Reconciling Antimicrobial Susceptibility Testing and Clinical Response in Antimicrobial Treatment of Chronic Cystic Fibrosis Lung Infections

Abstract

Median cystic fibrosis (CF) survival has increased dramatically over time due to several factors, including greater availability and use of antimicrobial therapies. During the progression of CF lung disease, however, the emergence of multidrug antimicrobial resistance can limit treatment effectiveness, threatening patient longevity. Current planktonic-based antimicrobial susceptibility testing lacks the ability to predict clinical response to antimicrobial treatment of chronic CF lung infections. There are numerous reasons for these limitations including bacterial phenotypic and genotypic diversity, polymicrobial interactions, and impaired antibiotic efficacy within the CF lung environment. The parallels to other chronic diseases such as non-CF bronchiectasis are discussed as well as research priorities for moving forward.

“It Takes a Village”: Mechanisms Underlying Antimicrobial Recalcitrance of Polymicrobial Biofilms

“…Unfortunately, that is exactly how we currently measure the antimicrobial susceptibility of disease-causing organisms in the clinical setting. Indeed, a recent publication called into question the utility of using MIC testing to guide the treatment of the chronic, polymicrobial communities that are characteristic of CF airway infections (182).…”

Ecological Succession of Polymicrobial Communities in the Cystic Fibrosis Airways

“…Despite this understanding, the traditional pathogens are typically assumed to be the primary drivers of CF lung disease. The reliance on this assumption may help explain why antimicrobial therapies fail all too frequently (17,18). Characterizing CF lung infections as ecologically homogeneous and driven by a few dominant species minimizes the potential importance of complex and dynamic ecological interactions.…”

In Vitro Activities of β-Lactam–β-Lactamase Inhibitor Antimicrobial Agents against Cystic Fibrosis Respiratory Pathogens

“…Airway infection in CF typically involves complex polymicrobial bacterial communities that often include more than one opportunistic pathogen (13). As such, in vitro susceptibility testing of a single species isolated from the community performs poorly in predicting clinical outcomes of antimicrobial therapy (14). Despite this limitation, the relative activity of antimicrobial agents against species recovered in culture is an important consideration in guiding antibiotic choice.…”