streptococcus
gallolyticus was found in one patient, who was subse-
quently diagnosed with carcinoma of the colon.
All patients underwent revision surgery (Table I), 22 PJIs
were treated with a two-stage revision (eight hips and 14
knees), six cases with debridement and prosthesis retention
(three hips and three knees) and two with one-stage revi-
sion (one hip and one knee). In two-stage exchanges, resec-
tion arthroplasty, without a temporary spacer, was
performed in the hip joint and a temporary static spacer
was fashioned for the knee joint. In two infected hips, re-
implantation was not performed due to persistent infection
after a follow-up of 42 and 18 months respectively. The

VOL. 99-B, No. 5, MAY 2017

656 D. AKGN, A. TRAMPUZ, C. PERKA, N. RENZ

Table III. Characteristics of the 12 failures of treatment of streptococcal periprosthetic joint infections (PJI)

Interval from
index surgery
until diagnosis Previous septic Route of Microorganism Administration Final Interval Micro-organism
n Joint of PJI (mths) revision (n) infection (first revision) Type of surgery of rifampin surgery* (days) (second revision)

1 Hip 41 - Peri-operative S. mitis/oralis Resection No - - -

arthroplasty
2 Hip 0.7 - Peri-operative S. agalactiae Debridement and Yes 2-stage 15 No organism
retention exchange
3 Hip 69 2 Haematogenous S. mitis/oralis Resection No - - -
arthroplasty
4 Hip 3 5 Peri-operative S. agalactiae 2-stage exchange Yes 2-stage 287 S. agalactiae
exchange
5 Knee 118 - Haematogenous S. agalactiae Debridement and Yes 2-stage 182 S. agalactiae
retention exchange
6 Knee 123 - Peri-operative S. mitis/oralis 2-stage exchange Yes Retention 181 S. gallolyticus
7 Knee 52 - Haematogenous S. mitis/oralis 2-stage exchange No 2-stage 246 S. mitis/oralis
exchange
8 Knee 95 2 Peri-operative S. thermophilus 2-stage exchange No Retention 93 No organism
9 Knee 4 - Peri-operative S. agalactiae 2-stage exchange No Retention 225 S. agalactiae
10 Knee 130 1 Peri-operative S. mitis/oralis 2-stage exchange Yes 2-stage 231 S. mitis/oralis
exchange
11 Knee 17 - Haematogenous S. gordonii 2-stage exchange No 2-stage 146 S. gordonii
exchange
12 Knee 57 - Haematogenous S. dysagalactiae 2-stage exchange No Retention 388 S. dysgalactiae
*surgical treatment after diagnosis of treatment failure
resection arthroplasty without re-implantation of prosthesis was performed due to uncontrolled infection in two patients with hip PJI
time from first revision surgery until treatment failure
recurrence of infection (attributed to missed infectious endocarditis at first revision)
S., Streptococcus

trimoxazol. In ten PJIs (33%) rifampin was part of the

Probability of infection-free survival (%)

100 combination antimicrobial therapy.

The median follow-up after revision surgery was 15
80 months (0 to 75). Successfully treated cases had a median
follow-up of 39.2 months (12 to 75), whereas all treatment
60 failures occurred within a year of revision surgery. Treat-
ment failed in 12 PJIs (40%) and their characteristics are
shown in Table III. The Kaplan-Meier estimated infection-
40
free survival after three years was 59% (95% CI 39% to
75%) with 12 patients at risk and remained unchanged up
20
to five years after revision surgery with five patients at risk
(Fig. 1). In patients with previous revision surgery for infec-
0 tion, the failure rate was higher (four of six PJIs, 66%) than
0 1 2 3 4 5 in those without preceding infection (eight of 24 PJIs,
Time after revison surgery (yrs)
33%).
No. at risk 30 18 13 12 7 5
Analysing surgical treatment strategies, treatment failed
Fig. 1
in ten of 22 cases (45%) with two-stage revisions. Two hips
Probability of infection-free survival of 30 patients with streptococcal underwent resection arthroplasty without re-implantation
periprosthetic joint infection. The dotted lines represent the 95% con-
fidence intervals. The vertical marks indicate censored events. due to persistent infection. Two recurrent infections
occurred within one month after the re-implantation,
despite antibiotic treatment (at 15 and 24 days, respec-
tively). In one patient the same Streptococcus species was
median interval between removal of the infected arthro- isolated, in the other the causing pathogen was not identi-
plasty and re-implantation was 84 days (71 to 183) for hips fied. Five PJIs relapsed within the first year after completion
and 69 days (50 to 122) for knees. of antimicrobial treatment with the same Streptococcus
Intravenous antimicrobial treatment included penicillin species and in one case, re-infection with another Strepto-
derivatives in all cases and was followed by an oral regimen coccus species 72 days after stopping antibiotics.
with penicillin derivatives in 28 cases. Other oral antibiot- In patients treated with debridement and prosthesis
ics prescribed were levofloxacin, clindamycin and co- retention, two of six PJIs failed (one hip and one knee) and

