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Background and Aims: This study aimed to evaluate the efficacy and safety of vonoprazan and tetracycline (VT) dual therapy as first-line treatment for Helicobacter pylori infection in patients with penicillin allergy., Methods: In this randomised controlled trial, treatment-naïve adults with H. pylori infection and penicillin allergy were randomised 1:1 to receive either open-label VT dual therapy (vonoprazan 20 mg two times per day+tetracycline 500 mg three times a day) or bismuth quadruple therapy (BQT; lansoprazole 30 mg two times per day+colloidal bismuth 150 mg three times a day+tetracycline 500 mg three times a day+metronidazole 400 mg three times a day) for 14 days. The primary outcome was non-inferiority in eradication rates in the VT dual group compared with the BQT group. Secondary outcomes included assessing adverse effects., Results: 300 patients were randomised. The eradication rates in the VT group and the BQT group were: 92.0% (138/150, 95% CI 86.1% to 95.6%) and 89.3% (134/150, 95% CI 83.0% to 93.6%) in intention-to-treat analysis (difference 2.7%; 95% CI -4.6% to 10.0%; non-inferiority p=0.000); 94.5% (138/146, 95% CI 89.1% to 97.4%) and 93.1% (134/144, 95% CI 87.3% to 96.4%) in modified intention-to-treat analysis (difference 1.5%; 95% CI -4.9% to 8.0%; non-inferiority p=0.001); 95.1% (135/142, 95% CI 89.7% to 97.8%) and 97.7% (128/131, 95% CI 92.9% to 99.4%) in per-protocol analysis (difference 2.6%; 95% CI -2.9% to 8.3%; non-inferiority p=0.000). The treatment-emergent adverse events (TEAEs) were significantly lower in the VT group (14.0% vs 48.0%, p=0.000), with fewer treatment discontinuations due to TEAEs (2.0% vs 8.7%, p=0.010)., Conclusions: VT dual therapy demonstrated efficacy and safety as a first-line treatment for H. pylori infection in the penicillin-allergic population, with comparable efficacy and a lower incidence of TEAEs compared with traditional BQT., Trial Registration Number: ChiCTR2300074693., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Current guidelines recommend bismuth-containing quadruple therapy for patients newly diagnosed with Helicobacter pylori (H. pylori) infection. We aimed to compare the efficacy and safety of tetracycline administered three times daily versus four times daily in bismuth-containing quadruple therapy for first-line treatment of H. pylori infection., Methods: This multicenter, noninferiority, randomized controlled study, conducted in China, recruited treatment-naïve adults with H. pylori infection, randomized 1:1 into two treatment groups to receive either of the following bismuth-containing quadruple therapies: esomeprazole 20 mg twice-daily; bismuth 220 mg twice-daily; amoxicillin 1000 mg twice-daily; and tetracycline 500 mg three times daily (TET-T) versus 500 mg four times daily (TET-F). At least 6 weeks post-treatment, a 13 C-urea breath test was performed to evaluate H. pylori eradication., Results: In total, 406 patients were randomly assigned to the two treatment groups. Intention-to-treat eradication rates were 91.63% (186/203; 95% confidence interval [CI] 87.82%-95.44%) versus 90.15% (183/203; 95% CI 86.05%-94.25%) (p = 0.0005) and per-protocol eradication rates were 95.34% (184/193; 95% CI 92.36%-98.31%) versus 95.72% (179/187; 95% CI 92.82%-98.62%) (p = 0.0002) for the TET-T and TET-F group, respectively. TET-T-treated patients had a lower incidence of adverse effects than TET-F-treated patients (21.61% vs. 31.63%, p = 0.024), with no significant differences in compliance to treatment between the groups., Conclusion: As a first-line therapy for H. pylori infection, the eradication rate of the TET-T therapy was noninferior to that of the TET-F therapy while significantly reducing the incidence of adverse reactions., Trial Registration: ClinicalTrials.gov identifier: NCT05431075., (© 2024 John Wiley & Sons Ltd.)

Background: The optimal dosage of tetracycline remains unclear for Helicobacter pylori eradication. Frequent dosing requirements may decrease patient adherence and increase the incidence of adverse events, potentially reducing treatment efficacy. This study aimed to compare the efficacy of different tetracycline dosages in rescue treatment for H. pylori infection., Methods: A total of 406 patients needing H. pylori rescue treatment were enrolled. Patients were randomized into two groups and received bismuth-containing quadruple therapies as follows: esomeprazole 40 mg twice daily, bismuth 220 mg twice daily, amoxicillin 1000 mg twice daily, and tetracycline 500 mg either three (TET-T group) or four (TET-F group) times daily. At least 6 weeks after treatment completion, a 13 C-urea breath test was performed to evaluate H. pylori eradication., Results: The intention-to-treat (ITT) eradication rates were 91.13% (185/203) and 90.15% (183/203) (p = 0.733), the modified ITT (MITT) eradication rates were 94.87% (185/195) and 95.31% (183/192) (p = 0.841), and the per-protocol (PP) eradication rates were 94.79% (182/192) and 95.21% (179/188) (p = 0.851) in the TET-T group and TET-F group, respectively. The eradication rates for the TET-T group were not inferior to those of the TET-F group in ITT, MITT, and PP analyses. The incidence of adverse effects was significantly lower in the TET-T group than in the TET-F group (23.65% vs. 33.50%, p = 0.028). No significant differences were observed in treatment compliance between the groups., Conclusions: The dose of tetracycline administered three times daily showed comparable efficacy to that administered four times daily, while significantly reducing the incidence of adverse events. The combination of tetracycline and amoxicillin in bismuth-containing quadruple therapy achieved a high eradication rate in H. pylori rescue treatment., (© 2024 John Wiley & Sons Ltd.)

Introduction: We aim to evaluate the efficacy of 2 different 1-week quadruple therapies given back-to-back consecutive therapy in patients with difficult-to-treat Helicobacter pylori infection., Methods: Patients with proven H. pylori infection were recruited after >3 failed standard quadruple eradication. They received consecutive therapy consisting of esomeprazole 40 mg or rabeprazole 20 mg twice daily, amoxicillin 1,000 mg twice daily, tetracycline 500 mg 4 times daily, and furazolidone 100 mg 3 times daily for the first 7 days, followed by colloidal bismuth pectin 200 mg twice daily in place of furazolidone 100 mg for another 7 days. Eradication rates, treatment-emergent adverse events (TEAEs), and compliance were assessed., Results: Sixty-five patients were enrolled. The mean number of previous eradications was 3.6 (range: 3-7). The intention-to-treat and per-protocol eradication rates were 90.8% (59/65) and 95.1% (58/61). In total, 23.4% (15/64) of patients experienced drug-related TEAEs. No serious adverse events were observed. None of the patients required treatment for TEAEs, and 95.3% (61/64) showed good compliance. Overall, 51 patients (78.5%) were with the available antimicrobial susceptibility testing results. The resistance rates to clarithromycin, metronidazole, levofloxacin, and amoxicillin were 60.8% (31/51), 100% (51/51), 70.6% (36/51), and 2.0% (1/51), respectively. No resistance was detected to either furazolidone or tetracycline. However, in 54.9% of patients (28/51), H. pylori was resistant to 3 antibiotics (metronidazole, levofloxacin, and clarithromycin)., Discussion: Consecutive therapy, including amoxicillin, tetracycline, and furazolidone, achieved a good eradication rate (>90%), with desirable compliance and tolerability in difficult-to-treat H. pylori infection., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Encapsulation of probiotic bacteria can enhance their functionality when used in combination with antibiotics for treating intestinal tract infections. The interaction strength of encapsulating shells, however, varies among the encapsulation methods and impacts encapsulation. Here, we compared the protection offered by encapsulating shells with different interaction strengths toward probiotic Bifidobacterium breve against simulated gastric fluid and tetracycline, including protamine-assisted SiO 2 nanoparticle yolk-shell packing (weak interaction across a void), alginate gelation (intermediate interaction due to hydrogen binding), and ZIF-8 mineralization (strong interaction due to coordinate covalent binding). The presence of encapsulating shells was demonstrated using X-ray-photoelectron spectroscopy, particulate microelectrophoresis, and dynamic light scattering. Strong interaction upon ZIF-8 encapsulation caused demonstrable cell wall damage to B. breve and slightly reduced bacterial viability, delaying the growth of encapsulated bacteria. Cell wall damage and reduced viability did not occur upon encapsulation with weakly interacting yolk-shells. Only alginate-hydrogel-based shells yielded protection against simulated gastric acid and tetracycline. Accordingly, only alginate-hydrogel-encapsulated B. breve operated synergistically with tetracycline in killing tetracycline-resistant Escherichia coli adhering to intestinal epithelial layers and maintained surface coverage of transwell membranes by epithelial cell layers and their barrier integrity. This synergy between alginate-hydrogel-encapsulated B. breve and an antibiotic warrants further studies for treating antibiotic-resistant E. coli infections in the gastrointestinal tract.

