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    Pentti O Huovinen

    s/Posters: Pulkki J, Rautakorpi U-M, Huikko S, Honkanen P, Klaukka T, Mäkelä M, palva E, Roine R, sarkkinen H, Huovinen P and Varonen H for the MIKSTRA Collaborative Study Group. Use of symptomatic medication in threastment of acute... more
    s/Posters: Pulkki J, Rautakorpi U-M, Huikko S, Honkanen P, Klaukka T, Mäkelä M, palva E, Roine R, sarkkinen H, Huovinen P and Varonen H for the MIKSTRA Collaborative Study Group. Use of symptomatic medication in threastment of acute sinusitis in primary health care. 23rd Annual Meeting of the Scandinavian Society for Antimicrobial Chemotherapy, Uppsala, Ruotsi 26.29.10.2006. Koskinen H, Rautakorpi U-M, Sintonen H, Mäkelä M and the MIKSTRA Collaborative Study Group. Uncomplicated urinary tract infections in women: Cost-effectiveness of implementing national guidelines in Finland. 2nd Annual HTAi Meeting, Rooma, Italia 20.-22.6.2005. Rautakorpi U-M, Huikko S, Honkanen P, Klaukka T, Mäkelä M, Palva E, Roine R, Sarkkinen H, Varonen H and Huovinen P for the MIKSTRA Collaborative Study Group. MIKSTRA Programme A fi ve year follow-up of indication based antibiotic prescribing and implementation of evidence based treatment guidelines in primary care. 2nd Annual HTAi Meeting, Rooma, Italia 2...
    Äkillisellä välikorvatulehduksella tarkoitetaan äkillisesti alkanutta, lyhytkestoista ja kliinisesti todennettavissa olevaa tulehdusta välikorvassa [1,2]. Sen merkkinä tärykalvon ulkonäkö poikkeaa normaalista ja välikorvassa on nestettä.... more
    Äkillisellä välikorvatulehduksella tarkoitetaan äkillisesti alkanutta, lyhytkestoista ja kliinisesti todennettavissa olevaa tulehdusta välikorvassa [1,2]. Sen merkkinä tärykalvon ulkonäkö poikkeaa normaalista ja välikorvassa on nestettä. Lisäksi taudinkuvaan kuuluu vähintään yksi yleiseen tai paikalliseen infektioon viittaava oire tai löydös, kuten nuha, yskä, kuume, kurkkukipu, korvakipu, kuulon heikkeneminen, yölevottomuus, ärtyisyys, ruokahaluttomuus, oksentelu tai ripuli. Myös tärykalvon ilmastointiputken tai puhkeaman kautta tuleva äkillisesti alkanut märkävuoto katsotaan akuutiksi otiitiksi [1].
    We have studied the resistance of urinary strains of Escherichia coli in relation to patients' age. A total of 4146 samples of urine was collected during 1984-1990 from patients staying in an acute care university hospital and in... more
    We have studied the resistance of urinary strains of Escherichia coli in relation to patients' age. A total of 4146 samples of urine was collected during 1984-1990 from patients staying in an acute care university hospital and in a long-term care city hospital in Finland. In the city hospital, the proportion of strains resistant to either ampicillin, trimethoprim, sulphonamides, or to all of these simultaneously (multi-resistant), correlated with increase in age of the patients. In the university hospital, a clear increase was observed in trimethoprim-resistant and multiresistant isolates. Such correlation with age was not observed among catheterised patients in either hospital. Whether this is due to cumulative lifetime use of antimicrobials remains to be studied. We conclude that the incidence of resistant strains of E. coli correlates with patients' age among both chronic and acute care patients who are not catheterised. This is important in the choice of empirical treatment for urinary tract infections of elderly people.
