Browsing by Subject "ANTIBIOTICS"

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  • McVey, Alyssa; Bartlett, Sean; Kajbaf, Mahmoud; Pellacani, Annalisa; Gatta, Viviana; Tammela, Päivi; Spring, David R.; Welch, Martin (2020)
    Pseudomonas aeruginosa is an opportunistic pathogen responsible for many hospital-acquired infections. P. aeruginosa can thrive in diverse infection scenarios by rewiring its central metabolism. An example of this is the production of biomass from C-2 nutrient sources such as acetate via the glyoxylate shunt when glucose is not available. The glyoxylate shunt is comprised of two enzymes, isocitrate lyase (ICL) and malate synthase G (MS), and flux through the shunt is essential for the survival of the organism in mammalian systems. In this study, we characterized the mode of action and cytotoxicity of structural analogs of 2-aminopyridines, which have been identified by earlier work as being inhibitory to both shunt enzymes. Two of these analogs were able to inhibit ICL and MS in vitro and prevented growth of P. aeruginosa on acetate (indicating cell permeability). Moreover, the compounds exerted negligible cytotoxicity against three human cell lines and showed promising in vitro drug metabolism and safety profiles. Isothermal titration calorimetry was used to confirm binding of one of the analogs to ICL and MS, and the mode of enzyme inhibition was determined. Our data suggest that these 2-aminopyridine analogs have potential as anti-pseudomonal agents.
  • Mgbeahuruike, Eunice Ego; Stålnacke, Milla; Vuorela, Heikki; Holm, Yvonne (2019)
    Microbial resistance to currently available antibiotics is a public health problem in the fight against infectious diseases. Most antibiotics are characterized by numerous side effects that may be harmful to normal body cells. To improve the efficacy of these antibiotics and to find an alternative way to minimize the adverse effects associated with most conventional antibiotics, piperine and piperlongumine were screened in combination with conventional rifampicin, tetracycline, and itraconazole to evaluate their synergistic, additive, or antagonistic interactions against Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. The fractional inhibitory concentration index was used to estimate the synergistic effects of various combination ratios of the piperamides and antibiotics against the bacterial and fungal strains. Both piperine and piperlongumine showed synergistic effects against S. aureus when combined at various ratios with rifampicin. Synergistic interaction was also observed with piperine in combination with tetracycline against S. aureus, while antagonistic interaction was recorded for piperlongumine and tetracycline against S. aureus. All the piperamide/antibacterial combinations tested against P. aeruginosa showed antagonistic effects, with the exception of piperine and rifampicin, which recorded synergistic interaction at a ratio of 9:1 rifampicin/piperine. No synergistic interaction was observed when the commercial compounds were combined with itraconazole and tested against C. albicans. The results showed that piperine and piperlongumine are capable of improving the effectiveness of rifampicin and tetracycline. Dosage combinations of these bioactive compounds with the antibiotics used may be a better option for the treatment of bacterial infections that aims to minimize the adverse effects associated with the use of these conventional antibacterial drugs.
