BACKGROUND: Bismuth quadruple therapies (BQTs) including bismuth, a proton pump inhibitor (PPI) and two antibiotics have been shown to be highly effective for treating Helicobacter pylori infection even in areas of high bacterial antibiotic resistance. OBJECTIVE: To describe the time trends of use, effectiveness and safety of BQT in Europe using the European Registry on Helicobacter pylori Management (Hp-EuReg). DESIGN: Patients registered in the Hp-EuReg from 2013 to 2021 who had received BQT were included. The regimens prescribed, the number of eradication attempts, effectiveness, adherence and safety were analysed. The effectiveness was assessed by modified intention to treat (mITT). Time-trend and multivariate analyses were performed to determine variables that predicted treatment success. RESULTS: Of the 49 690 patients included in the Hp-EuReg, 15 582 (31%) had received BQT. BQT use increased from 8.6% of all treatments in 2013 to 39% in 2021. Single-capsule BQT-containing bismuth, metronidazole and tetracycline-plus a PPI (single-capsule BQT, ScBQT) was the most frequent treatment mode (43%). Schemes that obtained an effectiveness above 90% were the 10-day ScBQT and 14-day BQT using tetracycline plus metronidazole, or amoxicillin plus either clarithromycin or metronidazole. Only ScBQT achieved above 90% cure rates in all the geographical areas studied. Using the ScBQT scheme, adherence, the use of standard or high-dose PPIs, 14-day prescriptions and the use of BQT as first-line treatment were significantly associated with higher mITT effectiveness. CONCLUSION: The use of BQT increased notably in Europe over the study period. A 10-day ScBQT was the scheme that most consistently achieved optimal effectiveness. TRIAL REGISTRATION NUMBER: NCT02328131.

• Klíčová slova
• ANTIBIOTIC THERAPY, HELICOBACTER PYLORI - TREATMENT, HELICOBACTER THERAPY,
• MeSH
• amoxicilin terapeutické užití   aplikace a dávkování   MeSH
• antibakteriální látky * terapeutické užití   škodlivé účinky   aplikace a dávkování   MeSH
• bismut * terapeutické užití   aplikace a dávkování   MeSH
• dospělí MeSH
• Helicobacter pylori * účinky léků   MeSH
• infekce vyvolané Helicobacter pylori * farmakoterapie   MeSH
• inhibitory protonové pumpy * terapeutické užití   aplikace a dávkování   škodlivé účinky   MeSH
• klarithromycin terapeutické užití   aplikace a dávkování   MeSH
• kombinovaná farmakoterapie * MeSH
• lidé středního věku MeSH
• lidé MeSH
• metronidazol terapeutické užití   aplikace a dávkování   MeSH
• registrace * MeSH
• senioři MeSH
• tetracyklin terapeutické užití   aplikace a dávkování   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• amoxicilin MeSH
• antibakteriální látky * MeSH
• bismut * MeSH
• inhibitory protonové pumpy * MeSH
• klarithromycin MeSH
• metronidazol MeSH
• tetracyklin MeSH

INTRODUCTION AND PURPOSE: Mycobacterium (M.) chelonae is responsible for a half of relatively rare nontuberculous mycobacteria (NTM) keratitis. We report a case of M. chelonae keratitis in a woman following sclerocorneal suture extraction after cataract surgery. RESULTS: A 70-year-old woman presented with a red eye and corneal infiltration of her left eye six weeks following sclerocorneal suture extraction after an elective cataract surgery in another institute. She complained of a sharp, cutting pain and photophobia. Since initial corneal scrapes and conjunctival swabs proved no pathogen using culture and PCR methods, non-specific antibiotics and antifungal agents were administered. As keratitis was complicated by an inflammation in the anterior chamber and vitreous, samples of the vitreous fluid were sent for microbiologic examination. DNA of Epstein-Barr virus (EBV) was repeatedly detected. Since the intrastromal abscess had formed, corneal re-scrapings were performed and M. chelonae was detected using culture, MALDI-TOF MS and PCR methods. Therapy was changed to a combination of oral and topical clarithromycin, intravitreal, topical and intracameral amikacin, and oral and topical moxifloxacin. The successful therapy led to stabilization. The optical penetrating keratoplasty was performed and no signs of the infection recurrence were found. CONCLUSIONS: The diagnosis of nontuberculous mycobacterial keratitis is difficult and often delayed. An aggressive and prolonged antimicrobial therapy should include systemic and topical antibiotics. Surgical intervention in the form of corneal transplantation may be required in the active and nonresponsive infection. In the presented case this was necessary for visual rehabilitation due to scarring.