    The frequency of beta-lactamase production was analyzed in a study of 1,452 strains of Moraxella catarrhalis and 2,738 strains of Haemophilus influenzae isolated from middle-ear fluid of children < 6 years of age at Tampere University... more
    The frequency of beta-lactamase production was analyzed in a study of 1,452 strains of Moraxella catarrhalis and 2,738 strains of Haemophilus influenzae isolated from middle-ear fluid of children < 6 years of age at Tampere University Hospital in Tampere, Finland, between 1978 and 1993. In addition, 401 isolates of M. catarrhalis from similar samples collected in different parts of Finland in 1988-1990 were tested for beta-lactamase production; minimal inhibitory concentrations of ampicillin, cefaclor, cephalothin, erythromycin, tetracycline, and trimethoprim-sulfamethoxazole for these strains were determined. These data were compared with figures for the annual consumption of beta-lactam antimicrobials in the community in 1978-1993. A bimodal increase in the proportion of strains of M. catarrhalis producing beta-lactamase was detected: from 0 to 60% in 1978-1983 and from 60% to 80% in 1988-1990. Concurrently with the second increase, the consumption of cephalosporins increased substantially in the community. The frequency of beta-lactamase-producing strains of H. influenzae did not increase between 1978 and 1993.
    The frequency of trimethoprim resistance among Escherichia coli isolates from urine samples collected at Turku City Hospital, Turku, Finland, remained at 40% during 1984 to 1988. The proportion of highly resistant (MIC, greater than or... more
    The frequency of trimethoprim resistance among Escherichia coli isolates from urine samples collected at Turku City Hospital, Turku, Finland, remained at 40% during 1984 to 1988. The proportion of highly resistant (MIC, greater than or equal to 1,024 micrograms/ml) isolates increased, however, and most of these harbored the type I dihydrofolate reductase gene. Only a few isolates possessed type II or VII genes.
    Transposon Tn7 codes for resistance to trimethoprim and streptomycin. For detection of Tn7 by DNA-DNA hybridization, two recombinant plasmids were constructed. The former contained a 1-kilobase BamHI fragment and the latter contained a... more
    Transposon Tn7 codes for resistance to trimethoprim and streptomycin. For detection of Tn7 by DNA-DNA hybridization, two recombinant plasmids were constructed. The former contained a 1-kilobase BamHI fragment and the latter contained a 4.3-kilobase EcoRI-BamHI fragment of Tn7. These DNA fragments, which did not include the drug resistance genes, were used as probes for detecting Tn7-like sequences in bacterial strains by colony hybridization. They hybridized strongly to bacterial DNA known to carry Tn7 but not to DNA known to carry transposons other than Tn7. These probes were used to study the occurrence of Tn7 in bacterial strains isolated in the Turku City Hospital in Finland. Transposon Tn7 was present in 47.2% of 199 trimethoprim-resistant enterobacteria (MIC greater than or equal to 8 micrograms/ml). Among the 69 Proteus mirabilis strains studied, 75% contained Tn7, although none of these strains transferred trimethoprim resistance in conjugation tests. The reliability of colo...
    beta-Lactamase identification by colony hybridization with 32P-labeled DNA probes for TEM-1, SHV-1, OXA-1, OXA-2, PSE-1, PSE-2, and PSE-4 was compared with isoelectric focusing in 122 clinical isolates making a variety of enzyme types.... more
    beta-Lactamase identification by colony hybridization with 32P-labeled DNA probes for TEM-1, SHV-1, OXA-1, OXA-2, PSE-1, PSE-2, and PSE-4 was compared with isoelectric focusing in 122 clinical isolates making a variety of enzyme types. All strains producing a probe-type enzyme gave a positive hybridization reaction. Cross-hybridization was observed between TEM-1 and TEM-2 or TLE-1, between SHV-1 and SHV-2, between OXA-1 and OXA-4, between OXA-2 and OXA-3 (weak), between PSE-2 and OXA-6 or OXA-5 (weak), and among PSE-1, PSE-4, and CARB-3. With allowance for such cross-hybridization, only six strains gave false-positive reactions, and the procedure was 99% specific.
