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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 2022) | Viewed by 55450

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Special Issue Editors

Dr. Alessandra Oliva

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Guest Editor

Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
Interests: biofilm-related infections; antimicrobial resistance; nosocomial infections; anti-biofilm antibiotics
Special Issues, Collections and Topics in MDPI journals

Dr. María Guembe

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Guest Editor

1. Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, 28007 Madrid, Spain;
2. Instituto de Investigación Sanitaria Gregorio Marañón, 28007 Madrid, Spain
Interests: biofilm; catheter; prosthesis; diagnosis; prevention
Special Issues, Collections and Topics in MDPI journals

Dr. Enea G. Di Domenico

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Guest Editor

Department of Biology and Biotechnology "C. Darwin", Sapienza University of Rome, 00185 Rome, Italy
Interests: biofilm; infection; inflammation; resistance; antibiotic

Special Issue Information

Dear Colleagues,

Biofilm-related infections occur due to the presence of bacterial or fungal cells deposited on the surface of tissues or devices (skin, lungs, catheter, prosthesis, etc.). As a result, an extracellular matrix composed of water, polysaccharides, lipids, proteins, and extracellular DNA is formed, making the biofilm highly resistant to antibiotic treatment and the host’s immune response. During biofilm development, cells from the uppermost layers begin to spread and may invade other tissues, such as the blood, causing bacteremia/fungemia. Therefore, the role of biofilm is crucial in the management and clinical outcome of patients.

In this Special Issue of Microorganisms, dedicated to “Biofilm-Related Infections in Healthcare”, we invite you to send contributions concerning any aspects related to the role of bacterial and fungal biofilms on devices and tissue-related infections, including pathogenicity and clinical impact, how to diagnose biofilm production and its limitations (such as deficiencies on in vitro models, lack of reproducibility techniques, etc.), and the emergence of new preventive and therapeutic approaches based on nanobiotechnology.

Dr. Alessandra Oliva
Dr. María Guembe
Dr. Enea G. Di Domenico
Guest Editors

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Keywords

biofilm
pathogenesis
prosthesis
nanoparticles
prevention

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Published Papers (12 papers)

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Editorial

Jump to: Research, Review, Other

3 pages, 184 KiB

Open AccessEditorial

Biofilm-Related Infections in Healthcare: Moving towards New Horizons

by Enea Gino Di Domenico, Alessandra Oliva and María Guembe

Microorganisms 2024, 12(4), 784; https://doi.org/10.3390/microorganisms12040784 - 12 Apr 2024

Viewed by 1149

Abstract

In this Special Issue, titled “Biofilm-Related Infections in Healthcare”, we have reported considerable progress in understanding the physiology and pathology of biofilms [...] Full article

(This article belongs to the Special Issue Biofilm-Related Infections in Healthcare)

Research

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16 pages, 2185 KiB

Open AccessArticle

Differential Susceptibility of Mixed Polymicrobial Biofilms Involving Ocular Coccoid Bacteria (Staphylococcus aureus and S. epidermidis) and a Filamentous Fungus (Fusarium solani) on Ex Vivo Human Corneas

by Sisinthy Shivaji, Banka Nagapriya and Konduri Ranjith

Microorganisms 2023, 11(2), 413; https://doi.org/10.3390/microorganisms11020413 - 6 Feb 2023

