Fracture-related infection (FRI) is a common and serious complication in trauma surgery. Accurately estimating the impact of this complication has been hampered by the lack of a clear definition. The ...absence of a working definition of FRI renders existing studies difficult to evaluate or compare. In order to address this issue, an expert group comprised of a number of scientific and medical organizations has been convened, with the support of the AO Foundation, in order to develop a consensus definition.
The process that led to this proposed definition started with a systematic literature review, which revealed that the majority of randomized controlled trials in fracture care do not use a standardized definition of FRI. In response to this conclusion, an international survey on the need for and key components of a definition of FRI was distributed amongst all registered AOTrauma users. Approximately 90% of the more than 2000 surgeons who responded suggested that a definition of FRI is required. As a final step, a consensus meeting was held with an expert panel. The outcome of this process led to a consensus definition of FRI.
Two levels of certainty around diagnostic features were defined. Criteria could be confirmatory (infection definitely present) or suggestive. Four confirmatory criteria were defined: Fistula, sinus or wound breakdown; Purulent drainage from the wound or presence of pus during surgery; Phenotypically indistinguishable pathogens identified by culture from at least two separate deep tissue/implant specimens; Presence of microorganisms in deep tissue taken during an operative intervention, as confirmed by histopathological examination. Furthermore, a list of suggestive criteria was defined. These require further investigations in order to look for confirmatory criteria.
In the current paper, an overview is provided of the proposed definition and a rationale for each component and decision. The intention of establishing this definition of FRI was to offer clinicians the opportunity to standardize clinical reports and improve the quality of published literature. It is important to note that the proposed definition was not designed to guide treatment of FRI and should be validated by prospective data collection in the future.
Fracture-related infection (FRI) is a severe complication after bone injury and can pose a serious diagnostic challenge. Overall, there is a limited amount of scientific evidence regarding diagnostic ...criteria for FRI. For this reason, the AO Foundation and the European Bone and Joint Infection Society proposed a consensus definition for FRI to standardize the diagnostic criteria and improve the quality of patient care and applicability of future studies regarding this condition. The aim of this article was to summarize the available evidence and provide recommendations for the diagnosis of FRI. For this purpose, the FRI consensus definition will be discussed together with a proposal for an update based on the available evidence relating to the diagnostic value of clinical parameters, serum inflammatory markers, imaging modalities, tissue and sonication fluid sampling, molecular biology techniques, and histopathological examination. Second, recommendations on microbiology specimen sampling and laboratory operating procedures relevant to FRI will be provided.
LEVEL OF EVIDENCE:Diagnostic Level V. See Instructions for Authors for a complete description of levels of evidence.
Purpose
This systematic review determined the reported treatment strategies, their individual success rates, and other outcome parameters in the management of critical-sized bone defects in ...fracture-related infection (FRI) patients between 1990 and 2018.
Methods
A systematic literature search on treatment and outcome of critical-sized bone defects in FRI was performed. Treatment strategies identified were, autologous cancellous grafts, autologous cancellous grafts combined with local antibiotics, the induced membrane technique, vascularized grafts, Ilizarov bone transport, and bone transport combined with local antibiotics. Outcomes were bone healing and infection eradication after primary surgical protocol and recurrence of FRI and amputations at the end of study period.
Results
Fifty studies were included, describing 1530 patients, the tibia was affected in 82%. Mean age was 40 years (range 6–80), with predominantly male subjects (79%). Mean duration of infection was 17 months (range 1–624) and mean follow-up 51 months (range 6–126). After initial protocolized treatment, FRI was cured in 83% (95% CI 79–87) of all cases, increasing to 94% (95% CI 92–96) at the end of each individual study. Recurrence of infection was seen in 8% (95% CI 6–11) and amputation in 3% (95% CI 2–3). Final outcomes overlapped across treatment strategies.
Conclusion
Results should be interpreted with caution due to the retrospective and observational design of most studies, the lack of clear classification systems, incomplete data reports, potential underreporting of adverse outcomes, and heterogeneity in patient series. A consensus on classification, treatment protocols, and outcome is needed to improve reliability of future studies.
The recent consensus definition for the diagnosis of fracture-related infection (FRI) includes the identification of indistinguishable microorganisms in at least 2 surgical deep-tissue specimens as a ...confirmatory criterion. However, this cut-off, and the total number of specimens from a patient with suspected FRI that should be sent for microbiological testing, have not been validated. We endeavored to estimate the accuracy of different numbers of specimens and diagnostic cut-offs for microbiological testing of deep-tissue specimens in patients undergoing surgical treatment for possible FRI.
A total of 513 surgical procedures in 385 patients with suspected FRI were included. A minimum of 2 surgical deep-tissue specimens were submitted for microbiological testing; 5 or more specimens were analyzed in 345 procedures (67%). FRI was defined by the presence of any confirmatory criteria other than microbiology. Resampling was utilized to model the sensitivity and specificity of diagnostic cut-offs for the number of surgical specimens yielding indistinguishable microorganisms and for the total number of specimens. The likelihood of detecting all clinically relevant microorganisms was also assessed.
