Selection of new pathogens during antibiotic treatment or prolonged antibiotic prophylaxis in orthopedic surgery

Main Article Content

Susanne Friedl Senta Faulhaber Markus Hupp Ilker Uçkay


In orthopedic surgery regarding open or infected wounds, both the current antibiotic therapy as well as the perioperative antibiotic prophylaxis, may select new pathogens leading to iterative debridement and changing the antibiotic regimens targeting more resistant microorganisms.

The risk of finding new and more resistant pathogens is relatively high (5%-15%) and exceeds the incidence of primary surgical site infections (SSI) after elective orthopedic surgery with primary wound closures. Based on a narrative review of the current scientific literature, we summarize mechanisms and associations of such a pathogen selection by therapeutic or prophylactic agents and focus on the importance of an adequate initial debridement and on an effective antibiotic stewardship.

Keywords: antibiotic therapy; antibiotic prophylaxis; osteoarticular infection; selection pressure; new surgical site infections

Article Details

How to Cite
FRIEDL, Susanne et al. Selection of new pathogens during antibiotic treatment or prolonged antibiotic prophylaxis in orthopedic surgery. Medical Research Archives, [S.l.], v. 12, n. 4, apr. 2024. ISSN 2375-1924. Available at: <>. Date accessed: 27 may 2024. doi:
Review Articles


1. Murray AK, Zhang L, Snape J, Gaze WH. Comparing the selective and co-selective effects of different antimicrobials in bacterial communities. Int J Antimicrob Agents 53 (2019): 767-773, doi: 10.1016/j.ijantimicag.2019.03.001.

2. Uçkay I, Hoffmeyer P, Lew D, Pittet D. Prevention of surgical site infections in orthopaedic surgery and bone trauma: state-of-the-art update. J Hosp Infect 84 (2013): 5-12, doi: 10.1016/j.jhin.2012.12.014.

3. Vardakas KZ, Rafailidis PI, Konstantelias AA, Falagas ME. Predictors of mortality in patients with infections due to multi-drug resistant Gram negative bacteria: the study, the patient, the bug or the drug? J Infect 66 (2013): 401-414.

4. Falagas ME, Bliziotis IA, Kasiakou SK, Samonis G, Athanassopoulou P et al. Outcome of infections due to pandrug-resistant (PDR) Gram-negative bacteria. BMC Infect Dis 5 (2005): 24, doi: 10.1186/1471-2334-5-24.

5. Carattoli A. Plasmids and the spread of resistance. Int J Med Microbiol 303 (2013): 298-304, doi: 10.1016/j.ijmm.2013.02.001.

6. Pfeifer Y, Cullik A, Witte W. Resistance to cephalosporins and carbapenems in Gram-negative bacterial pathogens. Int J Med Microbiol 300 (2010): 371-379, doi:10.1016/j.ijmm.2010.04.005.

7. Uçkay I, Lebowitz D, Kressmann B, Lipsky BA, Gariani K. Influence of Skin Commensals on Therapeutic Outcomes of Surgically Debrided Diabetic Foot Infections-A Large Retrospective Comparative Study. Antibiotics (Basel) 3 (2023): 316. doi: 10.3390/antibiotics12020316

8. Carrara E, Pfeffer I, Zusman O, Leibovici L, Paul M. Determinants of inappropriate empirical antibiotic treatment: systematic review and meta-analysis, Int J Antimicrob Agents 51 (2018): 548-553, doi: 10.1016/j.ijantimicag.2017.12.013.

9. Sax H, Kuster SP, Tehrany YA, Ren R, Uçkay I et al. Eight-year sustainability of a successful intervention to prevent urinary tract infection: A mixed-methods study. Am J Infect Control 44 (2016): 820-824, doi: 10.1016/j.ajic.2016.01.013

10. Uçkay I, Sax H, Gayet-Agéron A, Ruef C, Mühlemann K et al. High proportion of healthcare-associated urinary tract infection in the absence of prior exposure to urinary catheter: a cross-sectional study. Antimicrob Resist Infect Control 2 (2013): 5, doi: 10.1186/2047-2994-2-5

11. Wuarin L, Abbas M, Harbarth S, Waibel F, Holy D et al. Changing perioperative prophylaxis during antibiotic therapy and iterative debridement for orthopedic infections? PLoS One 14 (2019): 0226674,
doi: 10.1371/journal.pone.0226674

12. Burnett RS, Aggarwal A, Givens SA, McClure JT, Morgan PM et al. Prophylactic antibiotics do not affect cultures in the treatment of an infected TKA: a prospective trial. Clin Orthop Relat Res 468 (2010): 127-134, doi: 10.1007/s11999-009-1014

13. Stephan A, Thürmer A, Glauche I, Nowotny J, Zwingenberger S et al., Does preoperative antibiotic prophylaxis affect sonication-based diagnosis in implant-associated infection? J Orthop Res 39 (2021): 2646-2652,
doi: 10.1002/jor.25015.

