The Value of Preoperative Ultrasound-Determined Fluid Film and Joint Aspiration in Revision Hip Arthroplasty.

BACKGROUND: Data regarding the diagnostic value of ultrasound (US)-determined fluid film and joint aspiration prior to revision total hip arthroplasty for suspected periprosthetic joint infections (PJIs) are limited. This study aimed to analyze the value of US-determined fluid film, characterized the preoperative and intraoperative microbiological spectrum and resistance patterns, and compared the concordance between preoperative synovial fluid and intraoperative culture results. METHODS: We analyzed 366 US examinations from 324 patients prior to revision total hip arthroplasty. Selected cases were grouped into clearly infected, noninfected, and inconclusive cohorts, according to the International Consensus Meeting 2018 Criteria. For US-determined fluid film <1 mm, no aspiration was performed based on our institutional protocol. Patients were grouped into no aspiration (144 of 366; [39.3%]), dry tap (21 of 366; [5.7%]), and a successful tap (201 of 366; [54.9%]). The microbiological spectrum and antibiograms were compared between preoperative and intraoperative results. RESULTS: The absence of US-determined fluid film showed no correlation with the presence of a hip PJI. Overall, 31.9% cases of the no-aspiration group had a PJI. In total, 13.5% discrepancies were found between successful taps and intraoperative cultures. The most prevalent microorganisms in preoperative synovial fluid were Staphylococcus epidermidis and Staphylococcus aureus (20.8%), while intraoperatively S. epidermidis (26.3%) and Cutibacterium acnes (14.5%) were leading. Additional microorganisms were identified in 32.5% of intraoperative cultures. There were no differences between resistance patterns of preoperative and intraoperative concordant microorganisms. CONCLUSIONS: Absence of US-determined fluid film cannot rule out the presence of a hip PJI. Combined microbiological results from hip US aspirations and subsequent surgical procedures are crucial to design an effective treatment for suspected hip PJI.

Different microbial and resistance patterns in primary total knee arthroplasty infections - a report on 283 patients from Lithuania and Sweden.

BACKGROUND: The microbiology and the susceptibility patterns of infected total knee arthroplasties (TKAs) vary depending on demographic, local antimicrobial stewardship, and surgical factors. We wanted to compare the recent microbial profile and antimicrobial resistance pattern in revisions due to infections after primary TKAs in Sweden and Lithuania. Our hypothesis was that there is a difference in bacteriology and resistance pattern based on patient related, societal and local hospital factors as almost similar praxis have been applied for TKA surgery, short term systemic prophylaxis and routine use of local gentamicin containing bone cement. METHODS: Primary TKAs revised for the first time due to verified or suspected infection were collected nationwide in Sweden during 2018, and in Lithuania between 2011 and 2020 from a single major TKA revision centre in Kaunas. We identified 202 TKAs in Sweden from the Swedish Knee Arthroplasty Register and 84 from Kaunas revised due to infection. We collected available culture reports and evaluated the type of microorganisms with antimicrobial resistance pattern at revision. RESULTS: The majority of the infected cases in Sweden were early-type prosthetic joint infection (PJI) (44%), whereas late-type PJI (52%) were more common in the Kaunas cases. Gram-positive bacteria prevailed in both Sweden (55%) and Lithuania (80%). Staphylococcus aureus was the most frequent organism identified in both countries (33% in Sweden and 34% in Lithuania). More polymicrobial infections were observed in Sweden than in Lithuania (16 and 6% respectively). Methicillin resistance in Staphylococcus aureus and coagulase-negative staphylococci were higher in Lithuania (4/28 and 19/29) than in Sweden (1/42 and 9/41). CONCLUSIONS: The type of infections, microbial profile, and drug resistance pattern differed between Sweden and Lithuania. Societal and local hospitals factors with emerging resistance in Lithuania are the most plausible explanation for the difference. Lack of complete data on a national level in Lithuania underlines the importance of adding microbiology of PJIs in implant registers for national aggregation and allow cross country comparisons.

