scholarly journals In Vitro Activity of 3-Bromopyruvate, an Anticancer Compound, Against Antibiotic-Susceptible and Antibiotic-Resistant Helicobacter pylori Strains

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 229 ◽  
Author(s):  
Paweł Krzyżek ◽  
Roman Franiczek ◽  
Barbara Krzyżanowska ◽  
Łukasz Łaczmański ◽  
Paweł Migdał ◽  
...  

Helicobacter pylori (H. pylori) is a bacterium capable of inducing chronic active gastritis, which in some people, develops into gastric cancers. One of the substances that may be useful in the eradication of this microorganism is 3-Bromopyruvate (3-BP), an anticancer compound with antimicrobial properties. The aim of this article was to determine the activity of 3-BP against antibiotic-susceptible and antibiotic-resistant H. pylori strains. The antimicrobial activity was determined using a disk-diffusion method, broth microdilution method, time-killing assay, and checkerboard assay. The research was extended by observations using light, fluorescence, and scanning electron microscopy. The growth inhibition zones produced by 2 mg/disk with 3-BP counted for 16–32.5 mm. The minimal inhibitory concentrations (MICs) ranged from 32 to 128 μg/mL, while the minimal bactericidal concentrations (MBCs) for all tested strains had values of 128 μg/mL. The time-killing assay demonstrated the concentration-dependent and time-dependent bactericidal activity of 3-BP. The decrease in culturability below the detection threshold (<100 CFU/mL) was demonstrated after 6 h, 4 h, and 2 h of incubation for MIC, 2× MIC, and 4× MIC, respectively. Bacteria treated with 3-BP had a several times reduced mean green/red fluorescence ratio compared to the control samples, suggesting bactericidal activity, which was independent from an induction of coccoid forms. The checkerboard assay showed the existence of a synergistic/additive interaction of 3-BP with amoxicillin, tetracycline, and clarithromycin. Based on the presented results, it is suggested that 3-BP may be an interesting anti-H. pylori compound.

Pathogens ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 228 ◽  
Author(s):  
Paweł Krzyżek ◽  
Roman Franiczek ◽  
Barbara Krzyżanowska ◽  
Łukasz Łaczmański ◽  
Paweł Migdał ◽  
...  

Antibiotic resistance of Helicobacter pylori, a spiral bacterium associated with gastric diseases, is a topic that has been intensively discussed in last decades. Recent discoveries indicate promising antimicrobial and antibiotic-potentiating properties of sertraline (SER), an antidepressant substance. The aim of the study, therefore, was to determine the antibacterial activity of SER in relation to antibiotic-sensitive and antibiotic-resistant H. pylori strains. The antimicrobial tests were performed using a diffusion-disk method, microdilution method, and time-killing assay. The interaction between SER and antibiotics (amoxicillin, clarithromycin, tetracycline, and metronidazole) was determined by using a checkerboard method. In addition, the study was expanded to include observations by light, fluorescence, and scanning electron microscopy. The growth inhibition zones were in the range of 19–37 mm for discs impregnated with 2 mg of SER. The minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) counted for 2–8 µg/mL and 4–8 µg/mL, respectively. The time-killing assay showed the time-dependent and concentration-dependent bactericidal activity of SER. Bacteria exposed to MBCs (but not sub-MICs and MICs ≠ MBCs) underwent morphological transformation into coccoid forms. This mechanism, however, was not protective because these cells after a 24-h incubation had a several-fold reduced green/red fluorescence ratio compared to the control. Using the checkerboard assay, a synergistic/additive interaction of SER with all four antibiotics tested was demonstrated. These results indicate that SER may be a promising anti-H. pylori compound.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Laure Brigitte Kouitcheu Mabeku ◽  
Bertrand Eyoum Bille ◽  
Cromwell Tepap Zemnou ◽  
Lionel Danny Tali Nguefack ◽  
Hubert Leundji

