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Erschienen in: BMC Infectious Diseases 1/2021

Open Access 01.12.2021 | Case report

Prosthetic hip joint infection by Bacillus Calmette-Guerin therapy following intravesical instillation for bladder cancer identified using whole-genome sequencing: a case report

verfasst von: Michael Riste, Pretin Davda, E. Grace Smith, David H. Wyllie, Martin Dedicoat, Simantini Jog, Steven Laird, Gerald Langman, Neil Jenkins, Jonathan Stevenson, Matthew K. O’Shea

Erschienen in: BMC Infectious Diseases | Ausgabe 1/2021

Abstract

Background

Joint replacement is an effective intervention and prosthetic joint infection (PJI) is one of the most serious complications of such surgery. Diagnosis of PJI is often complex and requires multiple modalities of investigation. We describe a rare cause of PJI which highlights these challenges and the role of whole-genome sequencing to achieve a rapid microbiological diagnosis to facilitate prompt and appropriate management.

Case presentation

A 79-year-old man developed chronic hip pain associated with a soft-tissue mass, fluid collection and sinus adjacent to his eight-year-old hip prosthesis. His symptoms started after intravesical Bacillus Calmette-Guerin (BCG) therapy for bladder cancer. Synovasure™ and 16S polymerase chain reaction (PCR) tests were negative, but culture of the periarticular mass and genome sequencing diagnosed BCG infection. He underwent a two-stage joint revision and a prolonged duration of antibiotic therapy which was curative.

Conclusions

BCG PJI after therapeutic exposure can have serious consequences, and awareness of this potential complication, identified from patient history, is essential. In addition, requesting appropriate testing is required, together with recognition that traditional diagnostics may be negative in non-pyogenic PJI. Advanced molecular techniques have a role to enhance the timely management of these infections.
Hinweise

Publisher’s Note

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Abkürzungen
BCG
Bacillus Calmette-Guérin
DST
Drug susceptibility testing
MRI
Magnetic resonance imaging
NAMP
Neutrophil antimicrobial peptides
PCR
Polymerase chain reaction
PJI
Prosthetic joint infection
rDNA
Ribosomal deoxyribonucleic acid
WGS
Whole-genome sequencing

Background

Joint replacement is a highly effective intervention and with an aging population and advancements in joint arthroplasty, demand is expected to increase [1]. Prosthetic joint infection (PJI) is one of the most serious complications of joint replacement surgery and is associated with significant morbidity. PJI affects 1–2% of all primary total hip and knee arthroplasties over the lifetime of the prosthetic joint and diagnosis and management can be difficult, prolonged and costly [2]. Diagnosis often relies on the results of multiple investigations including radiological, biochemical, microbiological and molecular. In the following case we describe a rare cause of PJI which highlights some of these diagnostic challenges.

