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Background The ability to degrade hyaluronic acid (HA)-based fillers with hyaluronidase allows for better management of adverse effects and reversal of suboptimal treatment outcomes. Objectives The aim of this study was to compare the enzymatic degradation kinetics of 16 commercially available HA-based fillers, representing 6 manufacturing technologies. Methods In this nonclinical study, a recently developed in vitro multidose hyaluronidase administration protocol was used to induce degradation of HA-based fillers, enabling real-time evaluation of viscoelastic properties under near-static conditions. Each filler was exposed to repeated doses of hyaluronidase at intervals of 5 minutes to reach the degradation threshold of G ' ≤ 30 Pa. Results Noticeable differences in degradation characteristics were observed based on the design and technology of different filler classes. Vycross fillers were the most difficult to degrade and the Cohesive Polydensified Matrix filler was the least difficult to degrade. Preserved Network Technology products demonstrated proportional increases in gel degradation time and enzyme volume required for degradation across the individual resilient hyaluronic acid (RHA) products and indication categories. No obvious relationship was observed between gel degradation characteristics and the individual parameters of HA concentration, HA chain length, or the degree of modification of each filler when analyzed separately; however, a general correlation was identified with certain physicochemical properties. Conclusions Manufacturing technology was the most important factor influencing the reversibility of an HA product. An understanding of the differential degradation profiles of commercially available fillers will allow clinicians to select products that offer a higher margin of safety due to their preferential reversibility. Level of Evidence: 4 [ABSTRACT FROM AUTHOR]

Postoperative management of esophagocutaneous fistulas in pediatric patients is challenging, often resulting in prolonged hospitalization and increased morbidity. Platelet-rich plasma (PRP) has emerged as a promising adjunctive treatment for such complications. We present the case of a 7-month-old infant who developed an esophago-cutaneous fistula following esophagocoloplasty for esophageal atresia type A. Despite initial conservative management, the fistula persisted, prompting the application of PRP gel derived from umbilical cord blood. After four applications of PRP, complete closure of the fistula was achieved, leading to both functional and aesthetic results. This case highlights the potential of PRP in managing refractory postoperative esophageal fistulas in pediatric patients and underscores the need for further research to optimize treatment protocols and validate its efficacy for this sort of complications [ABSTRACT FROM AUTHOR]

In the late nineties, polyacrylamide gel (PAAG) gained popularity in China as a soft tissue filler for breast augmentation and contouring, but was banned 10 years later due to the increasing incidence of complications. We report a case of PAAG complication that occurred 20 years after the initial injection, where the patient had significant unilateral breast swelling and an intracapsular lesion. Surgical removal of the breast filler and immediate breast reconstruction was successfully performed, and histology confirmed a benign breast lesion. These findings highlight the importance of clinical awareness of PAAG breast filler complications. [ABSTRACT FROM AUTHOR]

Aims This study aimed to develop essential oil-containing biopolymer-based vapor gel formulations for the postharvest management of blue mould of apples. Apples are one of the widely cultivated fruits. They are susceptible to a wide range of fungus leading to high losses in overall production. Many research articles have highlighted the applications of essential oil-biopolymer coatings in the postharvest storage of fruits. However, no studies have yet tried to explore the potential of a vapour gel formulation for postharvest applications. Methods and results Contaminated apples were collected from the local market. The causative fungus was isolated and identified. Minimum fungicidal concentrations of Monarda citriodora essential oil (MEO) and hexanal/linalool in the vapour phase were determined in vitro. In vitro and in vivo , checkerboard assays were used to demonstrate the synergistic activity between MEO and hexanal/linalool vapours against the isolated pathogen. MEO and linalool (M + L) combinatorial treatment indicated synergy in vivo and in vitro. In vivo treatment of M + L on apples by direct fumigation showed phytotoxicity. Gel formulations (carrageenan-guar gum, carbopol gel, and soft gel) were developed and evaluated to address phytotoxicity. M + L combination synergistically remediated the phytotoxicity in both carbopol (FICI = 0.625) and soft gels (FICI = 0.5625). The physicochemical parameters (pH, weight loss, TSS, and ascorbic acid (AsAC) of the treated apples were analysed. Reduction in weight loss and increase in AsAC were observed for treated fruits when compared to control, and no change in pH and TSS was observed. Conclusions Biopolymer vapour gel formulations containing M + L vapours effectively protect apples from the postharvest blue mould for extended storage. [ABSTRACT FROM AUTHOR]

Preclinical studies have demonstrated carrageenan's anti–human papillomavirus (HPV) activity. We assessed efficacy of a carrageenan-based gel compared to a placebo gel in increasing the clearance of anal HPV infections among gay, bisexual, and other men who have sex with men (gbMSM). Of 255 enrolled gbMSM, 134 were HPV positive at baseline and had valid HPV results for ≥2 visits. Carrageenan did not differ from placebo in clearing all baseline infections (hazard ratio, 0.84 [95% confidence interval,.31–2.27]), based on having 2 consecutive HPV-negative visits following at least 1 HPV-positive visit. There were no remarkable differences for analyses at the HPV type level or by human immunodeficiency virus status. Clinical Trials Registration NCT02354144. [ABSTRACT FROM AUTHOR]

Objectives: Histologic findings after endoscopic resection using submucosal lifting agents Eleview and ORISE gel are described.Methods: Four cases were identified based on the histologic presence of ORISE gel. Cases were selected to illustrate the histologic appearance of the lifting agent immediately after injection (day 0) and after an interval of approximately 2 months.Results: Immediately after injection, the gel had an appearance similar to acellular mucin on H&E stain and showed mucicarmine positivity but was negative for periodic acid-Schiff stain and Alcian blue. At 2 months, the appearance changed drastically and was characterized by a hard, homogenous eosinophilic quality and elicited a robust foreign body-type giant cell reaction; we have proposed the name lifting agent granuloma for this histologic appearance. The aged material may be mistaken for amyloid or a pulse (legume) granuloma; however, the material was negative on Congo red stain and had a different clinical history and distribution in the tissue from those of a pulse granuloma.Conclusions: It is important to take note of the histologic appearance of these new submucosal lifting agents over a varying time interval, as outlined here, so that they are readily recognized and not mistaken for other entities. [ABSTRACT FROM AUTHOR]

Objective To test a hybrid polyethylene glycol (PEG)/gel method, specifically to attempt to increase reaction strength of accidentally overdiluted anti-Cob and broadly for proof of concept. Methods Methods were divided into 2 basic steps: sensitization and antiglobulin (AHG) testing. Sensitization was performed with PEG tubes, followed by AHG using the gel method. One wash was performed between the 2 steps. We tested 7 plasma antibody specimens. Results In addition to the first specimen, 6 additional antibodies were selected for detection by the PEG/gel hybrid method. Antibody reactivity was detected in all specimens tested with both methods. The PEG/gel method yielded enhanced reactivity in 3 of 7 antibodies (42.9%) and the equivalent of enhanced reactivity in 4 of 7 antibodies tested (57.1%). Conclusion The reactivity of diluted anti-Cob (specimen 1) was increased; thus, our concept proved to be viable. The hybrid PEG/gel method showed the equivalent of enhanced or enhanced reactivity with all specimens tested and provided a stable medium. [ABSTRACT FROM AUTHOR]

Objective To evaluate how clinical practice was affected by the change in direct antiglobulin testing (DAT) methodologies and subsequent stronger reported DAT results at our large academic medical center. Method We retrospectively reviewed DAT results of umbilical cord blood from infants with blood type A or B born to mothers with antibody-negative type O blood, based on records kept at the University of Alabama at Birmingham (UAB) Hospital, a 1400-bed academic medical center. Results We randomly chose 50 neonates with positive DAT results who had been tested using the tube method and 50 whose testing had used the gel method. Although 86% of results with the tube method were positive microscopically, 52% and 40% of the DAT results with the gel method were 1+ and 2+ positive, respectively. Further, we observed an increase in the number of neonates treated with phototherapy who had been tested using the gel method. Conclusion We report that DATs performed using the gel method had increased DAT strength compared with tube testing, which led to increased use of phototherapy by our clinical colleagues. [ABSTRACT FROM AUTHOR]

Introduction: The mechanical response of brain tissue to high-speed forces in the blast and blunt traumatic brain injury is poorly understood. Object-to-object variation and interspecies differences are current limitations in animal and cadaver studies conducted to study damage mechanisms. Biofidelic and transparent tissue simulants allow the use of high-speed optical diagnostics during a blast event, making it possible to observe deformations and damage patterns for comparison to observed injuries seen post-mortem in traumatic brain injury victims.Methods: Material properties of several tissue simulants were quantified using standard mechanical characterization techniques, that is, shear rheometric, tensile, and compressive testing.Results: Polyacrylamide simulants exhibited the best optical and mechanical property matching with the fewest trade-offs in the design of a cranial test object. Polyacrylamide gels yielded densities of ~1.04 g/cc and shear moduli ranging 1.3-14.55 kPa, allowing gray and white matter simulant tuning to a 30-35% difference in shear for biofidelity.Conclusions: These materials are intended for use as layered cranial phantoms in a shock tube and open field blasts, with focus on observing phenomena occurring at the interfaces of adjacent tissue simulant types or material-fluid boundaries. Mechanistic findings from these studies may be used to inform the design of protective gear to mitigate blast injuries. [ABSTRACT FROM AUTHOR]

