In vitro evaluation of tobramycin and aztreonam versus Pseudomonas aeruginosa biofilms on cystic fibrosis-derived human airway epithelial cells

Yu, Qianru; Griffin, Edward F; Moreau‐Marquis, Sophie; Schwartzman, Joseph D.; Stanton, Bruce A.; O’Toole, George A.

doi:10.1093/jac/dks296

Cited by 64 publications

(61 citation statements)

References 41 publications

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“…The ability of b-lactam antibiotics to function in the CF lung could be limited by the slow, anaerobic biofilm growth of organisms (71). In vitro studies of biofilm growth of P. aeruginosa on CF airway cells have demonstrated little additional benefit of aztreonam in combination with tobramycin, likely due to bacterial exopolysaccharide production causing tolerance to aztreonam (72). In addition, in an ongoing clinical trial of biofilm susceptibility testing of more than 1,000 clinical P. aeruginosa CF isolates, the percentage of b-lactam-susceptible isolates was reduced when grown as a biofilm compared with planktonically.…”

Section: Ats Seminarsmentioning

confidence: 99%

Antibiotic Management of Lung Infections in Cystic Fibrosis. I. The Microbiome, Methicillin-Resistant Staphylococcus aureus, Gram-Negative Bacteria, and Multiple Infections

et al. 2014

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Despite significant advances in treatment strategies targeting the underlying defect in cystic fibrosis (CF), airway infection remains an important cause of lung disease. In this two-part series, we review recent evidence related to the complexity of CF airway infection, explore data suggesting the relevance of individual microbial species, and discuss current and future treatment options. In Part I, the evidence with respect to the spectrum of bacteria present in the CF airway, known as the lung microbiome is discussed. Subsequently, the current approach to treat methicillin-resistant Staphylococcus aureus, gram-negative bacteria, as well as multiple coinfections is reviewed. Newer molecular techniques have demonstrated that the airway microbiome consists of a large number of microbes, and the balance between microbes, rather than the mere presence of a single species, may be relevant for disease pathophysiology. A better understanding of this complex environment could help define optimal treatment regimens that target pathogens without affecting others. Although relevance of these organisms is unclear, the pathologic consequences of methicillin-resistant S. aureus infection in patients with CF have been recently determined. New strategies for eradication and treatment of both acute and chronic infections are discussed. Pseudomonas aeruginosa plays a prominent role in CF lung disease, but many other nonfermenting gram-negative bacteria are also found in the CF airway. Many new inhaled antibiotics specifically targeting P. aeruginosa have become available with the hope that they will improve the quality of life for patients. Part I concludes with a discussion of how best to treat patients with multiple coinfections.

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Section: Ats Seminarsmentioning

confidence: 99%

Antibiotic Management of Lung Infections in Cystic Fibrosis. I. The Microbiome, Methicillin-Resistant Staphylococcus aureus, Gram-Negative Bacteria, and Multiple Infections

et al. 2014

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“…In the mucus or sputum of cystic fibrosis patients biofilms are referred to as microbial aggregates and are dispersed within the mucus itself. 38 These ''microbial aggregates'' are dispersed rather than confluent entities. These biofilm aggregates often appear in wound slough and may also be part of the dislodged or debrided biofilm that still have the general characteristics of the mother biofilm, from which they detached.…”

Section: Identification Of a Biofilmmentioning

confidence: 99%

Biofilms and Wounds: An Identification Algorithm and Potential Treatment Options

Percival

Vuotto

Donelli

et al. 2015

Advances in Wound Care

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“…Peak concentration of tobramycin in the BAL and sputum samples of CF patients was reported as 1mg/ml/ (243,275,276). No cytotoxic effect was observed in human bronchial epithelial cells with this concentration of tobramycin.…”

Section: Effects Of Tobramycin On Macrophage Polarization and Functionsmentioning

confidence: 83%

“…Similar concentration (1mg/ml) of tobramycin had been shown to prevent biofilm formation of P. aeruginosa as well as disrupt already formed biofilms (243,275,310,311 …”