14. Al-Mayahi M, Cian A, Lipsky BA, Suvà D, Müller C et al. Administration of antibiotic agents before intraoperative sampling in orthopedic infections alters culture results. J Infect 71 (2015): 518-525, doi: 10.1016/j.jinf.2015.08.002.

15. Cohen ME, Salmasian H, Li J, Liu J, Zachariah P et al. Surgical Antibiotic Prophylaxis and Risk for Postoperative Antibiotic-Resistant Infections. J Am Coll Surg 255 (2017): 631-638, doi: 10.1016/j.jamcollsurg.2017.08.010.

16. Jamei O, Gjoni S, Zenelaj B, Kressmann B, Belaieff W et al. Which Orthopaedic Patients Are Infected with Gram-negative Non-fermenting Rods? J Bone Jt Infect 2 (2017): 73-76, doi: 10.7150/jbji.17171

17. Uçkay I, Pires D, Agostinho A, Guanziroli N, Öztürk M et al. Enterococci in orthopaedic infections: Who is at risk getting infected? J Infect 75 (2017): 309-314, doi: 10.1016/j.jinf.2017.06.008.

18. Cooper CC, Stein GE, Mitra S, Abubaker A, Havlichek DH. Long-Acting Lipoglycopeptides for the Treatment of Bone and Joint Infections. Surg Infect (Larchmt) 22 (2021): 771-779, doi: 10.1089/sur.2020.413.

19. Uçkay I, Kressmann B, Malacarne S, Toumanova A, Jaafar J et al. A randomized, controlled study to investigate the efficacy and safety of a topical gentamicin-collagen sponge in combination with systemic antibiotic therapy in diabetic patients with a moderate or severe foot ulcer infection. BMC Infect Dis 18 (2018): 361, doi: 10.1186/s12879-018-3253-z

20. Soldevila-Boixader L, Fernández AP, Laguna JM, Uçkay I. Local Antibiotics in the Treatment of Diabetic Foot Infections: A Narrative Review. Antibiotics (Basel) 12 (2023): 124, doi: 10.3390/antibiotics12010124.

21. Hasler A, Unterfrauner I, Olthof MGL, Jans P, Betz M et al. Deep surgical site infections following double-dose perioperative antibiotic prophylaxis in adult obese orthopedic patients. Int J Infect Dis 108 (2021): 537-542, doi: 10.1016/j.ijid.2021.06.008.

22. Uçkay I, Harbarth S, Ferry T, Lübbeke A, Emonet S et al. Meticillin resistance in orthopaedic coagulase-negative staphylococcal infections. J Hosp Infect 79 (2011): 248-253, doi: 10.1016/j.jhin.2011.06.014

23. Uçkay I, Lübbeke A, Harbarth S, Emonet S, Tovmirzaeva L et al. Low risk despite high endemicity of methicillin-resistant Staphylococcus aureus infections following elective total joint arthroplasty: a 12-year experience. Ann Med 44 (2012): 360-368, doi: 10.3109/07853890.2010.550932.

24. National Nosocomial Infections Surveillance System. National Nosocomial Infections Surveillance (NNIS) system report, data summary from January 1992 through June 2004, issued October 2004. Am J Infect Control 32 (2004): 470-485, doi: 10.1016/S0196655304005425.

25. Khalil D, Hultin M, Rashid MU, Lund B. Oral microflora and selection of resistance after a single dose of amoxicillin. Clin Microbiol Infect 11 (2016): 1-4, doi: 10.1016/j.cmi.2016.08.008

26. Davat M, Wuarin L, Stafylakis D, Abbas M, Harbarth S et al. Should antibiotic prophylaxis before orthopedic implant surgery depend on the duration of pre-surgical hospital stay? Antimicrob Resist Infect Control 7 (2018): 131, doi: 10.1186/s13756-018-0421-2.

