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A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Biofilm".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 46535

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Dr. Lorenzo Drago

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Department of Biochemical Sciences for Health, University of Milan, Milan, Italy
Interests: microbiota and probiotics; prosthetic and joint infections; biofilm implant related infections; osteomyelitis; diagnosis for bone-joint infections; antimicrobials and antimicrobial devices
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Dear Colleagues,

Biofilm formation is the key factor in the pathogenesis of implant-associated infections. The most common pathogens isolated are Staphylococcus species, opportunists belonging to the physiological flora of the skin, but other bacteria or fungi can also be involved in these types of infections. Biofilm formation starts with the adhesion of microorganisms and colonization preferentially occurring on the surfaces of a foreign body material. As an interactive symbiotic “city of microbes”, biofilm formation represents an efficient survival strategy for bacteria. In clinically apparent infections, biofilm induces a local host response with infiltration of phagocytic immune cells. Biofilm implant-related infections represent a serious acute and chronic complication, with high morbidity for the patient and elevated costs for the healthcare system. These infections are typically due to the presence of several bacterial species that are able to produce biofilm. Biofilms are able to adhere to implanted biomaterials (e.g., prosthetic implants, endotracheal tubes, intravenous catheters, indwelling urinary catheters, tissue fillers). Microbial biofilms make infections more refractory to the treatments, while slowing tissue repair by stimulating chronic inflammation at the implant site. Preventive measures should be focused primarily on discouraging biofilm formation by protecting implant surfaces with coatings that are able to inhibit bacterial adhesion while maintaining the functional activity of host cells for a good implant integration. Further investigations are needed to develop reliable animal models that would more closely mimic different infections and allow evaluation of the efficacy of surgical procedures as well as systemic or local therapies. To enhance detection of implant-related infections, additional investigative methods are being explored, such as culture-independent molecular techniques. The purpose of this Research Topic is to provide the reader with an updated overview of infections related to the implants. We welcome manuscript representing the current state-of-the-art and providing novel scientific knowledge in view of an improvement of knowledge on implants, new etiologic agents, and biofilm-related infections.

Dr. Lorenzo Drago
Guest Editor

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Keywords

biofilm-related infections
implants
diagnosis
treatment

Related Special Issue

Biofilm Implant Related Infections, 2nd Edition in Microorganisms

Published Papers (11 papers)

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Editorial

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3 pages, 201 KiB

Open AccessEditorial

Viral Bone Infection: A Neglected Disease?

by Lorenzo Drago, Carlo L. Romanò, Ilaria Morelli and Thami Benzakour

Microorganisms 2020, 8(6), 797; https://doi.org/10.3390/microorganisms8060797 - 26 May 2020

Cited by 3 | Viewed by 2790

Abstract

Bone structures reveal viral DNA/RNA, but little is known of the interaction and pathogenesis of viruses and bone diseases. Their detection and identification is often overlooked and not considered by many clinicians and researchers. In this Editorial, we suggest the role of viruses [...] Read more.

(This article belongs to the Special Issue Biofilm Implant Related Infections)

Research

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16 pages, 3877 KiB

Open AccessArticle

Non-Invasive Luciferase Imaging of Type I Interferon Induction in a Transgenic Mouse Model of Biomaterial Associated Bacterial Infections: Microbial Specificity and Inter-Bacterial Species Interactions

by Muhammad Imran Rahim, Andreas Winkel, Stefan Lienenklaus, Nico S. Stumpp, Szymon P. Szafrański, Nadine Kommerein, Elmar Willbold, Janin Reifenrath, Peter P. Mueller, Michael Eisenburger and Meike Stiesch

Microorganisms 2020, 8(10), 1624; https://doi.org/10.3390/microorganisms8101624 - 21 Oct 2020

