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Antibiotic Therapy in Implant Related Orthopedic Infections

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A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Antibiotics Use and Antimicrobial Stewardship".

Deadline for manuscript submissions: 15 September 2024 | Viewed by 19016

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Special Issue Editor

Dr. Heinz Winkler

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Guest Editor

Osteitis Centre, Privatklinik Döbling, 1190 Vienna, Austria
Interests: total joint replacement; infection; biofilm

Special Issue Information

Dear Colleagues,

Total joint replacement (TJR) and the internal fixation of fractures (ORIF) have been among the most successful surgical interventions in recent decades; millions of implants each year provide relief to millions of affected patients. However, complications may occur, among which bacterial infection is considered the most difficult to treat. Given the estimated 1.0% to 2.5% annual incidence of prosthetic joint infection (PJI) and even the higher incidences after ORIF, implant-related infections (IRI) continue to pose a challenge and place a substantial burden on patients, surgeons, and the healthcare system. Diagnosis is not always straightforward and in chronic cases requires a combination of different diagnostic tools. Usually, some kind of surgical intervention is unavoidable, whereas revisions may be implant-sparing in early infection but may become very complex in chronic ones. Meanwhile, it has become widely accepted that at least chronic cases (persisting for longer than 6 weeks) can be mediated by biofilms, while they cannot be eradicated with conventional antibiotic therapy. The removal of an implant is mandatory for cure, whereas there is ongoing debate around whether re-implantation should be executed in a single- or multi-stage approach. Concomitant antibiotic therapy should be tailored to the causal pathogens at play, both locally and systemically. The complexity and extended length of the treatment pathway for IRI highlights it as an area for research to identify the most clinically and cost-effective interventions. With this Special Issue, we intend to provide up-to-date information on the most recent developments, presented by the most experienced experts in the field of IRI.

Dr. Heinz Winkler
Guest Editor

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Keywords

total joint replacement infection
biofilm
antibiotics resistance tolerance MIC
MBEC

Published Papers (9 papers)

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Research

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10 pages, 228 KiB

Open AccessArticle

Evaluating the Clinical Relevance of Routine Sonication for Periprosthetic Hip or Knee Joint Infection Diagnosis

by Anas Zouitni, Jakob van Oldenrijk, P. Koen Bos, Peter D. Croughs, Erlangga Yusuf and Ewout S. Veltman

Antibiotics 2024, 13(4), 366; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics13040366 - 17 Apr 2024

Viewed by 142

Abstract

Periprosthetic joint infection (PJI) is a serious complication after joint arthroplasty. PJI screening and conventional cultures may be inconclusive. Sonication fluid culturing stands out as a valuable adjunct technique for PJI diagnosis. This study aims to determine the clinical relevance of routine sonication for all (a)septic revisions. All patients who underwent (partial) hip or knee revision arthroplasty between 2012 and 2021 were retrospectively reviewed. We formed three groups based on the European Bone and Joint Society PJI criteria: infection confirmed, likely, and unlikely. We analyzed clinical, laboratory, and radiological screening. Sensitivity and specificity were calculated for synovial fluid (preoperative), tissue, and sonication fluid cultures. We determined the clinical relevance of sonication as the percentage of patients for whom sonication confirmed PJI; 429 patients who underwent (partial) revision of hip or knee arthroplasty were included. Sensitivity and specificity were 69% and 99% for synovial fluid cultures, 76% and 92% for tissue cultures, and 80% and 89% for sonication fluid cultures, respectively. Sonication fluid cultures improved tissue culture sensitivity and specificity to 83% and 99%, respectively. In 11% of PJIs, sonication fluid cultures were decisive for diagnosis. This is applicable to acute and chronic infections. Sonication fluid cultures enhanced the sensitivity and specificity of PJI diagnostics. In 11% of PJI cases, causative pathogens were confirmed by sonication fluid culture results. Sonication fluid culture should be performed in all revision arthroplasties. Full article

(This article belongs to the Special Issue Antibiotic Therapy in Implant Related Orthopedic Infections)

8 pages, 228 KiB

Open AccessArticle

What Is the Rate of Antimicrobial Resistance of a Prosthetic Joint Infection in a Major Orthopaedic Centre?

