scholarly journals 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

2021 ◽  
Vol 8 ◽  
Author(s):  
Tristan Ferry ◽  
Cécile Batailler ◽  
Aubin Souche ◽  
Cara Cassino ◽  
Christian Chidiac ◽  
...  

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.

2021 ◽  
Vol 14 (3) ◽  
pp. 231
Author(s):  
James B. Doub ◽  
Vincent Y. Ng ◽  
Eleanor Wilson ◽  
Lorenzo Corsini ◽  
Benjamin K. Chan

Here, we present a case of a 79-year-old female with a recalcitrant Staphylococcal epidermidis prosthetic knee infection that was successfully treated with a single dose of adjuvant intra-articular bacteriophage therapy after debridement and implant retention surgery. The bacteriophage used in this case, PM448, is the first ɛ2 bacteriophage to be used in vivo. Currently the patient is without evidence of clinical recurrence and, interestingly, the patient had also suffered from debilitating aplastic anemia for over 2 years, which is recovering since receiving adjuvant bacteriophage therapy.


2015 ◽  
Vol 57 (7) ◽  
pp. 1633-1639 ◽  
Author(s):  
Nadav Sarid ◽  
Erel Joffe ◽  
Lili Gibstein ◽  
Irit Avivi ◽  
Aaron Polliack ◽  
...  

2021 ◽  
Vol 14 (2) ◽  
pp. e238339
Author(s):  
Sunny Chaudhary ◽  
Subhajit Maji ◽  
Varun Garg ◽  
Vivek Singh

Isolated multidrug-resistant (MDR) tubercular tenosynovitis of the flexor tendons of finger without involvement of wrist is a rare presentation. Tenosynovitis of hand is an uncommon manifestation of extrapulmonary tuberculosis. Pyogenic flexor tenosynovitis of hand is frequently seen and is the closest differential. Non-specific clinical signs may lead to delay in diagnosis, which is often made after biopsy. Management includes surgical excision of necrotic tissue and infected synovium along with antitubercular therapy after histopathological diagnosis. MDR tuberculosis of hand is extremely rare and, to the best of our knowledge, has not been reported in the literature so far. We report an interesting case of MDR tubercular flexor tendon tenosynovitis of the little finger without any pulmonary involvement in an immunocompetent patient. The case was managed by complete synovectomy and second-line antitubercular therapy with complete resolution of disease and had no functional limitation.


mBio ◽  
2013 ◽  
Vol 4 (4) ◽  
Author(s):  
François Lebreton ◽  
Willem van Schaik ◽  
Abigail Manson McGuire ◽  
Paul Godfrey ◽  
Allison Griggs ◽  
...  

ABSTRACTEnterococcus faecium, natively a gut commensal organism, emerged as a leading cause of multidrug-resistant hospital-acquired infection in the 1980s. As the living record of its adaptation to changes in habitat, we sequenced the genomes of 51 strains, isolated from various ecological environments, to understand howE. faeciumemerged as a leading hospital pathogen. Because of the scale and diversity of the sampled strains, we were able to resolve the lineage responsible for epidemic, multidrug-resistant human infection from other strains and to measure the evolutionary distances between groups. We found that the epidemic hospital-adapted lineage is rapidly evolving and emerged approximately 75 years ago, concomitant with the introduction of antibiotics, from a population that included the majority of animal strains, and not from human commensal lines. We further found that the lineage that included most strains of animal origin diverged from the main human commensal line approximately 3,000 years ago, a time that corresponds to increasing urbanization of humans, development of hygienic practices, and domestication of animals, which we speculate contributed to their ecological separation. Each bifurcation was accompanied by the acquisition of new metabolic capabilities and colonization traits on mobile elements and the loss of function and genome remodeling associated with mobile element insertion and movement. As a result, diversity within the species, in terms of sequence divergence as well as gene content, spans a range usually associated with speciation.IMPORTANCEEnterococci, in particular vancomycin-resistantEnterococcus faecium, recently emerged as a leading cause of hospital-acquired infection worldwide. In this study, we examined genome sequence data to understand the bacterial adaptations that accompanied this transformation from microbes that existed for eons as members of host microbiota. We observed changes in the genomes that paralleled changes in human behavior. An initial bifurcation within the species appears to have occurred at a time that corresponds to the urbanization of humans and domestication of animals, and a more recent bifurcation parallels the introduction of antibiotics in medicine and agriculture. In response to the opportunity to fill niches associated with changes in human activity, a rapidly evolving lineage emerged, a lineage responsible for the vast majority of multidrug-resistantE. faeciuminfections.


