Periprostetik Eklem Enfeksiyonlarında Antimikrobiyal Yan Etkiler: Sıklık, İlaç Sınıfına Özgü Toksisiteler ve Risk Faktörleri Üzerine Anlatısal Bir İnceleme
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DERLEME
CİLT: 15 SAYI: 1
P: 255 - 263
Ocak 2026

Periprostetik Eklem Enfeksiyonlarında Antimikrobiyal Yan Etkiler: Sıklık, İlaç Sınıfına Özgü Toksisiteler ve Risk Faktörleri Üzerine Anlatısal Bir İnceleme

Mediterr J Infect Microb Antimicrob 2026;15(1):255-263
Bilgi mevcut değil.
Bilgi mevcut değil
Alındığı Tarih: 01.04.2026
Kabul Tarihi: 03.09.2026
Online Tarih: 05.10.2026
Yayın Tarihi: 05.10.2026
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Periprostetik eklem enfeksiyonu (PJI), sıklıkla uzun süreli antimikrobiyal tedavi gerektiren, artroplastinin ciddi bir komplikasyonudur. Enfeksiyon kontrolü için gerekli olmasına rağmen, uzun süreli antibiyotik maruziyeti hastaları, etkinliği ve hasta güvenliğini tehlikeye atabilecek advers ilaç olaylarına (ADE) yatkın hale getirir. Bu derleme, PJI’da antimikrobiyal ilaçlara bağlı ADE görülme sıklığı, yelpazesi ve risk faktörlerine ilişkin güncel kanıtları özetlemeyi amaçlamakta olup, ilaç sınıfına özgü toksik etkilere ve bunların terapötik sonuçlarına vurgu yapmaktadır. Ocak 2010 ile Eylül 2025 tarihleri arasında PubMed, Embase ve Cochrane Kütüphanesi’nde anlatısal bir literatür taraması yapılmıştır. PJI’ya yönelik antimikrobiyal tedaviyle ilişkili ADE’leri değerlendiren randomize çalışmalar, prospektif ve retrospektif kohortlar ve sistematik incelemeler çalışmaya dahil edilmiştir. İnsidans, şiddet, ilaç sınıfları, tedavi değişiklikleri ve belirlenen risk faktörlerine dair veriler çıkarılmıştır. Metodolojik heterojenlik nedeniyle anlatısal bir sentez yapılmıştır. Analiz edilen literatürde, bildirilen ADE’lerin insidansı %7,8 ile %46 arasında değişmekte olup, yaklaşık %7,8 ile %20,4’ü şiddetli olaylar olarak sınıflandırılmıştır. Vankomisin ve piperasilin-tazobaktam kombinasyonları en yüksek nefrotoksisite oranlarını gösterirken, rifampin ve linezolid sırasıyla hepatotoksisite ve hematolojik toksisite ile ilişkilendirilmiştir. Uzun süreli tedavi, intravenöz uygulama, ileri yaş, obezite ve eşlik eden hastalıklar ADE riskini önemli ölçüde artırmıştır. Ortaya çıkan kanıtlar, oral kademeli tedavi ve daha kısa antimikrobiyal rejimlerin, daha iyi güvenlik profilleri sunarken, karşılaştırılabilir etkinlik sağlayabileceğini göstermektedir. Antimikrobiyal ilişkili ADE’ler, PJI yönetiminde sık olarak ortaya çıkar ve klinik olarak önemlidir ve genellikle tedavi değişikliğine veya tedavinin sonlandırılmasına yol açar. Periprostetik eklem enfeksiyonu tedavisinde güvenliği ve terapötik sonuçları iyileştirmek için rejim seçiminin, süresinin ve takibinin optimize edilmesi ve standartlaştırılmış ADE raporlama çerçevelerinin benimsenmesi esastır.

Anahtar Kelimeler:
Periprostetik eklem enfeksiyonu, antimikrobiyal toksisite, advers ilaç reaksiyonları, antimikrobiyal güvenlik, risk faktörleri

Kaynaklar

1
Kunutsor SK, Whitehouse MR, Blom AW, Beswick AD; INFORM Team. Patient-Related Risk Factors for Periprosthetic Joint Infection after Total Joint Arthroplasty: A systematic review and meta-analysis. PLoS One. 2016;11:e0150866.
