Low‐level resistance and clonal diversity of Pseudomonas aeruginosa among chronically colonized cystic fibrosis patients

Abstract

A prospective study was conducted in Brazil to evaluate antimicrobial resistance patterns and molecular epidemiology of Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients with chronic lung infection. All isolates were obtained between May 2009 and June 2010 from 75 patients seen in four reference centers in Brazil: HCPA (20 patients) and HEOM (15 patients), located in southern and northeastern Brazil, respectively; IFF (20 patients) and HUPE (20 patients), both in southwestern Brazil. Antimicrobial susceptibility testing, PCR for detection of carpapenemases, and pulsed-field gel electrophoresis (PFGE) were performed in 274 isolates. A total of 224 PFGE types were identified and no clones were found circulating among the centers or within the same center. Despite the chronic infection, most patients were colonized by intermittent clones. Only three patients (4%) maintained the same clone during the study. The resistance rates were lower than 30% for the majority of antimicrobials tested in all centers and only 17% of isolates were multiresistant. Isolates (n = 54) with reduced susceptibility to imipenem and/or meropenem presented negative results for blaSPM-1, blaIMP-1, blaVIM , and blaKPC genes. Our results indicate an unexpected low level of antimicrobial resistance and a high genotypic diversity among P. aeruginosa from Brazilian chronic CF patients.

Antimicrobial Susceptibility of Pseudomonas aeruginosa Isolated from Cystic Fibrosis Patients in Northern Europe

“…In this study, we examined antibiotic susceptibility within a collection of P. aeruginosa isolates from CF patients in three northern European countries collected during routine examination, which provides a broader view than the majority of previous surveys, which have focused on a single country (18)(19)(20) or a single center (21)(22)(23). A key observation is that resistance rates were high in this population, confirming previous studies with CF patients (2), and notably much higher than that which has been reported for isolates collected in northern Europe from intensive care units (24)(25)(26).…”

“…The first of these studies was performed in Australia and examined successively a collection of 662 carbapenem-resistant isolates assembled in 2007 to 2009 from diverse CF centers and of 517 isolates collected in a single CF center in 2011 (32). The second study was performed in Brazil and analyzed isolates from 75 patients collected from 2010 to 2011 (19). In contrast, carbapenemases have been detected in 63 out of 217 P. aeruginosa isolates collected from CF patients in China (22).…”

Dendrimer-based selective autophagy-induction rescues ΔF508-CFTR and inhibits Pseudomonas aeruginosa infection in cystic fibrosis

“…CF patients with ΔF508-CFTR mutation experience chronic Pa infections, an important cause of morbidity/mortality in these patients [ 13 ]. Based on the known autophagy inducing properties of cysteamine, we postulated that PAMAM-DEN CYS would not only function to restore ΔF508-CFTR to the cell membrane, but also decrease Pa infection and thus diminish bacterial virulence in CF airway epithelial cells by autophagy mediated bacterial clearance, in addition to its other anti-microbial effects.…”

“…The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel found on epithelial cell membranes [ 1 – 10 ], and its dysfunction is associated with cystic fibrosis (CF) that involves dysregulation of epithelial fluid transport in the lungs, pancreas, and other organs of the body [ 7 , 8 , 11 , 12 ]. Mutations in the Cftr gene (most common being the ΔF508) is characterized by build-up of thick mucus, frequent respiratory infections (such as Pseudomonas aeruginosa , Pa ) and inflammation leading to severe lung damage [ 7 – 9 , 13 – 17 ]. These pathological manifestations caused by dysfunctional CFTR potentially involve autophagy-impairment as an important cellular mechanism associated with pathogenesis of CF lung disease [ 8 , 18 , 19 ].…”

“…It has been reported that 50% of CF patients under the age of 18 are infected by Pa , with its prevalence significantly increased to 80% in patients over that age [ 13 ]. Furthermore, lung infection with Pa correlates clinically with impaired lung function and increased morbidity and mortality [ 1 , 10 , 12 – 17 , 20 ].…”