Neisseria meningitidis is a rare cause of prosthetic joint infection (PJI), with only three cases
previously reported. Here we report three further cases, all of which were
successfully treated with implant retention and short-course antibiotics (<6 weeks).
Introduction
Neisseria meningitidis is a Gram-negative, aerobic, oxidase-positive diplococcus, for which humans
are the only natural host. The organism is best known as a cause of purpura
fulminans with bacteraemia and meningitis; however, urogenital infections, pneumonia, chronic bacteraemia, and native joint infections also occur
(Murray et al., 2016; Barahona et al., 2017). Whilst virulent, N. meningitidis is typically
very sensitive to beta-lactam antibiotics and fluoroquinolones, with
successful outcomes using short courses of antimicrobials in the absence of
surgical intervention reported in native joint septic arthritis (Cabellos et
al., 2012). Similarly, it has long been recognised that the curative
treatment of meningococcal ventriculitis, for example, in the context of a
cerebrospinal fluid ventricular shunt does not necessitate removal of the device (Anderson and Yogev, 2005). Therefore, we hypothesised that
meningococcal prosthetic joint infection (PJI) could be safely managed with
minimal surgical intervention and short-course antibiotics, in contrast to
more common PJI pathogens such as Staphylococcus aureus.
To our knowledge, there are only three previously reported cases of
meningococcal prosthetic joint infection (Vikram et al., 2001; Becerril
Carral et al., 2017; Mc Carthy et al., 2020). These cases were managed with
at least 12 weeks of antimicrobial therapy, commencing with an intravenous
beta-lactam followed by oral ciprofloxacin or amoxicillin (Table 1). We
present three further cases of late acute haematogenous PJI due to N. meningitidis, demonstrating successful treatment with 6 weeks or less of antimicrobial therapy and a range of surgical interventions involving implant retention from single-needle arthrocentesis to multiple arthrotomies.
Case presentationsCase 1
A 70-year old woman presented 6 months following an elective right total knee arthroplasty (TKA) with 48 h of fever, rigors, nausea, and vomiting and 24 h of severe right knee pain and swelling. The right knee was warm
and erythematous, with an effusion and reduced range of motion (ROM). Serum
C-reactive protein (CRP) was 451 mgL-1 (<6.0mgL-1), with neutrophilia of
13.9×109L-1 (2.0–8.0×109L-1). Blood cultures taken at
presentation showed no growth after 5 d of incubation.
Empiric treatment with intravenous piperacillin-tazobactam was commenced and
rationalised to intravenous flucloxacillin (an anti-staphylococcal
penicillin) 2 g 6-hourly after 24 h. On day 2 of admission 50 mL of purulent fluid was aspirated from the right knee under ultrasound guidance
with 36000×106L-1 leukocytes (95 % polymorphonuclear) and no
organisms or crystals seen on microscopy. Synovial fluid culture was
negative after 5 d of incubation.
Rapid clinical improvement was demonstrated, and she was able to mobilise
independently with pain well controlled by the third day of admission. No
surgical intervention was performed, and she was discharged home with a plan
for 4 weeks of intravenous flucloxacillin via outpatient parenteral
antimicrobial therapy for the treatment of probable PJI.
The result of 16s rRNA gene sequence analysis, performed on the initial synovial fluid specimen, was available following 3 weeks of intravenous flucloxacillin and detected genetic material demonstrating a 100 % match
with N. meningitidis. Remel meningococcus agglutination serum test identified the meningococcus as serogroup W. Treatment was changed to ceftriaxone 2 g daily
for a further 7 d, with no relapse of infection 5 years post treatment cessation. She achieved an excellent functional outcome. Antimicrobial prophylaxis was not recommended by public health in this
setting given the prolonged period between patient contact and diagnosis.
Case 2
An 83-year old woman presented with 24 h of fever, headache, vomiting, diarrhoea and a painful swollen right knee on a background of elective right
TKA 3 years earlier for osteoarthritis. She had a warm, swollen, irritable
right knee with reduced ROM and no skin rash or meningism. Initial serum CRP was elevated at 72 mgL-1 (<6mgL-1), with neutrophilia of 10.2×109L-1 (2.0–8.0×109L-1). A plain X-ray of her right knee showed no signs of component loosening. Synovial white blood cell count was
>100000×106L-1 (100 % polymorphonuclear leukocytes).
N. meningitidis was cultured from blood and synovial fluid samples with identification of colonies using VITEK MS MALDI-TOF (database V3.0 KB-clinical use), while
bioMerieux Etest method and Clinical Laboratory Standards Institute (CLSI)
interpretive criteria demonstrated susceptibility to ceftriaxone,
ciprofloxacin, and rifampicin. Remel meningococcus agglutination serum test identified the meningococcus as serogroup W. The patient's husband was
identified as a close contact and prescribed prophylaxis with oral
ciprofloxacin in the community.