Case presentation

A 79-year-old male presented to a tertiary orthopaedic hospital in the United Kingdom with worsening pain and difficulty weight bearing localised to his previously asymptomatic total hip replacement. He had undergone an uncomplicated metal on polyethylene total hip replacement in 2008. Eighteen months prior to presentation to our unit he had developed a fluctuant swelling over the right hip. The swelling intermittently discharged serous fluid via a sinus which resolved spontaneously 2 months prior to presentation, after which he reported persistent pain in the joint and significant weight loss but no fevers or other systemic symptoms.
His past medical history included osteoarthritis of the spine, ischaemic heart disease, two myocardial infarctions, benign prostatic hyperplasia, pulmonary embolism following a trans-urethral resection of the prostate and transitional cell carcinoma of the bladder. For the latter he received six intravesical BCG vaccine instillations (Tice strain, Alliance Pharmaceuticals) over a 2 month period. Within a month of receiving the final BCG instillation the swelling over his right hip developed.
In view of the intermittently discharging sinus, the clinical diagnosis at initial orthopaedic assessment was PJI. Computed tomography of the pelvis showed a large collection around the right hip extending into the adductor compartment. The urinary tract appeared normal and there was no evidence that the collection was associated with any part of it. Magnetic resonance imaging (MRI) of the hip demonstrated a large, lobulated soft tissue mass arising in relation to the hip joint and prosthesis, which was felt to be consistent with a diagnosis of metallosis and pseudotumour due to aseptic lymphocyte-dominated vasculitis-associated lesions (Fig. 1) [3].
The joint was aspirated and blood-stained fluid was obtained which was negative on Gram staining and standard microbiological testing (culture of fluid from a normally sterile site including blood, chocolate, fastidious anaerobic and Sabouraud agar; continuous monitoring blood culture system and fastidious anaerobic enrichment broth) [4]. One month later the patient underwent explantation of the joint, with insertion of a vancomycin and meropenem impregnated articulating cement spacer. Intraoperatively, extensive damage to the ilium, ischium and pubis was noted, together with multiple turbid fluid collections in the adductor compartment and around the medial aspect of the hip. Synovial fluid alpha-defensin was negative (Synovasure™; an assay for neutrophil antimicrobial peptides (NAMP) used to support the diagnosis of PJI) [5]. Multiple intraoperative bone and tissue samples underwent histological examination and microbiological culture, and post-operatively the patient was treated empirically with meropenem and vancomycin. Antimicrobial therapy was subsequently discontinued when standard microbiological cultures were negative. While histology was not consistent with active infection, samples did show a fibrinous exudate replacing the synovial lining with abundant macrophages laden with particulate debris (Fig. 2). No granulomas were identified and no acid and alcohol fast bacilli were seen on Ziehl Neelsen staining. Following discussion at the regional bone infection multidisciplinary team meeting, residual intra-operative samples underwent broad-range bacterial 16S ribosomal deoxyribonucleic acid (rDNA) PCR, which was negative, and mycobacterial culture.
Five weeks post-operatively, tissue samples grew acid alcohol fast bacilli in liquid culture with a time to positivity of 28–31 days (BD BACTEC™ MGIT™ Automated Mycobacterial Detection System, Becton Dickson, NJ, USA). Within 5 days of the positive mycobacterial culture, the bacilli were identified by whole-genome sequencing (WGS) as Mycobacterium bovis (BCG lineage), and a genotypic drug susceptibility profile was determined.
Although we had identified BCG from intra-operative samples which was presumed to be a complication of previous intravesical therapy, we went on to further investigate the origin of the BCG by comparing our patient’s isolate with clinical BCG isolates from the Midlands and North of England (ca 15 M population) in the 2 years from January 2017 (a period during which sequencing of M. tuberculosis complex isolates was operational). A maximal likelihood phylogeny reconstructed using iqTree 1.6.1 with a GTR model, outgroup rooted using a lineage 1 isolate [6, 7]. We identified 28 isolates from 27 patients, which grouped into three, presumably corresponding to the BCG preparations marketed by different suppliers for vaccination or intravesical instillation (Fig. 3). The isolate received by our patient, and eight other older men who presumably also received intravesical BCG therapy, differs from the BCG strains isolated from children in the same time period (Fig. 3).
A six-month treatment regime with rifampicin, isoniazid, ethambutol and moxifloxacin was commenced (pyrazinamide was excluded due to the intrinsic resistance of M. bovis). The second stage revision was delayed until completion of 12 weeks of this therapy, approximately 6 months after the first stage revision (explantation), with an uncemented modular titanium femoral stem and modular titanium revision shell with metal on polyethylene articulation. The patient is presently walking without aid and without pain or clinical recurrence of PJI. 

