A New Antifungal-Loaded Sol-Gel Can Prevent Candida albicans Prosthetic Joint Infection

Fungal PJI is one of the most feared complications after arthroplasty. Although a rare finding, its high associated morbidity and mortality makes it an important object of study. The most frequent species causing fungal PJI is C. albicans. New technology to treat this type of PJI involves organic–inorganic sol-gels loaded with antifungals, as proposed in this study, in which anidulafungin is associated with organophosphates. This study aimed to evaluate the efficacy of an anidulafungin-loaded organic–inorganic sol-gel in preventing prosthetic joint infection (PJI), caused by Candida albicans using an in vivo murine model that evaluates many different variables. Fifty percent (3/6) of mice in the C. albicans-infected, non-coated, chemical-polished (CP)-implant group had positive culture and 100% of the animals in the C. albicans-infected, anidulafungin-loaded, sol-gel coated (CP+A)-implant group had a negative culture (0/6) (p = 0.023). Taking the microbiology and pathology results into account, 54.5% (6/11) of C. albicans-infected CP-implant mice were diagnosed with a PJI, whilst only 9.1% (1/11) of C. albicans-infected CP+A-implant mice were PJI-positive (p = 0.011). No differences were observed between the bone mineral content and bone mineral density of noninfected CP and noninfected CP+A (p = 0.835, and p = 0.181, respectively). No histological or histochemical differences were found in the tissue area occupied by the implant among CP and CP+A. Only 2 of the 6 behavioural variables evaluated exhibited changes during the study: limping and piloerection. In conclusion, the anidulafungin-loaded sol-gel coating showed an excellent antifungal response in vivo and can prevent PJI due to C. albicans in this experimental model.

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A New Antibiotic-Loaded Sol-Gel Can Prevent Bacterial Prosthetic Joint Infection: From in vitro Studies to an in vivo Model

Frontiers in Microbiology ◽

10.3389/fmicb.2019.02935 ◽

2020 ◽

Vol 10 ◽

Cited By ~ 4

Author(s):

John Jairo Aguilera-Correa ◽

Amaya Garcia-Casas ◽

Aranzazu Mediero ◽

David Romera ◽

Francisca Mulero ◽

...

Keyword(s):

Prosthetic Joint Infection ◽

Joint Infection ◽

Sol Gel ◽

In Vitro Studies ◽

In Vivo Model ◽

Prosthetic Joint

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Adjunctive Rifampin Is Crucial to Optimizing Daptomycin Efficacy against Rabbit Prosthetic Joint Infection Due to Methicillin-Resistant Staphylococcus aureus

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00675-11 ◽

2011 ◽

Vol 55 (10) ◽

pp. 4589-4593 ◽

Cited By ~ 66

Author(s):

Azzam Saleh-Mghir ◽

Claudette Muller-Serieys ◽

Aurélien Dinh ◽

Laurent Massias ◽

Anne-Claude Crémieux

Keyword(s):

Staphylococcus Aureus ◽

Prosthetic Joint Infection ◽

Joint Infection ◽

Detection Threshold ◽

High Dose ◽

Prosthesis Infection ◽

Methicillin Resistant ◽

Prosthetic Joint ◽

Mutant Strains

ABSTRACTDaptomycin is an attractive option for treating prosthetic joint infection, but the 6-mg/kg of body weight/day dose was linked to clinical failure and emergence of resistance. Using a methicillin-resistantStaphylococcus aureus(MRSA) knee prosthesis infection in rabbits, we studied the efficacies of high-dose daptomycin (22 mg/kg given intravenously [i.v.] once daily [o.d.]; equivalent to 8 mg/kg/day in humans) or vancomycin (60 mg/kg given intramuscularly [i.m.] twice daily [b.i.d.]), both either alone or with adjunctive rifampin (10 mg/kg i.m. b.i.d.). After partial knee replacement with a silicone implant, 107MRSA CFU was injected into the knees. Treatment started 7 days postinoculation and lasted 7 days. Positive cultures were screened for the emergence of mutant strains, defined as having 3-fold-increased MICs. Althoughin vivomean log10CFU/g of daptomycin-treated (4.23 ± 1.44;n= 12) or vancomycin-treated (4.63 ± 1.08;n= 12) crushed bone was significantly lower than that of controls (5.93 ± 1.15;n= 9) (P< 0.01), neither treatment sterilized bone (2/12 and 0/12 rabbits with sterile bone, respectively). Daptomycin mutant strains were found in 6/12, 3/12, and 2/9 daptomycin-treated, vancomycin-treated, and control rabbits, respectively; no resistant strains emerged (MIC was always <1 mg/liter). Adjunctive rifampin with daptomycin (1.47 ± 0.04 CFU/g of bone [detection threshold]; 11/11 sterile bones) or vancomycin (1.5 ± 0.12 CFU/g of bone; 6/8 sterile bones) was significantly more effective than monotherapy (P< 0.01) and prevented the emergence of daptomycin mutant strains. In this MRSA joint prosthesis infection model, combining rifampin with daptomycin was highly effective. Daptomycin mutant strains were isolatedin vivoeven without treatment, but adjunctive rifampin prevented this phenomenon, previously found after monotherapy in humans.