by Belgin Coskun, Müge Ayhan, Merve Bozer, Halil Ibrahim Ozaslan, Metin Dogan, Mustafa Citak and Mustafa Akkaya

Antibiotics 2024, 13(4), 306; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics13040306 - 28 Mar 2024

Viewed by 451

Abstract

Periprosthetic joint infections (PJIs) are important factors in decreasing the success of hip and knee arthroplasties. It is a necessity to explore the epidemiological data and develop applications for rational antibiotic use, to address future infection control concerns. We aimed to investigate the microorganisms that were responsible and the related antibiograms in 121 patients with PJI, who were managed by two-stage revision surgery. Patients’ data records, demographics, comorbidities, sites of arthroplasty, synovial fluid and deep tissue culture results and antibiotic treatment were summarized on a standardized case report form. There were 43 (35.5%) culture-negative PJI cases and 12 (9.9%) polymicrobial growths. The causative pathogens included Gram-positive (50.4%) and Gram-negative microorganisms (23.1%) and fungi (0.8%). Methicillin resistance was 64.3% for S. aureus and 89.5% for coagulase-negative staphylococcus (CoNS). The extended spectrum beta lactamase (ESBL) rate for Enterobacteriaceae was 68.4%. This study shows that antibiotic resistance is encountered in more than half of the cases, which is valid for all microorganisms most common in PJI. The success of treatment decreases significantly in cases where antibiotic-resistant microorganisms are isolated or in cases where the culture is negative. Full article

(This article belongs to the Special Issue Antibiotic Therapy in Implant Related Orthopedic Infections)

12 pages, 1423 KiB

Open AccessArticle

The Microbiological Profile and Antibiotic Susceptibility of Fracture Related Infections in a Low Resource Setting Differ from High Resource Settings: A Cohort Study from Cameroon

by Loïc Fonkoue, Elizabeth K. Tissingh, Michelle Tognia Ngouateu, Kennedy Olivier Muluem, Olivier Ngongang, Pretty Mbouyap, Perrin Ngougni Pokem, Kuetche Fotsing, Jean Bahebeck, Martin McNally and Olivier Cornu

Antibiotics 2024, 13(3), 236; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics13030236 - 04 Mar 2024

Viewed by 1243

Abstract

Fracture-related infection (FRI) is a common and devastating complication of orthopedic trauma in all settings. Data on the microbiological profile and susceptibility of FRI to antibiotics in low-income countries are scarce. Therefore, this study aimed to investigate the microbial patterns and antimicrobial susceptibility of FRI in a sub-Saharan African setting in order to provide guidance for the formulation of evidence-based empirical antimicrobial regimens. We conducted a retrospective analysis of patients treated for FRI with deep tissue sampling for microbiological culture from January 2016 to August 2023 in four tertiary-level hospitals in Yaoundé, Cameroon. There were 246 infection episodes in 217 patients. Cultures were positive in 209 (84.9%) cases and polymicrobial in 109 (44.3%) cases. A total of 363 microorganisms from 71 different species were identified, of which 239 (65.8%) were Gram-negative. The most commonly isolated pathogens were Staphylococcus aureus (n = 69; 19%), Enterobacter cloacae (n = 43; 11.8%), Klebsiella pneumoniae (n = 35; 9.6%), Escherichia coli (n = 35; 9.6%), and Pseudomonas aeruginosa (n = 27; 7.4%). Coagulase-negative staphylococci (CoNS) were isolated in only 21 (5.9%) cases. Gram-negative bacteria accounted for the majority of the infections in early (70.9%) and delayed (73.2%) FRI, but Gram-positive bacteria were prevalent in late FRI (51.7%) (p < 0.001). Polymicrobial infections were more frequent in the early (55.9%) and delayed (41.9%) groups than in the late group (27.6%) (p < 0.001). Apart from Staphylococcus aureus, there was no significant difference in the proportions of causative pathogens between early, delayed, and late FRI. This study found striking resistance rates of bacteria to commonly used antibiotics. MRSA accounted for 63% of cases. The most effective antibiotics for all Gram-positive bacteria were linezolid (96.4%), vancomycin (92.5%), clindamycin (85.3%), and fucidic acid (89.4%). For Gram-negative bacteria, only three antibiotics displayed a sensitivity >50%: amikacin (80.4%), imipenem (74.4%), and piperacillin + tazobactam (57%). The most effective empirical antibiotic therapy (with local availability) was the combination of vancomycin and amikacin or vancomycin and imipenem. In contrast to the literature from high-resource settings, this study revealed that in a sub-Saharan African context, Gram-negative bacteria are the most common causative microorganisms of FRI. This study revealed striking resistance rates to commonly used antibiotics, which will require urgent action to prevent antimicrobial resistance in low and middle-income countries. Full article