  • Vanic, Zeljka; Rukavina, Zora; Manner, Suvi; Fallarero, Adyary; Uzelac, Lidija; Kralj, Marijeta; Klaric, Daniela Amidzic; Bogdanov, Anita; Raffai, Timea; Virok, Dezso Peter; Filipovic-Grcic, Jelena; Skalko-Basnet, Natasa (2019)
    Background: Efficient localized cervicovaginal antibacterial therapy, enabling the delivery of antibiotic to the site of action at lower doses while escaping systemic drug effects and reducing the risk of developing microbial resistance, is attracting considerable attention. Liposomes have been shown to allow sustained drug release into vaginal mucosa and improve delivery of antibiotics to bacterial cells and biofilms Azithromycin (AZI), a potent broad-spectrum macrolide antibiotic, has not yet been investigated for localized therapy of cervicovaginal infections, although it is administered orally for the treatment of sexually transmitted diseases. Encapsulation of AZI in liposomes could improve its solubility, antibacterial activity, and allow the prolonged drug release in the cervicovaginal tissue, while avoiding systemic side effects. Purpose: The objective of this study was to develop AZI-liposomes and explore their potentials for treating cervicovaginal infections. Methods: AZI-liposomes that differed in bilayer elasticity/rigidity and surface charge were prepared and evaluated under simulated cervicovaginal conditions to yield optimized liposomes, which were assessed for antibacterial activity against several planktonic and biofilm-forming Escherichia coli strains and intracellular Chlamydia trachomatis, ex vivo AZI vaginal deposition/penetration, and in vitro cytotoxicity toward cervical cells. Results: Negatively charged liposomes with rigid bilayers (CL-3), propylene glycol liposomes (PGL-2) and deformable propylene glycol liposomes (DPGL-2) were efficient against planktonic E. coli ATCC 700928 and K-12. CL-3 was superior for preventing the formation of E. coli ATCC 700928 and K-12 biofilms, with IC50 values (concentrations that inhibit biofilm viability by 50%) up to 8-fold lower than those of the control (free AZI). DPGL-2 was the most promising for eradication of already formed E. coli biofilms and for treating C. trachomatis infections. All AZI-liposomes were biocompatible with cervical cells and improved localization of the drug inside vaginal tissue compared with the control. Conclusion: The performed studies confirm the potentials of AZI-liposomes for localized cervicovaginal therapy.
  • Mali, Juha; Mentula, Panu; Leppäniemi, Ari; Sallinen, Ville (2019)
    BackgroundDiverticular abscess diameter of 3-6cm is generally accepted as a cutoff determining whether percutaneous drainage is recommended in addition to antibiotics, but this is not based on high-quality evidence. The aim of this study was to analyze the treatment choices and outcomes of patients with diverticular abscesses.MethodsThis was a retrospective cohort study conducted in an academic teaching hospital functioning as a secondary and tertiary referral center. Altogether, 241 patients with computer tomography-verified acute left-sided colonic diverticulitis with intra-abdominal abscess were collected from a database containing all patients treated for colonic diverticulitis in our institution during 2006-2013. The main measured outcomes were need of emergency surgery and 30-day mortality, and these were compared between antibiotics only and percutaneous drainage groups. Treatment choices, including surgery, were also analyzed for all patients.ResultsAbscesses under 40mm were mostly treated with antibiotics alone with a high success rate (93 out of 107, 87%). In abscesses over 40mm, the use of emergency surgery increased and the use of antibiotics alone decreased with increasing abscess size, but the proportion of successful drainage remained at 13-18% regardless of the abscess size. There were no differences in failure rate, 30-day mortality, the need of emergency surgery, permanent stoma, recurrence, or length of stay in patients treated with percutaneous drainage vs. antibiotics alone, even when groups were adjusted for potential confounders.ConclusionsPercutaneous drainage as a treatment for large abscess does not seem to be superior to the treatment with only antibiotics.
  • Laulajainen-Hongisto, Anu; Aarnisalo, Antti A.; Jero, Jussi (2016)
    Acute otitis media is a common infection in children. Most acute otitis media episodes can be treated at an outpatient setting with antimicrobials, or only expectant observation. Hospital treatment with parenteral medication, and myringotomy or tympanostomy, may be needed to treat those with severe, prolonged symptoms, or with complications. The most common intratemporal complication of acute otitis media is acute mastoiditis. If a child with acute mastoiditis does not respond to this treatment, or if complications develop, further examinations and other surgical procedures, including mastoidectomy, are considered. Since the treatment of complicated acute otitis media and complicated acute mastoiditis differs, it is important to differentiate these two conditions. This article focuses on the differential diagnostics of acute otitis media and acute mastoiditis in children.