Purpose: Tegoprazan is a potassium-competitive acid blocker used for gastric acid suppression, which may be used with Helicobacter pylori eradication therapies. The goal of this study was to evaluate the pharmacokinetic interaction between tegoprazan and triple-antibiotic therapy containing metronidazole, tetracycline, and bismuth., Methods: An open-label, 2-cohort, randomized, multiple-dose, crossover study was conducted in healthy subjects. In cohort 1, tegoprazan (100 mg/d) was administered orally with or without triple-antibiotic therapy (1500 mg/d metronidazole, 2000 mg/d tetracycline, and 1200 mg/d bismuth) for 7 days in each period. In cohort 2, triple-antibiotic therapy was administered orally with or without tegoprazan for 7 days in each period. Pharmacokinetic blood samples were collected within 24 h after the last dose. Safety assessments were performed., Findings: Eleven cohort 1 subjects and ten cohort 2 subjects were included in the pharmacokinetic analysis. The AUC τ and C max at steady state geometric mean ratios (90% CIs) were 0.78 (0.73-0.83) and 0.75 (0.68-0.82) for tegoprazan; 0.77 (0.68-0.88) and 0.84 (0.72-0.98) for tegoprazan metabolite M1; 1.03 (0.98-1.08) and 1.08 (0.99-1.18) for metronidazole; 0.63 (0.56-0.70) and 0.64 (0.56-0.74) for tetracycline; and 1.55 (0.99-2.44) and 1.38 (0.72-2.66) for bismuth, respectively. All reported adverse events were mild., Implications: Changes in the tegoprazan, tetracycline, and bismuth pharmacokinetic parameters were detected after concurrent administration. These changes were considered mainly due to the pharmacodynamic effect of tegoprazan. The adverse events were predictable and reported as frequent adverse events during triple-antibiotic therapy. There were no significant differences in safety or tolerability between quadruple therapy, including tegoprazan and triple-antibiotic therapy. ClinicalTrials.gov identifier: NCT04066257., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: There has been resurgence in the use of bismuth quadruple therapy (proton pump inhibitor, bismuth, tetracycline and metronidazole) for treating Helicobacter pylori infection thanks to a three-in-one single-capsule formulation., Objective: To evaluate the effectiveness and safety of the single-capsule bismuth quadruple therapy., Methods: Data were collected in a multicentre, prospective registry of the clinical practice of gastroenterologists on the management of H. pylori infection, where patients were registered at the Asociación Española de Gastroenterologia REDCap database on an electronic case report form until January 2020. Effectiveness by modified intention-to-treat and per-protocol as well as multivariable analysis were performed. Independent factors evaluated were: age, gender, indication, compliance, proton pump inhibitor dose and treatment line., Results: Finally, 2100 patients were prescribed single-capsule bismuth quadruple therapy following the technical sheet (i.e., three capsules every 6 h for 10 days). The majority of these patients were naive (64%), with an average age of 50 years, 64% women and 16% with peptic ulcer. An overall modified intention-to-treat effectiveness of 92% was achieved. Eradication was over 90% in first-line treatment (95% modified intention-to-treat, n = 1166), and this was maintained as a rescue therapy, both in second (89% modified intention-to-treat, n = 375) and subsequent lines of therapy (third to sixth line: 92% modified intention-to-treat, n = 236). Compliance was the factor most closely associated with treatment effectiveness. Adverse events were generally mild to moderate, and 3% of patients reported a severe adverse event, leading to discontinuation of treatment in 1.7% of cases., Conclusions: Single-capsule bismuth quadruple therapy achieved H. pylori eradication in approximately 90% of patients in real-world clinical practice, both as a first-line and rescue treatment, with good compliance and a favourable safety profile., (© 2020 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.)

Oral tetracyclines are the most widely prescribed systemic antibiotic for acne. Synthesis of efficacy and safety of traditional and novel oral tetracyclines is highly informative to clinical practice. We conducted a systematic search of PubMed to identify large interventional and observational studies utilizing oral tetracyclines as an acne treatment. We identified 13 articles meeting inclusion for this review, which represented 226,019 pediatric and adult acne patients. Oral tetracyclines that were included in this systematic review were sarecycline (a novel narrow-spectrum tetracycline), doxycycline, minocycline, and tetracycline. Based on shared and divergent outcome measures, different oral tetracyclines were variably effective against facial acne. Sarecycline also demonstrated efficacy in truncal acne. Members of the oral tetracycline class also differed in their ability to minimize antibiotic resistance and gut dysbiosis. J Drugs Dermatol. 2020;19:11(Suppl):s4-11.

Aim: To compare the efficacy and safety between modified quadruple- and bismuth-containing quadruple therapy as first-line eradication regimen for Helicobacter pylori infection., Methods: This study was a multicenter, randomized-controlled, non-inferiority trial. Subjects endoscopically diagnosed with H. pylori infection were randomly allocated to receive modified quadruple- (rabeprazole 20 mg bid, amoxicillin 1 g bid, metronidazole 500 mg tid, bismuth subcitrate 300 mg qid [elemental bismuth 480 mg]; PAMB) or bismuth-containing quadruple therapy (rabeprazole 20 mg bid, bismuth subcitrate 300 mg qid, metronidazole 500 mg tid, tetracycline 500 mg qid; PBMT) for 14 days. Rates of eradication success and adverse events were investigated. Antibiotic resistance was determined using the agar dilution and DNA sequencing of the clarithromycin resistance point mutations in the 23 S rRNA gene of H. pylori ., Results: In total, 233 participants were randomized, 27 were lost to follow-up, and four violated the protocol. Both regimens showed an acceptable eradication rate in the intention-to-treat (PAMB: 87.2% vs. PBMT: 82.8%, P = .37), modified intention-to-treat (96.2% vs. 96%, P > .99), and per-protocol (96.2% vs. 96.9%, P > .99) analyses. Non-inferiority in the eradication success between PAMB and PBMT was confirmed. The amoxicillin-, metronidazole-, tetracycline-, clarithromycin-, and levofloxacin-resistance rates were 8.3, 40, 9.4, 23.5, and 42.2%, respectively. Antimicrobial resistance did not significantly affect the efficacy of either therapy. Overall compliance was 98.1%. Adverse events were not significantly different between the two therapies., Conclusion: Modified quadruple therapy comprising rabeprazole, amoxicillin, metronidazole, and bismuth is an effective first-line treatment for the H. pylori infection in regions with high clarithromycin and metronidazole resistance.