Discussion and conclusions

BCG is a live attenuated strain of M. bovis and has been used as an intravesical immunotherapy for superficial bladder cancer since 1976 [8]. Local complications of intravesical BCG therapy are well recognised and include cystitis and granulomatous prostatitis [9]. Systemic complications due to disseminated BCG infection (e.g. pneumonitis or granulomatous hepatitis) have also been described. However, reports of M. bovis osteoarticular infections following intravesical BCG instillation, and in particular PJI, are extremely rare.
A review of the literature suggests that only eight such cases have been reported to date, six of prosthetic hip replacements and two in prosthetic knees [9]. The time between intravesical instillation to the development of symptomatic BCG PJI ranges from 7 days to years [916]. It has been suggested that early infection results from haematogenous dissemination, which may be reduced by delaying BCG therapy after surgical interventions and urethral catheterisation [17]. Several hypotheses have been proposed to account for the delayed presentation of BCG PJI. BCG is often found in the urine for > 12 months after therapy so probably breaches the bladder mucosa and is transiently bloodborne, leading to seeding of the prosthesis [18, 19]. In our case the route of infection was likely haematogenous as there was no evidence of malignant spread from the bladder cancer or extension of the soft tissue abnormalities to the bladder or renal tract.
One of the common features of other cases of BCG PJI is the prolonged time between patient presentation and final diagnosis. Possible reasons include lack of clinical suspicion and appropriate diagnostic testing for mycobacteria, different patterns of inflammation relative to other bacteria, as well as the extended culture time required due to slow mycobacterial replication rate. Such delay may have significant implications for the initiation of appropriate treatment. In addition, the speciation of bacilli in mycobacterial cultures and traditional phenotypic drug sensitivity testing may increase laboratory turnaround times by several weeks.
In this case, diagnostic delay was due to low clinical suspicion and therefore mycobacterial cultures were not initially attempted. Once material was cultured in liquid cultures, and analysed by WGS, a microbiological diagnosis was rapidly achieved and appropriate surgical and medical management instituted, including targeted anti-mycobacterial chemotherapy based on genotypic drug susceptibility testing (DST) data [20]. However, WGS still relies on bacterial culture and while it offers advantages over other molecular methods of speciation, it remains relatively costly and requires complex analytical pipelines [21]. A recent advancement on the targeted amplicon sequencing used in pan-bacterial 16S rDNA PCR is shotgun metagenomic next-generation sequencing which has the potential to broaden the unbiased detection of pathogens directly from clinical samples in culture-negative PJI [2224]. However, it is still predominantly a research technique and its widespread adoption in routine clinical diagnostics is currently limited by low yields of pathogenic DNA recovered from samples, high costs and complex data processing [25].
It should be noted that while the inclusion of synovial alpha-defensin testing, such as Synovasure™, in the diagnostic pathway for PJI is being increasingly advocated, our case demonstrates that negative NAMP assays occur in non-pyogenic infections, potentially resulting in the exclusion of PJI with implications for subsequent surgical decision-making (e.g. whether to proceed to a one or two stage revision) [5].
As this case illustrates, BCG infection after therapeutic exposure can have serious consequences, and monitoring the frequency of this complication is important. Three distinct groups of BCG isolates were identified, presumably corresponding to the products of different suppliers; WGS-based approaches to identifying the likely source may contribute to this goal, as well as unambiguously differentiating BCG from more virulent M. bovis isolates.
In summary, we describe the use of mycobacterial WGS for the rapid identification of M. bovis PJI occurring after intravesical BCG therapy. The benefits of this approach included a rapid diagnosis, definitive exclusion of infections with other M. tuberculosis complex members, and the timely initiation of appropriate antimicrobial therapy. Ongoing advances in sample processing, including culture-independent techniques, have the potential to reduce turnaround times further. This case also highlights the application of WGS for detecting and monitoring rare but serious complications following BCG exposure (which should be considered in PJI cases), contributing to detection and surveillance of such serious complications.

Acknowledgements

None.
Not required.
Written informed consent for publication of their clinical details and clinical images was obtained from the patient. A copy of the consent form is available for review by the Editor of this journal.

