scholarly journals Risk assessment of antibiotic resistance development by antibiotic-loaded bone cements: is it a clinical concern?

2019 ◽  
Vol 4 (10) ◽  
pp. 576-584 ◽  
Author(s):  
Christof Berberich ◽  
Pablo Sanz-Ruiz

Because of the risk of bacterial biofilm infections, prophylactic use of antibiotics in orthopaedic procedures involving the implantation of large prosthesis systems is considered mandatory. A strategy based on the rationale that local antibiotics released from bone cement or other carriers establish a second antibacterial frontline in and around the prosthesis is considered complementary to the administration of systemic antibiotics. Although less common as a consequence of the initially very high drug concentrations of local antibiotics in the tissues, a selection process of previous high resistance bacteria may occur, leading to antibiotic resistance. The use of antibiotic combinations in bone cement is generally accepted to improve antibiotic efficacy and minimizes the treatment failure risk due to antibiotic resistance. This is important in septic revisions and/or in patients at particularly high risk of infection. On an individual basis, the benefit of a lower infection probability with combined systemic and local antibiotic application should outweigh the risk of the selection of more resistant bacteria. Each prevented infection means that a complex and extended antibiotic therapy with risk of resistance development over time has been avoided. On an epidemiological level there is no clinical evidence that the routine use of bone cement impregnated with appropriate bactericidal antibiotics promotes the widespread development of antibiotic resistance and thereby puts the successful treatment of a prosthetic joint infection at higher risk. Cite this article: EFORT Open Rev 2019;4:576-584. DOI: 10.1302/2058-5241.4.180104

Author(s):  
Kaspar Tootsi ◽  
Victoria Heesen ◽  
Martin Lohrengel ◽  
Andreas Eugen Enz ◽  
Sebastian Illiger ◽  
...  

Abstract Purpose One of the preventive strategies for periprosthetic joint infection (PJI) is the use of antibiotic-loaded bone cement (ALBC) in primary total joint arthroplasty (TJA). Even though it is widely used, there are concerns about the development of antibacterial resistance. The aim of the study was to investigate whether using ALBC in primary TJA increases the antibiotic-resistant PJI. The hypothesis was that the regular use of ALBC does not increase the rate of resistant PJI. Methods Patients with confirmed PJI who had revision surgery from year 2010 to 2019 were included in this international multicenter study. The ALBC group was compared to the non-ALBC TJA group from the same time period. Medical records were used to collect clinical (age, gender, body mass index, comorbidities), TJA-related (type of operation, implant type and survival) and PJI-related (cultured microorganism, antibiogram) data. Resistance to gentamicin, clindamycin and vancomycin were recorded from the antibiograms. Multiple logistic regression model was used to identify risk factors and account for the potential confounders. Results 218 patients with PJI were included in the study: 142 with gentamicin-loaded bone cement and 76 in the non-ALBC group. The average age in the ALBC group was 71 ± 10 years and 62 ± 12 years in the comparison group (p < 0.001). Coagulase negative Staphylococci (CONS) were the most common (49%) isolated pathogens. The use of ALBC did not increase the rate of any resistant bacteria significantly (OR = 0.79 (0.42–1.48), p = 0.469). The presence of CONS was associated with higher risk of antibiotic resistance. Conclusions The current study demonstrates no increase in antibiotic resistance due to ALBC after primary TJA. Thus, the use of ALBC during primary TJA should not be feared in the context of antimicrobial resistance. Level of evidence III.


Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 871
Author(s):  
Mohammed F. Aldawsari ◽  
El-Sayed Khafagy ◽  
Ahmed Al Saqr ◽  
Ahmed Alalaiwe ◽  
Hisham A. Abbas ◽  
...  

The bacterial resistance development due to the incessant administration of antibiotics has led to difficulty in their treatment. Natural adjuvant compounds can be co-administered to hinder the pathogenesis of resistant bacteria. Sotolon is the prevailing aromatic compound that gives fenugreek its typical smell. In the current work, the anti-virulence activities of sotolon on Pseudomonas aeruginosa have been evaluated. P. aeruginosa has been treated with sotolon at sub-minimum inhibitory concentration (MIC), and production of biofilm and other virulence factors were assessed. Moreover, the anti-quorum sensing (QS) activity of sotolon was in-silico evaluated by evaluating the affinity of sotolon to bind to QS receptors, and the expression of QS genes was measured in the presence of sotolon sub-MIC. Furthermore, the sotolon in-vivo capability to protect mice against P. aeruginosa was assessed. Significantly, sotolon decreased the production of bacterial biofilm and virulence factors, the expression of QS genes, and protected mice from P. aeruginosa. Conclusively, the plant natural substance sotolon attenuated the pathogenicity of P. aeruginosa, locating it as a plausible potential therapeutic agent for the treatment of its infections. Sotolon can be used in the treatment of bacterial infections as an alternative or adjuvant to antibiotics to combat their high resistance to antibiotics.