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 HIGH FAILURE RATES IN TREATMENT OF STREPTOCOCCAL PERIPROSTHETIC JOINT INFECTION 657

100

Probability of infection-free survival (%)

p = 0.175
80

60

40
Without rifampin
20
With rifampin

0
0 1 2 3 4 5
Time after revison surgery (yrs)
No. at risk:
without rifampin 18 15 13 12 7 5
with rifampin 10 4 0 0 0 0
Fig. 2

Probability of infection-free survival of 28 patients treated with and without addition of

rifampin to the antimicrobial treatment (two patients with permanent hip resection were
excluded from analysis). The vertical marks indicate censored events.

subsequently underwent a two-stage revision arthroplasty. for treatment failure of PJI compared with other patho-
In one patient this occurred 15 days after initial debride- gens.1 High treatment failure rates have been previously
ment, due to persistent and prolonged wound discharge, reported in PJI with difficult-to-treat microorganisms, such
despite appropriate antibiotic treatment. In the second, as rifampin-resistant staphylococci, ciprofloxacin-resistant
relapse of infection occurred with the same Streptococcus gram-negative rods, enterococci and candida species, for
species (Streptococcus agalactiae) 98 days after stopping which no anti-biofilm treatment is available.18 Retention of
antibiotics. In this patient, bacterial endocarditis was sub- implants or one-stage revision is not recommended in this
sequently diagnosed, which was the focus of the recurrent type of infection.18 Our results raise the question as to
infection. whether streptococcal infections should be considered as
Both patients with PJI treated by one-stage revision sur- difficult-to-treat, and current thoughts on treatment
gery remained infection-free with follow-up of 61.5 months options should be reviewed. The administration of pro-
and 20 months, respectively. longed suppressive antimicrobial therapy should be consid-
Figure 2 shows the Kaplan-Meier estimated infection- ered and might prevent relapses, however, data to support
free survival of patients treated with and without addition this view are lacking.
of rifampin to the antimicrobial treatment. The infection- All treatment failures in our study occurred within a year
free survival rate after one year with rifampin was 48% of revision surgery, reflecting the high virulence of strepto-
(95% CI 16% to 75%) with four patients at risk and with- cocci or the further haematogenous spread from an unrec-
out rifampin was 72% (95% CI 61% to 99%) with 15 ognised infectious focus. The high failure rate was
patients at risk (log rank, p = 0.175). irrespective of Streptococcus species, type and duration of
antimicrobial treatment or type of surgical intervention.
Discussion Although in greater than 50% of the cases the presumed
In our study the infection-free survival rate of treated strep- route of infection was haematogenous, we were only able
tococcal PJI with a mean of three years of follow-up was to identify the primary focus in two cases. Similarly, other
surprisingly low (59%). As streptococci are highly sensitive authors report low rates of source identification, at around
to antibiotics, including penicillin derivatives, streptococcal 50% of cases at best. 19,20 Nonetheless, we recommend that
PJI were thought to be readily amenable to treatment. Pre- an active search for a primary focus should be pursued in
vious reports have described high success rates in strepto- all patients with streptococcal PJI in order to minimise the
coccal PJI, even if the prosthesis was retained.7-10,17 An risk of recurrent infection.
exception was Streptococcus agalactiae (group B strepto- The role of anti-biofilm antibiotics against streptococcal
cocci), which was shown to be an independent risk factor biofilms remains unclear. Whereas rifampin plays the key

