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The resistance to the antibiotics was lower than expected from patient sample studies, especially for clarithromycin, most probably due to a restrictive prescription policy in the area. Introduction of a test-and-treat strategy in Sweden would only marginally affect the usage of clarithromycin.
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Vonoprazan fumarate (Takecab) is a first-in-class potassium-competitive acid blocker that has been available in the market in Japan since February 2015. Vonoprazan is administered orally at 20 mg once daily for the treatment of gastroduodenal ulcer, at 20 and 10 mg once daily for the treatment and secondary prevention of reflux esophagitis, respectively, at 10 mg once daily for the secondary prevention of low-dose aspirin- or non-steroidal anti-inflammatory drug-induced peptic ulcer, and at 20 mg twice daily in combination with clarithromycin and amoxicillin for the eradication of Helicobacter pylori. It inhibits H(+),K(+)-ATPase activities in a reversible and potassium-competitive manner with a potency of inhibition approximately 350 times higher than the proton pump inhibitor, lansoprazole. Vonoprazan is absorbed rapidly and reaches maximum plasma concentration at 1.5-2.0 h after oral administration. Food has minimal effect on its intestinal absorption. Oral bioavailability in humans remains unknown. The plasma protein binding of vonoprazan is 80% in healthy subjects. It distributes extensively into tissues with a mean apparent volume of distribution of 1050 L. Being a base with pKa of 9.6 and with acid-resistant properties, vonoprazan is highly concentrated in the acidic canaliculi of the gastric parietal cells and elicited an acid suppression effect for longer than 24 h after the administration of 20 mg. The mean apparent terminal half-life of the drug is approximately 7.7 h in healthy adults. Vonoprazan is metabolized to inactive metabolites mainly by cytochrome P450 (CYP)3A4 and to some extent by CYP2B6, CYP2C19, CYP2D6, and SULT2A1. A mass balance study showed that 59 and 8% of the orally administered radioactivity was recovered in urine as metabolites and in an unchanged form, respectively, indicating extensive metabolism. Genetic polymorphism of CYP2C19 may influence drug exposure but only to a clinically insignificant extent (15-29%), according to the population pharmacokinetic study performed in Japanese patients. When vonoprazan was co-administered with clarithromycin, the mean AUC from time 0 to time of the next dose (dosing interval) of vonoprazan and clarithromycin were increased by 1.8 and 1.5 times, respectively, compared with the corresponding control values, indicating mutual metabolic inhibition. The mean area under the curve from time zero to infinity obtained from patients with severe liver and renal dysfunction were elevated by 2.6 and 2.4 times, respectively, compared with healthy subjects, with no significant changes in plasma protein binding. Vonoprazan increases intragastric pH above 4.0 as early as 4 h after an oral dose of 20 mg, and the extensive anti-secretory effect is maintained up to 24 h post-dose. During repeated dosing of 20 mg once daily, the 24-h intragastric pH >4 holding time ratios were 63 and 83 % on days 1 and 7, respectively. Because vonoprazan elicited a more extensive gastric acid suppression than the proton pump inhibitor, lansoprazole, it also gave rise to two to three times greater serum gastrin concentrations as compared with lansoprazole. In pre-approval clinical studies for the treatment of acid-related disorders, mild to moderate adverse drug reactions (mostly constipation or diarrhea) occurred at frequencies of 8-17%. Neither severe liver toxicity nor neuroendocrine tumor has been reported in patients receiving vonoprazan.
We conducted a retrospective prevalence study using data from the RER health care database. Outpatient prescription drug data were reconciled for RER residents who delivered a baby in a hospital between January 1, 2004 and December 31, 2004. Drug data were stratified by trimester of use, pregnancy risk categorization, and anatomical classification.
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Low-dose rabeprazole in combination with amoxicillin and metronidazole is an effective, economical and well-tolerated therapy for the treatment of H. pylori infection in Chinese population.
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Single-nanopores have recently been used to electrically detect a wide range of analytes. Similarly, using electrophysiology, we demonstrate how a system comprised of an ion channel formed by α-hemolysin (α-HL) and single-cyclic γ-cyclodextrin (γ-CD) molecule permits the detection of, and differentiation between three different antibiotics from the β-lactam family. Specifically, histograms of the time between the successive binding events, and the residence time distributions of the antibiotic in the γ-CD molecular adapter vary with the antibiotic type. The results show that the association times of amoxicillin, azlocillin, and ampicillin are τ(on) = 2.1 ± 0.2, 2.2 ± 0.3, and 3.1 ± 0.4 ms, respectively. Interestingly, we found that the residence time of the bulkier and negatively charged azlocillin (τ(off) = 0.008 ± 0.0005 ms) is much less than that of ampicillin (τ(off) = 0.07 ± 0.005 ms) and amoxicillin (τ(off) = 0.1 ± 0.02 ms), even though the γ-CD-α-HL complex is anionic selective. The data were also used to estimate the standard free energy of binding between ampicillin to γ-CDs binding (-12 kJ mol(-1) [corrected]). The difference in association times might be due to γ-CDs-imposed steric hindrance or an energetically more expensive desolvation step for the antibiotics to gain access to the binding site in the CD. We suggest that this technique may be used to detect other analytes used in pharmaceutical applications.