A diagnostic cut-off of at least 2 of 5 specimens with indistinguishable microorganisms identified by culture was 68% sensitive (95% confidence interval CI, 62% to 74%) and 87% specific (95% CI, 81% to 94%) for the diagnosis of FRI. Two out of 3 specimens were 60% sensitive (95% CI, 55% to 66%) and 92% specific (95% CI, 88% to 96%). Submitting only 3 deep-tissue specimens risked missing clinically relevant microorganisms in at least 1 in 10 cases.
The present study was the first to validate microbiological criteria for the diagnosis of FRI, supporting the current confirmatory diagnostic criteria for FRI. Analysis of at least 5 deep-tissue specimens in patients with possible FRI is recommended.
Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.
•Standardised intraoperative sampling for FRI should consist of ≥5 deep tissue samples, each obtained with sterile instruments.•A tailored FRI microbiology request form raises awareness in both ...surgeon and microbiologist, optimizing culture approaches.•The standardised protocol for intraoperative sampling for bacterial identification in FRI is superior to an ad-hoc approach.•Resulting in a more complete overview of the infected tissue, more trustworthy culture results, and a more targeted treatment.
Fracture-related infection (FRI) is an important complication following surgical fracture management. Key to successful treatment is an accurate diagnosis. To this end, microbiological identification remains the gold standard. Although a structured approach towards sampling specimens for microbiology seems logical, there is no consensus on a culture protocol for FRI. The aim of this study is to evaluate the effect of a structured microbiology sampling protocol for fracture-related infections compared to ad-hoc culture sampling.
We conducted a pre-/post-implementation cohort study that compared the effects of implementation of a structured FRI sampling protocol. The protocol included strict criteria for sampling and interpretation of tissue cultures for microbiology. All intraoperative samples from suspected or confirmed FRI were compared for culture results. Adherence to the protocol was described for the post-implementation cohort.
In total 101 patients were included, 49 pre-implementation and 52 post-implementation. From these patients 175 intraoperative culture sets were obtained, 96 and 79 pre- and post-implementation respectively. Cultures from the pre-implementation cohort showed significantly more antibiotic use during culture sampling (P = 0.002). The post-implementation cohort showed a tendency more positive culture sets (69% vs. 63%), with a significant difference in open wounds (86% vs. 67%, P = 0.034). In all post-implementation culture sets causative pathogens were cultured more than once per set, in contrast to pre-implementation. Despite stricter tissue sampling and culture interpretation criteria, the number of polymicrobial infections was similar in both cohorts, approximately 29% of all culture sets and 44% of all positive culture sets. Significantly more polymicrobial cultures were found in early infections in the post-implementation cohort (P = 0.048). This indicates a better yield in the new protocol.
A standardised protocol for intraoperative sampling for bacterial identification in FRI is superior than an ad-hoc approach. It has a positive effect on both surgeon and microbiologist by increasing awareness about the problem at hand. This resulted in more microbiologically confirmed infections and more certainty when identifying causative pathogens.
Chronic osteomyelitis may recur if dead space management, after excision of infected bone, is inadequate. This study describes the results of a strategy for the management of deep bone infection and ...evaluates a new antibiotic-loaded biocomposite in the eradication of infection from bone defects.
We report a prospective study of 100 patients with chronic osteomyelitis, in 105 bones. Osteomyelitis followed injury or surgery in 81 patients. Nine had concomitant septic arthritis. 80 patients had comorbidities (Cierny-Mader (C-M) Class B hosts). Ten had infected nonunions. All patients were treated by a multidisciplinary team with a single-stage protocol including debridement, multiple sampling, culture-specific systemic antibiotics, stabilisation, dead space filling with the biocomposite and primary skin closure.
Patients were followed up for a mean of 19.5 months (12 to 34). Infection was eradicated in 96 patients with a single procedure and all four recurrences were successfully managed with repeat surgery. Adverse events were uncommon, with three fractures, six wound leaks and three unrelated deaths. Outcome was not dependant on C-M host class, microbial culture, wound leakage or presence of nonunion.
This single-stage protocol, facilitated by the absorbable local antibiotic, is effective in the treatment of chronic osteomyelitis. It offers a more patient-friendly treatment compared with other published treatment options. Cite this article: Bone Joint J 2016;98-B:1289-96.
This study aimed to investigate the role of quantitative histological analysis in the diagnosis of fracture-related infection (FRI).