Introduction: Infection frequently complicates the treatment of combat-related wounds, impairs healing, and leads to worse outcomes. To better manage wound infections, antimicrobial therapies that are effective against biofilm and designed for direct wound application are needed. The primary objective of this work was to evaluate a chitosan matrix for delivery of two engineered antimicrobial peptides, (ASP)-1 and ASP-2, to treat biofilm-associated bacteria. A secondary objective was to determine whether replacing the levorotatory (L) form amino acids in ASP-2 with dextrorotatory (D) form amino acids would impact peptide activity.Materials and Methods: Chitosan gels loaded with antimicrobial peptides were evaluated for peptide release over 7 days and tested for efficacy against biofilms grown both in vitro on polymer mesh and ex vivo on porcine skin.Results: When delivered via chitosan, 70% to 80% of peptides were released over 7 days. Gels eradicated biofilms of gram-positive and gram-negative, drug-resistant bacteria in vitro and ex vivo. Under the conditions tested, no meaningful differences in peptide activity between the L and D forms of ASP-2 were detected.Conclusions: Chitosan serves as an effective delivery platform for ASP-1 and ASP-2 to treat biofilm-embedded bacteria and warrants further development as a topical treatment. [ABSTRACT FROM AUTHOR]

Objectives: Increasing numbers of linezolid-resistant Enterococcus carrying optrA are being reported across different niches worldwide. We aimed to characterize the first optrA-carrying Enterococcus faecalis obtained from food-producing animals and retail meat samples in Tunisia.Methods: Seven optrA-carrying E. faecalis obtained from chicken faeces (n=3, August 2017) and retail chicken meat (n=4, August 2017) in Tunisia were analysed. Antimicrobial susceptibility was determined by disc diffusion, broth microdilution and Etest against 13 antibiotics, linezolid and tedizolid, respectively (EUCAST/CLSI). optrA stability (∼600 bacterial generations), transfer (filter mating) and location (S1-PFGE/hybridization) were characterized. WGS (Illumina-HiSeq) was done for four representatives that were analysed through in silico and genomic mapping tools.Results: Four MDR clones carrying different virulence genes were identified in chicken faeces (ST476) and retail meat (the same ST476 clone plus ST21 and ST859) samples. MICs of linezolid and tedizolid were stably maintained at 8 and 1-2 mg/L, respectively. optrA was located in the same transferable chromosomal Tn6674-like element in ST476 and ST21 clones, similar to isolates from pigs in Malaysia and humans in China. ST859 carried a non-conjugative plasmid of ∼40 kb with an impB-fexA-optrA segment, similar to plasmids from pigs and humans in China.Conclusions: The same chromosomal and transferable Tn6674-like element was identified in different E. faecalis clones from humans and animals. The finding of retail meat contaminated with the same linezolid-resistant E. faecalis strain obtained from a food-producing animal highlights the potential role of the food chain in the worrisome dissemination of optrA that can be stably maintained without selective pressure over generations. [ABSTRACT FROM AUTHOR]

Objectives: To determine the prevalence of Escherichia coli STs and associated resistance mechanisms carried by the community in North-East India.Methods: E. coli (108) were isolated from sewage collected from 19 sites across the city of Silchar by plating on MacConkey agar with/without selection (50 mg/L cefotaxime). Species identification was confirmed by MALDI-TOF MS for 82 isolates. Common resistance mechanisms were determined by WGS of pooled E. coli isolates. PFGE combined with specific probes determined the presence of common resistance mechanisms in all isolates. Phylotypes, multilocus STs, core-genome multilocus STs, resistance genes and virulence genes were determined by in silico analysis of 38 genomes.Results and Conclusions: Analysis of isolates collected without selection (n=33) indicated that cefotaxime resistance in E. coli was 42% (14/33) and estimated meropenem resistance at 9%. The remaining 58% (19/33) were additionally susceptible to ampicillin, trimethoprim, ciprofloxacin and aminoglycosides. The most common ST among the cefotaxime-resistant E. coli was ST167 (29%), followed by ST410 (17%) and ST648 (10%). E. coli ST131 was absent from the collection. Sixty-three isolates were resistant to cefotaxime and harboured blaCTX-M-15 [54% (34/63)] or blaCMY-42 [46% (29/63)], of which 10% (6/63) harboured both genes. Carbapenem resistance was due to blaNDM-5, found in 10/63 cefotaxime-resistant isolates, and/or blaOXA-181, found in 4/63 isolates. NDM-5 was encoded by IncX3 and/or IncFII plasmids and CMY-42 was mostly encoded by IncI plasmids. NDM-5 appears to have replaced NDM-1 in this region and CMY-42 appears to be in the process of replacing CTX-M-15. [ABSTRACT FROM AUTHOR]

Background Reoperation after primary breast augmentation remains an important clinical issue. Objective The authors sought to evaluate incidence and causes of reoperation in patients who underwent primary augmentation. Methods This retrospective, noninterventional study conducted at 16 Canadian sites reviewed medical records and patient-completed questionnaires of women who underwent primary breast augmentation with smooth or textured Natrelle Inspira implants containing TruForm 1 or TruForm 2 gel. Patients were aged ≥22 years, received implants via inframammary fold incision, and returned for follow-up at 2 to 4 years. Results A total of 319 women received Inspira implants (smooth TruForm 2, n = 205; textured TruForm 2, n = 99; smooth or textured TruForm 1, n = 15). At follow-up, 30 women (9.4%) had undergone reoperation, including 19 (9.3%) in the smooth TruForm 2 subgroup and 9 (9.1%) in the textured TruForm 2 subgroup. The mean time to reoperation was 1.2 years; the risk rate for reoperation was 9.9% at 3 years. The most common reasons for reoperation were implant malposition (36.7%), capsular contracture (33.3%), and the patient's request for a change in implant size or style (20.0%). Most women were very or somewhat satisfied with the initial surgery (89.3% overall; 90.7% smooth TruForm 2; 86.9% textured TruForm 2). Thirty-four women (10.7%) reported adverse events, including 20 (9.8%) in the smooth TruForm 2 subgroup and 14 (14.1%) in the textured TruForm 2 subgroup. Conclusions This analysis suggests that Natrelle Inspira TruForm 2 implants are safe when used in primary breast augmentation, resulting in low reoperation rates that are consistent with those for other breast implants. Level of Evidence: 4 [ABSTRACT FROM AUTHOR]

Objectives: In 2015 and 2016 Poland recorded rapid proliferation of New Delhi MBL (NDM)-producing Enterobacterales, with at least 470 and 1780 cases, respectively. We addressed the roles of the Klebsiella pneumoniae ST11 NDM-1 outbreak genotype, already spreading in 2012-14, and of newly imported organisms in this increase.Methods: The study included 2136 NDM-positive isolates identified between April 2015 and December 2016, following transfer of patients with K. pneumoniae ST147 NDM-1 from Tunisia to Warsaw in March 2015. The isolates were screened by PCR mapping for variants of blaNDM-carrying Tn125-like elements. Selected isolates were typed by PFGE and MLST. NDM-encoding plasmids were analysed by nuclease S1/hybridization, transfer assays, PCR-based replicon typing and PCR mapping.Results: The organisms were mainly K. pneumoniae containing the Tn125A variant of the ST11 epidemic lineage (n = 2094; ∼98%). Their representatives were of the outbreak pulsotype and ST11, and produced NDM-1, encoded by specific IncFII (pKPX-1/pB-3002cz)-like plasmids. The isolates were recovered in 145 healthcare centres in 13/16 administrative regions, predominantly the Warsaw area. The 'Tunisian' genotype K. pneumoniae ST147 NDM-1 Tn125F comprised 18 isolates (0.8%) from eight institutions. The remaining 24 isolates, mostly K. pneumoniae and Escherichia coli of diverse STs, produced NDM-1 or NDM-5 specified by various Tn125 derivatives and plasmids.Conclusions: The K. pneumoniae ST11 NDM-1 outbreak has dramatically expanded in Poland since 2012, which may bring about a countrywide endemic situation in the near future. In addition, the so-far limited K. pneumoniae ST147 NDM-1 outbreak plus multiple NDM imports from different countries were observed in 2015-16. [ABSTRACT FROM AUTHOR]