Staged Reimplantation of a Total Hip Prosthesis After Co-infection with Candida tropicalis and Staphylococcus haemolyticus: A Case Report.

Fungal prosthetic joint infection is a rare complication in total joint arthroplasty. There are no established guidelines for management of these infections. We present a case of a 53-year-old male with a hip joint prosthesis co-infected with Candida tropicalis and Staphylococcus haemolyticus. A two-stage exchange arthroplasty was performed. The patient underwent implant removal, debridement, irrigation with saline solution and application of cement spacer impregnated with vancomycin followed by aggressive antimicrobial treatment in first stage. Complete eradication of infection was demonstrated by negative culture of sonicated cement spacer fluid and negative 16S rRNA and 18S rRNA gene PCR of sonicate fluid, synovial fluid and periprosthetic tissue samples. He underwent second-stage revision hip arthroplasty after 9 months of the first stage. At the latest follow-up, there was no evidence of recurrence of infection. This case illustrates the utility of sonication of biomaterials and molecular techniques for microbiological confirmation of absence of infection in staged surgeries which is required for a successful outcome.

Hydroxyapatite: An antibiotic recruiting moiety for local treatment and prevention of bone infections.

Treatment of chronic osteomyelitis by radical debridement and filling of the dead space with antibiotic containing calcium sulfate/hydroxyapatite (CaS/HA) bone substitute has shown excellent long-term outcomes. However, in extensive infections, sessile bacteria may remain in bone cells or soft tissues protected by biofilm leading to recurrences. The primary aim of this study was to evaluate if systemically administrated tetracycline (TET) could bind to pre-implanted HA particles and impart an antibacterial effect locally. In vitro studies indicated that the binding of TET to nano- and micro-sized HA particles was rapid and plateaued already at 1 h. Since protein passivation of HA after in-vivo implantation could affect HA-TET interaction, we investigated the effect of serum exposure on HA-TET binding in an antibacterial assay. Although, serum exposure reduced the zone of inhibition (ZOI) of Staphylococcus aureus, a significant ZOI could still be observed after pre-incubation of HA with serum. We could in addition show that zoledronic acid (ZA) competes for the same binding sites as TET and that exposure to high doses of ZA led to reduced TET-HA binding. In an in-vivo setting, we then confirmed that systemically administered TET seeks HA particles that were pre-implanted in muscle and subcutaneous pouches in rats and mice respectively, preventing HA particles from being colonized by S. aureus. Clinical Significance: This study describes a new drug delivery method that could prevent bacterial colonization of a HA biomaterial and reduce recurrences in bone infection.

Systemic rifampicin shows accretion to locally implanted hydroxyapatite particles in a rat abdominal muscle pouch model.

Introduction: biomaterials combined with antibiotics are routinely used for the management of bone infections. After eluting high concentrations of antibiotics during the first week, sub-inhibitory concentrations of antibiotics may lead to late repopulation of recalcitrant bacteria. Recent studies have shown that systemically given antibiotics like tetracycline and rifampicin (RIF) could seek and bind to locally implanted hydroxyapatite (HA). The aim of this in vivo study was to test if systemically administered rifampicin could replenish HA-based biomaterials with or without prior antibiotic loading to protect the material from late bacterial repopulation. Methods: in vivo accretion of systemically administered RIF to three different types of HA-based materials was tested. In group 1, nano (n)- and micro (m)-sized HA particles were used, while group 2 consisted of a calcium sulfate / hydroxyapatite (CaS / HA) biomaterial without preloaded antibiotics gentamycin (GEN) or vancomycin (VAN), and in group 3, the CaS / HA material contained GEN (CaS / HA + GEN) or VAN (CaS / HA + VAN). The above materials were implanted in an abdominal muscle pouch model in rats, and at 7 d post-surgery, the animals were assigned to a control group (i.e., no systemic antibiotic) and a test group (i.e., animals receiving one single intraperitoneal injection of RIF each day (4 mg per rat) for 3 consecutive days). Twenty-four hours after the third injection, the animals were sacrificed and the implanted pellets were retrieved and tested against Staphylococcus aureus ATCC 25923 in an agar diffusion assay. After overnight incubation, the zone of inhibition (ZOI) around the pellets were measured. Results: in the control group, 2 / 6 CaS / HA + GEN pellets had a ZOI, while all other harvested pellets had no ZOI. No pellets from animals in test group 1 had a ZOI. In test group 2, 10 / 10 CaS / HA pellets showed a ZOI. In test group 3, 5 / 6 CaS / HA + GEN and 4 / 6 CaS / HA + VAN pellets showed a ZOI. Conclusions: in this proof-of-concept study, we have shown that a locally implanted biphasic CaS / HA carrier after 1 week can be loaded by systemic RIF administration and exert an antibacterial effect. Further in vivo infection models are necessary to validate our findings.

Sustained delivery of a heterodimer bone morphogenetic protein-2/7 via a collagen hydroxyapatite scaffold accelerates and improves critical femoral defect healing.

Despite the glimmer of hope provided by the discovery and commercialization of bone morphogenetic protein-2 (BMP-2) as a bone graft substitute, side effects related to the use of supraphysiological doses have hindered its clinical usage. In this study, we compared the osteoinductive potential of BMP-2 homodimer with a heterodimer of BMP-2/7, both delivered via a collagen-hydroxyapatite (CHA) scaffold delivery system, with the aim to reduce the overall therapeutic BMP doses and the associated side-effects. We first show that the incorporation of hydroxyapatite in collagen-based BMP delivery systems is pivotal for achieving efficient BMP sequestration and controlled release. Using an ectopic implantation model, we then showed that the CHA+BMP-2/7 was more osteoinductive than CHA+BMP-2. Further evaluation of the molecular mechanisms responsible for this increased osteoinductivity at an early stage in the regeneration process indicated that the CHA+BMP-2/7 enhanced progenitor cell homing at the implantation site, upregulated the key transcriptomic determinants of bone formation, and increased the production of bone extracellular matrix components. Using fluorescently labelled BMP-2/7 and BMP-2, we demonstrated that the CHA scaffold provided a long-term delivery of both molecules for at least 20 days. Finally, using a rat femoral defect model, we showed that an ultra-low dose (0.5 µg) of BMP-2/7 accelerated fracture healing and performed at a level comparable to 20-times higher BMP-2 dose. Our results indicate that the sustained delivery of BMP-2/7 via a CHA scaffold could bring us a step closer in the quest for the use of physiological growth factor doses in fracture healing. STATEMENT OF SIGNIFICANCE: • Incorporation of hydroxyapatite (HA) in a collagen scaffold dramatically improves bone morphogenic protein (BMP) sequestration via biophysical interactions with BMP, thereby providing more controlled BMP release compared with pristine collagen. • We then investigate the molecular mechanisms responsible for increased osteoinductive potential of a heterodimer BMP-2/7 with is clinically used counterpart, the BMP-2 homodimer. • The superior osteoinductive properties of BMP-2/7 are a consequence of its direct positive effect on progenitor cell homing at the implantation site, which consequently leads to upregulation of cartilage and bone related genes and biochemical markers. • An ultra-low dose of BMP-2/7 delivered via a collagen-HA (CHA) scaffold leads to accelerated healing of a critical femoral defect in rats while a 20-times higher BMP-2 dose was required to achieve comparable results.

Extended local release and improved bacterial eradication by adding rifampicin to a biphasic ceramic carrier containing gentamicin or vancomycin.