(This article belongs to the Special Issue Antibiotic Therapy in Implant Related Orthopedic Infections)

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10 pages, 587 KiB

Open AccessArticle

Soluble Urokinase Plasminogen Activator Receptor (SuPAR) Analysis for Diagnosis of Periprosthetic Joint Infection

by Sebastian M. Klim, Jürgen Prattes, Florian Amerstorfer, Tobias Niedrist, Christoph Zurl, Martin Stradner, Barbara Dreo, Gunther Glehr, Andreas Leithner, Mathias Glehr, Patrick Reinbacher, Patrick Sadoghi and Georg Hauer

Antibiotics 2024, 13(2), 179; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics13020179 - 12 Feb 2024

Viewed by 867

Abstract

Soluble urokinase plasminogen activator receptors (suPARs) are a biomarker for inflammatory diseases. This study aims to investigate its diagnostic properties regarding periprosthetic joint infections (PJI). This retrospective cohort study included adult patients who underwent joint puncture for suspected PJI. The presence of PJI was determined according to the criteria of the European Bone and Joint Infection Society (EBJIS). Laboratory study analyses included the determination of white blood cells (WBC) in whole blood, C-reactive protein (CRP) in blood plasma, and suPAR in both blood plasma and synovial fluid. Appropriate diagnostic cut-off values were identified utilizing Youden’s J, and their diagnostic performance was determined by calculating the positive (PPV) and negative predictive value (NPV) for each marker. Sixty-seven cases were included in the final analysis. Forty-three samples (64%) were identified as periprosthetic joint infection (PJI) and twenty-four specimen (36%) were PJI negative cases. The PPV and NPV were 0.80 and 0.70 for synovial suPAR, 0.86 and 0.55 for CRP, 0.84 and 0.31 for WBC and 1.00 and 0.31 for plasma suPAR. Synovial suPAR showed a solid diagnostic performance in this study and has the potential to be an alternative or complementary biomarker for PJI. Further investigations in larger patient collectives are indicated. Full article

(This article belongs to the Special Issue Antibiotic Therapy in Implant Related Orthopedic Infections)

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11 pages, 969 KiB

Open AccessArticle

Incidence of Rifampicin Resistance in Periprosthetic Joint Infection: A Single-Centre Cohort Study on 238 Patients

by Stergios Lazarinis, Nils P. Hailer, Josef D. Järhult and Anders Brüggemann

Antibiotics 2023, 12(10), 1499; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics12101499 - 30 Sep 2023

Cited by 1 | Viewed by 1197

Abstract

Background. Rifampicin is a pillar in the treatment of periprosthetic joint infection (PJI). However, rifampicin resistance is an increasing threat to PJI treatment. This study explores the incidence of rifampicin-resistant bacteria over time in a Swedish tertiary referral centre and the association of rifampicin resistance with infection-free survival after PJI. Methods. The study included 238 staphylococcal PJIs treated between 2001 and 2020 for which susceptibility data for rifampicin were available. Data on causative bacteria, rifampicin resistance, treatment, and outcome were obtained. Kaplan–Meier survival analysis and Cox regression modelling estimated the infection-free cumulative survival and adjusted hazard ratios (HRs) for the risk of treatment failure. Results. Rifampicin-resistant causative bacteria were identified in 40 cases (17%). The proportion of rifampicin-resistant agents decreased from 24% in 2010–2015 to 12% in 2016–2020. The 2-year infection-free survival rates were 78.6% (95% CI, 66.4–93.1%) for the rifampicin-resistant group and 90.0% (95% CI, 85.8–94.4%) for the rifampicin-sensitive group. Patients with PJI caused by rifampicin-resistant bacteria had an increased risk of treatment failure (adjusted HR, 4.2; 95% CI, 1.7–10.3). Conclusions. The incidence of PJI caused by rifampicin-resistant bacteria did not increase over the past 20 years. The risk of treatment failure in PJI caused by rifampicin-resistant bacteria is more than four times that caused by rifampicin-sensitive bacteria, highlighting the importance of limiting the development of rifampicin resistance. Full article

