Initial Pseudomonas aeruginosa infection in patients with cystic fibrosis: characteristics of eradicated and persistent isolates

Abstract

Despite intensive eradication therapy, some CF patients with early Pseudomonas aeruginosa infection rapidly develop a chronic infection. To elucidate factors associated with this persistence, bacterial characteristics of early P. aeruginosa isolates were analysed that were either eradicated rapidly or persisted despite multiple antimicrobial treatments. Eighty-six early infection episodes were studied. First P. aeruginosa isolates from patients with eradication (36) or persistent infection (16) were included; isolates from patients with intermittent infection (34) were omitted from the study. Virulence assays, antimicrobial resistance, cytotoxicity and mutation frequencies were analysed in vitro. P. aeruginosa was genotyped by SNP-array. Transcriptomic profiles of two eradicated and two persistent strains were compared. Nineteen per cent of patients developed persistent infection; 42% achieved eradication. Secretion of virulence factors and mutation frequencies were highly variable among both eradicated and persistent isolates and were not different between the groups. Cytotoxicity was present in 57% of eradicated vs. 100% of persistent isolates (p <0.01). None of the isolates were resistant to antibiotics. The isolates were genotypically highly diverse. Multivariate analysis showed that in vitro determined bacterial characteristics could not predict persistence after first P. aeruginosa infection. Preliminary transcriptomic data showed increased expression of some genes related to a metabolic pathway. The early onset of chronic infection was not associated with (in vitro determined) bacterial characteristics only. Although the persistent isolates were more often cytotoxic, for the individual patient it was not possible to predict the risk of persistence based on bacterial characteristics. Unknown factors such as host-pathogen and pathogen-pathogen interactions should be further explored.

Diversity of metabolic profiles of cystic fibrosis Pseudomonas aeruginosa during the early stages of lung infection

“…The lack of difference between strains collected from CF patients that followed different courses of lung infection is in accordance with another study, where some phenotypic and genotypic properties were studied on isolates from intermittently colonized CF patients. Here, some patients got rid of the intermittent P. aeruginosa colonization whereas others became chronically infected, and no differences were found between the isolates from the two groups of patients (Tramper-Stranders et al, 2012).…”

“…Cystic fibrosis P. aeruginosa diversity malate, fumarate and succinate as carbon and energy sources, and the transport system for C 4 dicarboxylates has recently been described (Rojo, 2010;Valentini et al, 2011). An upregulation of the C 4 -dicarboxylate transport system in two persistent isolates compared to two intermittent colonizing isolates has previously been shown by transcriptomic analysis (Tramper-Stranders et al, 2012), a finding that led to the hypothesis that the C 4 -dicarboxylates transport system may be important for early persisting infection with P. aeruginosa. However, some of the P. aeruginosa isolates included in the present study showed reduced respiration on succinate compared to the controls (Tables 2 and 3), suggesting that upregulation of the C 4 -transport system is not absolutely required for persistence in the CF lung.…”

Population Structure and Antimicrobial Susceptibility of Both Nonpersistent and Persistent Pseudomonas aeruginosa Isolates Recovered from Cystic Fibrosis Patients

“…olecular typing tools applied to Pseudomonas aeruginosa isolates recovered from cystic fibrosis (CF) patients have demonstrated not only local epidemiological differences (1)(2)(3)(4) but also the spread of particular multiresistant clones through different CF units (5)(6)(7)(8) and the in vivo evolution of single clones involving multilocus sequence type (MLST) shifts (9). Nevertheless, studies addressing differences in terms of population structure between nonpersistent and persistent isolates from CF patients have not yet been reported.…”

“…Nevertheless, studies addressing differences in terms of population structure between nonpersistent and persistent isolates from CF patients have not yet been reported. This work was performed to describe the genetic diversity of P. aeruginosa colonizing CF patients from a CF unit in a university hospital in Spain, differentiating between nonpersistent isolates (isolates recovered once or during a Ͻ6-month period in consecutive sputum cultures) and persistent isolates (genetically related isolates recovered during a minimum of 6 months) (4,10). All morphologically different colonies cultured from each sputum sample during the follow-up period were analyzed.…”

Consenso español para la prevención y el tratamiento de la infección bronquial por Pseudomonas aeruginosa en el paciente con fibrosis quística

“…Se debe realizar un cultivo de control 1-2 semanas después de finalizar el tratamiento de erradicación 52,88,[90][91][92] . Si es negativo, se debe prolongar el tratamiento de uno (28 días) a 3 ciclos, en régi-men on-off con TNS o con AZLI (máximo 3-6 meses), o 3-6 meses de forma continua, con colistimetato (II-A).…”