Empiric intravenous flucloxacillin, gentamicin, and ciprofloxacin were rationalised to intravenous ceftriaxone 2 g twice daily on day 2, as meningitis had not been ruled out, and lumbar puncture was contraindicated
due to anticoagulation. Operative open right knee washout for debridement
and implant retention (DAIR), including polyethylene liner exchange and
extensive synovectomy, was performed on day 2. Copious pus was present within the joint capsule. There was no growth on tissue, swab, or sonication specimens.
Rapid clinical and biochemical improvement was noted post-operatively. She received 7 d of intravenous ceftriaxone 2 g twice daily, followed by
a further 14 d of oral ciprofloxacin 750 mg twice daily. At 20 months
following surgical debridement, her functional state was at premorbid level,
with no clinical signs or symptoms of relapse.
Summary of meningococcal prosthetic joint infection case reports.
Case no. (ref.)Patient detailsDiagnostic testOperative managementAntimicrobial management1 (this report)70 F, 6 months post index R TKAN. meningitidis (serogroup W) identified in synovial fluid using 16s rRNA gene sequence analysisNo surgical intervention performed3 weeks IV flucloxacillin 8 gd-1 continuous infusion, followed by 7 d IV ceftriaxone 2 g OD (4 weeks total therapy)2 (this report)83 F, 3 years post index R TKAN. meningitidis (serogroup W) cultured from blood and synovial fluidDAIR including polyethylene liner exchange and extensive synovectomy7 d IV ceftriaxone 2 g BD, followed by 14 d PO ciprofloxacin 750 mg BD (3 weeks total therapy)3 (this report)75 M, 3 years post index L TKA. Polymicrobial infection involving L TKA, R hip and L wristN. meningitidis (serotype Y) cultured from bloodOpen washout days 3 and 8. DAIR and polyethylene liner exchange day 103 d IV ceftriaxone 2 g OD, followed by 12 d IV benzylpenicillin 10.8 gd-1 followed by 4 weeks PO ciprofloxacin 750 mg BD (6 weeks total therapy)4 (Vikram et al., 2001)80 F, 3 years post index R TKAN. meningitidis (serogroup Y) cultured from synovial fluidOpen surgical drainage with implant retention6 weeks IV ceftriaxone (dose unspecified), followed by indefinite PO penicillin V (dose unspecified)(indefinite course)5 (Becerril Carral et al., 2017)78 F, 7 months post index L TKAN. meningitidis (serogroup B) cultured from synovial fluidArthroscopic debridement with implant retention3 weeks IV ceftriaxone 2 g OD, followed by 9 weeks PO ciprofloxacin 750 mg BD (12 weeks total therapy)6 (Mc Carthy et al., 2020)72 F, 7 years post index L TKAN. meningitidis cultured from synovial fluid and Gram-negative diplococci on Gram stain of blood culturesDAIR and polyethylene tibial insert exchange6 weeks IV ceftriaxone 2 g OD, followed by 6 weeks PO amoxicillin (dose unspecified) (12 weeks total therapy)
Abbreviations: IV: intravenous; F: female; M: male; TKA: total knee
arthroplasty; R: right; L: left; DAIR: debridement and implant retention;
OD: once daily; BD: twice daily; PO: per oral
Case 3
A 75-year old man presented with 4 d of fevers, rigors, myalgia, and lethargy following a 1 d history of pharyngeal pain. Past medical history
included an elective left TKA performed 3 years prior for osteoarthritis. No
focal infective features were initially noted, and empiric treatment with
flucloxacillin was commenced pending blood culture results. Repeat physical
examination in the first 24 h of admission revealed pain and reduced
range of motion in the right hip, left wrist, and left knee. There was no
rash at any time.
Needle aspirates of synovial fluid from the affected native right hip and
left wrist performed on day 1 of admission revealed leukocyte counts of
468000×106L-1 and 126000×106L-1, respectively. Gram-negative diplococci were seen on Gram stain of both samples with antibiotics
subsequently changed to intravenous ceftriaxone 2 g daily. The symptomatic
left prosthetic knee joint was not aspirated.
N. meningitidis serotype Y was grown from blood within 24 h of collection (VITEK MS MALDI-TOF). Minimum inhibitory concentration was 0.064 mgL-1 for penicillin
and 0.004 mgL-1 for ciprofloxacin (Etest, BioMérieux Inc, Marcy L'Etoil,
France). Ceftriaxone was ceased and intravenous benzylpenicillin 10.8 gd-1
was started on day 4 once antimicrobial sensitivities were finalised.
