Is Only Clarithromycin Susceptibility Important for the Successful Eradication of Helicobacter pylori?

Kim, Young Min; Lee, Kyoung Hwa; Kim, Joo Hang; Park, Soon Young; Song, Young Goo; Jeon, Soo-Young; Park, Hyojin

doi:10.3390/antibiotics9090589

Cited by 6 publications

(10 citation statements)

References 37 publications

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“…A total of 31 studies reported data on therapeutic outcomes [ 31 - 61 ]. Of these, 19 studies compared the cure rates between culture-tailored and empiric therapies [ 31 - 42 , 52 - 58 ], whilst only the cure rates of tailored therapies were reported in the remaining 12 studies [ 43 - 51 , 59 - 61 ].…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, the attempt to guide first-line therapy for H. pylori failed in 1 of every 5 infected patients. On the other hand, when the culture was attempted in unselected naïve patients who underwent upper endoscopy, the antibiotic susceptibility testing was achieved in only 247 (13.3%) of 1862 cases [ 59 ]. Based on all these observations, tailoring first-line therapy seems to be impractical in clinical practice.…”

Section: Discussionmentioning

confidence: 99%

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Culture-based antibiotic susceptibility testing for Helicobacter pylori infection: a systematic review

Francesco¹

2022

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Background Primary antibiotic resistance in Helicobacter pylori ( H. pylori ) strains is increasing worldwide, affecting therapy success. The use of therapies tailored on susceptibility pre-testing at culture has been proposed, but data are still conflicting. Method We performed a systematic review to evaluate the role of a culture-based therapeutic approach for H. pylori treatment, taking into account the sensitivity of culture and the success rates achieved with tailored therapies in different therapeutic steps. Results We analyzed data from 51 studies. Overall, H. pylori strains were isolated in 80.7% of 7889 patients, the success rates being 78.1%, 77.5%, 86.3% and 86.6%, before first-, second-, third-line or more therapies, respectively. In comparative studies, the infection was cured in 89.9% of 2052 patients treated with tailored therapies, and in 77.6% of 2516 patients receiving empiric therapy (P<0.001). However, in the subanalysis, the tailored approach achieved optimal eradication rates (>90%) only when it was applied before first- and second-line therapies, but not before third-line or more attempts (<80%). Moreover, no significant difference emerged between the 2 approaches when data from only the most recent (last 5 years) studies were considered, as well as in those performed in Western populations. Conclusions The attempt to achieve antibiotic susceptibility testing before treatment failed in 20% of infected patients managed in dedicated laboratories. Culture-tailored therapies administered after 2 or more therapies achieved suboptimal eradication rates. The role of bacterial culture in patients whose therapeutic management failed to eradicate H. pylori probably needs to be corroborated by further data.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Culture-based antibiotic susceptibility testing for Helicobacter pylori infection: a systematic review

Francesco¹

2022

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“…In this approach, the cellular uptake is quantified by measuring the reduction of the inhibitor concentration in the external culture medium, and numerous detection methods were shown to be suitable: LC-MS and UV absorption, as well as the inhibition of the target enzyme. The method has been confirmed using metronidazole, an antibiotic used in H. pylori therapies (e.g., Min Kim et al, 2020;Olmedo et al 2020).…”

Section: Discussionmentioning

confidence: 95%

“…Hadacidin is a structural analogue of one of the AdSS substrates, aspartate, and is a potent inhibitor of this enzyme (Iancu et al 2006;Bubić et al 2018). Metronidazole is an antibiotic efficiently used in therapy against H. pylori (e.g., Min Kim et al;Olmedo et al 2020), and it is used in this study as a positive control of the cellular uptake 1 3…”

Section: Methodsmentioning

confidence: 99%

A comprehensive method for determining cellular uptake of purine nucleoside phosphorylase and adenylosuccinate synthetase inhibitors by H. pylori

Wojtyś

Jaźwiec

Kazazić

et al. 2021

Appl Microbiol Biotechnol

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Due to the growing number of Helicobacter pylori strains resistant to currently available antibiotics, there is an urgent need to design new drugs utilizing different molecular mechanisms than those that have been used up to now. Enzymes of the purine salvage pathway are possible targets of such new antibiotics because H. pylori is not able to synthetize purine nucleotides de novo. The bacterium’s recovery of purines and purine nucleotides from the environment is the only source of these essential DNA and RNA building blocks. We have identified formycins and hadacidin as potent inhibitors of purine nucleoside phosphorylase (PNP) and adenylosuccinate synthetase (AdSS) from H. pylori — two key enzymes of the purine salvage pathway. However, we have found that these compounds are not effective in H. pylori cell cultures. To address this issue, we have developed a universal comprehensive method for assessing H. pylori cell penetration by drug candidates, with three alternative detection assays. These include liquid chromatography tandem mass spectrometry, UV absorption, and inhibition of the target enzyme by the tested compound. Using this approach, we have shown that cellular uptake by H. pylori of formycins and hadacidin is very poor, which reveals why their in vitro inhibition of PNP and AdSS and their effect on H. pylori cell cultures are so different. The cell penetration assessment method developed here will be extremely useful for validating the cellular uptake of other drug candidates, facilitating the design of new potent therapeutic agents against H. pylori. Key points • A method for assessing H. pylori cells penetration by drug candidates is described. • Three alternative detection assays that complement each other can be used. • The method may be adapted for other bacteria as well.

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“…The success rate of culture was evaluated in different settings of clinical practice, from before first-line therapy to following more treatment failures. In a large Korean study, where the prevalence of H. pylori infection in the general population is high, antibiotic susceptibility testing was achieved in only 247 (13.3%) of 1862 unselected naïve patients undergoing upper endoscopy in whom bacterial culture was attempted [ 23 ]. This would mean that bacterial culture was useless in as many as 9 of every 10 cases who underwent upper endoscopy.…”

Section: Introductionmentioning

confidence: 99%

Helicobacter pylori culture: from bench to bedside

Zullo¹

2022

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Helicobacter pylori ( H. pylori ) infection is a widespread infection that causes various gastroduodenal diseases and some extraintestinal disorders. Curing this infection remains challenging for clinicians, mainly because of bacterial resistance towards the few available antibiotics. Therefore, as for other infectious diseases, therapeutic approaches should be opportunely designed using the principles of antimicrobial stewardship. Theoretically, only susceptibility-based antimicrobial therapy should be considered as appropriate for treating this infection. Unfortunately, H. pylori owns some particular characteristics that make the infection slightly peculiar. More specifically, it is “fastidious” about growing in culture, and its isolation is not easily achieved, even in dedicated laboratories that, to make matters worse, are only scantily spread among countries. We examined the pros and cons of bacterial culture for antibiotic susceptibility testing before different therapy lines, and its applicability in the real clinical life.

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Is Only Clarithromycin Susceptibility Important for the Successful Eradication of Helicobacter pylori?

Cited by 6 publications

References 37 publications

Culture-based antibiotic susceptibility testing for Helicobacter pylori infection: a systematic review

Culture-based antibiotic susceptibility testing for Helicobacter pylori infection: a systematic review

A comprehensive method for determining cellular uptake of purine nucleoside phosphorylase and adenylosuccinate synthetase inhibitors by H. pylori

Helicobacter pylori culture: from bench to bedside

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