|Year : 2021 | Volume
| Issue : 2 | Page : 85-92
A retrospective analysis of the prosthetic joint infections of the hip and knee at a tertiary care center of India
Suresh Babu1, Raju Vaishya1, Hena Butta2, Raman Sardana2, Leena Mehndiratta2, Yashpal Gulati1, Yatinder Kharbanda1, Havind Tandon1
1 Department of Orthopaedics and Joint Replacement Surgery, Indraprastha Apollo Hospitals, New Delhi, India
2 Department of Microbiologist, Indraprastha Apollo Hospitals, New Delhi, India
|Date of Submission||23-Jan-2021|
|Date of Decision||23-Mar-2021|
|Date of Acceptance||08-Apr-2021|
|Date of Web Publication||31-May-2021|
Department of Orthopaedics and Joint Replacement Surgery, Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi - 110 076
Source of Support: None, Conflict of Interest: None
Introduction: An increase in the number of primary total joint arthroplasties has correspondingly led to an increase in revisions as a result of various complications. The prosthetic joint infection (PJI) is a major complication with concordantly increased morbidity and costs. Through this study, we aimed to determine the bacteriological profiles of PJI diagnosed at our institute and analyze them in the context of patient profiles, joints affected, and the center where the index procedure was done. Materials and Methods: A retrospective study of the revision surgeries for PJI in hip and knee arthroplasties during the period between 2014 and 2019 was conducted. An analysis of 43 patient profiles, with 29 of those being knees and the rest 14 being hips was done, concerning the clinical picture, microbiological profile, and co-morbidities. Results: PJI constituted 31.03% of the revision cases. The knee joint was involved in 67.44% (n = 29) and the hip joint in 32.56% (n = 14). Early infection was seen in 2 (4.65%) and late infections in the remaining 41 (95.34%). 51.66% (n = 22) were culture-positive PJI, whereas 48.34% (n = 21) were culture-negative (CN) PJI. Preoperative C-reactive protein was elevated in 46.51% of the patients (48.27% knees and 42.87% hips). The erythrocyte sedimentation rate was preoperatively elevated by 65.12%. Of the comorbidities PJI was associated with, diabetes mellitus in 30.23%, hypertension in 39.53%, hypothyroidism in 16.28%, skin disorders in 4.65% (psoriasis and eczema), and immunosuppression in 4.65% cases. Conclusions: Microbial growth on routine culture is not mandatorily positive in several clinically suspected PJI. Hence, a stringent protocol requires to be followed in the use of antibiotics, the collection and transportation of samples, and in the selection of media for cultures in the cases of PJI. Notwithstanding the limitations of this study, we conclude that bacterial infections do not follow any predictable patterns, and constant vigilance with a low threshold to suspect and investigate PJI is needed in the management of PJI. We propose based on our study findings that no antibiotics should be used only after a bacteriological diagnosis and antibiotic sensitivity is obtained, else it results in a high rate of CN PJIs.
Keywords: Arthroplasty, culture negative, culture positive, infection, microorganism, revision
|How to cite this article:|
Babu S, Vaishya R, Butta H, Sardana R, Mehndiratta L, Gulati Y, Kharbanda Y, Tandon H. A retrospective analysis of the prosthetic joint infections of the hip and knee at a tertiary care center of India. Apollo Med 2021;18:85-92
|How to cite this URL:|
Babu S, Vaishya R, Butta H, Sardana R, Mehndiratta L, Gulati Y, Kharbanda Y, Tandon H. A retrospective analysis of the prosthetic joint infections of the hip and knee at a tertiary care center of India. Apollo Med [serial online] 2021 [cited 2021 Sep 19];18:85-92. Available from: https://www.apollomedicine.org/text.asp?2021/18/2/85/317418
| Introduction|| |
Total joint arthroplasty (TJA) of the knee and hip has become a reliable, consistent, and lasting procedure with excellent long-term results in the treatment of end-stage arthritis of these joints. With the aging of populations globally and the human desire to stay physically independent, the number of primary TJA procedures has seen a significant increase and so has the corresponding revision arthroplasty procedures.
Prosthetic joint infections (PJI) are the important reason for revision arthroplasty and entails poor outcomes and a significant cost burden to the patients. Although the rate of revisions as a result of PJIs has been constant between 0.7% and 1.9% after the primary TJAs, there has been an increase in absolute numbers corresponding to the increase in primary TJAs. Added to patients suffering, PJI puts tremendous stress on the financial resources of health-care providers, hospital workforce, bed occupancy, rehabilitation facilities, and the socioeconomic well-being of the patients. Its impact on middle- and low-income societies, like India is profound.
