ABSTRACT
The application of antimicrobials in the management of wounds is a complex procedure requiring appropriate clinical decision making, judgment and a thorough understanding of antimicrobial ...therapies, together with their potential disadvantages. There is considerable direct and indirect evidence for the presence of bacterial biofilms in the chronic wound bed, and it has been demonstrated that bacteria within these biofilms may exhibit both specific and nonspecific antimicrobial tolerance. The antimicrobial tolerance of biofilms is a major concern in the treatment of both infected and nonhealing chronic wounds and an understanding of the mechanisms involved is of fundamental importance in managing wound infections and developing future wound management strategies. The aim of this review is therefore to provide an overview of our current understanding of the mechanisms by which bacteria in wound biofilms can resist conventional antibiotic and antibacterial therapies which is very important to wound healing.
Management of oral candidosis, most frequently caused by
, is limited due to the relatively low number of antifungal drugs and the emergence of antifungal tolerance. In this study, the antifungal ...activity of a range of commercial essential oils, two terpenes, chlorhexidine and triclosan was evaluated against
in planktonic and biofilm form. In addition, cytotoxicity of the most promising compounds was assessed using murine fibroblasts and expressed as half maximal inhibitory concentrations (IC50). Antifungal activity was determined using a broth microdilution assay. The minimum inhibitory concentration (MIC) was established against planktonic cells cultured in a range of concentrations of the test agents. The minimal biofilm eradication concentration (MBEC) was determined by measuring re-growth of cells after pre-formed biofilm was treated for 24 h with the test agents. All tested commercial essential oils demonstrated anticandidal activity (MICs from 0.06% (
/
) to 0.4% (
/
)) against planktonic cultures, with a noticeable increase in resistance exhibited by biofilms (MBECs > 1.5% (
/
)). The IC50s of the commercial essential oils were lower than the MICs, while a one hour application of chlorhexidine was not cytotoxic at concentrations lower than the MIC. In conclusion, the tested commercial essential oils exhibit potential as therapeutic agents against
, although host cell cytotoxicity is a consideration when developing these new treatments.
Phage therapy recently passed a key milestone with success of the first regulated clinical trial using systemic administration. In this single-arm non-comparative safety study, phages were ...administered intravenously to patients with invasive
infections with no adverse reactions reported. Here, we examined features of 78 lytic
phages, most of which were propagated using a
host modified to be broadly susceptible to staphylococcal phage infection. Use of this host eliminates the threat of contamination with staphylococcal prophage - the main vector of
horizontal gene transfer. We determined the host range of these phages against an international collection of 185
isolates with 56 different multilocus sequence types that included multiple representatives of all epidemic MRSA and MSSA clonal complexes. Forty of our 78 phages were able to infect > 90% of study isolates, 15 were able to infect > 95%, and two could infect all 184 clinical isolates, but not a phage-resistant mutant generated in a previous study. We selected the 10 phages with the widest host range for
characterization by planktonic culture time-kill analysis against four isolates:- modified
strain TM300H, methicillin-sensitive isolates D329 and 15981, and MRSA isolate 252. Six of these 10 phages were able to rapidly kill, reducing cell numbers of at least three isolates. The four best-performing phages, in this assay, were further shown to be highly effective in reducing 48 h biofilms on polystyrene formed by eight ST22 and eight ST36 MRSA isolates. Genomes of 22 of the widest host-range phages showed they belonged to the
subfamily of the order
in three main groups corresponding to
, and two distinct groups of
. These genomes assembled as single-linear dsDNAs with an average length of 140 kb and a GC content of
30%. Phages that could infect > 96% of
isolates were found in all three groups, and these have great potential as therapeutic candidates if, in future studies, they can be formulated to maximize their efficacy and eliminate emergence of phage resistance by using appropriate combinations.
To study how the choice of the first assisted reproductive technology treatment type affects the cumulative live birth rate (CLBR) in couples with high sperm DNA fragmentation index (DFI).
...Longitudinal cohort study.
University-affiliated fertility clinic.
A total of 2,713 infertile couples who underwent assisted reproductive technology treatment between 2007 and 2017 were included in the study. All in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatments (up to three fresh treatments and all associated frozen-thawed embryo transfers) offered to the couples by the public health care system were included, in total 5,422 cycles.
