Special Issue "Biofilm-Based Nosocomial Infections"

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A special issue of Pathogens (ISSN 2076-0817).

Deadline for manuscript submissions: closed (30 September 2014)

Special Issue Editor

Guest Editor
Prof. Dr. Gianfranco Donelli

Microbial Biofilm Laboratory (LABIM), IRCCS "Fondazione Santa Lucia", Via Ardeatina 306, 00179 Rome, Italy
Website | E-Mail
Fax: +39 06 51501306
Interests: microbiology; microbial biofilms; healthcare-associated infections; biomaterial-associated infections; role of toxins and other virulence factors in microbial pathogenesis

Special Issue Information

Dear Colleagues,

Microbial biofilms have been implicated in a large number of acute and chronic infections, as well as in the failure of antibiotic treatment, particularly in hospitalized patients. In fact, the well-known persistence in the nosocomial environment of multidrug resistant microorganisms is believed to be highly promoted by the ability of the great majority of the involved bacterial and fungal species to adhere on living or abiotic surfaces, and to grow in sessile mode, to form single- or multi-species biofilms. In these communities, microbes grow encased in a hydrated matrix of extracellular polymeric substances produced by themselves and are well protected from the host immune response and the attack of antimicrobial molecules. Thus, the establishment of microbial biofilm communities on the mucosal and soft tissues of hospitalized patients, as well as on the surfaces of indwelling devices and medical instruments, is expected to have a great influence on the success of the antibiotic therapies against most of the bugs involved in nosocomial infections, being biofilm-growing bacteria and fungi much less susceptible to antibiotics.

The aim of this Special Issue will be to report the state-of-art developments in the field of  biofilm-based nosocomial infections that can be acquired by patients in both general hospitals and long-term care settings. Particularly, the involvement of biofilms in medical device-related infections and other healthcare-associated infections, which have so far been underestimated and scarcely investigated, will be reviewed.

 

Prof. Dr. Gianfranco Donelli
Guest Editor

Submission

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Keywords

  • bacterial biofilms
  • fungal biofilms
  • nosocomial Infections
  • antibiotic resistance
  • healthcare-associated infections
  • multidrug resistant microorganisms
  • medical devices
  • prostheses
  • medical instruments
  • general hospitals
  • long-term care settings

Published Papers (11 papers)

