Dataset Information

Can Aminoglycosides Be Used as a New Treatment for Helicobacter pylori? In vitro Activity of Recently Isolated Helicobacter pylori.

ABSTRACT: BACKGROUND:Smectite can serve as a drug delivery system and gentamicin-intercalated smectite hybrids are expected to supersede the standard therapy for Helicobacter pylori eradication. The aim of this study was to confirm whether the minimum inhibitory concentration (MIC) of aminoglycosides applied as smectite hybrids remained low against recently isolated H. pylori strains. MATERIALS AND METHODS:A total of 140 strains were collected for a minimum period of 3 years. Antimicrobial susceptibility tests were performed, and the MICs of eight antibiotics (amoxicillin, clarithromycin, metronidazole, tetracycline, levofloxacin, gentamicin, netilmicin, and tobramycin) were determined by using the Epsilometer test and following the European Committee on Antimicrobial Susceptibility Testing recommendations. RESULTS:The resistance rate of clarithromycin was high, up to 30.7%, although it is a major antimicrobial agent used in standard therapy. The MIC?? and MIC?? of gentamicin (0.25 mg/L and 0.75 mg/L) and netilmicin (0.19 mg/L and 0.75 mg/L) were lower than other alternative therapies for H. pylori eradication. In clarithromycin-resistant strains, the MIC?? was 0.25 mg/L and the MIC?? was 1 mg/L for gentamicin; for netilmicin, the values were 0.25 mg/L and 0.75 mg/L, respectively. CONCLUSION:Through the use of gentamicin and netilmicin, which have low MICs for H. pylori, aminoglycoside-intercalated smectite hybrids are expected to emerge as a new standard therapy for H. pylori eradication.

SUBMITTER: Lee KH

PROVIDER: S-EPMC6446016 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Can Aminoglycosides Be Used as a New Treatment for <i>Helicobacter pylori</i>? <i>In vitro</i> Activity of Recently Isolated <i>Helicobacter pylori</i>.

Lee Kyoung Hwa KH Park Soon Young SY Jeong Su Jin SJ Jung Da Hyun DH Kim Jie Hyun JH Jeong Seok Hoon SH Kang Il Mo IM Song Young Goo YG

Infection & chemotherapy 20190301 1

<h4>Background</h4>Smectite can serve as a drug delivery system and gentamicin-intercalated smectite hybrids are expected to supersede the standard therapy for <i>Helicobacter pylori</i> eradication. The aim of this study was to confirm whether the minimum inhibitory concentration (MIC) of aminoglycosides applied as smectite hybrids remained low against recently isolated <i>H. pylori</i> strains.<h4>Materials and methods</h4>A total of 140 strains were collected for a minimum period of 3 years. ...[more]

PMID: 30941933

Similar Datasets

Project description:The most evident challenge to treatment of Helicobacter pylori, a bacterium responsible for gastritis, peptic ulcers and gastric cancer, is the increasing rate of resistance to all currently used therapeutic antibiotics. Thus, the development of novel therapies is urgently required. N-geranyl-N'-(2-adamantyl) ethane-1, 2-diamine (SQ109) is an ethylene diamine-based antitubercular drug that is currently in clinical trials for the treatment of tuberculosis (TB). Previous pharmacokinetic studies of SQ109 revealed that persistently high concentrations of SQ109 remain in the stomach 4 hours post oral administration in rats. This finding, combined with the need for new anti-Helicobacter therapies, prompted us to define the in vitro efficacy of SQ109 against H. pylori. Liquid broth micro-dilution was used for susceptibility studies to determine the antimicrobial activity of SQ109 against a total of 6 laboratory strains and 20 clinical isolates of H. pylori; the clinical isolates included a multi-drug resistant strain. All strains tested were susceptible to SQ109 with MIC and MBC ranges of 6-10 µM and 50-60 µM, respectively. SQ109 killing kinetics were concentration- and time-dependent. SQ109 killed H. pylori in 8-10 h at 140 µM (2MBCs) or 4-6 h at 200 µM (~3MBCs). Importantly, though the kinetics of killing were altered, SQ109 retained potent bactericidal activity against H. pylori at low pH. Additionally, SQ109 demonstrated robust thermal stability and was effective at killing slow growing or static bacteria. In fact, pretreatment of cultures with a bacteriostatic concentration of chloramphenicol (Cm) synergized the effects of typically bacteriostatic concentrations of SQ109 to the level of five-logs of bacterial killing. A molar-to-molar comparison of the efficacy of SQ109 as compared to metronidazole (MTZ), amoxicillin (AMX), rifampicin (RIF) and clarithromycin (CLR), revealed that SQ109 was superior to MTZ, AMX and RIF but not to CLR. Finally, the frequency of resistance to SQ109 was low and electron microscopy studies revealed that SQ109 interacted with bacterial inner membrane and cytoplasmic content(s). Collectively, our in vitro data demonstrate that SQ109 is an effective monotherapy against susceptible and multi-drug resistant strains of H. pylori and may be useful alone or in combination with other antibiotics for development as a new class of anti-Helicobacter drugs.

Project description:Gastric problems are often caused by the well-known Helicobacter pylori (H. pylori) bacterium. One of the biggest obstacles to the treatment of H. pylori infections is increasing the antibiotic resistance. During our search for naturally derived anti-H. pylori compounds, six major compounds were isolated from the methylene chloride (CH2Cl2) and ethyl acetate (EtOAc) fractions of Rumex acetosa that showed anti-H. pylori activity. Three anthraquinones and three anthraquinone glucosides were identified as the major chemical constituents of the CH2Cl2 and EtOAc fractions, respectively. The chemical structures were identified to be emodin (1), chrysophanol (2), physcion (3), emodin-8-O-β-d-glucoside (4), chrysophanol-8-O-β-d-glucoside (5), and physcion-8-O-β-d-glucoside (6) by UV, 1H NMR, 13C NMR, and mass spectrometry. Anti-H. pylori activity, including the minimum inhibitory concentration (MIC) value of each compound, was evaluated against two H. pylori strains. All isolates exhibited anti-H. pylori activity with different potencies, with an MIC value ranging between 3.13 and 25 μM. However, some variations were found between the two strains. While compound 5 displayed the most potent antibacterial activity with an MIC50 value of 8.60 μM and an MIC90 value of 15.7 μM against H. pylori strain 51, compound 1 exhibited the most potent inhibitory activity against H. pylori strain 43504. The two compounds also showed moderate urease inhibitory activity, with compound 1 demonstrating activity higher than that of compound 5. Furthermore, a molecular docking study revealed the high binding ability of compounds 1 and 5 to the active site of H. pylori urease. The present study suggests that the six anthraquinones isolated from R. acetosa with the whole parts of this plant may be natural candidates for the treatment of H. pylori infection. Further studies are required to determine the exact mechanism of action and to evaluate safety issues in the human body.

Dataset Information

Can Aminoglycosides Be Used as a New Treatment for Helicobacter pylori? In vitro Activity of Recently Isolated Helicobacter pylori.

Publications

Can Aminoglycosides Be Used as a New Treatment for <i>Helicobacter pylori</i>? <i>In vitro</i> Activity of Recently Isolated <i>Helicobacter pylori</i>.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets