Effect of Chronic Intermittent Administration of Inhaled Tobramycin on Respiratory Microbial Flora in Patients with Cystic Fibrosis

Abstract

Pseudomonas aeruginosa endobronchial infection causes significant morbidity and mortality among cystic fibrosis patients. Microbiology results from two multicenter, double-blind, placebo-controlled trials of inhaled tobramycin in cystic fibrosis were monitored for longitudinal changes in sputum microbial flora, antibiotic susceptibility, and selection of P. aeruginosa isolates with decreased tobramycin susceptibility. Clinical response was examined to determine whether current susceptibility standards are applicable to aerosolized administration. Treatment with inhaled tobramycin did not increase isolation of Burkholderia cepacia, Stenotrophomonas maltophilia, or Alcaligenes xylosoxidans; however, isolation of Candida albicans and Aspergillus species did increase. Although P. aeruginosa tobramycin susceptibility decreased in the tobramycin group compared with that in the placebo group, there was no evidence of selection for the most resistant isolates to become most prevalent. The definition of resistance for parenteral administration does not apply to inhaled tobramycin: too few patients had P. aeruginosa with a tobramycin MIC >/=16 microgram/mL to define a new break point on the basis of clinical response.

Cystic fibrosis, atopy, asthma and ABPA

“…81 Although previous works detected no association between ABPA and P. aeruginosa colonisation. 82 Nikolaizik et al reported a positive correlation between the two entities, suggesting that P. aeruginosa colonisation favours the process of A. fumigatus sensitisation.…”

Role of persister cells in chronic infections: clinical relevance and perspectives on anti-persister therapies

“…Resistanceconferring mutations do occur, probably selected for by intensive antibiotic treatments. However, isolates of P. aeruginosa strains do not always develop resistance (Burns et al, 1999;Gibson et al, 2003;Gilligan, 2006;Mulcahy et al, 2010). Lewis (2007) suggested that the recalcitrant nature of P. aeruginosa infections in CF lungs is largely the consequence of the presence of a drug-tolerant subpopulation of persister cells.…”

A phase 2 study of aztreonam lysine for inhalation to treat patients with cystic fibrosis and Pseudomonas aeruginosa infection

“…Expectorated sputum samples were cultured quantitatively and throat swabs were cultured semi-quantitatively on selective media, as previously reported. 20 Minimal inhibitory concentrations (MIC) of aztreonam were determined for all P. aeruginosa isolates using a semiautomated broth microdilution technique (Sensititre, Trek Diagnostic Systems, Cleveland, OH) according to Clinical Laboratory and Standards Institute (CLSI) standards. MIC testing was performed on each distinctive P. aeruginosa morphotype isolated from an individual sample.…”