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    The efficacy of adjuvant N acetyl cysteine for the eradication of H pylori infections: A systematic review and meta-analysis of randomized clinical trials. Clinics and research in hepatology and gastroenterology BACKGROUND:Biofilm-producing bacteria are relatively resistant to antibiotics, as the penetration of antibiotics into the endopolysaccharide envelope is incomplete. N Acetyl cysteine (NAC) is known to destabilize the biofilms, as it cleaves the disulfide bonds of mucus glycoproteins, reducing the viscosity and thickness of mucus. This allows NAC to act synergistically with antibiotics for the eradication of H Pylori. The meta-analysis evaluates the evidence of the efficacy of adjuvant N acetyl cysteine (NAC) compared to standard therapies in the eradication of H. Pylori infections. METHODS:We searched randomized clinical trials in MEDLINE, Cochrane Central Register of Clinical Trials (CENTRAL), EBSCO, Database of Abstracts of Reviews of Effects (DARE), and Google Scholar. We included trials comparing standard treatment protocols plus adjuvant NAC and the same regimen without NAC. These studies included adults with a diagnosis of Helicobacter pylori infection. Our primary outcome was the successful eradication of H. Pylori. The results were pooled using a random-effects model, and data were analyzed using RevMan 5.0 software. Cochrane collaboration's tool was used to assess the risk of bias. Publication bias and other inconsistencies were assessed. Sensitivity analyses and grading of evidence were performed. FINDINGS:Eight studies, comprising 1167 patients, were included in the meta-analysis, the pooled outcomes of patients on adjuvant NAC+ standard eradication therapy noted an eradication rate of 76.1% (n=581) compared to the patients in standard eradication therapy with a rate of 72.18% (n=586), RR 1.17 [95% CI (0.99, 1.39); I2= 64%; p value=0.07]. Moderate to severe heterogeneity was noted. These pooled results show that adjuvant NAC plus standard treatment protocols are not superior to standard treatment protocols for H pylori eradication. Similar results were seen in the use of adjuvant NAC with 'currently used standard treatment protocols' (78.3% versus 76.3%, RR 1.08, [95% CI 0.94 to 1.25]; I2=55%; p=0.28; n= 829 patients], as well as in the treatment of naïve patients (79.8% versus 80.9%, RR 1.00[95% CI 0.87 to 1.15]; i2=27%; P=-0.98; n= 775 patients]. CONCLUSION:Adjuvant NAC plus standard treatment protocols are not superior to standard treatment protocols for H. pylori eradication. These findings are consistent with the use of adjuvant NAC with 'currently used standard treatment protocols' (clarithromycin-based triple therapies) and also with adjuvant NAC used in the treatment of naïve patients. We are moderately certain of these findings. Future studies could explore the use of NAC as a pretreatment before using the current standard therapies in the eradication of H. Pylori rather than NAC as adjuvant therapy. FUNDING:None. 10.1016/j.clinre.2021.101832
    Biofilm Formations in Pediatric Respiratory Tract Infection Part 2: Mucosal Biofilm Formation by Respiratory Pathogens and Current and Future Therapeutic Strategies to Inhibit Biofilm Formation or Eradicate Established Biofilm. Hamilos Daniel L Current infectious disease reports PURPOSE OF REVIEW:The purpose of this review is to discuss the unique pathways of biofilm formation utilized by respiratory pathogens and current and future therapeutic strategies to inhibit biofilm formation or eradicate established biofilm in the context of these pathogens. Both nonselective and selective strategies for inhibiting biofilm formation or disrupting established biofilm are discussed. RECENT FINDINGS:Numerous strategies are being actively pursued to inhibit biofilm formation or eradicate established biofilm in respiratory pathogens. These can be broadly categorized by the stage of biofilm formation (adhesion, extracellular polysaccharide synthesis or structure, EPS, and matrix degradation) that they target and by their selectivity or lack thereof for specific biofilm pathogens. Nonselective inhibitors of adhesion include N-acetylcysteine and artificial surfactants and biosurfactants. Selective inhibitors