  • Ding, Yaping; Li, Wei; Correia, Alexandra; Yang, Yuyun; Zheng, Kai; Liu, Dongfei; Schubert, Dirk W.; Boccaccini, Aldo R.; Santos, Helder A.; Roether, Judith A. (2018)
    Electrospun hybrid scaffolds are an effective platform to deliver drugs site specifically for the prevention and treatment of diseases in addition to promote tissue regeneration because of the flexibility to load drugs therein. In the present study, electrospun hybrid scaffolds containing antibiotics were developed to support cellular activities and eliminate potential postoperative inflammation and infection. As a model drug, levofloxacin (LFX) was successfully incorporated into pure polyhydroxybutyrate/poly(epsilon-caprolactone) (PHB/PCL) scaffolds and PHB/PCL/sol-gel-derived silica (SGS) scaffolds. The influence of LFX on the morphology, mechanical performance, chemical structure, drug release profile, and antibacterial effect of the scaffolds was thoroughly and comparatively investigated. MG-63 osteoblast-like cell cultivation on both scaffolds certified that LFX inclusion did not impair the biocompatibility. In addition to the favorable cellular proliferation and differentiation, scaffolds containing both LFX and SGS displayed highly increased mineralization content. Therefore, the present multifunctional hybrid scaffolds are promising in tissue engineering applications.
  • Heß, Stefanie; Hiltunen, Teppo; Berendonk, Thomas U.; Kneis, David (2020)
    The horizontal transfer of plasmids is a key mechanism behind the spread of antibiotic resistance in bacteria. So far, transfer rate constants were measured for a variety of plasmids, donors and recipients. The employed strains typically had a long history in laboratories. Existing data are, therefore, not necessarily representative for real-world environments. Moreover, information on the inter-strain variability of plasmid transfer rates is scarce. Using a high-throughput approach, we studied the uptake of RP4 by various Escherichia coli recipients using Serratia marcescens as the donor. The recipient strains were isolated from human-borne sewage and river sediments. The rate constants of plasmid transfer generally followed a log-normal distribution with considerable variance. The rate constants for good and poor recipients (95 and 5% quantile) differed by more than three orders of magnitude. Specifically, the inter-strain variability of the rate constant was large in comparison to alterations induced by low-level antibiotic exposure. We did not find evidence for diverging efficiencies of plasmid uptake between E. coli recipients of different origin. On average, strains isolated from river bottom sediments were equally efficient in the acquisition of RP4 as isolates extracted from sewage. We conclude that E. coli strains persisting in the aquatic environment and those of direct human origin share a similar intrinsic potential for the conjugative uptake of certain plasmids. In view of the large inter-strain variability, we propose to work towards probabilistic modeling of the environmental spread of antibiotic resistance.
  • Cruz, Cristina D; Wrigstedt, Pauli; Moslova, Karina; Iashin, Vladimir; Mäkkylä, Heidi; Ghemtio, Leo; Heikkinen, Sami; Tammela, Päivi; Perea-Buceta, Jesus Enrique (2021)
    N-aryl-oxazolidinones is a prominent family of antimicrobials used for treating infections caused by clinically prevalent Gram-positive bacteria. Recently, boron-containing compounds have displayed intriguing potential in the antibiotic discovery setting. Herein, we report the unprecedented introduction of a boron-containing moiety such as an aryl boronic acid in the external region of the oxazolidinone structure via a chemoselective acyl coupling reaction. As a result, we accessed a series of analogues with a distal aryl boronic pharmacophore on the oxazolidinone scaffold. We identified that a peripheric linear conformation coupled with freedom of rotation and no further substitution on the external aryl boronic ring, an amido linkage with hydrogen bonding character, in addition to a para-relative disposition between boronic group and linker, are the optimal combination of structural features in this series for antimicrobial activity. In comparison to linezolid, the analogue comprising all those features, compound 20b, displayed levels of antimicrobial activity augmented by an eight-fold to a thirty-two-fold against a panel of Gram-positive strains, and a near one hundred-fold against Escherichia coli JW5503, a Gram-negative mutant strain with a defective efflux capability.
