期刊
EXPERT REVIEW OF ANTI-INFECTIVE THERAPY
卷 16, 期 2, 页码 89-110出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/14787210.2018.1425139
关键词
Gram-negative bacteria; glucose-non-fermenting; antimicrobial resistance; nosocomial infections; mechanisms of resistance; combination therapy; precision medicine
资金
- Cleveland Department of Veterans Affairs, the Veterans Affairs Merit Review Program [1I01BX001974]
- National Institute of Allergy and Infectious Diseases of the National Institutes of Health [R01AI063517, R01AI10056]
- Antibiotic Resistance Leadership Group under National Institutes of Health [UM1AI104681]
- Clinical and Translational Science Collaborative of Cleveland from the National Center for Advancing Translational Sciences (NCATS) component of the National Institutes of Health [UL1TR000439]
Introduction: Non-fermenting Gram-negative bacilli are at the center of the antimicrobial resistance epidemic. Acinetobacter baumannii and Pseudomonas aeruginosa are both designated with a threat level to human health of serious' by the Centers for Disease Control and Prevention. Two other major non-fermenting Gram-negative bacilli, Stenotrophomonas maltophilia and Burkholderia cepacia complex, while not as prevalent, have devastating effects on vulnerable populations, such as those with cystic fibrosis, as well as immunosuppressed or hospitalized patients.Areas covered: In this review, we summarize the clinical impact, presentations, and mechanisms of resistance of these four major groups of non-fermenting Gram-negative bacilli. We also describe available and promising novel therapeutic options and strategies, particularly combination antibiotic strategies, with a focus on multidrug resistant variants.Expert commentary: We finally advocate for a therapeutic approach that incorporates in vitro antibiotic susceptibility testing with molecular and genotypic characterization of mechanisms of resistance, as well as pharmacokinetics and pharmacodynamics (PK/PD) parameters. The goal is to begin to formulate a precision medicine approach to antimicrobial therapy: a clinical-decision making model that integrates bacterial phenotype, genotype and patient's PK/PD to arrive at rationally-optimized combination antibiotic chemotherapy regimens tailored to individual clinical scenarios.
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