Cited by 2 | Viewed by 2200

Abstract

The performance of biomaterials is often compromised by bacterial infections and subsequent inflammation. So far, the conventional analysis of inflammatory processes in vivo involves time-consuming histology and biochemical assays. The present study employed a mouse model where interferon beta (IFN-β) is monitored as a marker for non-invasive rapid detection of inflammation in implant-related infections. The mouse model comprises subcutaneous implantation of morphologically modified titanium, followed by experimental infections with four taxonomically diverse oral bacteria: Streptococcus oralis, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Treponema denticola (as mono culture or selected mixed-culture). IFN-β expression increased upon infections depending on the type of pathogen and was prolonged by the presence of the implant. IFN-β expression kinetics reduced with two mixed species infections when compared with the single species. Histological and confocal microscopy confirmed pathogen-specific infiltration of inflammatory cells at the implant-tissue interface. This was observed mainly in the vicinity of infected implants and was, in contrast to interferon expression, higher in infections with dual species. In summary, this non-invasive mouse model can be used to quantify longitudinally host inflammation in real time and suggests that the polymicrobial character of infection, highly relevant to clinical situations, has complex effects on host immunity. Full article

(This article belongs to the Special Issue Biofilm Implant Related Infections)

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13 pages, 1921 KiB

Open AccessArticle

Cutibacterium acnes Biofilm Study during Bone Cells Interaction

by Céline Mongaret, Jennifer Varin-Simon, Fabien Lamret, Taghrid S. El-Mahdy, Lucien Brasme, Véronique Vernet-Garnier, Sophie C. Gangloff, Xavier Ohl and Fany Reffuveille

Microorganisms 2020, 8(9), 1409; https://doi.org/10.3390/microorganisms8091409 - 12 Sep 2020

Cited by 6 | Viewed by 3801

Abstract

Cutibacterium acnes is an opportunistic pathogen involved in Bone and Prosthesis Infections (BPIs). In this study, we observed the behavior of commensal and BPI C. acnes strains in the bone environment through bacterial internalization by osteoblast-like cells and biofilm formation. For the commensal strains, less than 1% of the bacteria were internalized; among them, about 32.7 ± 3.9% persisted intracellularly for up to 48 h. C. acnes infection seems to have no cytotoxic effect on bone cells as detected by LDH assay. Interestingly, commensal C. acnes showed a significant increase in biofilm formation after osteoblast-like internalization for 50% of the strains (2.8-fold increase). This phenomenon is exacerbated on a titanium support, a material used for medical devices. For the BPI clinical strains, we did not notice any increase in biofilm formation after internalization despite a similar internalization rate by the osteoblast-like cells. Furthermore, fluorescent staining revealed more live bacteria within the biofilm after osteoblast-like cell interaction, for all strains (BPIs and commensal). The genomic study did not reveal any link between their clinical origin and phylotype. In conclusion, we have shown for the first time the possible influence of internalization by osteoblast-like cells on commensal C. acnes. Full article

(This article belongs to the Special Issue Biofilm Implant Related Infections)

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11 pages, 1463 KiB

Open AccessArticle

Radial Extracorporeal Shock Wave Therapy against Cutibacterium acnes Implant-Associated Infections: An in Vitro Trial

by Konstantinos Tsikopoulos, Lorenzo Drago, Georgios Koutras, Panagiotis Givissis, Eleni Vagdatli, Prodromos Soukiouroglou and Paraskevi Papaioannidou

Microorganisms 2020, 8(5), 743; https://doi.org/10.3390/microorganisms8050743 - 15 May 2020

Cited by 5 | Viewed by 2153

Abstract

Background: Antibiotic management of low-virulent implant-associated infections induced by Cutibacterium acnes may be compromised by multi-drug resistance development, side effects, and increased cost. Therefore, we sought to assess the effects of shock wave therapy against the above pathogen using an in vitro model of infection. Methods: We used a total of 120 roughened titanium alloy disks, simulating orthopedic biomaterials, to assess the results of radial extracorporeal shock wave therapy (rESWT) against C. acnes (ATCC 11827) biofilms relative to untreated control. In particular, we considered 1.6 to 2.5 Bar with a frequency ranging from 8–11 Hz and 95 to 143 impulses per disk to investigate the antibacterial effect of rESWT against C. acnes planktonic (free-floating) and biofilm forms. Results: Planktonic bacteria load diminished by 54% compared to untreated control after a 1.8-bar setting with a frequency of 8 Hz and 95 impulses was applied (median absorbance (MA) for intervention vs. control groups was 0.9245 (IQR= 0.888 to 0.104) vs. 0.7705 (IQR = 0.712 to 0.864), respectively, p = 0.001). Likewise, a statistically significant reduction in the amount of biofilm relative to untreated control was documented when the above setting was considered (MA for treatment vs biofilm control groups was 0.244 (IQR= 0.215–0.282) and 0.298 (IQR = 0.247–0.307), respectively, p = 0.033). Conclusion: A 50% biofilm eradication was documented following application of low-pressure and low-frequency radial shock waves, so rESWT could be investigated as an adjuvant treatment to antibiotics, but it cannot be recommended as a standalone treatment against device-associated infections induced by C. ances. Full article