Many antibiotics carry caution stickers that warn against alcohol consumption. Data regarding concurrent use are sparse. An awareness of data that address this common clinical scenario is important so health care professionals can make informed clinical decisions and address questions in an evidence-based manner. The purpose of this systematic review was to determine the evidence behind alcohol warnings issued for many common antimicrobials. The search was conducted from inception of each database to 2018 using PubMed, Medline via Ovid, and Embase. It included studies that involved interactions, effects on efficacy, and toxicity/adverse drug reactions (ADR) due to concomitant alcohol consumption and antimicrobials. All interactions were considered in terms of three components: (i) alteration in pharmacokinetics/pharmacodynamics (PK/PD) of antimicrobials and/or alcohol, (ii) change in antimicrobial efficacy, and (iii) development of toxicity/ADR. Available data support that oral penicillins, cefdinir, cefpodoxime, fluoroquinolones, azithromycin, tetracycline, nitrofurantoin, secnidazole, tinidazole, and fluconazole can be safely used with concomitant alcohol consumption. Data are equivocal for trimethoprim-sulfamethoxazole. Erythromycin may have reduced efficacy with alcohol consumption, and doxycycline may have reduced efficacy in chronic alcoholism. Alcohol low in tyramine may be consumed with oxazolidinones. The disulfiram-like reaction, though classically associated with metronidazole, occurs with uncertain frequency and with varied severity. Cephalosporins with a methylthiotetrazole (MTT) side chain or a methylthiodioxotriazine (MTDT) ring, ketoconazole, and griseofulvin have an increased risk of a disulfiram-like reaction. Alcohol and antimicrobial interactions are often lacking evidence. This review questions common beliefs due to poor, often conflicting data and identifies important knowledge gaps., (Copyright © 2020 American Society for Microbiology.)

Background: Although antibiotic-induced hepatotoxicity is recoverable with mild impairment, and some cases were reported to cause morbidity. However, an adjuvant is essential in reducing such incidences., Objective: The aim of this study is to evaluate the protective effect of ascorbic acid on antibiotic induced liver toxicity using liver slices., Method: Fresh liver slices were incubated with different concentrations of sulfamethoxazole tetracycline and clavulanic acid along with ascorbic acid (200μg/ml) for 2 hours. The liver homogenate was assessed for markers like ALT, AST, MDA and CAT levels. Cytotoxicity assessment was performed using MTT assay., Results: Incubating liver slices with all three antibiotics shows elevated levels of aminotransferases, MDA and CAT enzyme when compared to the control groups which indicates the level of hepatotoxicity. In the presence of ascorbic acid, the elevated levels of TBARS, ALT and AST were significantly reduced which showcases the protective effect of ascorbic acid. The percentage survival of cell was also shown to have improved while accessed using cell viability assay., Conclusion: Obtained data suggests that consuming vitamin C or vitamin C containing food like citrus fruits or green leafy vegetables equivalent to 3g/day during antibiotic treatment, perhaps put down the risk of liver toxicity to a greater extent., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Microbial symbiosis is essential for the normal development and growth of hosts. Past attention has mostly been paid to its effects on plants and vertebrates. The effects of environmental pressures such as antibiotics on the microbiome of soil fauna remain largely elusive. We used bacterial 16S rRNA gene high-throughput sequencing to examine the response of microbiome of soil invertebrate Enchytraeus crypticus to oral tetracycline exposure. After two-week exposure, tetracycline-free oat was used as food to monitor the restoration of E. crypticus microbiome. The results showed that Proteobacteria, Actinobacteria and Planctomycetes were the three dominant phyla in all samples, Rhizobiaceae and Kaistia were the most abundant family and genus in all samples, respectively. After 14 days tetracycline exposure, Planctomycetes declined dramatically from 33.05% to 3.28% (P = 0.016), but Actinobacteria elevated substantially from 2.47% to 23.65% (P = 0.004). The alpha-diversity of microbial community increased significantly after tetracycline exposure compared to the control (P = 0.014). Terminating tetracycline exposure led to the recovery of E. crypticus microbiome back to the background level within 14 days. Our results suggest that while tetracycline can disturb the microbiome in E. crypticus significantly, the effects of the antibiotic on E. crypticus microbiome may not be permanent but reversibly diminish after stopping exposure for a period of time. The results may contribute to extending our understanding of the effect of antibiotics on microbiome of soil invertebrates. CAPSULE: The microbiome of E. crypticus exposed to tetracycline is perturbed and reversibly restored after terminating the exposure., (Copyright © 2018. Published by Elsevier B.V.)

Background: Bismuth quadruple therapy is the treatment of choice for the first-line therapy of Helicobacter pylori infection in areas of high clarithromycin resistance. Currently, the impact of the promising treatment on gut microbiota remains unclear., Aim: To investigate the short-term and long-term impacts of bismuth quadruple therapy on gut microbiota., Methods: Adult patients with H. pylori-related gastritis were treated with 14-day bismuth quadruple therapy. Fecal samples were collected before treatment at week 2, week 8, and week 48. Nucleic acid extraction from fecal samples was performed. The V3-V4 region of the bacterial 16S rRNA gene was amplified by polymerase chain reaction and sequenced with the MiSeq followed by data analysis using Qiime pipeline., Results: Eleven patients received complete follow-up. Before treatment, the most abundant phyla were Firmicutes (45.3%), Bacteroidetes (24.3%), Proteobacteria (9.9%), and Actinobacteria (5.0%). At the end of bismuth therapy, the relative abundances of Bacteroidetes and Actinobacteria decreased to 0.5% (P < .001) and 1.3% (P = .038), respectively. Additionally, the relative abundance of Verrucomicrobia also decreased from 3.2% to 1.11E-3% (P = .034). In contrast, the relative abundances of Proteobacteria and Cyanobacteria increased (P < .001 and P = .003, respectively). At week 8, the relative abundances of all phyla restored to the levels at baseline. The relative abundances of all phyla at week 48 also did not significantly differ from those at baseline. During eradication therapy, 6 patients (55%) reported at least 1 adverse event. The relative abundance of phylum Proteobacteria in patients with adverse effects was more than that in patients without adverse effects (68.7% ± 8.8% vs 43.4% ± 25.5%; P = .048)., Conclusions: Bismuth quadruple therapy for H. pylori eradication can lead to short-term dysbiosis of gut microbiota. The increase in Proteobacteria in gut microbiota may attribute to the development of adverse effects during bismuth quadruple therapy., (© 2018 John Wiley & Sons Ltd.)

Background: Clinical trials have shown a good efficacy of the "three-in-one" formulation of bismuth quadruple therapy (BQT) for Helicobacter (H.) pylori eradication. We aimed to assess the efficacy and safety of the three-in-one BQT in clinical practice, and investigate the effect of probiotic supplementation, in Italy., Materials and Methods: A retrospective database, multicentre observational study was conducted in seven Italian Hospitals. Consecutive H. pylori-positive patients who received the three-in-one BQT for 10 days were included in the analysis. H. pylori eradication was assessed by histology, 13 C-urea breath test, or stool antigen test. Compliance and adverse events were evaluated by interview., Results: A total of 376 patients were included in the intention-to-treat (ITT) and 352 in the per protocol (PP) analyses. One hundred and ninety-three subjects received probiotics supplementation. Overall, eradication rates were 90.2% (95% Confidence Interval (CI):86.7-93.0) in ITT and 94.6% (95% CI: 91.7-96.7) in PP analyses. The compliance was good (≥90% of treatment taken) in 94.9% of patients. The proportion of patients with a good compliance was not different with and without probiotics supplementation (94.8% vs 95.1%). Eradication rates were equally high for first-line (91.4%), second-line (87.5%), and third-line treatments (91.7%) in the ITT analysis (P = .48). Adverse events were reported by 32.4% of patients, but only 6.1% of patients discontinued treatment., Conclusions: The three-in-one BQT is highly effective and well tolerated for H. pylori eradication in daily clinical practice. Probiotics supplementation fails to improve compliance., (© 2018 John Wiley & Sons Ltd.)