Cited by 4 | Viewed by 1960

Abstract

Biofilms confer several advantages to the organisms associated with them, such as increased resistances to antibacterial and antifungal compounds compared to free living cells. Compared to monomicrobial biofilms involving a single microorganism, biofilms composed of microorganisms affiliated to bacterial and fungal kingdoms are predominant in nature. Despite the predominance of polymicrobial biofilms, and more so mixed polymicrobial biofilms, they are rarely studied. The objective of the current study is to evaluate the potential of ocular bacteria and a filamentous fungus to form monomicrobial and mixed polymicrobial biofilms on synthetic and natural substrates and to monitor their response to antibiotics. In this sense, we demonstrated that the ocular pathogens Staphylococcus aureus, S. epidermidis, and Fusarium solani form monomicrobial and mixed polymicrobial biofilms both on tissue culture polystyrene plates and on ex vivo human corneas from cadavers using confocal microscopy and scanning electron microscopy. Additionally, the mixed polymicrobial biofilms involving the above ocular bacteria and a filamentous fungus were less susceptible to different antibacterials and antifungals in relation to the corresponding control planktonic cells. Further, the MICs to the screened antibacterials and antifungals in polymicrobial biofilms involving a bacterium or a fungus was either increased, decreased, or unchanged compared to the corresponding individual bacterial or fungal biofilm. The results would be useful to the ophthalmologist to plan effective treatment regimens for the eye since these are common pathogens of the eye causing keratitis, endophthalmitis, conjunctivitis, etc. Full article

(This article belongs to the Special Issue Biofilm-Related Infections in Healthcare)

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20 pages, 1323 KiB

Open AccessArticle

Are There Any Changes in the Causative Microorganisms Isolated in the Last Years from Hip and Knee Periprosthetic Joint Infections? Antimicrobial Susceptibility Test Results Analysis

by Mihai Dan Roman, Bogdan-Axente Bocea, Nicolas-Ionut-Catalin Ion, Andreea Elena Vorovenci, Dan Dragomirescu, Rares-Mircea Birlutiu, Victoria Birlutiu and Sorin Radu Fleaca

Microorganisms 2023, 11(1), 116; https://doi.org/10.3390/microorganisms11010116 - 1 Jan 2023

Cited by 12 | Viewed by 2570

Abstract

Background: PJIs following total hip and knee arthroplasty represent severe complications with broad implications, and with significant disability, morbidity, and mortality. To be able to provide correct and effective management of these cases, an accurate diagnosis is needed. Classically, acute PJIs are characterized by a preponderance of virulent microorganisms, and chronic PJIs are characterized by a preponderance of less-virulent pathogens like coagulase-negative staphylococci or Cutibacterium species. This paper aims to analyze if there are any changes in the causative microorganisms isolated in the last years, as well as to provide a subanalysis of the types of PJIs. Methods: In this single-center study, we prospectively included all retrospectively consecutive collected data from patients aged over 18 years that were hospitalized from 2016 through 2022, and patients that underwent a joint arthroplasty revision surgery. A standardized diagnostic protocol was used in all cases, and the 2021 EBJIS definition criteria for PJIs was used. Results: 114 patients were included in our analysis; of them, 67 were diagnosed with PJIs, 12 were acute/acute hematogenous, and 55 were chronic PJIs. 49 strains of gram-positive aerobic or microaerophilic cocci and 35 gram-negative aerobic bacilli were isolated. Overall, Staphylococcus aureus was the most common isolated pathogen, followed by coagulase-negative staphylococci (CoNS). All cases of acute/acute hematogenous PJIs were caused by gram-positive aerobic or microaerophilic cocci pathogens. Both Staphylococcus epidermidis and methicillin-resistant S. aureus were involved in 91.66% of the acute/acute hematogenous PJIs cases. 21.8% of the chronic PJIs cases were caused by pathogens belonging to the Enterobacterales group of bacteria, followed by the gram-negative nonfermenting bacilli group of bacteria, which were involved in 18.4% of the cases. 12 chronic cases were polymicrobial. Conclusion: Based on our findings, empiric broad-spectrum antibiotic therapy in acute PJIs could be focused on the bacteria belonging to the gram-positive aerobic or microaerophilic cocci, but the results should be analyzed carefully, and the local resistance of the pathogens should be taken into consideration. Full article

(This article belongs to the Special Issue Biofilm-Related Infections in Healthcare)

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8 pages, 2664 KiB

Open AccessCommunication

Norepinephrine Effects on Uropathogenic Strains Virulence

by Nadezhda Ignatova, Alina Abidullina, Olga Streltsova, Vadim Elagin and Vladislav Kamensky