2
Tornero E, Morata L, Martínez-Pastor JC, Angulo S, Combalia A, Bori G, García-Ramiro S, Bosch J, Mensa J, Soriano A. Importance of selection and duration of antibiotic regimen in prosthetic joint infections treated with debridement and implant retention. J Antimicrob Chemother. 2016;71:1395-401.
3
Prendki V, Ferry T, Sergent P, Oziol E, Forestier E, Fraisse T, Tounes S, Ansart S, Gaillat J, Bayle S, Ruyer O, Borlot F, Le Falher G, Simorre B, Dauchy FA, Greffe S, Bauer T, Bell EN, Martha B, Martinot M, Froidure M, Buisson M, Waldner A, Lemaire X, Bosseray A, Maillet M, Charvet V, Barrelet A, Wyplosz B, Noaillon M, Denes E, Beretti E, Berlioz-Thibal M, Meyssonnier V, Fourniols E, Tliba L, Eden A, Jean M, Arvieux C, Guignery-Kadri K, Ronde-Oustau C, Hansmann Y, Belkacem A, Bouchand F, Gavazzi G, Herrmann F, Stirnemann J, Dinh A. Prolonged suppressive antibiotic therapy for prosthetic joint infection in the elderly: a national multicentre cohort study. Eur J Clin Microbiol Infect Dis. 2017;36:1577-85.
4
Granger MF, Leis JA, Hempel A, Pincus D, Ravi B, Daneman N, Lam PW. Factors influencing the use of highly bioavailable oral antibiotic therapy for the treatment of prosthetic joint infections. Infect Control Hosp Epidemiol. 2024;45:1366-9.
5
Harrabi H, Mamona-Kilu C, Meyer E, d’Anglejan Chatillon E, Dournon N, Bouchand F, Duran C, Perronne V, Jaffal K, Dinh A. Treatment duration in bacterial prosthetic joint infections: a narrative review of current evidence. Antibiotics (Basel). 2025;14:1066.
6
Harrabi H, Meyer E, Dournon N, Bouchand F, Kilu CM, Perronne V, Jaffal K, d’Anglejan E, Duran C, Dinh A. Suppressive antibiotic therapy in prosthetic joint infections: A contemporary overview. Antibiotics (Basel). 2025;14:277.
7
Lora-Tamayo J, Mancheño-Losa M, Meléndez-Carmona MÁ, Hernández-Jiménez P, Benito N, Murillo O. Appropriate duration of antimicrobial treatment for prosthetic joint infections: A narrative review. Antibiotics (Basel). 2024;13:293.
8
Renz N, Trampuz A, Zimmerli W. Controversy about the role of rifampin in biofilm infections: Is it justified? Antibiotics (Basel). 2021;10:165.
9
Rybak MJ, Le J, Lodise TP, Levine DP, Bradley JS, Liu C, Mueller BA, Pai MP, Wong-Beringer A, Rotschafer JC, Rodvold KA, Maples HD, Lomaestro BM. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: A revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm. 2020;77:835-64.
10
Reinecke P, Morovic P, Niemann M, Renz N, Perka C, Trampuz A, Meller S. Adverse events associated with prolonged antibiotic therapy for periprosthetic joint infections-a prospective study with a special focus on rifampin. Antibiotics (Basel). 2023;12:1560.
11
Triffault-Fillit C, Valour F, Guillo R, Tod M, Goutelle S, Lustig S, Fessy MH, Chidiac C, Ferry T; Lyon BJI Study Group. Prospective cohort study of the tolerability of prosthetic joint infection empirical antimicrobial therapy. Antimicrob Agents Chemother. 2018;62:e00163-18.
12
Hong H, Chen Y, Zhou L, Bao J, Ma J. Risk factors analysis and construction of predictive models for acute kidney injury in overweight patients receiving vancomycin treatment. Expert Opin Drug Saf. 2025;24:1323-32.
13
Pupaibool J. The role of rifampin in prosthetic joint infections: efficacy, challenges, and clinical evidence. Antibiotics (Basel). 2024;13:1223.
14
Morata L, Senneville E, Bernard L, Nguyen S, Buzelé R, Druon J, Tornero E, Mensa J, Soriano A. A retrospective review of the clinical experience of linezolid with or without rifampicin in prosthetic joint infections treated with debridement and implant retention. Infect Dis Ther. 2014;3:235-43.