• Klíčová slova
• Antibiotic therapy, keratoplasty, Keratitis, Mycobacterium chelonae,
• MeSH
• amikacin terapeutické užití   MeSH
• antibakteriální látky * terapeutické užití   MeSH
• atypické mykobakteriální infekce * diagnóza   farmakoterapie   mikrobiologie   chirurgie   MeSH
• fluorochinolony terapeutické užití   MeSH
• keratitida * diagnóza   farmakoterapie   mikrobiologie   chirurgie   MeSH
• klarithromycin terapeutické užití   MeSH
• lidé MeSH
• moxifloxacin * terapeutické užití   MeSH
• Mycobacterium chelonae * izolace a purifikace   MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• přehledy MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• amikacin MeSH
• antibakteriální látky * MeSH
• fluorochinolony MeSH
• klarithromycin MeSH
• moxifloxacin * MeSH

BACKGROUND: Adherence to Helicobacter pylori (H. pylori) eradication treatment is a cornerstone for achieving adequate treatment efficacy. OBJECTIVE: To determine which factors influence compliance with treatment. METHODS: A systematic prospective non-interventional registry (Hp-EuReg) of the clinical practice of European gastroenterologists. Compliance was considered adequate if ≥90% drug intake. Data were collected until September 2021 using the AEG-REDCap e-CRF and were subjected to quality control. Modified intention-to-treat analyses were performed. Multivariate analysis carried out the factors associated with the effectiveness of treatment and compliance. RESULTS: Compliance was inadequate in 646 (1.7%) of 38,698 patients. The non-compliance rate was higher in patients prescribed longer regimens (10-, 14-days) and rescue treatments, patients with uninvestigated dyspepsia/functional dyspepsia, and patients reporting adverse effects. Prevalence of non-adherence was lower for first-line treatment than for rescue treatment (1.5% vs. 2.2%; p < 0.001). Differences in non-adherence in the three most frequent first-line treatments were shown: 1.1% with proton pump inhibitor + clarithromycin + amoxicillin; 2.3% with proton pump inhibitor clarithromycin amoxicillin metronidazole; and 1.8% with bismuth quadruple therapy. These treatments were significantly more effective in compliant than in non-compliant patients: 86% versus 44%, 90% versus 71%, and 93% versus 64%, respectively (p < 0.001). In the multivariate analysis, the variable most significantly associated with higher effectiveness was adequate compliance (odds ratio, 6.3 [95%CI, 5.2-7.7]; p < 0.001). CONCLUSIONS: Compliance with Helicobacter pylori eradication treatment is very good. Factors associated with poor compliance include uninvestigated/functional dyspepsia, rescue-treatment, prolonged treatment regimens, the presence of adverse events, and the use of non-bismuth sequential and concomitant treatment. Adequate treatment compliance was the variable most closely associated with successful eradication.

• Klíčová slova
• adherence, adverse effects, bismuth, dyspepsia, effectiveness, efficacy, first line, rate, regimens, rescue,
• MeSH
• amoxicilin * terapeutické užití   aplikace a dávkování   MeSH
• antibakteriální látky * terapeutické užití   škodlivé účinky   MeSH
• bismut terapeutické užití   aplikace a dávkování   škodlivé účinky   MeSH
• dospělí MeSH
• dyspepsie farmakoterapie   mikrobiologie   MeSH
• Helicobacter pylori * účinky léků   MeSH
• hodnocení adherence k farmakoterapii * MeSH
• infekce vyvolané Helicobacter pylori * farmakoterapie   MeSH
• inhibitory protonové pumpy * terapeutické užití   aplikace a dávkování   MeSH
• klarithromycin terapeutické užití   MeSH
• kombinovaná farmakoterapie * MeSH
• lidé středního věku MeSH
• lidé MeSH
• metronidazol terapeutické užití   aplikace a dávkování   MeSH
• prospektivní studie MeSH
• registrace * MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• amoxicilin * MeSH
• antibakteriální látky * MeSH
• bismut MeSH
• inhibitory protonové pumpy * MeSH
• klarithromycin MeSH
• metronidazol MeSH