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Research

Jump to: Review

Open AccessArticle Antimicrobial and Antibiofilm Activity of Chitosan on the Oral Pathogen Candida albicans
Pathogens 2014, 3(4), 908-919; doi:10.3390/pathogens3040908
Received: 26 September 2014 / Revised: 3 December 2014 / Accepted: 4 December 2014 / Published: 11 December 2014
Cited by 6 | PDF Full-text (1065 KB) | HTML Full-text | XML Full-text
Abstract
Oral candidiasis is particularly evident, not only in cancer patients receiving chemotherapy, but also in elderly people with xerostomy. In general, Candida is an opportunistic pathogen, causing infections in immunocompromised people and, in some cases, when the natural microbiota is altered. Chitosan, a
[...] Read more.
Oral candidiasis is particularly evident, not only in cancer patients receiving chemotherapy, but also in elderly people with xerostomy. In general, Candida is an opportunistic pathogen, causing infections in immunocompromised people and, in some cases, when the natural microbiota is altered. Chitosan, a natural derivative of chitin, is a polysaccharide that has been proven to possess a broad spectrum of antimicrobial activity that encompasses action against fungi, yeast and bacteria. While recent studies have revealed a significant antibiofilm activity upon several microorganisms, including C. albicans, little is known regarding the impact of chitosan upon the adhesive process or mature biofilms. With that in mind, the purpose of this work was to evaluate, in vitro, the capability of chitosan to inhibit C. albicans growth and biofilm formation. The results obtained showed that chitosan is capable of inhibiting C. albicans planktonic growth (HMW, 1 mg/mL; LMW, 3 mg/mL). Regarding biofilm growth, chitosan inhibited C. albicans adhesion (ca. 95%), biofilm formation (percentages above 90%) and reduced mature biofilms by ca. 65% and dual species biofilms (C. albicans and S. mutans) by ca. 70%. These results display the potential of this molecule to be used as an effective anti-Candida agent capable of acting upon C. albicans infections. Full article
(This article belongs to the Special Issue Biofilm-Based Nosocomial Infections) Print Edition available
Open AccessArticle Role of Daptomycin in the Induction and Persistence of the Viable but Non-Culturable State of Staphylococcus Aureus Biofilms
Pathogens 2014, 3(3), 759-768; doi:10.3390/pathogens3030759
Received: 26 June 2014 / Revised: 22 August 2014 / Accepted: 12 September 2014 / Published: 18 September 2014
Cited by 2 | PDF Full-text (235 KB) | HTML Full-text | XML Full-text
Abstract
We have recently demonstrated that antibiotic pressure can induce the viable but non-culturable (VBNC) state in Staphylococcus aureus biofilms. Since dormant bacterial cells can undermine anti-infective therapy, a greater understanding of the role of antibiotics of last resort, including daptomycin, is crucial. Methicillin-resistant
[...] Read more.
We have recently demonstrated that antibiotic pressure can induce the viable but non-culturable (VBNC) state in Staphylococcus aureus biofilms. Since dormant bacterial cells can undermine anti-infective therapy, a greater understanding of the role of antibiotics of last resort, including daptomycin, is crucial. Methicillin-resistant S. aureus 10850 biofilms were maintained on non-nutrient (NN) agar in the presence or absence of the MIC of daptomycin until loss of culturability. Viable cells were monitored by epifluorescence microscopy and flow cytometry for 150 days. All biofilms reached non-culturability at 40 days and showed a similar amount of viable cells; however, in biofilms exposed to daptomycin, their number remained unchanged throughout the experiment, whereas in those maintained on NN agar alone, no viable cells were detected after 150 days. Gene expression assays showed that after achievement of non-culturability, 16S rDNA and mecA were expressed by all biofilms, whereas glt expression was found only in daptomycin-exposed biofilms. Our findings suggest that low daptomycin concentrations, such as those that are likely to obtain within biofilms, can influence the viability and gene expression of non-culturable S. aureus cells. Resuscitation experiments are needed to establish the VBNC state of daptomycin-exposed biofilms. Full article
(This article belongs to the Special Issue Biofilm-Based Nosocomial Infections) Print Edition available
Open AccessArticle Exploring Dangerous Connections between Klebsiella pneumoniae Biofilms and Healthcare-Associated Infections