15
Pradier M, Robineau O, Boucher A, Titecat M, Blondiaux N, Valette M, Loïez C, Beltrand E, Nguyen S, Dézeque H, Migaud H, Senneville E. Suppressive antibiotic therapy with oral tetracyclines for prosthetic joint infections: a retrospective study of 78 patients. Infection. 2018;46:39-47.
16
Chao R, Rothenberger SD, Frear AJ, Hamlin BR, Klatt BA, Shah NB, Urish KL. Benefits and adverse events associated with extended antibiotic use for one year following periprosthetic joint infection in total knee arthroplasty: A prospective cohort analysis. J Arthroplasty. 2025;40:S528-34.
17
Furukawa D, Dunning M, Shen S, Chang A, Aronson J, Amanatullah DF, Suh GA, Kappagoda S. No differences in outcomes with stopping or continuing antibiotic suppression in periprosthetic joint infections. J Bone Jt Infect. 2024;9:143-8.
18
Teng C, Reveles KR, Obodozie-Ofoegbu OO, Frei CR. Clostridium difficile infection risk with important antibiotic classes: An analysis of the FDA adverse event reporting system. Int J Med Sci. 2019;16:630-5.
19
Cobo J, Escudero-Sanchez R. Suppressive antibiotic treatment in prosthetic joint infections: A perspective. Antibiotics (Basel). 2021;10:743.
20
Bruniera FR, Ferreira FM, Saviolli LR, Bacci MR, Feder D, da Luz Gonçalves Pedreira M, Sorgini Peterlini MA, Azzalis LA, Campos Junqueira VB, Fonseca FL. The use of vancomycin with its therapeutic and adverse effects: a review. Eur Rev Med Pharmacol Sci. 2015;19:694-700.
21
Klasan A, Patel CK, Young SW. Intraosseous regional administration of vancomycin in primary total knee arthroplasty does not increase the risk of vancomycin-associated complications. J Arthroplasty. 2021;36:1633-7.
22
Gauzit R, Kabir-Ahmadi M, Thompson N, Pea F, Tattevin P. Safety of high loading doses of teicoplanin: POSY-TEICO, a prospective, multicentre, observational study. Int J Antimicrob Agents. 2023;62:106940.
23
Joseph C, Robineau O, Titecat M, Putman S, Blondiaux N, Loiez C, Valette M, Schmit JL, Beltrand E, Dézeque H, Nguyen S, Migaud H, Senneville E. Daptomycin versus vancomycin as post-operative empirical antibiotic treatment for prosthetic joint infections: A case-control study. J Bone Jt Infect. 2019;4:72-5.
24
Yusuf E, Perrottet N, Orasch C, Borens O, Trampuz A. Daptomycin-associated eosinophilic pneumonia in two patients with prosthetic joint infection. Surg Infect (Larchmt). 2014;15:834-7.
25
Pham TT, Garreau R, Craighero F, Cottin V, Said BB, Goutelle S, Ferry T. Seventeen cases of daptomycin-induced eosinophilic pneumonia in a cohort of patients treated for bone and joint infections: Proposal for a new algorithm. Open Forum Infect Dis. 2022;9:ofac577.
26
Zhang C, Li J, Lin L, Liu M, Chen Y, Cai Y, Huang J, Huang Z, Zhang C, Zhang W, Fang X, Li W. The impact of rifampin on the efficacy of implant retention and prosthesis removal in staphylococcal periprosthetic joint infection. Front Cell Infect Microbiol. 2025;15:1587436.
27
Vollmer NJ, Rivera CG, Stevens RW, Oravec CP, Mara KC, Suh GA, Osmon DR, Beam EN, Abdel MP, Virk A. Safety and tolerability of fluoroquinolones in patients with staphylococcal periprosthetic joint infections. Clin Infect Dis. 2021;73:850-6.
28
Theil C, Schmidt-Braekling T, Gosheger G, Schwarze J, Dieckmann R, Schneider KN, Möllenbeck B. Clinical use of linezolid in periprosthetic joint infections - a systematic review. J Bone Jt Infect. 2020;6:7-16.
29
Sawada M, Oe K, Hirata M, Kawamura H, Ueda N, Nakamura T, Iida H, Saito T. Linezolid versus daptomycin treatment for periprosthetic joint infections: a retrospective cohort study. J Orthop Surg Res. 2019;14:334.