BACKGROUND & AIMS: After a first Helicobacter pylori eradication attempt, approximately 20% of patients will remain infected. The aim of the current study was to assess the effectiveness and safety of second-line empiric treatment in Europe. METHODS: This international, multicenter, prospective, non-interventional registry aimed to evaluate the decisions and outcomes of H pylori management by European gastroenterologists. All infected adult cases with a previous eradication treatment attempt were registered with the Spanish Association of Gastroenterology-Research Electronic Data Capture until February 2021. Patients allergic to penicillin and those who received susceptibility-guided therapy were excluded. Data monitoring was performed to ensure data quality. RESULTS: Overall, 5055 patients received empiric second-line treatment. Triple therapy with amoxicillin and levofloxacin was prescribed most commonly (33%). The overall effectiveness was 82% by modified intention-to-treat analysis and 83% in the per-protocol population. After failure of first-line clarithromycin-containing treatment, optimal eradication (>90%) was obtained with moxifloxacin-containing triple therapy or levofloxacin-containing quadruple therapy (with bismuth). In patients receiving triple therapy containing levofloxacin or moxifloxacin, and levofloxacin-bismuth quadruple treatment, cure rates were optimized with 14-day regimens using high doses of proton pump inhibitors. However, 3-in-1 single capsule or levofloxacin-bismuth quadruple therapy produced reliable eradication rates regardless of proton pump inhibitor dose, duration of therapy, or previous first-line treatment. The overall incidence of adverse events was 28%, and most (85%) were mild. Three patients developed serious adverse events (0.3%) requiring hospitalization. CONCLUSIONS: Empiric second-line regimens including 14-day quinolone triple therapies, 14-day levofloxacin-bismuth quadruple therapy, 14-day tetracycline-bismuth classic quadruple therapy, and 10-day bismuth quadruple therapy (as a single capsule) provided optimal effectiveness. However, many other second-line treatments evaluated reported low eradication rates. ClincialTrials.gov number: NCT02328131.

• Klíčová slova
• Bismuth, Clarithromycin, Helicobacter pylori, Levofloxacin, Rescue,
• MeSH
• amoxicilin MeSH
• antibakteriální látky terapeutické užití   MeSH
• bismut MeSH
• chinolony * terapeutické užití   MeSH
• dospělí MeSH
• Helicobacter pylori * MeSH
• infekce vyvolané Helicobacter pylori * farmakoterapie   MeSH
• inhibitory protonové pumpy MeSH
• klarithromycin terapeutické užití   MeSH
• kombinovaná farmakoterapie MeSH
• levofloxacin MeSH
• lidé MeSH
• moxifloxacin terapeutické užití   MeSH
• peniciliny škodlivé účinky   MeSH
• prospektivní studie MeSH
• registrace MeSH
• tetracyklin terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• amoxicilin MeSH
• antibakteriální látky MeSH
• bismut MeSH
• chinolony * MeSH
• inhibitory protonové pumpy MeSH
• klarithromycin MeSH
• levofloxacin MeSH
• moxifloxacin MeSH
• peniciliny MeSH
• tetracyklin MeSH