AIMS: There is a lack of biomaterial-based carriers for the local delivery of rifampicin (RIF), one of the cornerstone second defence antibiotics for bone infections. RIF is also known for causing rapid development of antibiotic resistance when given as monotherapy. This in vitro study evaluated a clinically used biphasic calcium sulphate/hydroxyapatite (CaS/HA) biomaterial as a carrier for dual delivery of RIF with vancomycin (VAN) or gentamicin (GEN). METHODS: The CaS/HA composites containing RIF/GEN/VAN, either alone or in combination, were first prepared and their injectability, setting time, and antibiotic elution profiles were assessed. Using a continuous disk diffusion assay, the antibacterial behaviour of the material was tested on both planktonic and biofilm-embedded forms of standard and clinical strains of Staphylococcus aureus for 28 days. Development of bacterial resistance to RIF was determined by exposing the biofilm-embedded bacteria continuously to released fractions of antibiotics from CaS/HA-antibiotic composites. RESULTS: Following the addition of RIF to CaS/HA-VAN/GEN, adequate injectability and setting of the CaS/HA composites were noted. Sustained release of RIF above the minimum inhibitory concentrations of S. aureus was observed until study endpoint (day 35). Only combinations of CaS/HA-VAN/GEN + RIF exhibited antibacterial and antibiofilm effects yielding no viable bacteria at study endpoint. The S. aureus strains developed resistance to RIF when biofilms were subjected to CaS/HA-RIF alone but not with CaS/HA-VAN/GEN + RIF. CONCLUSION: Our in vitro results indicate that biphasic CaS/HA loaded with VAN or GEN could be used as a carrier for RIF for local delivery in clinically demanding bone infections.Cite this article: Bone Joint Res 2022;11(11):787-802.

Longitudinal in vivo biodistribution of nano and micro sized hydroxyapatite particles implanted in a bone defect.

Hydroxyapatite (HA) has been widely used as a bone substitute and more recently as a carrier for local delivery of bone targeted drugs. Majority of the approved HA based biomaterials and drug carriers comprise of micrometer sized particulate HA (mHA) or granules and can therefore only be used for extracellular drug release. This shortcoming could be overcome with the use of cell penetrating HA nanoparticles (nHA) but a major concern with the clinical use of nHA is the lack of data on its in vivo biodistribution after implantation. In this study, we aimed to study the in vivo biodistribution of locally implanted nHA in a clinically relevant tibial void in rats and compare it with mHA or a combination of mHA and nHA. To enable in vivo tracking, HA particles were first labelled with 14C-zoledronic acid (14C-ZA), known to have a high binding affinity to HA. The labelled particles were then implanted in the animals and the radioactivity in the proximal tibia and vital organs was detected at various time points (Day 1, 7 and 28) post-implantation using scintillation counting. The local distribution of the particles in the bone was studied with micro-CT. We found that majority (>99.9%) of the implanted HA particles, irrespective of the size, stayed locally at the implantation site even after 28 days and the findings were confirmed using micro-CT. Less than 0.1% radioactivity was observed in the kidney and the spleen at later time points of day 7 and 28. No pathological changes in any of the vital organs could be observed histologically. This is the first longitudinal in vivo HA biodistribution study showing that the local implantation of nHA particles in bone is safe and that nHA could potentially be used for localized drug delivery.

Bone mineral: A trojan horse for bone cancers. Efficient mitochondria targeted delivery and tumor eradication with nano hydroxyapatite containing doxorubicin.