Competing interests

The authors declare that they have no competing interests.
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Literatur
1.
Zurück zum Zitat Cram P, Lu X, Kates SL, Singh JA, Li Y, Wolf BR. Total knee arthroplasty volume, utilization, and outcomes among Medicare beneficiaries, 1991-2010. JAMA. 2012;308(12):1227–36.CrossRef Cram P, Lu X, Kates SL, Singh JA, Li Y, Wolf BR. Total knee arthroplasty volume, utilization, and outcomes among Medicare beneficiaries, 1991-2010. JAMA. 2012;308(12):1227–36.CrossRef
2.
Zurück zum Zitat Osmon DR, Berbari EF, Berendt AR, et al. Diagnosis and management of prosthetic joint infection: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2013;56(1):e1–e25.CrossRef Osmon DR, Berbari EF, Berendt AR, et al. Diagnosis and management of prosthetic joint infection: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2013;56(1):e1–e25.CrossRef
3.
Zurück zum Zitat Watters TS, Cardona DM, Menon KS, Vinson EN, Bolognesi MP, Dodd LG. Aseptic lymphocyte-dominated vasculitis-associated lesion: a clinicopathologic review of an underrecognized cause of prosthetic failure. Am J Clin Pathol. 2010;134(6):886–93.CrossRef Watters TS, Cardona DM, Menon KS, Vinson EN, Bolognesi MP, Dodd LG. Aseptic lymphocyte-dominated vasculitis-associated lesion: a clinicopathologic review of an underrecognized cause of prosthetic failure. Am J Clin Pathol. 2010;134(6):886–93.CrossRef
4.
Zurück zum Zitat Public Health England. Investigation of Fluids from Normally Sterile Sites. Vol. B26 Issue 6.2, 2018. Public Health England. Investigation of Fluids from Normally Sterile Sites. Vol. B26 Issue 6.2, 2018.
5.
Zurück zum Zitat Goswami K, Parvizi J, Maxwell CP. Current recommendations for the diagnosis of acute and chronic PJI for hip and knee-cell counts, alpha-Defensin, leukocyte esterase, Next-generation Sequencing. Curr Rev Musculoskelet Med. 2018;11(3):428–38.CrossRef Goswami K, Parvizi J, Maxwell CP. Current recommendations for the diagnosis of acute and chronic PJI for hip and knee-cell counts, alpha-Defensin, leukocyte esterase, Next-generation Sequencing. Curr Rev Musculoskelet Med. 2018;11(3):428–38.CrossRef
6.
Zurück zum Zitat Bradley P, Gordon NC, Walker TM, et al. Rapid antibiotic-resistance predictions from genome sequence data for Staphylococcus aureus and Mycobacterium tuberculosis. Nat Commun. 2015;6:10063.CrossRef Bradley P, Gordon NC, Walker TM, et al. Rapid antibiotic-resistance predictions from genome sequence data for Staphylococcus aureus and Mycobacterium tuberculosis. Nat Commun. 2015;6:10063.CrossRef
7.
Zurück zum Zitat Nguyen LT, Schmidt HA, von Haeseler A, Minh BQ. IQ-TREE: a fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies. Mol Biol Evol. 2015;32(1):268–74.CrossRef Nguyen LT, Schmidt HA, von Haeseler A, Minh BQ. IQ-TREE: a fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies. Mol Biol Evol. 2015;32(1):268–74.CrossRef
8.
Zurück zum Zitat Morales A, Eidinger D, Bruce AW. Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumors. J Urol. 1976;116(2):180–3.CrossRef Morales A, Eidinger D, Bruce AW. Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumors. J Urol. 1976;116(2):180–3.CrossRef
9.
Zurück zum Zitat Gomez E, Chiang T, Louie T, Ponnapalli M, Eng R, Huang DB. Prosthetic joint infection due to Mycobacterium bovis after Intravesical instillation of Bacillus Calmette-Guerin (BCG). Int J Microbiol. 2009;2009:527208.CrossRef Gomez E, Chiang T, Louie T, Ponnapalli M, Eng R, Huang DB. Prosthetic joint infection due to Mycobacterium bovis after Intravesical instillation of Bacillus Calmette-Guerin (BCG). Int J Microbiol. 2009;2009:527208.CrossRef
10.
