Current and Emerging Therapies to Combat Cystic Fibrosis Lung Infections

被引:20
|
作者
Manos, Jim [1 ]
机构
[1] Univ Sydney, Fac Med & Hlth, Sch Med Sci, Infect Immun & Inflammat, Sydney, NSW 2006, Australia
关键词
cystic fibrosis; lung infection; CF bacteria; antibiotic; combined therapy; novel therapy; CFTR modulator; PSEUDOMONAS-AERUGINOSA INFECTION; GRAM-NEGATIVE BACTERIA; BURKHOLDERIA-CEPACIA COMPLEX; QUORUM-SENSING SYSTEMS; ORAL N-ACETYLCYSTEINE; HAEMOPHILUS-INFLUENZAE; DORNASE ALPHA; HOST-DEFENSE; NONTUBERCULOUS MYCOBACTERIA; ANTIMICROBIAL RESISTANCE;
D O I
10.3390/microorganisms9091874
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The ultimate aim of any antimicrobial treatment is a better infection outcome for the patient. Here, we review the current state of treatment for bacterial infections in cystic fibrosis (CF) lung while also investigating potential new treatments being developed to see how they may change the dynamics of antimicrobial therapy. Treatment with antibiotics coupled with regular physical therapy has been shown to reduce exacerbations and may eradicate some strains. Therapies such as hypertonic saline and inhaled Pulmozyme(TM) (DNase-I) improve mucus clearance, while modifier drugs, singly and more successfully in combination, re-open certain mutant forms of the cystic fibrosis transmembrane conductance regulator (CFTR) to enable ion passage. No current method, however, completely eradicates infection, mainly due to bacterial survival within biofilm aggregates. Lung transplants increase lifespan, but reinfection is a continuing problem. CFTR modifiers normalise ion transport for the affected mutations, but there is conflicting evidence on bacterial clearance. Emerging treatments combine antibiotics with novel compounds including quorum-sensing inhibitors, antioxidants, and enzymes, or with bacteriophages, aiming to disrupt the biofilm matrix and improve antibiotic access. Other treatments involve bacteriophages that target, infect and kill bacteria. These novel therapeutic approaches are showing good promise in vitro, and a few have made the leap to in vivo testing.
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页数:33
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