Purpose: To evaluate the clinical effectiveness of cold-light whitening technique on tetracycline pigmentation teeth and aged extrinsic stain teeth., Methods: One hundred and fifty-two cases bleached by cold-light whitening technique were included in this study. The patients' teeth were divided into 3 groups: aged extrinsic stain teeth, mild tetracycline pigmentation teeth and moderate tetracycline pigmentation teeth. Visual determination of shade and Olympus crystaleye spectrophotometer were used to measure the tooth discoloration after bleaching. SPSS17.0 software package was used for statistical analysis., Results: Visual determination showed that the efficiency of aged extrinsic stain teeth was significantly higher than that of mild and moderate tetracycline teeth group (P<0.05). Colorimetric method showed that the △E of moderate tetracycline teeth was significantly lower than aged extrinsic teeth and mild tetracycline teeth (P<0.05) . The △E of cervix changed more significantly than that of central and incisal edge in both mild and moderate tetracycline teeth group (P<0.05)., Conclusions: The effect of cold-light whitening technique on aged extrinsic stain teeth is better than that of the tetracycline pigmentation teeth. Cold-light whitening technique can improve pigmentation of tetracycline teeth cervix．.

Aim: The aim of this study was to critically assess all available evidence suggesting an association between antibiotic exposure and new onset of inflammatory bowel disease (IBD)., Materials and Methods: This systematic review was conducted according to the PRISMA statement and eligible studies were identified through search of PubMed, Embase and the Cochrane Library. Data on patient demographics, antibiotic exposure and confounding factors were analyzed. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of eligible studies., Results: A total of 15 observational studies (10 case control and five cohort) including 8748 patients diagnosed with IBD were systematically reviewed. Antibiotic exposure was mostly associated with Crohn's disease but not with ulcerative colitis. In particular, penicillin's, cephalosporins, metronidazole and fluoroquinolones were most commonly associated with the onset of Crohn's disease. The impact of tetracycline-family antibiotics on the pathogenesis of IBD was not clear., Conclusion: There may be an association between antibiotic exposure and the development of IBD; especially Crohn's disease. Even though, clinicians should be cautious when prescribing certain antibiotic regimens to patients with a strong family history of IBD, it should be emphasized that available data are not granular enough to reach any definitive conclusions.

Background and Aims: Helicobacter pylori (H. pylori) eradication in patients who failed one or more therapeutic attempts remains challenging. This study aimed to assess the efficacy of three-in-one capsules bismuth-based quadruple therapy (Pylera®) in these patients managed in clinical practice., Methods: This was a prospective, open-label, multicenter study enrolling consecutive, adult patients with persistent H. pylori infection following at least one standard therapy. All patients received a rescue quadruple therapy with Pylera (3 capsules four times daily) and esomeprazole 20 mg (1 tablet twice daily) for 10 days. H. pylori eradication was assessed by using Urea Breath Test 4-6 weeks following therapy ending. H. pylori eradication rates, compliance, and side-effects were calculated., Results: A total of 208 patients in the 9 participating centres were enrolled. Overall, 180 patients were successfully cured from the infection, accounting for 86.5% (95% CI 81.9-91.2) and 92.3% (95% CI 88.6-96.1) eradication rates at intention-to-treat analysis and at per protocol analysis, respectively. Cure rates were similar across patients who failed one to three previous therapy attempts, but the success rate fell to 67% after 4 or more therapy failures. Compliance to therapy was good in 198 (95.2%) patients, whilst in 7 (5.3%) cases the therapy was interrupted within 5 days due to side effects. A total of 97 (46.6%) patients complained of at least one side effect; nausea, diarrhea and vomiting were the most frequently reported., Conclusions: Our study found that this bismuth-based quadruple therapy is highly effective as second-line and rescue therapy for H. pylori eradication in clinical practice.

Objective: To evaluate the efficacy and safety of a quadruple regimen (BMTO) of the "3-in-1 capsule" (containing bismuth subcitrate potassium, metronidazole and tetracycline) plus omeprazole in naïve and previously treated patients diagnosed with Helicobacter pylori (H. pylori) infection in the clinical setting in Seville (Spain)., Methods: This is a prospective study carried out on consecutive patients with a confirmed H. pylori infection and upper gastrointestinal symptoms. After providing their informed consent, the patients were treated for ten days with a 3-in-1 capsule containing bismuth subcitrate potassium (140 mg), metronidazole (125 mg) and tetracycline (125 mg: Pylera®), three capsules four times daily, plus omeprazole (20 or 40 mg) twice daily. Eradication of infection was determined by a negative urea breath test at least 28 days after the end of treatment., Results: A total of 58 consecutive patients were enrolled into this study, two of whom withdrew early due to vomiting on days three and five, respectively. In this cohort, 17 patients (29.3%) had a prior history of medication to treat H. pylori. In the intent-to-treat population, eradication was achieved in 97.6% (40/41) and 82.4% (14/17) of cases in patients treated with BMTO as a first-line or rescue therapy, respectively. At least one adverse event was reported by 28 (48%) patients, mostly mild effects (86%)., Conclusion: A ten day treatment with BMTO is an effective and safe strategy to combat confirmed H. pylori infection in patients.

Background: Rising antibiotic resistance requires the evaluation of new and effective therapies., Aims: To test the efficacy and safety of the new bismuth-containing quadruple therapy in patients infected with Helicobacter pylori., Material and Methods: Consecutive H. pylori-positive dyspeptic patients were enrolled, either naïve or with previous failure treatment. Patients were treated with Pylera ® (three-in-one capsules containing bismuth subcitrate potassium 140 mg, metronidazole 125 mg, and tetracycline 125 mg) three capsules q.i.d. plus omeprazole 20 mg or esomeprazole 40 mg b.i.d. for 10 days. Eradication was confirmed using an urea breath test (at least 30 days after the end of treatment). Efficacy was assessed by UBT and safety by means of treatment-emergent adverse events., Results: One hundred and thirty-one patients were included in the study: 42% of patients were naïve, and 58%, with previous failure treatment. H. pylori eradication was achieved in 124 patients (94.7%, 95% confidence intervals (CIs) 89.3-97.8) in ITT population. In the PP population, the percentage was 97.6% (95%, CIs 93.3-99.2). No difference in eradication rate was found either between naïve and previously treated patients (92.7% vs 96.0%, P=.383), or smoking and nonsmoking ones, or in patients taking omeprazole or esomeprazole. Treatment-emergent adverse events occurred in 35 patients (26.7%, 95% CIs 19.9-34.9). They were mild in all cases except in four, who discontinued the study due to diarrhea (three patients) and diffuse urticarial rush (one patient)., Conclusions: Pylera ® achieved a remarkable eradication rate in clinical practice, irrespective if it was used as first treatment or as a rescue therapy. Treatment-emergent adverse events were uncommon generally mild., (© 2017 John Wiley & Sons Ltd.)