Microorganisms 2022, 10(11), 2248; https://doi.org/10.3390/microorganisms10112248 - 14 Nov 2022

Cited by 2 | Viewed by 1529

Abstract

The degree of virulence correlates with adhesion, biofilm formation, motility and the capacity to quickly colonize biological surfaces. The virulence of the bacteria that have colonized the urinary tract may be modified by substances dissolved in urine. One such substance is the norepinephrine (NE) hormone, which may be present in human urine, especially in times of stress and under changes in the activity of the renin-angiotensin-aldesterone system. In this work, we study the influence of NE on the biomass, biofilm formation, matrix production, adhesion, motility and metabolism of uropathogenic strains of E. coli and S. aureus. We used Congo red and gentian violet staining for detection of matrix and biomass formation, respectively. The optical density was measured by a multichannel spectrophotometer. The motility of bacterial cells was measured on semi-solid agar at 24 h and 48 h. The metabolic activity was analyzed by MTT assay. It was shown that the metabolic activity of E. coli was stimulated by NE, which led to the increasing synthesis of virulence factors such as biofilm production, adhesion, and motility. At the same time, NE did not activate the S. aureus strain’s metabolism and did not change its adhesion and motility. Thus, the virulence activity of uropathogenic E. coli may be modified by NE in urine. Full article

(This article belongs to the Special Issue Biofilm-Related Infections in Healthcare)

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13 pages, 4645 KiB

Open AccessArticle

Cell-Free Supernatants (CFSs) from the Culture of Bacillus subtilis Inhibit Pseudomonas sp. Biofilm Formation

by Shirmin Islam, Md. Liton Mahmud, Waleed H. Almalki, Suvro Biswas, Md. Ariful Islam, Md. Golam Mortuza, Mohammad Akbar Hossain, Md. Akhtar-E Ekram, Md. Salah Uddin, Shahriar Zaman and Md. Abu Saleh

Microorganisms 2022, 10(11), 2105; https://doi.org/10.3390/microorganisms10112105 - 24 Oct 2022

Cited by 7 | Viewed by 2794

Abstract

Biofilm inhibition has been identified as a novel drug target for the development of broad-spectrum antibiotics to combat infections caused by drug-resistant bacteria. Although several plant-based compounds have been reported to have anti-biofilm properties, research on the anti-biofilm properties of bacterial bioactive compounds has been sparse. In this study, the efficacy of compounds from a cell-free supernatant of Bacillus subtilis against a biofilm formation of Pseudomonas sp. was studied through in vitro, in vivo and in silico studies. Here, in well diffusion method, Bacillus subtilis demonstrated antibacterial activity, and more than 50% biofilm inhibition activity against Pseudomonas sp. was exhibited through in vitro studies. Moreover, molecular docking and molecular dynamics (MD) simulation gave insights into the possible mode of action of the bacterial volatile compounds identified through GC-MS to inhibit the biofilm-formation protein (PDB ID: 7M1M) of Pseudomonas sp. The binding energy revealed from docking studies ranged from −2.3 to −7.0 kcal mol⁻¹. Moreover, 1-(9H-Fluoren-2-yl)-2-(1-phenyl-1H-ttetrazole5-ylsulfanyl)-ethanone was found to be the best-docked compound through ADMET and pharmacokinetic properties. Furthermore, MD simulations further supported the in vitro studies and formed a stable complex with the tested protein. Thus, this study gives an insight into the development of new antibiotics to combat multi-drug-resistant bacteria. Full article

(This article belongs to the Special Issue Biofilm-Related Infections in Healthcare)

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12 pages, 2636 KiB

Open AccessArticle

An Experimental Murine Model to Assess Biofilm Persistence on Commercial Breast Implant Surfaces

by Francisco Carmona-Torre, Leire Fernández-Ciriza, Carlos Berniz, Cristina Gomez-Martinez de Lecea, Ana Ramos, Bernardo Hontanilla and Jose L. del Pozo

Microorganisms 2022, 10(10), 2004; https://doi.org/10.3390/microorganisms10102004 - 11 Oct 2022

