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Paper of the week: Mortality During Total Hip Periprosthetic Joint Infection.

Paper of the week. Mortality During Total Hip Periprosthetic Joint Infection. Natsuhara KM, Shelton TJ, Meehan JP, Lum ZC. J Arthroplasty. 2018 Dec 24. pii: S0883-5403(18)31225-7. doi: 10.1016/j.arth.2018.12.024.

Summary and Editorial by Sreeram Penna

This publication is a systemic review of the literature and its main aim is to identify the mortality rate following two-stage procedure for total hip periprosthetic joint infection (PJI). The review included 23 studies on 19169 patients. Average weighted age of the patients was 65 years and average follow up was 3.7 years. Researchers showed that average overall mortality after total hip PJI was 5.4% and mortality per year increased 4.22% year after year following total hip PJI. This data translates to around 21.12% five-year mortality for total hip PJI. This pooled data result is similar to big studies included in this review. [1,2] Among the issues highlighted by researchers include underreported mortality and inadequate follow up in the studies included in the systemic review. Researchers also noticed no change in trends of mortality rate over time. Although some studies show that a substantial decline in PJI mortality rate without changes in PJI risk over time.[3] Overall this research highlights fact that PJI has considerable mortality and morbidity and considerable research needed to be done in this respect.

References

[1] Zmistowski B, Karam JA, Durinka JB, Casper DS, Parvizi J. Periprosthetic Joint Infection Increases the Risk of One-Year Mortality. The Journal of Bone and Joint Surgery-American Volume 2013;95:2177–2184. doi:10.2106/JBJS.L.00789.

[2] Cancienne JM, Werner BC, Bolarinwa SA, Browne JA. Removal of an Infected Total Hip Arthroplasty: Risk Factors for Repeat Debridement, Long-term Spacer Retention, and Mortality. J Arthroplasty 2017;32:2519–22. doi:10.1016/j.arth.2017.03.018.

[3] Kurtz SM, Lau EC, Son M-S, Chang ET, Zimmerli W, Parvizi J. Are We Winning or Losing the Battle With Periprosthetic Joint Infection: Trends in Periprosthetic Joint Infection and Mortality Risk for the Medicare Population. J Arthroplasty 2018;33:3238–45. doi:10.1016/j.arth.2018.05.042.

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Paper of the week: Reconsidering Strategies for Managing Chronic Periprosthetic Joint Infection in Total Knee Arthroplasty: Using Decision Analytics to Find the Optimal Strategy Between One-Stage and Two-Stage Total Knee Revision

Paper of the Week: Reconsidering Strategies for Managing Chronic Periprosthetic Joint Infection in Total Knee Arthroplasty: Using Decision Analytics to Find the Optimal Strategy Between One-Stage and Two-Stage Total Knee Revision. Srivastava K, Bozic KJ, Silverton C, Nelson AJ, Makhni EC, Davis JJ.J Bone Joint Surg Am. 2019 Jan 2;101(1):14-24. doi: 10.2106/JBJS.17.00874.

Summary and Editorial by Sreeram Penna

In this study, researchers used decision analysis to determine the optimal decision for the management of chronic periprosthetic infection (PJI) following total knee arthroplasty (TKA). Researchers constructed an expected-value decision tree to estimate the quality-adjusted-life-years (QALYs) and costs associated with 1-stage and 2-stage revision. Two decision trees were created one was for all pathogens, a second decision tree was constructed for difficult to treat organisms including methicillin-resistant. A Markov model was used to calculate the QALYs over a 15-year period. The model input was based on values such as mortality rates and reinfection rates published in original studies since 2000. Cost data were obtained from Medicare data.