Abstract Background Antibiotic resistance is a leading cause of treatment failure in Helicobacter pylori infection. In Africa, there are very little data concerning the susceptibility of Helicobacter pylori isolates to antibiotics. The purpose of this study was to evaluate the resistance prevalence of Helicobacter pylori strains circulating in Cameroon, and to assess overexpression of efflux pump as a possible multi-drug resistance mechanisms. Methods A total of 140 H. pylori isolates were recovered from gastric biopsies of dyspeptic patients in two reference hospitals in Cameroon and analyzed for their antimicrobial susceptibility to amoxicillin, co-amoxiclav, ampicillin, penicillin, imipenem, metronidazole, rifabutin, erythromycin, clarithromycin, azithromycin, levofloxacin, ciprofloxacin, norfloxacin, tetracycline, doxycycline and minocycline. Antibiotic sensitivity was tested by disk diffusion method. Phe-Arg-naphthylamide (PAßN) was used as efflux pump inhibitor. INT broth microdilution method in supplemented Brain Heart Infusion broth was used to determine the MIC of ampicillin, amoxicillin, metronidazole, erythromycin, clarithromycin and doxycycline in the absence and the presence of PAßN against 32 selected MDR isolates. Results Overall H. pylori resistance rate was 100% to ampicillin, penicillin and co-amoxiclav; 97.14% to amoxicillin, 97.85% to metronidazole, 47.85% to erythromycin, 13.57% to clarithromycin; 5, 2.86 and 0.71% to doxycycline, tetracycline and minocycline respectively. No resistance to azithromycin, rifabutin, imipenem, ciprofloxacin, norfloxacin and levofloxacin was detected among H. pylori isolates. Seventy percent (70%) of the tested isolates elicited a multiple drugs resistance pattern; 42.57% double, 15.71% triple and 5.71% quadruple drugs resistance. Metronidazole and amoxicillin were more concerned with double resistance pattern (86.76%). The spectrum of activity recorded with metronidazole, doxycycline, clarithromycin and erythromycin ranged from 0 to 100% in the absence to the presence of PAßN against the tested MDR isolates. An 8 to 128-fold increase in potency was also noticed with these antibiotics in the presence of PAßN. Conclusion With regard to the high resistance rate to both amoxicillin and metronidazole, these drugs should be avoided as components of triple therapy in our milieu. In contrast, ciprofloxacin, norfloxacin, levofloxacin and tetracyclines could be used to achieve a better eradication rate and to reduce the risk of selection of H. pylori resistant strains.


2020 ◽  
Vol 92 (8) ◽  
pp. 24-28
Author(s):  
I. V. Maev ◽  
D. N. Andreev ◽  
V. M. Govorun ◽  
E. N. Ilina ◽  
Yu. A. Kucheryavyy ◽  
...  

Aim. Determine the primary antibiotic resistance of Helicobacter pylori (H. pylori) strains isolated from patients living in the European part of the Russian Federation. Materials and methods. As part of a clinical laboratory study, from 2015 to 2018, 27 gastrobiopsy samples obtained from H. pylori-infected patients were analyzed. H. pylori infection was verified using a rapid urease test or a 13C-urea breath test. The values of the minimum inhibitory concentration (MIC) of antibiotics were determined by the diffusion method using E-test strips (BioMerieux, France) according to the recommendations of the manufacturer. The sensitivity of the isolates was determined for 6 antibacterial drugs (amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline, rifampicin). Results. According to the data obtained, resistance to amoxicillin was 0%, clarithromycin 11.1%, metronidazole 59.3%, levofloxacin 3.7%, tetracycline 0%, and rifampicin 14.8%. Dual resistance to clarithromycin and metronidazole was recorded in two isolates (7.4%). Conclusion. Thus, the first results of the evaluation of H. pylori antibiotic resistance in the European part of the Russian Federation indicate a low resistance of the microorganism to clarithromycin and quite high to metronidazole.


2018 ◽  
Vol 13 (7) ◽  
pp. 1934578X1801300 ◽  
Author(s):  
Subrat Kumar Bhattamisra ◽  
Chew Hui Kuean ◽  
Lee Boon Chieh ◽  
Vivian Lee Yean Yan ◽  
Chin Koh Lee ◽  
...  

The antibacterial activity of geraniol and its effect in combination with ampicillin, amoxicillin and clarithromycin against Staphylococcus aureus, Escherichia coli and Helicobacter pylori was tested. The minimum inhibitory concentrations (MICs) and combinatory effects of geraniol against the bacteria were assessed by using the modified broth microdilution and checkerboard assay, respectively. The combinatory effect is expressed as fractional inhibitory concentration index (FICI). The MIC of geraniol against S. aureus, E. coli and H. pylori was found to be 11200, 5600, and 7325 μg/mL, respectively. A significant synergistic effect was observed with geraniol and ampicillin against S. aureus with FICI in the range 0.19 to 0.32. Geraniol and ampicillin exhibited a partial synergistic effect against E. coli. A similar effect was observed with geraniol and clarithromycin against S. aureus. A partial synergistic effect was observed with clarithromycin and geraniol against H. pylori with the FICI value in the range 0.86 to 0.89. An additive effect was observed with geraniol and amoxicillin combination against H. pylori. However, the amoxicillin and clarithromycin dose was reduced by thirty-two fold when combined with geraniol against H. pylori. The anti- H. pylori effect of geraniol with clarithromycin and amoxicillin could be of potential interest in the treatment of H. pylori infection and associated ulcers in humans. Further, geraniol, in combination with other antibiotics, has substantial therapeutic potential against S. aureus and E.coli infection.