PJI is a devastating complication of TJA and every effort should be made to prevent it. Although there has been a delay in evolving consensus guidelines for the diagnosis and treatment of PJI, the effort has always been to prevent this complication.
Sebastian et al., in their study of PJI, have concluded that Gram-negative bacteria were the most frequent infecting microbe and that 16S polymerase chain reaction (PCR) showed high sensitivity and specificity in culture-negative (CN) infections.
Manning et al. in a study of 783 patients showed that late acute infections were the commonest mode of presentation likely reflecting hematogenous seeding. They also found that the management was heterogenous reflecting a poor evidence base and a need for randomized control trials.
Marschall et al., in their review of antibiotic practices in members of the emerging infections network, have shown considerable variation in the treatment of both culture-positive (CP) and culture-negative infections.
Jordan et al., in a review of the microbiological culture technique techniques for the diagnosis of PJIs, have found that fluids in blood culture vials have the best specificity and predictive value.
The literature on the diagnosis and management of PJI is skewed by contrarian findings, heterogeneity in management strategies, and nonuniform culture techniques.
We, therefore, studied the patterns of PJI at our hospital to understand the problem.
Aim of the study
The aim of this study is to study the incidence, microbiological, and patient profile of PJI at our institution.
| Materials and Methods|| |
The Electronic Medical Records (EMR) of the patients undergoing revision TJA at our hospital in the period between January 2014 and September 2019 were retrieved for this study and analysis. The patient's demography, medical history, presenting complaints, and physical evaluation findings were collected. The clinical observation of the treating physician, the anesthetist's notes, and the intraoperative findings were retrieved from the EMR of the patient. In coordination with the departments of microbiology and pathology, the records relating to the laboratory workup and microbiological culture and antibiotic sensitivity were retrieved.
The protocol followed to diagnose prosthetic joint infection at our institution
A detailed clinical history, general physical, and local examination are done by the treating surgeon. A history of pain, swelling, fever, discharge from the wound, and any problems related to the healing of the primary operative wound are elicited. The surgical site is examined carefully for the presence of sinus, condition of the skin (erythema and excoriation), presence of discharge from the surgical wound site, localized warmth, tenderness, and range of motion.
Laboratory investigations included a complete blood count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), blood sugar, and glycosylated hemoglobin (HbA1C). A urine examination was also done. In equivocal cases, the joint was aspirated and aspirate was sent for microbiological culture and antibiotic sensitivity. Intraoperatively, joint fluid and tissue from five different sites were collected and sent for Gram stain for bacteria, Zeil–Nelson stain for Mycobacterium and hanging drop examination for fungus and microbiological culture and antibiotic sensitivity testing for bacteria and fungus.
The history of antibiotics was not elucidated owing to the heterogeneity of the patient population and the unreliability of such information. Preoperative antibiotics were on hold till the intraoperative samples were collected.
The compiled data were analyzed for various parameters such as age, gender, presenting complaints, place, and date of index surgery, preoperative CRP, and the ESR values. The significant threshold values of CRP and ESR to diagnose PJI were taken as >10 mg/l for CRP and more than 30 mm/h for ESR. The PJI was diagnosed based on the criteria laid down in the ICM 2018 document [Table 1].
The findings are represented in tables and bar charts, and the results are discussed.
| Results|| |
Of the 145 patients who underwent revision arthroplasty during the period of the study, 45 (31.03%) were clinically diagnosed to be due to PJI. Of which one patient expired due to a cardiac event and one patient did not undergo any procedure at our institute after being diagnosed with PJI and were excluded. The remaining 43 patients were included in the analysis [Chart 1]. Ten patients (23.55%) underwent the index procedure at our institute and in the rest 33 (76.45%) patients index procedure was done at a different center.
PJI constituted 31.03% of our revision cases. Females were more (60.47%; n = 26) compared to males (39.53%; n = 17). The knee joints were more involved than the hips (67.44% vs. 32.56%). Early infection was seen in only two cases (4.65%) and late infections in the remaining 41 cases (95.34%) [Table 2] and [Chart 2] and [Chart 3]. The pain was the presenting complaint in all patients (100%), whereas a discharging sinus was present in 20.93% of cases.
Of the 43 cases, two presented acutely within 4 weeks of symptoms and the remaining 41 cases were chronic infections (with symptoms of more than 4 weeks duration).