2021 ◽  
Author(s):  
Fernando Sanz-García ◽  
Sara Hernando-Amado ◽  
José Luis Martínez

ABSTRACTBACKGROUNDAntibiotic pollution of non-clinical environments might have a relevant impact on human health if resistant pathogens are selected. However, this potential risk is often overlooked, since drug concentrations in nature are usually below their minimal inhibitory concentrations (MICs). Albeit, antibiotic resistant bacteria can be selected even at sub-MIC concentrations, in a range that is dubbed the sub-MIC selective window, which depends on both the antibiotic and the pathogen.OBJECTIVESDetermine the sub-MIC selective windows of seven antibiotics of clinical relevance in the opportunistic pathogen Pseudomonas aeruginosa and evaluate the risk for selecting resistant mutants in nature, based on published data about the amount of antimicrobials detected in natural environments.METHODSWe conducted evolution experiments of P. aeruginosa PA14 in presence of sub-MIC concentrations of ceftazidime, amikacin, levofloxacin, ciprofloxacin, tetracycline, polymyxin B or imipenem, and measured drug susceptibility of the evolved populations.RESULTSSub-MIC selective window of quinolones was the largest, and the ones of polymyxin B and imipenem, the narrowest. Clinically relevant multidrug resistant (MDR) mutants (presenting MICs above EUCAST clinical breakpoints) arose within the sub-MIC selective windows of the majority of antibiotics tested, being these phenotypes probably mediated by efflux pumps′ activity.DISCUSSIONOur data show that the concentration of antibiotics reported in aquatic ecosystems -colonizable by P. aeruginosa- are, in occasions, higher than the ones able to select MDR mutants. This finding has implications for understanding the role of different ecosystems and conditions in the emergence of antibiotic resistance from a One-Health point of view. Further, it highlights the importance of delineating the sub-MIC selective windows for drugs of clinical value in pathogens with environmental niches, in order to evaluate the health risks due to antibiotic pollution of natural ecosystems and ultimately tackle antibiotic resistance.


2016 ◽  
Vol 54 (6) ◽  
pp. 1656-1659 ◽  
Author(s):  
Kyung-Hwa Park ◽  
Kerryl E. Greenwood-Quaintance ◽  
Arlen D. Hanssen ◽  
Matthew P. Abdel ◽  
Robin Patel

We compared culture results to investigate the influence of antimicrobial-loaded cement on sonicate fluid culture positivity for the diagnosis of prosthetic joint infection. Fifty-four subjects were assessed. The sensitivities of sonicate fluid culture were 77.8% (14 of 18) in subjects with an antimicrobial-loaded cemented prosthesis and 58.3% (21 of 36) in subjects with an antimicrobial-free prosthesis.


2020 ◽  
Vol 11 ◽  
Author(s):  
Jonas D. Van Belleghem ◽  
Robert Manasherob ◽  
Ryszard Miȩdzybrodzki ◽  
Paweł Rogóż ◽  
Andrzej Górski ◽  
...  

Prosthetic joint infection (PJI) is a devastating complication after a joint replacement. PJI and its treatment have a high monetary cost, morbidity, and mortality. The lack of success treating PJI with conventional antibiotics alone is related to the presence of bacterial biofilm on medical implants. Consequently, surgical removal of the implant and prolonged intravenous antibiotics to eradicate the infection are necessary prior to re-implanting a new prosthetic joint. Growing clinical data shows that bacterial predators, called bacteriophages (phages), could be an alternative treatment strategy or prophylactic approach for PJI. Phages could further be exploited to degrade biofilms, making bacteria more susceptible to antibiotics and enabling potential combinatorial therapies. Emerging research suggests that phages may also directly interact with the innate immune response. Phage therapy may play an important, and currently understudied, role in the clearance of PJI, and has the potential to treat thousands of patients who would either have to undergo revision surgery to attempt to clear an infections, take antibiotics for a prolonged period to try and suppress the re-emerging infection, or potentially risk losing a limb.


