Does local implantation of gentamicin impair renal function in patients undergoing surgery for chronic bone infection?

Background: The treatment of chronic bone infection often involves excision of dead bone and implantation of biomaterials which elute antibiotics. Gentamicin is a preferred drug for local delivery, but its systemic use carries a well-established risk of nephrotoxicity.  We aim to establish the risk of acute kidney injury (AKI) with local delivery in a ceramic carrier.Methods: 163 patients with Cierny-Mader type 3 or 4 chronic osteomyelitis had a single-stage operation including filling of the osseous defect with a calcium sulphate-hydroxyapatite carrier containing gentamicin. Mean gentamicin dosing was 191.3 mg (maximum 525 mg). Glomerular filtration rate (GFR) was calculated pre-operatively and during the first seven days post-operatively. Renal impairment was graded using the chronic kidney disease (CKD) staging system, and AKI was assessed using the RIFLE criteria.Results: 155 cases had adequate data to allow calculation of pre- and post-operative GFR. 7 had pre-existing renal disease. 70 patients (45.2%) had a temporary GFR drop post-operatively, with the greatest decrease occurring at a mean of 3.06 days following surgery. Twenty cases had a >10% decline in GFR, but 12 resolved within 7 days. 7 patients transiently fell into the “Risk” category according to RIFLE criteria, but no patient had a change consistent with “Injury”, “Failure” or “Loss” of renal function and none had clinical signs of new acute renal impairment post-operatively. Conclusions: Renal function is not significantly affected by local implantation of gentamicin up to 525 mg. The presence of pre-existing renal disease is not a contraindication to local gentamicin therapy.

Excisional treatment in women with cervical adenocarcinoma in situ (AIS): a prospective randomised controlled noninferiority trial to compare AIS persistence/recurrence after loop electrosurgical excision procedure with cold knife cone biopsy: protocol for a pilot study

Introduction: Adenocarcinoma in situ (AIS) of the uterine cervix is the precursor to invasive endocervical adenocarcinoma. An excisional biopsy such as a cold knife cone biopsy (CKC) should be performed to exclude invasive adenocarcinoma. Loop electrosurgical excision procedure (LEEP) is an alternative modality to CKC but is controversial in AIS. There is a perception that there is a greater likelihood of incomplete excision of AIS with LEEP because the depth of excised tissue tends to be smaller and the tissue margins may show thermal artefact which can interfere with pathology assessment. In the USA, guidelines recommend that any treatment modality can be used to excise AIS, provided that the specimen remains intact with interpretable margins. However, there are no high-quality studies comparing LEEP with CKC and well-designed prospective studies are needed. If such a study were to show that LEEP was non-inferior to CKC for the outcomes of post-treatment persistence, recurrence and adenocarcinoma, LEEP could be recommended as an appropriate treatment option for AIS in selected patients. This would benefit women because, unlike CKC, LEEP does not require general anaesthesia and may be associated with reduced morbidity. Methods and analysis: The proposed exploratory study is a parallel group trial with an allocation ratio of 2:1 in favour of the intervention (LEEP: CKC). Participants are women aged ≥18 to ≤45 years diagnosed with AIS on cervical screening and/or colposcopically directed biopsy in Australia and New Zealand, who are to receive excisional treatment in a tertiary level centre. Ethics and dissemination: Ethical approval for the study has been granted by the St John of God Healthcare Human Research Ethics Committee (reference number #1137)

Causative Pathogens Do Not Differ between Early, Delayed or Late Fracture-Related Infections

