Background
Vonoprazan is a novel gastric acid suppressant that is applied in Japan to treat gastric diseases including Helicobacter pylori (H. pylori) infection. This meta‐analysis aimed to summarize ...the ability of vonoprazan to eradicate clarithromycin‐susceptible and clarithromycin‐resistant H. pylori strains.
Materials and Methods
A systematic search was performed using PubMed, EMBASE, Web of Science, and Cochrane Library. Studies were included if they evaluated eradication rates of vonoprazan‐based and conventional PPI‐based triple therapies and checked for clarithromycin susceptibility of H. pylori.
Results
We identified 5 studies including a total of 1599 patients containing data regarding H. pylori with clarithromycin susceptibility. Among those infected with clarithromycin‐susceptible H. pylori, eradication rates for vonoprazan‐based and conventional PPI‐based therapies did not significantly differ in either the randomized (RCT; pooled eradication rates, 95.4% vs 92.8%; pooled odds ratio OR, 1.63; 95% confidence intervals CI, 0.74‐3.61; P = .225) and nonrandomized (NRCT; pooled eradication rates, 92.9% vs 86.2%; OR, 4.58; 95% CI, 0.67‐31.45; P = .122) controlled trials. However, vonoprazan‐based triple therapy was significantly superiority to PPI‐based therapy for patients with clarithromycin‐resistant strains in both RCT (pooled eradication rates, 82.0% vs 40.0%; OR, 6.83; 95% CI, 3.63‐12.86; P < .0001) and NRCT (pooled eradication rates, 80.8% vs 41.8%; OR, 4.98; 95% CI, 2.47‐10.03; P < .0001).
Conclusions
Vonoprazan‐based and conventional PPI‐based therapies are similarly effective for the eradication of clarithromycin‐susceptible H. pylori strains. Vonoprazan is superior to conventional PPI‐based therapy for the eradication of clarithromycin‐resistant H. pylori strains. However, clarithromycin was misused because the combination of vonoprazan and amoxicillin cures approximately 80% of infections without clarithromycin.
Resistance to clarithromycin (CLA) and levofloxacin (LFX) of
is increasing in severity, and successful eradication is essential. Presently, the eradication success rate has greatly declined, leaving ...a large number of patients with previous treatment histories.
To investigate secondary resistance rates, explore risk factors for antibiotic resistance, and assess the efficacy of susceptibility-guided therapy.
We recruited 154 subjects positive for Urea Breath Test who attended The First Affiliated Hospital of China Medical University between July 2022 and April 2023. Participants underwent a string test after an overnight fast. The gastric juice was obtained and transferred to vials containing storage solution. Subsequently, DNA extraction and the specific DNA amplification were performed using quantitative polymerase chain reaction (qPCR). Demographic information was also analyzed as part of the study. Based on these results, the participants were administered susceptibility-guided treatment. Efficacy was compared with that of the empiric treatment group.
A total of 132 individuals tested positive for the
gene by qPCR technique. CLA resistance rate reached a high level of 82.6% (
= 109), LFX resistance rate was 69.7% (
= 92) and dual resistance was 62.1% (
= 82). Gastric symptoms odds ratio (OR) = 2.782; 95% confidence interval (95%CI): 1.076-7.194;
= 0.035 and rural residence (OR = 5.152; 95%CI: 1.407-18.861;
= 0.013) were independent risk factors for secondary resistance to CLA and LFX, respectively. A total of 102 and 100 individuals received susceptibility-guided therapies and empiric treatment, respectively. The antibiotic susceptibility-guided treatment and empiric treatment groups achieved successful eradication rates of 75.5% (77/102) and 59.0% (59/411) by the intention-to-treat (ITT) analysis and 90.6% (77/85) and 70.2% (59/84) by the per-protocol (PP) analysis, respectively. The eradication rates of these two treatment strategies were significantly different in both ITT (
= 0.001) and PP (
= 0.012) analyses.
presented high secondary resistance rates to CLA and LFX. For patients with previous treatment failures, treatments should be guided by antibiotic susceptibility tests or regional antibiotic resistance profile.
Although intermittent, three-times-weekly therapy is recommended for the initial treatment of noncavitary nodular bronchiectatic Mycobacterium avium complex (MAC) lung disease, supporting data are ...limited.