27. Dunkel N, Pittet D, Tovmirzaeva L, Suvà D, Bernard L et al. Short duration of antibiotic prophylaxis in open fractures does not enhance risk of subsequent infection. Bone Joint J 95-B (2013): 831-837,
doi: 10.1302/0301-620X.95B6.30114.

28. Gonzalez A, Suvà D, Dunkel N, Nicodeme JD, Lomessy A et al. Are there clinical variables determining antibiotic prophylaxis-susceptible versus resistant infection in open fractures? Int Orthop 38 (2014): 2323-2327, doi: 10.1007/s00264-014-2395-x.

29. Uçkay I, Agostinho A, Belaieff W, Toutous-Trellu L, Scherer-Pietramaggiori S et al. Noninfectious wound complications in clean surgery: epidemiology, risk factors, and association with antibiotic use. World J Surg 35 (2011): 973-980, doi: 10.1007/s00268-011-0993-y.

30. Pérez-Prieto D, Portillo ME, Puig-Verdié L, Alier A, Gamba C et al. Preoperative antibiotic prophylaxis in prosthetic joint infections: not a concern for intraoperative cultures. Diagn Microbiol Infect Dis 86 (2016): 442-445,
doi: 10.1016/j.diagmicrobio.2016.09.014.

31. Ghanem E, Parvizi J, Clohisy J, Burnett S, Sharkey PF et al. Perioperative antibiotics should not be withheld in proven cases of periprosthetic infection. Clin Orthop Relat Res 461 (2007): 44-47,
doi: 10.1097/BLO.0b013e318065b780.

32. Berbari EF, Marculescu C, Sia I, Lahr BD, Hanssen AD et al. Culture-negative prosthetic joint infection. Clin Infect Dis 45 (2007): 1113-1119, doi: 10.1086/522184.

33. Malekzadeh D, Osmon DR, Lahr BD, Hanssen AD, Berbari EF. Prior use of antimicrobial therapy is a risk factor for culture-negative prosthetic joint infection. Clin Orthop Relat Res 468 (2010): 2039-2045, doi: 10.1007/s11999-010-1338-0.

34. Shahi A, Deirmengian C, Higuera C, Chen A, Restrepo C et al. Premature Therapeutic Antimicrobial Treatments Can Compromise the Diagnosis of Late Periprosthetic Joint Infection. Clin Orthop Relat Res 473 (2015): 2244-2249, doi: 10.1007/s11999-015-4142-z.

35. Siegert P, Frank BJH, Simon S, Meraner D, Pokorny-Olsen A et al. Changes in microbiological spectrum and antibiotic susceptibility in two-stage exchange for periprosthetic shoulder infections. Arch Orthop Trauma Surg 143 (2022): 3871-3878, doi: 10.1007/s00402-022-04635-7.

36. Benito N, Mur I, Ribera A, Soriano A, Rodríguez-Pardo D et al. The Different Microbial Etiology of Prosthetic Joint Infections according to Route of Acquisition and Time after Prosthesis Implantation, Including the Role of Multidrug-Resistant Organisms. J Clin Med 8 (2019): 673, doi: 10.3390/jcm8050673.

37. Young BC, Dudareva M, Vicentine MP, Hotchen AJ, Ferguson J et al. Microbial Persistence, Replacement and Local Antimicrobial Therapy in Recurrent Bone and Joint Infection. Antibiotics (Basel) 12 (2023): 708, doi: 10.3390/antibiotics12040708

38. Olsen AS, Wilson A, OʼMalley MJ, Urish KL, Klatt BA. Are Sonication Cultures of Antibiotic Cement Spacers Useful During Second-stage Reimplantation Surgery for Prosthetic Joint Infection? Clin Orthop Relat Res 476 (2018): 1986-1992, doi:10.1007/s11999.0000000000000257.

39. Phillips JE, Crane TP, Noy M, Elliott TSJ, Grimer RJ. The incidence of deep prosthetic infections in a specialist orthopaedic hospital. J Bone Joint Surg Br 88-B (2006): 943-948, doi: 10.1302/0301-620X.88B7.17150.

40. Lee Y, Cho YS, Sohn YJ, Hyun JH, Ahn SM et al. Clinical Characteristics and Causative Pathogens of Infective Arthritis and Risk Factors for Gram-Negative Bacterial Infections. Infect Chemother 52 (2020): 503-515,
doi: 10.3947/ic.2020.52.4.503.