Author(s):  
Umraz Khan ◽  
Graeme Perks ◽  
Rhidian Morgan-Jones ◽  
Peter James ◽  
Colin Esler ◽  
...  

This chapter discusses specific microbiology issues relating to prosthetic joint infection (PJI) and includes discussion on antibiotic prophylaxis (including elective joint replacement in the uninfected case), choice of ‘prophylaxis/treatment’ in the infected, or presumed, infected case, a suggested framework for a safe practice, antibiotic use in PJI in the age of resistance, background on rising antibiotic resistance, approach to one- and two-stage surgical management, outpatient antibiotic therapy and when to use it, monitoring/stopping rules, the particular problems of Pseudomonas and Candida in PJI, and myths and facts about what ‘immunosuppression’ actually means in practice (including MRSA), and a conclusion.


2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Tiao Lin ◽  
Xun-Zi Cai ◽  
Ming-Min Shi ◽  
Zhi-Min Ying ◽  
Bin Hu ◽  
...  

Ultrasound (US) has been used to increase elution of antibiotic from an antibiotic-loaded poly(methyl methacrylate) (PMMA) bone cement (ALBC). We aimed to further investigate whether microbubbles-mediated US (US + MB) facilitate elution of vancomycin (VAN) from cylindrical specimens and enhance the activity of the eluted antibiotic againstStaphylococcus aureus(S. aureus) in vitro. The study groups comprised cylindrical bone cement fabricated with VAN (VAN), ALBC using US (VAN + US), and ALBC using MB-mediated US (VAN + US + MB). We also carried out an in vivo study involving the activity of VAN from cylindrical cement implanted in tibiae of New Zealand white rabbits inoculated withS. aureus. We found that (1) in vitro, elution from VAN + US + MB cylinders was significantly higher than from either the VAN or VAN + US specimens; (2) the activity of the eluted VAN from the VAN + US + MB cylinders against planktonicS. aureuswas significantly higher than from either the control or VAN or VAN + US specimens; and (3) in the rabbits, the activity of the eluted VAN from the VAN + US + MB cylinders againstS. aureuswas significantly higher than from either the control or VAN or VAN + US specimens. The present results suggest that VAN-loaded PMMA cement irradiated with MB-mediated US may have a role in controlling prosthetic joint infection.


2013 ◽  
Vol 47 (1) ◽  
pp. e2-e2 ◽  
Author(s):  
Nicholas J Cortes ◽  
John M Lloyd ◽  
Leszek Koziol ◽  
Lawrence O'Hara

OBJECTIVE To describe the safe and successful use of daptomycin-impregnated polymethyl methacrylate (PMMA) bone cement in the treatment of a case of recurrent prosthetic joint infection in a patient with multiple antibiotic allergies and past colonization with multiply antibiotic-resistant organisms. CASE SUMMARY A 79-year-old female had a history of chronic recurrent left prosthetic hip infection. The patient had confirmed allergies to multiple antibiotics and a past history of colonization with methicillin-resistant Staphylococcus aureus. At first-stage revision surgery, the infected prosthesis was removed and samples were sent for microbiologic culture. A spacer device was fashioned, with incorporation of daptomycin and gentamicin into the PMMA bone cement at a concentration of 5% w/w for each antibiotic. Systemic daptomycin and gentamicin were administered postoperatively for 14 days. Propionibacterium acnes was isolated from deep-tissue specimens. The patient made excellent postoperative progress and was discharged after 2 weeks. Second-stage revision surgery was performed at 6 months, with no signs of persistent infection. She remained well, pain free, and mobilizing independently 2 years later. DISCUSSION Daptomycin, a cyclic lipopeptide antibiotic, is approved for systemic treatment of endocarditis and skin and soft tissue infections. In vitro data demonstrate acceptable drug elution from and tensile strength of daptomycin-impregnated PMMA bone cement; however, clinical data are lacking. In our patient's case, the cement formulation was well tolerated, with no adverse effects detected, and demonstrated adequate mechanical strength in vivo. Infection with P. acnes, an unusual pathogen, was successfully treated. Further clinical studies are required to assess the efficacy of daptomycin-impregnated cement in infection with more typical pathogens, such as S. aureus. CONCLUSIONS Daptomycin impregnation of PMMA bone cement may be an option in cases in which patient or pathogen factors preclude use of routinely incorporated agents.


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