(This article belongs to the Special Issue Biofilm Implant Related Infections)

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9 pages, 1105 KiB

Open AccessArticle

Does Intra-Wound Vancomycin Powder Affect the Action of Intra-Articular Tranexamic Acid in Total Joint Replacement?

by Antonios A. Koutalos, Athanasios Drakos, Apostolos Fyllos, Nikos Doxariotis, Sokratis Varitimidis and Konstantinos N. Malizos

Microorganisms 2020, 8(5), 671; https://doi.org/10.3390/microorganisms8050671 - 06 May 2020

Cited by 8 | Viewed by 2099

Abstract

The intra-articular use of tranexamic acid (TXA) has contributed to reduced blood loss in total joint arthroplasty (TJA). The purpose of this study is to assess the efficacy of simultaneously topical use of tranexamic acid and vancomycin powder within the TJA space. From 2016 to 2017, 219 consecutive total hip arthroplasties (THAs) and 272 total knee arthroplasties (TKAs) were performed in a tertiary care center, with a group of patients receiving intra-articular TXA and vancomycin, compared to patients receiving only TXA and to a control group that did not receive anything. Haemoglobin and hematocrit were measured preoperatively, on the first and third days. Transfusions and adverse events were recorded. Haemoglobin and hematocrit dropped significantly in all THA and TKA groups till the third day postoperatively, with a major reduction in the control group, compared to the other two treatment groups. Infections and thromboembolic events were similar in either group of the TJAs. In conclusion, the topical use of tranexamic acid mixed with the vancomycin powder within the joint space after the TJAs of the hip and knee did not alter the anti-fibrinolytic effect of TXA. Full article

(This article belongs to the Special Issue Biofilm Implant Related Infections)

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11 pages, 1353 KiB

Open AccessArticle

Antibiotic-Loaded Hydrogel Coating to Reduce Early Postsurgical Infections in Aseptic Hip Revision Surgery: A Retrospective, Matched Case-Control Study

by Daniele De Meo, Valeria Calogero, Lorenzo Are, Armando U. Cavallo, Pietro Persiani and Ciro Villani

Microorganisms 2020, 8(4), 571; https://doi.org/10.3390/microorganisms8040571 - 15 Apr 2020

Cited by 16 | Viewed by 2950

Abstract

Periprosthetic joint infections (PJIs) are a cause of frequent implant failure in revision hip replacement surgery. The purpose of this study is to evaluate the onset of early postoperative infections in patients who underwent hip surgery with cementless prostheses treated with an antibiotic loaded hydrogel on their surface, in addition to systemic prophylaxis, and compare them to a control group. The secondary objective was to evaluate the onset of any local and systemic adverse effects and interference with bone ingrowth processes and functional recovery. A retrospective observational study was conducted on patients who underwent revision hip surgery by performing a 1:1 match between patients treated with an antibiotic hydrogel (ALH) and the control patients. The incidence of PJIs was assessed with a minimum of six months follow-up. Seventeen patients treated with the ALH were compared with 17 patients from the control group. No PJIs were reported in the ALH group versus the six cases encountered in the control group (p < 0.0001). No significant differences were reported with regard to prosthetic osseointegration and functional results, nor were there side effects in the ALH group. Despite the low sample size, the use of on-site prophylaxis with ALH has proven effective and safe in reducing the risk of PJIs in patients with a high risk for infections. Further studies are needed to validate these results in other implant-related surgeries. Full article

(This article belongs to the Special Issue Biofilm Implant Related Infections)

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12 pages, 1897 KiB

Open AccessArticle

Allium ursinum and Allium oschaninii against Klebsiella pneumoniae and Candida albicans Mono- and Polymicrobic Biofilms in In Vitro Static and Dynamic Models

by Emilia Galdiero, Valeria Di Onofrio, Angela Maione, Edvige Gambino, Renato Gesuele, Bruno Menale, Martina Ciaravolo, Federica Carraturo and Marco Guida