41. Moojen DJ, Zwiers JH, Scholtes VAB, Verheyen CCPM, Poolman RW. Similar success rates for single and multiple debridement surgery for acute hip arthroplasty infection. Acta Orthop 85 (2014): 383-388,
doi: 10.3109/17453674.2014.927729.

42. Kelly MP, Gililland JM, Blackburn BE, Anderson LA, Pelt CE et al. Extended Oral Antibiotics Increase Bacterial Resistance in Patients Who Fail 2-Stage Exchange for Periprosthetic Joint Infection. J Arthroplasty 37 (2022): 989-996, doi: 10.1016/j.arth.2022.01.027.

43. Wouthuyzen-Bakker M, Kheir MM, Moya I, Rondon AJ, Kheir M et al. Failure After 2-Stage Exchange Arthroplasty for Treatment of Periprosthetic Joint Infection: The Role of Antibiotics in the Cement Spacer. Clin Infect Dis 68 (2019): 2087-2093, doi: 10.1093/cid/ciy851.

44. Levy PY, Fournier PE, Fenollar F, Raoult D. Systematic PCR detection in culture-negative osteoarticular infections. Am J Med 126 (2013): 1125-1133, doi:10.1016/j.amjmed.2013.04.027

45. Uçkay I, Sax H, Harbarth S, Bernard L, Pittet D. Multi-resistant infections in repatriated patients after natural disasters: lessons learned from the 2004 tsunami for hospital infection control. J Hosp Infect 68 (2008): 1-8, doi: 10.1016/j.jhin.2007.10.018.

46. Yusuf E, Steinrücken J, Buchegger T, Trampuz A, Borens O. A descriptive study on the surgery and the microbiology of Gustilo type III fractures in a university hospital in Switzerland. Acta Orthop Belg 81 (2015): 327-332.

47. Velmahos GC, Toutouzas KG, Sarkisyan G, Chan LS, Jindal A et al. Severe Trauma Is Not an Excuse for Prolonged Antibiotic Prophylaxis. Arch Surg 137 (2002): 537-542, doi: 10.1001/archsurg.137.5.537.

48. Ukai T, Hamahashi K, Uchiyama Y, Kobayashi Y, Watanabe M et al. Retrospective analysis of risk factors for deep infection in lower limb Gustilo-Anderson type III fractures. J Orthop Traumatol 21 (2020): 10, doi: 10.1186/s10195-020-00549-5.

49. Suzuki T, Inui T, Sakai M, Ishii K, Kurozumi T et al. Type III Gustilo-Anderson open fracture does not justify routine prophylactic Gram-negative antibiotic coverage. Sci Rep 13 (2023): 7085, doi: 10.1038/s41598-023-34142-7

50. Lebowitz D, Kressmann B, Gjoni S, Zenelaj B, Grosgurin O et al. Clinical features of anaerobic orthopaedic infections. Infect Dis (Lond) 49 (2017): 137-140, doi: 10.1080/23744235.2016.1225979

51. Benkabouche M, Racloz G, Spechbach H, Lipsky BA, Gaspoz JM et al. Four versus six weeks of antibiotic therapy for osteoarticular infections after implant removal: a randomized trial. J Antimicrob Chemother 74 (2019): 2394-2399, doi: 10.1093/jac/dkz202.

52. Patanwala AE, Radosevich JJ, Meshay I, Naderi M, Culver MA et al. Cefazolin Monotherapy Versus Cefazolin Plus Aminoglycosides for Antimicrobial Prophylaxis of Type III Open Fractures. Am J Ther 28 (2019): 284-291, doi: 10.1097/MJT.0000000000001121.

53. Redfern J, Wasilko SM, Groth ME, McMillian WD, Bartlett CS, 3rd. Surgical Site Infections in Patients With Type 3 Open Fractures: Comparing Antibiotic Prophylaxis With Cefazolin Plus Gentamicin Versus Piperacillin/Tazobactam. J Orthop Trauma 30 (2016): 415-419, doi: 10.1097/BOT.0000000000000554.

54. Declercq P, Zalavras C, Nijssen A, Mertens B, Mesure J et al. Impact of duration of perioperative antibiotic prophylaxis on development of fracture-related infection in open fractures. Arch Orthop Trauma Surg 141 (2021): 235-243, doi: 10.1007/s00402-020-03474-8.