Background: The <80 % Helicobacter pylori eradication rate with sequential therapy is unsatisfactory. Modified bismuth quadruple therapy, replacing metronidazole with amoxicillin, could be promising because H. pylori resistance to tetracycline or to amoxicillin is relatively low. A 14-day modified bismuth quadruple protocol as first-line H. pylori treatment was compared with 10-day sequential therapy., Methods: In total, 390 H. pylori-infected subjects participated in the randomized clinical trial: 10-day sequential therapy (40 mg pantoprazole plus 1 g amoxicillin twice a day for 5 days, then 40 mg pantoprazole and 500 mg clarithromycin twice a day and 500 mg metronidazole three times a day for 5 days) or 14-day modified bismuth quadruple therapy (40 mg pantoprazole, 600 mg bismuth subcitrate, 1 g tetracycline, and 1 g amoxicillin, twice a day). (13)C-urea breath test, rapid urease testing, or histology was performed to check for eradication., Results: Intention-to-treat (ITT) eradication rates of 10-day sequential and 14-day quadruple therapy were 74.6 % and 68.7 %, respectively, and the per-protocol (PP) rates were 84.2 and 76.5 %, respectively. The eradication rate was higher in the sequential therapy group, but neither the ITT nor the PP analyses had a significant difference (P = 0.240 and P = 0.099, respectively). However, the adverse events were significantly lower in the modified bismuth quadruple therapy group than the sequential therapy group (36.9 vs. 47.7 %, P = 0.040)., Conclusions: Ten-day sequential therapy appears to be more effective despite frequent adverse events. However, both 10-day SQT and 14-day PBAT did not reach the excellent eradication rates that exceed 90 %. Additional trials are needed to identify a more satisfactory first-line eradication therapy., Trial Registration: ClinicalTrials.gov ( NCT02159976 ); Registration date: 2014-06-03, CRIS ( KCT0001176 ); Registration date: 2014-07-23.

A 14-year-old girl presented with a history of left-sided headache and acute bilateral blurred vision. She had a remote history of oral tetracycline use for the treatment of acne vulgaris, which had been discontinued for 1 month. The patient was diagnosed with drug-induced intracranial hypertension (IH) and treated with oral acetazolamide with subsequent resolution of symptoms. IH, a known rare complication of the tetracycline class of antibiotics, can also have a delayed presentation after discontinuation of the medication.

Background & Aims: Rosacea is an inflammatory skin disease. Case reports have shown rosacea as a comorbidity of inflammatory bowel disease (IBD), but no epidemiologic studies have examined rosacea and risk of subsequent IBD. The association between tetracycline use and risk of IBD was assessed, but this study produced limited findings. We examined the association between rosacea, use of tetracycline, and risk of incident Crohn's disease (CD) and ulcerative colitis (UC)., Methods: We analyzed data from 96,314 participants in the Nurses' Health Study II (1991-2011). Information on IBD was confirmed by medical review. Participants were asked in 2005 about their lifetime histories of clinician-diagnosed rosacea and year of diagnosis. Information on ever use of tetracycline was collected in 1993., Results: During 1,856,587 person-years (1991-2011), we identified 149 cases of CD and 215 cases of UC. Rosacea was not associated with risk of UC. In contrast, rosacea was significantly associated with increased risk of subsequent CD (hazard ratio [HR], 2.20; 95% confidence interval [CI], 1.15-4.18), which appeared particularly stronger for a longer duration after a diagnosis of rosacea (Ptrend = .01). Tetracycline use was associated with increased risk of CD (HR, 1.56; 95% CI, 1.09-2.24) and UC (HR, 1.34; 95% CI, 1.00-1.80); there was a trend toward increased risk with increased duration of use (both Ptrend < .05) (1993-2011)., Conclusions: On the basis of an analysis of data from the Nurses' Health Study II, ever use of tetracycline at baseline is associated with an increased risk of CD and UC. Personal history of rosacea is associated with an increased risk of only CD., (Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: To review the phenomenon and implications of temporal bone and craniofacial bone staining in the context of prolonged exposure to tetracycline antibiotic., Methods: Case report and literature review., Results: A 52-year-old male with a 5-year history of tetracycline use presented to undergo tympanomastoidectomy and was found to have an unusual rusty green pigmentation of the entire aspect of the exposed temporal bone. A literature review revealed more than 20 cases of tetracycline-induced pigmentation of intraoral maxillary and mandibular bone, and 2 prior cases involving the cranial bones., Conclusion: Tissue and organ pigmentation is an unexpected and unfavourable consequence of the use of tetracyclines, particularly minocycline. Tetracycline is contraindicated in children because of the risk for dysosteogenesis and enamel hypoplasia. In adults, although the unusual staining may present as an unexpected dilemma upon surgical exposure, current research shows no significant clinical consequences for this type of pigmentation.

Aim: To access the efficacy of combination with amoxicillin and tetracycline for eradication of Helicobacter pylori (H. pylori), thus providing clinical practice guidelines., Methods: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Science Citation Index, China National Knowledge Infrastructure, Wanfang, and Chinese Biomedical Literature databases and abstract books of major European, American, and Asian gastroenterological meetings were searched. All clinical trials that examined the efficacy of H. pylori eradication therapies and included both tetracycline and amoxicillin in one study arm were selected for this systematic review and meta-analysis. Statistical analysis was performed with Comprehensive Meta-Analysis Software (Version 2). Subgroup, meta-regression, and sensitivity analyses were also carried out., Results: Thirty-three studies met the inclusion criteria. The pooled odds ratio (OR) was 0.90 (95%CI: 0.42-1.78) for quadruple therapy with amoxicillin and tetracycline vs other quadruple regimens, and total eradication rates were 78.1% by intention-to-treat (ITT) and 84.5% by per-protocol (PP) analyses in the experimental groups. The pooled eradication rates of 14-d quadruple regimens with a combination of amoxicillin and tetracycline were 82.3% by ITT and 89.0% by PP, and those of 10-d regimens were 84.6% by ITT and 93.7% by PP. The OR by ITT were 1.21 (95%CI: 0.64-2.28) for triple regimens with amoxicillin and tetracycline vs other regimens and 1.81 (95%CI: 1.37-2.41) for sequential treatment with amoxicillin and tetracycline vs other regimens, respectively., Conclusion: The effectiveness of regimens employing amoxicillin and tetracycline for H. pylori eradication may be not inferior to other regimens, but further study should be necessary.

Background: To eradicate Helicobacter pylori in human pylorus and to heal duodenal ulcers, recently, a new formulation of combination tablets containing metronidazole 125 mg, tetracycline hydrochloride 125 mg and bismuth oxide 40 mg has been developed., Objective: To investigate the pharmacokinetics of metronidazole, tetracycline and bismuth in healthy Chinese volunteers after oral administration of the test formulation., Methods: A one-sequence, 3-period study was conducted in 12 Chinese healthy volunteers (6 male, 6 female). Volunteers each received single low dose (1 tablet) under fed condition in period 1, single high dose (3 tablets) under fasted condition in period 2, and single high dose (3 tablets) and multiple doses (3 tablets at once, 4 times daily for 7 consecutive days) under fed condition in period 3. Blood samples were collected and determined over 48 h in every period., Results and Conclusion: After single high dose administration under fed condition, the C max of metronidazole, tetracycline and bismuth were 6.833 ± 0.742 μg/mL, 0.8513 ± 0.1253 μg/mL and 3.32 ± 1.89 ng/mL, respectively. The C max and AUC 0-48 of metronidazole increased in proportion to the doses within the tested dose range, but tetracycline and bismuth did not. Food caused 10% and 80% decrease of the C max for metronidazole and bismuth, respectively, but did not affect tetracycline. No gender effect was found on the pharmacokinetics of the 3 ingredients. In the steady state, the C av of metronidazole, tetracycline and bismuth were 20.75 ± 3.52 μg/mL, 1.900 ± 0.243 μg/mL and 5.61 ± 1.34 ng/mL, respectively., (© Georg Thieme Verlag KG Stuttgart · New York.)