Objectives: The epidemiology of Enterococcus resistant to priority antibiotics including linezolid has mainly been investigated in developed countries and especially in hospitals. We aimed to evaluate the contribution of different non-human reservoirs for the burden of MDR enterococci in Tunisia, where scarce data are available.Methods: Samples (n = 287) were collected from urban wastewater (n = 57), retail meat (n = 29; poultry/bovine/ovine), milk (n = 89; bovine/ovine), farm animal faeces (n = 80; poultry/bovine/ovine) and pets (n = 32; rabbit/dogs/cats/birds) in different Tunisian regions (2014-17). They were plated onto Slanetz-Bartley agar after pre-enrichment without antibiotics. Standard methods were used for bacterial identification and characterization of antibiotic resistance and virulence genes (PCR), antibiotic susceptibility testing (disc diffusion/broth microdilution; EUCAST/CLSI) and clonality (SmaI-PFGE/MLST).Results: All samples carried Enterococcus (n = 377 isolates) resistant to antibiotics considered to be critical or highly important by WHO. Even without antibiotic selection, 38% of Enterococcus faecalis (Efs) and 22% of Enterococcus faecium (Efm) were identified as MDR. Linezolid-resistant isolates (5%; MIC = 8 mg/L) comprised six poxtA-carrying Efm (cow milk), seven optrA-carrying Efs (chicken faeces/meat) and five Efm lacking cfr/optrA/poxtA (poultry/bovine/ovine/wastewater). Clinically relevant Efm clones (clade A1) were identified in animal/meat sources. Ampicillin resistance (1%) was confined to ST18/ST78-like MDR Efm clones from bovine meat/milk samples carrying relevant virulence markers (e.g. ptsD/IS16).Conclusions: This study provides evidence of the contribution of livestock and foodstuffs to the dispersal of acquired linezolid resistance genes including poxtA and optrA. We report the first poxtA-carrying Efm in Tunisia, and for the first time in bovine samples, stressing the urgent need for alternative measures to counteract the spread of linezolid-resistant enterococci globally. [ABSTRACT FROM AUTHOR]

Objectives: The emergence of carbapenemase-positive Enterobacteriaceae poses a serious threat to public health worldwide. Here we conducted a molecular surveillance study on carbapenem-resistant Enterobacteriaceae (CRE) colonization among migratory birds at Qinghai Lake in China.Methods: A total of 420 samples from migratory birds and their surrounding environment were collected at three sites along the Qinghai Lake bird island. Carbapenem-non-susceptible isolates were identified by 16S rDNA sequencing and MALDI-TOF MS. Carbapenemase producers were determined by Carba NP testing. Antimicrobial susceptibility testing, transfer ability and PFGE were also performed, and 46 isolates from different pulsotypes were analysed by WGS.Results: Three hundred and fifty isolates were carbapenemase producers based on Carba NP testing, while 233 Klebsiella spp. and 2 Escherichia coli isolates were NDM-5-carriers. PFGE was performed and showed that the isolates were grouped into five pulsotypes; among these, type A was predominant (86.7%, n = 202) and belonged to a novel Klebsiella lineage, ST1697. WGS analysis indicated that ST1697 strains may be a hybrid of the recombination of Klebsiella quasipneumoniae subsp. similipneumoniae and Klebsiella pneumoniae genomes.Conclusions: This high frequency of carbapenemase producers in migratory birds is unexpected. These results provide new insight into the spread of antibiotic resistance, and highlight that continued vigilance for MDR carbapenemase-producing Enterobacteriaceae in migratory birds is urgently needed. [ABSTRACT FROM AUTHOR]

Background Mycobacterium abscessus , an emerging pathogen in healthcare settings, has rarely been associated with community outbreaks. During February–May 2013, Idaho public health officials and pediatric infectious disease physicians investigated an outbreak of M abscessus skin infections in children whose only common exposure was an indoor wading pool. Methods Healthcare providers and parents reported possible M abscessus cases. We used a standardized questionnaire to interview parents of affected children. Clinical specimens were submitted for mycobacterial examination. We conducted an environmental investigation of the pool. Microbial isolates from clinical and environmental samples were identified by sequencing polymerase chain reaction amplicons and underwent pulsed-field gel electrophoresis. Results Twelve cases were identified. Specimens from 4 of 7 children grew M abscessus or Mycobacterium abscessus/Mycobacterium chelonae. Ten (83%) of 12 children were female; median age was 3 years (range, 2 to 6 years); and all were immunocompetent. Pool maintenance did not fully comply with Idaho state rules governing pool operation. Mycobacterium abscessus / chelonae was isolated from pool equipment. Pulsed-field gel electrophoresis composite patterns were 87% similar between isolates from the pool ladder and 1 patient, and they were 90% similar between isolates from 2 patients. Environmental remediation included hyperchlorination, scrubbing and disinfection of pool surfaces, draining the pool, and replacement of worn pool materials. Conclusions Immunocompetent children acquired M abscessus cutaneous infection involving hands and feet after exposure to a wading pool. Environmental remediation and proper pool maintenance likely halted transmission. Medical and public health professionals' collaboration effectively detected and controlled an outbreak caused by an emerging recreational waterborne pathogen. [ABSTRACT FROM AUTHOR]

Objectives: To characterize the oxazolidinone resistance gene poxtA on broad-host-range Inc18 plasmids from CC17 Enterococcus faecium of pig origin.Methods: Oxazolidinone-resistant E. faecium isolates were screened for the presence of poxtA. The poxtA-carrying isolates were characterized by antimicrobial susceptibility testing, conjugation, S1-PFGE and hybridization. The poxtA-carrying plasmids were completely sequenced and their instability was verified.Results: Two individual CC17 E. faecium strains were positive for poxtA. S1-PFGE and hybridization revealed the presence of a poxtA-carrying plasmid of ∼62 kb in both WZ27-2 and the transconjugant, while poxtA-carrying plasmids of different sizes were observed in QF25-1 and the transconjugant. The two poxtA-carrying plasmids, pC25-1 and pC27-2, belonged to the broad-host-range plasmids of the Inc18 family and carried dfrG, aadE, Δsat4, aph(3')-III, erm(B), tet(M), tet(L) and fexB. Plasmid pC27-2 was virtually identical to pC25-1, with minor differences. The calculated transfer frequency was ∼0.87 × 10-8 and ∼1.03 × 10-7 per recipient to plasmids pC25-1 and pC27-2, respectively. Instability assays of the region with four adjacent IS1216Es, which forms three IS1216E translocatable units, revealed the formation of a series of mosaic circular intermediates.Conclusions: We report the emergence of the plasmid-mediated oxazolidinone resistance gene poxtA in E. faecium from different farms in China. Comparison of the poxtA genetic context suggests that IS1216E elements play an important role in the dissemination of poxtA. The co-occurrence of poxtA with other antimicrobial and heavy metal resistance genes on the broad-host-range plasmids of the Inc18 family may lead to the co-selection of poxtA, contributing to its persistence and accelerating its dissemination. [ABSTRACT FROM AUTHOR]

Objectives Carbapenem-resistant Pseudomonas aeruginosa are emerging worldwide with increasing reports of carbapenemase-producing isolates. Carbapenem-resistant isolates may also be XDR. This study characterized carbapenem-resistant and XDR P. aeruginosa isolated from patients receiving care at Canadian hospitals from 2007 to 2016. Methods Antimicrobial susceptibility testing was performed using CLSI broth microdilution methods. PCR was used to detect carbapenemases (GES, KPC, NDM, IMP, VIM, OXA-48) and other resistance markers; specific carbapenemase gene variants were identified by DNA sequencing. Genetic relatedness was assessed by MLST and PFGE. Results From 2007 to 2016, 3864 isolates of P. aeruginosa were collected; 466 (12.1%) isolates were carbapenem resistant. The prevalence of carbapenem-resistant P. aeruginosa reached a peak of 17.3% in 2014. Colistin (94% susceptible) and ceftolozane/tazobactam (92.5%) were the most active agents against carbapenem-resistant P. aeruginosa. XDR P. aeruginosa comprised 4.5% of isolates; they were found to be genetically diverse and remained susceptible to colistin and ceftolozane/tazobactam. Only 4.3% (n  = 20) of carbapenem-resistant P. aeruginosa harboured a carbapenemase; most were bla GES-5 (35%, n  = 7). Wide genetic diversity was observed among carbapenem-resistant P. aeruginosa with >200 different sequence types identified. Conclusions Although the prevalence of carbapenem-resistant P. aeruginosa in Canada spiked in 2014 and 2015, carbapenemase-producing P. aeruginosa remain rare with only 20 (4.3%) isolates identified over a 10 year period. Broad genetic diversity was observed among both carbapenem-resistant and XDR phenotypes of P. aeruginosa. Pan-drug-resistant P. aeruginosa have not yet been identified in Canada. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the occurrence, the genetic environment and the functionality of novel variants of the MDR gene cfr(C) in Campylobacter from China.Methods: A total of 370 Campylobacter isolates of porcine and chicken origin collected from three regions of China in 2015 were screened for cfr(C) by PCR. The phenotypes and genotypes of cfr(C)-positive isolates were investigated by antimicrobial susceptibility testing, PFGE, MLST, S1-PFGE, Southern blotting and WGS. Quantitative RT-PCR was used to compare the expression levels of the cfr(C) variants in their original isolate and clone constructs in Campylobacter jejuni NCTC 11168.Results: Four (1.1%) porcine Campylobacter coli isolates were positive for cfr(C). They failed to show elevated MICs of phenicols. The deduced Cfr(C) sequences identified exhibited 2-6 amino acid changes compared with the original Cfr(C) reported in the USA. Cloning of the cfr(C) variant genes into C. jejuni NCTC 11168 resulted in ≥32-fold increases in the MICs of phenicols, indicating that the cfr(C) variant genes are functional. The cfr(C)-carrying isolates belonged to three genotypes and WGS analysis revealed the cfr(C) genes were chromosomally located in MDR genomic islands, which contained multiple antibiotic resistance genes of Gram-positive origin.Conclusions: This study identified chromosomal cfr(C) genes in C. coli isolates from China. They appeared functionally dormant in the original isolates but were fully functional when cloned and expressed in C. jejuni. The cfr(C) genes were co-transferred with other antibiotic resistance genes, possibly from Gram-positive bacteria. These findings reveal new insights into the function and transmission of cfr(C) in Campylobacter. [ABSTRACT FROM AUTHOR]