Microorganisms 2020, 8(3), 336; https://doi.org/10.3390/microorganisms8030336 - 27 Feb 2020

Cited by 15 | Viewed by 3742

Abstract

The present study assesses the in vitro antibiofilm potential activity of extracts of wild Allium ursinum and Allium oschaninii. The active ingredients of the extracts were obtained with a technique named Naviglio (rapid solid–liquid dynamic extraction, RSLDE) which is based on an innovative and green solid–liquid extraction methodology. The extracts were tested against models of mono- and polymicrobial biofilm structures of clinically antibiotic-resistant pathogens, Klebsiella pneumoniae ATCC 10031 and Candida albicans ATCC 90028. Biofilms were studied using a static and a dynamic model (microtiter plates and a CDC reactor) on three different surfaces reproducing what happens on implantable medical devices. Antimicrobic activities were determined through minimum inhibitory concentration (MIC), while antibiofilm activity was assessed by minimum biofilm eradication concentration (MBEC) using a crystal violet (CV) biofilm assay and colony forming unit (CFU) counts. Results showed that both Allium extracts eradicated biofilms of the tested microorganisms well; biofilms on Teflon were more susceptible to extracts than those on polypropylene and polycarbonate, suggesting that when grown on a complex substrate, biofilms may be more tolerant to antibiotics. Our data provide significant advances on antibiotic susceptibility testing of biofilms grown on biologically relevant materials for future in vitro and in vivo applications. Full article

(This article belongs to the Special Issue Biofilm Implant Related Infections)

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11 pages, 839 KiB

Open AccessArticle

Investigation on Antibiotic-Resistance, Biofilm Formation and Virulence Factors in Multi Drug Resistant and Non Multi Drug Resistant Staphylococcus pseudintermedius

by Gabriele Meroni, Joel F. Soares Filipe, Lorenzo Drago and Piera A. Martino

Microorganisms 2019, 7(12), 702; https://doi.org/10.3390/microorganisms7120702 - 16 Dec 2019

Cited by 42 | Viewed by 3874

Abstract

Staphylococcus pseudintermedius is a commensal bacterium frequently isolated from canine skin and recognized as a zoonotic agent especially for dog-owners. This study focused on (a) the antibiotic-resistance phenotypes; (b) the ability to produce biofilm (slime); and (c) the dissemination of virulence factors in S. pseudintermedius strains. Seventy-three S. pseudintermedius strains were screened for antibiotic-resistance against 22 different molecules by means of Kirby-Bauer assay. The ability to produce biofilm was investigated using the microtiter plate assay (MtP) and the amplification of icaA and icaD genes. Virulence factors such as cytotoxins (lukI), enterotoxins (seC), and exfoliative toxins (siet, expA, and expB) were evaluated. The antibiotic-resistance profiles revealed 42/73 (57%) multi-drug resistant (MDR) strains and 31/73 (43%) not-MDR. All the MDR strains and 8/31 (27%) of not-MDR resulted in biofilm producers. Leukotoxin LukI was found in 70/73 (96%) of the isolates. Moreover, the enterotoxin gene seC was detected in 47/73 (64%) of the strains. All the isolates carried the siet gene, whereas expA and expB were found in 3/73 (4%) and 5/73 (7%), respectively. In conclusion, S. pseudintermedius should be considered a potential zoonotic and human agent able to carry different virulence determinants and capable of producing biofilm which facilitates horizontal gene transfer. Full article

(This article belongs to the Special Issue Biofilm Implant Related Infections)

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Review

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19 pages, 5790 KiB

Open AccessReview

Diagnosis of Osteoarticular Tuberculosis: Perceptions, Protocols, Practices, and Priorities in the Endemic and Non-Endemic Areas of the World—A WAIOT View

by Vikas M. Agashe, Ashok N. Johari, Mudit Shah, Rashid Anjum, Carlo Romano, Lorenzo Drago, Hemant K. Sharma and Thami Benzakour

Microorganisms 2020, 8(9), 1312; https://doi.org/10.3390/microorganisms8091312 - 28 Aug 2020