of adhesion include mannosides that target host-EPS interactions, EPS-targeted antibodies, and other inhibitors of bacterial adhesion. Nonselective inhibitors of EPS synthesis and structure include cyclic di-GMP and cyclic di-AMP-through disruption of glucan-producing exoenzymes. Selective inhibitors of EPS synthesis and structure include antibodies that target proteins essential for biofilm structure (such as DNABII proteins and type IV pilin protein in NTHi) or antibodies that target critical molecules in biofilm formation (such as DNA adenine methyltransferase in Streptococcus pneumoniae). Nonselective agents for EPS or biofilm matrix degradation include peptidoglycan hydrolases that enzymatically degrade bacterial cell wall peptidoglycan and DNase, which degrades extracellular DNA from neutrophils and microorganism-derived DNA. Selective agents for EPS or biofilm matrix degradation include exopolysaccharide-degrading enzymes, such as glycoside hydrolases active against Staphylococcus aureus or exopolysaccharide-degrading enzymes that target Psl and Pel from Pseudomonas aeruginosa. Current strategies toward inhibiting biofilm formation or disrupting established biofilm represent an exciting new approach toward treatment of chronic infectious diseases. Application of these strategies toward treatment of pediatric respiratory tract infections also offers promise of a better understanding of the significance of mucosal biofilm in the pathogenesis of these conditions. 10.1007/s11908-019-0657-x
    N-acetylcysteine as an adjuvant therapy for Helicobacter pylori eradication. Fontes Luís Eduardo S,Martimbianco Ana Luiza C,Zanin Carolina,Riera Rachel The Cochrane database of systematic reviews BACKGROUND:Helicobacter pylori (H pylori) is one of the most common pathogens to establish and cause infection in human beings, affecting about 50% of the world's population. Prevalence may be as high as 83% in Latin American countries and as low as 17% in North America. Approximately 20% of infected people will manifest disease; people at high risk include those who live in low- and middle-income countries with poor sanitary conditions, since the mechanism of transmission seems to be oral-oral or faecal-oral (mostly during infancy). There are several antibiotic regimens to treat the infection, but antibiotic resistance is growing around the world. New adjuvant drugs - such as probiotics, statins, curcumin, and N-acetylcysteine (NAC) - are being tested to enhance eradication rates.N-acetylcysteine can destabilise the biofilm structure; it also has synergic action with antibiotics, and bactericidal effects. In addition, NAC has antioxidant properties, and has a primary mucolytic effect by reducing the thickness of the gastric mucus layer, both of which may exert beneficial adjuvant effects on H pylori eradication. OBJECTIVES:To assess the efficacy and safety of N-acetylcysteine as an adjuvant therapy to antibiotics for Helicobacter pylori eradication. SEARCH METHODS:We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1966 to April 2018), Embase (1988 to April 2018), CINAHL (1982 to April 2018), LILACS (1982 to April 2018), grey literature databases and trials registries. We handsearched the reference lists of relevant studies. We screened 726 articles and assessed 18 for eligibility. SELECTION CRITERIA:We included randomised controlled trials (RCTs) of any antibiotic regimen plus NAC, in adults infected with H pylori. To be included, trials had to use a control consisting of the same antibiotic regimen with or without placebo. Outcomes of interest were eradication rates, and gastrointestinal, toxic, and allergic adverse events. Reporting of the primary outcomes listed here was not an inclusion criterion for the review. DATA COLLECTION AND ANALYSIS:Two review authors independently reviewed and extracted data and completed the 'Risk of bias' assessments. A third review author independently confirmed the 'Risk of bias' assessments. We used Review Manager 5 software for data analysis. We contacted study authors if there was missing information. MAIN RESULTS:We included eight RCTs (with a total of 559 participants) in this review. The studies recruited outpatients aged between 17 and 76 years who were referred to endoscopy centres