JAC Advance Access published online on September 12, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg427
© 2003 by The British Society for Antimicrobial Chemotherapy
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Original article
1 Antibiotic Research Unit,
Department of Medical Sciences, Section of Clinical Bacteriology, Uppsala University
Hospital, Uppsala
* Corresponding author. E-mail: dan.andersson{at}smi.ki.se.
Received 26 May 2003
; revised 13 July 2003
; accepted 23 July 2003
Background: We examined how prolonged
antibiotic treatment affected the resistance and mutation frequency
of human microflora isolated from intestine (Escherichia
coli, enterococci spp.), pharynx ( Methods: Samples were collected from patients
at the Center of Cystic Fibrosis (n = 18)
and the haematology ward (n = 18) of the
University Hospital, Uppsala, Sweden. The individually used amount
of antibiotics for 1 year was recorded as the defined
daily dose (DDD). Primary health care patients (n = 30),
with no antibiotic treatment for 1 year before sampling, were used
as controls. Three isolates of each bacterium from each patient
were examined. Antibiotic susceptibilities were determined by disc
diffusion. Mutation frequencies to rifampicin resistance were measured
on 30 independent cultures of each bacterial species from each individual
by plating on rifampicin agar plates. For Results: Isolates from patients with high antibiotic
use showed a pronounced shift towards increased resistance and a
small but significant increase in the mutation frequency compared
with isolates from the controls. For E. coli, enterococci
and CoNS the increase in geometric mean mutation frequency in the
patient group was 3-, 1.8- and 1.5-fold, respectively (P values
0.0001, 0.016 and 0.012). For Conclusions: High antibiotic use selected for
commensals with highly increased resistance and a slight increase
in mutation frequency.
Keywords: human microflora, antibiotic treatment, selection,
mutators
Bacteria with increased mutation frequency and
antibiotic
resistance are enriched in the commensal flora of patients with
high antibiotic usage
2 Section of Infectious Diseases, Uppsala University Hospital, Uppsala
3 Uppsala CF Center, Department
of Womens' and Childrens' Health, Uppsala University
Hospital, Uppsala
4 Antibiotic Research Unit,
Department of Medical Sciences, Section of Clinical Bacteriology, Uppsala University
Hospital, Uppsala; Swedish
Institute for Infectious Disease Control, Department of Bacteriology,
SE-171 82 Solna, Sweden
5 Swedish
Institute for Infectious Disease Control, Department of Bacteriology,
SE-171 82 Solna, Sweden
-streptococci)
and nostril (coagulase-negative staphylococci, CoNS).
-streptococci
the mutation frequency to streptomycin resistance was also determined.
-streptococci
there was a significant difference in geometric mean mutation
frequency between patient and control groups for streptomycin resistance
(P = 0.024) but not for rifampicin resistance
(P = 0.74).![]()
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