Section: Introductionmentioning

confidence: 91%

“…Six different independent studies showed significant improvement of lung functions in patients with moderate to severe CF and decreased chronic P. aeruginosa count and weight gain following tobramycin treatment compared to placebo or standard treatment (174,(238)(239)(240)(241)(242). Tobramycin delayed biofilm formation of P. aeruginosa as well as disruption of already formed biofilms thereby limits the growth of P. aeruginosa (243). P. aeruginosa count dropped in the infected lungs following intratracheal instillation of tobramycin (300g/kg body weight) suggesting decreased pulmonary bacterial load in the infected animals (239).…”

Section: Current Therapeutic Optionsmentioning

confidence: 99%

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Macrophage Polarization and Function in Cystic Fibrosis

Tarique¹

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If "Diversity is the rule of nature", macrophages, one of the innate immune cells of our body, have proven to be a true apostle. At the early stage of infection, they protect the host by exhibiting the pro-inflammatory phenotype (M1). Upon clearance of microbial threats, macrophages engage themselves in the repair process of the damaged tissue by showing anti-inflammatory or wound healing (M2) attributes. While incomplete microbial clearance leads to recurrent infections, defects in macrophage-mediated tissue repair mechanism result in immunopathology. The classical (M1) and alternatively (M2) polarized macrophages are the two extreme ends of a spectrum of in vivo macrophages phenotypes that dictate the nature, duration and severity of inflammation. Murine models of chronic inflammatory and autoimmune diseases showed the necessity of an adequate balance between macrophage subsets to maintain homeostasis, while imbalance is likely to lead exaggerated inflammation. In humans, an association between defective macrophage function and disease severity has been reported in many diseases including asthma, cystic fibrosis (CF), COPD, and atherosclerosis. Unfortunately, human M1 and M2 macrophages have not been well characterized. Firstly, the lack of homologs for certain murine genes in humans makes murine markers of limited use in humans. Secondly, there was no consensus method for in vitro differentiation of human M1 and M2 macrophages. Therefore, the first part of this thesis aimed to develop a novel method to differentiate and characterize human M1 and M2 macrophages. Initial studies with THP-1 cell line derived macrophage-like cells demonstrated that they didn't fully represent human monocyte-derived macrophages (MDMs). MDMs were therefore chosen as starting materials for the rest of the study. MDMs were considered as uncommitted "M0" macrophages. A number of inducers were employed to polarize M0 macrophages into either M1s or M2s. LPS treated M1 macrophages showed CD64 + CD80 + phenotype, whereas, IFN- induced M1s exhibited CD64 ++ CD80 -phenotype. These M1s secreted pro-inflammatory cytokines including TNF-, IL-1, IL-8 and were highly phagocytic. On the contrary, IL-4/IL-13 induced M2 macrophages were identified as CD11b + CD209 + cell population and were endocytic. Once polarized, macrophages then were left in cytokine-deficient medium to assess the persistence of polarized phenotype over time. In cytokine-free condition, previously polarized macrophages reverted to M0 state by 12 days.Treatment with IL-13 on previously polarized M1 macrophages resulted in a switch to CD209 + M2sand vice versa indicating the plasticity nature of human macrophages.Excessive neutrophilic pulmonary inflammation is the hallmark of cystic fibrosis (CF).However, factors that trigger such dysregulated neutrophilic inflammation and why this is not

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In vitro evaluation of tobramycin and aztreonam versus Pseudomonas aeruginosa biofilms on cystic fibrosis-derived human airway epithelial cells

Cited by 64 publications

References 41 publications

Antibiotic Management of Lung Infections in Cystic Fibrosis. I. The Microbiome, Methicillin-Resistant Staphylococcus aureus, Gram-Negative Bacteria, and Multiple Infections

Antibiotic Management of Lung Infections in Cystic Fibrosis. I. The Microbiome, Methicillin-Resistant Staphylococcus aureus, Gram-Negative Bacteria, and Multiple Infections

Biofilms and Wounds: An Identification Algorithm and Potential Treatment Options

Macrophage Polarization and Function in Cystic Fibrosis

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