Efficient systemic pharmacological treatment of solid tumors is hampered by inadequate tumor concentration of cytostatics necessitating development of smart local drug delivery systems. To overcome this, we demonstrate that doxorubicin (DOX), a cornerstone drug used for osteosarcoma treatment, shows reversible accretion to hydroxyapatite (HA) of both nano (nHA) and micro (mHA) size. nHA particles functionalized with DOX get engulfed in the lysosome of osteosarcoma cells where the acidic microenvironment causes a disruption of the binding between DOX and HA. The released DOX then accumulates in the mitochondria causing cell starvation, reduced migration and apoptosis. The HA+DOX delivery system was also tested in-vivo on osteosarcoma bearing mice. Locally delivered DOX via the HA particles had a stronger tumor eradication effect compared to the controls as seen by PET-CT and immunohistochemical staining of proliferation and apoptosis markers. These results indicate that in addition to systemic chemotherapy, an adjuvant nHA could be used as a carrier for intracellular delivery of DOX for prevention of tumor recurrence after surgical resection in an osteosarcoma. Furthermore, we demonstrate that nHA particles are pivotal in this approach but a combination of nHA with mHA could increase the safety associated with particulate nanomaterials while maintaining similar therapeutic potential.

The utility of dithiothreitol treatment of periprosthetic tissues and explanted implants in the diagnosis of prosthetic joint infection.

PURPOSE: The methods used for the processing of periprosthetic tissues and explanted implants to improve culture outcome especially in biofilm mediated prosthetic joint infections (PJIs) are still debated upon. Studies have reported that Dithiothreitol (DTT) pretreatment of infected devices gives similar results as sonication. However, none of them evaluated the DTT treatment of periprosthetic tissues and explanted implants in the same cohort. We evaluated the diagnostic utility of DTT treatment of periprosthetic tissue and explanted implants, as compared to the normal saline treatment of periprosthetic tissues and sonication of explanted implants for the diagnosis of PJI. METHODS: Seventy-three revision arthroplasty cases were prospectively included in this study. Three to five tissue specimens and the explanted implants were collected from each patient. Periprosthetic tissue samples were processed by both normal saline and DTT treatments. Explanted implants were subjected to both DTT treatment and sonication. Musculoskeletal Infection Society (MSIS) PJI criteria was used as the reference standard for the diagnosis of PJI. RESULTS: Of the 73 cases enrolled, 34 had PJI and 39 were aseptic failures. The sensitivity of DTT treated periprosthetic tissue culture (PTC) and saline treated PTC was similar (66.6% vs 58.8%, P = 0.25). The specificity of both was 100%. Sonication and DTT treatment of explanted implants showed comparable sensitivity (85.3% vs 82.4%) and specificity (100% vs 97.4%), P > 0.99. Compared to DTT treated PTC, culture of DTT treated explanted implants significantly improved the diagnosis of PJI (P = 0.03). CONCLUSIONS: We could verify that DTT can be used to improve culture outcome in laboratories where biofilm detaching sonication techniques are not available for infected implants. In addition, we showed that it is possible to use DTT for treating tissue biopsies, but larger studies are required to confirm our findings.

Sustained and controlled delivery of doxorubicin from an in-situ setting biphasic hydroxyapatite carrier for local treatment of a highly proliferative human osteosarcoma.

Doxorubicin (DOX) is a cornerstone drug in the treatment of osteosarcoma. However, achieving sufficient concentration in the tumor tissue after systemic administration with few side effects has been a challenge. Even with the most advanced nanotechnology approaches, less than 5% of the total administered drug gets delivered to the target site. Alternatives to increase the local concentration of DOX within the tumor using improved drug delivery methods are needed. In this study, we evaluate a clinically approved calcium sulfate/hydroxyapatite (CaS/HA) carrier, both in-vitro and in-vivo, for local, sustained and controlled delivery of DOX to improve osteosarcoma treatment. In-vitro drug release studies indicated that nearly 28% and 36% of the loaded drug was released over a period of 4-weeks at physiological pH (7.4) and acidic pH (5), respectively. About 63% of the drug had been released after 4-weeks in-vivo. The efficacy of the released drug from the CaS/HA material was verified on two human osteosarcoma cell lines MG-63 and 143B. It was demonstrated that the released drug fractions functioned the same way as the free drug without impacting its efficacy. Finally, the carrier system with DOX was assessed using two clinically relevant human osteosarcoma xenograft models. Compared to no treatment or the clinical standard of care with systemic DOX administration, the delivery of DOX using a CaS/HA biomaterial could significantly hinder tumor progression by inhibiting angiogenesis and cell proliferation. Our results indicate that a clinically approved CaS/HA biomaterial containing cytostatics could potentially be used for the local treatment of osteosarcoma. STATEMENT OF SIGNIFICANCE: The triad of doxorubicin (DOX), methotrexate and cisplatin has routinely been used for the treatment of osteosarcoma. These drugs dramatically improved the prognosis, but 45-55% of the patients respond poorly to the treatment with low 5-year survival. In the present study, we repurpose the cornerstone drug DOX by embedding it in a calcium sulfate/hydroxyapatite (CaS/HA) biomaterial, ensuring a spatio-temporal drug release and a hypothetically higher and longer lasting intra-tumoral concentration of DOX. This delivery system could dramatically hinder the progression of a highly aggressive osteosarcoma compared to systemic administration, by inhibiting angiogenesis and cell proliferation. Our data show an efficient method for supplementary osteosarcoma treatment with possible rapid translational potential due to clinically approved constituents.

