Implant-associated infections are the most costly problem in modern orthopedics due to the continued increase in the occurrence of antibiotic-resistant bacterial strains that requires the development of new effective antimicrobials. A non-randomized, prospective, open-label, with historical control study on the use of combined phage/antibiotic therapy of periprosthetic joint infection (PJI) was carried out. Forty-five adult patients with deep PJI of the hip joint were involved in the study, with a 12-month follow-up after one-stage revision surgery. Patients from a prospective study group (SG, n = 23) were treated with specific phage preparation and etiotropic antibiotics, whereas patients from a retrospective comparator group (CG, n = 22) received antibiotics only. The rate of PJI relapses in the SG was eight times less than that in the CG: one case (4.5%) versus eight cases (36.4%), p = 0.021. The response rate to treatment was 95.5% (95% confidence interval (CI) = 0.7511–0.9976) in the SG and only 63.6% (95% CI = 0.4083–0.8198) in the CG. The odds ratio for PJI relapse in patients of the SG was 0.083 (95% CI = 0.009–0.742), which was almost 12 times lower than that in the CG. The obtained results support the efficacy of the combined phage-antibiotic treatment of PJI.
Background: The problem of bacterial colonization of implants used in medical practice continues to be relevant regardless of the material of the implant. Particular attention deserves polymeric implants, which are prepared ex tempore from polymethyl methacrylate, for example - duting orthopedic surgical interventions (so-called "bone cement"). The protection of such implants by antibiotic impregnation is subjected to multiple criticisms, therefore, as an alternative to antibiotics, lytic bacteriophages with a number of unique advantages can be used - however, no experimental studies have been published on the possibility of impregnating bacteriophages into polymethyl methacrylate and their antibacterial activity assessment under such conditions.Aims: to evaluate the possibility of physical placement of bacteriophages in polymethylmethacrylate and to characterize the lytic antibacterial effect of two different strains of bacteriophages when impregnated into polymer carrier ex tempore during the polymerization process in in vitro model.Materials and methods: First stage - Atomic force microscopy (AFM) of polymethyl methacrylate samples for medical purposes was used to determine the presence and size of caverns in polymethyl methacrylate after completion of its polymerization at various reaction temperatures (+6…+25°C and +18…+50°C).The second stage was performed in vitro and included an impregnation of two different bacteriophage strains (phage ph20 active against S. aureus and ph57 active against Ps. aeruginosa) into polymethyl methacrylate during the polymerization process, followed by determination of their antibacterial activity.Results: ACM showed the possibility of bacteriophages placement in the cavities of polymethyl methacrylate - the median of the section and the depth of cavities on the outer surface of the polymer sample polymerized at +18…+50°C were 100.0 and 40.0 nm, respectively, and on the surface of the transverse cleavage of the sample - 120.0 and 100.0 nm, respectively, which statistically did not differ from the geometric dimensions of the caverns of the sample polymerized at a temperature of +6…+25°C.The study of antibacterial activity showed that the ph20 bacteriophage impregnated in polymethyl methacrylate at +6…+25°C lost its effective titer within the first six days after the start of the experiment, while the phage ph57 retained an effective titer for at least 13 days.Conclusion: the study confirmed the possibility of bacteriophages impregnation into medical grade polymethyl methacrylate, maintaining the effective titer of the bacteriophage during phage emission into the external environment, which opens the way for the possible application of this method of bacteriophage delivery in clinical practice. It is also assumed that certain bacteriophages are susceptible to aggressive influences from the chemical components of "bone cement" and / or polymerization reaction products, which requires strict selection of bacteriophage strains that could be suitable for this method of delivery.
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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