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Microorganisms
Special Issues
Challenges of Biofilm-Associated Bone and Joint Infections
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Challenges of Biofilm-Associated Bone and Joint Infections

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Biofilm".

Deadline for manuscript submissions: 31 January 2026 | Viewed by 7173

Special Issue Editors

Dr. Christof Berberich

E-Mail Website
Guest Editor
JDepartment of Medical Training, Heraeus Medical GmbH, 612173 Wehrheim, Germany
Interests: bacterial biofilm
Dr. Jaime Esteban

E-Mail Website
Guest Editor
Departamento de Microbiología Clínica, Universitario Fundación Jiménez Díaz, 28040 Madrid, Spain
Interests: clinical microbiology; biofilms; mycobacteria; implant-associated infections
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The incidence of bone and joint infections is increasing owing to factors such as ageing of the global population, higher prevalence of patient comorbidities, and growing numbers of surgical procedures with the incorporation of foreign materials. However, appropriate diagnosis and treatment remains a challenge due to the presence of biofilms on implants. Bone and joint infections include sequelae such as septic arthritis, osteomyelitis, infections after fracture repair or after endoprosthetic replacement of a joint, and spinal infections. Although guidelines and recommendations exist, solid evidence is still lacking in many aspects of the diagnostic, preventive, and therapeutic framework. This also refers to the use of local antibiotics, which have the potential advantage of delivering high concentrations directly at the infected situs while reducing the burden of long-lasting systemic antimicrobial therapy.

Interdisciplinary case discussions among orthopaedic and trauma surgeons, infectious disease specialists, microbiologists, pathologists, plastic surgeons, and other disciplines have been reported to improve the likelihood of good clinical outcomes of bone and joint infections. This not only relates to the eradication of the pathogens but also to the relief of pain and restoration of limb and joint function.

We would like to invite esteemed researchers and clinicians to contribute to this Special Issue with the objective of advancing our knowledge and expanding our perspectives on the prevention, diagnosis, and management of bone and joint infections. We also aim to capture a global perspective, since we are aware that the pathogen environment, the diagnostic algorithms, and the therapeutic options do widely differ between the countries and the continents.

Dr. Christof Berberich
Dr. Jaime Esteban
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Microorganisms is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • diagnostics
  • prevention
  • antibiotic

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Published Papers (7 papers)