Pathogens 2014, 3(3), 720-731; doi:10.3390/pathogens3030720
Received: 26 June 2014 / Revised: 4 August 2014 / Accepted: 12 August 2014 / Published: 19 August 2014
Cited by 4 | PDF Full-text (743 KB) | HTML Full-text | XML Full-text
Abstract
Healthcare-associated infections (HAI) are a huge public health concern, particularly when the etiological agents are multidrug resistant. The ability of bacteria to develop biofilm is a helpful skill, both to persist within hospital units and to increase antibiotic resistance. Although the links between
[...] Read more.
Healthcare-associated infections (HAI) are a huge public health concern, particularly when the etiological agents are multidrug resistant. The ability of bacteria to develop biofilm is a helpful skill, both to persist within hospital units and to increase antibiotic resistance. Although the links between antibiotic resistance, biofilms assembly and HAI are consensual, little is known about biofilms. Here, electron microscopy was adopted as a tool to investigate biofilm structures associated with increased antibiotic resistance. The K. pneumoniae strains investigated are able to assemble biofilms, albeit with different kinetics. The biofilm structure and the relative area fractions of bacteria and extracellular matrix depend on the particular strain, as well as the minimal inhibitory concentration (MIC) for the antibiotics. Increased values were found for bacteria organized in biofilms when compared to the respective planktonic forms, except for isolates Kp45 and Kp2948, the MIC values for which remained unchanged for fosfomycin. Altogether, these results showed that the emergence of antimicrobial resistance among bacteria responsible for HAI is a multifactorial phenomenon dependent on antibiotics and on bacteria/biofilm features. Full article
(This article belongs to the Special Issue Biofilm-Based Nosocomial Infections) Print Edition available
Open AccessArticle Iron and Acinetobacter baumannii Biofilm Formation
Pathogens 2014, 3(3), 704-719; doi:10.3390/pathogens3030704
Received: 10 July 2014 / Revised: 9 August 2014 / Accepted: 12 August 2014 / Published: 18 August 2014
Cited by 6 | PDF Full-text (583 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Acinetobacter baumannii is an emerging nosocomial pathogen, responsible for infection outbreaks worldwide. The pathogenicity of this bacterium is mainly due to its multidrug-resistance and ability to form biofilm on abiotic surfaces, which facilitate long-term persistence in the hospital setting. Given the crucial role
[...] Read more.
Acinetobacter baumannii is an emerging nosocomial pathogen, responsible for infection outbreaks worldwide. The pathogenicity of this bacterium is mainly due to its multidrug-resistance and ability to form biofilm on abiotic surfaces, which facilitate long-term persistence in the hospital setting. Given the crucial role of iron in A. baumannii nutrition and pathogenicity, iron metabolism has been considered as a possible target for chelation-based antibacterial chemotherapy. In this study, we investigated the effect of iron restriction on A. baumannii growth and biofilm formation using different iron chelators and culture conditions. We report substantial inter-strain variability and growth medium-dependence for biofilm formation by A. baumannii isolates from veterinary and clinical sources. Neither planktonic nor biofilm growth of A. baumannii was affected by exogenous chelators. Biofilm formation was either stimulated by iron or not responsive to iron in the majority of isolates tested, indicating that iron starvation is not sensed as an overall biofilm-inducing stimulus by A. baumannii. The impressive iron withholding capacity of this bacterium should be taken into account for future development of chelation-based antimicrobial and anti-biofilm therapies. Full article
(This article belongs to the Special Issue Biofilm-Based Nosocomial Infections) Print Edition available
Open AccessArticle Antimicrobial Activity of Selected Phytochemicals against Escherichia coli and Staphylococcus aureus and Their Biofilms
Pathogens 2014, 3(2), 473-498; doi:10.3390/pathogens3020473
Received: 4 May 2014 / Revised: 4 June 2014 / Accepted: 5 June 2014 / Published: 18 June 2014
Cited by 8 | PDF Full-text (397 KB) | HTML Full-text | XML Full-text
Abstract
Bacteria can be resistant to multiple antibiotics and we are fast approaching a time when antibiotics will not work on some bacterial infections. New antimicrobial compounds are urgently necessary. Plants are considered the greatest source to obtain new antimicrobials. This study aimed to