2012 ◽  
Vol 67 (3-4) ◽  
pp. 172-180 ◽  
Author(s):  
Somayeh Shahani ◽  
Hamid R. Monsef-Esfahani ◽  
Soodabeh Saeidnia ◽  
Parastoo Saniee ◽  
Farideh Siavoshi ◽  
...  

Geum iranicum Khatamsaz, belonging to the Rosaceae family, is an endemic plant of Iran. The methanol extract of the roots of this plant showed signifi cant activity against one of the clinical isolates of Helicobacter pylori which was resistant to metronidazole. The aim of this study was the isolation and evaluation of the major compounds of G. iranicum effective against H. pylori. The compounds were isolated using various chromatographic methods and identifi ed by spectroscopic data (1H and 13C NMR, HMQC, HMBC, EI-MS). An antimicrobial susceptibility test was performed employing the disk diffusion method against clinical isolates of H. pylori and a micro dilution method against several Gram-positive and Gram-negative bacteria; additionally the inhibition zone diameters (IZD) and minimum inhibitory concentrations (MIC) values were recorded. Nine compounds were isolated: two triterpenoids, uvaol and niga-ichigoside F1, three sterols, β-sitosterol, β-sitosteryl acetate, and β-sitosteryl linoleate, one phenyl propanoid, eugenol, one phenolic glycoside, gein, one fl avanol, (+)-catechin, and sucrose. The aqueous fraction, obtained by partitioning the MeOH extract with water and chloroform, was the most effective fraction of the extract against all clinical isolates of H. pylori. Further investigation of the isolated compounds showed that eugenol was effective against H. pylori but gein, diglycosidic eugenol, did not exhibit any activity against H. pylori. The subfraction D4 was the effective fraction which contained tannins. It appeared that tannins were probably the active compounds responsible for the anti-H. pylori activity of G. iranicum. The aqueous fraction showed a moderate inhibitory activity against both Gram-positive and Gram-negative bacteria. The MIC values indicated that Gram-positive bacteria including Staphylococcus aureus, Staphylococcus epidermidis, and Bacillus subtilis are more susceptible than Gram-neagative bacteria including Escherichia coli and Pseudomonas aeruginosa.


2006 ◽  
Vol 50 (9) ◽  
pp. 3062-3069 ◽  
Author(s):  
Osamu Kamoda ◽  
Kinsei Anzai ◽  
Jun-ichi Mizoguchi ◽  
Masatoshi Shiojiri ◽  
Toshiharu Yanagi ◽  
...  

ABSTRACT Due to concerns about the current therapeutic modalities for Helicobacter pylori infection, e.g., the increased emergence of drug-resistant strains and the adverse reactions of drugs currently administered, there is a need to develop an anti-H. pylori agent with higher efficacy and less toxicity. The antibacterial activity of TG44, an anti-H. pylori agent with a novel structural formula, against 54 clinical isolates of H. pylori was examined and compared with those of amoxicillin (AMX), clarithromycin (CLR), and metronidazole (MNZ). Consequently, TG44 inhibited the growth of H. pylori in an MIC range of 0.0625 to 1 μg/ml. The MIC ranges of AMX, CLR, and MNZ were 0.0078 to 8 μg/ml, 0.0156 to 64 μg/ml, and 2 to 128 μg/ml, respectively. The antibacterial activity of TG44 against AMX-, CLR-, and MNZ-resistant strains was nearly comparable to that against drug-susceptible ones. In a pH range of 3 to 7, TG44 at 3.13 to 12.5 μg/ml exhibited potent bactericidal activity against H. pylori in the stationary phase of growth as early as 1 h after treatment began, in contrast to AMX, which showed no bactericidal activity at concentrations of up to 50 μg/ml at the same time point of treatment. TG44 at 25 μg/ml exhibited no antibacterial activity against 13 strains of aerobic bacteria, suggesting that its antibacterial activity against H. pylori is potent and highly specific. The present study indicated that TG44 possesses antibacterial activity which manifests quickly and is potentially useful for eradicating not only the antibiotic-susceptible but also the antibiotic-resistant strains of H. pylori by monotherapy.