30
Nandi S, Doub JB, De Palma BJ, Potter GR, Stronach BM, Stambough JB, Brilliant ZR, Mears SC. Suppressive antibiotic therapy after debridement, antibiotics, and implant retention is well-tolerated without inducing resistance: A multicenter study. J Arthroplasty. 2024;39:795-800.
31
Lecomte R, Deschanvres C, Le Bourgeois A, Bart G, Mahieu R, Le Moal G, Ansart S, Asseray N, Ruffier d’Epenoux L, Corvec S, Boutoille D; CRIOGO network. Efficacy and safety of co-trimoxazole in device-related bone and joint infections: a CRIOGO multicentre case-control study. J Antimicrob Chemother. 2024;79:3109-15.
32
Jamard S, Lartigue MF, Le Nail LR, Tuloup V, Lacasse M, Lemaignen A; CRIOGO local group. Evaluation of clindamycin use in bone and joint infections: is monotherapy a safe option? A monocentric observational study 2014-19. JAC Antimicrob Resist. 2025;7:dlaf164.
33
Abedi AA, Svensson JM, Pedersen AB, Varnum C, Nielsen SM, Laigaard JH, Christensen R, Overgaard S. Comparative effectiveness of antibiotic prophylaxis for preventing serious adverse events after primary total hip arthroplasty: a systematic review and network meta-analysis of randomized trials. Acta Orthop. 2025;96:640-9.
34
Tsegka KG, Voulgaris GL, Kyriakidou M, Kapaskelis A, Falagas ME. Intravenous fosfomycin for the treatment of patients with bone and joint infections: a review. Expert Rev Anti Infect Ther. 2022;20:33-43.
35
Carli AV, Miller AO, Kapadia M, Chiu YF, Westrich GH, Brause BD, Henry MW. Assessing the role of daptomycin as antibiotic therapy for staphylococcal prosthetic joint infection. J Bone Jt Infect. 2020;5:82-8.
36
Leijtens B, Elbers JBW, Sturm PD, Kullberg BJ, Schreurs BW. Clindamycin-rifampin combination therapy for staphylococcal periprosthetic joint infections: a retrospective observational study. BMC Infect Dis. 2017;17:321.
37
Kobayashi S, Tagawa S, Ogura T, Kitaoka A, Yasu T. Safety of linezolid, rifampicin, and clindamycin combination therapy in patients with prosthetic joint infection. Drug Discov Ther. 2022;16:142-4.
38
Valour F, Karsenty J, Bouaziz A, Ader F, Tod M, Lustig S, Laurent F, Ecochard R, Chidiac C, Ferry T; Lyon BJI Study Group. Antimicrobial-related severe adverse events during treatment of bone and joint infection due to methicillin-susceptible Staphylococcus aureus. Antimicrob Agents Chemother. 2014;58:746-55.
39
Triffault-Fillit C, Mabrut E, Corbin K, Braun E, Becker A, Goutelle S, Chaudier P, Fessy MH, Dupieux C, Laurent F, Gunst S, Lustig S, Chidiac C, Ferry T, Valour F. Tolerance and microbiological efficacy of cefepime or piperacillin/tazobactam in combination with vancomycin as empirical antimicrobial therapy of prosthetic joint infection: a propensity-matched cohort study. J Antimicrob Chemother. 2020;75:2299-306.
40
Kelly MP, Gililland JM, Blackburn BE, Anderson LA, Pelt CE, Certain LK. Extended oral antibiotics increase bacterial resistance in patients who fail 2-stage exchange for periprosthetic joint infection. J Arthroplasty. 2022;37:S989-96.
41
Shah NB, Hersh BL, Kreger A, Sayeed A, Bullock AG, Rothenberger SD, Klatt B, Hamlin B, Urish KL. Benefits and adverse events associated with extended antibiotic use in total knee arthroplasty periprosthetic joint infection. Clin Infect Dis. 2020;70:559-65.
42
Bouji N, Wen S, Dietz MJ. Intravenous antibiotic duration in the treatment of prosthetic joint infection: systematic review and meta-analysis. J Bone Jt Infect. 2022;7:191-202.
43
Yen HT, Hsieh RW, Huang CY, Hsu TC, Yeh T, Chen YC, Chen WS, Lee CC. Short-course versus long-course antibiotics in prosthetic joint infections: a systematic review and meta-analysis of one randomized controlled trial plus nine observational studies. J Antimicrob Chemother. 2019;74:2507-16.