[...] Read more.
Bacteria can be resistant to multiple antibiotics and we are fast approaching a time when antibiotics will not work on some bacterial infections. New antimicrobial compounds are urgently necessary. Plants are considered the greatest source to obtain new antimicrobials. This study aimed to assess the antimicrobial activity of four phytochemicals—7-hydroxycoumarin (7-HC), indole-3-carbinol (I3C), salicylic acid (SA) and saponin (SP)—against Escherichia coli and Staphylococcus aureus, either as planktonic cells or as biofilms. These bacteria are commonly found in hospital-acquired infections. Some aspects on the phytochemicals mode of action, including surface charge, hydrophobicity, motility and quorum-sensing inhibition (QSI) were investigated. In addition, the phytochemicals were combined with three antibiotics in order to assess any synergistic effect. 7-HC and I3C were the most effective phytochemicals against E. coli and S. aureus. Both phytochemicals affected the motility and quorum-sensing (QS) activity, which means that they can play an important role in the interference of cell-cell interactions and in biofilm formation and control. However, total biofilm removal was not achieved with any of the selected phytochemicals. Dual combinations between tetracycline (TET), erythromycin (ERY) and ciprofloxacin (CIP) and I3C produced synergistic effects against S. aureus resistant strains. The overall results demonstrates the potential of phytochemicals to control the growth of E. coli and S. aureus in both planktonic and biofilm states. In addition, the phytochemicals demonstrated the potential to act synergistically with antibiotics, contributing to the recycling of old antibiotics that were once considered ineffective due to resistance problems. Full article
(This article belongs to the Special Issue Biofilm-Based Nosocomial Infections) Print Edition available
Open AccessArticle Antibiofilm Effect of Octenidine Hydrochloride on Staphylococcus aureus, MRSA and VRSA
Pathogens 2014, 3(2), 404-416; doi:10.3390/pathogens3020404
Received: 20 March 2014 / Revised: 23 April 2014 / Accepted: 28 April 2014 / Published: 6 May 2014
Cited by 6 | PDF Full-text (848 KB) | HTML Full-text | XML Full-text
Abstract
Millions of indwelling devices are implanted in patients every year, and staphylococci (S. aureus, MRSA and vancomycin-resistant S. aureus (VRSA)) are responsible for a majority of infections associated with these devices, thereby leading to treatment failures. Once established, staphylococcal
[...] Read more.
Millions of indwelling devices are implanted in patients every year, and staphylococci (S. aureus, MRSA and vancomycin-resistant S. aureus (VRSA)) are responsible for a majority of infections associated with these devices, thereby leading to treatment failures. Once established, staphylococcal biofilms become resistant to antimicrobial treatment and host response, thereby serving as the etiological agent for recurrent infections. This study investigated the efficacy of octenidine hydrochloride (OH) for inhibiting biofilm synthesis and inactivating fully-formed staphylococcal biofilm on different matrices in the presence and absence of serum protein. Polystyrene plates and stainless steel coupons inoculated with S. aureus, MRSA or VRSA were treated with OH (zero, 0.5, one, 2 mM) at 37 °C for the prevention of biofilm formation. Additionally, the antibiofilm effect of OH (zero, 2.5, five, 10 mM) on fully-formed staphylococcal biofilms on polystyrene plates, stainless steel coupons and urinary catheters was investigated. OH was effective in rapidly inactivating planktonic and biofilm cells of S. aureus, MRSA and VRSA on polystyrene plates, stainless steel coupons and urinary catheters in the presence and absence of serum proteins. The use of two and 10 mM OH completely inactivated S. aureus planktonic cells and biofilm (>6.0 log reduction) on all matrices tested immediately upon exposure. Further, confocal imaging revealed the presence of dead cells and loss in biofilm architecture in the OH-treated samples when compared to intact live biofilm in the control. Results suggest that OH could be applied as an effective antimicrobial to control biofilms of S. aureus, MRSA and VRSA on appropriate hospital surfaces and indwelling devices. Full article
(This article belongs to the Special Issue Biofilm-Based Nosocomial Infections) Print Edition available

