Next-Generation Sequencing for Pathogen Identification in Infected Foot Ulcers

Choi, Yoon-Jung; Oda, Eimi; Waldman, Olivia; Sajda, Thomas; Beck, Christopher A.; Oh, Irvin

doi:10.1177/24730114211026933

Cited by 14 publications

(18 citation statements)

References 22 publications

(91 reference statements)

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“…36 In a study of infected foot ulcers, complete concordance of NGS and culture was found in 14 cases (46.7%), partial concordance in 8 cases (26.7%), and discordance in 8 cases (26.7%). 37 The 70% concordance rate in our study is similar to literature reports.…”

Section: Discussionsupporting

confidence: 91%

Metagenomic Next-Generation Sequencing Detects Pathogens in Endophthalmitis Patients

Zhu

Tang

et al. 2022

Retina

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Purpose: To investigate the utility of metagenomic next-generation sequencing (mNGS) in identifying the pathogens in endophthalmitis.Methods: In this prospective study, 36 cases of endophthalmitis were recruited. All patients received surgical treatment and intraocular drug lavage. The samples of vitreous or aqueous humor were extracted for mNGS and microbiological culture. The diagnostic performance of pathogens was compared between mNGS and culture.Results: The positive rates of mNGS and culture were 88.89% (32/36) and 27.78% (10/ 36), respectively. There was a statistically significant difference between mNGS and culture (Chi-square = 27.657; P , 0.01). Staphylococcus epidermidis, Streptococcus pneumoniae, and Klebsiella pneumoniae were the most pathogenic bacteria in traumatic, postoperative, and endogenous endophthalmitis, respectively. The concordance of pathogen identified by mNGS and culture was 70% for culture-positive cases. Antibiotic resistance genes were identified in 9 cases. There was a marginal correlation between the final visual acuity and the microbial sequence read (Spearman correlation coefficient = 0.498; P = 0.05).Conclusion: Metagenomic next-generation sequencing has a higher positive rate of identifying pathogens in endophthalmitis than in culture. It can also provide information on antibiotic resistance and visual prognosis. However, caution must be taken when interpreting the results of mNGS because they may not be concordant with culture.

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Section: Discussionsupporting

confidence: 91%

Metagenomic Next-Generation Sequencing Detects Pathogens in Endophthalmitis Patients

Zhu

Tang

et al. 2022

Retina

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“…[78][79][80][81][82] Our systematic review identified 4 recent single-centre prospective studies that compared the results of different non-culture (molecular microbiological) methods to those of conventional culture. 49,[83][84][85][86] These studies addressed this question in both skin and soft-tissue infections and osteomyelitis of the foot.…”

Section: Rationalementioning

confidence: 99%

“…82 The studies also confirmed that non-culture techniques, especially metagenomic next-generation sequencing (mNGS) (NGS), identify more bacteria from tissue samples, including bone, than conventional cultures. [83][84][85][86] Currently, the use of mNGS techniques does not lead to a shorter time until pathogen identification, but this might change with the deployment of newer techniques. These techniques may help choose the empirical antibiotic therapy and reduce the risk of inappropriate treatment (i.e., failing to cover bacteria involved, including multiresistant ones).…”

Section: Rationalementioning

confidence: 99%

IWGDF/IDSA guidelines on the diagnosis and treatment of diabetes‐related foot infections (IWGDF/IDSA 2023)

Senneville,

Albalawi,

van Asten

et al. 2023

Diabetes Metabolism Res

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The International Working Group on the Diabetic Foot (IWGDF) has published evidence‐based guidelines on the management and prevention of diabetes‐related foot diseases since 1999. The present guideline is an update of the 2019 IWGDF guideline on the diagnosis and management of foot infections in persons with diabetes mellitus.The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was used for the development of this guideline. This was structured around identifying clinically relevant questions in the P(A)ICO format, determining patient‐important outcomes, systematically reviewing the evidence, assessing the certainty of the evidence, and finally moving from evidence to the recommendation. This guideline was developed for healthcare professionals involved in diabetes‐related foot care to inform clinical care around patient‐important outcomes. Two systematic reviews from 2019 were updated to inform this guideline, and a total of 149 studies (62 new) meeting inclusion criteria were identified from the updated search and incorporated in this guideline. Updated recommendations are derived from these systematic reviews, and best practice statements made where evidence was not available. Evidence was weighed in light of benefits and harms to arrive at a recommendation. The certainty of the evidence for some recommendations was modified in this update with a more refined application of the GRADE framework centred around patient important outcomes. This is highlighted in the rationale section of this update. A note is also made where the newly identified evidence did not alter the strength or certainty of evidence for previous recommendations.The recommendations presented here continue to cover various aspects of diagnosing soft tissue and bone infections, including the classification scheme for diagnosing infection and its severity. Guidance on how to collect microbiological samples, and how to process them to identify causative pathogens, is also outlined. Finally, we present the approach to treating foot infections in persons with diabetes, including selecting appropriate empiric and definitive antimicrobial therapy for soft tissue and bone infections; when and how to approach surgical treatment; and which adjunctive treatments may or may not affect the infectious outcomes of diabetes‐related foot problems.We believe that following these recommendations will help healthcare professionals provide better care for persons with diabetes and foot infections, prevent the number of foot and limb amputations, and reduce the patient and healthcare burden of diabetes‐related foot disease.

