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Activities of Dual Combinations of Antibiotics Against Multidrug-Resistant Nontuberculous Mycobacteria Recovered from Patients with Cystic Fibrosis.

ABSTRACT: Patients with cystic fibrosis (CF) are at risk for recurrent pulmonary infections due to increased viscosity of airway secretions, leading to persistent colonization with pathogenic bacteria, including nontuberculous mycobacteria (NTM). Extensive antibiotic use for treatment of infections has led to increasing antimicrobial resistance, which is a significant barrier to the treatment of NTMs. We examined the in vitro activity of several antibiotics against a selection of the most drug-resistant clinical isolates of Mycobacterium abscessus, Mycobacterium chelonae, and Mycobacterium avium complex recovered from CF patients at our institution, as well as paired combinations of antibiotics against a subset of M. abscessus strains, to determine whether they exhibit synergy in inhibiting bacterial growth. Most isolates displayed resistance to at least six of the nine antibiotics tested for which phenotypic interpretation is available, and elevated minimum inhibitory concentrations (MICs) were observed for many of the other drugs. The major exception was clofazimine, which had relatively low MICs for most isolates across all species. When synergy testing was performed by using paired combinations of drugs, clofazamine and clarithromycin exhibited 100% synergy for all combinations tested, as did amikacin, with the exception of one isolate. These results suggest that synergistic antibiotic combinations are capable of overcoming drug resistance in vitro, and laboratories might consider implementation of synergy testing in multidrug-resistant (MDR)-NTM organisms to guide treatment decisions in the setting of extensive antimicrobial resistance.

SUBMITTER: Schwartz M

PROVIDER: S-EPMC6200022 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Activities of Dual Combinations of Antibiotics Against Multidrug-Resistant Nontuberculous Mycobacteria Recovered from Patients with Cystic Fibrosis.

Schwartz Matthew M Fisher Stefanie S Story-Roller Elizabeth E Lamichhane Gyanu G Parrish Nicole N

Microbial drug resistance (Larchmont, N.Y.) 20180125 8

Patients with cystic fibrosis (CF) are at risk for recurrent pulmonary infections due to increased viscosity of airway secretions, leading to persistent colonization with pathogenic bacteria, including nontuberculous mycobacteria (NTM). Extensive antibiotic use for treatment of infections has led to increasing antimicrobial resistance, which is a significant barrier to the treatment of NTMs. We examined the in vitro activity of several antibiotics against a selection of the most drug-resistant c ...[more]

PMID: 29368988

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Project description:Rationale: Healthcare-associated transmission of nontuberculous mycobacteria (NTM) among people with cystic fibrosis (pwCF) has been investigated at CF centers worldwide, with conflicting conclusions. We investigated transmission at the Colorado Adult CF Program. Objectives: To systematically investigate healthcare-associated transmission and/or acquisition of NTM to determine similarity among respiratory and environmental isolates, and to compare home residence watershed mapping among pwCF having genetically similar NTM isolates. Methods: Whole-genome sequencing of NTM isolates from 80 pwCF was conducted to identify genetically similar isolate clusters (⩽30 SNP differences). Epidemiology, comparison of respiratory and environmental isolates, and home residence watershed mapping were analyzed. Measurements and Main Results: Whole-genome sequencing analysis revealed 11 clusters of NTM [6 Mycobacterium abscessus subspecies (ssp.) abscessus, 1 M. abscessus ssp. massiliense, 2 Mycobacterium avium, and 2 Mycobacterium intracellulare] among pwCF. Epidemiologic investigation demonstrated opportunities for healthcare-associated transmission in two M. abscessus and two M. avium clusters. Respiratory and healthcare environmental isolate comparisons revealed no genetic similarity. Individuals comprising one M. abscessus cluster, with no plausible healthcare-associated transmission, resided in the same watershed. Conclusions: This study suggests healthcare-associated transmission of M. abscessus is rare and includes a report of potential healthcare-associated transmission of M. avium among pwCF. One M. abscessus cluster possibly had common acquisition arising from residing in the same watershed. The presence of genetically similar isolates is insufficient to demonstrate healthcare-associated NTM transmission. Standardizing epidemiologic investigation, combined with environmental sampling and watershed analysis, will improve understanding of the frequency and nature of healthcare-associated NTM transmission among pwCF.