Objectives: NDM-producing Enterobacteriaceae clinical isolates remain uncommon in the European region. We describe the emergence and broad dissemination of one successful NDM-1-producing Klebsiella pneumoniae clone in Greek hospitals.Methods: During a 4 year survey (January 2013-December 2016), 480 single-patient carbapenem non-susceptible K. pneumoniae isolates, phenotypically MBL positive, were consecutively recovered in eight Greek hospitals from different locations and subjected to further investigation. Antimicrobial susceptibility testing, combined-disc test, identification of resistance genes by PCR and sequencing, molecular fingerprinting by PFGE, plasmid profiling, replicon typing, conjugation experiments and MLST were performed.Results: Molecular analysis confirmed the presence of the blaNDM-1 gene in 341 (71%) K. pneumoniae isolates. A substantially increasing trend of NDM-1-producing K. pneumoniae was noticed during the survey (R2 = 0.9724). Most blaNDM-1-carrying isolates contained blaCTX-M-15, blaOXA-1, blaOXA-2 and blaTEM-1 genes. PFGE analysis clustered NDM-1 producers into five distinct clonal types, with five distinct STs related to each PFGE clone. The predominant ST11 PFGE clonal type was detected in all eight participating hospitals, despite adherence to the national infection control programme; it was identical to that observed in the original NDM-1 outbreak in Greece in 2011, as well as in a less-extensive NDM-1 outbreak in Bulgaria in 2015. The remaining four ST clonal types (ST15, ST70, ST258 and ST1883) were sporadically detected. blaNDM-1 was located in IncFII-type plasmids in all five clonal types.Conclusions: This study gives evidence of possibly the largest NDM-1-producing K. pneumoniae outbreak in Europe; it may also reinforce the hypothesis of an NDM-1 clone circulating in the Balkans. [ABSTRACT FROM AUTHOR]

Objectives: Young children could act as important carriers of cefotaxime-resistant Enterobacteriaceae. However, most studies on these bacteria have focused on hospitalized adults. Therefore, we determined the prevalence and characteristics of ESBL-, plasmid-determined AmpC-type β-lactamase (PABL)- and carbapenemase-producing diarrhoeagenic Escherichia coli isolates mainly from infants and children in the south-west region of Korea over a 10 year period.Methods: Non-duplicate E. coli clinical isolates were recovered from diarrhoeagenic patient specimens at 12 hospitals in Gwangju, Korea, between January 2007 and December 2016. Antimicrobial susceptibilities and molecular features of ESBL- and carbapenemase-producing isolates were determined.Results: A total of 1047 pathogenic E. coli isolates were collected and 58 cefotaxime-resistant E. coli isolates (5.5%) were identified. The prevalence and types of β-lactamase genes increased steadily from 5.7% in 2007 to 11.6% in 2016 with some fluctuations. CTX-M-14 (53.4%) was the predominant CTX-M genotype. PFGE revealed high genetic heterogeneities among diarrhoeagenic E. coli isolates, suggesting horizontal transfer of antibiotic resistance genes, which was also proved by conjugation assay.Conclusions: Progressive increases in carriage rates and the number of β-lactamase types, and the possibility of community outbreaks of these food-borne bacteria in young children, may pose tangible public health threats. [ABSTRACT FROM AUTHOR]

Throughout the body, epithelial tissues contain curved features (e.g. cysts, ducts and crypts) that influence cell behaviors. These structures have varied curvature, with flat structures having zero curvature and structures such as crypts having large curvature. In the ovary, cortical inclusion cysts (CICs) of varying curvatures are found, and fallopian tube epithelial (FTE) cells have been found trapped within these cysts. FTE are the precursor for ovarian cancer, and the CIC niche has been proposed to play a role in ovarian cancer progression. We hypothesized that variations in ovarian CIC curvature that occur during cyst resolution impact the ability of trapped FTE cells to invade into the surrounding stroma. Using a lumen model in collagen gels, we determined that increased curvature resulted in more invasions of mouse FTE cells. To isolate curvature as a system parameter, we developed a novel technique to pattern concave curvatures into collagen gels. When FTE cells were seeded to confluency on curved substrates, increases in curvature increased the number of invading FTE cells and the invasion distance. FTE invasion into collagen substrates with higher curvature depended on matrix metalloproteinases (MMPs), but expression of collagen I degrading Mmps was not different on curved and flat regions. A finite-element model predicted that contractility and cell–cell connections were essential for increased invasion on substrates with higher curvature, while cell–substrate interactions had minimal effect. Experiments supported these predictions, with invasion decreased by blebbistatin, ethylene glycol-bis(β-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) or N-cadherin-blocking antibody, but with no effect from a focal adhesion kinase inhibitor. Finally, experimental evidence supports that cell invasion on curved substrates occurs in two phases—a cell–cell-dependent initiation phase where individual cells break away from the monolayer and an MMP-dependent phase as cells migrate further into the collagen matrix. [ABSTRACT FROM AUTHOR]

Objectives: To undertake a Spanish nationwide survey on Pseudomonas aeruginosa molecular epidemiology and antimicrobial resistance.Methods: Up to 30 consecutive healthcare-associated P. aeruginosa isolates collected in 2017 from each of 51 hospitals were studied. MICs of 13 antipseudomonal agents were determined by broth microdilution. Horizontally acquired β-lactamases were detected by phenotypic methods and PCR. Clonal epidemiology was evaluated through PFGE and MLST; at least one XDR isolate from each clone and hospital (n = 185) was sequenced.Results: The most active antipseudomonals against the 1445 isolates studied were colistin and ceftolozane/tazobactam (both 94.6% susceptible, MIC50/90 = 1/2 mg/L) followed by ceftazidime/avibactam (94.2% susceptible, MIC50/90 = 2/8 mg/L). Up to 252 (17.3%) of the isolates were XDR. Carbapenemases/ESBLs were detected in 3.1% of the isolates, including VIM, IMP, GES, PER and OXA enzymes. The most frequent clone among the XDR isolates was ST175 (40.9%), followed by CC235 (10.7%), ST308 (5.2%) and CC111 (4.0%). Carbapenemase production varied geographically and involved diverse clones, including 16.5% of ST175 XDR isolates. Additionally, 56% of the sequenced XDR isolates showed horizontally acquired aminoglycoside-modifying enzymes, which correlated with tobramycin resistance. Two XDR isolates produced QnrVC1, but fluoroquinolone resistance was mostly caused by QRDR mutations. Beyond frequent mutations (>60%) in OprD and AmpC regulators, four isolates showed AmpC mutations associated with resistance to ceftolozane/tazobactam and ceftazidime/avibactam.Conclusions: ST175 is the most frequent XDR high-risk clone in Spanish hospitals, but this nationwide survey also indicates a complex scenario in which major differences in local epidemiology, including carbapenemase production, need to be acknowledged in order to guide antimicrobial therapy. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the genetic features of the blaVIM-1 gene first detected in a cephalosporin-resistant Vibrio alginolyticus isolate, Vb1978.Methods: The MICs of V. alginolyticus strain Vb1978 were determined, and the β-lactamases produced were screened and analysed using conjugation, S1-PFGE and Southern blotting. The complete sequence of the blaVIM-1-encoding plasmid was also obtained using the Illumina and MinION sequencing platforms.Results: V. alginolyticus strain Vb1978, isolated from a retail shrimp sample, was resistant to cephalosporins and exhibited reduced susceptibility to carbapenems. A novel blaVIM-1-carrying conjugative plasmid, designated pVb1978, was identified in this strain. Plasmid pVb1978 had 50 001 bp and comprised 59 predicted coding sequences (CDSs). The plasmid backbone of pVb1978 was homologous to those of IncP-type plasmids, while its replication region was structurally similar to non-IncP plasmids. The blaVIM-1 gene was found to be carried by the class 1 integron In70 and associated with a defective Tn402-like transposon.Conclusions: A novel blaVIM-1-carrying conjugative plasmid, pVb1978, was reported for the first time in V. alginolyticus, which warrants further investigation in view of its potential pathogenicity towards humans and widespread occurrence in the environment. [ABSTRACT FROM AUTHOR]

Background: The mcr-1 gene has been widely reported in both bacterial chromosomes and plasmids, while its stability in these genetic materials is not well understood.Objectives: Our aim was to characterize the stability and dynamics of Tn6330 elements in both a plasmid and the chromosome in a single bacterial population.Methods: Plasmid-borne and chromosomal Tn6330 were characterized by PCR, conjugation, S1-PFGE, stability assay, single-molecule long-read sequencing and bioinformatics analysis.Results: Tn6330 was simultaneously detected in both a plasmid and the chromosome of a clinical Escherichia coli strain. The plasmid was found to comprise the IncFIB replicon and a phage-like replicon, as well as two integrons that harboured various mobile elements and resistance genes including mcr-1, floR, blaTEM-1b and strAB. Both plasmid-borne and chromosomal Tn6330 transposons could be re-organized into a circular intermediate that played a role in transmission of the mcr-1 gene. Tn6330 was found to be very stable in both the plasmid and chromosome after 30 passages of 12 h with or without colistin selective pressure. The decayed structure of Tn6330 in the genuine single DNA molecules of bacterial populations, although occurring at a very low frequency, could be detected for the first time, in which Tn6330 was degraded into a single ISApl1 element.Conclusions: Long-read sequencing technology is a good tool to study the evolution and stability of genetic elements in bacteria. The ultrastability of an mcr-1-encoding element in a bacterial plasmid and chromosome renders it unlikely to be eradicated quickly by the reduced use of colistin, and factors leading to the frequent demise of Tn6330 warrant further studies. [ABSTRACT FROM AUTHOR]

