A systematic review of the infectious complications of colchicine and the use of colchicine to treat infections.

OBJECTIVE: Colchicine has been used historically as an anti-inflammatory agent for a wide range of diseases. Little is known regarding the relationship between colchicine use and infectious disease outcomes. The objective of this study was to systematically examine infectious adverse events associated with colchicine usage and the clinical use of colchicine for infectious diseases. METHODS: A systematic review was conducted in accordance with PRISMA methodology. PubMed, EMBASE, Scopus and Cochrane Library databases were searched (up to 12th October, 2020) for interventional and observational studies that included colchicine usage associated with infectious adverse events or infectious disease outcomes. RESULTS: A total of 9,237 studies were initially identified and after exclusions, 36 articles comprising 21 interventional studies and 15 observational studies were included in this systematic review. There were 19 studies that reported infectious adverse events and 17 studies that examined the efficacy of colchicine in treating infectious disease. Only two out of six studies reported a significant benefit using colchicine in the management of viral liver disease. There was some evidence colchicine is beneficial in managing COVID-19 by reducing time to deterioration, length of stay in hospital and mortality. Colchicine had some benefit in managing malaria, condyloma accuminata and verruca vulgaris, viral myocarditis and erythema nodosum leprosum based on case-series or small, pilot clinical studies. Two of the clinical trials and five of the observational studies reported significant associations between infections adverse events and colchicine usage. Risk of pneumonia was found in three studies and post-operative infections were reported in two studies. Risks of urinary tract infections, H. pylori and C.difficile were only reported by one study each. CONCLUSION: There is a current lack of clinical evidence that colchicine has a role in treating or managing infectious diseases. Preliminary studies have demonstrated a possible role in the management of COVID-19 but results from more clinical trials are needed. There is inconclusive evidence that suggests colchicine is associated with increased risk of infections, particularly pneumonia.

Discovery of Cephalosporin-3'-Diazeniumdiolates That Show Dual Antibacterial and Antibiofilm Effects against Pseudomonas aeruginosa Clinical Cystic Fibrosis Isolates and Efficacy in a Murine Respiratory Infection Model.

The formation of biofilms provides a formidable defense for many bacteria against antibiotics and host immune responses. As a consequence, biofilms are thought to be the root cause of most chronic infections, including those occurring on medical indwelling devices, endocarditis, urinary tract infections, diabetic and burn wounds, and bone and joint infections. In cystic fibrosis (CF), chronic Pseudomonas aeruginosa (P. aeruginosa) respiratory infections are the leading cause of morbidity and mortality in adults. Previous studies have shown that many bacteria can undergo a coordinated dispersal event in the presence of low concentrations of nitric oxide (NO), suggesting that NO could be used to initiate biofilm dispersal in chronic infections, enabling clearance of the more vulnerable planktonic cells. In this study, we describe efforts to create "all-in-one" cephalosporin-based NO donor prodrugs (cephalosporin-3'-diazeniumdiolates, C3Ds) that show both direct ß-lactam mediated antibacterial activity and antibiofilm effects. Twelve novel C3Ds were synthesized and screened against a panel of P. aeruginosa CF clinical isolates and other human pathogens. The most active compound, AMINOPIP2 ((Z)-1-(4-(2-aminoethyl)piperidin-1-yl)-2-(((6R,7R)-7-((Z)-2-(2-aminothiazol-4-yl)-2-(((2-carboxypropan-2-yl)oxy)imino)acetamido)-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl)methoxy)diazene 1-oxide)-ceftazidime 12, showed higher antibacterial potency than its parent cephalosporin and front-line antipseudomonal antibiotic ceftazidime, good stability against ß-lactamases, activity against ceftazidime-resistant P. aeruginosa in vitro biofilms, and efficacy equivalent to ceftazidime in a murine P. aeruginosa respiratory infection model. The results support further evaluation of AMINOPIP2-ceftazidime 12 for P. aeruginosa lung infections in CF and a broader study of "all-in-one" C3Ds for other chronic infections.