Operative washout of all three affected joints was performed on day 3, at which time the total leukocyte count in synovial fluid from the left prosthetic
knee joint was 86000×106L-1, with no organisms seen on Gram stain and no growth from culture. Two further debridement and washout procedures were
performed on the prosthetic knee joint on days 8 and 10 of admission. The
polyethylene liner was replaced during the final procedure, with the implant
retained. Intravenous benzylpenicillin was continued until day 12, followed
by ciprofloxacin 750 mg orally 12-hourly to complete 6 weeks of total
antibiotic therapy. There were no symptoms or signs of relapse at time of
follow-up 24 months post cessation of antibiotics.
Discussion
To date, only three cases of meningococcal PJI have been reported (Table 1),
all of which were treated with either open or arthroscopic debridement with
the implant retained and at least 12 weeks of antibiotics. Native joint septic arthritis (SA) is also an unusual presentation of meningococcal
infection, accounting for just 1.4 % or 4 of 278 reported cases of invasive meningococcal disease in one case series in 2018 (Lahra et al.,
2020), typically involving the knee and preceded by upper respiratory tract infection in 25 %–50 % of cases (Mc Carthy et al., 2020). In Australia, 1.4 % of invasive meningococcal isolates were resistant to penicillin in 2018
(Lahra et al., 2020).
Data from small case series suggest that, when meningococcal SA complicates another invasive meningococcal disease syndrome, it may be safely treated
with as few as 4 d of antibiotics. Cabellos et al. (2012) identified 15
cases of “probable” SA between 1977 and 2010, all of whom were treated
with a 4 d course of targeted antimicrobial therapy with no surgical
intervention. Cure was achieved in all cases, with excellent functional outcomes.
The treatment of a PJI typically requires combined surgical and medical
management, with a goal of removal or reduction of the biofilm burden to
allow effective penetration of post-operative antibiotic therapy (Tande et al., 2017). Following DAIR, the treatment of most pathogens typically
necessitates a 12–24-week course of either specific intravenous or highly bioavailable oral antimicrobial therapy (Li et al., 2018). While
rifampicin-containing regimens are recommended for staphylococcal PJIs due
to an association with higher cure rates (Tande et al., 2017), rifampicin
was not used in any of the cases presented, and there is no evidence to
support its use for meningococcal PJI.
While the authors remain confident that case 1 represents a true case of N. meningitidis PJI, it is important to note that certain factors cast possible doubt, including a
failure to culture the organism from joint fluid following administration of
piperacillin-tazobactam for the preceding 24 h and the subsequent clinical improvement despite use of an anti-staphylococcal penicillin. The
rapid clinical improvement in the three cases described, despite short-course antimicrobial therapy and the absence of surgical debridement in case
1, may reflect a lack of certain virulence factors amongst meningococci, such as the ability to form biofilm. Although capable of biofilm formation,
isolates from cases of invasive meningococcal disease in experimental models
were less likely to form biofilm when compared to carriage strains (12 %
vs. 30 %) (Yi et al., 2004). The ability of a strain to form biofilm is
related to capsular expression, with non-biofilm-forming strains tending to
be encapsulated (Lappann and Vogel, 2010). Encapsulated strains are poorer
long-term colonisers but appear to demonstrate higher transmission frequency and thus persist in the human population. A lack of biofilm
formation may explain successful treatment with antibiotics alone for
meningococcal joint infections.
Although these patients were all over the age of 65 years, none of them had
received meningococcal vaccination as they did not meet current Australian
indications given the absence of risk factors for invasive meningococcal
disease.
Conclusion
The clinical literature describing native joint meningococcal SA
demonstrates that cure can be achieved with short antibiotic durations, even
in the absence of synovial fluid drainage. Microbiology literature
demonstrates that N. meningitidis strains isolated from cases of invasive meningococcal
disease are unlikely to form biofilm. The three cases described above demonstrate the potential for meningococcal PJI to be cured with
short-course antimicrobial therapy (3 to 6 weeks in total) and minimal
surgical intervention and suggests that the potential risks associated with repeated orthopaedic interventions and prolonged antibiotic therapy could be
safely avoided in future cases.
Data availability
No data sets were used in this article.
Author contributions
SB, HNW, and TR contributed to the methodology and writing (original draft preparation). RP, ML, JAT, AH, and JSD contributed to
conceptualisation and writing (reviewing and editing).
Competing interests
The authors declare that they have no conflict of interest.
Acknowledgements
The authors wish to acknowledge the contributions of the
NSW Health Pathology Department of Microbiology, namely Rodney Givney,
Ian Marr, and Syeda Naqvi.
Review statement
This paper was edited by Parham Sendi and reviewed by four anonymous referees.
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