The clinical features, microbiology culture results, and ...histological analysis in 156 surgically treated nonunions were used to stratify the likelihood of associated infection. There were 64 confirmed infected nonunions (one or more confirmatory criteria: pus, sinus, and bacterial growth in two or more samples), 66 aseptic nonunions (no confirmatory criteria), and 26 possibly infected nonunions (pathogen identified from a single specimen and no confirmatory criteria). The histological inflammatory response was assessed by average neutrophil polymorph (NPs) counts per high-power field (HPF) and compared with the established diagnosis.
Assuming a cut-off of over five neutrophils per high-power field to diagnose septic nonunion, there was 80% sensitivity and 100% specificity (accuracy 90%). Using a cut-off of no neutrophils seen in any high-power field to diagnose aseptic nonunion, there was a sensitivity of 85% and a specificity of 98% (accuracy 92%).
Histology can be used in a bimodal fashion as a diagnostic test for FRI. The presence of more than five NPs/HPF had a positive predictive value for infected nonunion of 100%, while the complete absence of any NPs is almost always indicative of an aseptic nonunion (positive predictive value of 98%). Cite this article: Bone Joint J 2018;100-B:966-72.
Summary Objectives This study describes the microbiological spectrum of chronic osteomyelitis and so guides the choice of empirical antibiotics for this condition. Methods We performed a prospective ...review of a 166 prospective patient series of chronic osteomyelitis from Oxford, UK in which a standardised surgical sampling protocol was used. Results Staphylococcus aureus was most commonly isolated (32%) amongst a wide range of organisms including gram negative bacilli, anaerobes and coagulase negative staphylococci. Low grade pathogens were not confined to patients with a history of metalwork, a high proportion of cases were polymicrobial (29%) and culture negative cases were common (28%). No clear predictors of causative organism could be established. Many isolates were found to be resistant to commonly used empirical anti-microbial regimens. Conclusions The wide range of causative organisms and degree of resistance to commonly used anti-microbials supports the importance of extensive intra-operative sampling and provides important information to guide clinicians' choice of empirical antibiotics.
Introduction
Standardized guidelines for treatment of fracture-related infection (FRI) are lacking. Worldwide many treatment protocols are used with variable success rates. Awareness on the need of ...standardized, evidence-based guidelines has increased in recent years. This systematic literature review gives an overview of available diagnostic criteria, classifications, treatment protocols, and related outcome measurements for surgically treated FRI patients.
Methods
A comprehensive search was performed in all scientific literature since 1990. Studies in English that described surgical patient series for treatment of FRI were included. Data were collected on diagnostic criteria for FRI, classifications used, surgical treatments, follow-up protocols, and overall outcome. A systematic review was performed according to the PRISMA statement. Proportions and weighted means were calculated.
Results
The search yielded 2051 studies. Ninety-three studies were suitable for inclusion, describing 3701 patients (3711 fractures) with complex FRI. The population consisted predominantly of male patients (77%), with the tibia being the most commonly affected bone (64%), and a mean of three previous operations per patient. Forty-three (46%) studies described FRI at one specific location. Only one study (1%) used a standardized definition for infection. A total of nine different classifications were used to guide treatment protocols, of which Cierny and Mader was used most often (36%). Eighteen (19%) studies used a one-stage, 50 (54%) a two-stage, and seven (8%) a three-stage surgical treatment protocol. Ten studies (11%) used mixed protocols. Antibiotic protocols varied widely between studies. A multidisciplinary approach was mentioned in only 12 (13%) studies.
Conclusions
This extensive literature review shows a lack of standardized guidelines with respect to diagnosis and treatment of FRI, which mimics the situation for prosthetic joint infection identified many years ago. Internationally accepted guidelines are urgently required to improve the quality of care for patients suffering from this significant complication.
The spectrum and frequency of cancers associated with germline TP53 mutations are uncertain. To address this issue a cohort of individuals from 28 families with Li-Fraumeni syndrome, segregating ...germline TP53 mutations was established. Predicted cancers were estimated by applying age, morphology, site and sex-specific UK cancer statistics to person-years at risk. Observed and predicted cancers were compared and two-sided P-values calculated. Cancer types occurring to excess and showing P-values <0.02, were designated strongly associated with germline TP53 mutations. These were removed from the data and a second round of analyses performed. Cancer types with P-values <0.02 and 0.02-0.05 in the second round analyses were considered moderately and weakly associated respectively. Strongly associated cancers were: breast carcinoma, soft tissue sarcomas, osteosarcoma, brain tumours, adrenocortical carcinoma, Wilms' tumour and phyllodes tumour. Carcinoma of pancreas was moderately associated. Leukaemia and neuroblastoma were weakly associated. Other common carcinomas including lung, colon, bladder, prostate, cervix and ovary did not occur to excess. Although breast carcinoma and sarcomas were numerically most frequent, the greatest increases relative to general population rates were in adrenocortical carcinoma and phyllodes tumour. We conclude that germline TP53 mutations do not simply increase general cancer risk. There are tissue-specific effects.
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