44
Henry TW, Entezari V, Ghoraishian M, Williams GR, Namdari S. Complications associated with intravenous antibiotic treatment for Cutibacterium acnes periprosthetic shoulder infection. Orthopedics. 2021;44:e422-6.
45
Malahias MA, Gu A, Harris EC, Adriani M, Miller AO, Westrich GH, Sculco PK. The role of long-term antibiotic suppression in the management of peri-prosthetic joint infections treated with debridement, antibiotics, and implant retention: A systematic review. J Arthroplasty. 2020;35:1154-60.
46
Gallagher CK, Cummins H, Benefield RJ, Certain LK. Switching from intravenous vancomycin to oral antibiotics reduces adverse events in a retrospective cohort of outpatients with orthopedic infections. Pharmacotherapy. 2023;43:1277-85.
47
Scarborough M, Li HK, Rombach I, Zambellas R, Walker AS, McNally M, Atkins B, Kümin M, Lipsky BA, Hughes H, Bose D, Warren S, Mack D, Folb J, Moore E, Jenkins N, Hopkins S, Seaton RA, Hemsley C, Sandoe J, Aggarwal I, Ellis S, Sutherland R, Geue C, McMeekin N, Scarborough C, Paul J, Cooke G, Bostock J, Khatamzas E, Wong N, Brent A, Lomas J, Matthews P, Wangrangsimakul T, Gundle R, Rogers M, Taylor A, Thwaites GE, Bejon P. Oral versus intravenous antibiotics for bone and joint infections: the OVIVA non-inferiority RCT. Health Technol Assess. 2019;23:1-92.
48
Yao JJ, Jurgensmeier K, Whitson AJ, Pottinger PS, Matsen FA 3rd, Hsu JE. Oral and IV antibiotic administration after single-stage revision shoulder arthroplasty: study of survivorship and patient-reported outcomes in patients without clear preoperative or intraoperative infection. J Bone Joint Surg Am. 2022;104:421-9.
49
Bahoravitch TJ, Jami M, Nayar SK, Agarwal A, Kreulen RT, Best MJ, Srikumaran U. Total shoulder arthroplasty: Antibiotic allergies increase risk of postoperative complications. J Am Acad Orthop Surg. 2022;30:e1249-59.
50
Li HK, Rombach I, Zambellas R, Walker AS, McNally MA, Atkins BL, Lipsky BA, Hughes HC, Bose D, Kümin M, Scarborough C, Matthews PC, Brent AJ, Lomas J, Gundle R, Rogers M, Taylor A, Angus B, Byren I, Berendt AR, Warren S, Fitzgerald FE, Mack DJF, Hopkins S, Folb J, Reynolds HE, Moore E, Marshall J, Jenkins N, Moran CE, Woodhouse AF, Stafford S, Seaton RA, Vallance C, Hemsley CJ, Bisnauthsing K, Sandoe JAT, Aggarwal I, Ellis SC, Bunn DJ, Sutherland RK, Barlow G, Cooper C, Geue C, McMeekin N, Briggs AH, Sendi P, Khatamzas E, Wangrangsimakul T, Wong THN, Barrett LK, Alvand A, Old CF, Bostock J, Paul J, Cooke G, Thwaites GE, Bejon P, Scarborough M; OVIVA Trial Collaborators. Oral versus intravenous antibiotics for bone and joint infection. N Engl J Med. 2019;380:425-36.
51
Bouza E, Valerio M, Soriano A, Morata L, Carus EG, Rodríguez-González C, Hidalgo-Tenorio MC, Plata A, Muñoz P, Vena A; DALBUSE Study Group (Dalbavancina: Estudio de su uso clinico en España). Dalbavancin in the treatment of different gram-positive infections: a real-life experience. Int J Antimicrob Agents. 2018;51:571-7.
52
Buzón Martín L, Mora Fernández M, Perales Ruiz JM, Ortega Lafont M, Álvarez Paredes L, Morán Rodríguez MA, Fernández Regueras M, Machín Morón MA, Mejías Lobón G. Dalbavancin for treating prosthetic joint infections caused by Gram-positive bacteria: A proposal for a low dose strategy. A retrospective cohort study. Rev Esp Quimioter. 2019;32:532-8.