Antibiotic containing bone cement in prevention of hip and knee prosthetic joint infections: A systematic review and meta-analysis.

BACKGROUND: Prosthetic joint infection (PJI) is the most serious total joint arthroplasty (TJA) complication despite several aseptic and antiseptic preventive measures. There is no clear evidence or even consensus, whether antibiotic-loaded bone cement (ALBC) should be used, in addition to systemic short-term routine antibiotic prophylaxis, to reduce the risk of PJI in primary TJA. We aimed to analyze the efficacy of ALBC for prevention of PJI in patients undergoing primary TJA. METHODS: We searched systematically for randomized controlled trials (RCTs) in PubMed, Scopus, Embase, Web of Science and Cochrane library. Two reviewers independently screened potentially eligible studies according to predefined selection criteria and assessed the risk of bias using a modified version of the Cochrane risk of bias tool. PJI was prespecified as the primary outcome of interest. The meta-analyses were based on risk ratios using random-effects model per default. For the purpose of sensitivity, the corresponding fixed effects model odds ratios were calculated with the use of the Peto method as well. To evaluate a potential difference in effect sizes using different types (subgroups) of antibiotics used in bone cement, and at different follow-up periods, we performed stratified meta-analyses. RESULTS: Thirty-seven studies were eligible for the systematic review and qualitative synthesis, and 9 trials (6507 total joint arthroplasties) were included in this meta-analysis. Overall ALBC significantly reduced the risk of PJI following primary TJAs (RRs, 0.36; 95% CIs, 0.16 to 0.80; P = 0.01) with a moderate degree of inconsistency (I2 = 47%). Based on stratified meta-analyses the use of gentamicin appeared to have a better effect (P = 0.0005) in the total hip arthroplasty. Pooled data of different antibiotics used in knee arthroplasties showed a significant association of cefuroxime (RRs, 0.08; 95% CIs, 0.01 to 0.63; P = 0.02). Further, ALBCs significantly reduced the PJI at one and two years of follow-up (P = 0.03 and P = 0.005 respectively). CONCLUSIONS: The evidence suggests that ALBCs are effective in reducing the PJI following primary TJA; i.e. between 20 and 84% reduced risk. However, the clear limitations of the available trial evidence highlight the need for joint-specific confirmatory trials, that will need to be designed as cluster-randomized trials of clinics in countries with well-functioning arthroplasty registries.The translational potential of this article: This meta-analysis highlights the prophylactic potential of ALBCs in lowering the risk of infection following primary hip or knee arthroplasties but emphasizes the need for more recent confirmatory trials.

A Clinico-Microbiological Study of Prosthetic Joint Infections in an Indian Tertiary Care Hospital: Role of Universal 16S rRNA Gene Polymerase Chain Reaction and Sequencing in Diagnosis.