Aim: Tetracycline-stained tooth structure is difficult to bleach using nightguard tray methods. The possible benefits of in-office light-accelerated bleaching systems based on the photo-Fenton reaction are of interest as possible adjunctive treatments. This study was a proof of concept for possible benefits of this approach, using dentine slabs from human tooth roots stained in a reproducible manner with the tetracycline antibiotic demeclocycline hydrochloride., Materials and Methods: Color changes overtime in tetra-cycline stained roots from single rooted teeth treated using gel (Zoom! WhiteSpeed(®)) alone, blue LED light alone, or gel plus light in combination were tracked using standardized digital photography. Controls received no treatment. Changes in color channel data were tracked overtime, for each treatment group (N = 20 per group)., Results: Dentin was lighter after bleaching, with significant improvements in the dentin color for the blue channel (yellow shade) followed by the green channel and luminosity. The greatest changes occurred with gel activated by light (p < 0.0001), which was superior to effects seen with gel alone. Use of the light alone did not significantly alter shade., Conclusion: This proof of concept study demonstrates that bleaching using the photo-Fenton chemistry is capable of lightening tetracycline-stained dentine. Further investigation of the use of this method for treating tetracycline-stained teeth in clinical settings appears warranted., Clinical Significance: Because tetracycline staining may respond to bleaching treatments based on the photo-Fenton reaction, systems, such as Zoom! WhiteSpeed, may have benefits as adjuncts to home bleaching for patients with tetracycline-staining.

Introduction: Inappropriate antibiotics prescription in dental healthcare delivery that may result in the emergence of antibiotic-resistant bacteria, is a worldwide concern. The objective of the study was to determine the antibiotics knowledge and prescription patterns among dentists in Nigeria., Materials and Methods: A total of 160 questionnaires were distributed to dentists attending continuing education courses organized by two organizations in Southern and Northern parts of Nigeria. Data analysis was done using SPSS version 17.0., Results: A total of 146 questionnaires were returned, properly filled, out of 160 questionnaires, giving an overall response rate 91.3%. The clinical factors predominantly influenced the choice of therapeutic antibiotics among the respondents. In this study, the most commonly prescribed antibiotics among the respondents was a combination of amoxicillin and metronidazole. Of the respondents, 136 (93.2%) of them considered antibiotic resistance as a major problem in Nigeria and 102 (69.9%) have experienced antibiotics resistance in dental practice. The major reported conditions for prophylactic antibiotics among the respondents were diabetic mellitus, HIV/AIDS, history of rheumatic fever, other heart anomalies presenting with heart murmur and presence of prosthetic hip. The knowledge of adverse effects of antibiotics was greatest for tooth discoloration which is related to tetracycline., Conclusion: Data from this study revealed the most commonly prescribed antibiotics as a combination of amoxicillin and metronidazole. There existed gaps in prophylactic antibiotic prescription, consideration in the choice of therapeutic antibiotics and knowledge of adverse effects of antibiotics among the studied dentists.

Background: Helicobacter pylori infection occurs in children and adults worldwide. Standard triple therapy of omeprazole, amoxicillin and clarithromycin (OAC) may not be optimal., Aim: To evaluate quadruple therapy with bismuth subcitrate potassium, metronidazole and tetracycline hydrochloride, given with omeprazole in H. pylori infected subjects who failed previous OAC eradication therapy., Methods: This was a multicenter, open-label, single-arm, multinational study. Helicobacter pylori-positive subjects who had failed ≥1 previous course of OAC therapy with or without up to three supplemental treatments in the previous year. Subjects were treated for 10 days with a combination formulation containing bismuth subcitrate potassium 140 mg, tetracycline hydrochloride 125 mg, and metronidazole 125 mg, three capsules four times daily (q.d.s.), and omeprazole 20 mg twice daily (b.d.). The primary endpoint was H. pylori eradication rate defined as one negative (13) C-urea breath test ≥28 days post-treatment., Results: Helicobacter pylori eradication rates ranged from 93.2% to 93.8% in the intent-to-treat population (n = 49), and from 94.7% to 95.0% in the PP population (n = 40). No clinically meaningful differences were observed when analysed by country. Metronidazole resistance was observed in 16/49 (32.7%) subjects and clarithromycin resistance in 31/49 (63.3%) subjects. Thirty-three subjects (67.3%) reported 87 adverse events, and only one (2%) discontinued the study for an adverse event., Conclusions: A quadruple regimen of bismuth, metronidazole and tetracycline plus omeprazole produces a high eradication rate in subjects previously failing H. pylori eradication regimens. This bismuth-based regimen offers an effective option as rescue therapy., (© 2014 John Wiley & Sons Ltd.)

New and more aggressive antibiotic resistant bacteria arise at an alarming rate and represent an ever-growing challenge to global health care systems. Consequently, the development of new antimicrobial agents is required to overcome the inefficiency of conventional antibiotics and bypass treatment limitations related to these pathologies. In this study, we present a synthesis protocol, which was able to entrap tetracycline antibiotic into silica nanospheres. Bactericidal efficacy of these structures was tested against bacteria that were susceptible and resistant to antibiotics. For nonresistant bacteria, our composite had bactericidal efficiency comparable to that of free-tetracycline. On the other hand, the synthesized composites were able to avoid bacterial growth of resistant bacteria while free-tetracycline has shown no significant bactericidal effect. Finally, we have investigated the cytotoxicity of these nanoparticles against mammalian cells to check any possible poisoning effect. It was found that these nanospheres are not apoptosis-inducers and only a reduction on the cell replication rate was seen when compared to the control without nanoparticles.

Background: Sequential therapy has been recommended in the Maastricht IV/Florence Consensus Report as the first-line treatment for Helicobacter pylori eradication in regions with high clarithromycin resistance. However, it fails in 5-24% of infected subjects, and the recommended levofloxacin-containing triple rescue therapy only achieves a 77% eradication rate after failure of sequential therapy., Aim: To investigate the efficacy of a novel quadruple therapy comprising proton-pump inhibitor, bismuth, tetracycline, and levofloxacin for rescue treatment of sequential therapy., Methods: This was a multicenter study in which H. pylori-infected patients who had failed sequential therapy received a 10-day quadruple therapy (esomeprazole (40 mg b.d), tripotassium dicitrato bismuthate (120 mg q.d.s.), tetracycline (500 mg q.d.s.), and levofloxacin (500 mg o.d.) for 10 days). H. pylori status was examined 6 weeks after the end of treatment., Results: From July 2007 to June 2012, twenty-four subjects received 10-day quadruple therapy. The eradication rates according to intention-to-treat and per-protocol analyses were both 95.8% (23 of 24; 95% confidence interval, 87.8-103.8%). Adverse events were seen in 25.0% (6 of 24) of the patients. Drug compliance was 100.0% (24/24)., Conclusions: The 10-day quadruple therapy comprising proton-pump inhibitor, bismuth, tetracycline, and levofloxacin achieves a very high eradication rate for H. pylori infection after failure of sequential therapy. It is well tolerated and has great potential to become a good choice of rescue treatment following non-bismuth-containing quadruple therapy in regions with high clarithromycin resistance., (© 2013 John Wiley & Sons Ltd.)

Tetracycline and doxycycline are commonly used antibiotics in acne treatment during puberty in humans. The long-term effect of these antibiotics on male reproductive tract development has not been fully elucidated. For this reason we tested the effect of antibiotics on the reproductive parameters of mice males during puberty with the therapeutic dose used in humans, and with lower and higher doses. The outbred mouse strain CD1 with higher heterozygosity was exposed for 14 days at puberty. Adult males at the age of 70 days were used for the measurements. We observed a significant decrease in anogenital distance and thickness of the seminiferous epithelium in the treated animals. Pathological changes in the testes had an impact on sperm quality; a higher number of sperm positively stained with Annexin V and TUNEL and a lower number of acrosome-intact sperm was detected. In conclusion, the treatment of male mice with antibiotics in puberty led to long-lasting effects on reproductive organs and spermatozoa in adult males., (Copyright © 2013 Elsevier GmbH. All rights reserved.)