in several different countries. The certainty of evidence was reduced for most outcomes due to the poor methodological quality of included studies; issues mainly related to the generation of allocation sequence, allocation concealment, and blinding (this last domain related specifically to adverse outcomes).We are uncertain whether the addition of NAC to antibiotics improves H pylori eradication rates, compared with the addition of placebo or no NAC (38.8% versus 49.1%, risk ratio (RR) 0.74, 95% confidence interval (CI) 0.51 to 1.08; participants = 559; studies = eight; very low-certainty evidence). A post-hoc sensitivity analysis, in which we removed studies that tested antibiotic regimens no longer recommended in clinical practice, showed that the addition of NAC may improve eradication rates compared to control (27.2% versus 37.6%, RR 0.71, 95% CI 0.53 to 0.94; participants = 397; published studies = five).We are uncertain whether NAC is associated with a higher risk of gastrointestinal adverse events compared to control (23.9% versus 18.9%, RR 1.25, 95% CI 0.85 to 1.85; participants = 336; studies = five; very low-certaintyevidence), or allergic adverse events (2% versus 0%, RR 2.98, 95% CI 0.32 to 27.74; participants = 336; studies = five; very low-certainty evidence). There were no reports of toxic adverse events amongst included studies. AUTHORS' CONCLUSIONS:We are uncertain whether the addition of NAC to antibiotics improves H pylori eradication rates compared with the addition of placebo or no NAC. Due to the clinical, statistical and methodological heterogeneity found in included studies, and the uncertainty observed when analysing therapy subgroups, any possible beneficial effect of NAC should be regarded cautiously.We are uncertain whether NAC is associated with a higher risk of gastrointestinal or allergic adverse events compared with placebo or no NAC. There were no reports of toxic adverse events amongst the included studies.Further large, well-designed, randomised clinical studies should be conducted, with good reporting standards and appropriate collection of efficacy and safety outcomes, especially for current recommended antibiotic regimens. 10.1002/14651858.CD012357.pub2
    Biofilms and infections of the upper respiratory tract. Pintucci J P,Corno S,Garotta M European review for medical and pharmacological sciences Biofilms are microbial communities consisting of bacteria that either are self-reproducing on biological surfaces or are present in the lifeless environment. Biofilms are quite diffuse entities frequently found in human pathological conditions. The formation of bacterial biofilms involves mainly the contamination of artificial medical devices, such as valves and catheters, and their direct implant on mucous membranes, with subsequent development of chronic or recurrent infections. Bacterial biofilms show a complex organization consisting of bacterial cells adherent to a surface and surrounded by a large extracellular matrix mostly made up of polysaccharides and proteins. The resistance observed in biofilms does not appear to be genotypic; instead, it is due to multicellular strategies and/or to the ability of each cell, contained inside the biofilm, to differentiate into a protected phenotypic state which tolerates the antibiotic action. In fact, biofilms are subject to changes following their recurrent exposure to antimicrobial agents, thus incrementing their resistance. Biofilms play an important role in otitis media, sinusitis, chronic cholesteatomatous otitis media, tonsillitis and adenoiditis, thus demonstrating that adenoidectomy may be helpful to children suffering from such a morbid conditions. It is presently estimated that biofilm formation is involved in at least 60% of all chronic and/or recurrent infections. In addition, 30% of the exudates developing in the course of otitis media has shown to be positive for the presence of biofilms; likewise biofilms have been found in tonsillar crypts and in odontostomatologic infections as well. Studies have been carried out on both the use and the efficacy of N-acetylcysteine (NAC) in biofilm breakdown. It has been shown that NAC, used at different concentrations, is able to reduce bacterial adhesion in several anatomical districts.