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2020 John Charnley Award: The antimicrobial potential of bacteriophage-derived lysin in a murine debridement, antibiotics, and implant retention model of prosthetic joint infection

The Bone & Joint Journal ◽

10.1302/0301-620x.102b7.bjj-2019-1590.r1 ◽

2020 ◽

Vol 102-B (7_Supple_B) ◽

pp. 3-10 ◽

Cited By ~ 1

Author(s):

Branden R. Sosa ◽

YingZhen Niu ◽

Kathleen Turajane ◽

Kevin Staats ◽

Vincentius Suhardi ◽

...

Keyword(s):

Prosthetic Joint Infection ◽

Joint Infection ◽

Bacterial Load ◽

In Vitro Models ◽

Periprosthetic Tissue ◽

Retention Model ◽

Prosthetic Joint ◽

Implant Retention

Aims Current treatments of prosthetic joint infection (PJI) are minimally effective against Staphylococcus aureus biofilm. A murine PJI model of debridement, antibiotics, and implant retention (DAIR) was used to test the hypothesis that PlySs2, a bacteriophage-derived lysin, can target S. aureus biofilm and address the unique challenges presented in this periprosthetic environment. Methods The ability of PlySs2 and vancomycin to kill biofilm and colony-forming units (CFUs) on orthopaedic implants were compared using in vitro models. An in vivo murine PJI model of DAIR was used to assess the efficacy of a combination of PlySs2 and vancomycin on periprosthetic bacterial load. Results PlySs2 treatment reduced 99% more CFUs and 75% more biofilm compared with vancomycin in vitro. A combination of PlySs2 and vancomycin in vivo reduced the number of CFUs on the surface of implants by 92% and in the periprosthetic tissue by 88%. Conclusion PlySs2 lysin was able to reduce biofilm, target planktonic bacteria, and work synergistically with vancomycin in our in vitro models. A combination of PlySs2 and vancomycin also reduced bacterial load in periprosthetic tissue and on the surface of implants in a murine model of DAIR treatment for established PJI. Cite this article: Bone Joint J 2020;102-B(7 Supple B):3–10.

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Successful Clinical Use of Daptomycin-Impregnated Bone Cement in Two-Stage Revision Hip Surgery for Prosthetic Joint Infection

Annals of Pharmacotherapy ◽

10.1345/aph.1r486 ◽

2013 ◽

Vol 47 (1) ◽

pp. e2-e2 ◽

Cited By ~ 13

Author(s):

Nicholas J Cortes ◽

John M Lloyd ◽

Leszek Koziol ◽

Lawrence O'Hara

Keyword(s):

Bone Cement ◽

Prosthetic Joint Infection ◽

Revision Surgery ◽

Past History ◽

Joint Infection ◽

Pmma Bone Cement ◽

Prosthetic Joint ◽

History Of

OBJECTIVE To describe the safe and successful use of daptomycin-impregnated polymethyl methacrylate (PMMA) bone cement in the treatment of a case of recurrent prosthetic joint infection in a patient with multiple antibiotic allergies and past colonization with multiply antibiotic-resistant organisms. CASE SUMMARY A 79-year-old female had a history of chronic recurrent left prosthetic hip infection. The patient had confirmed allergies to multiple antibiotics and a past history of colonization with methicillin-resistant Staphylococcus aureus. At first-stage revision surgery, the infected prosthesis was removed and samples were sent for microbiologic culture. A spacer device was fashioned, with incorporation of daptomycin and gentamicin into the PMMA bone cement at a concentration of 5% w/w for each antibiotic. Systemic daptomycin and gentamicin were administered postoperatively for 14 days. Propionibacterium acnes was isolated from deep-tissue specimens. The patient made excellent postoperative progress and was discharged after 2 weeks. Second-stage revision surgery was performed at 6 months, with no signs of persistent infection. She remained well, pain free, and mobilizing independently 2 years later. DISCUSSION Daptomycin, a cyclic lipopeptide antibiotic, is approved for systemic treatment of endocarditis and skin and soft tissue infections. In vitro data demonstrate acceptable drug elution from and tensile strength of daptomycin-impregnated PMMA bone cement; however, clinical data are lacking. In our patient's case, the cement formulation was well tolerated, with no adverse effects detected, and demonstrated adequate mechanical strength in vivo. Infection with P. acnes, an unusual pathogen, was successfully treated. Further clinical studies are required to assess the efficacy of daptomycin-impregnated cement in infection with more typical pathogens, such as S. aureus. CONCLUSIONS Daptomycin impregnation of PMMA bone cement may be an option in cases in which patient or pathogen factors preclude use of routinely incorporated agents.