Objectives: Topical treatment for cutaneous leishmaniasis (CL) would be useful for treatment of some forms of the disease. The aim of this study was to develop and then evaluate a topical miltefosine gel for anti-leishmanial activity and toxicity in BALB/c mice infected with New World (NW)-CL species.Methods: A Carbopol-based gel of 0.5% miltefosine was prepared and physicochemical (colour, pH, consistency and antioxidant activity) and stability properties were determined using standard methodologies. Anti-leishmanial activities for Leishmania (Viannia) braziliensis and Leishmania (Viannia) panamensis were determined both in cultured parasites and in infected BALB/c mice after topical miltefosine gel treatment administered for 20 days. The gel was evaluated for its capacity to inhibit parasites at a 50% level after 3 days of treatment in vitro, and its capacity to reduce lesion size (mm2) and parasitic load after 20 days of treatment. Dermal irritation, contact hypersensitivity (CHS), clinical biochemical profile and the weight of the animals were determined after treatment.Results: The 0.5% miltefosine gel was transparent, homogeneous, colourless, of neutral pH, spreadable and stable at 4°C for at least 3 months. It was active against parasites in vitro and in vivo, reducing CL lesion size by 84%-100% with no detected parasites. No signs of irritation, CHS or changes in weight, food intake, urea or transaminase serum levels were observed after treatment.Conclusions: The topical 0.5% miltefosine gel formulation was efficacious and non-toxic when administered topically in NW-CL murine models. This miltefosine formulation could be an appropriate candidate for further development. [ABSTRACT FROM AUTHOR]

Background: Pectus excavatum (PE) is sometimes associated with psychological and physiological difficulties influencing a patient's quality of life. Treatment with a hyaluronic acid (HA)-based gel may benefit patients and be an alternative to other more invasive treatments.Objectives: The authors sought to evaluate the effectiveness in terms of satisfaction, duration, and safety of HA gel treatment for PE including impact on quality of life.Methods: Males ≥18 years having PE without functional problems received HA gel injections (50 - 150 mL) at the site of deformity and in some cases at the medial pectoralis muscle borders to optimize the aesthetic result. Follow-up visits were performed after 1, 3, 6, 12, and 24 months with optional retreatment at the 24-month visit including a 1-month follow-up. Evaluations included Pectus Excavatum Evaluation Questionnaire, patient satisfaction, magnetic resonance imaging, and safety assessments.Results: The treatment significantly improved patients' self-esteem (P < 0.001) and psychosocial function (P ≤ 0.038) throughout the study, as assessed by Pectus Excavatum Evaluation Questionnaire. Patients were satisfied with the aesthetic outcome and considered the treatment mild in terms of level of pain during injection. Treatment effects were maintained up to 24 months and 58% of the HA gel remained at this visit, shown by Magnetic Resonance Imaging measurements. The treatment was well tolerated.Conclusions: Treatment of PE with HA gel improved patient quality of life related to self-esteem and psychosocial functioning including aesthetically pleasing results. The treatment may also offer benefits in terms of safety and tolerability compared with other treatments.Level Of Evidence:4: [ABSTRACT FROM AUTHOR]

Background: With the rise of fluconazole resistance in Candida tropicalis in Asian countries, the rapid detection of resistance is required to optimize therapy.Objectives: We evaluated a stable isotope labelling by/with amino acids in cell culture (SILAC) approach for rapid detection of fluconazole resistance in C. tropicalis by MALDI-TOF MS.Methods: Twenty-six fluconazole-resistant and 19 -susceptible C. tropicalis isolates were used. Isolates were grown in media containing normal lysine (NL), isotopically labelled ('heavy') lysine (HL) and fluconazole (FLC) with labelled lysine (HL + FLC). MALDI-TOF MS was performed, acquired spectra were visually compared and composite correlation index (CCI) values were calculated. The results were analysed by CCI matrix, virtual gel and principal component analysis (PCA).Results: The MICs of fluconazole in 26 resistant and 19 susceptible isolates were 16-256 mg/L and 0.5-1 mg/L, respectively. The m/z values of 15 peaks specific for media containing NL and their corresponding peaks specific for media with HL were detected to differentiate resistant and susceptible isolates. The CCI cut-off values for susceptible and resistant isolates were significant (P < 0.05). The CCI matrix, virtual gel and PCA dendrogram confirmed the results. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of this method for detection of fluconazole resistance were 92.31%, 100%, 100%, 90.48% and 95.56%, respectively.Conclusions: SILAC, a promising approach for rapid resistance detection in C. tropicalis using MALDI-TOF MS, may be used in the routine laboratory in the near future. [ABSTRACT FROM AUTHOR]

Objectives: To characterize the antimicrobial susceptibility, molecular epidemiology and carbapenem resistance mechanisms in Pseudomonas aeruginosa isolates recovered from respiratory tract samples from patients with ventilator-associated pneumonia enrolled in the MagicBullet clinical trial.Methods: Isolates were collected from 53 patients from 12 hospitals in Spain, Italy and Greece. Susceptibility was determined using broth microdilution and Etest. MALDI-TOF MS was used to detect carbapenemase activity and carbapenemases were identified by PCR and sequencing. Molecular epidemiology was investigated using PFGE and MLST.Results: Of the 53 isolates, 2 (3.8%) were considered pandrug resistant (PDR), 19 (35.8%) were XDR and 16 (30.2%) were MDR. Most (88.9%) of the isolates from Greece were MDR, XDR or PDR, whereas fewer of the isolates from Spain (33.3%) and Italy (43.5%) showed antibiotic resistance. Three Greek isolates were resistant to colistin. Overall, the rates of resistance of P. aeruginosa isolates to imipenem, ciprofloxacin, ceftolozane/tazobactam and ceftazidime/avibactam were 64.1%, 54.7%, 22.6% and 24.5%, respectively. All isolates resistant to ceftolozane/tazobactam and ceftazidime/avibactam (Greece, n = 10; and Italy, n = 2) carried blaVIM-2. Spanish isolates were susceptible to the new drug combinations. Forty-eight restriction patterns and 27 STs were documented. Sixty percent of isolates belonged to six STs, including the high-risk clones ST-111, ST-175 and ST-235.Conclusions: MDR/XDR isolates were highly prevalent, particularly in Greece. The most effective antibiotic against P. aeruginosa was colistin, followed by ceftolozane/tazobactam and ceftazidime/avibactam. blaVIM-2 is associated with resistance to ceftolozane/tazobactam and ceftazidime/avibactam, and related to highly resistant phenotypes. ST-111 was the most frequent and disseminated clone and the clonal diversity was lower in XDR and PDR strains. [ABSTRACT FROM AUTHOR]

Lubricating agents facilitate effective harvesting of split-thickness skin grafts. Multiple agents, including water-based gel, mineral oil, glycerin, and poloxamer 188, have been utilized in this capacity. The agent selected is typically at the discretion of the provider and institution, as a single "ideal" lubricant remains to be objectively established. Furthermore, a recent discontinuation of Shur-Clens® Skin Wound Cleanser1 (a wound cleansing solution consisting of the surfactant poloxamer 188) has prompted the search for a suitable substitute for many providers. The purpose of this study is to directly compare five lubricants (including a novel surgical lubricant-based solution) to select a preferred agent. Four practitioners blindly tested five lubricants while harvesting a split-thickness skin graft on a porcine skin model (glycerin, mineral oil, saline, poloxamer 188, and a novel lubricant solution created with surgical lube and sterile water). The results were recorded on a Likert scale where 1 indicated poor performance and 5 indicated excellent performance. Data were pooled, and means were compared with analysis of variance and post hoc Tukey test. The cost of each lubricating solution was also reported. Mean scores for each of the solutions were as follows: dry control = 1.1 ± 0.1; glycerin = 2.62 ± 1.02, saline = 3.88 ± 0.81, mineral oil = 3.75 ± 1.00, novel water-based lubricant solution = 4.63 ± 0.71, and poloxamer 188 = 3.88 ± 0.81. All solutions were superior to dry control (P < .01). Glycerin was noted to have statistically lower scores than all of the other solutions (P < .01). The novel water-based surgical lubricant solution had significantly higher mean scores than both glycerin (P < .01) and mineral oil (P < .05). Each solution was compared according to dollars per 100cc with glycerin and Shur-Clens® representing the most expensive options at almost $3/100cc and saline the least expensive at less than $0.15/100cc. In a porcine skin model, the novel water-based surgical lubricant solution had the best performance. It was statistically superior to glycerin and mineral oil and was also found to be the most cost-effective option in terms of overall performance compared with relative cost. Glycerin had the worst performance with statistically lower scores than all other solutions. Glycerin was also found to be the least cost-effective due to a large discrepancy between high cost and low overall performance. Saline performed better than expected. These results may be skewed due to the inherently greasy nature of the butcher shop porcine skin, creating limitations and decreasing the fidelity of the model. In a search for the "ideal" lubricant, other models should be further studied. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the transferability of antibiotic resistance from an MDR clade B Enterococcus faecium and to characterize the genetic elements involved.Methods: The erm(B)-positive strain E. faecium 37BA (donor) and strains E. faecium 64/3 and Listeria welshimeri 11857RF (recipients) were used in mating experiments. Donors and transconjugants were characterized using MIC assays, PFGE, Southern blotting and hybridization, quantitative RT-PCR (RT-qPCR), next-generation sequencing and PCR mapping.Results: One E. faecium and one L. welshimeri transconjugant were selected for in-depth investigation. Both acquired an ∼40 kb plasmid carrying erm(B). An additional plasmid of ∼200 kb, encoding the full conjugation machinery, was detected in the donor and in the E. faecium transconjugant. Next-generation sequencing revealed a new 40 396 bp plasmid that was designated pEf37BA; it contained 10 antibiotic resistance genes, tet(M), tet(L), erm(B), aadE, sat4, aphA, spw, lsa(E), lnu(B) and pbp5, resulting from the recombination of pM7M2 of E. faecium with an MDR chromosomal region of Erysipelothrix rhusiopathiae. A pbp5-carrying circular form was also detected. The PBP5 amino acid sequence differed from the C46 variant by two mutations (S39T and D644N). Its expression was documented in both transconjugants. pEf37BA persisted in the absence of selective pressure.Conclusions: The MDR clade B E. faecium plasmid, deriving from the recombination of two different resistance regions, carried a pbp5 element and was transferable to different bacterial species. This finding further documents the dissemination of ampicillin resistance among community-associated E. faecium and the key role of commensal strains in the spread of antibiotic resistance. [ABSTRACT FROM AUTHOR]