Review

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Open AccessReview Biofilms in Infections of the Eye
Pathogens 2015, 4(1), 111-136; doi:10.3390/pathogens4010111
Received: 21 January 2015 / Revised: 12 March 2015 / Accepted: 13 March 2015 / Published: 23 March 2015
Cited by 3 | PDF Full-text (809 KB) | HTML Full-text | XML Full-text
Abstract
The ability to form biofilms in a variety of environments is a common trait of bacteria, and may represent one of the earliest defenses against predation. Biofilms are multicellular communities usually held together by a polymeric matrix, ranging from capsular material to cell
[...] Read more.
The ability to form biofilms in a variety of environments is a common trait of bacteria, and may represent one of the earliest defenses against predation. Biofilms are multicellular communities usually held together by a polymeric matrix, ranging from capsular material to cell lysate. In a structure that imposes diffusion limits, environmental microgradients arise to which individual bacteria adapt their physiologies, resulting in the gamut of physiological diversity. Additionally, the proximity of cells within the biofilm creates the opportunity for coordinated behaviors through cell–cell communication using diffusible signals, the most well documented being quorum sensing. Biofilms form on abiotic or biotic surfaces, and because of that are associated with a large proportion of human infections. Biofilm formation imposes a limitation on the uses and design of ocular devices, such as intraocular lenses, posterior contact lenses, scleral buckles, conjunctival plugs, lacrimal intubation devices and orbital implants. In the absence of abiotic materials, biofilms have been observed on the capsule, and in the corneal stroma. As the evidence for the involvement of microbial biofilms in many ocular infections has become compelling, developing new strategies to prevent their formation or to eradicate them at the site of infection, has become a priority. Full article
(This article belongs to the Special Issue Biofilm-Based Nosocomial Infections) Print Edition available
Open AccessReview Evolution of Antimicrobial Peptides to Self-Assembled Peptides for Biomaterial Applications
Pathogens 2014, 3(4), 791-821; doi:10.3390/pathogens3040791
Received: 30 June 2014 / Revised: 17 September 2014 / Accepted: 25 September 2014 / Published: 3 October 2014
Cited by 7 | PDF Full-text (1196 KB) | HTML Full-text | XML Full-text
Abstract
Biomaterial-related infections are a persistent burden on patient health, recovery, mortality and healthcare budgets. Self-assembled antimicrobial peptides have evolved from the area of antimicrobial peptides. Peptides serve as important weapons in nature, and increasingly medicine, for combating microbial infection and biofilms. Self-assembled peptides
[...] Read more.
Biomaterial-related infections are a persistent burden on patient health, recovery, mortality and healthcare budgets. Self-assembled antimicrobial peptides have evolved from the area of antimicrobial peptides. Peptides serve as important weapons in nature, and increasingly medicine, for combating microbial infection and biofilms. Self-assembled peptides harness a “bottom-up” approach, whereby the primary peptide sequence may be modified with natural and unnatural amino acids to produce an inherently antimicrobial hydrogel. Gelation may be tailored to occur in the presence of physiological and infective indicators (e.g. pH, enzymes) and therefore allow local, targeted antimicrobial therapy at the site of infection. Peptides demonstrate inherent biocompatibility, antimicrobial activity, biodegradability and numerous functional groups. They are therefore prime candidates for the production of polymeric molecules that have the potential to be conjugated to biomaterials with precision. Non-native chemistries and functional groups are easily incorporated into the peptide backbone allowing peptide hydrogels to be tailored to specific functional requirements. This article reviews an area of increasing interest, namely self-assembled peptides and their potential therapeutic applications as innovative hydrogels and biomaterials in the prevention of biofilm-related infection. Full article
(This article belongs to the Special Issue Biofilm-Based Nosocomial Infections) Print Edition available
Open AccessReview Antibiotic Resistance Related to Biofilm Formation in Klebsiella pneumoniae
Pathogens 2014, 3(3), 743-758; doi:10.3390/pathogens3030743
Received: 10 July 2014 / Revised: 2 September 2014 / Accepted: 3 September 2014 / Published: 5 September 2014
Cited by 14 | PDF Full-text (3639 KB) | HTML Full-text | XML Full-text
Abstract
The Gram-negative opportunistic pathogen, Klebsiella pneumoniae, is responsible for causing a spectrum of community-acquired and nosocomial infections and typically infects patients with indwelling medical devices, especially urinary catheters, on which this microorganism is able to grow as a biofilm. The increasingly frequent
[...] Read more.