The standard treatment for peptic ulcer associated with Helicobacter pylori is a combination of omeprazole, amoxicillin and clarithromycin, which renders the bacterium undetectable in about 70% of cases. A fixed-dose combination of bismuth subcitrate potassium + metronidazole + tetracycline has been authorised in some European countries for use in this setting, combined with high-dose omeprazole. In a European trial with 440 patients, the 4-drug combination of omeprazole + bismuth subcitrate + metronidazole + tetracycline was significantly more active than the standard 3-drug regimen in terms of H. pylori eradication, as measured with the urea breath test (79.8% with bismuth, 55.4% without bismuth). In a North American trial with 275 patients the success rate was similar with the two treatments, again based on the urea breath test. There are no comparative trials of the 4-drug regimen in patients in whom standard treatment has failed. The main adverse effects of the 4-drug regimen observed in clinical trials were black stools, nausea, headache and dizziness. However, the trials were too small to detect infrequent but serious adverse effects such as bismuth encephalopathy. Safety during pregnancy is not known. Some patients included in clinical trials had detectable plasma bismuth concentrations. Omeprazole increases the absorption of bismuth subcitrate potassium. In practice, the 4-drug regimen combining omeprazole + bismuth subcitrate potassium + metronidazole + tetracycline is probably more effective than standard 3-drug therapy against H. pylori, at least in Europe, but this combination should be avoided due to uncertainties on the possible neurotoxicity of bismuth. Other antibiotic combinations are preferable, and there are too many questions surrounding the adverse effects of this combination for it to replace the standard 3-drug regimen in France.

Background: The treatment for the eradication of Helicobacter pylori (H. pylori) is complex; full effectiveness is rarely achieved and it has many adverse effects. In developing countries, increased resistance to antibiotics and its cost make eradication more difficult. Probiotics can reduce adverse effects and improve the infection treatment efficacy.If the first-line therapy fails a second-line treatment using tetracycline, furazolidone and proton-pump inhibitors has been effective and low cost in Brazil; however it implies in a lot of adverse effects. The aim of this study was to minimize the adverse effects and increase the eradication rate applying the association of a probiotic compound to second-line therapy regimen., Methods: Patients with peptic ulcer or functional dyspepsia infected by H. pylori were randomized to treatment with the furazolidone, tetracycline and lansoprazole regimen, twice a day for 7 days. In a double-blind study, patients received placebo or a probiotic compound (Lactobacillus acidophilus, Lactobacillus rhamnosus, Bifidobacterium bifidum and Streptococcus faecium) in capsules, twice a day for 30 days. A symptom questionnaire was administered in day zero, after completion of antibiotic therapy, after the probiotic use and eight weeks after the end of the treatment. Upper digestive endoscopy, histological assessment, rapid urease test and breath test were performed before and eight weeks after eradication treatment., Results: One hundred and seven patients were enrolled: 21 men with active probiotic and 19 with placebo plus 34 women with active probiotic and 33 with placebo comprising a total of 55 patients with active probiotic and 52 with placebo. Fifty-one patients had peptic ulcer and 56 were diagnosed as functional dyspepsia. The per-protocol eradication rate with active probiotic was 89.8% and with placebo, 85.1% (p=0.49); per intention to treat, 81.8% and 79.6%, respectively (p=0.53). The rate of adverse effects at 7 days with the active probiotic was 59.3% and 71.2% with placebo (p=0.20). At 30 days, it was 44.9% and 60.4%, respectively (p=0.08)., Conclusions: The use of this probiotic compound compared to placebo in the proposed regimen in Brazilian patients with peptic ulcer or functional dyspepsia showed no significant difference in efficacy or adverse effects., Trial Registration: Current Controlled Trials ISRCTN04714018.

Objective: To determine whether childhood antianaerobic antibiotic exposure is associated with the development of inflammatory bowel disease (IBD)., Methods: This retrospective cohort study employed data from 464 UK ambulatory practices participating in The Health Improvement Network. All children with ≥ 2 years of follow-up from 1994 to 2009 were followed between practice enrollment and IBD development, practice deregistration, 19 years of age, or death; those with previous IBD were excluded. All antibiotic prescriptions were captured. Antianaerobic antibiotic agents were defined as penicillin, amoxicillin, ampicillin, penicillin/β-lactamase inhibitor combinations, tetracyclines, clindamycin, metronidazole, cefoxitin, carbapenems, and oral vancomycin., Results: A total of 1072426 subjects contributed 6.6 million person-years of follow-up; 748 developed IBD. IBD incidence rates among antianaerobic antibiotic unexposed and exposed subjects were 0.83 and 1.52/10000 person-years, respectively, for an 84% relative risk increase. Exposure throughout childhood was associated with developing IBD, but this relationship decreased with increasing age at exposure. Exposure before 1 year of age had an adjusted hazard ratio of 5.51 (95% confidence interval [CI]: 1.66-18.28) but decreased to 2.62 (95% CI: 1.61-4.25) and 1.57 (95% CI: 1.35-1.84) by 5 and 15 years, respectively. Each antibiotic course increased the IBD hazard by 6% (4%-8%). A dose-response effect existed, with receipt of >2 antibiotic courses more highly associated with IBD development than receipt of 1 to 2 courses, with adjusted hazard ratios of 4.77 (95% CI: 2.13-10.68) versus 3.33 (95% CI: 1.69-6.58)., Conclusions: Childhood antianaerobic antibiotic exposure is associated with IBD development.

Background and Aims: Failure in the eradication of H. pylori is a frequent occurrence. We assessed the effectiveness of a third-line, levofloxacin-containing, 10-day sequential treatment, in order to obtain eradication of H. pylori resistant patients in a clinical setting., Methods: One-hundred and nineteen consecutive patients with proven two consecutive failures in curing H. pylori infection, containing either clarithromycin, bismuth or levofloxacin, were prospectively assessed. All patients received a 10-day sequential therapy with proton pump inhibitor (PPI) plus amoxicillin 1 g for the first 5 days, followed by PPI, levofloxacin 500 mg and tetracycline 500 mg for the remaining 5 days (all twice daily). One month after conclusion of therapy, endoscopy was performed in those patients for whom the examinations were clinically relevant. The remaining patients were checked by ¹³C-urea breath test., Results: H. pylori eradication was obtained in 80 patients (per-protocol: 68.38%; on intention-to-treat: 67.23%). Twenty-nine patients (24.37%) experienced side-effects, but only two of them (1.68%) were withdrawn from the study., Conclusion: A 10-day sequential triple therapy containing amoxicillin, levofloxacin and tetracycline seems to be effective and safe in curing resistant H. pylori infection.

Objective: To evaluate the suggested association between tetracycline and acute pancreatitis in a large pharmacoepidemiological study., Design: The use of tetracycline in relation to the risk of acute pancreatitis was examined in a nationwide case-control study of people aged 40-84 years between 2006 and 2008 in Sweden. The Swedish Patient Register was used to identify 6161 cases of first-episode acute pancreatitis. The Register of the Total Population was used to randomly select 61,637 control subjects from the general population using frequency-based density sampling, matched for age, sex, and calendar year. Tetracycline use was defined as 'current', 'recent', 'past' or 'former' if the drug had been dispensed 0-30 days, 31-180 days, 181-365 days or 1-3½ years before the index date, respectively. The risk of acute pancreatitis was estimated by unconditional logistic regression, providing ORs with 95% CIs, adjusted for potential confounding factors., Results: There was a 60% increased risk of acute pancreatitis among current users of tetracycline after adjustment for potential confounders (OR=1.6, 95% CI 1.2 to 2.1). There was no increased OR for any category of previous use., Conclusion: Current use of tetracycline is associated with an increased risk of acute pancreatitis, verifying previous case reports.

