Short-term results of treatment of staphylococcal periprosthetic hip joint infection with combined antibiotics and bacteriophages treatment

Infectious complications after primary implantation of the hip joint are 0.5–3 %, and in the case of re-endoprosthetics, the risk of periprosthetic infection can reach 30 %. Also, we should not forget about the high percentage (16–20 %) of recurrence of periprosthetic infection of the hip joint, which leads to an unsatisfactory result of treatment up to amputation of a limb or even death of the patient. The reasons for the recurrence of the infectious process can be antibiotic resistance and antibiotic tolerance of microorganisms, as well as the ability of microorganisms to form biofilms on implants. In this regard, there is a constant need to search for alternative means of antimicrobial therapy, as well as to select the optimal ways of their delivery and deposition, which is of practical importance when performing surgical interventions in traumatology and orthopedics to protect the implantable structure from possible infection of the surgical site. One of the methods currently available to combat bacterial infections acquired antibiotic resistance and antibiotic tolerance is the use of natural viruses that infect bacterial bacteriophages. The above suggests a more effective suppression of periprosthetic infection, including persisters that deviate from antibiotics. It is, as a rule, associated with biofilms if used in conjunction with antibiotics and phages, when the use of bacteriophages predetermines the effectiveness of treatment. With the use of sensitive bacteriophages in the treatment of periprosthetic infections, a significant (p = 0.030) reduction in the rate of recurrence of infection (from 31 to 4.5 %) was observed. The use of lytic bacteriophages in traumatology and orthopedics is of great interest for phagotherapy of infections caused by antibiotic-resistant and biofilm-forming strains of bacteria. A clinical study using a single-stage surgical revision with simultaneous application of antibiotics and phages in the treatment of deep periprosthesis infection of the hip joint endoprosthesis, followed by 12 months follow-up for periprosthetic infection recurrence, demonstrated the effectiveness of the use of combined antibiotic and bacteriophages treatment.

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The choice of a spacer at the first stage of treatment for late deep periprosthetic hip joint infection

Genij Ortopedii ◽

10.18019/1028-4427-2021-27-5-548-554 ◽

2021 ◽

Vol 27 (5) ◽

pp. 548-554

Author(s):

S.A. Linnik ◽

◽

G.E. Afinogenov ◽

A.G. Afinogenova ◽

G.E. Kvinikadze ◽

...

Keyword(s):

Bone Cement ◽

Hip Joint ◽

Periprosthetic Infection ◽

Joint Infection ◽

Revision Arthroplasty ◽

Infectious Complications ◽

Mechanisms Of Action ◽

Antibiotic Resistant ◽

The Third ◽

Two Component

Abstract. Introduction Periprosthetic infection in hip arthroplasty is a social and economic problem. Its main reason is multidrug resistance of microorganisms. Purpose To evaluate the effectiveness of the first stage in two-stage revision arthroplasty for the treatment of deep periprosthetic infection of the hip joint by improving the constructive and antibacterial features of spacers. Materials and methods The treatment results of 127 patients with late deep periprosthetic hip joint infection who underwent two-stage revision arthroplasty in the period from 2015 to 2019 were analyzed. In the first group, 42 patients were fitted with a two-component (total) spacer based on the developed antimicrobial composition of bone cement with gentamicin, antiseptics and polymer (patent RU 191236). In the second group, a two-component spacer (patent RU 174697) based on conventional bone cement with gentamicin was implanted in 43 patients; the third group of 42 patients had a preformed spacer. Results A bactericidal and antiadhesive, nontoxic composition based on bone cement with gentamicin with antiseptics poviargol, dioxidine and high molecular weight polyvinylpyrrolidone with a prolonged action for 348 days against gentamicin-resistant staphylococci has been developed. All patients underwent the first stage of hip arthroplasty with removal of the implant and installation of a spacer. Recurrence of periprosthetic infection was observed in 1 (2.3 %) patient of the first group, in 5 (11.6 %) in the second and in 6 (14.2 %) patients of the third group. Non-infectious complications such as spacer dislocation and instability were observed in 12 cases, one case (2.3 %) in the first, 2 (4.6 %) in the second and 9 (21.4 %) in the third group. The average time from the first stage of treatment to the second stage of re-implantation was 7.5 months (range, 4–13 months). Discussion According to the literature, the introduction of new antibiotics into the bone cement with gentamicin does not increase the antimicrobial action of the spacer, especially against antibiotic-resistant isolates, and the use of a preformed spacer contributes to an increase in the number of non-infectious complications. Antiseptics with different mechanisms of action are able to act on antibiotic-resistant bacteria, and the polymer can prolong this effect. Conclusions Creation of two-component spacers based on bone cement with gentamicin using antiseptics with different mechanisms of action and polymer promotes long-term bactericidal action of the spacer, which leads to effective sanation of the joint area, reducing non-infectious complications.