    The randomized controlled Special Turku Coronary Risk Factor Intervention Project (STRIP) has completed a 20-year infancy-onset dietary counselling intervention to reduce exposure to atherosclerotic cardiovascular disease risk factors via... more
    The randomized controlled Special Turku Coronary Risk Factor Intervention Project (STRIP) has completed a 20-year infancy-onset dietary counselling intervention to reduce exposure to atherosclerotic cardiovascular disease risk factors via promotion of a heart-healthy diet. The counselling on, e.g., low intake of saturated fat and cholesterol and promotion of fruit, vegetable, and whole-grain consumption has affected the dietary characteristics of the intervention participants. By leveraging this unique cohort, we further investigated whether this long-term dietary intervention affected the gut microbiota bacterial profile six years after the intervention ceased. Our sub-study comprised 357 individuals aged 26 years (intervention n = 174, control n = 183), whose gut microbiota were profiled using 16S rRNA amplicon sequencing. We observed no differences in microbiota profiles between the intervention and control groups. However, out of the 77 detected microbial genera, the Veillonella...
    Suomalainen Lääkäriseura Duodecimin ja Suomen Akatemian konsensuskokous 1997 : Antibioottiresistenssi - säilyykö lääkkeiden teho?
    Suomalainen Lääkäriseura Duodecimin ja Suomen Akatemian konsensuskokous 1997 : Antibioottiresistenssi - säilyykö lääkkeiden teho?
    Studying bacterial resistance has direct importance for the antimicrobial treatment of individual patients. In addition, surveillancedatapooled from individual diagnostic reportshelpphysicians tochoose themost effective drug for empirical... more
    Studying bacterial resistance has direct importance for the antimicrobial treatment of individual patients. In addition, surveillancedatapooled from individual diagnostic reportshelpphysicians tochoose themost effective drug for empirical therapy. However, this is not the limit of what can be done with the resistance data. There is an increasing need to synthesize the available strands of data in order to construct math-ematicalmodels that canbeusedas tools topredict the likelyoutcomesof variousantibioticpolicyoptions.
    Carita Savolainen-Kopra (carita.savolainen-kopra@thl.fi) Jaason Haapakoski (jaason.haapakoski@thl.fi) Piia A Peltola (piia.a.peltola@thl.fi) Thedi Ziegler (thedi.ziegler@thl.fi) Terttu Korpela (tkorpela9@gmail.com) Pirjo Anttila... more
    Carita Savolainen-Kopra (carita.savolainen-kopra@thl.fi) Jaason Haapakoski (jaason.haapakoski@thl.fi) Piia A Peltola (piia.a.peltola@thl.fi) Thedi Ziegler (thedi.ziegler@thl.fi) Terttu Korpela (tkorpela9@gmail.com) Pirjo Anttila (pirjo.anttila@kesko.fi) Ali Amiryousefi (amiryous@mappi.helsinki.fi) Pentti Huovinen (pentti.huovinen@thl.fi) Markku Huvinen (markku.huvinen@outokumpu.com) Heikki Noronen (heikki.noronen@nordea.fi) Pia Riikkala (pia.riikkala@nordea.fi) Merja Roivainen (merja.roivainen@thl.fi) Petri Ruutu (petri.ruutu@thl.fi) Erkki Vartiainen (erkki.vartiainen@thl.fi) Tapani Hovi (tapani.hovi@thl.fi)
    The aim of the present study was to determine whether oral targeted recombinant beta-lactamase (TRBL) administration could overcome the development of ampicillin-induced resistance in the gut microbiota. Eighteen laboratory beagles with... more
    The aim of the present study was to determine whether oral targeted recombinant beta-lactamase (TRBL) administration could overcome the development of ampicillin-induced resistance in the gut microbiota. Eighteen laboratory beagles with permanent jejunal fistula were randomised to receive ampicillin + placebo, ampicillin + TRBL or placebo. A total of 982 coliform isolates, collected from jejunal and faecal samples before, during and after the treatment were tested against nine antimicrobials. The proportion of ampicillin resistance (multi-resistance) among coliform isolates increased from 20 to 36% in the ampicillin + placebo group but far less, 20-36%, in the ampicillin + TRBL group. These results indicate that TRBL may prevent the emergence of beta-lactam-associated resistance in coliforms in the gut.
