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- Gustafsson, Ingegerd, et al.
(författare)
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Bacteria with increased mutation frequency and antibiotic resistance are enriched in the commensal flora of patients with high antibiotic usage
- 2003
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 52:4, s. 645-650
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We examined how prolonged antibiotic treatment affected the resistance and mutation frequency of human microflora isolated from intestine (Escherichia coli, enterococci spp.), pharynx (alpha-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 alpha-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 alpha-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.
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- Sjölund, Maria, 1975-
(författare)
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Development and Stability of Antibiotic Resistance
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Antibiotic resistance is of current concern. Bacteria have become increasingly resistant to commonly used antibiotics and we are facing a growing resistance problem. The present thesis was aimed at studying the impact of antibiotic treatment on pathogenic bacteria as well as on the normal human microbiota, with focus on resistance development.Among the factors that affect the appearance of acquired antibiotic resistance, the mutation frequency and biological cost of resistance are of special importance. Our work shows that the mutation frequency in clinical isolates of Helicobacter pylori was generally higher than for other studied bacteria such as Enterobacteriaceae; ¼ of the isolates displayed a mutation frequency higher than Enterobacteriaceae defective mismatch repair mutants and could be regarded as mutator strains.In H. pylori, clarithromycin resistance confers a biological cost, as measured by decreased competitive ability of the resistant mutants in mice. In clinical isolates, this cost could be reduced, consistent with compensatory evolution stabilizing the presence of the resistant phenotype in the population. Thus, compensation is a clinically relevant phenomenon that can occur in vivo.Furthermore, our results show that clinical use of antibiotics selects for stable resistance in the human microbiota. This is important for several reasons. First, many commensals occasionally can cause severe disease, even though they are part of the normal microbiota. Therefore, stably resistant populations increase the risk of unsuccessful treatment of such infections. Second, resistance in the normal microbiota might contribute to increased resistance development among pathogens by interspecies transfer of resistant determinants.
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- Sjölund, Maria, et al.
(författare)
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Long-term persistence of resistant Enterococcus species after antibiotics to eradicate Helicobacter pylori
- 2003
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Ingår i: Annals of Internal Medicine. - : American College of Physicians. - 0003-4819 .- 1539-3704. ; 139:6, s. 483-7
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND: Antibiotic treatment selects for resistance not only in the pathogen to which it is directed but also in the indigenous microflora. OBJECTIVE: To determine whether a widely used regimen (clarithromycin, metronidazole, and omeprazole) for Helicobacter pylori eradication affects resistance development in enterococci. DESIGN: Cohort study. SETTING: Endoscopy units at 3 community hospitals in Sweden. PATIENTS: 5 consecutive dyspeptic patients who were colonized with H. pylori, had endoscopy-confirmed duodenal ulcer, and received antibiotic treatment, and 5 consecutive controls with dyspepsia but no ulcer who did not receive treatment. MEASUREMENTS: Fecal samples were obtained from patients and controls before, immediately after, 1 year after, and 3 years after treatment. From each patient and sample, enterococci were isolated and analyzed for DNA fingerprint, clarithromycin susceptibility, and presence of the erm(B) gene. RESULTS: In treated patients, all enterococci isolated immediately after treatment showed high-level clarithromycin resistance due to erm(B). In 3 patients, resistant enterococci persisted for 1 to 3 years after treatment. No resistance developed among controls. CONCLUSION: A common H. pylori treatment selects for highly resistant enterococci that can persist for at least 3 years without further selection.
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