Infectious diseases are worldwide a major cause of morbidity and mortality. Fast and specific detection of pathogens such as bacteria is needed to combat these diseases. Optimal methods would be non-invasive and without extensive sample-taking/processing. Here, we developed a set of near infrared (NIR) fluorescent nanosensors and used them for remote fingerprinting of clinically important bacteria. The nanosensors are based on single-walled carbon nanotubes (SWCNTs) that fluoresce in the NIR optical tissue transparency window, which offers ultra-low background and high tissue penetration. They are chemically tailored to detect released metabolites as well as specific virulence factors (lipopolysaccharides, siderophores, DNases, proteases) and integrated into functional hydrogel arrays with 9 different sensors. These hydrogels are exposed to clinical isolates of 6 important bacteria (Staphylococcus aureus, Escherichia coli,…) and remote (≥25 cm) NIR imaging allows to identify and distinguish bacteria. Sensors are also spectrally encoded (900 nm, 1000 nm, 1250 nm) to differentiate the two major pathogens P. aeruginosa as well as S. aureus and penetrate tissue (>5 mm). This type of multiplexing with NIR fluorescent nanosensors enables remote detection and differentiation of important pathogens and the potential for smart surfaces. Fast and specific detection of pathogenic bacteria is needed to combat infections. Here the authors generate an array of near-infrared biosensors based on carbon nanotubes to detect released metabolites and virulence factors and use them to distinguish pathogens such as S. aureus and P. aeruginosa.

/pdf/remote-near-infrared-identification-of-pathogens-with-4k73cwaskt.pdf

Remote near infrared identification of pathogens with multiplexed nanosensors

The increasing awareness of the significance of microbial biofilms across different sectors is continuously revealing new areas of opportunity in the development of innovative technologies in translational research, which can address their detrimental effects, as well as exploit their benefits. Due to the extent of sectors affected by microbial biofilms, capturing their real financial impact has been difficult. This perspective highlights this impact globally, based on figures identified in a recent in-depth market analysis commissioned by the UK's National Biofilms Innovation Centre (NBIC). The outputs from this analysis and the workshops organised by NBIC on its research strategic themes have revealed the breath of opportunities for translational research in microbial biofilms. However, there are still many outstanding scientific and technological challenges which must be addressed in order to catalyse these opportunities. This perspective discusses some of these challenges. 

/pdf/economic-significance-of-biofilms-a-multidisciplinary-and-194vaj37.pdf

Economic significance of biofilms: a multidisciplinary and cross-sectoral challenge

Over the last several decades, periprosthetic joint infection has been increasing in incidence and is occurring in more complex patients. While there have been advances in both surgical and medical treatment strategies, there remain important gaps in our understanding. Here, we share our current approaches to the diagnosis and management of periprosthetic joint infection, focusing on frequent clinical challenges and collaborative interdisciplinary care.

Periprosthetic Joint Infection: Current Clinical Challenges.

Exebacase, a recombinantly produced lysin has recently (i) reported proof-of-concept data from a phase II study in S. aureus bacteremia and (ii) demonstrated antibiofilm activity in vitro against S. epidermidis. In patients with relapsing multidrug-resistant (MDR) S. epidermidis prosthetic knee infection (PKI), the only surgical option is prosthesis exchange. In elderly patients who have undergone several revisions, prosthesis explantation could be associated with definitive loss of function and mortality. In our BJI reference regional center, arthroscopic debridement and implant retention with local administration of exebacase (LysinDAIR) followed by suppressive tedizolid as salvage therapy is proposed for elderly patients with recurrent MDR S. epidermidis PKI with no therapeutic option or therapeutic dead end (for whom revision or transfemoral amputation is not feasible and no other oral option is available). Each use was decided in agreement with the French health authority and in accordance with the local ethics committee. A written consent was obtained for each patient. Exebacase (75 mg/mL; 30 mL) was administered directly into the joint during arthroscopy. Four patients (79-89 years old) were treated with the LysinDAIR procedure. All had several previous prosthetic knee revisions without prosthesis loosening. Three had relapsing PKI despite suppressive antibiotics following open DAIR. Two had clinical signs of septic arthritis; the two others had sinus tract. After the LysinDAIR procedure, no adverse events occurred during arthroscopy; all patients received daptomycin 8 mg/kg and linezolid 600 mg bid (4-6 weeks) as primary therapy, followed by tedizolid 200 mg/day as suppressive therapy. At 6 months, recurrence of the sinus tract occurred in the two patients with sinus tract at baseline. After >1 year follow up, the clinical outcome was favorable in the last two patients with total disappearance of clinical signs of septic arthritis even if microbiological persistence was detected in one of them. Exebacase has the potential to be used in patients with staphylococci PKI during arthroscopic DAIR as salvage therapy to improve the efficacy of suppressive antibiotics and to prevent major loss of function.

