English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background  Cystic fibrosis (CF) patients are often colonized with  Pseudomonas aeruginosa  (PSA). During treatment, PSA can develop subpopulations exhibiting variable  in vitro  antimicrobial susceptibility patterns. Heteroresistance may underlie the reported discordant  in vitro  results and clinical responses to various antimicrobials. Here, we sought to examine the presence and nature of PSA heteroresistance to ceftolozane-tazobactam (C-T) in isolates originating from CF pulmonary exacerbations.    Methods  Respiratory cultures from 26 adult CF patients were collected. From each sample, 5-10 PSA colonies were selected. Susceptibility testing was conducted via E-test for C-T, ceftazidime-avibactam (CZA), and imipenem-relebactam (I-R). Polyclonal-heteroresistance (PHR) was defined as the presence of different susceptibility profiles among the colonies that originated from a single patient specimen. Population analysis profile (PAPs) were performed to assess the presence of monoclonal-heteroresistance (MHR), defined as ≥ 4 fold change in the C-T MIC from a single colony over 24-48 hours.    Results  246 PSA isolates from 26 adult CF patients were included. The C-T MIC 50  and MIC 90  were 1/4 and ≥ 256/4 µg/mL, respectively (Figure 1). Sixteen of the 26 patients (62%) demonstrated ≥ 2 fold change in C-T MIC between isolates from the same culture. Of these 16 isolates, the fold change in C-T MIC was >2 fold for 7 isolates (27%) and resulted in a susceptibility interpretation change in 6 of the isolates (23%). Of the 32 isolates that underwent PAP testing, 7 grew on MH plates at 2-fold the C-T MIC concentration. One isolate, PSA 1311, demonstrated growth on PAPs up to 4 fold the MIC (16/4 µg/mL) (Figure 2).  Figure 1. Ceftolozane-tazobactam, ceftazidime-avibactam, and imipenem-relebactam MIC distributions against PSA isolates from 26 adult CF patientsFigure 2. Monoclonal heteroresistance to C-T (PSA 1311 [C-T MIC 1/4 µg/mL] PAPs at 2, 4, 6, and 8-fold the C-T MIC).Conclusion  Susceptibilities to C-T and CZA were similar across our CF PSA isolates. Comparatively, I-R retained better  in vitro  potency. C-T PHR exists among PSA isolates in the majority of our CF patients. Approximately 25% of these PHR isolates resulted in susceptibility interpretation changes supporting concerns surrounding the utility of traditional susceptibility testing methodology for CF isolates. These data suggest MHR also exists, albeit rare in this small subset. Additional data are needed to better understand these results in clinical context.Disclosures    David E. Greenberg, MD ,  Shionogi  (Grant/Research Support) Solenic Medical  (Shareholder)

1222. Ceftolozane-Tazobactam Heteroresistance in Cystic Fibrosis Related Pseudomonas aeruginosa Infections