Metallic biomaterials are engineered systems designed to provide internal support to biological tissues and they are being used largely in joint replacements, dental implants, orthopaedic fixations and stents. Higher biomaterial usage is associated with an increased incidence of implant-related complications due to poor implant integration, inflammation, mechanical instability, necrosis and infections, and associated prolonged patient care, pain and loss of function. In this review, we will briefly explore major representatives of metallic biomaterials along with the key existing and emerging strategies for surface and bulk modification used to improve biointegration, mechanical strength and flexibility of biometals, and discuss their compatibility with the concept of 3D printing.

Metallic Biomaterials: Current Challenges and Opportunities.

Bacterial biofilms are associated with a wide range of infections, from those related to exogenous devices, such as catheters or prosthetic joints, to chronic tissue infections such as those occurring in the lungs of cystic fibrosis patients. Biofilms are recalcitrant to antibiotic treatment due to multiple tolerance mechanisms (phenotypic resistance). This causes persistence of biofilm infections in spite of antibiotic exposure which predisposes to antibiotic resistance development (genetic resistance). Understanding the interplay between phenotypic and genetic resistance mechanisms acting on biofilms, as well as appreciating the diversity of environmental conditions of biofilm infections which influence the effect of antibiotics are required in order to optimize the antibiotic treatment of biofilm infections. Here, we review the current knowledge on phenotypic and genetic resistance in biofilms and describe the potential strategies for the antibiotic treatment of biofilm infections. Of note is the optimization of PK/PD parameters in biofilms, high-dose topical treatments, combined and sequential/alternate therapies or the use antibiotic adjuvants.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/apm.12673

Antibiotic treatment of biofilm infections.

Introduction: Biofilm formation represents a protected mode of growth that renders bacterial cells less susceptible to antimicrobials and to killing by host immune effector mechanisms and so enable...

Biofilm-related disease.

Titanium implants are widely used clinically, but postoperative implant infection remains a potential severe complication. The purpose of this study was to investigate the antibacterial activity of nano-silver(Ag)-functionalized Ti surfaces against epidemic Staphylococcus from the perspective of the regulation of biofilm-related genes and based on a bacteria-cell co-culture study. To achieve this goal, two representative epidemic Staphylococcus strains, Staphylococcus epidermidis (S. epidermidis, RP62A) and Staphylococcus aureus (S. aureus, USA 300), were used, and it was found that an Ag-nanoparticle-modified Ti surface could regulate the expression levels of biofilm-related genes (icaA and icaR for S. epidermidis; fnbA and fnbB for S. aureus) to inhibit bacterial adhesion and biofilm formation. Moreover, a novel bacteria-fibroblast co-culture study revealed that the incorporation of Ag nanoparticles on such a surface can help mammalian cells to survive, adhere and spread more successfully than Staphylococcus. Therefore, the modified surface was demonstrated to possess a good anti-infective capability against both sessile bacteria and planktonic bacteria through synergy between the effects of Ag nanoparticles and ion release. This work provides new insight into the antimicrobial action and mechanism of Ag-nanoparticle-functionalized Ti surfaces with bacteria-killing and cell-assisting capabilities and paves the way towards better satisfying the clinical needs.

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Silver-nanoparticles-modified biomaterial surface resistant to staphylococcus : new insight into the antimicrobial action of silver

Antibiotic resistance has become a serious global concern, and the discovery of antimicrobial herbal constituents may provide valuable solutions to overcome the problem. In this study, the effects of therapies combining antibiotics and four medicinal herbs on methicillin-resistant Staphylococcus aureus (MRSA) were investigated. Specifically, the synergistic effects of Magnolia officinalis, Verbena officinalis, Momordica charantia, and Daphne genkwa in combination with oxacillin or gentamicin against methicillin-resistant (ATCC43300) and methicillin-susceptible (ATCC25923) S. aureus were examined. In vitro susceptibility and synergistic testing were performed to measure the minimum inhibitory concentration and fractional inhibitory concentration (FIC) index of the antibiotics and medicinal herbs against MRSA and methicillin-susceptible S. aureus. To identify the active constituents in producing these synergistic effects, in silico molecular docking was used to investigate the binding affinities of 139 cons...

