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Antibiotic Combinations in Bone Cement Spacers: Efficacy and Considerations in Clinical Practice

Explore the use of antibiotics in bone cement spacers, optimal dosages, antibiotic characteristics, and potential antibiotic combinations. Understand the implications of gentamicin and vancomycin combination spacers in the clinical setting. Investigate infection eradication, resistance rates, and clinical outcomes.

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Antibiotic Combinations in Bone Cement Spacers: Efficacy and Considerations in Clinical Practice

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  1. Is there any ideal antibiotic or antibiotic-combination to be added in the spacers in the clinical setting? Clinical Infectious Diseases 2012, 55(11) …mainly case series data with only one randomized trial..

  2. Son eficaces los espaciadores-AB en recambio dos tiempos Garvin KL, 1995 (29 estudios): EFICACIA: SIN AB CON AB 82% 91% (con AB) Liberación es máxima durante las 1ª 48h (>30 mg/dl) y dismunuye progresivamente (15-30d) • ¿Características del antibiótico? • Activo frente al microorganismo • Termoestables (candinas no son termoestables AB) • Hidrosolubles (no hidrosolubles mala liberación) • Polvo (líquido no se mezcla con cemento) • Escasosefectossecundarios (IR ?  se desconoce) • Dextrano (> porosidad, > 25% liberación)

  3. Que antibióticos y dosificación • Aminoglicósidos (G, T), clinda (macrólidos), vancomicina,.. • Dosis • Se desconoce dosis idónea (1-10% del cemento) • Genta: 1-4g, Vanco: 1,2-4,8g por 40 gr cemento • > dósis: < resistencia cemento (< 8g AB por 40 g cemento) • Comercial = Manual • MejoreluciónDósis > elevadas • Liberaciónconocida Elegir AB • Ventajas trauma • Resistente (dificil) • Dósisbajas (1-2g) Peortraumatol • Coste: 3x Liberación ?

  4. Antibioticos solos o combinación? • In the initial models, the chosen antibiotic was gentamicin [or tobramycin • Pitto et al. 2005,Pattyn et al. 2011,Wan et al. 2012,Romano et al. 2010]. Vancomycin -gentamicin • Emergence of gentamicin-resistant bacteria (mostly GPC)  the addition of two potentially synergistic antibiotics to bone cement become attractive. • The potential combination of vancomicin and gentamicin in cement spacers has been suggested:

  5. Cultivos 2T y del espaciador Problema: difcoloniz de inf - 1tej + 1 espaciador: probable

  6. Rise in aminoglycoside resistance in staphylococci causing PJI?? …GPC susceptibility to aminoglycosides has not been reported routinely in PJI scenarios… Potential contribution of the antibiotic-loaded cement spacers to select resistant mutants in case of infection relapse? … there is no strong evidence to affirm this as a conclusive fact…this risk has brought to attention among scientific community.. Despite the theoretic advantages…are the vanco-genta spacers superior to the genta-spacers in the clinical setting? …whether adding vancomycin to gentamicin-prefabricated antibiotic spacers results in improved infection eradication, less pain, or better function is unknown…

  7. J. Arthroplasty 2014 Aug;29 (8) Increase in GPC gentamicin resistant rate? Risk of select resistances after spacer use?

  8. Retrospectiveanalysis of 113consecutivechronic PJI. Group A: 61cases without previous GenCS use Group B:52cases with previous GenCS use. 32% CGP Gentamicin-R GPC Resist-Rate: 41 %CGP Tobramicin-R 0 % CGP Vancomycin-R CoN-Staphylococcus (73% of GPC) 39 % Gentamicin-R 44 %Tobramicin-R ...may “potentially impact” the utility of only-aminoglycoside impregnated cement spacers… Corona PS et al. J. Arthroplasty 2014 Aug;29 (8)

  9. Previous exposure to gentamicin cement spacer: (…no antibioticossistémicos) Higher resistance rate among the relapsed cases group • 49.2% vs. 19.3 % gentamicin-R (p: 0.0001) • 57.4% vs. 25% de CoNSgentamicin-R(p: 0.001) Corona PS et al. J. Arthroplasty 2014 Aug;29 (8)

  10. Clinical superiority of vanco-genta spacers? Microbiological and Clinical Effectiveness Of Vancomycin Plus Gentamicin Or Gentamicin Loaded Spacers: A Comparative Study T Domingues Frada1, JC. Martínez-Pastor2, G Bori2, E Tornero2, J M Segur2, J Bosch2, S Garcia-Ramiro2, A Soriano2 Praga, Mayo 2015 Clin Orthop Relat Res. 2014 Mar;472 (3)

  11. Retrospectiveanalysis of 51consecutivechronic PJI. • Coagulase-negative staphylococci (43%). • Propionibacterium acnes (18%) • Negative culturs (10%) Final Follow-Up: 12.4 - 64.7 months Overall infection control rate: 83% Corona PS et al. Clin Orthop Relat Res. 2014 Mar;472 (3)

  12. Retrospective study (seguimiento 56 meses) Methods January 2003 December 2013 146 patients Gentamicin Group (G) n=83 Vanco + Gentamicin Group (V/G) n=63

  13. Results • Global rate of infection healing = 75% • At more then 4.5 years of follow up • Healing significantly superior for chronic infections (84%) • 84% vs 60% for acute p=0.002 • Healing significantly superior with negative cultures on 2nd stage • 81.5% vs 39.1% for positive cultures • Rate of negative cultures in second stage was superior in G/V • 23.2% vs 6.7% for G, p= 0.001 • Healing shows a trend to be superior with V/G spacers (81.9%) • 81.9% vs 69.5% for Gentamicin spacers

  14. Results Univariate Analysis No significance for Gender, Diabetes, COPD, Steroid Medication, Renal Failure, Rheumatoid Arthritis, Cirrhosis, ASA score, CRP, BMI, Linezolid intake

  15. Results Logistic Regression Model for Positive Cultures on 2nd Stage Logistic Regression Model for infection control at last follow up

  16. Elevadastasas recidiva: 25-50% con recambio 2T - >ía Azoles prolongados Caso HVH: PTC Candida albicans 2T + AnfoBlip(3m)  VoriconF 2T + EspAnfoB + Anidalafungina (3m) R (3a)

  17. Guia diagnóstico-terapéutica infección osteoarticular • En el recambio en 2 T se aconsejautilizar un espaciadorcon • antibióticos. (B-II) • La dosis de AB local recomendada es de 1,2-4,8g para Vancomicina • y 1-4 g para genta y tobramicina (x 40g cemento). (C-III) • En espera de una evidencia mejor, es razonableutilizarespaciadores • con la combinaciónvanco-genta. (C-III) • En infecciones por multiresistentespuedenutilizarseespaciadores • activosfrente a éstemicroorganismo. (C-III) • En infecciones por Candida spp, se recomiendautilizar un espaciador • de anfo B (C-III)

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