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Clinical and microbiological characteristics of periprosthetic hip and knee infections

Clinical Microbiology and Antimicrobial Chemotherapy ◽

10.36488/cmac.2020.3.237-240 ◽

2020 ◽

pp. 237-240

Author(s):

Vladimir A. Ivantsov ◽

I.P. Bogdanovich ◽

V.V. Lashkovskiy ◽

V.S. Anosov

Keyword(s):

Surgical Treatment ◽

Knee Joint ◽

Hip Joint ◽

Joint Replacement ◽

Periprosthetic Infection ◽

Joint Infection ◽

Knee Joints ◽

Knee Joint Replacement ◽

Hip Joint Replacement ◽

Total Knee

Objective. To characterize periprosthetic joint infection in patients undergoing a total hip and knee joint replacement. Materials and Methods. A total of 77 patients with periprosthetic infection following hip and knee joint replacement hospitalized in Grodno City Clinical Hospital were studied over the period of 2014-2018. Wound discharge, tissue samples, and fistula’s wall swab were used for microbiological tests. The analysis of surgical treatment of patients with deep periprosthetic knee and hip joint infection has been performed. Results. Periprosthetic infection after hip joint arthroplasty was observed in 32 (41.6%) patients, and after total knee joint arthroplasty in 45 (58.4%) patients. Surgical treatment was performed in 18 (56.3%) and 32 (71.1%) patients with periprosthetic infection following total knee and hip joint replacement, respectively. A total of 10 (31.2%) of 32 cultures from patients with periprosthetic infection after total hip joint replacement and 8 (17.8%) of 45 cultures from patients with periprosthetic infection after total knee joint replacement were positive. Overall, Staphylococcus aureus was detected in 9 (50%) of 18 positive cultures. Gram-negative aerobic bacteria (Acinetobacter baumannii, Klebsiella pneumoniae Pseudomonas aeruginosa) were detected in 4⁄10 and 5⁄8 of positive cultures from patients with periprosthetic infection of hip and knee joints, respectively. Conclusions. The most common pathogens causing periprosthetic infection of hip and knee joints were S. aureus (50%) and Gram-negative bacteria. The surgical treatment was performed in 71.4% of patients with periprosthetic joint infection.

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Predicting antibiotic-associated virulence of Pseudomonas aeruginosa using an ex-vivo lung biofilm model

10.1101/2020.02.24.963173 ◽

2020 ◽

Cited By ~ 1

Author(s):

Marwa M. Hassan ◽

Niamh E. Harrington ◽

Esther Sweeney ◽

Freya Harrison

Keyword(s):

Pseudomonas Aeruginosa ◽

Antibiotic Resistance ◽

Bacterial Infections ◽

Ex Vivo ◽

Bacterial Load ◽

Realistic Model ◽

Antibiotic Tolerance ◽

Minimal Effect ◽

Biofilm Model

AbstractBackgroundBacterial biofilms are known to have high antibiotic tolerance which directly affects clearance of bacterial infections in people with cystic fibrosis (CF). Current antibiotic susceptibility testing methods are either based on planktonic cells or do not reflect the complexity of biofilms in vivo. Consequently, inaccurate diagnostics affect treatment choice, preventing bacterial clearance and potentially selecting for antibiotic resistance. This leads to prolonged, ineffective treatment.MethodsIn this study, we use an ex-vivo lung biofilm model to study antibiotic tolerance and virulence of Pseudomonas aeruginosa. Sections of pig bronchiole were dissected, prepared and infected with clinical isolates of P. aeruginosa and incubated in artificial sputum media to form biofilms, as previously described. Then, lung-associated biofilms were challenged with antibiotics, at therapeutically relevant concentrations, before their bacterial load and virulence were quantified and detected, respectively.ResultsThe results demonstrated minimal effect on the bacterial load with therapeutically relevant concentrations of ciprofloxacin and meropenem, with the later causing an increased production of proteases and pyocyanin. A combination of meropenem and tobramycin did not show any additional decrease in bacterial load but demonstrated a slight decrease in total proteases and pyocyanin production.ConclusionsWe demonstrate a realistic model for understanding antibiotic resistance and tolerance in biofilms clinically and for molecules screening in anti-biofilm drug development. P. aeruginosa showed high levels of antibiotic tolerance, with minimal effect on bacterial load and increased proteases production, which could negatively affect lung function. This may potentially contribute to exacerbations and eventual lung failure.

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Efficiency of combined action of antimicrobial preparations against poly-resistant strains of conditionally-pathogenic bacteria isolated from wounds of surgery patients

Regulatory Mechanisms in Biosystems ◽

10.15421/022060 ◽

2020 ◽

Vol 11 (3) ◽

Author(s):

T. V. Sklyar ◽

K. V. Lavrentievа ◽

O. M. Rudas ◽

О. V. Bilotserkivska ◽

N. V. Kurahina ◽

...