/pdf/arthroscopic-debridement-and-implant-retention-with-local-3y1hwkhe08.pdf

Arthroscopic "Debridement and Implant Retention" With Local Administration of Exebacase (Lysin CF-301) Followed by Suppressive Tedizolid as Salvage Therapy in Elderly Patients for Relapsing Multidrug-Resistant S. epidermidis Prosthetic Knee Infection.

The treatment of prosthetic joint infections (PJIs) is a complex matter in which surgical, microbiological and pharmacological aspects must be integrated and, above all, placed in the context of each patient to make the best decision. Sometimes it is not possible to offer curative treatment of the infection, and in other cases, the probability that the surgery performed will be successful is considered very low. Therefore, indefinite administration of antibiotics with the intention of "suppressing" the course of the infection becomes useful. For decades, we had little information about suppressive antibiotic treatment (SAT). However, due to the longer life expectancy and increase in orthopaedic surgeries, an increasing number of patients with infected joint prostheses experience complex situations in which SAT should be considered as an alternative. In the last 5 years, several studies attempting to answer the many questions that arise on this issue have been published. The aim of this publication is to review the latest published evidence on SAT.

https://www.mdpi.com/2079-6382/10/6/743/pdf

Suppressive Antibiotic Treatment in Prosthetic Joint Infections: A Perspective.

Prosthetic joint infection (PJI) remains one of the major challenges facing orthopaedic surgeons. There is a paucity of evidence on non-operative management of PJI. We present the results of prolonged antibiotic suppression therapy (PSAT) in PJI from a single centre. A retrospective study was performed. Twenty-six patients were included. Two patients were excluded due to the lack of follow-up data. Failure was defined as admission for sepsis from the joint or amputation. Average age was 72 years (range 35–93). Mean Charlson co-morbidity index was 4.3. Mean follow-up was 3.2 years (range 1.3–5.7). Staphylococcal species were isolated in 11 cases (44%) (MRSA 1, MSSA 5, Staph. epidermidis 4 and Staph Pasteuri 1). Other bacteria included E. Coli (2), Streptococci spp. (3), Propionebacterium acnes (1) and Pseudomonas aeruginosa (1). Four cases were polymicrobial infection (16%), and no organisms were identified in two cases (8%). Candida albicans was identified in one case. All cases of bacterial infection were treated with prolonged oral doxycycline or amoxicillin. Twenty patients (80%) received 6 weeks of intravenous antibiotics prior to commencing prolonged oral antibiotics. Two patients experienced persistent symptoms and required amputation (both TKA). Two patients experienced sepsis but were treated successfully with IV antibiotics alone. The success rate of PSAT was 84% (21/25) successful at an average 3.2-year follow-up. Prolonged suppressive antibiotic therapy is a viable option for the management of PJI with a low incidence of complications.

Prolonged suppressive antibiotic therapy is successful in the management of prosthetic joint infection.

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Prolonged suppressive antibiotic therapy is successful in the management of prosthetic joint infection.