55. Bankhead-Kendall B, Gutierrez T, Murry J, Holland D, Agrawal V et al. Antibiotics and open fractures of the lower extremity: less is more. Eur J Trauma Emerg Surg 45 (2019): 125-129, doi: 10.1007/s00068-017-0847-x.

56. Müller D, Kaiser D, Sairanen K, Studhalter T, Uçkay I. Antimicrobial Prophylaxis for the Prevention of Surgical Site Infections in Orthopaedic Oncology - A Narrative Review of Current Concepts. J Bone Jt Infect 4 (2019): 254263, doi: 10.7150/jbji.39050.

57. Rod-Fleury T, Uçkay I. Microbiological Particularities of Surgical Site Infections in Oncologic Orthopedic Surgery Compared to Non-Oncologic Surgery-Single Center Experience and Literature Review. Clin Surg 4 (2019): 2443.

58. Nagano S, Yokouchi M, Setoguchi T, Sasaki H, Shimada H et al. Analysis of surgical site infection after musculoskeletal tumor surgery: risk assessment using a new scoring system. Sarcoma (2014) 2014: 645496, doi: 10.1155/2014/645496.

59. Geller DS, Hornicek FJ, Mankin HJ, Raskin KA. Soft tissue sarcoma resection volume associated with wound-healing complications. Clin Orthop Relat Res 459 (2007): 182-185, doi: 10.1097/BLO.0b013e3180514c50.

60. Saddegh MK, Bauer HC. Wound complication in surgery of soft tissue sarcoma. Analysis of 103 consecutive patients managed without adjuvant therapy. Clin Orthop Relat Res 289 (1993): 247-253.

61. Uçkay I, Berli M, Sendi P, Lipsky BA. Principles and practice of antibiotic stewardship in the management of diabetic foot infections. Curr Opin Infect Dis 32 (2019): 95-101, doi: 10.1097/QCO.0000000000000530.

62. Lebowitz D, Gariani K, Kressmann B, von Dach E, Huttner B et al. Are antibiotic-resistant pathogens more common in subsequent episodes of diabetic foot infection? Int J Infect Dis 59 (2017): 61-64,
doi: 10.1016/j.ijid.2017.04.012.

63. Bellova P, Knop-Hammad V, Königshausen M, Mempel E, Frieler S et al. Sonication of retrieved implants improves sensitivity in the diagnosis of periprosthetic joint infection. BMC Musculoskelet Disord 20 (2019): 623, doi: 10.1186/s12891-019-3006-1.

64. Uçkay I, Bomberg H, Risch M, Betz M, Müller D, Farshad M. Broad-spectrum Antibiotic Prophylaxis in Tumor and Infected Orthopedic Surgery - the prospective-randomized, microbiologist-blinded, stratified, superiority Trials - BAPTIST trials. Research Square (2022) 2209767/v1, University of Zurich, doi: 10.1186/s13063-023-07605-5.

65. Chotai S, Wright PW, Hale AT, Jones WA, McGirt MJ et al. Does Intrawound Vancomycin Application During Spine Surgery Create Vancomycin-Resistant Organism? Neurosurgery 80 (2017): 746-753,
doi: 10.1093/neuros/nyw097.

66. Bell S, Davey P, Nathwani D, Marwick C, Vadiveloo T et al. Risk of AKI with gentamicin as surgical prophylaxis. J Am Soc Nephrol 25 (2014): 2625-2632, doi: 10.1681/ASN.2014010035

67. Branch-Elliman W, Ripollone JE, O'Brien WJ, Itani KMF, Schweizer ML et al. Risk of surgical site infection, acute kidney injury, and Clostridium difficile infection following antibiotic prophylaxis with vancomycin plus a beta-lactam versus either drug alone: A national propensity-score-adjusted retrospective cohort study. PLoS Med 14 (2017): 1002340, doi: 10.1371/journal.pmed.1002340.

68. Cranny G, Elliott R, Weatherly H, Chambers D, Hawkins N et al. A systematic review and economic model of switching from non-glycopeptide to glycopeptide antibiotic prophylaxis for surgery. Health Technol Assess 12 (2008): 1-147, doi: 10.3310/hta12010

69. Vaudaux P, Ferry T, Uçkay I, François P, Schrenzel J et al. Prevalence of isolates with reduced glycopeptide susceptibility in orthopedic device-related infections due to methicillin-resistant Staphylococcus aureus. Eur J Clin Microbiol Infect Dis 31 (2012): 3367-3374, doi: 10.1007/s10096-012-1705-8.