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“…Reverse Transcription Polymerase Chain reaction (qRT-PCR) 30 DNA sequencing, 32,33 16S ribosomal ribonucleic gene sequencing 34 and immunoassay. 31 Data about the coexistence of peripheral artery disease in the included patients and whether patients received antibiotics prior to tissue sampling (except in Choi's study 29 ) were not provided in these studies. Three studies [29][30][31] assessed mNGS in skin structure DFIs.…”

Section: Summary Of the Literaturementioning

confidence: 99%

Diagnosis of infection in the foot of patients with diabetes: A systematic review

Senneville,

Albalawi,

van Asten

et al. 2023

Diabetes Metabolism Res

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BackgroundSecuring an early accurate diagnosis of diabetic foot infections and assessment of their severity are of paramount importance since these infections can cause great morbidity and potential mortality and present formidable challenges in surgical and antimicrobial treatment.MethodsIn June 2022, we searched the literature using PubMed and EMBASE for published studies on the diagnosis of diabetic foot infection (DFI). On the basis of pre‐determined criteria, we reviewed prospective controlled, as well as non‐controlled, studies in English. We then developed evidence statements based on the included papers.ResultsWe selected a total of 64 papers that met our inclusion criteria. The certainty of the majority of the evidence statements was low because of the weak methodology of nearly all of the studies. The available data suggest that diagnosing diabetic foot infections on the basis of clinical signs and symptoms and classified according to the International Working Group of the Diabetic Foot/Infectious Diseases Society of America scheme correlates with the patient's likelihood of the need for hospitalisation, lower extremity amputation, and risk of death. Elevated levels of selected serum inflammatory markers such as erythrocyte sedimentation rate (ESR), C‐reactive protein and procalcitonin are supportive, but not diagnostic, of soft tissue infection. Culturing tissue samples of soft tissues or bone, when care is taken to avoid contamination, provides more accurate microbiological information than culturing superficial (swab) samples. Although non‐culture techniques, especially next‐generation sequencing, are likely to identify more bacteria from tissue samples including bone than standard cultures, no studies have established a significant impact on the management of patients with DFIs. In patients with suspected diabetic foot osteomyelitis, the combination of a positive probe‐to‐bone test and elevated ESR supports this diagnosis. Plain X‐ray remains the first‐line imaging examination when there is suspicion of diabetic foot osteomyelitis (DFO), but advanced imaging methods including magnetic resonance imaging (MRI) and nuclear imaging when MRI is not feasible help in cases when either the diagnosis or the localisation of infection is uncertain. Intra‐operative or non‐per‐wound percutaneous biopsy is the best method to accurately identify bone pathogens in case of a suspicion of a DFO. Bedside percutaneous biopsies are effective and safe and are an option to obtain bone culture data when conventional (i.e. surgical or radiological) procedures are not feasible.ConclusionsThe results of this systematic review of the diagnosis of diabetic foot infections provide some guidance for clinicians, but there is still a need for more prospective controlled studies of high quality.

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Next-Generation Sequencing for Pathogen Identification in Infected Foot Ulcers

Cited by 14 publications

References 22 publications

Metagenomic Next-Generation Sequencing Detects Pathogens in Endophthalmitis Patients

Metagenomic Next-Generation Sequencing Detects Pathogens in Endophthalmitis Patients

IWGDF/IDSA guidelines on the diagnosis and treatment of diabetes‐related foot infections (IWGDF/IDSA 2023)

Diagnosis of infection in the foot of patients with diabetes: A systematic review

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