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Ceftaroline-Fosamil Efficacy against Methicillin-Resistant Staphylococcus aureus in a Rabbit Prosthetic Joint Infection Model

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.03600-14 ◽

2014 ◽

Vol 58 (11) ◽

pp. 6496-6500 ◽

Cited By ~ 13

Author(s):

Laure Gatin ◽

Azzam Saleh-Mghir ◽

Jason Tasse ◽

Idir Ghout ◽

Frédéric Laurent ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Prosthetic Joint Infection ◽

Joint Infection ◽

Infection Model ◽

Ceftaroline Fosamil ◽

Methicillin Resistant ◽

Prosthetic Joint ◽

Intramedullary Canal

ABSTRACTCeftaroline (CPT), the active metabolite of the prodrug ceftaroline-fosamil (CPT-F), demonstratesin vitrobactericidal activity against methicillin-resistantStaphylococcus aureus(MRSA) and is effective in rabbit models of difficult-to-treat MRSA endocarditis and acute osteomyelitis. However, itsin vivoefficacy in a prosthetic joint infection (PJI) model is unknown. Using a MRSA-infected knee PJI model in rabbits, the efficacies of CPT-F or vancomycin (VAN) alone and combined with rifampin (RIF) were compared. After each partial knee replacement with a silicone implant that fit into the tibial intramedullary canal was performed, 5 × 107MRSA CFU (MICs of 0.38, 0.006, and 1 mg/liter for CPT, RIF, and VAN, respectively) was injected into the knee. Infected animals were randomly assigned to receive no treatment (controls) or CPT-F (60 mg/kg of body weight intramuscularly [i.m.]), VAN (60 mg/kg i.m.), CPT-F plus RIF (10 mg/kg i.m.), or VAN plus RIF starting 7 days postinoculation and lasting for 7 days. Surviving bacteria in crushed tibias were counted 3 days after ending treatment. Although thein vivomean log10CFU/g of CPT-treated (3.0 ± 0.9,n= 12) and VAN-treated (3.5 ± 1.1,n= 12) crushed bones was significantly lower than those of controls (5.6 ± 1.1,n= 14) (P< 0.001), neither treatment fully sterilized the bones (3/12 were sterile with each treatment). The mean log10CFU/g values for the antibiotics in combination with RIF were 1.9 ± 0.5 (12/14 were sterile) for CPT-F and 1.9 ± 0.5 (12/14 were sterile) for VAN. In this MRSA PJI model, the efficacies of CPT-F and VAN did not differ; thus, CPT appears to be a promising antimicrobial agent for the treatment of MRSA PJIs.

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In vivo gene expression in a Staphylococcus aureus prosthetic joint infection characterized by RNA sequencing and metabolomics: a pilot study

BMC Microbiology ◽

10.1186/s12866-016-0695-6 ◽

2016 ◽

Vol 16 (1) ◽

Cited By ~ 18

Author(s):

Yijuan Xu ◽

Raluca Georgiana Maltesen ◽

Lone Heimann Larsen ◽

Henrik Carl Schønheyder ◽

Vang Quy Le ◽

...

Keyword(s):

Gene Expression ◽

Staphylococcus Aureus ◽

Pilot Study ◽

Rna Sequencing ◽

Prosthetic Joint Infection ◽

Joint Infection ◽

Prosthetic Joint

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Microbiological Epidemiology in Patients Experiencing Microbiological or Clinical Failure Following Reimplantation After a Two-Stage Exchange Strategy for Hip or Knee Prosthetic Joint Infection (PJI)

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx163.081 ◽

2017 ◽

Vol 4 (suppl_1) ◽

pp. S99-S99

Author(s):

Tristan Ferry ◽

Hassan Serrier ◽

Frederic Laurent ◽

Eugenie Mabrut ◽

Michel-Henri Fessy ◽

...