    ABSTRACT A nationwide survey of the prevalence of antimicrobial resistance among Streptococcus pneumoniae isolates from the middle ear fluid of children with acute otitis media (639 strains) and from throat-swab samples of healthy... more
    ABSTRACT A nationwide survey of the prevalence of antimicrobial resistance among Streptococcus pneumoniae isolates from the middle ear fluid of children with acute otitis media (639 strains) and from throat-swab samples of healthy children (149 strains) was conducted in Finland during 1987-1990. The MICs of penicillin, cephalothin, cefaclor, erythromycin, trimethoprim, and co-trimoxazole were determined by the agar dilution method. Low-level resistance to penicillin (MIC, 0.1-1 microgram/mL) was found in 1.7% of the otitis-related and 1.3% of the healthy-carrier strains. No highly penicillin-resistant strains (MIC, > or = 2 micrograms/mL) were found. Six multiresistant strains were detected, three of them possibly belonging to a previously identified clone present in Finland since 1985. Eighty-five percent of the resistant otitis-related strains, including 9 of the 11 moderately penicillin-resistant strains (4 of which were multiresistant), belonged to the three most common serogroups (6, 19, and 23).
    The microbiota of the small intestine is poorly known because of difficulties in sampling. In this study, we examined whether the organisms cultured from the jejunum and feces resemble each other. Small-intestinal fluid samples were... more
    The microbiota of the small intestine is poorly known because of difficulties in sampling. In this study, we examined whether the organisms cultured from the jejunum and feces resemble each other. Small-intestinal fluid samples were collected from 22 beagle dogs with a permanent jejunal fistula in parallel with fecal samples. In addition, corresponding samples from seven of the dogs were collected during a 4-week period (days 4, 10, 14, and 28) to examine the stability of the microbiota. In the jejunal samples, aerobic/facultative and anaerobic bacteria were equally represented, whereas anaerobes dominated in the fecal samples. Despite lower numbers of bacteria in the jejunum (range, 102 to 106 CFU/g) than in feces (range, 108 to 1011 CFU/g), some microbial groups were more prevalent in the small intestine: staphylococci, 64% versus 36%; nonfermentative gram-negative rods, 27% versus 9%; and yeasts, 27% versus 5%, respectively. In contrast, part of the fecal dominant microbiota (bil...
    The aim of this study was to examine the dynamics of the development of resistance in fecal Escherichia coli populations during treatment with ampicillin for 7 days in pigs. Before treatment, only 6% of the isolates were ampicillin... more
    The aim of this study was to examine the dynamics of the development of resistance in fecal Escherichia coli populations during treatment with ampicillin for 7 days in pigs. Before treatment, only 6% of the isolates were ampicillin resistant, whereas more than 90% of the isolates were resistant after days 4 and 7 of treatment. Ampicillin-resistant E. coli isolates were mainly multiresistant, and 53% of the isolates from the treated pigs had one phenotype that included resistance to six antibiotics (ampicillin, chloramphenicol, sulfonamides, tetracycline, trimethoprim, and streptomycin) at day 7. Determination of the frequency of the four phylogenetic groups showed that there was a shift in the E. coli population in ampicillin-treated pigs; before treatment 75% of the isolates belonged to phylogroup B1, whereas at day 7 85% of the isolates belonged to phylogroup A. Pulsed-field gel electrophoresis (PFGE) typing revealed that ampicillin treatment selected ampicillin-resistant isolates...
    The resistance patterns and macrolide resistance mechanisms of 910 Finnish invasive pneumococci isolated during 1999 and 2000 were studied. Macrolide resistance was detected in 6.9% of isolates. Penicillin resistance was detected in 1.5%... more
    The resistance patterns and macrolide resistance mechanisms of 910 Finnish invasive pneumococci isolated during 1999 and 2000 were studied. Macrolide resistance was detected in 6.9% of isolates. Penicillin resistance was detected in 1.5% of isolates, and penicillin intermediate resistance was detected in 4.0% of isolates. Active macrolide efflux, mediated by the mef(A) gene, was the most common macrolide resistance mechanism. Four macrolide-resistant isolates had mutations in rRNA or ribosomal protein L22.
