Aims. Gram-negative periprosthetic joint infection (PJI) has been poorly studied despite its rapidly increasing incidence. Treatment with one-stage revision using intra-articular (IA) infusion of antibiotics may offer a reasonable alternative with a distinct advantage of providing a means of delivering the drug in high concentrations. Carbapenems are regarded as the last line of defense against severe Gram-negative or polymicrobial infection. This study presents the results of one-stage revision using intra-articular carbapenem infusion for treating Gram-negative PJI, and analyzes the characteristics of bacteria distribution and drug sensitivity. Methods. We retrospectively reviewed 32 patients (22 hips and 11 knees) who underwent single-stage revision combined with IA carbapenem infusion between November 2013 and March 2020. The IA and intravenous (IV) carbapenem infusions were administered for a single Gram-negative infection, and IV vancomycin combined with IA carbapenems and vancomycin was applied for polymicrobial infection including Gram-negative bacteria. The bacterial community distribution, drug sensitivity, infection control rate, functional recovery, and complications were evaluated. Reinfection or death caused by PJI was regarded as a treatment failure. Results. Gram-negative PJI was mainly caused by Escherichia coli (8/34), Enterobacter cloacae (7/34), and Klebsiella pneumoniae (5/34). Seven cases (7/32) involved polymicrobial PJIs. The resistance rates of penicillin, cephalosporin, quinolones, and sulfonamides were > 10%, and all penicillin and partial cephalosporins (first and second generation) were > 30%. Of 32 cases, treatment failed to eradicate infection in only three cases (9.4%), at a mean follow-up of 55.1 months (SD 25 to 90). The mean postoperative Harris Hip Score and Hospital for Special Surgery knee score at the most recent follow-up were 81 (62 to 91) and 79 (56 to 89), respectively. One patient developed a fistula, and another presented with a local rash on an infected joint. Conclusion. The use of IA carbapenem delivered alongside one-stage revision effectively controlled Gram-negative infection and obtained acceptable clinical outcomes with few complications. Notably, first- and second-generation cephalosporins and penicillin should be administrated with caution, due to a high incidence of resistance. Cite this article: Bone Joint J 2023;105-B(3):284–293

The management of post-traumatic bone infections relies on antibiotic therapy and surgical debridement. Antibiotic concentration in infected bone is a major determinant of response to medical treatment.

The aim is to assess glycopeptides, fluoroquinolones and carbapenems diffusion in infected human bone, since they are widely used for treating bone infections.

Twenty-four patients with septic pseudoarthrosis undergoing surgical debridement and treated with glycopeptides/fluoroquinolones/carbapenems iv for > 1 week were studied. Plasma and bone specimens were collected intraoperatively at a mean of 4.8h after antibiotic administration. Antibiotic concentrations were measured by the HPLC-UV method.

Five patients received vancomycin: mean bone concentrations were 2.4mg/L in cortical and 7.1mg/L in cancellous bone, with a bone/plasma extraction of 12% and 36%, respectively.

Nine patients were treated with teicoplanin: bone concentrations were 2.5mg/L for cortical and 8.3mg/L for cancellous bone (14% and 46% of plasma levels).

Five patients received a fluoroquinolone. Ciprofloxacin concentrations were 1.8mg/L in cortical bone and 30.2mg/L in cancellous and newly formed bone (respective bone/plasma ratios 1.06 and 8.4). Levofloxacin concentrations were 0.3 and 2.69mg/L in cortical and cancellous bone, with diffusion rates of 12% and 108%, respectively.

Five patients received a carbapenem. Imipenem diffusion rates were respectively 7.5% and 58.3% for cortical and cancellous bone (bone concentrations 0.09 mg/L and 0.7 mg/L). Meropenem levels were 1.2 mg/L and 5.2 mg/L in cortical and cancellous bone, with respective diffusion rates of 3.6% and 15%.