Objectives: To characterize the population structure, antimicrobial resistance and virulence genes of Klebsiella spp. isolated from dogs, cats and humans with urinary tract infections (UTIs).Methods: Klebsiella spp. from companion animals (n = 27) and humans (n = 77) with UTI were tested by the disc diffusion method against 29 antimicrobials. Resistant/intermediate isolates were tested by PCR for 16 resistance genes. Seven virulence genes were screened for by PCR. All Klebsiella pneumoniae from companion animals and third-generation cephalosporin (3GC)-resistant isolates from humans were typed by MLST. All Klebsiella spp. were compared after PFGE XbaI macro-restriction using Dice/UPGMA with 1.5% tolerance.Results: bla CTX-M-15 was detected in >80% of 3GC-resistant strains. K. pneumoniae high-risk clonal lineage ST15 predominated in companion animal isolates (60%, n = 15/25). Most companion animal ST15 K. pneumoniae belonged to two PFGE clusters (C4, C5) that also included human strains. Companion animal and human ST15-CTX-M-15 K. pneumoniae shared a fimH-1/mrkD/entB/ycfM/kfu virulence profile, with a few (n = 4) also harbouring the yersiniabactin siderophore-encoding genes. The hospital-adapted ST11 K. pneumoniae clonal lineage was detected in a cat (n = 1) and a human (n = 1); both were MDR, had 81.1% Dice/UPGMA similarity and shared several virulence and resistance genes. Two 3GC-resistant ST348 strains with 86.7% Dice/UPGMA similarity were isolated from a cat and a human.Conclusions: Companion animals with UTI become infected with high-risk K. pneumoniae clonal lineages harbouring resistance and virulence genes similar to those detected in strains from humans. The ST15-CTX-M-15 K. pneumoniae clonal lineage was disseminated in companion animals with UTI. Caution must be applied by companion animal caretakers to avoid the spread of K. pneumoniae high-risk clonal lineages. [ABSTRACT FROM AUTHOR]

Background: Surgical applications using breast implants are individualized operations to fill and shape the breast. Physical properties beyond shape, size, and surface texture are important considerations during implant selection.Objectives: Compare form stability, gel material properties, and shell thickness of textured shaped, textured round, and smooth round breast implants from 4 manufacturers: Allergan, Mentor, Sientra, and Establishment Labs, through bench testing.Methods: Using a mandrel height gauge, form stability was measured by retention of dimensions on device movement from a horizontal to vertical supported orientation. Dynamic response of the gel material (gel cohesivity, resistance to gel deformation, energy absorption) was measured using a synchronized target laser following application of graded negative pressure. Shell thickness was measured using digital thickness gauge calipers.Results: Form stability, gel material properties, and shell thickness differed across breast implants. Of textured shaped devices, Allergan Natrelle 410 exhibited greater form stability than Mentor MemoryShape and Sientra Shaped implants. Allergan Inspira round implants containing TruForm 3 gel had greater form stability, higher gel cohesivity, greater resistance to gel deformation, and lower energy absorption than those containing TruForm 2 gel and in turn, implants containing TruForm 1 gel. Shell thickness was greater for textured vs smooth devices, and differed across styles.Conclusions: Gel cohesivity, resistance to gel deformation, and energy absorption are directly related to form stability, which in turn determines shape retention. These characteristics provide information to aid surgeons choosing an implant based on surgical application, patient tissue characteristics, and desired outcome. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the prevalence and molecular characteristics of ESBL-producing Escherichia coli (ESBL-EC) in faecal samples from dairy cows in China.Methods: In total, 651 faecal samples were collected from cows distributed among the 10 provinces of China. Potential ESBL-EC isolates were cultured on selective medium. The clonal relatedness of the ESBL-EC isolates was assessed using MLST. WGS was conducted on 3 mcr-positive isolates and 14 additional randomly selected ESBL-EC isolates. Southern blot, S1-PFGE and conjugation were performed for mcr-1-carrying isolates. The genetic environment of the pMCR-JLF4 plasmid was also analysed.Results: In total, 290 unique ESBL-EC isolates were detected from 284 cows (43.6%). Alleles of CTX-M were observed in 94.1% (273/290) of all isolates. The most prevalent genotypes observed in this study were blaCTX-M-14, blaCTX-M-15, blaCTX-M-17 and blaCTX-M-55. Differentiation of 79 STs with a polyclonal structure was accomplished using MLST. Clonal complex 10 was the most prevalent major complex detected here. Furthermore, the mcr-1 gene was detected in three isolates. The complete sequence of the mcr-1-containing pMCR-JLF4 was determined. The plasmid was 66.7 kb in length, with a genetic structure of nikA-nikB-mcr-1-pap2. Conjugation analysis confirmed that the mcr-1 gene in pMCR-JLF4 was transferable without the assistance of the ISApl1 gene.Conclusions: The data presented here suggest high prevalence of ESBL-EC in Chinese cow farms. Furthermore, it was clearly demonstrated that commensal E. coli strains can be reservoirs of blaCTX-M genes, potentially contributing to the dissemination and transfer of the mcr-1 gene to pathogenic bacteria among cows. [ABSTRACT FROM AUTHOR]

Objectives: Brazil is the greatest exporter of chicken meat (CM) in the world. It is of utmost importance to monitor resistance to extended-spectrum cephalosporins (ESCs) in this sector because resistance to ESCs in Escherichia coli isolated from food-producing animals may contaminate humans through the food chain. Thus, the aim of this study was to characterize and compare ESC-resistant E. coli isolated from chickens and retail CM produced in south-eastern Brazil.Methods: Five CM samples and 117 chicken cloacal swabs (CCSs) were inoculated on MacConkey agar supplemented with cefotaxime. Presumptive E. coli colonies were identified and antimicrobial susceptibility was tested. Virulence and acquired blaESBL and blaAmpC genes were sought and genetic environments characterized. Isolates were typed by phylogenetic grouping, XbaI-PFGE and MLST.Results: All five CM samples and 36 CCSs (30.8%) were positive for the presence of ESC-resistant E. coli, leading to the selection of 58 resistant isolates. ESC resistance was mostly due to the presence of the chromosome-encoded blaCTX-M-2 gene, but plasmid-mediated blaCTX-M-2, blaCTX-M-8, blaCTX-M-15, blaCTX-M-55 and blaCMY-2 were also detected. Multireplicon plasmids were sporadically identified, such as IncHI2/P-blaCTX-M-2 and IncFII/N-blaCTX-M-55. Phylogroup D predominated, while PFGE and MLST revealed a high genetic diversity.Conclusions: Live Brazilian chickens and CM act as reservoirs of ESC-resistant E. coli and resistance genes are located on highly diverse genetic determinants. Potentially pathogenic strains, which may represent a threat to human health and a source of environmental contamination, were also identified. Active surveillance is therefore essential in Brazil's chicken production line. [ABSTRACT FROM AUTHOR]