(This article belongs to the Special Issue Antibiotic Therapy in Implant Related Orthopedic Infections)

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18 pages, 1898 KiB

Open AccessArticle

Periprosthetic Joint Infection (PJI)—Results of One-Stage Revision with Antibiotic-Impregnated Cancellous Allograft Bone—A Retrospective Cohort Study

by Gregor Dersch and Heinz Winkler

Antibiotics 2022, 11(3), 310; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11030310 - 25 Feb 2022

Cited by 1 | Viewed by 2995

Abstract

Controversy exists regarding the optimal treatment of periprosthetic joint infection (PJI), considering control of infection, functional results as well as quality of life. Difficulties in treatment derive from the formation of biofilms within a few days after infection. Biofilms are tolerant to systemically applied antibiotics, requiring extreme concentrations for a prolonged period. Minimum biofilm eradicating concentrations (MBEC) are only feasible by the local application of antibiotics. One established approach is the use of allograft bone as a carrier, granting a sustained release of antibiotics in very high concentrations after appropriate impregnation. The purpose of this study was to determine the rate of reinfection after a one-stage revision of infected hip or knee prostheses, using antibiotic-impregnated allograft bone as the carrier and avoiding cement. Between 1 January 2004 and 31 January 2018, 87 patients with PJI, according to MSIS, underwent a one-stage revision with antibiotic-impregnated cancellous allograft bone. An amount of 17 patients had insufficient follow-ups. There were 70 remaining patients (34 male, 36 female) with a mean follow-up of 5.6 years (range 2–15.6) and with a mean age of 68.2 years (range 31.5–86.9). An amount of 38 hips and 11 knees were implanted without any cement; and 21 knees were implanted with moderate cementing at the articular surface with stems always being uncemented. Within 2 years after surgery, 6 out of 70 patients (8.6%, CI 2–15.1) showed reinfection and after more than 2 years, an additional 6 patients showed late-onset infection. Within 2 years after surgery, 11 out of 70 patients (15.7%, CI 7.2–24.2) had an implant failure for any reason (including infection) and after more than 2 years, an additional 7 patients had an implant failure. Using Kaplan-Meier analysis for all 87 patients, the estimated survival for reinfection was 93.9% (CI 88.8–99.1) at 1 year, 89.9% (CI 83.2–96.6) at 2 years and 81.5% (CI 72.1–90.9) at 5 years. The estimated survival for implant failure for any reason was 90.4% (CI 84.1–96.7) at 1 year, 80.9% (CI 72.2–89.7) at 2 years and 71.1% (CI 60.3–81.8) at 5 years. One-stage revision with antibiotic-impregnated cancellous allograft bone grants comparable results regarding infection control as with multiple stages, while shortening rehabilitation, improving quality of life for the patients and reducing costs for the health care system. Full article

(This article belongs to the Special Issue Antibiotic Therapy in Implant Related Orthopedic Infections)

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12 pages, 2821 KiB

Open AccessArticle

High Cefuroxime Concentrations and Long Elimination in an Orthopaedic Surgical Deadspace—A Microdialysis Porcine Study

by Sara Kousgaard Tøstesen, Maiken Stilling, Pelle Hanberg, Theis Muncholm Thillemann, Thomas Falstie-Jensen, Mikkel Tøttrup, Martin Knudsen, Emil Toft Petersen and Mats Bue

Antibiotics 2022, 11(2), 208; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11020208 - 07 Feb 2022

