JAC Advance Access originally published online on September 12, 2003
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Journal of Antimicrobial Chemotherapy (2003) 52, 645-650
© 2003 The British Society for Antimicrobial Chemotherapy
Bacteria with increased mutation frequency and antibiotic resistance are enriched in the commensal flora of patients with high antibiotic usage
1 Antibiotic Research Unit, Department of Medical Sciences, Section of Clinical Bacteriology, 2 Section of Infectious Diseases and 3 Uppsala CF Center, Department of Womens’ and Childrens’ Health, Uppsala University Hospital, Uppsala; 4 Swedish Institute for Infectious Disease Control, Department of Bacteriology, SE-171 82 Solna, Sweden
Received 26 May 2003; returned 30 June 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 (
-streptococci) and nostril (coagulase-negative staphylococci, CoNS).
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 -streptococci the mutation frequency to streptomycin resistance was also determined.
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 -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).
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
* Corresponding author. Tel: +46-8-4572432; Fax: +46-8-301797; E-mail: dan.andersson{at}smi.ki.se
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