Project description:BackgroundNontuberculous mycobacteria are mycobacteria, other than those in the Mycobacterium tuberculosis complex, and are commonly found in the environment. Nontuberculous mycobacteria species (most commonly Mycobacterium avium complex and Mycobacterium abscessus) are isolated from the respiratory tract of approximately 5% to 40% of individuals with cystic fibrosis; they can cause lung disease in people with cystic fibrosis leading to more a rapid decline in lung function and even death in certain circumstances. Although there are guidelines for the antimicrobial treatment of nontuberculous mycobacteria lung disease, these recommendations are not specific for people with cystic fibrosis and it is not clear which antibiotic regimen may be the most effective in the treatment of these individuals. This is an update of a previous review.ObjectivesThe objective of our review was to compare antibiotic treatment to no antibiotic treatment, or to compare different combinations of antibiotic treatment, for nontuberculous mycobacteria lung infections in people with cystic fibrosis. The primary objective was to assess the effect of treatment on lung function and pulmonary exacerbations and to quantify adverse events. The secondary objectives were to assess treatment effects on the amount of bacteria in the sputum, quality of life, mortality, nutritional parameters, hospitalizations and use of oral antibiotics.Search methodsWe searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and hand searching of journals and conference abstract books. Date of last search: 02 September 2016.We also searched a register of ongoing trials and the reference lists of relevant articles and reviews. Date of last search: 03 November 2016.Selection criteriaAny randomized controlled trials comparing nontuberculous mycobacteria antibiotics to no antibiotic treatment, as well as one nontuberculous mycobacteria antibiotic regimen compared to another nontuberculous mycobacteria antibiotic regimen, in individuals with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Data were not collected because in the one trial identified by the search, data specific to individuals with cystic fibrosis could not be obtained from the pharmaceutical company.Main resultsOne completed trial was identified by the searches, but data specific to individuals with cystic fibrosis could not be obtained from the pharmaceutical company.Authors' conclusionsThis review did not find any evidence for the effectiveness of different antimicrobial treatment for nontuberculous mycobacteria lung disease in people with cystic fibrosis. Until such evidence becomes available, it is reasonable for clinicians to follow published clinical practice guidelines for the diagnosis and treatment of nodular or bronchiectatic pulmonary disease due to Mycobacterium avium complex or Mycobacterium abscessus in patients with cystic fibrosis.

Project description:BackgroundNontuberculous mycobacteria are mycobacteria, other than those in the Mycobacterium tuberculosis complex, and are commonly found in the environment. Nontuberculous mycobacteria species (most commonly Mycobacterium avium complex and Mycobacterium abscessus) are isolated from the respiratory tract of approximately 5% to 40% of individuals with cystic fibrosis; they can cause lung disease in people with cystic fibrosis leading to more a rapid decline in lung function and even death in certain circumstances. Although there are guidelines for the antimicrobial treatment of nontuberculous mycobacteria lung disease, these recommendations are not specific for people with cystic fibrosis and it is not clear which antibiotic regimen may be the most effective in the treatment of these individuals. This is an update of a previous review.ObjectivesThe objective of our review was to compare antibiotic treatment to no antibiotic treatment, or to compare different combinations of antibiotic treatment, for nontuberculous mycobacteria lung infections in people with cystic fibrosis. The primary objective was to assess the effect of treatment on lung function and pulmonary exacerbations and to quantify adverse events. The secondary objectives were to assess treatment effects on the amount of bacteria in the sputum, quality of life, mortality, nutritional parameters, hospitalizations and use of oral antibiotics.Search methodsWe searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and hand searching of journals and conference abstract books. Date of last search: 24 February 2020. We also searched a register of ongoing trials and the reference lists of relevant articles and reviews. Date of last search: 21 March 2019.Selection criteriaAny randomized controlled trials comparing nontuberculous mycobacteria antibiotics to no antibiotic treatment, as well as one nontuberculous mycobacteria antibiotic regimen compared to another nontuberculous mycobacteria antibiotic regimen, in individuals with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Data were not collected because in the one trial identified by the search, data specific to individuals with cystic fibrosis could not be obtained from the pharmaceutical company.Main resultsOne completed trial was identified by the searches, but data specific to individuals with cystic fibrosis could not be obtained from the pharmaceutical company.Authors' conclusionsThis review did not find any evidence for the effectiveness of different antimicrobial treatment for nontuberculous mycobacteria lung disease in people with cystic fibrosis. Until such evidence becomes available, it is reasonable for clinicians to follow published clinical practice guidelines for the diagnosis and treatment of nodular or bronchiectatic pulmonary disease due to Mycobacterium avium complex or Mycobacterium abscessus in patients with cystic fibrosis.

Dataset Information

Activities of Dual Combinations of Antibiotics Against Multidrug-Resistant Nontuberculous Mycobacteria Recovered from Patients with Cystic Fibrosis.

Publications

Activities of Dual Combinations of Antibiotics Against Multidrug-Resistant Nontuberculous Mycobacteria Recovered from Patients with Cystic Fibrosis.

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