Keyword(s):

Candida Albicans ◽

Bacterial Isolate ◽

Joint Infection ◽

Clinical Signs ◽

Positive Culture ◽

Clinical Relapse ◽

Clinical Failure ◽

Two Stage ◽

Prosthetic Joint ◽

New Surgery

Abstract Background Patients with late PJI are at risk for superinfection at the time of reimplantation. Different commercially available antibiotic-loaded cements (gentamicin, vancomycin, gentamicin+clindamycin [G+C], gentamicin+vancomycin [G+V]) could be used for the fixation of the new prosthesis and could be effective to treat or prevent superinfection. We aim to determine the microbiological epidemiology in patients experiencing failure following reimplantation to establish, based on the drug susceptibilities, which cement could be the most active. Methods Prospective cohort study including all patients with a two-stage exchange in 2013–2015. Microbiological failure was defined by positive culture at the time of reimplantation. Clinical failure was defined by patients with clinical signs of infection requiring a new surgery. Results We included 117 patients (median age 70 years). Fourteen patients (12%) experienced a failure: seven patients with microbiological failure (four CoNS, one P. acnes, one corynebacterium, and three Candida albicans); seven patients with a clinical relapse requiring a new surgery (three Enterobacteriaceae, two P. aeruginosa, one streptococcus spp., one CoNS, one P. acnes, one E. faecalis). Considering the use of a vancomycin-loaded cement, this antibiotic was inactive on Candida (n = 3) and Gram-negative isolates (n = 5). Considering the use of gentamicin, this antibiotic was inactive on Candida (n = 3) and five bacterial isolates. These five letter isolates were also not susceptible to Clindamycin. Considering the use of G+V, this combination was inactive on Candida (n = 3) and only one bacterial isolate (a gentamicin-resistant K. pneumonia). Consequently, the vancomycin-, gentamicin- and G+C-loaded cements may effectively treat or prevent 42.9% of superinfections, only. Conversely, the G+V-loaded cement may effectively treat or prevent 71.4% of them. Conclusion Considering the commercially available antibiotic loaded: none of the Candida albicans superinfection could be locally treated, and the G+V-loaded cement could treat or prevent most bacterial superinfections. Disclosures T. Ferry, HERAEUS: Consultant, Speaker honorarium. S. Lustig, Heraeus: Consultant, Consulting fee

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A spacer infection by Candida albicans secondary to a Staphylococcus capitis prosthetic joint infection: a case report

BMC Infectious Diseases ◽

10.1186/s12879-021-06113-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Marta Bottagisio ◽

Alessandro Bidossi ◽

Nicola Logoluso ◽

Antonio Pellegrini ◽

Elena De Vecchi

Keyword(s):

Candida Albicans ◽

Synovial Fluid ◽

Prosthetic Joint Infection ◽

Revision Surgery ◽

Hip Prosthesis ◽

Joint Infection ◽

Microbiological Analysis ◽

Two Stage ◽

Staphylococcus Capitis ◽

Prosthetic Joint

Abstract Background Prosthetic joint infection (PJI) is one of the most feared complications following total arthroplasty surgeries. Gram-positive bacteria are the most common microorganisms implicated in PJIs, while infections mediated by fungi only account for 1% of cases. When dealing with PJIs, a two-stage revision arthroplasty is widely used. Briefly, a spacer is introduced until re-implantation of the definitive prosthesis to provide skeleton stabilization while delivering antibiotics in the site of the infection. Sometimes, antimicrobial therapy may fail, but the isolation of a second microorganism from the spacer is uncommon and even less frequent that of a yeast. Case presentation Here is described a case of a 75-year-old woman who underwent two-stage revision surgery of the left hip prosthesis secondary to a Staphylococcus capitis infection, whose spacer was found to be infected by Candida albicans at a later time. Briefly, the patient underwent revision surgery of the hip prosthesis for a suspected PJI. After the debridement of the infected tissue, an antibiotic-loaded spacer was implanted. The microbiological analysis of the periprosthetic tissues and the implant depicted a S. capitis infection that was treated according to the antimicrobial susceptibility profile of the clinical isolate. Three months later, the patient was admitted to the emergency room due to local inflammatory signs. Synovial fluid was sent to the laboratory for culture. No evidence of S. capitis was detected, however, a yeast was identified as Candida albicans. Fifteen days later, the patient was hospitalized for the removal of the infected spacer. Microbiological cultures confirmed the results of the synovial fluid analysis. According to the susceptibility profile, the patient was treated with fluconazole (400 mg/day) for 6 months. Seven months later, the patient underwent second-stage surgery. The microbiological tests on the spacer were all negative. After 12 months of follow-up, the patient has fully recovered and no radiological signs of infection have been detected. Conclusions Given the exceptionality of this complication, it is important to report these events to better understand the clinical outcomes after the selected therapeutic options to prevent and forestall the development of either bacterial or fungal spacer infections.

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