Zurück zum Zitat Reigstad O, Siewers P. A total hip replacement infected with mycobacterium bovis after intravesicular treatment with Bacille-Calmette-Guérin for bladder cancer. J Bone Joint Surg Br. 2008;90(2):225–7.CrossRef Reigstad O, Siewers P. A total hip replacement infected with mycobacterium bovis after intravesicular treatment with Bacille-Calmette-Guérin for bladder cancer. J Bone Joint Surg Br. 2008;90(2):225–7.CrossRef
11.
Zurück zum Zitat Segal A, Krauss ES. Infected total hip arthroplasty after intravesical bacillus Calmette-Guérin therapy. J Arthroplast. 2007;22(5):759–62.CrossRef Segal A, Krauss ES. Infected total hip arthroplasty after intravesical bacillus Calmette-Guérin therapy. J Arthroplast. 2007;22(5):759–62.CrossRef
12.
Zurück zum Zitat Guerra CE, Betts RF, O'Keefe RJ, Shilling JW. Mycobacterium bovis osteomyelitis involving a hip arthroplasty after intravesicular bacille Calmette-Guérin for bladder cancer. Clin Infect Dis. 1998;27(3):639–40.CrossRef Guerra CE, Betts RF, O'Keefe RJ, Shilling JW. Mycobacterium bovis osteomyelitis involving a hip arthroplasty after intravesicular bacille Calmette-Guérin for bladder cancer. Clin Infect Dis. 1998;27(3):639–40.CrossRef
13.
Zurück zum Zitat Chazerain P, Desplaces N, Mamoudy P, Leonard P, Ziza JM. Prosthetic total knee infection with a bacillus Calmette Guerin (BCG) strain after BCG therapy for bladder cancer. J Rheumatol. 1993;20(12):2171–2.PubMed Chazerain P, Desplaces N, Mamoudy P, Leonard P, Ziza JM. Prosthetic total knee infection with a bacillus Calmette Guerin (BCG) strain after BCG therapy for bladder cancer. J Rheumatol. 1993;20(12):2171–2.PubMed
14.
Zurück zum Zitat Rispler DT, Stirton JW, Gilde AK, Kane KR. Mycobacterium bovid infection of total knee arthroplasty after bacille Calmette-Guérin therapy for bladder cancer. Am J Orthop (Belle Mead NJ). 2015;44(2):E46–8. Rispler DT, Stirton JW, Gilde AK, Kane KR. Mycobacterium bovid infection of total knee arthroplasty after bacille Calmette-Guérin therapy for bladder cancer. Am J Orthop (Belle Mead NJ). 2015;44(2):E46–8.
15.
Zurück zum Zitat Patel A, Elzweig J. Mycobacterium bovis prosthetic joint infection following intravesical instillation of BCG for bladder cancer. BMJ Case Rep. 2019;12(12):e231830.CrossRef Patel A, Elzweig J. Mycobacterium bovis prosthetic joint infection following intravesical instillation of BCG for bladder cancer. BMJ Case Rep. 2019;12(12):e231830.CrossRef
16.
Zurück zum Zitat Storandt M, Nagpal A. Prosthetic joint infection: an extremely rare complication of intravesicular BCG therapy. BMJ Case Rep. 2019;12(12):e232809.CrossRef Storandt M, Nagpal A. Prosthetic joint infection: an extremely rare complication of intravesicular BCG therapy. BMJ Case Rep. 2019;12(12):e232809.CrossRef
17.
Zurück zum Zitat Lamm DL. Complications of bacillus Calmette-Guérin immunotherapy. Urol Clin North Am. 1992;19(3):565–72.PubMed Lamm DL. Complications of bacillus Calmette-Guérin immunotherapy. Urol Clin North Am. 1992;19(3):565–72.PubMed
18.
Zurück zum Zitat Böhle A, Kirsten D, Schröder KH, et al. Clinical evidence of systemic persistence of bacillus Calmette-Guerin: long-term pulmonary bacillus Calmette-Guerin infection after intravesical therapy for bladder cancer and subsequent cystectomy. J Urol. 1992;148(6):1894–7.CrossRef Böhle A, Kirsten D, Schröder KH, et al. Clinical evidence of systemic persistence of bacillus Calmette-Guerin: long-term pulmonary bacillus Calmette-Guerin infection after intravesical therapy for bladder cancer and subsequent cystectomy. J Urol. 1992;148(6):1894–7.CrossRef
19.