Viewed by 2154

Abstract

Capsular contracture is the most frequently associated complication following breast implant placement. Biofilm formation on the surface of such implants could significantly influence the pathogenesis of this complication. The objective of this study was to design an experimental model of breast implant infection that allowed us to compare the in vivo S. epidermidis ability to form and perpetuate biofilms on commonly used types of breast implants (i.e., macrotexturized, microtexturized, and smooth). A biofilm forming S. epidermidis strain (ATCC 35984) was used for all experiments. Three different implant surface types were tested: McGhan BIOCELL^® (i.e., macrotexturized); Mentor Siltex^® (i.e., microtexturized); and Allergan Natrelle Smooth^® (i.e., smooth). Two different infection scenarios were simulated. The ability to form biofilm on capsules and implants over time was evaluated by quantitative post-sonication culture of implants and capsules biopsies. This experimental model allows the generation of a subclinical staphylococcal infection associated with a breast implant placed in the subcutaneous tissue of Wistar rats. The probability of generating an infection was different according to the type of implant studied and to the time from implantation to implant removal. Infection was achieved in 88.9% of macrotextured implants (i.e., McGhan), 37.0% of microtexturized implants (i.e., Mentor), and 18.5% of smooth implants (i.e., Allergan Smooth) in the short-term (p < 0.001). Infection was achieved in 47.2% of macrotextured implants, 2.8% of microtexturized implants, and 2.8% of smooth implants (i.e., Allergan Smooth) in the long-term (p < 0.001). There was a clear positive correlation between biofilm formation on any type of implant and capsule colonization/infection. Uniformly, the capsules formed around the macro- or microtexturized implants were consistently macroscopically thicker than those formed around the smooth implants regardless of the time at which they were removed (i.e., 1–2 weeks or 3–5 weeks). We have shown that there is a difference in the ability of S epidermidis to develop in vivo biofilms on macrotextured, microtextured, and smooth implants. Smooth implants clearly thwart bacterial adherence and, consequently, biofilm formation and persistence are hindered. Full article

(This article belongs to the Special Issue Biofilm-Related Infections in Healthcare)

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12 pages, 1235 KiB

Open AccessArticle

Effect of Surface Roughness of Deciduous and Permanent Tooth Enamel on Bacterial Adhesion

by Bernardo Teutle-Coyotecatl, Rosalía Contreras-Bulnes, Laura Emma Rodríguez-Vilchis, Rogelio José Scougall-Vilchis, Ulises Velazquez-Enriquez, Argelia Almaguer-Flores and Jesús Angel Arenas-Alatorre

Microorganisms 2022, 10(9), 1701; https://doi.org/10.3390/microorganisms10091701 - 24 Aug 2022

Cited by 15 | Viewed by 2635

Abstract

The adhesion of some bacteria has been attributed to critical levels of roughness in hard tissues, which increases the risk of developing caries. The objective of this work was to assess the effect of deciduous and permanent tooth enamel surface roughness on bacterial adhesion. One hundred and eight samples of deciduous and permanent enamel were divided into two groups (n = 54). G1_DE deciduous enamel and G2_PE permanent enamel. The surface roughness was measured by profilometry and atomic force microscopy (AFM). Subsequently, the evaluation of bacterial adherence was carried out in triplicate by means of the XTT cell viability test. Additionally, bacterial adhesion was observed using scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). The average values of the micrometric roughness in both groups were similar; however, in the nanometric scale they presented significant differences. Additionally, the G1_DE group showed the highest amount of adhered S. mutans and S. sanguinis compared to the G2_EP group. Although the roughness of deciduous and permanent enamel showed contrasting results according to the evaluation technique (area and scale of analysis), bacterial adhesion was greater in deciduous enamel; hence, enamel roughness may not be a determining factor in the bacterial adhesion phenomenon. Full article

(This article belongs to the Special Issue Biofilm-Related Infections in Healthcare)