Cited by 2 | Viewed by 2287

Abstract

Deadspace is the tissue and bony defect in a surgical wound after closure. This space is presumably poorly perfused favouring bacterial proliferation and biofilm formation. In arthroplasty surgery, an obligate deadspace surrounding the prosthesis is introduced and deadspace management, in combination with obtaining therapeutic prophylactic antibiotic concentrations, is important for limiting the risk of acquiring a periprosthetic joint infection (PJI). This study aimed to investigate cefuroxime distribution to an orthopaedic surgical deadspace in comparison with plasma and bone concentrations during two dosing intervals (8 h × 2). In a setup imitating shoulder arthroplasty surgery, but without insertion of a prosthesis, microdialysis catheters were placed for cefuroxime sampling in a deadspace in the glenohumeral joint and in cancellous bone of the scapular neck in eighteen pigs. Blood samples were collected as a reference. Cefuroxime was administered according to weight (20 mg/kg). The primary endpoint was time above the cefuroxime minimal inhibitory concentration of the free fraction of cefuroxime for Staphylococcus aureus (fT > MIC (4 μg/mL)). During the two dosing intervals, mean fT > MIC (4 μg/mL) was significantly longer in deadspace (605 min) compared with plasma (284 min) and bone (334 min). For deadspace, the mean time to reach 4 μg/mL was prolonged from the first dosing interval (8 min) to the second dosing interval (21 min), while the peak drug concentration was lower and half-life was longer in the second dosing interval. In conclusion, weight-adjusted cefuroxime fT > MIC (4 μg/mL) and elimination from the deadspace was longer in comparison to plasma and bone. Our results suggest a deadspace consolidation and a longer diffusions distance, resulting in a low cefuroxime turn-over. Based on theoretical targets, cefuroxime appears to be an appropriate prophylactic drug for the prevention of PJI. Full article

(This article belongs to the Special Issue Antibiotic Therapy in Implant Related Orthopedic Infections)

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14 pages, 1456 KiB

Open AccessArticle

Experiences during Switching from Two-Stage to One-Stage Revision Arthroplasty for Chronic Total Knee Arthroplasty Infection

by Guillem Navarro, Luis Lozano, Sergi Sastre, Rosa Bori, Jordi Bosch and Guillem Bori

Antibiotics 2021, 10(12), 1436; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10121436 - 24 Nov 2021

Cited by 2 | Viewed by 1719

Abstract

The objective of this study was to evaluate our preliminary results after changing our surgical strategy from 2-stage revision arthroplasty to 1-stage revision arthroplasty for patients with chronic knee periprosthetic joint infection. We conducted a prospective study of knee arthroplasty patients that had been diagnosed with chronic infection and treated using a 1-stage revision regardless of the traditional criteria applied for indication thereof. We evaluated two main variables: infection control and economic costs. The definitive diagnosis of infection of the revision was determined by using the criteria proposed by the Musculoskeletal Infection Society. The costs were calculated as average costs in USD, as described by Srivastava (2019), for 1-stage or 2-stage revisions. Eighteen patients were included in the study, and infection was controlled in 17 patients. The total economic savings for our hospital from these 18 patients amounted to USD 291,152. This clinical success has led to major changes in how our hospital approaches the treatment of chronically infected knee replacements, in addition to substantial economic advantages for the hospital. Full article

(This article belongs to the Special Issue Antibiotic Therapy in Implant Related Orthopedic Infections)

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Review

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21 pages, 772 KiB

Open AccessReview

Antibiotic Therapy for Prosthetic Joint Infections: An Overview

by Benjamin Le Vavasseur and Valérie Zeller

Antibiotics 2022, 11(4), 486; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11040486 - 05 Apr 2022

Cited by 24 | Viewed by 6889

Abstract

Prosthetic joint infection (PJI) is a severe complication after arthroplasty. Its management combines surgical intervention, whose type depends on the clinical situation, and prolonged high-dose antibiotics adapted to the responsible microorganism(s) and the patient. Antibiotics are only one part of the therapeutic regimen and are closely related to the surgical strategy. Their efficacy depends to a large extent on the choice and quality of the surgical procedure, and the quality of the microbiological diagnosis. Although guidelines have been published, many aspects of antibiotic therapy remain poorly established. Choosing the optimal agent(s) is one aspect, with others being optimization of drugs’ pharmacokinetic/pharmacodynamic parameters, the choice of administration route, use of monotherapy or combination regimens, therapeutic drug-monitoring and patient education to improve compliance and tolerance. Herein, we address PJI management based on recent literature data, guidelines and the experience of our referral center for complex bone-and-joint infections. Full article

(This article belongs to the Special Issue Antibiotic Therapy in Implant Related Orthopedic Infections)

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