Antibiotic Tolerance and Treatment Outcomes in Cystic Fibrosis Methicillin-Resistant Staphylococcus aureus Infections

Article Infectious Diseases

Quantification of within-patient Staphylococcus aureus phenotypic heterogeneity as a proxy for the presence of persisters across clinical presentations

Julian Baer et al.

Summary: This study found that patient-derived Staphylococcus aureus from difficult-to-treat infections exhibited phenotypic heterogeneity, and this heterogeneity was associated with treatment with the antibiotic rifampicin.

CLINICAL MICROBIOLOGY AND INFECTION (2022)

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Article Respiratory System

Longitudinal changes and regional variation of incident infection rates at cystic fibrosis centers, United States 2010-2016

Marianne S. Muhlebach et al.

Summary: Changes in incident infection rates (IIR) for Pseudomonas aeruginosa (PA) and methicillin resistant Staphylococcus aureus (MRSA) were assessed across CF care centers, and factors such as location, ethnic background, and socio-economic variables were found to influence the rates. The IIR decreased for MRSA and PA at pediatric centers, while only PA IIR decreased at adult centers. Private insurance and a higher proportion of LatinX patients were associated with lower MRSA IIR, while larger center size, higher proportion of LatinX, and lower mean center-wide lung function were associated with higher PA IIR.

JOURNAL OF CYSTIC FIBROSIS (2022)

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Article Immunology

Convergent Evolution of Antibiotic Tolerance in Patients with Persistent Methicillin-Resistant Staphylococcus aureus Bacteremia

Mitra M. Elgrail et al.

Summary: Severe infections caused by methicillin-resistant Staphylococcus aureus (MRSA) often have persistent bacteremia (PB) despite active antibiotic therapy. This study found that genetic mutations in metabolic pathways were associated with antibiotic tolerance and emerged commonly in MRSA-PB cases. Understanding these pathways could contribute to improved treatment strategies for MRSA infections.

INFECTION AND IMMUNITY (2022)

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Article Multidisciplinary Sciences

Molecular reprogramming and phenotype switching in Staphylococcus aureus lead to high antibiotic persistence and affect therapy success

Markus Huemer et al.

Summary: Staphylococcus aureus persisters, formed under host-mediated stress, display unique growth characteristics and molecular reprogramming, requiring specific metabolic pathways for maintenance. These non-metabolically active persisters regain virulence potential upon regrowth, exhibiting a reversible state crucial for recurrent infections. Targeted antipersister combination therapy significantly reduces lag-phase heterogeneity and persisters, providing insights into the difficulty of treating persistent S. aureus infections.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

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Article Microbiology

Biofilm Formation in Methicillin-Resistant Staphylococcus aureus Isolated in Cystic Fibrosis Patients Is Strain-Dependent and Differentially Influenced by Antibiotics

Agathe Boudet et al.

Summary: Cystic fibrosis (CF) is a genetic disease that makes patients particularly susceptible to pulmonary infections, with Staphylococcus aureus being the most frequently identified pathogen. Multidrug-resistant strains have been associated with more severe lung dysfunction. This study compared the ability of genotyped MRSA isolates from CF patients to form biofilms, revealing challenges in antimicrobial therapy and the potential for some MRSA strains to adapt to the CF lung environment over time.

FRONTIERS IN MICROBIOLOGY (2021)

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Review Pharmacology & Pharmacy

Improving the ability of antimicrobial susceptibility tests to predict clinical outcome accurately: Adding metabolic evasion to the equation

Jason Tasse et al.

Summary: Antimicrobial susceptibility tests (AST) based on the minimal inhibitory concentration (MIC) are widely used globally to guide antimicrobial therapy, but may be misleading in cases where pathogens exhibit 'metabolic evasion' (ME), enabling bacteria to survive antimicrobials despite slow or uneven growth. Various bacterial mechanisms such as biofilms, intracellular growth, persisters, or dormancy can contribute to ME, influencing the effectiveness of MIC-based treatment strategies. New approaches that consider ME may be needed to improve patient management and drug evaluation.

DRUG DISCOVERY TODAY (2021)

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Article Immunology

Macrophage-Produced Peroxynitrite Induces Antibiotic Tolerance and Supersedes Intrinsic Mechanisms of Persister Formation

Jenna E. Beam et al.

Summary: Staphylococcus aureus is a common human pathogen that often leads to chronic infections, with persister cells contributing to the failure of antibiotic treatment; host-derived peroxynitrite is identified as a major mediator of antibiotic tolerance in macrophages infected by S. aureus; these findings highlight the significant impact of host-bacterial interactions on antibiotic tolerance and suggest that modulating the host response could be a potential therapeutic strategy to enhance S. aureus sensitivity to antibiotics.

INFECTION AND IMMUNITY (2021)

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Article Microbiology