Effect of mutator P. aeruginosa on antibiotic resistance acquisition and respiratory function in cystic fibrosis.
BACKGROUND
Cystic fibrosis patients suffer from recurrent bacterial infections that result in progressive deterioration of their respiratory function. Despite intensive antibiotic treatment, Pseudomonas aeruginosa is the main cause of such infections, with clones progressively developing multiple antibiotic resistance. We determined the relationship between the presence of P. aeruginosa mutator strains and cystic fibrosis clinical characteristics.


METHODS
We analyzed 136 strains of P. aeruginosa isolated from the expectorations of 36 CF patients. On all strains, mutation frequencies were determined by the mutation rate to rifampicin, and antibiotic susceptibility was determined by the disk diffusion method. The epidemiological relatedness of these 136 P. aeruginosa strains was studied by pulsed-field gel electrophoresis. The appearance of new antibiotic resistance by sequential analysis of genotypically identical strains was determined. Lung function test results, that is, forced expiratory volume in 1 sec and vital capacity, were also recorded from these patients.


RESULTS
We showed that bacteria with an enhanced mutation rate increase the rate of acquisition of new antibiotic resistance threefold and are associated with the deterioration of lung function.


CONCLUSIONS
This study demonstrates the effect of mutator bacteria on the efficiency of patient treatment and on their respiratory function. Given the consequence of antibiotic treatment failure and lung deterioration on the prognosis of CF patients, antibiotic treatment strategies may need to be optimized to prevent the emergence of mutator clones.
Ferroni
Agnes
A
Laboratoire de Microbiologie, Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Paris, France. agnes.ferroni@nck.aphp.fr
Guillemot
Didier
D
Moumile
Kaoutar
K
Bernede
Claire
C
Le Bourgeois
Muriel
M
Waernessyckle
Serge
S
Descamps
Philippe
P
Sermet-Gaudelus
Isabelle
I
Lenoir
Gérard
G
Berche
Patrick
P
Taddei
François
F
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000382:microbiology* / Q000503:physiopathology; D024881:Drug Resistance, Bacterial / Q000235:genetics; D005541:Forced Expiratory Volume; D005838:Genotype; D006801:Humans; D007223:Infant; D008826:Microbial Sensitivity Tests; D009154:Mutation; D011552:Pseudomonas Infections / Q000150:complications* / Q000188:drug therapy / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D014797:Vital Capacity