Of the comorbidities PJI was associated with, diabetes mellitus in 30.23%, hypertension (HTN) in 39.53%, hypothyroidism in 16.28%, skin disorders in 4.65% (psoriasis and eczema), and immunosuppression in 4.65% cases.
Preoperative CRP was elevated in 46.51% of the patients (48.27% knees and 42.87% hips) [Chart 4]. The ESR was preoperatively elevated by 65.12% [Chart 5].
The bacteriological culture was positive in 51.66% (n = 22) and these cases were termed as CP-PJI and 48.34% (n = 21) did not yield any growth on standard culture techniques and was termed CN-PJI. Microbiological profiles of CP-PJI revealed Gram-positive cocci in 40.91%, Gram-negative bacilli in 36.36%, mixed bacterial infections in 13.63%, and fungal infection in 9.09%. Among patients who underwent the index procedure of arthroplasty at our institute (n = 10), 33.33% of PJI was associated with Gram-positive cocci, 22.22% with Gram-negative bacilli, mixed bacterial infections, and fungal growth equally [Table 2].
It was observed that 67.45% of patients in our series had one or more medical comorbidities with diabetes in 30.23%, HTN in 39.53%, hypothyroidism in 16.28%, immunosuppression in 4.65%, and skin disorders in 4.65% (psoriasis and eczema).
All the cases satisfied the criteria as defined in the ICM-2018 guidelines, although to varying degrees. The distribution of data across the study group has been represented in the table [Table 3].
|Table 3: Incidence of culture-positive and negative results according to International Consensus Meeting Scores|
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The management of these cases involved, two-stage revision of implants in 83.72% (n = 36), a single-stage revision of implant in 6.98% (n = 3), and the remaining 9.30% (n = 4) underwent other procedures[knee arthrodesis (n = 2), Girdlestone's excision arthroplasty of the hip (n = 1) and three-stage revision surgery (n = 1)].
| Discussion|| |
The PJI following TJA remains a serious complication in arthroplasty practice because salvage of an infected prosthetic joint is often challenging and the revision procedures do not satisfactorily restore the preinfection status. With the improvement in medical technologies, better aseptic precautions, laminar air-flow, perioperative antibiotics, and preoperative optimization of the patient physiology, infection rates in TJA have decreased significantly. The infection rate after primary TJA is estimated to be between 0.3% and 1.9%, but increases to around 10%, in revision joint surgeries.
The diagnosis of PJI is often challenging. A combination of inflammatory parameters, histopathological findings of periprosthetic tissue, microbiological studies, and imaging studies are required to validate the clinical findings and diagnose the PJI precisely. There is no single diagnostic test that is 100% sensitive and specific.
Several modifiable and nonmodifiable factors have been identified as the risk factors for developing PJI. The modifiable factors include glycemic control, operative times, postoperative hematoma formation, blood transfusions, peri-operative urinary and respiratory tract infections, malnutrition, smoking, and certain immunosuppressive drugs. The nonmodifiable risk factors are diabetes, rheumatoid arthritis, malignancy, revision surgeries, and obesity.
PJIs are classified temporally into early (<4wks) and late (>4wks). Four weeks is the minimum required for a mature biofilm formation and bears significance as the treatment modality is different in acute and chronic PJI.
Acute infection presents within 4 weeks of the index surgery or onset of symptoms, and the clinical features include pain, fever, red or swollen joints, and persistent discharge from the wound. Acute infections are caused by highly virulent organisms such as Staphylococcus, enterococci, and enterobacter. The management consists of implant retention with irrigation and debridement and exchange of the mobile parts. Infections presenting later than 4 weeks are classified as late and have developed a mature biofilm that is resistant to eradication and requires aggressive interventions. It is usually the result of infection with an organism of low virulence such as coagulase-negative Staphylococcus, Klebsiella, fungus, and Mycobacterium species. Late infection is much more common in PJI than early infections. In our case series, there were only two of the total 43 cases that were early PJI. The late infections may vindicate the role of hematogenous seeding from transient bacteremia as compared to early infections. The clinical features in case of late infection are predominantly pain and sinus formation in some cases.
It warrants complete removal of the prosthesis for the eradication of infection and a staged revision of implants and antibiotic coverage for a minimum of 6 weeks. Late infections are clinically difficult to distinguish from aseptic failure. The ability of the micro-organisms to grow and persist on the implant surface and necrotic tissue in the form of a biofilm represents a basic survival mechanism by which micro-organisms resists antibiotic penetration. It has been studied that the presence of a foreign body as would be the case in a prosthetic joint reduces the minimal infecting inoculum of Staphylococcus aureus by more than 100,000 times, which is attributed to a locally acquired immune-deficient ecosystem from decreased phagocytic activity. The combination of a biofilm and diminished local immunity is mutually inclusive in perpetuating and persistence of infection.
