zithromax and Colitis

Ulcerative colitis (UC), a chronic autoimmune disease of the gut with a relapsing and remitting nature, considers a major health-care problem. DSS is a well-studied pharmacologically-induced model for UC. Toll-Like Receptor 4 (TLR4) and its close association with p-38-Mitogen-Activated Protein Kinase (p-38 MAPK) and nuclear factor kappa B (NF-κB) has important regulatory roles in inflammation and developing UC. Probiotics are gaining popularity for their potential in UC therapy. The immunomodulatory and anti-inflammatory role of azithromycin in UC remains a knowledge need. In the present rats-established UC, the therapeutic roles of oral probiotics (60 billion probiotic bacteria per kg per day) and azithromycin (40 mg per kg per day) regimens were evaluated by measuring changes in disease activity index, macroscopic damage index, oxidative stress markers, TLR4, p-38 MAPK, NF-κB signaling pathway in addition to their molecular downstream; tumor necrosis factor alpha (TNFα), interleukin (IL)1β, IL6, IL10 and inducible nitric oxide synthase (iNOS). After individual and combination therapy with probiotics and azithromycin regimens, the histological architecture of the UC improved with restoration of intestinal tissue normal architecture. These findings were consistent with the histopathological score of colon tissues. Each separate regimen lowered the remarkable TLR4, p-38 MAPK, iNOS, NF-κB as well as TNFα, IL1β, IL6 and MDA expressions and elevated the low IL10, glutathione and superoxide dismutase expressions in UC tissues. The combination regimen possesses the most synergistic beneficial effects in UC that, following thorough research, should be incorporated into the therapeutic approach in UC to boost the patients' quality of life.

Topics: Animals; Azithromycin; Colitis; Colitis, Ulcerative; Colon; Dextran Sulfate; Dextrans; Disease Models, Animal; Interleukin-10; Interleukin-6; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Quality of Life; Rats; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

Topics: Adult; Aged; Anti-Bacterial Agents; Antimalarials; Astringents; Azithromycin; Betacoronavirus; Colitis; Coronavirus Infections; COVID-19; Humans; Hydroxychloroquine; Male; Middle Aged; Pandemics; Pneumonia, Viral; Radiography, Abdominal; SARS-CoV-2; Tomography, X-Ray Computed; Treatment Outcome; Zinc Sulfate

Here we characterized the murine dextran sulfate sodium (DSS) model of acute colitis. Specifically, we evaluated azithromycin and metronidazole treatment regimens to assess their effects on animal wellbeing, pathologic changes, barrier function, cytokine and chemokine profiles, and neutrophil migration in colon tissue. Azithromycin treatment significantly reduced the severity of colitis, as assessed through body weight change, water consumption, macroscopic lesions, and animal behaviors (activity level, climbing, and grooming), but did not alter food consumption or feeding behavior. Mucosal barrier function (evaluated by using FITC-labeled dextran) was decreased after DSS exposure; azithromycin did not significantly alter barrier function in mice with colitis, whereas metronidazole exacerbated the colitis-related deficit in barrier function. In addition, metronidazole appeared to exacerbate disease as assessed through water consumption and animal behaviors (overall activity, climbing, grooming, and drinking) but had no effect on weight loss, macroscopic lesions, or eating behavior. Pathologic changes were typical for DSS treatment. Antibiotic treatment resulted in reduced levels of proinflammatory cytokines and chemokines and decreased neutrophil adhesion and emigration in DSS-exposed mice. The results highlight the importance of clinical and behavioral assessments in addition to laboratory evaluation as tools to evaluate animal welfare and therapeutic efficacy in disease models. Data from this study suggest that azithromycin may convey some benefits in the mouse DSS colitis model through modulation of the immune response, including neutrophil migration into tissues, whereas metronidazole may exacerbate colitis.

Topics: Animals; Azithromycin; Behavior, Animal; Cell Movement; Chemokines; Colitis; Colon; Dextran Sulfate; Disease Models, Animal; Metronidazole; Mice; Mice, Inbred C57BL; Neutrophils