BACKGROUND: Antimicrobial resistance of H. pylori can lead to treatment failure. Importantly, several studies have reported on heteroresistance, i.e. the presence of resistant and susceptible H. pylori populations in the same sample and/or a difference in the susceptibility patterns between biopsy samples. This meta-analysis aims to provide comprehensive data on the prevalence of metronidazole and clarithromycin heteroresistance and the approaches to their detection. MATERIAL AND METHODS: A systematic review was performed after the search of MEDLINE, Scopus and Web of Science. The study outcomes were the weighted pooled prevalence of heteroresistance to clarithromycin and metronidazole in H. pylori positive samples and/or isolates with a subanalysis by continent. RESULTS: A total of 22 studies that had investigated 3852 H. pylori positive patients were included in the meta-analysis. Heteroresistance to clarithromycin was reported in 20 studies, with a weighted pooled prevalence of 6.8% (95% CI 5.1-8.6; 3654 H. pylori positive patients; the substantial heterogeneity I2 = 55.6%). Heteroresistance to metronidazole was reported in 12 studies, with a weighted pooled prevalence of 13.8% (95% CI 8.9-18.6; 1670 H. pylori positive patients; the substantial heterogeneity I2 = 60.9%). The weighted pooled prevalence of clarithromycin heteroresistance was similar in Asia and Europe (p = 0.174584), however, metronidazole heteroresistance was detected more often in Europe (p < 0.00001). Clarithromycin heteroresistance was detected more often by phenotype rather than by using genotyping methods (12 vs 8 studies), whereas heteroresistance to metronidazole was detected only by phenotype. CONCLUSION: The prevalence of heteroresistance to clarithromycin and/or metronidazole is not negligible and can be detected in approximately 7 and 14% of H. pylori positive samples, respectively. These findings highlight the need to raise the awareness of gastroenterologists and microbiologists to the heteroresistance to clarithromycin and metronidazole in patients with a H. pylori infection.

• MeSH
• amoxicilin farmakologie   MeSH
• antibakteriální látky farmakologie   terapeutické užití   MeSH
• bakteriální léková rezistence genetika   MeSH
• Helicobacter pylori * MeSH
• infekce vyvolané Helicobacter pylori * diagnóza   farmakoterapie   MeSH
• klarithromycin farmakologie   terapeutické užití   MeSH
• lidé MeSH
• metronidazol farmakologie   terapeutické užití   MeSH
• mikrobiální testy citlivosti MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• přehledy MeSH
• systematický přehled MeSH
• Názvy látek
• amoxicilin MeSH
• antibakteriální látky MeSH
• klarithromycin MeSH
• metronidazol MeSH

BACKGROUND: The aim of this study was comparison the effectiveness of sequential and standard quadruple therapy on eradication of H. pylori infection. METHODS: This clinical trial study was conducted on 160 patients with dyspepsia or gastroduodenal ulcer. Patients were randomly divided into two groups. Group A (standard regimen) received omeprazole, amoxicillin, clarithromycin and bismuth subcitrate for 2 weeks. Group B (sequential regimen) received omeprazole and amoxicillin in 5 days and omeprazole, tinidazole and levofloxacin in 5 days. After the end of treatment regimens, 20 mg omeprazole was administered twice daily for 3 weeks. H. pylori eradication was assessed 2 months after antibiotic treatment via fecal antigen. RESULTS: Frequency of H. pylori eradication in group A and B was observed in 55 (68.8%) and 63 patients (78.8%), respectively. No significant difference was seen between two groups, regarding H. pylori eradication (p = 0.15). The most common side effects in group A, B were bitterness of mouth (63.8%) and nausea (16.2%), respectively (p H. pylori infection, higher rate of H. pylori eradication was seen in group B than group A. Thus, sequential regimen was a more appropriate regimen with fewer complications.

• Klíčová slova
• H. pylori infection, Sequential therapy, eradication, standard triple-drug therapy,
• MeSH
• amoxicilin aplikace a dávkování   MeSH
• dospělí MeSH
• Helicobacter pylori MeSH
• infekce vyvolané Helicobacter pylori farmakoterapie   MeSH
• klarithromycin aplikace a dávkování   MeSH
• kombinovaná farmakoterapie MeSH
• levofloxacin aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• omeprazol aplikace a dávkování   MeSH
• organokovové sloučeniny aplikace a dávkování   MeSH
• senioři MeSH
• tinidazol aplikace a dávkování   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• srovnávací studie MeSH
• Názvy látek
• amoxicilin MeSH
• bismuth tripotassium dicitrate MeSH Prohlížeč
• klarithromycin MeSH
• levofloxacin MeSH
• omeprazol MeSH
• organokovové sloučeniny MeSH
• tinidazol MeSH