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Review

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20 pages, 633 KiB

Open AccessReview

Larval Therapy and Larval Excretions/Secretions: A Potential Treatment for Biofilm in Chronic Wounds? A Systematic Review

by Daniel Morris, Micah Flores, Llinos Harris, John Gammon and Yamni Nigam

Microorganisms 2023, 11(2), 457; https://doi.org/10.3390/microorganisms11020457 - 11 Feb 2023

Cited by 9 | Viewed by 12061

Abstract

Chronic wounds present a global healthcare challenge and are increasing in prevalence, with bacterial biofilms being the primary roadblock to healing in most cases. A systematic review of the to-date knowledge on larval therapy’s interaction with chronic-wound biofilm is presented here. The findings detail how larval therapy—the controlled application of necrophagous blowfly larvae—acts on biofilms produced by chronic-wound-relevant bacteria through their principle pharmacological mode of action: the secretion and excretion of biologically active substances into the wound bed. A total of 12 inclusion-criteria-meeting publications were identified following the application of a PRISMA-guided methodology for a systematic review. The findings of these publications were qualitatively analyzed to provide a summary of the prevailing understanding of larval therapy’s effects on bacterial biofilm. A further review assessed the quality of the existing evidence to identify knowledge gaps and suggest ways these may be bridged. In summary, larval therapy has a seemingly unarguable ability to inhibit and degrade bacterial biofilms associated with impaired wound healing. However, further research is needed to clarify and standardize the methodological approach in this area of investigation. Such research may lead to the clinical application of larval therapy or derivative treatments for the management of chronic-wound biofilms and improve patient healing outcomes at a time when alternative therapies are desperately needed. Full article

(This article belongs to the Special Issue Biofilm-Related Infections in Healthcare)

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22 pages, 1464 KiB

Open AccessReview

Mixed Fungal Biofilms: From Mycobiota to Devices, a New Challenge on Clinical Practice

by Polyana de Souza Costa, Andressa Prado, Natalia Pecin Bagon, Melyssa Negri and Terezinha Inez Estivalet Svidzinski

Microorganisms 2022, 10(9), 1721; https://doi.org/10.3390/microorganisms10091721 - 26 Aug 2022

Cited by 11 | Viewed by 4814

Abstract

Most current protocols for the diagnosis of fungal infections are based on culture-dependent methods that allow the evaluation of fungal morphology and the identification of the etiologic agent of mycosis. Most current protocols for the diagnosis of fungal infections are based on culture-dependent methods that enable the examination of the fungi for further identification of the etiological agent of the mycosis. The isolation of fungi from pure cultures is typically recommended, as when more than one species is identified, the second agent is considered a contaminant. Fungi mostly survive in highly organized communities that provoke changes in phenotypic profile, increase resistance to antifungals and environmental stresses, and facilitate evasion from the immune system. Mixed fungal biofilms (MFB) harbor more than one fungal species, wherein exchange can occur that potentialize the effects of these virulence factors. However, little is known about MFB and their role in infectious processes, particularly in terms of how each species may synergistically contribute to the pathogenesis. Here, we review fungi present in MFB that are commensals of the human body, forming the mycobiota, and how their participation in MFB affects the maintenance of homeostasis. In addition, we discuss how MFB are formed on both biotic and abiotic surfaces, thus being a significant reservoir of microorganisms that have already been associated in infectious processes of high morbidity and mortality. Full article

(This article belongs to the Special Issue Biofilm-Related Infections in Healthcare)

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18 pages, 1151 KiB

Open AccessReview

Bacterial Interactions in the Context of Chronic Wound Biofilm: A Review

by Benjamin A. R. N. Durand, Cassandra Pouget, Chloé Magnan, Virginie Molle, Jean-Philippe Lavigne and Catherine Dunyach-Remy

Microorganisms 2022, 10(8), 1500; https://doi.org/10.3390/microorganisms10081500 - 25 Jul 2022

