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  • 1.
    Edlund, Charlotta
    et al.
    Södertörns högskola, Avdelning Naturvetenskap. Karolinska Institute.
    Alvan, G
    Barkholt, L
    Vacheron, F
    Nord, C E
    Pharmacokinetics and comparative effects of telithromycin (HMR 3647) and clarithromycin on the oropharyngeal and intestinal microflora2000Inngår i: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 46, nr 5, s. 741-749Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The pharmacokinetics in plasma and saliva of a new ketolide, telithromycin (HMR 3647), and the effect on the normal oropharyngeal and intestinal microflora were studied in healthy volunteers and compared with those of clarithromycin. Ten subjects received 800 mg telithromycin perorally once daily and 10 other subjects received 500 mg clarithromycin bid for 10 days. Blood, saliva and faecal specimens were collected at defined intervals before, during and after administration for pharmacokinetic and microbiological analyses. In subjects receiving telithromycin, the mean C(max), AUC and C(24) (24 h) in saliva exceeded the values obtained from plasma, while saliva and serum pharmacokinetic parameters were in the same range for the clarithromycin group. The quantitative ecological disturbances in the normal microflora during administration of telithromycin were moderate and comparable to those associated with clarithromycin administration. No overgrowth of yeasts or Clostridium difficile occurred. Emergence of resistant strains was seen in both treatment groups. Administration of both telithromycin and clarithromycin was associated with significant increases in MICs for intestinal Bacteroides isolates, which persisted 2 weeks after discontinuation of treatment. In addition, a significant emergence of highly clarithromycin-resistant a-haemolytic streptococci, intestinal enterococci and Enterobacteriaceae was detected at day 10 in the clarithromycin group. In conclusion, administration of telithromycin resulted in high drug levels in saliva, which indicates a good therapeutic profile for throat infections. Telithromycin seems to have a more favourable ecological profile compared with clarithromycin in terms of resistance development in the normal microflora.

  • 2.
    Edlund, Charlotta
    et al.
    Södertörns högskola, Avdelning Naturvetenskap. Karolinska Institute.
    Nord, C E
    Effect on the human normal microflora of oral antibiotics for treatment of urinary tract infections2000Inngår i: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 46, s. 41-48Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Oral administration of antibiotics for treatment of urinary tract infections (UTIs) can cause ecological disturbances in the normal intestinal microflora. Poorly absorbed drugs can reach the colon in active form, suppress susceptible microorganisms and disturb the ecological balance. Suppression of the normal microflora may lead to reduced colonization resistance with subsequent overgrowth of pre-existing, naturally resistant microorganisms, such as yeasts and Clostridium difficile. New colonization by resistant potential pathogens may also occur and may spread within the body or to other patients and cause severe infections. It is therefore important to learn more about the ecological effects of antibacterial agents on the human microflora. The impact on intestinal microorganisms of oral antibiotics used for the treatment of UTIs is reviewed here. Ampicillin, amoxycillin and co-amoxiclav suppress both the aerobic and anaerobic intestinal microflora with overgrowth of ampicillin-resistant Enterobacteriaceae. Pivmecillinam also affects the intestinal microflora, suppressing Escherichia coli, but does not have a major effect on the anaerobic microflora. Several orally administered cephalosporins, such as cefixime, cefpodoxime, cefprozil and ceftibuten, reduce the number of Enterobacteriaceae and increase the number of enterococci. Colonization with C. difficile has also been observed. Fluoroquinolones eliminate or strongly suppress intestinal Enterobacteriaceae, but affect enterococci and anaerobic bacteria only slightly. When antimicrobial agents are prescribed for the treatment of UTIs, not only the antimicrobial spectrum of the agent but also the potential ecological disturbances, including the risk of emergence of resistant strains, should be considered.

  • 3.
    Löfmark, Sonja
    et al.
    Karolinska Institute.
    Jernberg, Cecilia
    Södertörns högskola, Institutionen för livsvetenskaper. Karolinska Institute.
    Jansson, Janet K.
    Swedish University of Agricultural Sciences.
    Edlund, Charlotta
    Karolinska Institute / Medical Products Agency.
    Clindamycin-induced enrichment and long-term persistence of resistant Bacteroides spp. and resistance genes2006Inngår i: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 58, nr 6, s. 1160-1167Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: The aim was to study the long-term consequences of 1 week clindamycin administration regarding selection and persistence of resistance, resistance determinants and diversity of the Bacteroides spp. in the intestinal microflora. Methods: A total of 1306 Bacteroides isolates were collected from constitutively cultured faecal samples during a 2 year period from eight healthy volunteers. The strains were identified by biochemical and genotyping methods. MIC values were determined by the agar dilution method and presence of resistance genes was screened by real-time PCR. Results: Ecological changes in the intestinal microflora persisting up to 24 months were recorded after a 7 day clindamycin administration to four healthy volunteers. Compared to a control group, not exposed to clindamycin, an enrichment and stabilization of resistant Bacteroides strains and resistance determinants were discovered up to 2 years after clindamycin exposure. Conclusions: The results indicate that even a short-term antibiotic administration can cause long-term alterations in the commensal microbiota of individual subjects, detectable 2 years after dosing. The recorded selection and persistence of resistant strains and resistance genes, illustrates the importance of increasing our knowledge of the role of the abundant intestinal microbial community as a reservoir for spread of resistance.

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