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Research

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10 pages, 240 KB  
Article
The Impact of Antibiotic Therapy Options and Multidisciplinary Approach in Prosthetic Joint Infections
by João Lucas, José Queirós, Daniel Soares, André Carvalho, Filipa Pereira, Cláudia Santos, Ricardo Sousa and Miguel Araújo Abreu
Microorganisms 2025, 13(10), 2241; https://doi.org/10.3390/microorganisms13102241 - 24 Sep 2025
Viewed by 352
Abstract
Periprosthetic joint infection (PJI) remains one of the most challenging complications of arthroplasty. Optimal antibiotic strategies and the role of multidisciplinary teams (MDT) are not fully defined. We retrospectively analyzed 86 PJI surgical procedures performed between 2017 and 2023 at a tertiary referral [...] Read more.
Periprosthetic joint infection (PJI) remains one of the most challenging complications of arthroplasty. Optimal antibiotic strategies and the role of multidisciplinary teams (MDT) are not fully defined. We retrospectively analyzed 86 PJI surgical procedures performed between 2017 and 2023 at a tertiary referral center. Clinical data, microbiology, surgical strategy (debridement, antibiotics, and implant retention -DAIR, one-stage, two-stage) and antibiotic regimens were collected. Outcomes were compared across antibiotic classes and treatment teams: orthopaedics alone, orthopaedics with MDT input, and a dedicated MDT (GRIP). Success was defined as infection-free survival without further surgery. Median patient age was 70 years, with high comorbidity and predominance of Gram-positive, monomicrobial infections. Rifampicin-based regimens were associated with higher cure rates than non-anti-biofilm therapy (OR 4.9, 95% CI 1.4–17.8). Flucloxacillin plus rifampicin achieved outcomes comparable to rifampicin–fluoroquinolone combinations. The strongest predictor of success was MDT involvement: in DAIR procedures, cure reached 100% with MDT versus 48% with orthopaedics alone (p = 0.025). Outcomes were similar between teams in one- and two-stage revisions. In this cohort, rifampicin-based therapy improved outcomes in staphylococcal PJI, and flucloxacillin was a valid alternative partner drug. Crucially, MDT management—particularly in DAIR—was associated with superior results. These findings highlight the value of structured multidisciplinary PJI care pathways alongside optimised antibiotic strategies. Full article
(This article belongs to the Special Issue Challenges of Biofilm-Associated Bone and Joint Infections)
16 pages, 1351 KB  
Article
A Comparative Study of Extended Gentamicin and Tobramycin Release and Antibacterial Efficacy from Palacos and Simplex Acrylic Cements
by Débora Coraça-Huber, Martina Humez and Klaus-Dieter Kühn
Microorganisms 2025, 13(9), 2174; https://doi.org/10.3390/microorganisms13092174 - 17 Sep 2025
Viewed by 593
Abstract
Antibiotic-loaded bone cements (ALBCs) are used to prevent and treat periprosthetic joint infections (PJI). This study compares the in vitro release and antibacterial effectiveness of gentamicin from Palacos® R+G and tobramycin from Simplex® T. Standardized cylindrical specimens of Palacos® R+G [...] Read more.
Antibiotic-loaded bone cements (ALBCs) are used to prevent and treat periprosthetic joint infections (PJI). This study compares the in vitro release and antibacterial effectiveness of gentamicin from Palacos® R+G and tobramycin from Simplex® T. Standardized cylindrical specimens of Palacos® R+G and Simplex® T were incubated in phosphate-buffered saline. Antibiotic release was quantified using high-performance liquid chromatography (HPLC) over 14 and 42 days. Antibacterial efficacy was assessed using inhibition zone tests (IZT) against Staphylococcus aureus, Staphylococcus epidermidis, and Escherichia coli over 42 days. Palacos® R+G exhibited a significantly higher and more sustained antibiotic release of gentamicin compared to tobramycin from Simplex® T. The cumulative release of gentamicin from Palacos® R+G was 1.148 µg/cm2, while Simplex® T released 198.87 µg/cm2 tobramycin over 14 days. Inhibition zone tests showed that Palacos® R+G maintained antibacterial activity for 42 days, while Simplex® T’s activity diminished after 14 days. Statistical analysis confirmed significant differences in antibacterial efficacy between the two cements. Palacos® R+G demonstrated superior gentamicin release and sustained antibacterial activity compared to tobramycin from Simplex® T. These findings suggest that Palacos® R+G may offer better clinical outcomes in preventing and treating PJIs. Full article
(This article belongs to the Special Issue Challenges of Biofilm-Associated Bone and Joint Infections)
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13 pages, 1677 KB  
Article
A Single Tertiary-Care Center Case Series Using Vertical Rectus Abdominis Myocutaneous Flap in the Management of Complex Periprosthetic Joint Infection of the Hip
by Omar Salem, Jing Zhang, George Grammatopoulos, Simon Garceau and Hesham Abdelbary
Microorganisms 2025, 13(8), 1962; https://doi.org/10.3390/microorganisms13081962 - 21 Aug 2025
Viewed by 520
Abstract
Prosthetic joint infections (PJIs) pose significant challenges, often requiring multiple surgeries that lead to soft tissue loss, dead space, and fibrosis. Wound breakdown increases the risk of polymicrobial infection and treatment failure. The vertical rectus abdominis myocutaneous (VRAM) flap is a proven method [...] Read more.
Prosthetic joint infections (PJIs) pose significant challenges, often requiring multiple surgeries that lead to soft tissue loss, dead space, and fibrosis. Wound breakdown increases the risk of polymicrobial infection and treatment failure. The vertical rectus abdominis myocutaneous (VRAM) flap is a proven method for complex wound coverage, but its role in managing hip PJI is underexplored. This study evaluates outcomes of VRAM flap reconstruction in polymicrobial hip PJI. We retrospectively reviewed five patients who underwent VRAM flap reconstruction for polymicrobial hip PJI between December 2020 and December 2023. Primary outcomes included flap survival, infection control, and wound healing. Secondary outcomes were implant retention, postoperative complications, and functional status. At a mean follow-up of 28 months, four patients achieved wound healing and remained infection-free, while one had persistent sinus drainage but retained the implant. Flap survival was 100%, with no necrosis or failure. No major complications requiring reoperation occurred. Two patients developed deep collections, managed with ultrasound-guided drainage (Clavien-Dindo IIIa). Minor complications included donor-site dehiscence (three), flap dehiscence (one), edge necrosis (two), and hernias (two), all managed non-surgically (Clavien-Dindo I/II). All patients retained implants and remained ambulatory. VRAM flap reconstruction is a reliable option for managing complex polymicrobial hip PJI. Flap survival was excellent, and most patients achieved infection control. However, persistent infection and the need for suppressive antibiotics highlight the ongoing challenges in these cases. Full article
(This article belongs to the Special Issue Challenges of Biofilm-Associated Bone and Joint Infections)
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12 pages, 217 KB  
Article