2000 ◽  
Vol 14 (10) ◽  
pp. 879-882 ◽  
Author(s):  
Carlo A Fallone

BACKGROUND: The rate ofHelicobacter pyloriresistance to antibiotics determines the cure rate of treatment regimens containing such antibiotics. AIMS: To review the literature to determine the rates ofH pyloriresistance to metronidazole and clarithromycin in Canada, and whether these rates vary in different regions of Canada.METHODS: The literature was reviewed extensively for the prevalence of antibiotic-resistantH pyloriin Canada by searching MEDLINE from January 1980 to May 1999, as well as abstracts of the American Gastroenterology Association Digestive Disease Week, Canadian Digestive Disease Week and The EuropeanH pyloriStudy Group Meetings from January 1995 to May 1999.RESULTS: Eleven studies that estimatedH pyloriresistance to metronidazole resistance and nine that estimated resistance to clarithromycin in Canada were identified. Rates of resistance for metronidazole and clarithromycin varied from 11% to 48% and 0% to 12%, respectively. Studies that obtained their estimates using the E-test and those that did not clearly exclude patients who had undergone previous attempts atH pylorieradication had higher estimates of resistance, accounting for this variability in results.CONCLUSIONS: The prevalence of primaryH pyloriresistance in Canada appears to be 18% to 22% for metronidazole and less than 4% for clarithromycin. These rates appear to be consistent across the different regions studied in Canada, but many regions have not been studied.


Antibiotics ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 658 ◽  
Author(s):  
Paweł Krzyżek ◽  
Emil Paluch ◽  
Grażyna Gościniak

Helicobacter pylori is a Gram-negative bacterium responsible for the development of gastric diseases. The issue of spreading antibiotic resistance of H. pylori and its limited therapeutic options is an important topic in modern gastroenterology. This phenomenon is greatly associated with a very narrow range of antibiotics used in standard therapies and, as a consequence, an alarmingly high detection of multidrug-resistant H. pylori strains. For this reason, scientists are increasingly focused on the search for new substances that will not only exhibit antibacterial effect against H. pylori, but also potentiate the activity of antibiotics. The aim of the current review is to present scientific reports showing newly discovered or repurposed compounds with an ability to enhance the antimicrobial activity of classically used antibiotics against H. pylori. To gain a broader context in their future application in therapies of H. pylori infections, their antimicrobial properties, such as minimal inhibitory concentrations and minimal bactericidal concentrations, dose- and time-dependent mode of action, and, if characterized, anti-biofilm and/or in vivo activity are further described. The authors of this review hope that this article will encourage the scientific community to expand research on the important issue of synergistic therapies in the context of combating H. pylori infections.


2016 ◽  
pp. 88-93
Author(s):  
Thi Hoai Thai ◽  
Van Huy Tran

Background: H. pylori eradication still remains a challenge to clinicians, especially with the increasing antibiotic-resistant H. pylori. Concomitant therapy showed effective, even in some multiresistant population, but data in Vietnam is still very limited. The study ''Study of Helicobacter pylori eradication with RACM regimen in chronic gastritis patients at Da Nang Hospital from 1/4/2014 to 30/6/2015, is aimed at: (1) Evaluating the results of Helicobacter pylori eradication of Amoxicillin-Clarithromycin-Rabeprazole-Metronidazole therapy for 14 days.(2) Assessing some side effects of this regimen.Method: prospective, consisting of 83 patients examined and treated in Danang hospital from1/ 4/2014 to 30/6/2015, H.pylori was tested by rapid Urease test; H.pylori positive patients received RACM for 14 days. Results: H.pylori eradication rate was 83.1%. H. pylori eradication rates in different locations: antrum 63.8%, higher than corpus (17.4%), antrum and corpus (18.8%), with statistical significance at p<0.05. Common side effects was nausea (27.7%), diarrhea (19.3%). Abdominal pain, lightheadedness, dizziness, insomnia, headache account for low percentage: 8%; 6%; 3,6% and 2.4% respectively. Conclusion: The effect of 14 day RACM regimen for H. pylori eradication was 83.1%, common side effects are nausea (27.7%), diarrhea (19.3%). Key words: chronic gastritis;H. pylori; eradication of H. pylori(ITT); RACM regimen.


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