Objectives: To describe the incidence and microbiological features of carbapenemase-producing Enterobacteriaceae (CPE) from colonized patients in a Spanish university hospital during a cluster-randomized study [the Resistance of Gram-Negative Organisms: Studying Intervention Strategies (R-GNOSIS) project] on isolation strategies for faecal ESBL carriers.Methods: From March 2014 to March 2016, 15 556 rectal swabs from 8209 patients admitted in two surgical wards and two medical wards were collected and seeded on ESBL and CPE chromogenic agars. Carbapenemase characterization (PCR and sequencing) was performed, and antibiotic susceptibility (MIC), clonality (PFGE and MLST) and diversity (Simpson diversity index estimation) were determined.Results: One hundred and ninety-eight CPE isolates, mainly Klebsiella pneumoniae (53.5%) and Escherichia coli (19.2%), were identified in 162 patients (2%). Prevalence of CPE carriage remained unchanged over time. Overall, amikacin (9.6%), tigecycline (9.6%) and colistin (0.5%) showed low non-susceptibility. The most frequent carbapenemase was OXA-48 (64.1%), followed by VIM-1 (26.8%), NDM-1 (5.3%) and KPC-3 (3.5%), and these were co-produced with ESBLs in 43.9%. OXA-48 plus CTX-M-15 was the most frequent association. Two major K. pneumoniae clones were identified (OXA-48-CTX-M-15-ST11 and VIM-1-SHV-12-ST54) with considerable genetic diversity among the remaining isolates, including OXA-48-E. coli. Species diversity tended to decrease from 0.75 in the first 6 months of the study to 0.43 in the final months. The emergence of new clones (i.e. OXA-48-Kluyvera spp. and NDM-1-K. pneumoniae ST437 and ST101) and displacement of other particular clones were also demonstrated.Conclusions: We describe a polyclonal and changeable CPE population over time. Coexistence of worldwide disseminated clones, such as ST11-OXA-48- K. pneumoniae, with unrelated and emerging OXA-48-E. coli clones, depicts a disturbing CPE epidemiology in our institution. [ABSTRACT FROM AUTHOR]

Objectives: To analyse VIM/IMP-type MBL-producing Enterobacteriaceae isolates identified in Poland during 2006-12.Methods: Isolates were typed by PFGE, followed by MLST. blaVIM/IMP genes were amplified and sequenced within class 1 integrons. Their plasmidic versus chromosomal location was assessed by nuclease S1 and I-CeuI plus hybridization experiments. Plasmids were characterized by transfer assays and PCR-based replicon typing.Results: One hundred and nineteen VIM/IMP-positive Enterobacteriaceae cases were reported in Poland from the first case in 2006 until 2012. The patients were in 54 hospitals and were infected or colonized by 121 organisms, including Enterobacter cloacae complex (n = 64), Klebsiella oxytoca (n = 23), Serratia marcescens (n = 20) and Klebsiella pneumoniae (n = 11). The isolates represented numerous pulsotypes and mainly original STs, and carried eight integrons with blaVIM-1-like genes (blaVIM-1/-4/-28/-37/-40; n = 101), three with blaVIM-2 variants (blaVIM-2/-20; n = 17) and one with blaIMP-19 (n = 3). Six integrons were new, and five and two formed prevalent families of In238-like (n = 96) and In1008-like (n = 16) elements, respectively. In238 (aacA4-blaVIM-4rpt) and In1008 (blaVIM-2-aacA4) had been originally observed in Polish Pseudomonas aeruginosa, suggestive of their transfer to enterobacteria, followed by spread and diversification. Four organisms have disseminated inter-regionally, i.e. Enterobacter hormaechei ST90 with plasmidic In238/In238a integrons (n = 36), K. oxytoca ST145 with a chromosomal In237-like element (n = 18) and two subclones of E. hormaechei ST89 with In1008- or In238-type variants (n = 8 and n = 7, respectively).Conclusions: The epidemiology of VIM/IMP-producing Enterobacteriaceae in Poland has revealed a remarkable number of specific or novel characteristics of the organisms, with some possible links to other mid-southern European countries. [ABSTRACT FROM AUTHOR]

There remain significant uncertainties in estimation of risks with low doses of radiation. The small coastal belt in the southwestern state of Kerala, India, extending from Neendakara in the south to Purakkad in the north is one of the most extensively studied high-level natural background radiation areas (HLNRAs) of the world to address these concerns. The natural radioactivity here is due to occurrence of monazite sand bearing placer deposits along the coastline. In this study, proteomic approach was employed to study the response of human peripheral blood mononuclear cells (PBMCs) from individuals residing in HLNRA (N = 10; mean radiation dose: 15.60 ± 3.04 mGy/y) vis-à-vis responses in individuals from adjoining normal-level natural background radiation areas (NLNRA; N = 10; mean radiation dose: ≤1.50 mGy/y) using two-dimensional gel electrophoresis coupled with mass spectrometry. A total of 15 proteins were found to be statistically altered in individuals from HLNRA when compared to individuals from NLNRA (P ≤ 0.05). Most of the changes in expression were small. The mean coefficient of variation for the differentially altered proteins was found to be ~34%. Pathway enrichment analysis with Database for Annotation, Visualization and Integrated Discovery distinguished 44 biological processes significantly (P ≤ 0.05) modulated in HLNRA samples. More importantly, when challenged with an ex vivo dose of 2 Gy, HLNRA PBMCs responded with an up-regulation of many protective pro-survival proteins such as protein disulfide-isomerase A1 (PDIA1), peroxiredoxin 6 (PRDX6) and glucose-regulated protein 78 kDa (GRP78). PDIA1 and PRDX6 are known to play an important role in redox homeostasis. GRP78 is considered the master regulator of unfolded protein response that aims to restore endoplasmic reticulum homeostasis and thus, regulate cell survival. Principal component analysis identified clear clusters based on radiation dose. The expression changes of key proteins were validated by western blotting using additional samples from HLNRA and NLNRA. This indicates that the human cells respond to low dose of ionising radiation through dynamic changes in the proteome to maintain adaptive homeostasis. These findings emphasise that the dose–response relationship at low doses of radiation may not be linear and, thus, provide mechanistic challenge to the linear-no-threshold hypothesis. [ABSTRACT FROM AUTHOR]

Despite overall advances in burn therapy, wound infection remains one of the leading causes of morbidity and mortality in patients with severe burn injuries. This prospective, multicenter, noncomparative clinical trial was conducted to assess the efficacy and safety of Prontosan® Wound Gel X (PWX), a gel containing polihexanide and betaine, for moistening and cleansing in deep tissue burn wounds requiring split-thickness skin grafting. Patients with deep partial or full thickness burn wounds requiring split-thickness skin grafting were treated with the gel to evaluate its tolerability and safety as well as graft take and the healing of the skin graft. Target wounds were assessed clinically and by using a photo-planimetric analyzing software for re-epithelialization. From 04/2012 to 05/2015, burn patients from three burn centers in Germany were screened for the study, of which 51 patients met the inclusion criteria. Predominantly deep partial thickness burn wounds were found (88.2 %). Except for one graft failure, all patients reached complete re-epithelialization after one (n = 14), two (n = 31), or three (n = 5) administrations of the gel. The median time to complete graft take was 7 days and was below the average healing time reported in comparable studies. No wound infection or erythema occurred. This is the first study to document the outcomes of deep partial and full thickness burns treated with PWX for moistening and cleansing. The gel was shown to be efficacious, safe, and well tolerated for use in burn wounds requiring split-thickness skin grafts. [ABSTRACT FROM AUTHOR]

Background: Carbapenemase-producing Klebsiella pneumoniae causes high mortality owing to the limited therapeutic options available. Here, we investigated an emergent carbapenem-resistant K. pneumoniae strain with hypervirulence found among KPC-2-producing strains in Taiwan.Methods: KPC-producing K. pneumoniae strains were collected consecutively from clinical specimens at the Taipei Veterans General Hospital between January 2012 and December 2014. Capsular types and the presence of rmpA/rmpA2 were analysed, and PFGE and MLST performed using these strains. The strain positive for rmpA/rmpA2 was tested in an in vivo mouse lethality study to verify its virulence and subjected to WGS to delineate its genomic features.Results: A total of 62 KPC-2-producing K. pneumoniae strains were identified; all of these belonged to ST11 and capsular genotype K47. One strain isolated from a fatal case with intra-abdominal abscess (TVGHCRE225) harboured rmpA and rmpA2 genes. This strain was resistant to tigecycline and colistin, in addition to carbapenems, and did not belong to the major cluster in PFGE. TVGHCRE225 exhibited high in vivo virulence in the mouse lethality experiment. WGS showed that TVGHCRE225 acquired a novel hybrid virulence plasmid harbouring a set of virulence genes (iroBCDN, iucABCD, rmpA and rmpA2, and iutA) compared with the classic ST11 KPC-2-producing strain.Conclusions: We identified an XDR ST11 KPC-2-producing K. pneumoniae strain carrying a hybrid virulent plasmid in Taiwan. Active surveillance focusing on carbapenem-resistant hypervirulent K. pneumoniae strains is necessary, as the threat to human health is imminent. [ABSTRACT FROM AUTHOR]