To evaluate the clinical efficacy of intermittent therapy compared with daily therapy for nodular bronchiectatic MAC lung disease.
A retrospective cohort study of 217 patients with treatment-naive noncavitary nodular bronchiectatic MAC lung disease. All patients received either daily (n = 99) or intermittent therapy (n = 118) that included clarithromycin or azithromycin, rifampin, and ethambutol.
Modification of the initial antibiotic therapy occurred more frequently in the daily therapy group than in the intermittent therapy group (46 vs. 21%; P < 0.001); in particular, ethambutol was more frequently discontinued in the daily therapy group than in the intermittent therapy group (24 vs. 1%; P ≤ 0.001). However, the rates of symptomatic improvement, radiographic improvement, and sputum culture conversion were not different between the two groups (daily therapy vs. intermittent therapy: 75 vs. 82%, P = 0.181; 68 vs. 73%, P = 0.402; 76 vs. 67%, P = 0.154, respectively). In addition, the adjusted proportion of sputum culture conversion was similar between the daily therapy (71.3%; 95% confidence interval, 59.1-81.1%) and the intermittent therapy groups (73.6%; 95% confidence interval, 62.9-82.2%; P = 0.785).
These results suggest that intermittent three-times-weekly therapy with a macrolide, rifampin, and ethambutol is a reasonable initial treatment regimen for patients with noncavitary nodular bronchiectatic MAC lung disease. Clinical trial registered with www.clinicaltrials.gov (NCT 00970801).
•Low doses of CLA stimulated M. aeruginosa growth and photosynthetic activity.•CLA modified DOM produced by M. aeruginosa towards higher molecular weight.•CLA promoted the degree of humification of ...DOM produced by M. aeruginosa.
Antibiotics are commonly found in the aquatic environment, which can affect microbial community compositions and activities, and even have potential adverse impacts on human and ecosystem health. The current understanding of the effects of antibiotics on microalgae growth and algal dissolved organic matter (DOM) remains indistinct. To understand the toxic effects of antibiotics on the microalgae, Microcystis aeruginosa was exposed to clarithromycin (CLA) in this study. Cell density determination, chlorophyll content determination, and organic spectrum analysis were conducted to show the effect of CLA exposure on the growth, photosynthetic activity, and organic metabolic processes of Microcystis aeruginosa. The findings revealed that the physiological status of algae could be significantly influenced by CLA exposure in aquatic environments. Specifically, exposure to 1 μg/L CLA stimulated the growth and photosynthetic activity of algal cells. Conversely, CLA above 10 μg/L led to the inhibition of algal cell growth and photosynthesis. Notably, the inhibitory effects intensified with the increasing concentration of CLA. The molecular weight of DOM produced by Microcystis aeruginosa increased when exposed to CLA. Under the exposure of 60 μg/L CLA, a large number of algal cells ruptured and died, and the intracellular organic matter was released into the algal liquid. This resulted in an increase in high molecular weight substances and soluble microbial-like products in the DOM. Exposure to 1 and 10 μg/L CLA stimulated Microcystis aeruginosa to produce more humic acid-like substances, which may be a defense mechanism against CLA. The results were useful for assessing the effects of antibiotic pollution on the stability of the microalgae population and endogenous DOM characteristics in aquatic ecosystems.
Antibiotics are being increasingly detected in aquatic environments, and their potential ecological risk is of great concern. However, most antibiotic toxicity studies involve single-exposure ...experiments. Herein, we studied the effects and mechanisms of repeated versus single clarithromycin (CLA) exposure on Microcystis aeruginosa. The 96 h effective concentration of CLA was 13.37 μg/L upon single exposure but it reduced to 6.90 μg/L upon repeated exposure. Single-exposure CLA inhibited algal photosynthesis by disrupting energy absorption, dissipation and trapping, reaction center activation, and electron transport, thereby inducing oxidative stress and ultrastructural damage. In addition, CLA upregulated glycolysis, pyruvate metabolism, and the tricarboxylic acid cycle. Repeated exposure caused stronger inhibition of algal growth via altering photosynthetic pigments, reaction center subunits biosynthesis, and electron transport, thereby inducing more substantial oxidative damage. Furthermore, repeated exposure reduced carbohydrate utilization by blocking the pentose phosphate pathway, consequently altering the characteristics of extracellular polymeric substances and eventually impairing the defense mechanisms of M. aeruginosa. Risk quotients calculated from repeated exposure were higher than 1, indicating significant ecological risks. This study elucidated the strong influence of repeated antibiotic exposure on algae, providing new insight into antibiotic risk assessment.