Author(s):  
Maysa Serpa ◽  
Juliana Amália Fonte Bôa do Nascimento ◽  
Mirian Fátima Alves ◽  
Maria Isabel Maldonado Coelho Guedes ◽  
Adrienny Trindade Reis ◽  
...  

Antimicrobial resistance is a current and important issue to public health, and it is usually associated with the indiscriminate use of antimicrobials in animal production. This study aimed to evaluate the antimicrobial susceptibility profile in bacterial isolates from pigs with clinical respiratory signs in Brazil. One hundred sixty bacterial strains isolated from pigs from 51 pig farms in Brazil were studied. In vitro disk-diffusion method was employed using 14 antimicrobial agents: amoxicillin, penicillin, ceftiofur, ciprofloxacin, enrofloxacin, chlortetracycline, doxycycline, oxytetracycline, tetracycline, erythromycin, tilmicosin, florfenicol, lincomycin, and sulfadiazine/trimethoprim. The majority of isolates were resistant to at least one antimicrobial agent (98.75%; 158/160), while 31.25% (50/160) of the strains were multidrug resistant. Streptococcus suis and Bordetella bronchiseptica were the pathogens that showed higher resistance levels. Haemophilus parasuis showed high resistance levels to sulfadiazine/trimethoprim (9/18=50%). We observed that isolates from the midwestern and southern regions exhibited four times greater chance of being multidrug resistant than the isolates from the southeastern region studied. Overall, the results of the present study showed a great level of resistance to lincomycin, erythromycin, sulfadiazine/trimethoprim, and tetracycline among bacterial respiratory pathogens isolated from pigs in Brazil. The high levels of antimicrobial resistance in swine respiratory bacterial pathogens highlight the need for the proper use of antimicrobials in Brazilian pig farms.


2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Ryan K. Shields

ABSTRACT Cefiderocol is a newly approved siderophore cephalosporin that demonstrates expanded in vitro activity against multidrug-resistant Gram-negative bacteria. In two challenging cases reported here, cefiderocol shows potential utility as salvage therapy against difficult-to-treat pathogens with limited or no treatment options; however, two multicenter, randomized clinical trials have yielded mixed results among cefiderocol-treated patients. Taken together, clinicians must balance a clear need for cefiderocol in clinical practice with the uncertainties that have stemmed from the available data.


2013 ◽  
Vol 119 (6) ◽  
pp. 1596-1602 ◽  
Author(s):  
František Remeš ◽  
Robert Tomáš ◽  
Vlastimil Jindrák ◽  
Václav Vaniš ◽  
Michal Šetlík

Object To date, reports on the clinical efficacy of intraventricularly and intrathecally administered antibiotics for the treatment of neurosurgical ventriculitis and meningitis in adults are limited. The authors aimed to evaluate the efficacy and safety of the intraventricular (IVT) and lumbar intrathecal (IT) administration of antibiotics in critically ill neurosurgical patients. Methods Thirty-four postneurosurgical patients with meningitis and ventriculitis were studied. Intraventricular/lumbar intrathecal antibiotics were administered due to positive CSF cultures persisting despite the use of intravenous antibiotics. The time period until CSF sterilization, changes in clinical state, and efficacy of different routes of antibiotic administration were evaluated. Results The mean time necessary to obtain CSF sterilization was 2.9 ± 2.7 days (range 1–12 days). The CSF cultures became negative within 24 hours after the administration of IVT/IT antibiotics in 17 patients (50%) and up to 48 hours in a further 6 patients (18%). The clinical outcome of patients assessed by the modified Rankin Scale improved in 17 patients (50%), stayed unchanged in 10 patients (29%), and was impaired in 1 patient (3%). Six patients (18%) died; however, 2 of them died due to reasons not directly related to meningitis or ventriculitis, so the overall mortality rate for meningitis and/or ventriculitis was 11.8% in this group of patients. All patients with ventriculitis (n = 4) were treated by antibiotics administered via the IVT route. The average time to CSF sterilization was 6.5 days in the patients with ventriculitis. Thirty patients had clinical signs of meningitis without ventriculitis. Despite the higher ratio of unfavorable Gram-negative meningitis in the subgroup of patients treated via lumbar drainage, the mean duration of CSF sterilization was 2.2 days compared with 2.6 days in the subgroup treated via external ventricular drainage, a difference that was not statistically significant (p = 0.3). Adverse effects of IVT/IT antibiotics appeared in 3 of 34 patients and were of low clinical significance. Conclusions Intraventricular/lumbar intrathecal antibiotics can lead to very quick CSF sterilization in postneurosurgical patients with meningitis and ventriculitis. The relapse rate of meningitis and/or ventriculitis is also very low among patients treated by IVT/IT antibiotics. Intraventricular/lumbar intrathecal administration of antibiotics appears to be an effective and safe treatment for infections of the CNS caused by multidrug-resistant organisms. In patients with signs of ventriculitis, the authors prefer the IVT route of antibiotics. This study did not prove a lower efficacy of administration of antibiotics via lumbar drainage compared with the ventricular route in patients with meningitis.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S200-S201
Author(s):  
Cynthia Rivero ◽  
Santiago Martinez ◽  
Orlando Pardo ◽  
Cintia Jahan ◽  
Segundo Fuego ◽  
...  