Results showed that 1-stage revision was the optimal decision in producing greater health utility in both decision trees in the analysis. Some of the issues with research are that there is limited data on infection eradication 1-stage revisions for PJI. Seven studies included in the above simulation for 1-stage revision showed reinfection rates of 7% compared to 15% for 2-stage revision. Researchers contend that even if we assume reinfection rate for 2-stage revision to be around 10% infection rates of 1-stage be more than 30% to be considered non-optimal strategy compared to 2-stage revision as decision model captures significant morbidity and mortality associated with a 2-stage procedure. The simulation also captures cost savings of around $19,000 to $27,000 per infection (depending on pathogen) for 1-stage revision.

Normally in PJI treatment 2 stage revision procedure is considered the gold standard for infection eradication. However, it is known that such strategy place significant morbidity on the patient. In addition, a significant number of patients does not complete the reimplantation procedure in 2-stage operation.[1] This study gives an opportunity for orthopaedic community to rethink options in managing patients with PJI and further research is required.

References
[1] Gomez MM, Tan TL, Manrique J, Deirmengian GK, Parvizi J. The Fate of Spacers in the Treatment of Periprosthetic Joint Infection. J Bone Joint Surg Am 2015;97:1495–502. doi:10.2106/JBJS.N.00958.

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Paper of the week: Failure after two-stage exchange arthroplasty for treatment of periprosthetic joint infection: the role of antibiotics in the cement spacer

Paper of the week: Failure after two-stage exchange arthroplasty for treatment of periprosthetic joint infection: the role of antibiotics in the cement spacer. Wouthuyzen-Bakker M, Kheir MM, Moya I, Rondon AJ, Kheir M, Lozano L, Parvizi J, Soriano A.Clin Infect Dis. 2018 Oct 3. doi: 10.1093/cid/ciy851.

Summary and Editorial by Sreeram Penna

This retrospective multicenter trial looked at the incidence of positive cultures at the time of reimplantation and their relation to antibiotics in the spacer and also at failure following reimplantation. All patients who had a two-stage revision as a primary procedure for periprosthetic joint infection (PJI) or as salvage therapy following failed surgical irrigation debridement for acute PJIs were included in the study. Researchers excluded culture-negative PJIs, cases where no cultures were obtained during reimplantation and cases with no data on cement spacers. The final cohort consists of 344 patients.

Results showed that forty cases (11.6%) had positive cultures at reimplantation. Based on the results positive cultures consists of coagulase-negative Staphylococcus (CoNS) (35%), followed by Gram-negative rods (25.0%) and S. aureus (17.5%). Results based antibiotics in cement spacers showed 9.5% for cement spacers containing a glycopeptide (27/284) either monotherapy or combined with aminoglycoside versus 21.7% for those containing monotherapy with an aminoglycoside (13/60) (p 0.008). Also, the lower incidence of positive cultures in the glycopeptide group at reimplantation was mostly attributed to a decrease of spacer infections with CoNS (17% versus 2%, p < 0.001).

Researchers identified that failure was, significantly higher in those patients with positive cultures during reimplantation (40.0% [16/40]) compared to 15.8% [48/304] with negative cultures, p < 0.001) despite the use of post-operative antibiotics in positive cases. This study notes that use of a glycopeptide in the cement spacer was not associated with a lower failure rate after reimplantation. However, it was noted that in cases where glycopeptide was added to the spacer, had a lower failure rate due to CoNS compared to those without a glycopeptide (2.5% versus 13.3%, respectively, p < 0.001).

This study highlights the importance of adding glycopeptide antibiotic into spacer in addition to an aminoglycoside. In cases where only monotherapy of aminoglycoside was used, there was a higher incidence of positive infections with CoNS and the resulting failure of reimplantation procedure. Another study by Corona et al. showed that increase in resistance against aminoglycosides in the bacteria that commonly cause chronic PJI, particularly in gram-positive cocci.[1] The current study further provides evidence to combining glycopeptide antibiotic along with aminoglycoside in the cement spacer.