Polymicrobial Prosthetic Joint Infections: Unraveling Risk Factors and Outcomes in a Single-Center Study
by Álvaro Auñón, Ignacio Ortiz, Salvador Peñarrubia, Carmen Álvaro, Estíbaliz Torrecilla-Sádaba, Joaquin Garcia-Cañete and Jaime Esteban
Microorganisms 2025, 13(7), 1679; https://doi.org/10.3390/microorganisms13071679 - 16 Jul 2025
Viewed by 958
Abstract
Periprosthetic joint infection (PJI) is a serious complication after joint arthroplasty, with polymicrobial PJIs representing a distinct subset associated with worse outcomes. This study aims to characterize the risk factors, microbiological profiles, and clinical outcomes of polymicrobial PJIs in a single tertiary care [...] Read more.
Periprosthetic joint infection (PJI) is a serious complication after joint arthroplasty, with polymicrobial PJIs representing a distinct subset associated with worse outcomes. This study aims to characterize the risk factors, microbiological profiles, and clinical outcomes of polymicrobial PJIs in a single tertiary care center. A retrospective analysis was conducted on 499 patients diagnosed with PJI between 2010 and 2023. Polymicrobial infection was defined by isolation of ≥2 distinct pathogens from intraoperative samples. Demographic, microbiological, and clinical data were analyzed. Treatment success was defined as infection eradication without recurrence or chronic suppressive therapy. Polymicrobial PJIs accounted for 18.2% of cases. Patients with polymicrobial infections had higher rates of obesity, insulin-dependent diabetes, and higher Charlson comorbidity scores. Coagulase-negative staphylococci and gram-negative bacilli were more frequently isolated in polymicrobial infections, while S. aureus predominated in monomicrobial cases. Treatment success rates were significantly lower in polymicrobial infections, both in acute (61.5% vs. 94.5%, p = 0.003) and chronic settings (51.3% vs. 75.3%, p = 0.02). Polymicrobial PJIs are associated with distinct microbiological patterns, increased comorbidity burden, and significantly worse clinical outcomes. Recognition of specific risk factors and pathogen profiles is essential to optimize management strategies for this complex condition. Full article
(This article belongs to the Special Issue Challenges of Biofilm-Associated Bone and Joint Infections)
9 pages, 224 KB  
Communication
Clinical Outcome of Patients with Acute Periprosthetic Joint Infections Caused by Pseudomonas aeruginosa Compared to Other Gram-Negative Bacilli
by Wai-Yan Liu, Johannes G. E. Hendriks, Robin W. T. M. van Kempen, Walter van der Weegen, Wim H. C. Rijnen, Jon H. M. Goosen, Babette C. van der Zwaard, Yvette Pronk, Wierd P. Zijlstra, Bas L. E. F. ten Have, Joris J. W. Ploegmakers and Marjan Wouthuyzen-Bakker
Microorganisms 2025, 13(4), 904; https://doi.org/10.3390/microorganisms13040904 - 14 Apr 2025
Viewed by 1016
Abstract
Pseudomonas aeruginosa is considered as more difficult to treat than other Gram-negatives in patients with acute periprosthetic joint infections (PJIs). However, clinical data to support this hypothesis are lacking. This retrospective multicenter cohort study included 39 patients with acute PJIs caused by P. [...] Read more.
Pseudomonas aeruginosa is considered as more difficult to treat than other Gram-negatives in patients with acute periprosthetic joint infections (PJIs). However, clinical data to support this hypothesis are lacking. This retrospective multicenter cohort study included 39 patients with acute PJIs caused by P. aeruginosa and 84 control patients with another Gram-negative bacillus (i.e., Enterobacterales). Both groups were managed by surgical debridement, antibiotics, and implant retention (DAIR). Treatment failure within one-year follow-up was defined as prosthesis extraction, a clinical need for suppressive antibiotic treatment and/or PJI-related death. Distribution of affected joints, and revision versus primary arthroplasties, did not differ between groups. Most PJIs were polymicrobial (87% in cases, 81% in control patients, p = 0.451). Surgical and antibiotic management was similar between groups. Treatment failure did not differ between groups: 5/39 cases (12.8%) and 14/84 control patients (16.7%, p = 0.610). An acceptable success rate of acute PJI caused by P. aeruginosa when treated with DAIR was observed. This success rate did not differ compared to PJIs caused by Enterobacterales. Therefore, P. aeruginosa should not be considered a more difficult to treat microorganism compared to other Gram-negatives. No additional surgical or antimicrobial interventions are needed when patients can be treated with a fluoroquinolone. Full article
(This article belongs to the Special Issue Challenges of Biofilm-Associated Bone and Joint Infections)
13 pages, 977 KB  
Article
Saponin Improves Recovery of Bacteria from Orthopaedic Implants for Enhanced Diagnosis Ex Vivo
by Tiziano Angelo Schweizer, Adrian Egli, Philipp P. Bosshard and Yvonne Achermann
Microorganisms 2025, 13(4), 836; https://doi.org/10.3390/microorganisms13040836 - 7 Apr 2025
Viewed by 713
Abstract
Biofilm formation on orthopedic joint implants complicates diagnosis of periprosthetic joint infections (PJIs). Sonication of explanted orthopedic implants for diagnostic enhances pathogen detection, but it shows limitations in sensitivity and handling. We investigated whether the biosurfactant saponin could improve bacterial recovery from orthopaedic [...] Read more.
Biofilm formation on orthopedic joint implants complicates diagnosis of periprosthetic joint infections (PJIs). Sonication of explanted orthopedic implants for diagnostic enhances pathogen detection, but it shows limitations in sensitivity and handling. We investigated whether the biosurfactant saponin could improve bacterial recovery from orthopaedic implants and thereby enhance infection diagnosis ex vivo. Orthopaedic material discs of 1 cm diameter were contaminated with different clinical bacterial PJI isolates. Biofilms of Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, Cutibacterium avidum, and Cutibacterium acnes were grown on the discs, which were then treated with either saline solution or various concentrations of saponin. Next, the discs were vortexed or sonicated. Colony-forming units (CFUs) enumeration and time-to-positivity of liquid cultures were determined. Additionally, a novel 3D PJI soft tissue in vitro model was established to validate these findings in a more representative scenario. Median CFU enumeration showed that 0.001% (w/v) saponin as compared to saline solution increased CFUs recovery by 2.2 log10 for S. epidermidis, 0.6 log10 for S. aureus, 0.6 log10 for C. avidum, 1.1 log10 for C. acnes, and 0.01 log10 for E. coli. Furthermore, saponin treatment resulted in a >1 log10 increase in S. epidermidis CFU recovery from implants in the 3D tissue model compared to standard saline sonication. With that, we propose a novel two-component kit, consisting of a saponin solution and a specialized transportation box, for the efficient collection, transportation, and processing of potentially infected implants. Our data suggest that biosurfactants can enhance bacterial recovery from artificially contaminated orthopedic implants, potentially improving the diagnosis of PJIs. Full article
(This article belongs to the Special Issue Challenges of Biofilm-Associated Bone and Joint Infections)
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Review

