DOI: 10.5061/dryad.pc866t1t0
title: Personalized inhaled bacteriophage therapy for treatment of multidrug-resistant Pseudomonas aeruginosa in cystic fibrosis

description: Bacteriophage (phage) therapy, which uses lytic viruses as antimicrobials,
 is a potential strategy to address the antimicrobial resistance (AMR)
 crisis. Cystic fibrosis (CF), a disease complicated by recurrent
 Pseudomonas aeruginosa pulmonary infections, is an example of AMR’s
 clinical impact. Using a novel personalized phage therapy strategy that
 selects phages for a predicted evolutionary ‘trade-off’, nine CF adults (8
 female, 1 male) median age 32 (range 22-46) years were treated with phages
 on a compassionate basis because their clinical course was complicated by
 multi-drug resistant or pan-drug-resistant Pseudomonas that was refractory
 to prior courses of standard antibiotics. Individuals received nebulized
 cocktail or single phage therapy without adverse events. 5-18 days after
 phage therapy, sputum Pseudomonas decreased by a 104 CFU/mL median, or 102
 CFU/mL mean difference (p = 0.006, Two-way ANOVA with Dunnett’s multiple
 comparisons test) without altering sputum microbiome, and analysis of
 sputum Pseudomonas showed evidence for ‘trade-offs’ that decreased
 antibiotic resistance or bacterial virulence. In addition, an improvement
 of 6 (median) and 8 (mean) percent predicted FEV1 (ppFEV1) was observed
 21-35 days after phage therapy (p = 0.004, Wilcoxon signed rank t test)
 may reflect the combined effects of decreased bacterial sputum density and
 phage-driven trade-offs. These results show that a personalized, nebulized
 phage therapy ‘trade off’ strategy may affect clinical and microbiologic
 endpoints, which must be evaluated in larger clinical trials.
description: # Personalized Inhaled Bacteriophage Therapy for Treatment of
 Multidrug-Resistant Pseudomonas aeruginosa in Cystic Fibrosis
 [https://doi.org/10.5061/dryad.pc866t1t0](https://doi.org/10.5061/dryad.pc866t1t0) ## Description of the data and file structure ### Files and variables Psa = *Pseudomonas aeruginosa* Blanks = data not available # File: Attachment.txt **Description:** Percent attached cells for Psa isolates from patient 2 pre and post therapy ##### Variables * Patient: subject numbers * Pre: percent attached cells pre therapy * Post: percent attached cells post therapy #### File: CFU.txt **Description:** CFU/ml  from 9 patients as measured from 10-fold serial dilutions of sputum in PBS plated on Pseudomonas isolation agar measured pre and post (14d vs 30d) therapy ##### Variables * Patient: subject numbers * Pre: CFU/ml (colony forming units per mL)  from 9 patients pre therapy * Post(14d): CFU/ml (colony forming units per mL)  from 9 patients post therapy (14 days) * Post(30d)L : CFU/ml (colony forming units per mL)  from 9 patients post therapy (30 days) #### File: ClincialMIC.txt **Description:** MIC (minimum inhibitory concentration) data reported by clinical lab for Psa isolates pre and post therapy for 10 antibiotics (1 = susceptible, 2 = intermediate, 3 = resistant) ##### Variables * Patient: subject numbers * Timepoint: Pre therapy or post therapy MIC was measured * Aztreonam: MIC scoring for this antibiotic * Piperacillin/ Tazobactam: MIC scoring for this antibiotic * Cefepime: MIC scoring for this antibiotic * Ceftazidime: MIC scoring for this antibiotic * Imipenem: MIC scoring for this antibiotic * Meropenem: MIC scoring for this antibiotic * Ciprofloxacin: MIC scoring for this antibiotic * Levofloxacin: MIC scoring for this antibiotic * Amikacin: MIC scoring for this antibiotic * Gentamicin: MIC scoring for this antibiotic * Tobramycin: MIC scoring for this antibiotic #### File: Elastase.txt **Description:** Elastase production (U/mL) of cultures of Psa isolates from patients pre and post therapy measured with EnzCheck Elastase Assay Kit (E12056) ##### Variables * Patient: subject numbers * Pre: Elastase production (U/mL) of cultures of Psa isolates from patients pre therapy * Post: Elastase production (U/mL) of cultures of Psa isolates from patients pre therapy #### File: FEV1.txt **Description:** FEV1 data from 9 patients measured pre and post therapy ##### Variables * Patient: subject numbers * Pre: FEV1 (forced expiratory volume in 1 second) data taken pre therapy * Post: FEV1 (forced expiratory volume in 1 second) data taken post therapy #### File: IsolateMIC.txt **Description:** MIC (minimum inhibitory concentration, in ug/mL) data measured for Psa isolates pre and post therapy for 10 antibiotics ##### Variables * Patient: subject numbers * MP: MIC to meropenem * P/T: MIC to piperacillin/tazobactam * CI: MIC to cirpofloxacin * TM: MIC to tobramycin * CO: MIC to colistin * AT: MIC to aztreonam * PM: MIC to cefepime * TZ: MIC to ceftazadime * DOR: MIC to doripenem * LE: MIC to levofloxacin #### File: LPS.txt **Description:** LPS (ng/CFU) from cells of Psa isolates from patients pre and post therapy, extracted with an LPS Extraction Kit (Abcam ab239718), measured via a Carbohydrate Assay Kit (Abcam ab155891) ##### Variables * Patient: subject numbers * Pre: LPS (ng/CFU) from cells of Psa isolates from patients pre therapy * Post: LPS (ng/CFU) from cells of Psa isolates from patients post therapy #### File: Pyocyanin.txt **Description:** Pyocyanin measured in ug/mL from cultures of Psa isolates pre and post therapy ##### Variables * Patient: subject numbers * Pre: pyocyanin produced (ug/mL) from cultures of Psa isolates pre therapy * Post: pyocyanin produced (ug/mL) from cultures of Psa isolates post therapy #### File: PRJNA1182815\_sample\_list.txt **Description:** List of file/sample names of raw sequencing data uploaded to SRA under project ID PRJNA1182815 ##### Variables * accession: accession number * sample_name: sample name * other_identifier: other identifier * bioproject_accession: accession number * organism: bacterial organism * collection_date: date of collection * patient: subject numbers * description: description of data ## Access information Other publicly accessible locations of the data: * SRA PRJNA1182815