Reference
[1] Corona PS, Espinal L, Rodríguez-Pardo D, Pigrau C, Larrosa N, Flores X. Antibiotic Susceptibility in Gram-Positive Chronic Joint Arthroplasty Infections: Increased Aminoglycoside Resistance Rate in Patients With Prior Aminoglycoside-Impregnated Cement Spacer Use. The Journal of Arthroplasty 2014;29:1617–21. doi:10.1016/j.arth.2014.03.029.

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Paper of the Week: Salvage Debridement, Antibiotics and Implant Retention (“DAIR”) With Local Injection of a Selected Cocktail of Bacteriophages: Is It an Option for an Elderly Patient With Relapsing Staphylococcus aureus Prosthetic-Joint Infection?

Paper of the week: Salvage Debridement, Antibiotics and Implant Retention (“DAIR”) With Local Injection of a Selected Cocktail of Bacteriophages: Is It an Option for an Elderly Patient With Relapsing Staphylococcus aureus Prosthetic-Joint Infection? Tristan Ferry, Gilles Leboucher, Cindy Fevre, Yannick Herry, Anne Conrad, Jérôme Josse, Cécile Batailler, Christian Chidiac, Mathieu Medina, S Lustig, Frédéric Laurent, and Lyon BJI Study Group. Open Forum Infect Dis. 2018 Nov; 5(11): ofy269. Published online 2018 Oct 24. doi: 10.1093/ofid/ofy269

Summary and editorial by Sreeram Penna

This publication is about the use of bacteriophage treatment in a patient with relapsing poly microbial periprosthetic joint infection. The study case is an 80-year-old patient with a known history of type 2 diabetes and mild chronic renal failure. The patient had multiple procedures for PJI and grew methicillin-susceptible Staphylococcus aureus (MSSA), fluoroquinolone-resistant Escherichia coli (E. coli) and multi-drug resistant Pseudomonas aeruginosa. During her DAIR procedure, she had a cocktail of four bacteriophages targeting Pseudomonas and MSSA, which was grown preop. Operative specimens grew MSSA and E. coli and Staphylococcus lugdunensis. The patient had a course of Daptomycin and amoxicillin post op. The patient required further DAIR procedure for Citrobacter koseri infection eight months later. Eighteen months post-procedure with bacteriophage treatment patient was without signs of infection but was on long-term amoxicillin.

Bacteriophages are natural viruses that target bacteria. Bacteriophages were used in the past in treatment of osteomyelitis where they were injected through the fistula.[1] Bacteriophages are particularly interesting because they act synergistically with antibiotics. [2] In addition bacteriophages amplify during treatment due to their replication in bacteria.[3] Phages are being used in multidrug-resistant life-threatening infections with authorization from Food and Drug Administration (FDA) to administer the cocktails as an emergency investigational new drug (eIND) as seen in case of a patient with multidrug-resistant Acinetobacter baumannii infection.[4] The phase treatment thus shows promise as a viable treatment in multidrug-resistant PJIs.

References

[1] Kutateladze M, Adamia R. Bacteriophages as potential new therapeutics to replace or supplement antibiotics. Trends in Biotechnology 2010;28:591–595. doi:10.1016/j.tibtech.2010.08.001.

[2] Oechslin F, Piccardi P, Mancini S, Gabard J, Moreillon P, Entenza JM, et al. Synergistic Interaction Between Phage Therapy and Antibiotics Clears Pseudomonas Aeruginosa Infection in Endocarditis and Reduces Virulence. The Journal of Infectious Diseases 2017;215:703–712. doi:10.1093/infdis/jiw632.

[3] Clokie MR, Millard AD, Letarov AV, Heaphy S. Phages in nature. Bacteriophage 2011;1:31–45. doi:10.4161/bact.1.1.14942.

[4] Schooley RT, Biswas B, Gill JJ, Hernandez-Morales A, Lancaster J, Lessor L, et al. Development and Use of Personalized Bacteriophage-Based Therapeutic Cocktails To Treat a Patient with a Disseminated Resistant Acinetobacter baumannii Infection. Antimicrob Agents Chemother 2017;61. doi:10.1128/AAC.00954-17.