    Effects of N-acetyl-cysteine and acetylsalicylic acid on the tonsil bacterial biofilm tissues by light and electron microscopy. Bulut F,Meric F,Yorgancilar E,Nergiz Y,Akkus M,Nergiz S,Nasir Y European review for medical and pharmacological sciences OBJECTIVE:The present study aimed to investigate the effects of the bacterial biofilm formation on the tonsil surface exposed N-acetyl-cysteine (NAC) and acetylsalicylic acid (ASA) of patients undergoing tonsillectomy by light and electron microscopy. The general process of biofilm formation comprises adhesion of free-living or planktonic bacteria to a surface, which subsequently develop into microcolonies and form a biofilm. Based on studies that have shown the presence of biofilms in common sites of chronic infections, it has become clear that bacteria may persist on mucosal surfaces through formation of biofilms. PATIENTS AND METHODS:Ten patients between 4 and 39 years of age (mean, 11.9 ± 11.2 years). In all cases, periodic acide Schiff (PAS) staining was found to be an accurate predictor of the presence or absence of biofilm using light microscopy as a control standard. Therapeutic doses of NAC and ASA were identificated as the effective on the tonsil bacterial biofilm using light and electron microscopy. RESULTS:Biofilm formation was detected on all samples. Tonsils removed from patients with ASA-10 had showed higher-grade inhibitory effect at the biofilm formation than the other group (p ≤ 0.0001). The correlation was found between drug dose and decrease at the biofilm formation. CONCLUSIONS:In chronic or recurrent tonsillitis patients, decrease on the tonsils surface biofilm formation may be associated with ASA dose. Whether effect on the tonsils surface biofilm formation of other agent have a role is not known. Key Words: Acetylsalicylic acid, Chronic tonsillitis, In vitro, Mucosal biofilm, N-Acetyl-cysteine.
    Protective effect of N-acetylcysteine in prosthetic joint infection: A nationwide population-based cohort study. Chang Chan-Yuan,Chien Wu-Chien,Chung Chi-Hsiang,Tsao Chang-Huei,Lin Fu-Huang,Chang Feng-Yee,Shang Shih-Ta,Wang Yung-Chih Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi PURPOSE:This nationwide population-based retrospective cohort study evaluated the protective effect of N-acetylcysteine against prosthetic joint infection after hip or knee joint replacement. METHODS:Patients receiving N-acetylcysteine after hip or knee joint replacement between 2000 and 2015 were identified from the Taiwan National Health Insurance Research Database. Each patient receiving N-acetylcysteine was matched to four controls based on age, sex, and index year. All subjects were followed-up from the index date to December 31, 2015. The Cox proportional hazards regression model was used to assess the risk of prosthetic joint infection. RESULTS:A total of 1478 patients were included in the study group, and 5912 matched subjects not receiving N-acetylcysteine were included in the control group. After adjusting for age, sex, insured premium, comorbidities, and immunosuppressive agent use, no significant difference in the risk of prosthetic joint infection was found between the two groups. A higher N-acetylcysteine dose (>360 cumulative defined daily dose) significantly decreased the risk of prosthetic joint infection (adjusted hazard ratio = 0.891; 95% confidence interval = 0.599-0.989; p = 0.042). The protective effect of N-acetylcysteine was observed only in the group of prosthetic joint infection within 5 years (adjusted hazard ratio = 0.801; 95% confidence interval = 0.581-0.980; p = 0.040). CONCLUSIONS:High cumulative dose of N-acetylcysteine (>360 cumulative defined daily dose) can effectively reduce the risk of prosthetic joint infection in patients undergoing knee or hip joint replacement surgery within 5 years. 10.1016/j.jmii.2018.08.014