The Gram-negative opportunistic pathogen, Klebsiella pneumoniae, is responsible for causing a spectrum of community-acquired and nosocomial infections and typically infects patients with indwelling medical devices, especially urinary catheters, on which this microorganism is able to grow as a biofilm. The increasingly frequent acquisition of antibiotic resistance by K. pneumoniae strains has given rise to a global spread of this multidrug-resistant pathogen, mostly at the hospital level. This scenario is exacerbated when it is noted that intrinsic resistance to antimicrobial agents dramatically increases when K. pneumoniae strains grow as a biofilm. This review will summarize the findings about the antibiotic resistance related to biofilm formation in K. pneumoniae. Full article
(This article belongs to the Special Issue Biofilm-Based Nosocomial Infections) Print Edition available
Open AccessReview Pseudomonas aeruginosa Diversification during Infection Development in Cystic Fibrosis Lungs—A Review
Pathogens 2014, 3(3), 680-703; doi:10.3390/pathogens3030680
Received: 1 July 2014 / Revised: 11 August 2014 / Accepted: 12 August 2014 / Published: 18 August 2014
Cited by 17 | PDF Full-text (442 KB) | HTML Full-text | XML Full-text
Abstract
Pseudomonas aeruginosa is the most prevalent pathogen of cystic fibrosis (CF) lung disease. Its long persistence in CF airways is associated with sophisticated mechanisms of adaptation, including biofilm formation, resistance to antibiotics, hypermutability and customized pathogenicity in which virulence factors are expressed according
[...] Read more.
Pseudomonas aeruginosa is the most prevalent pathogen of cystic fibrosis (CF) lung disease. Its long persistence in CF airways is associated with sophisticated mechanisms of adaptation, including biofilm formation, resistance to antibiotics, hypermutability and customized pathogenicity in which virulence factors are expressed according the infection stage. CF adaptation is triggered by high selective pressure of inflamed CF lungs and by antibiotic treatments. Bacteria undergo genetic, phenotypic, and physiological variations that are fastened by the repeating interplay of mutation and selection. During CF infection development, P. aeruginosa gradually shifts from an acute virulent pathogen of early infection to a host-adapted pathogen of chronic infection. This paper reviews the most common changes undergone by P. aeruginosa at each stage of infection development in CF lungs. The comprehensive understanding of the adaptation process of P. aeruginosa may help to design more effective antimicrobial treatments and to identify new targets for future drugs to prevent the progression of infection to chronic stages. Full article
(This article belongs to the Special Issue Biofilm-Based Nosocomial Infections) Print Edition available
Open AccessReview Biomolecular Mechanisms of Pseudomonas aeruginosa and Escherichia coli Biofilm Formation
Pathogens 2014, 3(3), 596-632; doi:10.3390/pathogens3030596
Received: 29 May 2014 / Revised: 10 July 2014 / Accepted: 14 July 2014 / Published: 18 July 2014
Cited by 19 | PDF Full-text (1109 KB) | HTML Full-text | XML Full-text
Abstract
Pseudomonas aeruginosa and Escherichia coli are the most prevalent Gram-negative biofilm forming medical device associated pathogens, particularly with respect to catheter associated urinary tract infections. In a similar manner to Gram-positive bacteria, Gram-negative biofilm formation is fundamentally determined by a series of steps
[...] Read more.
Pseudomonas aeruginosa and Escherichia coli are the most prevalent Gram-negative biofilm forming medical device associated pathogens, particularly with respect to catheter associated urinary tract infections. In a similar manner to Gram-positive bacteria, Gram-negative biofilm formation is fundamentally determined by a series of steps outlined more fully in this review, namely adhesion, cellular aggregation, and the production of an extracellular polymeric matrix. More specifically this review will explore the biosynthesis and role of pili and flagella in Gram-negative adhesion and accumulation on surfaces in Pseudomonas aeruginosa and Escherichia coli. The process of biofilm maturation is compared and contrasted in both species, namely the production of the exopolysaccharides via the polysaccharide synthesis locus (Psl), pellicle Formation (Pel) and alginic acid synthesis in Pseudomonas aeruginosa, and UDP-4-amino-4-deoxy-l-arabinose and colonic acid synthesis in Escherichia coli. An emphasis is placed on the importance of the LuxR homologue sdiA; the luxS/autoinducer-II; an autoinducer-III/epinephrine/norepinephrine and indole mediated Quorum sensing systems in enabling Gram-negative bacteria to adapt to their environments. The majority of Gram-negative biofilms consist of polysaccharides of a simple sugar structure (either homo- or heteropolysaccharides) that provide an optimum environment for the survival and maturation of bacteria, allowing them to display increased resistance to antibiotics and predation. Full article
(This article belongs to the Special Issue Biofilm-Based Nosocomial Infections) Print Edition available

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