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28 pages, 400 KB  
Review
Emerging Concepts for the Treatment of Biofilm-Associated Bone and Joint Infections with IV Fosfomycin: A Literature Review
by Sara Tedeschi, Efthymia Giannitsioti and Christian Mayer
Microorganisms 2025, 13(5), 963; https://doi.org/10.3390/microorganisms13050963 - 23 Apr 2025
Cited by 2 | Viewed by 2388
Abstract
Due to the involvement of biofilms in the pathogenesis of bone and joint infections (BJI), the treatment of these infections is often challenging, especially when multidrug- or extensively drug-resistant (MDR/XDR) pathogens are involved. Intravenous fosfomycin (FOS) is a phosphoenolpyruvate analogue with a unique [...] Read more.
Due to the involvement of biofilms in the pathogenesis of bone and joint infections (BJI), the treatment of these infections is often challenging, especially when multidrug- or extensively drug-resistant (MDR/XDR) pathogens are involved. Intravenous fosfomycin (FOS) is a phosphoenolpyruvate analogue with a unique mode of action and broad-spectrum activity against both Gram-positive (GP) and Gram-negative (GN) pathogens. It is used in various severe and deep-seated infections, including BJIs. This review article focuses on preclinical and clinical data surrounding the use of FOS for biofilm-related BJIs. Data from several in vitro and animal models of infection demonstrated that FOS, especially in combination with other antibiotics, is effective against biofilms of (methicillin-resistant) Staphylococcus spp., (vancomycin-resistant) Enterococcus spp., carbapenem-resistant and extended-spectrum beta-lactamase-producing Enterobacterales, and MDR Pseudomonas aeruginosa. Data from clinical studies, mostly retrospective observational studies and case reports/case series, revealed that FOS was typically used in combination with other antibiotics for the treatment of various BJI, including acute and chronic osteomyelitis, prosthetic joint infections, and fracture-related infections, in adult and pediatric patients. Success rates often exceeded 80%. FOS exhibits good and fast penetration into bone tissue and is generally well tolerated, with only a few adverse drug reactions, such as gastrointestinal disorders and electrolyte imbalances. Collectively, the data indicate that FOS is a valuable option as part of combination regimens for the treatment of BJIs caused by both GP and GN bacteria. Full article
(This article belongs to the Special Issue Challenges of Biofilm-Associated Bone and Joint Infections)
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