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Antimicrobial treatment of animals may select resistance in Campylobacter to antimicrobial agents belonging to several classes of compounds. We investigated the effect of widely used aminopenicillin therapy on the minimum inhibitory concentration (MIC) levels in porcine Campylobacter coli isolates and investigated the presence of a β-lactamase gene and β-lactamase production. Epidemiological cut-off values (ECOFFs) were applied to detect decreased susceptibility. Fifty-three isolates were obtained from aminopenicillin-treated (ampicillin or amoxicillin) sows and piglets during and up to 3 weeks post-treatment. All isolates had ampicillin MICs below the ECOFF (≤ 8 μg/mL). An additional 63 isolates were sampled before treatment or from other untreated sows and piglets. Of these isolates, four had ampicillin MICs above the ECOFF. All ciprofloxacin MICs were below the ECOFF (≤ 1 μg/mL), except for three isolates from untreated sows and four isolates after aminopenicillin therapy. One isolate originating from an untreated sow had an erythromycin MIC above the ECOFF (> 16 μg/mL). None of the isolates had MICs above the ECOFFs for two or three studied antimicrobials simultaneously. Of the 116 C. coli isolates, 90 (77.6%) isolates carried the bla(OXA-61) β-lactamase gene, and 63 (70.0%) of those produced β-lactamase. The isolates producing β-lactamase had higher ampicillin MICs than those without the bla(OXA-61) gene and production of β-lactamase. Proportion of the bla(OXA-61)-positive C. coli isolates was similar among untreated animals or during and after the treatment. In conclusion, C. coli isolates did not acquire high ampicillin MICs even though aminopenicillins were administered at therapeutic levels for several days. The bla(OXA-61) gene and production of β-lactamase increased ampicillin MICs in C. coli, but the values remained mainly under the ECOFF. We also demonstrated that aminopenicillin therapy did not select simultaneously resistance to the major antimicrobials used in human therapy against campylobacteriosis (i.e., erythromycin and ciprofloxacin).
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Drug-induced thrombocytopenia is a common adverse effect reported in the literature. Typically patients present with a low platelet count with signs and symptoms ranging from bruising to bleeding, and major organ damage. Penicillin-induced thrombocytopenia previously reported in the literature is explained primarily through the hapten-dependent antibody process. The goal of this report is to present a case of an amoxicillin/clavulanic acid-induced thrombocytopenia.
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Nineteen peripheral catheters were positive for microbiologic culture from 14 animals. Twenty organisms were isolated among which Staphylococcus species was the most common. Isolates displayed lower levels of resistance against the antimicrobial agents amoxicillin-clavulanate, cephalosporins and gentamicin than against other agents tested. Major risk factors predisposing to catheter-related colonisation included dextrose infusion, duration of catheter placement, local complications and immunosuppressive diseases or drugs.
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The new E plate serological test kit for H. pylori was useful for distinguishing success from failure 8 weeks after completion of eradication therapy for H. pylori.
A simple, fast, and fully automated FIA-SPE method with UV detection for the preconcentration and determination of the investigated penicillins has been developed. This paper provides adequate procedure for the preconcentration and determination of the studied compounds in pharmaceuticals and milk samples. Penicillins (penicillin G, amoxicillin, and ampicillin) are extracted in a mincolumn packed with methylene blue grafted polyurethane foam (MBGPUF) material. The antibiotics are eluted by hydrochloric acid solution to the flow cell of UV-vis spectrophotometer at 230 nm. The analytes are preconcentrated on the sorbent at pH 8.0-9.5 and sample flow rate 3.0 mL/min. Elution was performed with 200 microL 0.2 mol L(-1) hydrochloric acid at 2 mL min(-1). Sample throughput is 12h(-1) at 120 s preconcentration time. High selectivity of the sorbent for the analytes was achieved at the specified pH range. The enrichment factors achieved are 14, 16, and 11 with 3 sigma detection limits of 12, 15, and 19 ng mL(-1) for penicillin G, amoxicillin and ampicillin, respectively. The method was successfully applied to the determination of these antibiotics in pharmaceutical control and contaminated milk samples with RSD