Background
Emerging evidence shows that the eradication rate of proton pump inhibitor (PPI)-based triple therapy for the first-line treatment of
Helicobacter pylori
(
H. pylori
) has decreased.
Aims
...To clarify the trend of eradication rate of PPI-based triple therapy and to assess the related factors in Korea during the past decade.
Methods
We prospectively prescribed the triple regimen for seven days (PPI + amoxicillin 1.0 g + clarithromycin 500 mg, twice a day) from March 2003 to May 2013 in 2,202
H. pylori
-positive patients. Antibiotic susceptibility tests were performed by the agar dilution method, and the CYP2C19 genotype was determined by the PCR method.
Results
In the past decade, the annual eradication rate showed a decreasing trend in intention-to-treat and per-protocol analyses (
P
= 0.001, both). The antibiotic resistance was increased to amoxicillin (7.2–17.2 %,
P
= 0.003) and clarithromycin (23.2–37.3 %,
P
= 0.010) during the study period. The poor metabolizer genotype of CYP2C19 showed a high eradication rate compared to the extensive metabolizer (86.8 vs. 78.2 %,
P
= 0.035). In addition, age ≥ 50 years, female gender, BMI < 25 kg/m
2
, amoxicillin and/or clarithromycin resistance were associated with treatment failure on univariate analysis. However, on multivariate analysis, clarithromycin resistance was the only significant factor for treatment failure (OR, 12.76; 95 % CI, 5.58–29.18;
P
< 0.001).
Conclusions
An increase in clarithromycin resistance has led to decreased eradication rate of first-line triple therapy, and; hence, a new strategy is needed to improve the eradication rate of
H. pylori
.
Clarithromycin resistance in Mycobacterium abscessus subsp.
,
, and
occurs through induction of
(41) or mutations in
(23S rRNA) genes. Phenotypic detection of clarithromycin resistance is hindered by ...the need for extended incubation as well as co-occurrence of mixed populations of M. abscessus with different susceptibility profiles. We developed a quantitative EvaGreen-based droplet digital PCR (ddPCR) scheme for rapid detection of full-length or truncated
(41) and a probe based ddPCR screening assay for assessment of 23S rRNA
mutational resistance. We tested 100 M. abscessus strains, synthetic mixes with different susceptibility profiles, and 13 positive MGIT samples. Truncated and full-length
(41) genes were detected in 27/100 and 73/100 strains and 4/13 and 9/13 MGIT samples, respectively yielding a sensitivity and specificity of 100%. Clarithromycin resistance mutations in
were detected in 26/100 isolates, i.e., A2058G (18/100), A2058C (7/100), and A2059G (1/100), and in 3/13 MGIT samples, i.e., A2058G (2/13) and A2059G (1/13). A screening assay of
ddPCR (A2058A/A2058G probes) showed 100% sensitivity in detecting the wild type or A2058G mutation as well as identifying samples requiring further testing. Upon inclusion of additional ddPCR assays, we were able to detect A2058C and A2059G clarithromycin resistance-conferring mutations in the
gene. Our ddPCR scheme can differentiate between full-length and truncated
(41) and identify clarithromycin resistance-conferring mutations in the
gene from clinical isolates and positive MGIT samples as well as deconvolute and quantitate mixed populations of M. abscessus with different clarithromycin resistance traits.
The efficacy of triple therapy for Helicobacter pylori infection has dramatically declined over the last decade,largely related to increasing clarithromycin resistance rates.From a microbiological ...standpoint,bismuth quadruple therapy is the ideal replacement since it combines drugs for which resistance does not impair its efficacy.Nonetheless,several obstacles such as availability,complexity or tolerance prevent a general implementation of bismuth quadruple therapy,so nonbismuth quadruple regimens remain the best firstline treatment in clinical practice in many geographical areas.We review the rationale and efficacy of several optimization tools(increasing the length of duration,high-dose acid suppression,probiotics),which have been largely evaluated over the last 5 years to increase the effectiveness of standard triple therapy.Then,we update available evidence on the effectiveness of several non-bismuth quadruple therapies(sequential,concomitant,hybrid,miscellaneous therapy),which have gained interest lately.We also revise evidence on the efficacy of the aforementioned optimization tools for non-bismuth quadruples schemes and,finally we provide a novel regionalized therapeutic algorithm,based on novel formulas recently developed for predicting the outcome of non-bismuth quadruple regimens,upon local antibiotic resistance rates.