Guidelines recommend azithromycin or a quinolone antibiotic for treatment of Legionella pneumonia. No clinical study has compared these strategies.. We performed a retrospective cohort analysis of adults hospitalized in the United States with a diagnosis of Legionella pneumonia in the Premier Perspectives database (1 July 2008-30 June 2013). Our primary outcome was hospital mortality; we additionally evaluated hospital length of stay, development of Clostridium difficile colitis, and total hospital cost. We used propensity-based matching to compare patients treated with azithromycin vs a quinolone. All analyses were repeated on a subgroup of more severely ill patients, defined as requiring intensive care unit admission or mechanical ventilation or having a predicted probability of hospital mortality in the top quartile for all patients.. Legionella pneumonia was diagnosed in 3152 adults across 437 hospitals. Quinolones alone were used in 28.8%, azithromycin alone was used in 34.0%, and 1.8% received both. Crude hospital mortality was similar: 6.6% (95% confidence interval [CI], 5.0%-8.2%) for quinolones vs 6.4% (95% CI, 5.0%-7.9%) for azithromycin (P = .87); after propensity matching (n = 813 in each group), mortality remained similar (6.3% [95% CI, 4.6%-7.9%] vs 6.5% [95% CI, 4.8%-8.2%], P = .84 for the whole cohort, and 14.9% [95% CI, 10.0%-19.8%] vs 18.3% [95% CI, 13.0%-23.6%], P = .36 for the more severely ill). There was no difference in hospital length of stay, development of C. difficile, or total hospital cost.. Use of azithromycin alone or a quinolone alone for treatment of Legionella pneumonia was associated with similar hospital mortality. Few patients receive combination therapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Azithromycin; Clostridium Infections; Cohort Studies; Colitis; Female; Hospital Costs; Hospital Mortality; Humans; Legionellosis; Length of Stay; Male; Middle Aged; Quinolones; Retrospective Studies; Treatment Outcome; United States; Young Adult

Inflammation-driven immune dysfunction supports the development of several chronic human disorders including inflammatory bowel diseases and rheumatoid arthritis. Macrolides are effective antibiotics endowed with immunomodulatory effects. In this study we report the chemical synthesis and the pharmacological characterization of CSY0073, a non-antibiotic derivative of azithromycin. CSY0073 was tested for efficacy in two experimental models of colitis induced by administering mice with dextran sulfate (DSS) and trinitrobenzene sulphonic acid (TNBS) and in collagen induced arthritis. Like azithromycin, CSY0073 improved clinical, macroscopic and histopathological scores in mice administered DSS (12.5μmol/kg/day p.o.) and TNBS (45μmol/kg/day p.o.). When administered to TNBS-treated mice, CSY0073 effectively attenuated influx of neutrophils and macrophages into the colonic mucosa and reduced the intestinal expression pro-inflammatory cytokines TNFα, IL-2 and IFNγ. CSY0073 (0.1 to 10μM) counter-regulated TNFα, IFNγ, IL-12 and IL-23 release caused by exposure of mouse spleen monocytes and CD11b+ cells isolated from the colonic lamina propria to endotoxin. CSY0073 (25μmol/kg/day) reduced clinical scores in the collagen induced murine model of rheumatoid arthritis. In myeloid cells, CSY0073 (10μM) prevented the nuclear translocation of the p65 subunit of NF-κB and its binding to canonical NF-κB responsive elements. In summary, we report a novel class of non-antibiotic 14-member macrocycles with anti-inflammatory and immune-modulatory effects. CSY0073, the prototype of this new class of macrolides exerts counter-regulatory activity on NF-κB signaling. This study suggests the exploitation of non-antibiotic macrolides in the treatment of inflammatory disorders characterized by immune dysfunction.

Topics: Animals; Anti-Inflammatory Agents; Arthritis; Azithromycin; CD11b Antigen; Colitis; Collagen; Dextran Sulfate; Disease Models, Animal; Drug Discovery; Female; Humans; Immunologic Factors; Inflammation; Inflammatory Bowel Diseases; Male; Mice; Mucous Membrane; NF-kappa B; Signal Transduction; Trinitrobenzenesulfonic Acid

The aim of this study was to investigate the effect of the macrolide antibiotic azithromycin on mucosal changes and colonic bacterial load in a murine model of colitis.. Colitis was induced in CD1 mice using enema of 0.2% solution of dinitrofluorobenzene, combined with skin sensitization. Four experimental groups of animals (N = 10 per group) were treated with 50 mg/kg/day azithromycin (AZ) or metronidazole (MN) perorally, starting 24 h before (AZ-1, MN-1) or 6 h after (AZ+1, MN+1) induction of colitis and for consecutive 5 days. Additional experimental mice group was treated with 10 mg/kg/day methylprednisolone intraperitoneally after induction of experimental colitis in the same manner (MP). Two control groups consisted of healthy animals (C) that received the challenge enema with phosphate-buffered saline (PBS) and animals with experimental colitis (chall) treated with equivolume of PBS perorally. Clinical score (0-5) and histopathologic score (0-30) were used to assess inflammatory changes, and colon washings were used to determine changes in bacterial load.. The anti-inflammatory effect of azithromycin did not differ from the effect of methylprednisolone, when compared with control group with experimental colitis. Metronidazole did not show a significant anti-inflammatory effect. Number of colonic bacteria did not differ significantly between control and experimental groups of animals.. We documented the anti-inflammatory effect of azithromycin in a murine model of acute colitis, suggesting that effects were targeted to oxidative burst and on mucosal/bacterial interface, independent of luminal bacterial load. Further studies should be focused on effect of azithromycin on the role of bacterial biofilm in perpetuation of chronic intestinal inflammation.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Colitis; Colon; Inflammation; Male; Methylprednisolone; Metronidazole; Mice; Specific Pathogen-Free Organisms