    Erythromycin resistance among streptococci is commonly due to target site modification by an rRNA-methylating enzyme, which results in coresistance to macrolide, lincosamide, and streptogramin B antibiotics (MLSB resistance). Genes... more
    Erythromycin resistance among streptococci is commonly due to target site modification by an rRNA-methylating enzyme, which results in coresistance to macrolide, lincosamide, and streptogramin B antibiotics (MLSB resistance). Genes belonging to theermAM (ermB) gene class are the only erythromycin resistance methylase (erm) genes inStreptococcus pyogenes with MLSB resistance that have been sequenced so far. We identified a novelerm gene, designated ermTR, from an erythromycin-resistant clinical strain of S. pyogenes(strain A200) with an inducible type of MLSBresistance. The nucleotide sequence of ermTR is 82.5% identical to ermA, previously found, for example, in Staphylococcus aureus and coagulase-negative staphylococci. Our finding provides the first sequence of anerm gene other than ermAM that mediates MLSB resistance in S. pyogenes.
    Toll-like receptor 5 ligand, flagellin, and Vascular Adhesion Protein-1 (VAP-1) are involved in non-alcoholic fatty liver disease (NAFLD). This study aimed to determine whether VAP-1 mediates flagellin-induced hepatic fat accumulation.... more
    Toll-like receptor 5 ligand, flagellin, and Vascular Adhesion Protein-1 (VAP-1) are involved in non-alcoholic fatty liver disease (NAFLD). This study aimed to determine whether VAP-1 mediates flagellin-induced hepatic fat accumulation. The effects of flagellin on adipocyte VAP-1 expression were first studied in vitro. Then, flagellin (100 ng/mouse) or saline was intraperitoneally injected to C57BL/6J WT and C57BL/6-Aoc3-/- (VAP-1 KO) mice on high-fat diet twice a week every two weeks for 10-weeks. After that, the effects on inflammation, insulin signaling, and metabolism were studied in liver and adipose tissues. Hepatic fat was quantified histologically and biochemically. Because flagellin challenge increased VAP-1 expression in human adipocytes, we used VAP-1 KO mice to determine whether VAP-1 regulates the inflammatory and metabolic effects of flagellin in vivo. In mice, VAP-1 mediated flagellin-induced inflammation, leukocyte infiltration and lipolysis in visceral adipose tissue...
    Bacterial infections, especially by antimicrobial resistant (AMR) bacteria, are an increasing problem worldwide. AMR is especially a problem with health care-associated infections due to bacteria in hospital environments being easily... more
    Bacterial infections, especially by antimicrobial resistant (AMR) bacteria, are an increasing problem worldwide. AMR is especially a problem with health care-associated infections due to bacteria in hospital environments being easily transferred from patient to patient and from patient to environment, and thus, solutions to prevent bacterial transmission are needed. Hand washing is an effective tool for preventing bacterial infections, but other approaches such as nanoparticle-coated surfaces are also needed. In the current study, direct and indirect liquid flame spray (LFS) method was used to produce silver nanoparticle-coated surfaces. The antimicrobial properties of these nanoparticle surfaces were evaluated with the "touch test" method against Escherichia coli and Staphylococcus aureus. It was shown in this study that in glass samples one silver nanoparticle-coating cycle can inhibit E. coli growth, whereas at least two coating cycles were needed to inhibit S. aureus g...
    Next-generation sequencing (NGS) is currently the method of choice for analyzing gut microbiota composition. As gut microbiota composition is a potential future target for clinical diagnostics, it is of utmost importance to enhance and... more
    Next-generation sequencing (NGS) is currently the method of choice for analyzing gut microbiota composition. As gut microbiota composition is a potential future target for clinical diagnostics, it is of utmost importance to enhance and optimize the NGS analysis procedures. Here, we have analyzed the impact of DNA extraction and selected 16S rDNA primers on the gut microbiota NGS results. Bacterial DNA from frozen stool specimens was extracted with 5 commercially available DNA extraction kits. Special attention was paid to the semiautomated DNA extraction methods that could expedite the analysis procedure, thus being especially suitable for clinical settings. The microbial composition was analyzed with 2 distinct protocols: 1 targeting the V3-V4 and the other targeting the V4-V5 area of the bacterial 16S rRNA gene. The overall effect of DNA extraction on the gut microbiota 16S rDNA profile was relatively small, whereas the 16S rRNA gene target region had an immense impact on the resu...