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Paper of the week: Polymerase chain reaction assay using the restriction fragment length polymorphism technique in the detection of prosthetic joint infections: A Multi-Centered Study

Paper of the week: Polymerase chain reaction assay using the restriction fragment length polymorphism technique in the detection of prosthetic joint infections: A Multi-Centered Study. Moshirabadi A, Razi M, Arasteh P, Sarzaeem MM, Ghaffari S, Aminiafshar S, Hosseinian Khosroshahy K, Sheikholeslami FM. J Arthroplasty. 2018 Oct 25. pii: S0883-5403(18)31057-X. doi: 10.1016/j.arth.2018.10.017. [Epub ahead of print].

Summary and Editorial by Sreeram Penna

The main aim of this prospective study was to assess the diagnostic accuracy of polymerase chain reaction (PCR) using RFLP (restriction fragment length polymorphism) method. Researchers also obtained bacterial cultures at the same time. The study assessed 76 samples using this technique. International consensus meeting criteria were used to identify prosthetic joint infection. 50% of the samples were deemed infected based on the above criteria. Results showed that using PCR RFLP Sensitivity and specificity was found to be 97.4% and 100% respectively. This was superior compared to the culture where sensitivity and specificity was 31.6% and 100%. Researchers isolated a broad range of bacteria including fastidious organisms like Chlamydophila pneumonia, Stenotrophomonas maltophilia, Brucella melitensis. One advantage of this technique is the amount of time required to get the pathogen identification is approximately 3 to 4 hours compared to multiple days for microbiological culture methods.

Restriction fragment length polymorphism (RFLP) is a difference in homologous DNA sequences which are identified by the different length of sequences after digestion of DNA samples using specific restriction endonucleases. RFLP probes are widely used in genome mapping and variation analysis such as genotyping, forensics, paternity tests, hereditary disease diagnostics, etc. This process requires a large amount of DNA and is labor intensive.[1] Combining PCR along with RFLP (also called cleaved amplified polymorphic sequences or CAPS) solves the problem of the requirement of a large sample.[2] Using PCR RFLP method with 16s bacterial DNA has been used in bacterial identification in clinical situations, food safety and also identify different strains of bacteria.[3–6] Rohit et al., used this technique to rapidly diagnose bacterial species in the setting of neonatal sepsis.[3] This study provides importance of such technique in PJI setting where it is very important to identify pathogens as it has huge implications in the management.

References

[1] Restriction Fragment Length Polymorphism (RFLP) n.d. https://www.ncbi.nlm.nih.gov/probe/docs/techrflp/ (accessed December 17, 2018).

[2] Cleaved Amplified Polymorphic Sequences (CAPS) n.d. https://www.ncbi.nlm.nih.gov/probe/docs/techcaps/ (accessed December 17, 2018).

[3] Rohit A, Maiti B, Shenoy S, Karunasagar I. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for rapid diagnosis of neonatal sepsis. Indian J Med Res 2016;143:72–8. doi:10.4103/0971-5916.178613.

[4] Schütte UME, Abdo Z, Bent SJ, Shyu C, Williams CJ, Pierson JD, et al. Advances in the use of terminal restriction fragment length polymorphism (T-RFLP) analysis of 16S rRNA genes to characterize microbial communities. Appl Microbiol Biotechnol 2008;80:365–80. doi:10.1007/s00253-008-1565-4.

[5] Meyer R, Höfelein C, Lüthy J, Candrian U. Polymerase chain reaction-restriction fragment length polymorphism analysis: a simple method for species identification in food. J AOAC Int 1995;78:1542–51.

[6] González A, Moreno Y, González R, Hernández J, Ferrús MA. Development of a simple and rapid method based on polymerase chain reaction-based restriction fragment length polymorphism analysis to differentiate Helicobacter, Campylobacter, and Arcobacter species. Curr Microbiol 2006;53:416–21. doi:10.1007/s00284-006-0168-5.