Purpose
Ilaprazole, the latest proton pump inhibitor, can be used with clarithromycin and amoxicillin as a triple therapy regimen for eradicating
Helicobacter pylori
. The aim of this study was to ...evaluate pharmacokinetic drug interactions and safety profiles after coadministration of clarithromycin, amoxicillin, and ilaprazole.
Methods
A randomised, open-label, one-way crossover, two parallel sequences study was conducted in 32 healthy subjects. In part 1, the subjects received a single dose of ilaprazole 10 mg in period 1 and clarithromycin 500 mg and amoxicillin 1000 mg twice daily for 6 days in period 2. In part 2, the subjects received clarithromycin 500 mg and amoxicillin 1000 mg once in period 1 and ilaprazole 10 mg twice daily for 6 days in period 2. In both sequences, the three drugs were coadministrated once on day 5 in period 2. Pharmacokinetic evaluations of ilaprazole (part 1), and clarithromycin and amoxicillin (part 2) were conducted.
Results
Twenty-eight subjects completed the study. For ilaprazole, the peak concentration (C
max
) slightly decreased from 479 (ilaprazole alone) to 446 ng/mL (triple therapy) Geometric least square mean ratio (90% confidence interval), 0.93 (0.70–1.22). The area under the concentration-time curve from 0 h to the last measurable concentration (AUC
last
) slightly increased from 3301 to 3538 μg·h/mL 1.07 (0.85–1.35). For clarithromycin, the C
max
slightly decreased from 1.87 to 1.72 μg/mL 0.90 (0.70–1.15), and AUC
last
slightly increased from 14.6 to 16.5 μg·h/mL 1.09 (0.87–1.37). For amoxicillin, the C
max
slightly decreased from 9.37 to 8.14 μg/mL 0.86 (0.74–1.01), and AUC
last
slightly decreased from 27.9 to 26.7 μg·h/mL 0.98 (0.83–1.16). These changes in the PK parameters of each drug were not statistically significant.
Conclusions
The coadministration of ilaprazole, clarithromycin, and amoxicillin was tolerable and did not cause a significant PK drug interaction. Thus, a triple therapy regimen comprising ilaprazole, clarithromycin, and amoxicillin may be an option for the eradication of
H. pylori
.
Clinicaltrials.gov
number
: NCT02998437.
Background: Bovine lactoferrin BLF is a glycoprotein with antiviral, antibacterial, and antifungal activities. It is present in mucosal secretions such as saliva, tears, and seminal fluid. Due to its ...antibacterial properties, BLF may enhance the eradication rate of H. pylori when used in combination with traditional triple therapy.Aim of the work: To evaluate the impact of bovine lactoferrin when added to triple therapy for H. pylori eradication in Egyptian individuals. Patients and Methods: This randomized controlled comparative research was conducted at the Outpatient Clinic of the Hepatology and Gastroenterology Department in Nasser Institute Hospital. The study involved 200 individuals with a positive H. pylori antigen in stool, divided into four groups; Group A: Fifty individuals received clarithromycin-based triple therapy Clarithromycin 500 mg – amoxicillin 1 gm – p.p.i 20 mg twice daily for two weeks, Group B: Fifty individuals received levofloxacin-based triple therapy Levofloxacin 500 mg once daily – amoxicillin 1 gm twice daily – p.p.i 20 mg twice daily for two weeks, Group C: Fifty individuals received clarithromycin-based triple therapy with lactoferrin 100 mg twice daily for two weeks, and Group D: Fifty individuals received levofloxacin-based triple therapy with lactoferrin 100 mg twice daily for two weeks. H. pylori stool antigen tests were performed before and after treatment in all groups to assess treatment response.Results: Adding 200 mg of BLF potentiates the effect of clarithromycin-based triple therapy and levofloxacin-based triple therapy on H. pylori eradication rate, increasing the treatment response from 70% to 90% and from 76% to 96% respectively.Conclusion: Bovine lactoferrin has the potential to play a role when added to triple therapy in the eradication of Helicobacter pylori.
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