    Faecalibacterium prausnitzii is considered as one of the most important bacterial indicators of a healthy gut. We studied the effects of oral F. prausnitzii treatment on high-fat fed mice. Compared to the high-fat control mice, F.... more
    Faecalibacterium prausnitzii is considered as one of the most important bacterial indicators of a healthy gut. We studied the effects of oral F. prausnitzii treatment on high-fat fed mice. Compared to the high-fat control mice, F. prausnitzii-treated mice had lower hepatic fat content, aspartate aminotransferase and alanine aminotransferase, and increased fatty acid oxidation and adiponectin signaling in liver. Hepatic lipidomic analyses revealed decreases in several species of triacylglycerols, phospholipids and cholesteryl esters. Adiponectin expression was increased in the visceral adipose tissue, and the subcutaneous and visceral adipose tissues were more insulin sensitive and less inflamed in F. prausnitzii-treated mice. Further, F. prausnitzii treatment increased muscle mass that may be linked to enhanced mitochondrial respiration, modified gut microbiota composition and improved intestinal integrity. Our findings show that F. prausnitzii treatment improves hepatic health, and...
    Serotyping is widely used for epidemiologic investigation of group A streptococci (GAS). To evaluate molecular typing methods of GAS, restriction endonuclease analysis (REA) of genomic DNA and analysis of DNA restriction fragment length... more
    Serotyping is widely used for epidemiologic investigation of group A streptococci (GAS). To evaluate molecular typing methods of GAS, restriction endonuclease analysis (REA) of genomic DNA and analysis of DNA restriction fragment length polymorphism of rRNA genes (ribotyping) were used in parallel with serotyping. The genomic DNA of 239 epidemiologically unrelated GAS isolates from human invasive infections was digested with HindIII restriction enzyme. Both REA and ribotyping differentiated subclasses within serotypes. However, they did not consistently differentiate between isolates of different serotypes. Ribotyping was less discriminatory than REA. Within the T1M1 serotype, often associated with invasive GAS infections, 92% of the REA patterns were identical, suggesting a common origin for these isolates. Most other serotypes studied were more heterogenic. Among 32 isolates nontypeable by serotyping, 11 distinct REA patterns and 5 ribotypes were identified. REA and ribotyping are useful supplementary tools for classification of GAS and can add to the discriminatory power of serotyping.
    Utilizing an improved method for colony hybridization developed by Haas & Fleming, biotin and 32P-labelled TEM-1 probes were compared for sensitivity and specificity in identifying the type of beta-lactamase made by over 100... more
    Utilizing an improved method for colony hybridization developed by Haas & Fleming, biotin and 32P-labelled TEM-1 probes were compared for sensitivity and specificity in identifying the type of beta-lactamase made by over 100 clinical bacterial isolates. The new procedure was more reliable than a standard one, but still gave more than 20% false positive and false negative reactions.
    The in vitro activity of cefixime and 9 other orally used antimicrobial agents against 545 selected clinical respiratory tract pathogens was tested using the plate-dilution method. Of the strains tested, 144 were Haemophilus influenzae... more
    The in vitro activity of cefixime and 9 other orally used antimicrobial agents against 545 selected clinical respiratory tract pathogens was tested using the plate-dilution method. Of the strains tested, 144 were Haemophilus influenzae strains, 151 group A streptococci, 105 pneumococci and 145 Moraxella catarrhalis isolates. Ciprofloxacin was the most active drug, with a minimal inhibitory concentration (MIC) of < 0.06 mg/l for more than 87% of the isolates. With cefixime, a MIC of 0.06 mg/l inhibited 55% of the strains tested and a MIC of 1.0 mg/l inhibited all except one of the 545 strains. One pneumococcal strain was resistant to cefixime. Beta-lactamase producing H. influenzae and M. catarrhalis strains were clearly more susceptible to cefixime than to other oral cephalosporins (cephalexin, cefaclor, cefuroxime). However, penicillin, ampicillin and cefuroxime were more effective against beta-hemolytic streptococci and pneumococci than was cefixime. The new third generation cephalosporin, cefixime, showed markedly better in vitro activity against certain major respiratory tract pathogens than the other peroral antimicrobials commonly used against respiratory tract infections.

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