VOL. 99-B, No. 5, MAY 2017

658 D. AKGN, A. TRAMPUZ, C. PERKA, N. RENZ
role in the treatment of implant-associated infections, due
to most being gram-positive organisms (especially staphy-
lococci and Propionibacterium acnes),12,21-24 the activity of
rifampin on streptococcal biofilms is unknown. Strepto-
cocci usually demonstrate rapid spread in soft tissues and
fascia rather than the formation of abscesses or biofilms.9,25
However several studies have demonstrated that strepto-
cocci can produce biofilms. Kaur et al26 microscopically
detected biofilm production in Streptococcus agalactiae
with a peak after 48 hours. Other in vitro studies have dem-
onstrated that streptococci can form biofilms on abiotic
surfaces.27-29 Lack of biofilm-active antibiotics may explain
the high failure rate in streptococcal PJI. In a recent retro-
spective study including 95 streptococcal PJIs, the success
of treatment was 70.5%.11 Most patients were treated with
rifampin combinations, particularly with levofloxacin. The
authors demonstrated a favourable effect of rifampin on
the treatment outcome. However, our results showed no
beneficial treatment effect from the addition of rifampin.
We acknowledge the limitations of our study. First, we
have not performed a matched case-control study. In such a
study, the control group would have consisted of a hetero-
geneous group of non-streptococcal PJI cases; but the great
diversity in terms of causative organism, surgical and anti-
microbial treatment, and clinical outcome make compari-
sons difficult. Secondly, we describe only short- and mid-
term results. Some late relapses could have been over-
looked.16 Thirdly, the cohort consists of a heterogeneous
patient population with various routes of infection, types of
prosthesis and surgical treatments. Nevertheless, the high
failure rate remains similar in all investigated sub-groups.
In conclusion, despite the wide spectrum of antimicro-
bial sensitivity of streptococci, a high treatment failure rate
in streptococcal PJI was observed. Patients treated with
rifampin in combination did not have a better outcome.
The most common route of infection was haematogenous
and should prompt a search for the potential primary
source of infection. Most recurrent infections and treat-
ment relapses occur in the first year and close follow-up is
required until it is clear that infection has been eradicated.
Further research to investigate the relevance of biofilm for-
mation in vivo is required, to find new options in the treat-
ment of streptococcal infections, such as bacteriophages,
local application of high dose antimicrobial agents and
non-antimicrobial approaches. In addition, the reclassifica-
tion of streptococci as difficult-to-treat biofilm producing
pathogens should be re-evaluated.
Take home message:
- The outcome of streptococcal PJI is poor compared with
infections caused by other microorganisms.
- There should be a prompt search for potential primary sources of strep-
tococcal periprosthetic infection, since the most common route of infec-
tion was haematogenous.
- A close follow-up of the patients after septic revision surgery is required
due to early possible recurrence.
- Further research is required to find new options in the treatment of strep-
tococcal infections.
- Despite the wide spectrum of antimicrobial sensitivity of streptococci,
there is a high risk treatment failure in streptococcal PJI.
Author contributions:
D. Akgn: Design of the work, Data analysis, Drafting the paper.
A. Trampuz: Interpretation of data, Critical revision, Approval of the final ver-
sion.
C. Perka: Critical revision, Final approval of the final version.
N. Renz: Critical revision, Interpretation of data.
No benefits in any form have been received or will be received from a commer-
cial party related directly or indirectly to the subject of this article.
This article was primary edited by D. Johnstone and first proof edited by
G. Scott.
References
1. Zeller V, Lavigne M, Biau D, et al. Outcome of group B streptococcal prosthetic hip
infections compared to that of other bacterial infections. Joint Bone Spine
2009;76:491496.
2. Zeller V, Lavigne M, Leclerc P, et al. Group B streptococcal prosthetic joint infec-
tions: a retrospective study of 30 cases. Presse Med 2009;38:15771584.
3. Schwartz B, Schuchat A, Oxtoby MJ, et al. Invasive group B streptococcal dis-
ease in adults. A population-based study in metropolitan Atlanta. JAMA
1991;266:11121114.
4. Jenkins PJ, Clement ND, Gaston P, et al. Invasive group B streptococcal disease