  • Kelleher, Meredith A.; Lee, Ji Yeon; Roberts, Victoria; Novak, Christopher M.; Baschat, Ahmet A.; Morgan, Terry K.; Novy, Miles J.; Räsänen, Juha P.; Frias, Antonio E.; Burd, Irina (2020)
    BACKGROUND: Ureaplasma parvum infection is a prevalent cause of intrauterine infection associated with preterm birth, preterm premature rupture of membranes, fetal inflammatory response syndrome, and adverse postnatal sequelae. Elucidation of diagnostic and treatment strategies for infection-associated preterm labor may improve perinatal and long-term outcomes for these cases. OBJECTIVE: This study assessed the effect of intraamniotic Ureaplasma infection on fetal hemodynamic and cardiac function and the effect of maternal antibiotic treatment on these outcomes. STUDY DESIGN: Chronically catheterized pregnant rhesus monkeys were assigned to control (n=6), intraamniotic inoculation with Ureaplasma parvum (107 colony-forming units/mL, n=15), and intraamniotic infection plus azithromycin treatment (12.5 mg/kg twice a day intravenously, n=8) groups. At approximately 135 days' gestation (term=165 days), pulsed and color Doppler ultrasonography was used to obtain measurements of fetal hemodynamics (pulsatility index of umbilical artery, ductus venosus, descending aorta, ductus arteriosus, aortic isthmus, right pulmonary artery, middle cerebral artery and cerebroplacental ratio, and left and right ventricular cardiac outputs) and cardiac function (ratio of peak early vs late transmitral flow velocity [marker of ventricular function], Tei index [myocardial performance index]). These indices were stratified by amniotic fluid proinflammatory mediator levels and cardiac histology. RESULTS: Umbilical and fetal pulmonary artery vascular impedances were significantly increased in animals from the intraamniotic inoculation with Ureaplasma parvum group (P1.1) than in those with normal blood flow (P1.6, P CONCLUSION: Fetal hemodynamic alterations were associated with intraamniotic Ureaplasma infection and ameliorated after maternal antibiotic treatment. Doppler ultrasonographic measurements merit continuing investigation as a diagnostic method to identify fetal cardiovascular and hemodynamic compromise associated with intrauterine infection or inflammation and in the evaluation of therapeutic interventions or clinical management of preterm labor.
  • Pelkonen, Tuula; Roine, Irmeli; Cruzeiro, Manuel Leite; Pitkäranta, Anne; Kataja, Matti; Peltola, Heikki (2011)
  • El Fellah, Samira; Duporte, Geoffroy; Siren, Heli (2017)
    Steroid hormones, botrydial, and inorganic ions were studied from cold and hot tap water samples with capillary electrophoresis techniques using UV detection. Identification of the steroids and botrydial was made with ultra-high -performance liquid chromatography (UHPLC) coupled to electrospray ionization orbitrap high-resolution mass spectrometry. Solid phase extraction with nonpolar and ion-exchange sorbents was needed to enrich the compounds for CE and UHPLC studies. The steroids identified from the drinking water samples were estradiol glucoside, androstenedione, testosterone, and progesterone. However, only progesterone could be quantified in both cold and hot tap water samples from Helsinki households. Its concentration varied from 0.031 ng/L to 0.135 ng/L and from 0.054 ng/L to 0.191 ng/L, respectively. Chloride and nitrate amounts were 25 mg/L. Calcium, potassium, magnesium, and sodium were 20, 1, 1, and 17 mg/L at the highest, respectively. Copper, iron, sulphate, and ammonium were below the methods concentration limits. Botrydial from Botrytis cinerea mould was identified in all drinking waters. In both cold and hot tap waters its concentration was 861-3900% higher than in a drilled well water that was also used as the household tap water. The mould was also confirmed by identification of its metabolite abscisic acid. (C) 2017 Elsevier B.V. All rights reserved.