BACKGROUND: Preterm prelabor rupture of the membranes (PPROM) is frequently complicated by intraamniotic inflammatory processes such as intraamniotic infection and sterile intraamniotic inflammation. Antibiotic therapy is recommended to patients with PPROM to prolong the interval between this complication and delivery (latency period), reduce the risk of clinical chorioamnionitis, and improve neonatal outcome. However, there is a lack of information regarding whether the administration of antibiotics can reduce the intensity of the intraamniotic inflammatory response or eradicate microorganisms in patients with PPROM. OBJECTIVE: The first aim of the study was to determine whether antimicrobial agents can reduce the magnitude of the intraamniotic inflammatory response in patients with PPROM by assessing the concentrations of interleukin-6 in amniotic fluid before and after antibiotic treatment. The second aim was to determine whether treatment with intravenous clarithromycin changes the microbial load of Ureaplasma spp DNA in amniotic fluid. STUDY DESIGN: A retrospective cohort study included patients who had (1) a singleton gestation, (2) PPROM between 24+0 and 33+6 weeks, (3) a transabdominal amniocentesis at the time of admission, and (4) intravenous antibiotic treatment (clarithromycin for patients with intraamniotic inflammation and benzylpenicillin/clindamycin in the cases of allergy in patients without intraamniotic inflammation) for 7 days. Follow-up amniocenteses (7th day after admission) were performed in the subset of patients with a latency period lasting longer than 7 days. Concentrations of interleukin-6 were measured in the samples of amniotic fluid with a bedside test, and the presence of microbial invasion of the amniotic cavity was assessed with culture and molecular microbiological methods. Intraamniotic inflammation was defined as a bedside interleukin-6 concentration ≥745 pg/mL in the samples of amniotic fluid. Intraamniotic infection was defined as the presence of both microbial invasion of the amniotic cavity and intraamniotic inflammation; sterile intraamniotic inflammation was defined as the presence of intraamniotic inflammation without microbial invasion of the amniotic cavity. RESULTS: A total of 270 patients with PPROM were included in this study: 207 patients delivered within 7 days and 63 patients delivered after 7 days of admission. Of the 63 patients who delivered after 7 days following the initial amniocentesis, 40 underwent a follow-up amniocentesis. Patients with intraamniotic infection (n = 7) and sterile intraamniotic inflammation (n = 7) were treated with intravenous clarithromycin. Patients without either microbial invasion of the amniotic cavity or intraamniotic inflammation (n = 26) were treated with benzylpenicillin or clindamycin. Treatment with clarithromycin decreased the interleukin-6 concentration in amniotic fluid at the follow-up amniocentesis compared to the initial amniocentesis in patients with intraamniotic infection (follow-up: median, 295 pg/mL, interquartile range [IQR], 72-673 vs initial: median, 2973 pg/mL, IQR, 1750-6296; P = .02) and in those with sterile intraamniotic inflammation (follow-up: median, 221 pg/mL, IQR 118-366 pg/mL vs initial: median, 1446 pg/mL, IQR, 1300-2941; P = .02). Samples of amniotic fluid with Ureaplasma spp DNA had a lower microbial load at the time of follow-up amniocentesis compared to the initial amniocentesis (follow-up: median, 1.8 × 104 copies DNA/mL, 2.9 × 104 to 6.7 × 108 vs initial: median, 4.7 × 107 copies DNA/mL, interquartile range, 2.9 × 103 to 3.6 × 107; P = .03). CONCLUSION: Intravenous therapy with clarithromycin was associated with a reduction in the intensity of the intraamniotic inflammatory response in patients with PPROM with either intraamniotic infection or sterile intraamniotic inflammation. Moreover, treatment with clarithromycin was related to a reduction in the load of Ureaplasma spp DNA in the amniotic fluid of patients with PPROM <34 weeks of gestation.