Zurück zum Zitat Bowyer L, Hall RR, Reading J, Marsh MM. The persistence of bacille Calmette-Guérin in the bladder after intravesical treatment for bladder cancer. Br J Urol. 1995;75(2):188–92.CrossRef Bowyer L, Hall RR, Reading J, Marsh MM. The persistence of bacille Calmette-Guérin in the bladder after intravesical treatment for bladder cancer. Br J Urol. 1995;75(2):188–92.CrossRef
20.
Zurück zum Zitat Quan TP, Bawa Z, Foster D, et al. Evaluation of Whole-Genome Sequencing for Mycobacterial Species Identification and Drug Susceptibility Testing in a Clinical Setting: a Large-Scale Prospective Assessment of Performance against Line Probe Assays and Phenotyping. J Clin Microbiol. 2018;56(2):e01480–17.PubMedPubMedCentral Quan TP, Bawa Z, Foster D, et al. Evaluation of Whole-Genome Sequencing for Mycobacterial Species Identification and Drug Susceptibility Testing in a Clinical Setting: a Large-Scale Prospective Assessment of Performance against Line Probe Assays and Phenotyping. J Clin Microbiol. 2018;56(2):e01480–17.PubMedPubMedCentral
21.
Zurück zum Zitat Satta G, Lipman M, Smith GP, Arnold C, Kon OM, McHugh TD. Mycobacterium tuberculosis and whole-genome sequencing: how close are we to unleashing its full potential? Clin Microbiol Infect. 2018;24(6):604–9.CrossRef Satta G, Lipman M, Smith GP, Arnold C, Kon OM, McHugh TD. Mycobacterium tuberculosis and whole-genome sequencing: how close are we to unleashing its full potential? Clin Microbiol Infect. 2018;24(6):604–9.CrossRef
22.
Zurück zum Zitat Wang CX, Huang Z, Fang W, et al. Preliminary assessment of nanopore-based metagenomic sequencing for the diagnosis of prosthetic joint infection. Int J Infect Dis. 2020;97:54–9.CrossRef Wang CX, Huang Z, Fang W, et al. Preliminary assessment of nanopore-based metagenomic sequencing for the diagnosis of prosthetic joint infection. Int J Infect Dis. 2020;97:54–9.CrossRef
23.
Zurück zum Zitat Cai Y, Fang X, Chen Y, et al. Metagenomic next generation sequencing improves diagnosis of prosthetic joint infection by detecting the presence of bacteria in periprosthetic tissues. Int J Infect Dis. 2020;96:573–8.CrossRef Cai Y, Fang X, Chen Y, et al. Metagenomic next generation sequencing improves diagnosis of prosthetic joint infection by detecting the presence of bacteria in periprosthetic tissues. Int J Infect Dis. 2020;96:573–8.CrossRef
24.
Zurück zum Zitat Ivy MI, Thoendel MJ, Jeraldo PR, et al. Direct Detection and Identification of Prosthetic Joint Infection Pathogens in Synovial Fluid by Metagenomic Shotgun Sequencing. J Clin Microbiol. 2018;56(9):e00402–18.CrossRef Ivy MI, Thoendel MJ, Jeraldo PR, et al. Direct Detection and Identification of Prosthetic Joint Infection Pathogens in Synovial Fluid by Metagenomic Shotgun Sequencing. J Clin Microbiol. 2018;56(9):e00402–18.CrossRef
25.
Zurück zum Zitat Ruppe E, Lazarevic V, Girard M, et al. Clinical metagenomics of bone and joint infections: a proof of concept study. Sci Rep. 2017;7(1):7718.CrossRef Ruppe E, Lazarevic V, Girard M, et al. Clinical metagenomics of bone and joint infections: a proof of concept study. Sci Rep. 2017;7(1):7718.CrossRef
Metadaten
Titel
Prosthetic hip joint infection by Bacillus Calmette-Guerin therapy following intravesical instillation for bladder cancer identified using whole-genome sequencing: a case report
verfasst von
Michael Riste
Pretin Davda
E. Grace Smith
David H. Wyllie
Martin Dedicoat
Simantini Jog
Steven Laird
Gerald Langman
Neil Jenkins
Jonathan Stevenson
Matthew K. O’Shea
Publikationsdatum
01.12.2021
Verlag
BioMed Central
Erschienen in
BMC Infectious Diseases / Ausgabe 1/2021
Elektronische ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-021-05831-3

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