None.
The primary outcome was the CLBR. The secondary outcomes were the fertilization rate and the miscarriage rate. The IVF and ICSI groups were defined according to the method applied in the first treatment cycle.
In the IVF group, the CLBR values were higher for couples with normal DFI compared with those for couples with high DFI (≥20%) (48.1% vs. 41.6% for conservative CLBR estimate and 55.6% vs. 51.4% for optimal CLBR estimate after adjustment for female age, respectively). No DFI-dependent difference was seen in the ICSI group.
Our results demonstrated that a high DFI predicts a statistically significantly lower CLBR if IVF and not ICSI is applied in the first cycle of assisted reproduction.
Índice de fragmentación del ADN espermático y tasa acumulada de nacidos vivos en una cohorte de 2.713 parejas sometidas tratamiento de reproducción asistida.
Estudiar cómo la elección del primer tipo de tratamiento de reproducción asistida afecta la tasa acumulada de nacidos vivos (CLBR) en parejas con alto índice de fragmentación del ADN espermático (DFI).
Estudio de cohorte longitudinal.
Clínica de fertilidad afiliada a la universidad.
Un total de 2.713 parejas infértiles que se sometieron a tratamiento de reproducción asistida entre 2007 y 2017 fueran incluidas en el estudio. Todos los tratamientos de fertilización in vitro (FIV) / inyección intracitoplasmática de espermatozoides (ICSI) (hasta tres tratamientos frescos y todas las transferencias de embriones congeladas-descongeladas asociadas) ofrecidas a las parejas en el sistema público de salud fueron incluidas, en total 5.422 ciclos.
Ninguna.
El resultado principal fue el CLBR. Los resultados secundarios fueron la tasa de fertilización y el índice de aborto espontáneo. Los grupos de FIV e ICSI se definieron según el método aplicado en el primer ciclo de tratamiento.
En el grupo de FIV, los valores de CLBR fueron más altos para las parejas con DFI normal en comparación con los de las parejas con DFI alto (≥20%) (48,1% frente a 41,6% para la estimación de CLBR conservadora y 55,6% frente a 51,4% para la estimación de CLBR óptima después del ajuste por edad en mujeres, respectivamente). No se observó ninguna diferencia dependiente de DFI en el grupo de ICSI.
Nuestros resultados demostraron que un DFI alto predice un CLBR estadísticamente significativamente más bajo si se aplica FIV y no ICSI en el primer ciclo de reproducción asistida.
spp. are the most prevalent fungi of the human microbiota and are opportunistic pathogens that can cause oral candidiasis. Management of such infections is limited due to the low number of antifungal ...drugs available, their relatively high toxicity and the emergence of antifungal resistance. Therefore, much interest in the antimicrobial potential of natural compounds has recently been evident. The use of hydrogels in the delivery of biocides has been explored due to their biocompatibility, ease with drug encapsulation, and due to their potential to confer mechanical and structural properties similar to biological tissue. Methylcellulose hydrogels (10% (
/
)) with 1% (
/
) and 2% (
/
)
oil were synthesised. The rheological properties and gelation time of the hydrogels were evaluated. Antimicrobial action, the antifungal potential and ability to displace
were determined. Rheological tests revealed that the hydrogel jellified in three minutes at 37 °C. Loaded hydrogels successfully inhibited
growth as evident by zone of inhibition and time-kill assays. A significant reduction in retained
was demonstrated with the hydrogel at 2%
concentration. This work demonstrated that an essential oil-loaded hydrogel had the potential to provide a novel antimicrobial therapy for the treatment of oral candidiasis.
Biofilm formation in long-term urinary catheterized patients can lead to encrustation and blockage of urinary catheters with serious clinical complication. Catheter encrustation stems from infection ...with urease-producing bacteria, particularly Proteus mirabilis. Urease generates ammonia from urea, and the elevated pH of the urine results in crystallization of calcium and magnesium phosphates, which block the flow of urine. The aim of this research is to develop an "early warning" silicone sensor for catheter encrustation following bacterial infection of an in vitro bladder model system. The in vitro bladder model was infected with a range of urease positive and negative bacterial strains. Developed sensors enabled catheter blockage to be predicted ~17-24 h in advance of its occurrence. Signaling only occurred following infection with urease positive bacteria and only when catheter blockage followed. In summary, sensors were developed that could predict urinary catheter blockage in in vitro infection models. Translation of these sensors to a clinical environment will allow the timely and appropriate management of catheter blockage in long-term catheterized patients.