• Klíčová slova
• 16S ribosomal RNA, Ureaplasma, amniocentesis, amniotic fluid, bacteria, benzylpenicillin, biomarker, chorioamnionitis, clarithromycin, funisitis, genital mycoplasmas, great obstetrical syndromes, inflammation, interleukin-6, intraamniotic infection, microbial invasion of the amniotic cavity, neonatal outcome, neonatal sepsis, nucleic acid, polymerase chain reaction, pregnancy, prematurity, preterm birth, rapid point of care test, sterile intraamniotic inflammation,
• MeSH
• antibakteriální látky terapeutické užití   MeSH
• bakteriální infekce etiologie   prevence a kontrola   MeSH
• chorioamnionitida etiologie   prevence a kontrola   MeSH
• DNA bakterií analýza   MeSH
• dospělí MeSH
• interleukin-6 analýza   MeSH
• klarithromycin terapeutické užití   MeSH
• klindamycin terapeutické užití   MeSH
• kohortové studie MeSH
• lidé MeSH
• penicilin G terapeutické užití   MeSH
• plodová voda chemie   MeSH
• předčasný odtok plodové vody * MeSH
• retrospektivní studie MeSH
• těhotenství MeSH
• Ureaplasma genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• antibakteriální látky MeSH
• DNA bakterií MeSH
• IL6 protein, human MeSH Prohlížeč
• interleukin-6 MeSH
• klarithromycin MeSH
• klindamycin MeSH
• penicilin G MeSH

BACKGROUND: Experience in Helicobacter pylori eradication treatment of patients allergic to penicillin is very scarce. A triple combination with a PPI, clarithromycin (C), and metronidazole (M) is often prescribed as the first option, although more recently the use of a quadruple therapy with PPI, bismuth (B), tetracycline (T), and M has been recommended. AIM: To evaluate the efficacy and safety of first-line and rescue treatments in patients allergic to penicillin in the "European Registry of H pylori management" (Hp-EuReg). METHODS: A systematic prospective registry of the clinical practice of European gastroenterologists (27 countries, 300 investigators) on the management of H pylori infection. An e-CRF was created on AEG-REDCap. Patients with penicillin allergy were analyzed until June 2019. RESULTS: One-thousand eighty-four patients allergic to penicillin were analyzed. The most frequently prescribed first-line treatments were as follows: PPI + C + M (n = 285) and PPI + B + T + M (classic or Pylera® ; n = 250). In first line, the efficacy of PPI + C + M was 69%, while PPI + B + T + M reached 91% (P < .001). In second line, after the failure of PPI + C + M, two rescue options showed similar efficacy: PPI + B + T + M (78%) and PPI + C + levofloxacin (L) (71%) (P > .05). In third line, after the failure of PPI + C + M and PPI + C + L, PPI + B + T + M was successful in 75% of cases. CONCLUSION: In patients allergic to penicillin, a triple combination with PPI + C + M should not be generally recommended as a first-line treatment, while a quadruple regimen with PPI + B + T + M seems to be a better option. As a rescue treatment, this quadruple regimen (if not previously prescribed) or a triple regimen with PPI + C + L could be used but achieved suboptimal (<80%) results.

• Klíčová slova
• Helicobacter pylori, allergic, allergy, bismuth, clarithromycin, levofloxacin, penicillin,
• MeSH
• antibakteriální látky terapeutické užití   MeSH
• bismut terapeutické užití   MeSH
• Helicobacter pylori účinky léků   MeSH
• infekce vyvolané Helicobacter pylori farmakoterapie   MeSH
• inhibitory protonové pumpy terapeutické užití   MeSH
• klarithromycin terapeutické užití   MeSH
• kombinovaná farmakoterapie * MeSH
• léková alergie * MeSH
• levofloxacin terapeutické užití   MeSH
• lidé MeSH
• metronidazol terapeutické užití   MeSH
• peniciliny škodlivé účinky   terapeutické užití   MeSH
• prospektivní studie MeSH
• registrace statistika a číselné údaje   MeSH
• tetracyklin terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibakteriální látky MeSH
• bismut MeSH
• inhibitory protonové pumpy MeSH
• klarithromycin MeSH
• levofloxacin MeSH
• metronidazol MeSH
• peniciliny MeSH
• tetracyklin MeSH

