The pressing need to treat multi-drug resistant bacteria in the chronically infected lungs of cystic fibrosis (CF) patients has given rise to novel nebulized antimicrobials. We have synthesized a silver–carbene complex (SCC10) active against a variety of bacterial strains associated with CF and chronic lung infections. Our studies have demonstrated that SCC10-loaded into l-tyrosine polyphosphate nanoparticles (LTP NPs) exhibits excellent antimicrobial activity in vitro and in vivo against the CF relevant bacteria Pseudomonas aeruginosa. Encapsulation of SCC10 in LTP NPs provides sustained release of the antimicrobial over the course of several days translating into efficacious results in vivo with only two administered doses over a 72 h period.

The increasing incidence of multidrug-resistant (MDR) pulmonary infections in the cystic fibrosis (CF) population has prompted the investigation of innovative silver based therapeutics. The functionalization of the naturally occurring xanthine theobromine at the N1 nitrogen atom with an ethanol substituent followed by the methylation of the N9 nitrogen atom gives the N-heterocyclic carbene precursor 1-(2-hydroxyethyl)-3,7,9-trimethylxanthinium iodide. The reaction of this xanthinium salt with silver acetate produces the highly hydrophilic silver carbene complex SCC8. The in vitro antimicrobial efficacy of this newly synthesized complex was evaluated with excellent results on a variety of virulent and MDR pathogens isolated from CF patients. A comparative in vivo study between the known caffeine derived silver carbene SCC1 and SCC8 demonstrated the ability of both complexes to improve the survival rates of mice in a pneumonia model utilizing the clinically isolated infectious strain of Pseudomonas aeruginosa PA M57-15.

Background Outcome of infants with tracheostomy have not been well described in the literature. Our objective was to describe the respiratory, growth, and survival outcomes of infants with tracheostomy. Methods A retrospective study was conducted on 204 infants born between 2005 and 2015 with tracheostomy at <1 year of age and follow-up in the Infant Tracheostomy and Home Ventilator Clinic up to 4 years of age. Results The mean age at tracheostomy was 4.5 months with median age of 3 months. Median age of decannulation was 32 months. The time from tracheostomy placement to complete discontinuation of mechanical ventilation was 15.4 months and from tracheostomy to decannulation was 33.8 months. Mortality rate was 21% and median age of death was 18 months. Preterm infants with acquired airway and lung disease (BPD) and born at <28 weeks’ gestation had a significantly higher survival rate compared to term infants. The z -scores for weight and weight for length improved from the time of discharge (mean chronological age 6.5 months) to first year and remained consistent through 3 years. Conclusions Premature infants had a higher rate of discontinuation of mechanical ventilation and decannulation compared to term infants. These infants showed consistent growth and comparable survival rate. Impact Infants with tracheostomy and ventilator dependence followed in a multidisciplinary clinic model may have improved survival, growth, and earlier time to decannulation. Preterm infants with acquired airway and lung disease (BPD) with tracheostomy had a higher survival rate compared to term infants with various tracheostomy indications. The age at tracheostomy in infants was 4.5 months and of decannulation was 37 months. Time from tracheostomy to complete discontinuation of mechanical ventilation was 15.4 months. Addition of this data to the sparse literature will be crucial in counseling the families and education of medical staff.

Amphiphilic polymer nanoparticles loaded with silver cations or/and N-heterocyclic carbene-silver complexes were assessed as antimicrobial agents against Gram-negative pathogens Escherichia coli and Pseudomonas aeruginosa.Silver has long been prized as an antimicrobial; ancient Egyptians used silver in food storage. In the present day, silver compounds are widely used as antimicrobial agents, especially in the treatment of wounds and burns. 1,2 Silver cation (Ag + ) is highly toxic, or described as "oligodynamic," against a broad spectrum of microorganisms, probably because of its inhibition of certain oxidative enzymes, protein denaturation, or interference with DNA replication. 3 Unlike traditional antibiotics, Ag + is of low toxicity to human tissues and has elicited only rare instances of bacterial silver resistance. 4-6 A variety of silver-based antimicrobials, therefore, has been synthesized and evaluated. Fox introduced silver sulfadiazine (SSD) in the 1960s; 7 SSD remains routinely used as a topical treatment of burns. Although it has been recognized as an antimicrobial since at least the 1800s, Moyer repopularized AgNO 3 for treatment of burns, which prompted development of SSD. 2 Unfortunately, AgNO 3 is not practical in vivo, because Ag + complexes with salts and other biological agents in the bloodstream. 7 Over the past decade, an array of silver N-heterocyclic carbene (NHC) complexes, which exhibit improved stability to light and aqueous solution, have been synthesized and investigated by Youngs and Cannon as potential antimicrobial agents and have shown very promising results with both in vitro and in vivo studies in a variety of bacteria including BSL3 organisms. [8][9][10][11] Small molecule antibiotics also have a major problem, however, that of rapid clearance from the human body and, in the case of silver, reaction with sulfur-containing proteins and chloride in the bloodstream. 12 [17][18][19][20] as an antimicrobial device, designed to encapsulate and protect Ag + , SCCs, or the two agents coincidentally, and evaluate the relative efficacy of each system. The SCKs were constructed by the supramolecular assembly of amphiphilic block copolymers, poly(acrylic acid)-bpolystyrene (PAA-b-PS), into micelles, followed by covalent crosslinking throughout the shell layer to afford discrete nanostructures having a hydrophobic core domain and a hydrophilic shell region. Four procedures were then followed for loading of the SCKs with silver: (1) Ag + was incorporated from AgNO 3 into the hydrophilic PAA shell region (AgNO 3 -SCK); (2) 1-hexyl-3-methyl-4,5-dichloro-imidazole-2-ylidene silver(I) acetate (SCC10, which undergoes decomposition in the presence of saline solution to release active Ag + ) 21 was loaded into the hydrophobic PS core domain and/or the core-shell interface (SCC10-SCK); 22,23 (3) and (4) both methods were applied in opposite order of addition (AgNO 3 -SCC10-SCK or SCC10-AgNO 3 -SCK) (Fig. 1). In all cases, free silver was eliminated using a centrifugal filter device (100 kDa...