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•Antimicrobial silver-charged dental acrylic resin is prepared.•The material is active against C. albicans, S. mutans and F. nucleatum.•Antimicrobial activity against C. albicans ...remains unchanged for 45 d.
The insertion of prosthetic devices into the oral cavity affects the oral microflora and results in accumulation of microorganisms on the prosthetic surface. Such fouling of denture surfaces can lead to a number of oral diseases and consequently to the replacement of the denture. Here, we report the post-synthesis introduction of silver in zeolite-loaded dental acrylic (DAZ) resins that does not influence the mechanical or aesthetic properties of the DA resins, and provides them with a long-term antimicrobial activity. Na-FAU zeolite (2 wt%) was incorporated into DA resin, which was conventionally processed and cut into 10 mm × 20 mm × 3 mm coupons. The Na+ in the zeolite was then exchanged with Ag+ via immersion of the DAZ coupons in 0.01 M AgNO3 solution to obtain DAZ/Ag-treated coupons used in antimicrobial tests. Antimicrobial tests showed that the DAZ/Ag-treated coupons were active against Candida albicans (a reference and a clinically relevant strain), Streptococcus mutans and Fusobacterium nucleatum. Ag leaching tests on the Ag-charged coupons at 1, 2, 3, 4, 7, 14, 30 and 45 days of incubation in distilled water at 37 °C, indicated sustained release of silver. Antimicrobial tests using a reference Candida albicans strain showed that the leached coupons retained antimicrobial activity after 45 days immersion in distilled water, but, after 60 days incubation no antimicrobial activity was observed. Cytotoxicity assay results indicated that the DAZ/Ag-treated coupons showed no additional cytotoxicity compared to neat dental acrylic coupons.
1 Tissue Engineering and Reparative Dentistry, School of Dentistry, Cardiff University, Heath Park, Cardiff CF14 4XY, UK
2 School of Biosciences, Cardiff University, Park Place, Cardiff CF10 3US, UK
...3 School of Medicine, University of West Virginia, Morgantown, WV 26506, USA
Biofilms provide a reservoir of potentially infectious micro-organisms that are resistant to antimicrobial agents, and their importance in the failure of medical devices and chronic inflammatory conditions is increasingly being recognized. Particular research interest exists in the association of biofilms with wound infection and non-healing, i.e. chronic wounds. In this study, fluorescent in situ hybridization (FISH) was used in combination with confocal laser scanning microscopy (CLSM) to detect and characterize the spatial distribution of biofilm-forming bacteria which predominate within human chronic skin wounds ( Pseudomonas aeruginosa , Staphylococcus aureus , Streptococcus sp. and Micrococcus sp.). In vitro biofilms were prepared using a constant-depth film fermenter and a reconstituted human epidermis model. In vivo biofilms were also studied using biopsy samples from non-infected chronic venous leg ulcers. The specificity of peptide nucleic acid (PNA) probes for the target organisms was confirmed using mixed preparations of planktonic bacteria and multiplex PNA probing. Identification and location of individual bacterial species within multi-species biofilms demonstrated that P. aeruginosa was predominant. CLSM revealed clustering of individual species within mixed-species biofilms. FISH analysis of archive chronic wound biopsy sections showed bacterial presence and allowed bacterial load to be determined. The application of this standardized procedure makes available an assay for identification of single- or multi-species bacterial populations in tissue biopsies. The technique provides a reliable tool to study bacterial biofilm formation and offers an approach to assess targeted biofilm disruption strategies in vivo .
Correspondence Sladjana Malic malics{at}cardiff.ac.uk
Abbreviations: CLSM, confocal laser scanning microscopy; CDFF, constant-depth film fermenter; CVLU, chronic venous leg ulcer; FISH, fluorescent in situ hybridization; PNA, peptide nucleic acid; RHE, reconstituted human epidermis
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