Macrophage cells are present in high abundance in the lung to intercept invading microorganisms that gain access through airway mucosal surfaces. Several bacterial pathogens have evolved the capacity to evade the innate immune response by establishing infections within pulmonary macrophages upon phagocytosis, leading to prolonged disease. Macrolide antibiotics such as azithromycin and clarithromycin accumulate in phagocytic cells and have been shown to preferentially distribute in tissues where populations of these cells reside. We employed this class of molecules as targeting ligands to direct virus-like particles (VLPs) to lung-resident macrophages. VLP-macrolide conjugates showed enhanced uptake into RAW 264.7 macrophage cells in culture, with azithromycin displaying the greatest effect; distinct differences were also observed for different macrocycle structures and orientations on the particle surface. Activation of macrophage cells was stimulated by particle uptake toward an intermediate activation state, in contrast to previous reports using macrolide-functionalized gold nanorods that stimulated a cytotoxic macrophage response. Attached azithromycin was also able to direct VLPs to the lungs in mice, with significant accumulation within 2 h of systemic injection. These results suggest that this new class of bioconjugate could serve as an effective platform for intracellular drug delivery in the context of pulmonary infections.

• Klíčová slova
• azithromycin, clarithromycin, lung targeting, macrolide, macrophage, virus-like particles,
• MeSH
• Allolevivirus chemie   MeSH
• alveolární makrofágy metabolismus   MeSH
• antibakteriální látky chemie   farmakokinetika   MeSH
• azithromycin chemie   farmakokinetika   MeSH
• cytokiny metabolismus   MeSH
• Escherichia coli genetika   MeSH
• fagocytóza MeSH
• fenotyp MeSH
• klarithromycin chemie   farmakokinetika   MeSH
• lékové transportní systémy metody   MeSH
• myši MeSH
• plíce účinky léků   metabolismus   MeSH
• příprava léků metody   MeSH
• RAW 264.7 buňky MeSH
• tkáňová distribuce MeSH
• virové plášťové proteiny chemie   farmakokinetika   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• antibakteriální látky MeSH
• azithromycin MeSH
• cytokiny MeSH
• klarithromycin MeSH
• virové plášťové proteiny MeSH

Mixed infections and heteroresistance of Helicobacter pylori contribute to decreased efficacy of treatments. This study aimed to investigate frequency of clarithromycin heteroresistance and its link with mixed infections, medication history, and disease severity. A total of 40 pairs of H. pylori strains were isolated from the antrum and corpus of 97 patients. Susceptibility of the strains to clarithromycin was measured by agar dilution method. Site-specific mutations of 23S rRNA at A2143G, A2142G, and A2142C positions were analyzed by PCR and genomic relatedness of pairs of the strains was determined by random amplified polymorphic DNA (RAPD)-PCR. The results showed a prevalence of 35% (14/40) clarithromycin resistance. Diversity of the antrum and corpus isolates in resistance to clarithromycin was detected among 17.5% (7/40) of the patients. Similarly, diversity in MIC value was also detected in two patients infected with the sensitive strains. Significant difference in frequency of resistance was detected among patients with peptic ulcer disease (PUD) (MIC90 32 μg/mL) and severe gastritis (MIC90 16 μg/mL), compared with those who suffered from non-ulcer dyspepsia (NUD) (MIC90 8 μg/mL) and chronic gastritis (MIC90 0.25 μg/mL). MIC values showed 8-32 folds increased levels in the corpus. A2142G, A2143G, and A2142C mutations were detected in three, two, and two patients, respectively, but not observed in 46% of the resistant strains. RAPD-PCR fingerprints showed identical molecular patterns for the isolates of the corpus and antrum in each patient. In conclusion, microevolution of H. pylori strains during chronic infection, rather than mixed infection, and inappropriate medication appear to be main reasons of treatment failure in adults.

• MeSH
• antibakteriální látky farmakologie   MeSH
• bakteriální léková rezistence * účinky léků   genetika   MeSH
• dítě MeSH
• dospělí MeSH
• genetická variace MeSH
• Helicobacter pylori účinky léků   genetika   izolace a purifikace   MeSH
• infekce vyvolané Helicobacter pylori mikrobiologie   patologie   MeSH
• klarithromycin farmakologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mutace MeSH
• polymerázová řetězová reakce MeSH
• RNA ribozomální 23S genetika   MeSH
• senioři MeSH
• žaludek mikrobiologie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Írán MeSH
• Názvy látek
• antibakteriální látky MeSH
• klarithromycin MeSH
• RNA ribozomální 23S MeSH