Objectives: This study characterized the 11 most predominant serotypes of invasive Streptococcus pneumoniae infections collected by the annual SAVE study in Canada, between 2011 and 2015.Methods: A subset of the 11 most predominant serotypes (7F, 19A, 22F, 3, 12F, 11A, 9N, 8, 33F, 15A and 6C) collected by the SAVE study was analysed using PFGE and MLST, as well as PCR to identify pilus-encoding genes. WGS analyses were performed on a subset of the above isolates plus a random selection of background strains.Results: Of the predominant serotypes analysed, 7F, 33F and 19A were obtained more commonly from children <6 years of age, whereas 15A, 6C, 22F and 11A were more common in adults >65 years of age. Pneumococcal pilus PI-1 was identified in antimicrobial-susceptible serotype 15A (61/212) and <10% of 6C isolates (16/188). PI-2 was found in serotype 7F (683/701) and two-thirds of 11A isolates (162/241). Only serotype 19A-ST320 possessed both pili. Molecular and phylogenetic analyses identified serotypes 19A, 15A, 6C, 9N and 33F as highly diverse, whereas 7F, 22F and 11A demonstrated clonality. Antimicrobial resistance determinants were common within diverse serotypes, and usually similar within a clonal complex.Conclusions: Despite successful use of conjugate vaccines, S. pneumoniae remains a highly diverse organism in Canada. Several predominant serotypes, both antimicrobial susceptible and MDR, have demonstrated rapid clonal expansion or an increase in diversity. As S. pneumoniae continues to evolve in Canada, WGS will be a necessary component in the ongoing surveillance of antimicrobial-resistant and expanding clones. [ABSTRACT FROM AUTHOR]

Objectives: To discover the Escherichia coli STs and associated resistance mechanisms in the community in Islamabad, Pakistan by analysis of E. coli isolates in sewage.Methods: One hundred and ten E. coli were isolated from sewage across the city of Islamabad without antibiotic bias and confirmed as E. coli by MALDI-TOF MS. Isolates were characterized by fumC/fimH (CH) typing and core-genome MLST. Resistance mechanisms, virulence genes, phylotypes and plasmid incompatibility types were determined in a subset of isolates by in silico analysis. The genomic position of blaCTX-M-15 was determined using S1-PFGE, probing and Nanopore MinION sequencing.Results and conclusions: The most prevalent STs were ST394, ST10 and ST648, accounting for 39% of all isolates collected and were found at many sites across Islamabad. Carbapenemase genes were absent and only a single isolate of ST131 was found. The most prevalent resistance mechanisms were qnrS1 and blaCTX-M-15, with blaCTX-M-15 penetrating many STs and found in 31% of all collected isolates. However, the majority of the successful STs were blaCTX-M-15 negative indicating that resistance is not the main driver of prevalence. Twenty-three percent of blaCTX-M-15 genes were chromosomally encoded and large ISEcp1-mediated insertions included qnrS1 and several plasmid genes. In all chromosomally encoded isolates no plasmid copies of blaCTX-M-15 were found. The most prevalent ST (ST394) contained many enteroaggregative E. coli virulence genes and the fimH30 variant allele previously linked to the success of ST131. [ABSTRACT FROM AUTHOR]

Objectives: To characterize the mobile colistin resistance gene mcr-5 in Aeromonas hydrophila from backyard pigs in rural areas of China.Methods: Pig faecal samples from 194 households were directly tested for the presence of mcr-5 by PCR assay and the phenotypic antimicrobial susceptibility profiles of the mcr-5-positive isolates were determined using the broth dilution method. The genomic location and transferability of mcr-5 were analysed by S1-PFGE with Southern blotting and DNA hybridization, and natural transformation, respectively. One strain isolated from an mcr-5-positive sample was subjected to WGS and the stability of the mcr-5-harbouring plasmid over successive generations was examined by subculturing.Results: One mcr-5-positive A. hydrophila isolate showing resistance, with a colistin MIC of 4 mg/L, was isolated from a backyard pig faecal sample. mcr-5 was located on a 7915 bp plasmid designated pI064-2, which could naturally transform into a colistin-susceptible A. hydrophila strain of porcine origin and mediated colistin resistance in both the original isolate and its transformants. The plasmid backbone (3790 bp) of pI064-2 showed 81% nucleotide sequence identity to the corresponding region of the ColE2-type plasmid pAsa1 from Aeromonas salmonicida, while similar replication primases are widely distributed among aeromonads, Enterobacteriaceae and Pseudomonas species.Conclusions: To the best of our knowledge, this is the first identification of the novel colistin resistance gene mcr-5 in an A. hydrophila isolate from the faeces of a backyard pig. mcr-5 is expected to be able to disseminate among different bacterial species and genera. [ABSTRACT FROM AUTHOR]

Background: Candida auris has emerged as a serious threat to human health. Of particular concern are the resistance profiles of many clinical isolates, with some being resistant to multiple classes of antifungals.Objectives: Measure susceptibilities of C. auris isolates, in planktonic and biofilm forms, to ceragenins (CSAs). Determine the effectiveness of selected ceragenins in gel and cream formulations in eradicating fungal infections in tissue explants.Materials and methods: A collection of 100 C. auris isolates available at CDC was screened for susceptibility to a lead ceragenin. A smaller collection was used to characterize antifungal activities of other ceragenins against organisms in planktonic and biofilm forms. Effects of ceragenins on fungal cells and biofilms were observed via microscopy. An ex vivo model of mucosal fungal infection was used to evaluate formulated forms of lead ceragenins.Results: Lead ceragenins displayed activities comparable to those of known antifungal agents against C. auris isolates with MICs of 0.5-8 mg/L and minimum fungicidal concentrations (MFCs) of 2-64 mg/L. No cross-resistance with other antifungals was observed. Fungal cell morphology was altered in response to ceragenin treatment. Ceragenins exhibited activity against sessile organisms in biofilms. Gel and cream formulations including 2% CSA-44 or CSA-131 resulted in reductions of over 4 logs against established fungal infections in ex vivo mucosal tissues.Conclusions: Ceragenins demonstrated activity against C. auris, suggesting that these compounds warrant further study to determine whether they can be used for topical applications to skin and mucosal tissues for treatment of infections with C. auris and other fungi. [ABSTRACT FROM AUTHOR]

Objectives: Despite the fact that the blaOXA-48 and blaNDM-1 genes have successfully disseminated among Klebsiella pneumoniae isolates worldwide, outbreaks remain unidentified in Iran. Here we examined the molecular epidemiology of 96 carbapenem-resistant K. pneumoniae recovered from an Iranian hospital.Methods: A total of 96 non-replicate carbapenem-resistant K. pneumoniae were recovered from clinical specimens in a university hospital. Detection of ESBLs and carbapenemases produced by studied strains was performed using PCR and DNA sequencing. The bacterial isolates were assigned to clonal lineages by PFGE and MLST. In addition, plasmids were analysed by PCR-based replicon typing and conjugation assays.Results: All isolates harboured blaOXA-48 and blaNDM-1 genes together or alone. Almost all strains also carried ESBL genes. Eighty-seven isolates of K. pneumoniae were categorized into seven pulsotypes. The predominant strain clusters/pulsotypes associated with the outbreak corresponded to ST11 (48/96) and ST893 (31/96). Plasmids carrying blaOXA-48 and blaNDM-1 were successfully transferred to Escherichia coli K12 as the recipient strain. blaOXA-48 was located on IncL/M plasmids of ∼39 kb, while blaNDM-1 was carried by either an IncFII plasmid of ∼50 kb or an untypeable plasmid of ∼4 or 10 kb.Conclusions: We describe two separate outbreaks of blaOXA-48- and blaNDM-1-carrying K. pneumoniae strains associated with dissemination of the ST11 and ST893 clones, with the ICU acting as the epicentre. The spread of plasmids carrying carbapenemase genes resulting in fulminant antimicrobial resistance is a severe concern. [ABSTRACT FROM AUTHOR]

Background: Streptococcus gallolyticus ssp. gallolyticus (Sgg) is a commensal bacterium and an opportunistic pathogen. In humans it has been clinically associated with the incidence of colorectal cancer (CRC) and epidemiologically recognized as an emerging cause of infective endocarditis (IE). The standard therapy of Sgg includes the administration of a penicillin in combination with an aminoglycoside. Even though penicillin-resistant isolates have still not been reported, epidemiological studies have shown that this microbe is a reservoir of multiple acquired genes, conferring resistance to tetracyclines, aminoglycosides, macrolides and glycopeptides. However, the underlying antibiotic resistance mobilome of Sgg remains poorly understood.Objectives: To investigate the mobile genetic basis of antibiotic resistance in multiresistant clinical Sgg.Methods: Isolate NTS31106099 was recovered from a patient with IE and CRC at Nantes University Hospital, France and studied by Illumina WGS and comparative genomics. Molecular epidemiology of the identified mobile element(s) was performed using antibiotic susceptibility testing (AST), PCR, PFGE and WGS. Mobility was investigated by PCR and filter mating.Results: Two novel conjugative transposons, Tn6263 and Tn6331, confer aminoglycoside/macrolide co-resistance in clinical Sgg. They display classical family Tn916/Tn1545 modular architecture and harbour an aph(3')-III→sat4→ant(6)-Ia→erm(B) multiresistance gene cluster, related to pRE25 of Enterococcus faecium. These and/or closely related elements are highly prevalent among genetically heterogeneous clinical isolates of Sgg.Conclusions: Previously unknown Tn916-like mobile genetic elements conferring aminoglycoside/macrolide co-resistance make Sgg, collectively with other gut Firmicutes such as enterococci and eubacteria, a potential laterally active reservoir of these antibiotic resistance determinants among the mammalian gastrointestinal microbiota. [ABSTRACT FROM AUTHOR]