Both glycopeptides provided concentrations exceeding the MIC of infecting agents, with satisfactory bone diffusion. Fluoroquinolones, especially ciprofloxacin, displayed excellent diffusion. Ciprofloxacin concentrations in cancellous and new bone were far higher than in plasma, suggesting accumulation into highly vascularized tissue. Imipenem had better diffusion than meropenem, but bone levels were under the MIC of susceptible agents. Glicopeptides and fluoroquinolones appear excellent options for bone infections, while carbapenems should be a second choice treatment.

Aim. Gram negative bacteria (GNB) are emerging pathogens in chronic post-traumatic osteomyelitis. However, data on multi-drug (MDR) and extensively drug resistant (XDR) GNB are sparse. Methods. A multi-centre epidemiological study was performed in 10 countries by members of the ESGIAI (ESCMID Study Group on Implant Associated Infections). Osteosynthesis-associated osteomyelitis (OAO) of the lower extremities and MDR/XDR GNB were defined according to international guidelines. Data from 2000 to 2015 on demographics, clinical features, microbiology, surgical treatment and antimicrobial therapy were retrospectively analyzed. Cure was assessed after the end of treatment as the absence of any sign relevant to OAO. Factors associated with cure were evaluated by regression analysis. Results. A total of 53 infections of OAO of the lower extremities (hip, femur, tibia) were evaluated. Patients were female (n=32, 60.4%), with a mean age (SD) 57(3) years, history of trauma (83%), comorbidities (26.4%). The most frequent GNB were: E.coli (n=15), P.aeruginosa (n=14), Klebsiella spp (n=8), Enterobacter spp (n=8) and Acinetobacter spp (n=5). P.aeruginosa predominated the XDR group than the MDR one (n=6/10 vs n=8/43, p=0.01). Antibiotics were given mostly in combinations (64%) for a median duration of 117 days (SD:31.5). Carbapenems were the most frequently used agents (54.7%), followed by colistin (18.8%) and fluoroquinolones (15%). Surgical treatment included debridement with implant retention (n=22), implant explantation (n=22), new osteosynthesis (n=3), others(n=6). Only failure of the surgical treatment for OAO was associated with lack of cure [OR 8.924 (CI95%: 3.006–26.495), p<0.001] at the end of treatment, for a 12-month follow-up period. Patients' age, gender, comorbidities, history of trauma and surgery, clinical presentation of OAO, type of antimicrobial treatment (use of fluoroquinolones, carbapenems or colistin as monotherapy or in combination) as well as type of surgical intervention (explantation vs implant retention) were not found to significantly influence the patients' outcome. Overall, cure was assessed in 31 patients (58.5%). Death occurred in 7 patients, all older than 60, with failure of surgical treatment (p=0.016). These patients presented with many comorbidities (57%) and without difference in treatment outcome between XDR and MDR infection (p=0.114). Conclusion. Osteosynthesis-associated infections of the lower extremities caused by MDR/XDR GNB are a severe complication in orthopaedic surgery. The role of surgical treatment is independently associated with outcome regardless of the type of intervention (explantation or implant retention) and the type of antimicrobial treatment

Aims

The optimum type of antibiotics and their administration route for treating Gram-negative (GN) periprosthetic joint infection (PJI) remain controversial. This study aimed to determine the GN bacterial species and antibacterial resistance rates related to clinical GN-PJI, and to determine the efficacy and safety of intra-articular (IA) antibiotic injection after one-stage revision in a GN pathogen-induced PJI rat model of total knee arthroplasty.

Objectives

Thermal stability is a key property in determining the suitability of an antibiotic agent for local application in the treatment of orthopaedic infections. Despite the fact that long-term therapy is a stated goal of novel local delivery carriers, data describing thermal stability over a long period are scarce, and studies that avoid interference from specific carrier materials are absent from the orthopaedic literature.

Prophylactic antibiotics can decrease the risk of wound infection and have been routinely employed in orthopaedic surgery for decades. Despite their widespread use, questions still surround the selection of antibiotics for prophylaxis, timing and duration of administration. The health economic costs associated with wound infections are significant, and the judicious but appropriate use of antibiotics can reduce this risk.

This review examines the evidence behind commonly debated topics in antibiotic prophylaxis and highlights the uses and advantages of some commonly used antibiotics.

Cite this article: Bone Joint J 2016;98-B:1014–19.