Abstract Background Surgical site infections following spinal surgery affect 0. 3 to 20% of patients. The longer the infection, the greater the chance of antibiotic treatment failure due to the establishment of mature microbial biofilm on the hardware, requiring its removal for infection eradication. Methods Retrospective cohort of patients with microbiologically confirmed SII following spinal surgery treated with debridement and retention. SII was defined as the presence of clinical signs of deep surgical site infection with 2 or more positive culture results of tissue surrounding the implant taken during surgical debridement; or from CT guided biopsy. Inclusion criteria: adults with a 1º episode of microbiological confirmed SII diagnosed from 2008 to 2017 with >2 years of follow-up, treated with implant retention. Definitions Early-onset infection (EOI): infection < 1 month following implant placement. Late onset infection (LOI): between 30 days and 1 year after implant placement. Delayed onset infection (DOI): >1 year of implant placement. Statistical analysis made in Graph Pad Prism 5. 0. Results We analyzed 19 patients with SII treated with hardware retention. Mean age was 54 (21–70) years, 63% were female. Comorbidities, clinical manifestations and motive for surgery are in Table 1 and Figure 1. Hardware material used was titanium 15(79%) and steel 4(21%). In addition to the hardware,11 patients (57. 9%) underwent bone grafting, 4 experienced treatment failure (4/11 = 36. 4%); 2 patients had nonmetallic material inserted (carbon polymer), the 2 patients experienced failure. 16 patients (84. 2%) had EOI, 2 (10. 5%) LOI, 1 (5. 3%) DOI. Failure requiring implant removal was observed in 26. 3% (n = 5), 2 of the cases were EOI, 2 LOI and 1 DOI. Bacterial characteristics of patients are shown in Table 2. 47,4% of patients required more than one debridement (Figure 2). In the lineal regression model, treatment failure was associated with bone grafting (P = 0. 04) and the use of carbon polymer materials (P = 0. 007). Conclusion Treatment of SII with debridement plus antimicrobials treatment is acceptable, with a rate failure of 26%. In LOI and DOI spinal implant retention is more prone to fail. Bone grafting and the presence of polymers seem to be associated with treatment failure of conservative strategies. Disclosures All authors: No reported disclosures.


Author(s):  
Jorrit W. A. Schoenmakers ◽  
Marjolein Heuker ◽  
Marina López-Álvarez ◽  
Wouter B. Nagengast ◽  
Gooitzen M. van Dam ◽  
...  

Abstract Purpose Due to an increased human life expectancy, the need to replace arthritic or dysfunctional joints by prosthetics is higher than ever before. Prosthetic joints are unfortunately inherently susceptible to bacterial infection accompanied by biofilm formation. Accurate and rapid diagnosis is vital to increase therapeutic success. Yet, established diagnostic modalities cannot directly detect bacterial biofilms on prostheses. Therefore, the present study was aimed at investigating whether arthroscopic optical imaging can accurately detect bacterial biofilms on prosthetic joints. Methods Here, we applied a conjugate of the antibiotic vancomycin and the near-infrared fluorophore IRDye800CW, in short vanco-800CW, in combination with arthroscopic optical imaging to target and visualize biofilms on infected prostheses. Results We show in a human post-mortem prosthetic knee infection model that a staphylococcal biofilm is accurately detected in real time and distinguished from sterile sections in high resolution. In addition, we demonstrate that biofilms associated with the clinically most relevant bacterial species can be detected using vanco-800CW. Conclusion The presented image-guided arthroscopic approach provides direct visual diagnostic information and facilitates immediate appropriate treatment selection.


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