BACKGROUND: We determined the magnitude and clinico-microbiological profile of prosthetic joint infection (PJI) at a tertiary hospital. The diagnostic potential of 16S rRNA gene polymerase chain reaction (PCR) and sequencing on periprosthetic tissue samples was evaluated for the diagnosis of PJI. MATERIALS AND METHODS: This ambispective cohort study consisted of patients who underwent primary or revision hip or knee arthroplasty from June 2013 to June 2017. The patients were classified as either infected or noninfected according to criteria set out by the musculoskeletal infection society (MSIS). Three to five periprosthetic tissue samples were collected from each patient for culture and 16S rRNA gene PCR sequencing. RESULTS: Hundred and six patients were diagnosed to have PJI as per the MSIS Criteria. The cumulative incidence of PJI at our Institute at the end of 36 months was 1.1% (95% confidence interval [CI]: 0.59-2.91). Microorganisms were isolated by periprosthetic tissue culture (PTC) in 84 patients (sensitivity: 79% and specificity: 100%). Gram-negative aerobes were most frequently isolated (61%). Polymicrobial infections were present in 8.3% of cases. The most common infecting microorganism was Staphylococcus aureus (19.5%). Multidrug resistance and methicillin resistance were noted in 54% and 34% of bacterial isolates, respectively. The sensitivity and specificity of 16S rRNA PCR of periprosthetic tissue was 86% (95% CI: 74.9-89.9) and 100% (95% CI: 94.7-100), respectively. Periprosthetic tissue 16S rRNA PCR was more sensitive than PTC (P = 0.008), although both were 100% specific (P = 0.99). CONCLUSIONS: The incidence of PJI at our Institute compares well with other published reports. Contrary to previous reports, a predominance of Gram-negative PJI's was found. The preponderance of multidrug-resistant organisms in PJI's is worrisome. The high sensitivity and specificity of the 16S PCR assay used in our study support its use in culture-negative PJI suspected cases.

Sonication of antibiotic loaded cement spacers: A valuable technique for detection of infection persistence in two-stage revision for infected joint arthroplasty.

We evaluated the diagnostic utility of sonication of antibiotic loaded cement spacers comparing with periprosthetic tissue cultures for the detection of persisting infection in 14 patients undergoing staged procedures. Sonication improved microbial detection of intraoperative cultures from 14.2% to 28.5% (P = 0.481). Routine sonication of spacers is recommended.

Prosthetic joint infection: A major threat to successful total joint arthroplasty.

Total joint arthroplasty (TJA) is one of the most common and reliable orthopaedic procedures that has significantly improved the quality of life of patients with degenerative joint diseases. Following the increase in the ageing population, availability of trained orthopaedic surgeons and advances in implantation procedures, demand for TJA both globally and in India is significantly increasing. Though TJA is one of the most cost-successful orthopaedic procedures, prosthetic joint infection (PJI) is one of the major complications of joint arthroplasty. Accurate diagnosis of PJI is challenging. Since total hip and knee arthroplasties comprises the majority of TJAs, this review focuses on the current understanding of incidence, risk factors, pathogenesis, causative microorganisms, diagnosis, treatment and prevention of PJI related to these two procedures.

Sonication of orthopaedic implants: A valuable technique for diagnosis of prosthetic joint infections.