Cited by 19 | Viewed by 4840

Abstract

There has been a major resurgence of tuberculosis (TB) and drug-resistant tuberculosis in the last few decades. Although it has been brought under control in most Western countries, it is still a major cause of death in endemic regions like India. Osteoarticular tuberculosis (OA TB) forms a small proportion of the total cases of tuberculosis. Perceptions and practices of orthopedic surgeons are entirely different in endemic and non-endemic regions around the world, due to the vast difference in exposure. Literature from endemic areas puts stress on clinico-radiological diagnosis and empirical anti-tubercular treatment (ATT). Such practices, although non-invasive, simple to implement, and economical, carry a significant risk of missing TB mimics and developing drug resistance. However, OA TB is still perceived as a “diagnostic enigma” in non-endemic regions, leading to a delay in diagnosis. Hence, a high index of suspicion, especially in a high-risk population, is needed to improve the diagnosis. Evolving drug resistance continues to thwart efforts to control the disease globally. This review article discusses the perceptions and practices in different parts of the world, with India as an example of the endemic world, and lays down priorities for overcoming the challenges of diagnosing osteoarticular TB. Full article

(This article belongs to the Special Issue Biofilm Implant Related Infections)

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18 pages, 6399 KiB

Open AccessReview

Spinal Infections: An Update

by Andreas G. Tsantes, Dimitrios V. Papadopoulos, Georgia Vrioni, Spyridon Sioutis, George Sapkas, Ahmed Benzakour, Thami Benzakour, Andrea Angelini, Pietro Ruggieri and Andreas F. Mavrogenis

Microorganisms 2020, 8(4), 476; https://doi.org/10.3390/microorganisms8040476 - 27 Mar 2020

Cited by 83 | Viewed by 10501

Abstract

Spinal infection poses a demanding diagnostic and treatment problem for which a multidisciplinary approach with spine surgeons, radiologists, and infectious disease specialists is required. Infections are usually caused by bacterial microorganisms, although fungal infections can also occur. The most common route for spinal infection is through hematogenous spread of the microorganism from a distant infected area. Most patients with spinal infections diagnosed in early stages can be successfully managed conservatively with antibiotics, bed rest, and spinal braces. In cases of gross or pending instability, progressive neurological deficits, failure of conservative treatment, spinal abscess formation, severe symptoms indicating sepsis, and failure of previous conservative treatment, surgical treatment is required. In either case, close monitoring of the patients with spinal infection with serial neurological examinations and imaging studies is necessary. Full article

(This article belongs to the Special Issue Biofilm Implant Related Infections)

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12 pages, 276 KiB

Open AccessReview

Chloramphenicol Resurrected: A Journey from Antibiotic Resistance in Eye Infections to Biofilm and Ocular Microbiota

by Lorenzo Drago

Microorganisms 2019, 7(9), 278; https://doi.org/10.3390/microorganisms7090278 - 21 Aug 2019

Cited by 32 | Viewed by 6594

Abstract

The advent of multidrug resistance among pathogenic bacteria is devastating the worth of antibiotics and changing the way of their administration, as well as the approach to use new or old drugs. The crisis of antimicrobial resistance is also due to the unavailability of newer drugs, attributable to exigent regulatory requirements and reduced financial inducements. The emerging resistance to antibiotics worldwide has led to renewed interest in old drugs that have fallen into disuse because of toxic side effects. Thus, comprehensive efforts are needed to minimize the pace of resistance by studying emergent microorganisms and optimize the use of old antimicrobial agents able to maintain their profile of susceptibility. Chloramphenicol is experiencing its renaissance because it is widely used in the treatment and prevention of superficial eye infections due to its broad spectrum of activity and other useful antimicrobial peculiarities, such as the antibiofilm properties. Concerns have been raised in the past for the risk of aplastic anemia when chloramphenicol is given intravenously. Chloramphenicol seems suitable to be used as topical eye formulation for the limited rate of resistance compared to fluoroquinolones, for its scarce induction of bacterial resistance and antibiofilm activity, and for the hypothetical low impact on ocular microbiota disturbance. Further in-vitro and in vivo studies on pharmacodynamics properties of ocular formulation of chloramphenicol, as well as its real impact against biofilm and the ocular microbiota, need to be better addressed in the near future. Full article

(This article belongs to the Special Issue Biofilm Implant Related Infections)

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