Successful Bacteriophage Therapy for Treatment of Multidrug-Resistant Pseudomonas aeruginosa Infection in a Cystic Fibrosis Patient

Bacteriophages are host-specific lytic viruses that are of increasing interest as adjunctive therapy for treatment of multi-drug resistant (MDR) pathogens.
Source: The Journal of Heart and Lung Transplantation - Category: Transplant Surgery Authors: Tags: 69 Source Type: research

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We examined whether the high charge on ZmD32 would allow this defensin to retain activity in media with elevated salt concentrations. ZmD32 inhibited C. albicans, C. auris, C. glabrata, C. krusei, C. parapsilosis, and C. tropicalis growth with IC50 values ranging from 0.7 to 3.0 in ½ PDB medium containing 100 mM NaCl. In contrast, NaD1 was only active against C. parapsilosis and C. tropicalis with IC50 values of 3.4 and 1.3 μM, respectively, in medium with added NaCl. ZmD32 also retained activity against E. coli when NaC1 concentrations were raised to 100 mM while NaD1 did not (Table 1). For C. albicans and C. kr...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
ConclusionEvaluation of hypersusceptible mutants identified the association betweenlptG and a hypersusceptible phenotype. Modifications in lipopolysaccharide profiles suggests LptG modification interferes with lipopolysaccharide transport and contributes to hypersusceptibility.
Source: MicrobiologyOpen - Category: Microbiology Authors: Tags: SPECIAL ISSUE: ANTIMICROBIAL RESISTANCE Source Type: research
Raquel Ferrer-Espada1,2, Xiaojing Liu1,2, Xueping Sharon Goh1,2 and Tianhong Dai1,2* 1Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States 2Vaccine &Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States Polymicrobial biofilms, in which mixed microbial species are present, play a significant role in persistent infections. Furthermore, polymicrobial biofilms promote antibiotic resistance by allowing interspecies transfer of antibiotic resistance genes. In the present study, we investigated the effec...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
We describe the use of a decontamination protocol that allowed for successful lung transplantation in a patient with cystic fibrosis with necrotizing pneumonia from highly antibiotic-resistant pathogens (Burkholderia and Psuedomonas species). This strategy may allow for successful lung transplantation in patients with cystic fibrosis with multidrug-resistant infections previously considered nontransplantable.
Source: The Annals of Thoracic Surgery - Category: Cardiovascular & Thoracic Surgery Source Type: research
This study aimed to determine the prevalence of hypermutable P. aeruginosa isolates from adult patients with CF from a healthcare institution in Australia, and to characterize the genetic diversity and antibiotic susceptibility of these isolates. A total of 59 P. aeruginosa clinical isolates from patients with CF were characterized. For all isolates, rifampicin mutation frequencies and susceptibility to a range of antibiotics were determined. Of the 59 isolates, 13 (22%) were hypermutable. Whole genome sequences were determined for all hypermutable isolates. Core genome polymorphisms were used to assess genetic relatedness...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
In this study, we investigated the role of CAR in the regulation of cystic fibrosis transmembrane conductance regulator (CFTR)-mediated chloride transport in T84 human colonic epithelial cells and mouse intestinal tissues. Treatments of T84 cell monolayers with specific CAR agonists (CITCO and phenytoin at concentrations of 1 μM and 5 μM, respectively) for 24 h decreased transepithelial Cl− secretion in response to cAMP-dependent agonist. This inhibition was abolished by coincubation of CITCO with a CAR antagonist, CINPA1. We confirmed that an inhibitory effect of CAR agonists was no...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research
The objective of the current study is to evaluate whether ivacaftor enhances the antimicrobial activity of ciprofloxacin against Pseudomonas aeruginosa. METHODS: The planktonic growth of the PAO-1 strain of P. aeruginosa was studied in the presence of ciprofloxacin and/or ivacaftor. Effects were measured according to optical density of cultured PAO-1 at 600 nm. For a static PAO-1 biofilm assay, the PAO-1 strain was inoculated and cultured for 72 h in the presence of the drugs. Formed PAO-1 biofilms were quantified by crystal violet staining and imaged with confocal laser scanning microscopy (CLSM) and scanning electro...
Source: American Journal of Rhinology and Allergy - Category: ENT & OMF Authors: Tags: Am J Rhinol Allergy Source Type: research
Pseudomonas aeruginosa is an opportunistic pathogen that causes nosocomial pneumonia and infects patients with cystic fibrosis. P. aeruginosa lung infections are difficult to treat due to bacterial resistance to antibiotics, and strains with multidrug resistance are becoming more prevalent. Here, we examined the use of a small host defense peptide, innate defense regulator 1002 (IDR-1002), in an acute P. aeruginosa lung infection in vivo. IDR-1002 significantly reduced the bacterial burden in bronchoalveolar lavage fluid (BALF), as well as MCP-1 in BALF and serum, KC in serum, and interleukin 6 (IL-6) in BALF. Transcriptom...
Source: Infection and Immunity - Category: Infectious Diseases Authors: Tags: Host Response and Inflammation Source Type: research
Abstract Pseudomonas aeruginosa is an opportunistic pathogen that is a leading cause of morbidity and mortality in cystic fibrosis patients and immunocompromised individuals. Eradication of P. aeruginosa has become increasingly difficult due to its remarkable capacity to resist antibiotics. Strains of Pseudomonas aeruginosa are known to utilize their high levels of intrinsic and acquired resistance mechanisms to counter most antibiotics. In addition, adaptive antibiotic resistance of P. aeruginosa is a recently characterized mechanism, which includes biofilm-mediated resistance and formation of multidrug-tolerant ...
Source: Biotechnology Advances - Category: Biotechnology Authors: Tags: Biotechnol Adv Source Type: research
Conclusions: A relevant in vitro synergism of colistin/NAC combinations was observed against a highly colistin resistant P. aeruginosa strain, and further studies to consolidate this preliminary in vitro data are strongly encouraged.
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Cystic fibrosis Source Type: research
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