Introduction: This study aimed to compare the efficacy and safety of quadruple therapy containing doxycycline and routine quadruple therapy for Helicobacter (H.) pylori rescue eradication in patients who had failed the one-week triple therapy., Methods: Patients who failed the first-line eradication therapy were allocated into two groups. Group A patients (n = 43) were administered esomeprazole 20 mg, bismuth potassium citrate 220 mg, amoxicillin 1 g and doxycycline 100 mg, all bid for ten days, while Group B patients (n = 42) were administered esomeprazole 20 mg bid, bismuth potassium citrate 220 mg bid, metronidazole 400 mg bid and tetracycline 750 mg q.6h, for ten days. The results of H. pylori eradication were assessed with 13C urea breath test four weeks after the therapy, and the side effects were recorded., Results: A total of 85 patients (average age 46.9 years) were enrolled in the study. Successful eradication rate for H. pylori was 72.5% in Group A and 64.1% in Group B, with no significant difference between the two groups. 11.6% (5/43) of patients from group A and 31.0% (13/42) from group B reported at least one adverse event. The adverse events of all 18 patients disappeared after the therapy ceased., Conclusion: Quadruple therapy containing doxycycline is as effective as routine quadruple therapy for H. pylori rescue eradication. The regimen is well tolerated by most patients and causes fewer adverse events than routine quadruple therapy. Hence, it may be recommended as a suitable alternative H. pylori rescue regimen in China.

Unlabelled: This study evaluated the clinical response following extended daily use of a trayless 6.5% hydrogen peroxide (H2O2) tooth bleaching gel in patients with tetracycline stains., Materials and Methods: In this clinical trial, participants (N = 30) were assigned to a strip product following screening for tetracycline staining. Subjects used the product for 6 months, with clinical safety and efficacy measurements assessed at the end of each month. The strips were used for 30 minutes twice daily (maxillary arch only). Treatment efficacy was determined by the tooth color change from baseline using an expanded VITA shade guide. Additional shades were added on either side, representing colors whiter than B1 and darker than C4., Results: The strips averaged shade reduction in Months 1, 2, and 3 visits, respectively. Of all the subjects, 65% reached B1 color by Month 6. Treatment was generally well tolerated. Mild and transient tooth sensitivity (46.7%) and oral discomfort (43.3%) were the most common adverse events associated with daily bleaching, yet neither affected study participation., Conclusions: The 6.5% H2O2 bleaching strip provided significant tooth whitening in subjects with tetracycline stains., Clinical Significance: When used daily for 6 months, a 6.5% H2O2 bleaching strip can be effective in whitening tetracycline stains. The professional strip was well tolerated throughout the 6-month period. This extended use provides additional evidence of clinical safety associated with the use of this product for vital bleaching.

Backgrounds: Quadruple therapy using a proton-pump inhibitor, bismuth, metronidazole, and tetracycline is a standard second-line therapy for Helicobacter pylori infection, achieving an eradication rate of about 80% in Korea. A standard third-line therapy is not currently established, although various protocols have been proposed. We performed this study to evaluate the effectiveness of a retrial with quadruple therapy before starting a third-line treatment with new drugs., Materials and Methods: In 80 of 746 patients treated with a second-line quadruple therapy at the Korea University Ansan Hospital between January 2002 and September 2010, treatment for H. pylori had failed, and 45 of these patients were eligible for this study. Eradication of H. pylori was assessed by repeated endoscopy or by the (13) C-urea breath test at least 4 weeks after therapy. The patients with treatment failure were treated again with quadruple regimen for 2 weeks and reevaluated for treatment effectiveness and safety., Results: The eradication rate with second-line quadruple therapy was 86.9%. Of the 80 patients who failed treatment for H. pylori with the initial second-line quadruple therapy, 64 patients were treated again with the same regimen. Of the 45 retreated patients in this study, three patients were lost to follow-up and two complied poorly with medication. The eradication rate in the 40 patients retreated was 75.0% at per-protocol analysis. Seventeen patients experienced mild adverse events., Conclusions: A retrial of quadruple therapy before use of a third-line therapy may be safe and effective for patients who fail to respond to second-line quadruple therapy., (© 2011 Blackwell Publishing Ltd.)

Background: Helicobacter pylori is associated with benign and malignant diseases of the upper gastrointestinal tract, and increasing antibiotic resistance has made alternative treatments necessary. Our aim was to assess the efficacy and safety of a new, single-capsule treatment versus the gold standard for H pylori eradication., Methods: We did a randomised, open-label, non-inferiority, phase 3 trial in 39 sites in Europe, comparing the efficacy and safety of 10 days of quadruple therapy with omeprazole plus a single three-in-one capsule containing bismuth subcitrate potassium, metronidazole, and tetracycline (quadruple therapy) versus 7 days of omeprazole, amoxicillin, and clarithromycin (standard therapy) in adults with recorded H pylori infection. Patients were randomly assigned treatment according to a predetermined list independently generated by Quintiles Canada (Ville St-Laurent, QC, Canada). Our study was designed as a non-inferiority trial but was powered to detect superiority. Our primary outcome was H pylori eradication, established by two negative (13)C urea breath tests at a minimum of 28 and 56 days after the end of treatment. Our assessment for non-inferiority was in the per-protocol population, with subsequent assessment for superiority in the intention-to-treat population (ie, all participants randomly assigned treatment). This study is registered with ClinicalTrials.gov, number NCT00669955., Findings: 12 participants were lost to follow-up and 101 were excluded from the per-protocol analysis. In the per-protocol population (n=339), the lower bound of the CI for treatment with quadruple therapy was greater than the pre-established non-inferiority margin of -10% (95% CI 15·1-32·3; p<0·0001). In the intention-to-treat population (n=440), eradication rates were 80% (174 of 218 participants) in the quadruple therapy group versus 55% (123 of 222) in the standard therapy group (p<0·0001). Safety profiles for both treatments were similar; main adverse events were gastrointestinal and CNS disorders., Interpretation: Quadruple therapy should be considered for first-line treatment in view of the rising prevalence of clarithromycin-resistant H pylori, especially since quadruple therapy provides superior eradication with similar safety and tolerability to standard therapy., Funding: Axcan Pharma Inc., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Aim: To document the efficacy and tolerability of 14-day moxifloxacine-tetracycline-lansoprazole (MTL) regimens for Helicobacter pylori (Hp) eradication as a first-line therapy., Method: Fifty-six Hp-positive patients were enrolled. Patients were considered eligible for the study if they underwent upper gastrointestinal endoscopy, and Hp infection was diagnosed through histologic examination of antral and body bioptic samples. Primary end point of this study was to evaluate the eradication rate of 14-day MTL regimen therapies. Hp eradication was assessed using the 13C urea breath test performed. All patients were asked to fill in a validated questionnaire to report therapy-related side effects. Each symptom was graded from absent or present., Results: Fifty-six patients (29 men and 27 women) were enrolled. The studied therapeutic regimens were completed by 96.4% patients. Two dropouts occurred in the MTL group because of side effects. The eradication rate in MTL regimens was 55.4%. The overall prevalence of side effects was high in the MTL group., Conclusion: The MTL regimen failed to achieve the recommended eradication rates and had higher adverse effect rate. Hence, MTL regimen does not seem to be a suitable choice as a first-line Hp eradication therapy., (© 2011 Blackwell Publishing Ltd.)