Peptide dendrimers as "lead compounds" for the treatment of chronic lung infections by Pseudomonas aeruginosa in cystic fibrosis patients: in vitro and in vivo studies.

AIM: In the present work, the potential of the D-enantiomeric dendrimers dG3KL and dTNS18 was evaluated in relation to tobramycin (Tob), for the development of novel antibacterials to treat Pseudomonas aeruginosa chronic lung infections in patients with cystic fibrosis. RESULTS: The activity of dendrimers against planktonic P. aeruginosa cells was less than Tob against three of the four strains tested (median minimum inhibitory concentration [MIC] 8 vs 1 µg/mL, respectively), but 32-fold higher against the PaPh32 strain isolated at posttransplantation stage. Results from comparative minimum bactericidal concentration/MIC evaluation and time-kill assay suggested a bactericidal mechanism for all test agents. Subinhibitory concentrations of both dendrimers and Tob significantly affected biofilm formation by all strains in a dose-dependent manner, although the PaPh26 strain, isolated during the chronic stage of infection, was particularly susceptible to dendrimers. The activity of dendrimers against preformed P. aeruginosa biofilm was generally comparable to Tob, considering both dispersion and viability of biofilm. Particularly, exposure to the test agent at 10 × MIC caused significant biofilm death (>90%, even to eradication), though with strain-specific differences. Single administration of dendrimers or Tob at 10 × MIC was not toxic in Galleria mellonella wax-moth larvae over 96 hours. However, contrarily to Tob, dendrimers were not protective against systemic infection caused by P. aeruginosa in G. mellonella. Kinetics of P. aeruginosa growth in hemolymph showed that bacterial load increased over time in the presence of dendrimers. CONCLUSION: Overall, our findings indicated that dG3KL and dTNS18 peptide dendrimers show in vitro activity comparable to Tob against both P. aeruginosa planktonic and biofilm cells at concentrations not toxic in vivo. Further studies are warranted to explore different dosages and to increase the bioavailability of the peptides to solve the lack of protective effect observed in G. mellonella larvae.

Electrochemically Synthesized Silver Nanoparticles Are Active Against Planktonic and Biofilm Cells of Pseudomonas aeruginosa and Other Cystic Fibrosis-Associated Bacterial Pathogens.

A novel, electrochemically synthesized, silver nanoparticles (AgNPs) formulation was evaluated in vitro against Pseudomonas aeruginosa, Burkholderia cepacia, Stenotrophomonas maltophilia, and Staphylococcus aureus strains from cystic fibrosis (CF) patients. AgNPs were particularly active against P. aeruginosa and B. cepacia planktonic cells (median MIC: 1.06 and 2.12 µg/ml, respectively) by a rapid, bactericidal and concentration-dependent effect. AgNPs showed to be particularly effective against P. aeruginosa and S. aureus biofilm causing a viability reduction ranging from 50% (1×MIC) to >99.9% (4×MIC). Electron microscopy showed that AgNPs deconstruct extracellular matrix of P. aeruginosa biofilm, and accumulate at the cell surface causing cell death secondary to membrane damage. Compared to Tobramycin, AgNPs showed comparable, or even better, activity against planktonic and biofilm P. aeruginosa cells. AgNPs at concentrations effective against B. cepacia and P. aeruginosa were not toxic to G. mellonella larvae. Our silver-based formulation might be an alternative to antibiotics in CF patients. Further in vitro and in vivo studies are warranted to confirm this therapeutic potential.

Infection of recurrent calcaneal ulcer caused by a biofilm-producer Myroides odoratimimus strain.

We report a case of recurrent post-traumatic ulcer infection due to Myroides odoratimimus in an immunocompromised male. We have also reviewed the medical literature on isolated M. odoratimimus infections. The strain, isolated from ulcer discharge, was multidrug-resistant and treatment with meropenem, based on susceptibility testing, led to resolution of infection. The strain was also able to form a relevant amount of biofilm over time, thus suggesting a possible role of sessile communities in the chronicization of infection. To our knowledge, this is the first description of recurrent ulcer infection caused by a biofilm-producer M. odoratimimus strain. This case reminds us of the need to consider uncommon pathogens as etiology of skin and soft tissue infections, especially in immunocompromised patients. Further, since the treatment of infections due to M. odoratimimus is often difficult both due to multidrug resistance and scarce clinical experience, antibiotic therapy should be adapted to in vitro susceptibility testing.