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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.

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Paper of the week: Irrigation and debridement with chronic antibiotic suppression for the management of infected total knee arthroplasty

Irrigation and debridement with chronic antibiotic suppression for the management of infected total knee arthroplastyWeston JT, Watts CD, Mabry TM, Hanssen AD, Berry DJ, Abdel MP. Bone Joint J. 2018 Nov;100-B(11):1471-1476.
doi: 10.1302/0301-620X.100B11.BJJ-2018-0515.R1.

Summary and editorial by Sreeram Penna

Above study is a single center retrospective review of 134 infected total knee arthroplasty cases ( acute post-operative infection in 23 and acute hematogenous infection in 111). All patients had Irrigation debridement using normal saline and retention of components except modular poly-ethylene components which were replaced. All patients had organism-specific antibiotic followed by long-term antibiotic suppression.

The study found the infection-free survival of 72% at two years and 66% at five years. The study also showed that age less than 60 and infection with staphylococcal species was associated with increased risk of subsequent infection. Culture-negative infection cases have a lower risk of recurrence or subsequent infections. Musculoskeletal Infection Society host type, body mass index (BMI), the duration of symptoms, gender, and the presence of a monoblock tibial component did not have any influence on the outcome.

In another study Siqueira et al., has shown similar infection-free prosthetic implant survival (68.5% at five years) following irrigation and debridement, polyethylene exchange and chronic antibiotic suppression. [1] However in that study cases with staphylococcal infection fared better following chronic antibiotic suppression compared to those who did not receive suppressive antibiotics following irrigation and debridement. Similarly Rao et al., showed favorable results in 86% of patients at 5 years were able to maintain functioning prosthesis.[2] In another study on patients with osteomyelitis Nowak et al showed successful suppression of the disease. [3] In this study diabetes was associated with a high failure rate and also there was a high incidence (25%) of adverse reactions associated with suppressive antibiotics.

References

[1] Siqueira MBP, Saleh A, Klika AK, O’Rourke C, Schmitt S, Higuera CA, et al. Chronic Suppression of Periprosthetic Joint Infections with Oral Antibiotics Increases Infection-Free Survivorship. J Bone Joint Surg Am 2015;97:1220–32. doi:10.2106/JBJS.N.00999.

[2] Rao N, Crossett LS, Sinha RK, Le Frock JL. Long-term suppression of infection in total joint arthroplasty. Clin Orthop Relat Res 2003:55–60. doi:10.1097/01.blo.0000087321.60612.cf.

[3] Nowak MA, Winner JS, Beilke MA. Prolonged oral antibiotic suppression in osteomyelitis and associated outcomes in a Veterans population. Am J Health Syst Pharm 2015;72:S150-155. doi:10.2146/sp150022.

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Paper of the week: Staphylococcus epidermidis from prosthetic joint infections induces lower IL‐1β release from human neutrophils than isolates from normal flora

Staphylococcus epidermidis from prosthetic joint infections induces lower IL‐1β release from human neutrophils than isolates from normal flora
Emeli Månsson, Bo Söderquist, Åsa Nilsdotter‐Augustinsson, Eva Särndahl, Isak Demirel
APMIS. 2018 Aug;126(8):678-684.
doi: 10.1111/apm.12861.