    [Effect of N-acetylcysteine inhalation on ventilator-associated pneumonia caused by biofilm in endotracheal tubes]. Qu D,Ren X X,Guo L Y,Liang J X,Xu W J,Han Y H,Zhu Y M Zhonghua er ke za zhi = Chinese journal of pediatrics OBJECTIVE:To observe the formation of the biofilm in endotracheal tubes, the characteristics of etiology, drug resistance and effect on the biofilm and ventilator-associated pneumonia (VAP) of inhaled N-acetylcysteine (NAC). METHOD:We selected 117 tracheally intubated and undergoing mechanical ventilation for ≥48 h in our hospital ICU from September 2010 to August 2012. All the cases were randomly divided into control group (60 cases) and study group (57 cases). The patients in the study group were treated with different doses of aerosolized NAC according to different ages, starting the first administration within 12 hours of mechanical ventilation, once every 8 hours, until stopping mechanical ventilation. Comparison was performed on the two groups in biofilm structure under the scanning electron microscopy, biofilm culture positive rate, VAP incidence, the etiology and drug resistance of the lower airway secretions and biofilms. RESULT:(1) Electron microscopy showed that biofilm had formed in the endotracheal tube inner wall in early period of mechanical ventilation. With prolonged mechanical ventilation, biofilm structure improved. At the same time of mechanical ventilation, the thickness of biofilm in the study group decreased as compared with the control group. (2) Biofilm culture positive rate and incidence of ventilator-associated pneumonia decreased in the study group compared with in the control group (65%(37/57) vs. 80%(48/60), P<0.05; 11% (6/57)vs. 32%(19/60), P<0.01). (3) A large number of pathogenic bacteria colonized in the biofilm and gram-negative bacilli dominated. With prolonged mechanical ventilation, the cultured pathogens converged from the lower airway secretions and biofilm. CONCLUSION:With prolonged mechanical ventilation, biofilm structure was improved. Inhalation of NAC can inhibit biofilm formation and reduce the incidence of VAP. 10.3760/cma.j.issn.0578-1310.2016.04.010
    The effect of N-acetylcysteine on biofilms: Implications for the treatment of respiratory tract infections. Blasi Francesco,Page Clive,Rossolini Gian Maria,Pallecchi Lucia,Matera Maria Gabriella,Rogliani Paola,Cazzola Mario Respiratory medicine OBJECTIVES:In airway infections, biofilm formation has been demonstrated to be responsible for both acute and chronic events, and constitutes a genuine challenge in clinical practice. Difficulty in eradicating biofilms with systemic antibiotics has led clinicians to consider the possible role of non-antibiotic therapy. The aim of this review is to examine current evidence for the use of N-acetylcysteine (NAC) in the treatment of biofilm-related respiratory infections. METHODS:Electronic searches of PUBMED up to September 2015 were conducted, searching for 'biofilm', 'respiratory tract infection', 'N-acetylcysteine', 'cystic fibrosis', 'COPD', 'bronchiectasis', 'otitis', and 'bronchitis' in titles and abstracts. Studies included for review were primarily in English, but a few in Italian were also selected. RESULTS:Biofilm formation may be involved in many infections, including ventilator-associated pneumonia, cystic fibrosis, bronchiectasis, bronchitis, and upper respiratory airway infections. Many in vitro studies have demonstrated that NAC is effective in inhibiting biofilm formation, disrupting preformed biofilms (both initial and mature), and reducing bacterial viability in biofilms. There are fewer clinical studies on the use of NAC in disruption of biofilm formation, although there is some evidence that NAC alone or in combination with antibiotics can decrease the risk of exacerbations of chronic bronchitis, chronic obstructive pulmonary disease, and rhinosinusitis. However, the usefulness of NAC in the treatment of cystic fibrosis and bronchiectasis is still matter of debate. Most of the studies published to date have used oral or intramuscular NAC formulations. CONCLUSIONS:Evidence from in vitro studies indicates that NAC has good antibacterial properties and the ability to interfere with biofilm formation and disrupt biofilms. Results from clinical studies have provided some encouraging findings that need to be confirmed and expanded using other routes of administration of NAC such as inhalation. 10.1016/j.rmed.2016.06.015