in an orthopaedic unit. J Hosp Infect 2010;76:231233.
5. Corvec S, Illiaquer M, Touchais S, et al. Clinical features of group B Streptococ-
cus prosthetic joint infections and molecular characterization of isolates. J Clin
Microbiol 2011;49:380382.
6. Duggan JM, Georgiadis G, VanGorp C, Kleshinski J. Group B streptococcal pros-
thetic joint infections. J South Orthop Assoc 2001;10:209214.
7. Sendi P, Christensson B, Ukay I, et al. Group B streptococcus in prosthetic hip
and knee joint-associated infections. J Hosp Infect 2011;79:6469.
8. Meehan AM, Osmon DR, Duffy MC, Hanssen AD, Keating MR. Outcome of pen-
icillin-susceptible streptococcal prosthetic joint infection treated with debridement
and retention of the prosthesis. Clin Infect Dis 2003;36:845849.
9. Betz M, Abrassart S, Vaudaux P, et al. Increased risk of joint failure in hip pros-
theses infected with Staphylococcus aureus treated with debridement, antibiotics
and implant retention compared to Streptococcus. Int Orthop 2015;39:397401.
10. Everts RJ, Chambers ST, Murdoch DR, Rothwell AG, McKie J. Successful anti-
microbial therapy and implant retention for streptococcal infection of prosthetic
joints. ANZ J Surg 2004;74:210214.
11. Fiaux E, Titecat M, Robineau O, et al. Outcome of patients with streptococcal
prosthetic joint infections with special reference to rifampicin combinations. BMC
Infect Dis 2016;16:568.
12. Zimmerli W, Trampuz A, Ochsner PE. Prosthetic-joint infections. N Engl J Med
2004;351:16451654.
13. Osmon DR, Berbari EF, Berendt AR, et al. Diagnosis and management of pros-
thetic joint infection: clinical practice guidelines by the Infectious Diseases Society of
America. Clin Infect Dis 2013;56:125.
14. Krenn V, Morawietz L, Perino G, et al. Revised histopathological consensus clas-
sification of joint implant related pathology. Pathol Res Pract 2014;210:779786.
15. Trampuz A, Piper KE, Jacobson MJ, et al. Sonication of removed hip and knee
prostheses for diagnosis of infection. N Engl J Med 2007;357:654663.
16. Diaz-Ledezma C, Higuera CA, Parvizi J. Success after treatment of periprosthetic
joint infection: a Delphi-based international multidisciplinary consensus. Clin Orthop
Relat Res 2013;471:23742382.
17. Zrcher-Pfund L, Ukay I, Legout L, et al. Pathogen-driven decision for implant
retention in the management of infected total knee prostheses. Int Orthop
2013;37:14711475.
18. Zimmerli W, Moser C. Pathogenesis and treatment concepts of orthopaedic biofilm
infections. FEMS Immunol Med Microbiol 2012;65:158168.
19. Sendi P, Banderet F, Graber P, Zimmerli W. Clinical comparison between exog-
enous and haematogenous periprosthetic joint infections caused by Staphylococcus
aureus. Clin Microbiol Infect 2011;17:10981100.
20. Peersman G, Laskin R, Davis J, Peterson M. Infection in total knee replacement:
a retrospective review of 6489 total knee replacements. Clin Orthop Relat Res
2001;392:1523.
21. Dunne WM Jr, Mason EO Jr, Kaplan SL. Diffusion of rifampin and vancomycin
through a Staphylococcus epidermidis biofilm. Antimicrob Agents Chemother
1993;37:25222526.
THE BONE & JOINT JOURNAL
 HIGH FAILURE RATES IN TREATMENT OF STREPTOCOCCAL PERIPROSTHETIC JOINT INFECTION
22. Zheng Z, Stewart PS. Penetration of rifampin through Staphylococcus epidermidis
biofilms. Antimicrob Agents Chemother 2002;46:900903.
23. Singh R, Ray P, Das A, Sharma M. Penetration of antibiotics through Staphylococ-
cus aureus and Staphylococcus epidermidis biofilms. J Antimicrob Chemother
2010;65:19551958.
24. El Helou OC, Berbari EF, Lahr BD, et al. Efficacy and safety of rifampin containing
regimen for staphylococcal prosthetic joint infections treated with debridement and
retention. Eur J Clin Microbiol Infect Dis 2010;29:961967.
25. Chargui M, Suv D, Christofilopoulos P, et al. Deep soft tissue infections. Rev
Med Suisse 2014;10:920924. (In French)
VOL. 99-B, No. 5, MAY 2017
659
26. Kaur H, Kumar P, Ray P, Kaur J, Chakraborti A. Biofilm formation in clinical iso-
lates of group B streptococci from north India. Microb Pathog 2009;46:321327.
27. Borges S, Silva J, Teixeira P. Survival and biofilm formation by Group B strepto-
cocci in simulated vaginal fluid at different pHs. Antonie Van Leeuwenhoek
2012;101:677682.
28. Yang L, Liu Y, Wu H, et al. Combating biofilms. FEMS Immunol Med Microbiol
2012;65:146157.
29. Ho YR, Li CM, Yu CH, et al. The enhancement of biofilm formation in Group B strep-
tococcal isolates at vaginal pH. Med Microbiol Immunol 2013;202:105115.