Cited by 36 | Viewed by 5015

Abstract

Chronic wounds, defined by their resistance to care after four weeks, are a major concern, affecting millions of patients every year. They can be divided into three types of lesions: diabetic foot ulcers (DFU), pressure ulcers (PU), and venous/arterial ulcers. Once established, the classical treatment for chronic wounds includes tissue debridement at regular intervals to decrease biofilm mass constituted by microorganisms physiologically colonizing the wound. This particular niche hosts a dynamic bacterial population constituting the bed of interaction between the various microorganisms. The temporal reshuffle of biofilm relies on an organized architecture. Microbial community turnover is mainly associated with debridement (allowing transitioning from one major representant to another), but also with microbial competition and/or collaboration within wounds. This complex network of species and interactions has the potential, through diversity in antagonist and/or synergistic crosstalk, to accelerate, delay, or worsen wound healing. Understanding these interactions between microorganisms encountered in this clinical situation is essential to improve the management of chronic wounds. Full article

(This article belongs to the Special Issue Biofilm-Related Infections in Healthcare)

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17 pages, 1103 KiB

Open AccessReview

Clinical Infections, Antibiotic Resistance, and Pathogenesis of Staphylococcus haemolyticus

by Hala O. Eltwisy, Howida Omar Twisy, Mahmoud HR Hafez, Ibrahim M. Sayed and Mohamed A. El-Mokhtar

Microorganisms 2022, 10(6), 1130; https://doi.org/10.3390/microorganisms10061130 - 31 May 2022

Cited by 42 | Viewed by 12024

Abstract

Staphylococcus haemolyticus (S. haemolyticus) constitutes the main part of the human skin microbiota. It is widespread in hospitals and among medical staff, resulting in being an emerging microbe causing nosocomial infections. S. haemolyticus, especially strains that cause nosocomial infections, are more resistant to antibiotics than other coagulase-negative Staphylococci. There is clear evidence that the resistance genes can be acquired by other Staphylococcus species through S. haemolyticus. Severe infections are recorded with S. haemolyticus such as meningitis, endocarditis, prosthetic joint infections, bacteremia, septicemia, peritonitis, and otitis, especially in immunocompromised patients. In addition, S. haemolyticus species were detected in dogs, breed kennels, and food animals. The main feature of pathogenic S. haemolyticus isolates is the formation of a biofilm which is involved in catheter-associated infections and other nosocomial infections. Besides the biofilm formation, S. haemolyticus secretes other factors for bacterial adherence and invasion such as enterotoxins, hemolysins, and fibronectin-binding proteins. In this review, we give updates on the clinical infections associated with S. haemolyticus, highlighting the antibiotic resistance patterns of these isolates, and the virulence factors associated with the disease development. Full article

(This article belongs to the Special Issue Biofilm-Related Infections in Healthcare)

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Other

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16 pages, 1407 KiB

Open AccessPerspective

The Current Knowledge on the Pathogenesis of Tissue and Medical Device-Related Biofilm Infections

by Enea Gino Di Domenico, Alessandra Oliva and María Guembe

Microorganisms 2022, 10(7), 1259; https://doi.org/10.3390/microorganisms10071259 - 21 Jun 2022

Cited by 43 | Viewed by 5182

Abstract

Biofilm is the trigger for the majority of infections caused by the ability of microorganisms to adhere to tissues and medical devices. Microbial cells embedded in the biofilm matrix are highly tolerant to antimicrobials and escape the host immune system. Thus, the refractory nature of biofilm-related infections (BRIs) still represents a great challenge for physicians and is a serious health threat worldwide. Despite its importance, the microbiological diagnosis of a BRI is still difficult and not routinely assessed in clinical microbiology. Moreover, biofilm bacteria are up to 100–1000 times less susceptible to antibiotics than their planktonic counterpart. Consequently, conventional antibiograms might not be representative of the bacterial drug susceptibility in vivo. The timely recognition of a BRI is a crucial step to directing the most appropriate biofilm-targeted antimicrobial strategy. Full article

(This article belongs to the Special Issue Biofilm-Related Infections in Healthcare)

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