  • Aly, Ashraf A.; El-Sheref, Essmat M.; Mourad, Aboul-Fetouh E.; Brown, Alan B.; Bräse, Stefan; Bakheet, Momtaz E. M.; Nieger, Martin (2018)
    Quinoline-2,4-diones reacted with 2-(2-oxo-1,2-dihydroindol-3-ylidene)malononitrile in pyridine to give 2'-amino-2,5'-dioxo-5',6'-dihydrospiro(indoline-3,4'-pyrano[3,2-c]quinoline)-3'-carbonitriles in good to excellent yields. The structures of all new products were proven using one- and two-dimensional NMR, IR, and mass spectral data, and in five cases X-ray structural analyses. The possible mechanism for the reaction is also discussed. [GRAPHICS] .
  • Yun, Jinhyeon; Olkkola, Satu; Hänninen, Marja-Liisa; Oliviero, Claudio; Heinonen, Mari (2017)
    This study investigated the effects of a single amoxicillin treatment of newborn piglets on the prevalence of hernias and abscesses until the age of nine weeks. We also studied whether the treatment was associated with growth and mortality, the need for treatment of other diseases, the proportions of ampicillin resistant coliforms and antimicrobial resistance patterns of intestinal Escherichia coli (E. coli). A total of 7156 piglets, from approximately 480 litters, were divided into two treatment groups: ANT (N = 3661) and CON (N = 3495), where piglets were treated with or without a single intramuscular injection of 75 mg amoxicillin one day after birth, respectively. The umbilical and inguinal areas of weaned pigs were palpated at four and nine weeks of age. At the same time, altogether 124 pigs with hernias or abscesses and 820 non -defective pigs from three pens per batch were weighed individually. Mortality and the need to treat piglets for other diseases were recorded. Piglet faecal samples were collected from three areas of the floors of each pen at four weeks of age. The prevalence of umbilical hernias or abscesses did not differ between the groups at four weeks of age, but it was higher in the CON group than in the ANT group at nine weeks of age (2.3% vs. 0.7%, P
  • Yang, Weifeng; Wei, Qing; Tong, Qian; Cui, Kaiyu; He, Gaiying; Lin, Longfei; Ma, Lvyan Z.; Cornelis, Pierre; Wang, Yi (2020)
    Pseudomonas aeruginosa is an opportunistic pathogen that can infect a wide variety of hosts including humans, plants, and animals. The production of virulence factors is the determinant of the infection paradigm and is under orchestrated regulation via cell-to-cell communication process called quorum sensing (QS). To disable QS circuits and prevent bacterial infections, a large battery of anti-QS agents, particularly from traditional Chinese medicine have been developed. Here, we used P. aeruginosa as a model microorganism to investigate the effect of traditional Chinese medicine Tanreqing (TRQ) formula on bacterial pathogenicity. Phenotypic analysis showed that TRQ treatment could completely inhibit the production of phenazine pyocyanin and moderately inhibit the production of virulence factors such as rhamnolipids, elastase, and alkaline protease. Further transcriptomic analyses revealed that TRQ treatment could significantly attenuate the expression of QS-regulated genes in P. aeruginosa and TRQ-treated P. aeruginosa regulon shared a large overlap with QS regulon. Component contribution to QS inhibition shed light on the indispensable role of all five components in TRQ formula. Further genetic analysis indicated that upstream regulators of QS systems, including two-component systems GacS/GacA and PprA/PprB, were both inhibited by TRQ treatment. Finally, our TRQ formula could efficiently protect Caenorhabditis elegans from killing by P. aeruginosa. Altogether, we have proved TRQ formula as an effective and specific agent to attenuate bacterial virulence and combat bacterial infections.