Diagnosis of PJI is primarily by clinical signs validated by a combination of laboratory, histopathology, microbiology, and imaging studies. International Consensus Meeting (ICM) on musculoskeletal infections have drawn up criteria for the diagnosis of PJI [Table 1].
Evaluation for a PJI should begin with a clinical evaluation of the patient's symptoms by the treating surgeon and all the patients in our series presented with pain which was a constant but maybe a nonspecific feature. Only 20.93% of patients presented with more dramatic features like a discharging sinus. The strike through rate of detection of PJI by the clinical examination was an impressive 82.70% (validated by the laboratory, culture, and intraoperative findings) in our study. Nonetheless, we believe that in the evaluation of a painful TJA, the infection should be convincingly and consistently ruled out before an alternative diagnosis is entertained, using all the resources (laboratory and imaging) at our disposal.
None of the routine blood tests such as ESR, white blood cell (WBC), and CRP has sufficient sensitivity or specificity to diagnose PJI as a stand-alone marker. In PJI caused by low-virulence organisms, systemic inflammatory markers are often not indicative of PJI. In the present study, CRP levels greater than the threshold level of 10 mg/l were found in 46.51% and the ESR values greater than the diagnostic value of 30 mm/h were obtained in 65.12%. It has been our observation that CRP and ESR were not specific and sensitive enough to be used as stand-alone investigations in the diagnosis of PJI but have a high negative predictive value and should be used to complement the clinical diagnosis. Serum ESR and CRP levels below the threshold (as determined by the Musculoskeletal Infection Society and ICM) does not exclude the diagnosis of a PJI. Serum levels of ESR and CRP can be normal in some cases of PJI caused by slow-growing organisms.
CRP is increased after surgery for up to 4 weeks before it returns to baseline levels reflecting postsurgical inflammatory response. Serial measurements with a declining trend over time are needed for accurate interpretation. ESR is no longer relied upon as a specific marker for acute infection in the diagnosis of PJI.
Interleukin-6 (IL-6) is a promising investigation to diagnose PJI. IL-6 is produced by stimulated monocytes and macrophages with a mean half-life of 15 h, making it a useful marker in the early postoperative period. IL-6 is found to be the most accurate laboratory marker for diagnosing PJI when compared to ESR, CRP, and WBC. IL-6 above 10.4 pg/ml and CRP level above 18 mg/l will identify all patients with PJI and the combination of CRP and IL-6 is an excellent screening test with a sensitivity of 100% and a negative predictive value of 100%. IL-6 above 10.4 pg/ml and CRP level above 18 mg/l will identify all the cases of PJI.
Preoperative joint aspiration by the conventional technique or CT guided is a valuable diagnostic tool. Synovial fluid WBC and percentage of granulocytes represent a simple, rapid, and accurate test differentiating between PJI and aseptic loosening. Diagnostic levels are 2000 leukocytes/mL with 70% granulocytes. The sensitivity of synovial fluid culture is 45% to 75% with a specificity of 95%. Sensitivity from intraoperative samples can be diminished by long transportation time in the inadequate transport media. This can be prevented by inoculation into pediatric blood culture bottles immediately after the collection in the operation theater. An incubation time of 2 weeks is necessary to detect low virulence and difficult to detect pathogens.
Some other promising tests to diagnose PJI include (a) alpha defensin and (b) leukocyte esterase tests and (c) D-dimer. Alpha defensin is an antimicrobial peptide released by activated neutrophils as a response to bacterial infection. Alpha defensin lateral flow (ADLF) test is a quantitative test that determines the presence of alpha defensin in synovial fluid and can be performed in the operation theater or early postoperative period. Leukocyte esterase is an enzyme produced by activated neutrophils at the site of infection, and in the synovial fluid, it is detected by colorimetric strip tests., Both LE and ADLF tests provide a rapid and convenient diagnosis for PJI and have a high level of specificity.,
D-Dimer is a fibrin degradation product and serves as an important biomarker for systemic inflammatory response. Increased D-Dimer levels in serum and synovial fluid have been explored as possible candidates in the diagnosis of peri-prosthetic infection and have been incorporated in the latest ICM 2018 guidelines for the diagnosis of peri-PJIs.