Synergistic antibacterial effects of herbal extracts and antibiotics on methicillin-resistant Staphylococcus aureus: A computational and experimental study.

Antimicrobial efficacy of combined clarithromycin plus daptomycin against biofilms-formed methicillin-resistant Staphylococcus aureus on titanium medical devices

Mutant selection window of four quinolone antibiotics against clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis.

Objectives Trimethoprim/sulfamethoxazole (SXT) is used to treat Staphylococcus aureus infections. However, the effect of treatment with SXT is sometimes not sufficient and there are patients whose treatment has to be prolonged. There are few reports of isolated strains of SXT-resistant S. aureus, but it is possible that some resistant strains cannot be detected by current testing methods We have therefore developed a tool to identify these resistant strains. Methods The mutant selection window (MSW) of SXT for 40 clinical isolates of S. aureus, including 20 methicillin-resistant S. aureus (MRSA), was determined. The optimum concentration of SXT and thymidine in agar for detecting SXT-resistant small colony variants (SCVs) of S. aureus was investigated. Results The MSW50 and MSW90 of SXT, presented as a multiple of the minimum inhibitory concentration (MIC), were 16× MIC and >256× MIC, respectively. SCVs were detected within the MSW in 32 (80%) of the 40 clinical isolates studied. To maintain the morphology of SCVs, the most suitable concentrations of SXT and thymidine for screening were 4 mg/L and 0.01 μg/mL, respectively. All 32 SCVs were resistant to SXT (MIC >32 mg/L). The sensitivity and specificity of this screening method was 100% and 88.9%, respectively. Conclusions SXT-resistant SCVs are not usually detected by routine laboratory tests performed in hospitals. However, the screening test described here can easily distinguish SXT-resistant SCVs among S. aureus isolated from specimens. This newly developed screening test could become an important tool to prevent inappropriate use of SXT.

Screening method for trimethoprim/sulfamethoxazole-resistant small colony variants of Staphylococcus aureus

Pseudomonas aeruginosa is one of the most common causes of nosocomial infections. Hospital associated infection by multidrug resistant (MDR) strains constitute a serious problem worldwide. The aim of the present study was to evaluate whether exposure to sub-MIC levels of anti-pseudomonas antibiotics and reactive oxygen species (ROS), such as hydroxyl radicals, could lead to MDR of P. aeruginosa. P. aeruginosa standard strain PAO1 was used in this study. All five anti-pseudomonas agents, that is, piperacillin, levofloxacin, meropenem, ceftazidime and amikacin, were investigated for induction of resistance and cross-resistance in vitro. The reference strain was incubated 24 h and transferred 5 times after being exposed to 1 mM H2O2 in addition to a sub-MIC of each antibiotic by the agar dilution method. When cross-resistance to another antibiotic was confirmed, ampC, mexAB, and oprD expression and mutation of QRDR were investigated. Sub-MIC of piperacillin induced resistance to piperacillin and levofloxacin under stimulation with ROS. The mechanism of multi-resistance to β-lactams and levofloxacin was confirmed by RT-PCR. It was a decrease of oprD expression (p<0.05). The increase of MIC was inhibited by the ROS scavenger sodium zinc histidine dihydrolipoyl histidinate (DHL-His-Zn). In conclusion, for P. aeruginosa PAO1 to acquire multidrug resistance, stimulation with ROS was as important as exposure to sub-MIC of piperacillin.

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Emiko Furukawa

Papers

Antimicrobial efficacy of combined clarithromycin plus daptomycin against biofilms-formed methicillin-resistant Staphylococcus aureus on titanium medical devices

Mutant selection window of four quinolone antibiotics against clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis.

Screening method for trimethoprim/sulfamethoxazole-resistant small colony variants of Staphylococcus aureus

Exposure to Reactive Oxygen Species and Piperacillin Leads to MultidrugResistance in Pseudomonas aeruginosa PAO1