Keyword(s):

Antibiotic Resistance ◽

Bacterial Infections ◽

Pathogenic Bacteria ◽

Diffusion Method ◽

Bacterial Strains ◽

Disk Diffusion Method ◽

Antibiotic Resistant ◽

Simultaneous Application ◽

Strategic Approach ◽

Resistant Strains

The strategy of use of combination therapy of antibacterial preparations is being broadly introduced to clinical practice to fight bacterial infections caused by poly-resistant strains of microorganisms. From the wounds of surgery patients, we isolated 67 clinical strains of conditionally-pathogenic bacteria identified as Staphylococcus aureus, S. epidermidis, Escherichia coli, Klebsiella pneumoniaе, Proteus vulgaris, Proteus mirabilis, Pseudomonas aeruginosa. Using disk diffusion method, the isolated bacterial strains were found to be most resistant to penicillin preparations: ampicillin, oxacillin, amoxicillin/clavulanat; tetracycline and cephalosporin of the II generation – cefoxitin. The percentage of strains insusceptible to these antibacterial preparations accounted for 65.0%. The division of antibiotic-resistant cultures regarding phenotype groups according to the level of their antibiotic resistance allowed determination of 4 PDR-, 8 XDR- and 14 MDR-strains. During the studies on experimental determining of MIC of antibiotic and antiseptics in the condition of applying them as monopreparations against isolated bacterial cultures, we saw significant exceess in the threshold values of MIC, and, first of all, regarding pandrug-resistant and extensive drug-resistant clinical microbial isolates. Use of combinations of antibacterial preparations was found to show the synergic effect of antibiotics (ceftriaxone, ofloxacin, gentamicin) and antiseptics (chlorhexidine, decasan), which is expressed in simultaneous decrease in MIC of each of the tested preparations by 2–8 times compared with their isolative application. Such combinatory approach regarding simultaneous application of antibacterial preparations may be considered as one of the most promising ways to combat poly-resistant clinical isolates of conditionally-pathogenic microorganisms and to offer a new strategic approach to prevention of spread of antibiotic resistance as a phenomenon in medical practice.

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Phage-Encoded Endolysins

Antibiotics ◽

10.3390/antibiotics10020124 ◽

2021 ◽

Vol 10 (2) ◽

pp. 124

Author(s):

Fatma Abdelrahman ◽

Maheswaran Easwaran ◽

Oluwasegun I. Daramola ◽

Samar Ragab ◽

Stephanie Lynch ◽

...

Keyword(s):

Clinical Trials ◽

Cell Wall ◽

Antibiotic Resistance ◽

Bacterial Infections ◽

Therapeutic Strategies ◽

Therapeutic Application ◽

Significant Evidence ◽

Crucial Information

Due to the global emergence of antibiotic resistance, there has been an increase in research surrounding endolysins as an alternative therapeutic. Endolysins are phage-encoded enzymes, utilized by mature phage virions to hydrolyze the cell wall from within. There is significant evidence that proves the ability of endolysins to degrade the peptidoglycan externally without the assistance of phage. Thus, their incorporation in therapeutic strategies has opened new options for therapeutic application against bacterial infections in the human and veterinary sectors, as well as within the agricultural and biotechnology sectors. While endolysins show promising results within the laboratory, it is important to document their resistance, safety, and immunogenicity for in-vivo application. This review aims to provide new insights into the synergy between endolysins and antibiotics, as well as the formulation of endolysins. Thus, it provides crucial information for clinical trials involving endolysins.

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Silencing Antibiotic Resistance with Antisense Oligonucleotides

Biomedicines ◽

10.3390/biomedicines9040416 ◽

2021 ◽

Vol 9 (4) ◽

pp. 416

Author(s):

Saumya Jani ◽

Maria Soledad Ramirez ◽

Marcelo E. Tolmasky

Keyword(s):

Antibiotic Resistance ◽

Nucleic Acids ◽

Antisense Oligonucleotides ◽

Bacterial Infections ◽

Genetic Disorders ◽

Antibiotic Resistance Genes ◽

Short Review ◽

Rnase H ◽

Biological Processes ◽

Locked Nucleic Acids

Antisense technologies consist of the utilization of oligonucleotides or oligonucleotide analogs to interfere with undesirable biological processes, commonly through inhibition of expression of selected genes. This field holds a lot of promise for the treatment of a very diverse group of diseases including viral and bacterial infections, genetic disorders, and cancer. To date, drugs approved for utilization in clinics or in clinical trials target diseases other than bacterial infections. Although several groups and companies are working on different strategies, the application of antisense technologies to prokaryotes still lags with respect to those that target other human diseases. In those cases where the focus is on bacterial pathogens, a subset of the research is dedicated to produce antisense compounds that silence or reduce expression of antibiotic resistance genes. Therefore, these compounds will be adjuvants administered with the antibiotic to which they reduce resistance levels. A varied group of oligonucleotide analogs like phosphorothioate or phosphorodiamidate morpholino residues, as well as peptide nucleic acids, locked nucleic acids and bridge nucleic acids, the latter two in gapmer configuration, have been utilized to reduce resistance levels. The major mechanisms of inhibition include eliciting cleavage of the target mRNA by the host’s RNase H or RNase P, and steric hindrance. The different approaches targeting resistance to β-lactams include carbapenems, aminoglycosides, chloramphenicol, macrolides, and fluoroquinolones. The purpose of this short review is to summarize the attempts to develop antisense compounds that inhibit expression of resistance to antibiotics.

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