Intraoperative tissue cultures with samples numbering three to five, and in certain situations, even ten samples need to be obtained to obtain a microbiological diagnosis. The sensitivity of intraoperative tissue cultures ranges between 65% and 94%. The reported prevalence of CN-PJIs in the hip or knee has ranged from 5% to 42%. Diagnostic protocols for further investigating these cases include repeat sampling, longer incubation of culture samples, sonication of implants, the use of dithiothreitol (DTT) technology, PCR, and next-generation sequencing.,
CN-PJI has been reported to occur in 7%–15% of cases, where culture methods fail to detect any growth. CN-PJI poses a challenge to the eradication of infection as the antibiotics cannot be used in a targeted manner on a particular pathogen and hence complete eradication of infection becomes difficult. Studies are equivocal on the outcomes in CP-PJI and CN-PJI, where some studies have shown poorer outcomes for CN-PJI, on the other hand, the other studies showed no difference in the outcomes. The reasons can be hypothesized as (a) the precedence of repeated antibiotic use, (b) nonideal sample collection methods, (c) inappropriately long sample transport times, (d) inadequate incubation period, (e) failure to use sonication methods, (f) biofilm formation, and (g) noncultivable organisms. The future possibility of including highly sensitive methods such as reverse transcriptase-PCR (RTPCR) for noncultivable organisms and those exposed to antimicrobials must be explored.
Every effort should be made to identify, isolate, and check the antibiotic sensitivity of the causative pathogen in PJI. This involves the teamwork of the treating surgeon, the infection control team, the microbiologist, and the physician. Swabs from superficial wounds or sinus tracts can be misleading in detecting colonization. Intraoperative periprosthetic tissue Gram staining offers the chance to rapidly confirm the diagnosis of PJI in the operating room. The sensitivity of tissue Gram staining, however, ranges only from 0% to 27%, but with a specificity of >98%. Due to the poor sensitivity, it is not recommended in the current ICM 2018 guidelines.,
Sonication of the explanted implants is a novel technique to increase the yield of microorganisms in the PJI. The sonicate fluid can be submitted for culture onto aerobic and anaerobic plates. A cutoff of 50 CFU/ml of sonication fluid yields a sensitivity of 79% and a specificity of 99%. The culture of sonication fluid shows superior sensitivity compared with the standard culture of the periprosthetic tissue. DTT can be used to a similar effect and efficiency.
Histopathological periprosthetic tissue examination should be considered a standard procedure in the diagnosis of PJI. Neutrophil granulocytes can be detected through the immunohistochemical techniques.
The criteria to diagnose PJI are >10 neutrophils per HPF at ×400 and when compared to microbiological findings the diagnostic sensitivity of this method is 91% and specificity of 92%.
PCR can identify the pathogens in synovial fluid with a sensitivity and specificity of 84% and 89%, respectively, and in sonication fluid of 81% and 96%.
New generation sequencing is a sophisticated method to detect the genomes of the infecting pathogen.
Double-stage revision is being currently accepted as the gold standard for re-implantation in PJI.,,,
As a useful deduction of this study, an algorithm for the diagnosis of a suspected case of PJI has been presented [Table 4].
Limitations of the study
- It is a retrospective observational study
- A small sample size
- A heterogeneous sample
- There was no standardization of protocol on precedent antibiotic use due to nonhomogeneity in the geographic distribution of patients and standard of care, as index surgeries were performed at different institutions
- Newer technologies could have increased the yield of microorganisms and their growth.
| Conclusions|| |
Obtaining a bacteriological diagnosis, particularly in late PJI is a challenge. The bacteriological profiles in PJI are diverse. The failure to arrive at a bacteriological diagnosis and significant rates of CNPJI are due to varied reasons. Most of the microorganisms involved in the PJI are Gram-positive cocci or negative bacilli or mixed bacteria. Rarely, in immune-compromised cases, fungal organisms are discernible. A stringent protocol requires to be followed in the use of antibiotics, the collection and transportation of samples, and in the selection of media for cultures. All available modalities for the diagnosis of PJI (including sonication for breaking biofilms and utilization of RTPCR assay) should be utilized, for their cumulative value. Notwithstanding the limitations of our study, we conclude that bacterial infections do not follow any predictable patterns and constant vigilance and low threshold to suspect and investigate PJI is needed in the management of PJI. We propose based on our study findings that no antibiotics should be used only after a bacteriological diagnosis and antibiotic sensitivity is obtained, else it results in a high rate of CN PJIs.
The contribution of Ritu Setiya of the Medical Records Department and the Department of Pathology, from Indraprastha Apollo Hospitals, New Delhi, India, is sincerely acknowledged.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]