A Case of Phage Therapy against Pandrug-Resistant Achromobacter xylosoxidans in a 12-Year-Old Lung-Transplanted Cystic Fibrosis Patient

Abstract

Bacteriophages are a promising therapeutic strategy among cystic fibrosis and lung-transplanted patients, considering the high frequency of colonization/infection caused by pandrug-resistant bacteria. However, little clinical data are available regarding the use of phages for infections with Achromobacter xylosoxidans. A 12-year-old lung-transplanted cystic fibrosis patient received two rounds of phage therapy because of persistent lung infection with pandrug-resistant A. xylosoxidans. Clinical tolerance was perfect, but initial bronchoalveolar lavage (BAL) still grew A. xylosoxidans. The patient’s respiratory condition slowly improved and oxygen therapy was stopped. Low-grade airway colonization by A. xylosoxidans persisted for months before samples turned negative. No re-colonisation occurred more than two years after phage therapy was performed and imipenem treatment was stopped. Whole genome sequencing indicated that the eight A. xylosoxidans isolates, collected during phage therapy, belonged to four delineated strains, whereby one had a stop mutation in a gene for a phage receptor. The dynamics of lung colonisation were documented by means of strain-specific qPCRs on different BALs. We report the first case of phage therapy for A. xylosoxidans lung infection in a lung-transplanted patient. The dynamics of airway colonization was more complex than deduced from bacterial culture, involving phage susceptible as well as phage resistant strains.

Metaviromes reveal the dynamics of Pseudomonas host-specific phages cultured and uncultured by plaque assay

“…We al-so showed that three out of five phages isolated individually from the same sample virome with plaque assay are ineffective of lysis in liquid media or outcompeted by phages from the same virome. This has to be considered when deciding if the single isolated phages are good potential candidates for treatment in phage therapy or biocontrol [17,29,[68][69][70]. Furthermore, our analysis highlighted how much longread sequencing data improves the assembly of viral metagenomes as we saw an increase of 5.64% in the proportion of complete phage genomes from long-read assembly compared to short-read-only assemblies (p-value < 0.0001, Figure 2).…”

Metaviromes Reveal the Dynamics of Pseudomonas Host-Specific Phages Cultured and Uncultured by Plaque Assay

“…We also showed that three out of five phages isolated individually from the same sample virome using the plaque assay were ineffective in terms of lysis in liquid media or outcompeted by phages from the same virome. This has to be considered when deciding if single isolated phages are good potential candidates for treatment in phage therapy or biocontrol [ 17 , 29 , 70 , 71 , 72 ]. Furthermore, our analysis highlighted how much long-read sequencing data improve the assembly of viral metagenomes, as we saw an increase of 5.64% in the proportion of complete phage genomes from long-read assembly compared to short-read-only assemblies ( p -value < 0.0001, Figure 2 ).…”

Advances in Phage Therapy: Targeting the Burkholderia cepacia Complex

“…This principle is well established in modern phage therapy, since it is identical to the one that has been used to guide the successful development of chemical antimicrobial and antiviral cocktails since at least the late 1980s [ 232 , 233 ]. Consequently, the field is rife with phage therapy trials employing polyphage cocktails, including several successful human trials, with authors consistently reporting the predictable superiority of these cocktails over monophage therapy [ 135 , 172 , 182 , 187 , 193 , 195 , 196 , 213 , 234 , 235 , 236 , 237 , 238 ]. Despite the criticisms levelled against temperate phages by a number of authors, polyphage cocktails that combine temperate phages with more virulent types also appear to be highly effective [ 165 , 172 , 187 ].…”