Fracture-related infections (FRIs) are classically considered to be early (0-2 weeks), delayed (3-10 weeks) or late (>10 weeks) based on hypothesized differences in causative pathogens and biofilm formation. Treatment strategies often reflect this classification, with debridement, antimicrobial therapy and implant retention (DAIR) preferentially reserved for early FRI. This study examined pathogens isolated from FRI to confirm or refute these hypothesized differences in causative pathogens over time. Cases of FRI managed surgically at three centres between 2015-2019 and followed up for at least one year were included. Data were analysed regarding patient demographics, time from injury and pathogens isolated. Patients who underwent DAIR were also analysed separately. In total, 433 FRIs were studied, including 51 early cases (median time from injury of 2 weeks, interquartile range (IQR) of 1-2 weeks), 82 delayed cases (median time from injury of 5 weeks, IQR of 4-8 weeks) and 300 late cases (median time from injury of 112 weeks, IQR of 40-737 weeks). The type of infection was associated with time since injury; early or delayed FRI are most likely to be polymicrobial, whereas late FRIs are more likely to be culture-negative, or monomicrobial. Staphylococcus aureus was the most commonly isolated pathogen at all time points; however, we found no evidence that the type of pathogens isolated in early, delayed or late infections were different (p = 0.2). More specifically, we found no evidence for more virulent pathogens (S. aureus, Gram-negative aerobic bacilli) in early infections and less virulent pathogens (such as coagulase negative staphylococci) in late infections. In summary, decisions on FRI treatment should not assume microbiological differences related to time since injury. From a microbiological perspective, the relevance of classifying FRI by time since injury remains unclear

Does the Use of Local Antibiotics Affect Clinical Outcome of Patients with Fracture-Related Infection?

This international, multi-center study evaluated the effect of antibiotic-loaded carriers (ALCs) on outcome in patients with a fracture-related infection (FRI) and evaluated whether bacterial resistance to the implanted antibiotics influences their efficacy. All patients who were retrospectively diagnosed with FRI according to the FRI consensus definition, between January 2015 and December 2019, and who underwent surgical treatment for FRI at any time point after injury, were considered for inclusion. Patients were followed-up for at least 12 months. The primary outcome was the recurrence rate of FRI at follow-up. Inverse probability for treatment weighting (IPTW) modeling and multivariable regression analyses were used to assess the relationship between the application of ALCs and recurrence rate of FRI at 12 months and 24 months. Overall, 429 patients with 433 FRIs were included. A total of 251 (58.0%) cases were treated with ALCs. Gentamicin was the most frequently used antibiotic (247/251). Recurrence of infection after surgery occurred in 25/251 (10%) patients who received ALCs and in 34/182 (18.7%) patients who did not (unadjusted hazard ratio (uHR): 0.48, 95% CI: [0.29–0.81]). Resistance of cultured microorganisms to the implanted antibiotic was not associated with a higher risk of recurrence of FRI (uHR: 0.75, 95% CI: [0.32–1.74]). The application of ALCs in treatment of FRI is likely to reduce the risk of recurrence of infection. The high antibiotic concentrations of ALCs eradicate most pathogens regardless of susceptibility test results

The Role of Negative-Pressure Wound Therapy in Patients with Fracture-Related Infection:A Systematic Review and Critical Appraisal

INTRODUCTION: Fracture-related infection (FRI) is a severe musculoskeletal complication in orthopedic trauma surgery, causing challenges in bony and soft tissue management. Currently, negative-pressure wound therapy (NPWT) is often used as temporary coverage for traumatic and surgical wounds, also in cases of FRI. However, controversy exists about the impact of NPWT on the outcome in FRI, specifically on infection recurrence. Therefore, this systematic review qualitatively assesses the literature on the role of NPWT in the management of FRI. METHODS: A literature search of the PubMed, Embase, and Web of Science database was performed. Studies that reported on infection recurrence related to FRI management combined with NPWT were eligible for inclusion. Quality assessment was done using the PRISMA statement and the Newcastle-Ottawa Quality Assessment Scale. RESULTS: After screening and quality assessment of 775 unique identified records, eight articles could be included for qualitative synthesis. All eight studies reported on infection recurrence, which ranged from 2.8% to 34.9%. Six studies described wound healing time, varying from two to seven weeks. Four studies took repeated microbial swabs during subsequent vacuum dressing changes. One study reported newly detected pathogens in 23% of the included patients, and three studies did not find new pathogens. CONCLUSION: This review provides an assessment of current literature on the role of NPWT in the management of soft tissue defects in patients with FRI. Due to the lack of uniformity in included studies, conclusions should be drawn with caution. Currently, there is no clear scientific evidence to support the use of NPWT as definitive treatment in FRI. At this stage, we can only recommend early soft tissue coverage (within days) with a local or free flap. NPWT may be safe for a few days as temporarily soft tissue coverage until definitive soft tissue management could be performed. However, comparative studies between NPWT and early wound closure in FRI patients are needed