INTRODUCTION: Accurate and prompt microbiological diagnosis of prosthetic joint infection (PJI) is crucial for successful antimicrobial treatment. Studies have shown the diagnostic utility of sonication of explanted implants in total joint arthroplasty but all did not use consensus statements for defining PJI. We evaluated the diagnostic utility of culture of samples obtained by sonication of explanted implants compared with periprosthetic tissue cultures (PTC) for the diagnosis of PJI using Musculoskeletal Infection Society (MSIS) consensus criteria. We also assessed the utility of culture of sonicate fluid for determining the microbial profile of PJI compared with standard culture methods. MATERIALS AND METHODS: Forty consecutive revision arthroplasty cases were enrolled. Three to five periprosthetic tissue samples were obtained during each explant procedure. The 40 explanted implants were collected in sterile containers and sonicated under sterile conditions. MSIS criteria were used for the definition of PJI. RESULTS: Twenty - seven patients had PJI and thirteen were aseptic failures. Of the PJI cases, there were nine cases of early PJI's, 10 of delayed PJI's and eight of late PJI's. Twenty-five (92.5%) of the twenty-seven patients with PJI, had positive cultures in the sonicate fluid of implants and in 18 (66.7%) of them cultures of the periprosthetic tissues were also positive. Both PTC and SFC cultures of implants were negative in all the 13 cases of aseptic failure. Sensitivity of sonicate fluid culture (SFC) of implants was greater than PTC (92.5% vs. 66.7%), P = .02. The specificity of both was 100%. The incidence of gram-positive and gram-negative bacteria was nearly equal by both methods. However, SFC showed an increased ability to detect Gram-positive pathogens which was evidenced by better recovery of coagulase-negative staphylococci. CONCLUSIONS: Sonication of explanted implants is a simple and valuable microbiological technique and its routine use improves the diagnostic sensitivity of PJI.

A case of oropharyngeal Ureaplasma urealyticum infection in a human immunodeficiency virus positive bisexual male co-infected with human papilloma virus and Treponema pallidum.

INTRODUCTION: Management strategies for sexually transmitted infections (STIs) in their extragenital forms address Neisseria gonorrhoeae and Chlamydia trachomatis alone; whereas increased rates of isolation of other STI agents have been reported from various parts of the world. Their extragenital presence as a reservoir of infection emphasizes the need to screen and treat them at these sites. CASE PRESENTATION: A 35-year-old human immunodeficiency virus 1 infected bisexual male presented with urethral discharge and multiple ano-genital warts. He was reactive for the venereal disease research laboratory (VDRL) test. He tested positive for Ureaplasma spp. both by culture and PCR at urethral and oropharyngeal sites, but was negative at the rectal site. The patient was successfully treated with doxycycline and penicillin, and was followed up with a test of cure at 6 weeks. CONCLUSION: In view of the disseminating infections that can be caused by Ureaplasma spp., it makes it important to screen for these infections even at non-genital sites, especially in the immunocompromised. STIs may be asymptomatic and can serve as a reservoir of infection in a population. This report should promote all efforts to formulate guidelines for extragenital screening of all STI pathogens.

A case of sterile pyuria caused by Chlamydia trachomatis and Mycoplasma hominis: A diagnostic challenge.

Sterile pyuria is a highly prevalent condition with a wide aetiological spectrum, which often challenges the diagnostician. We describe the case of a middle-aged female admitted to the medical Intensive Care Unit for acute gastroenteritis, whose urinalysis revealed persistent sterile pyuria. Polymerase chain reaction assay in urine was positive for Chlamydia trachomatis and Mycoplasma hominis. She responded to antimicrobial therapy. We hereby reflect on the approach to a case of sterile pyuria and review the available literature on this entity.

Salmonella typhimurium infection in total knee arthroplasty: A case report with review of literature.

Salmonella enterica serotype Typhimurium is a rare cause of prosthetic joint infection (PJI). The recognized predisposing risk factors for Salmonella septic arthritis include diabetes mellitus, renal failure, human immunodeficiency virus infection and chronic corticosteroid use. We describe a case of PJI of the knee in a 74-year-old lady who was on antitubercular treatment. The patient presented with discharging sinus and raised inflammatory markers. She was successfully treated by the removal of prosthesis and debridement followed by ciprofloxacin therapy for 6 weeks. This case report highlights the potential virulence of Salmonella in immunocompromised patient with a joint prosthesis. Continuous monitoring and close collaboration of microbiologists and orthopedicians helped obtain the resolution of infection in our patient.