Anti-infective agent

Silver and its compounds have long been used as antimicrobial agents in medicine. The mechanisms of silver toxicity as they relate to human exposure to pharmaceuticals have been reviewed (328). Silver is active at low concentrations and has a low toxicity. The practice of instilling the eyes of infants with 1% of AgN03 solution immediately after birth is still common in some countries, for prevention of opthalmia neonatorum (329). Silver sulfadiazine 77 is clinically used as a topical antimicrobial and antifungal agent and applied as a cream to prevent bacterial infections in cases of severe burns. It is an insoluble polymeric compound and releases Ag(I) ions slowly. 

The mechanism of Ag(I) cytotoxicity is unknown. Cell wall damage may be important and it has been shown that Cys-150 in the enzyme phosphomannose isomerase, an essential enzyme for the biosynthesis of Candida albicans cell walls, is the Ag(I) target in this organism (330). Silver resistant bacteria are known, but only recently has significant progress been made in understanding the resistance mechanisms (637). 

Material-based approaches to metalloantimicrobial agents are being developed. For example, AgCl/Ti02 composite (e.g., 20 80) formulated with sulfosuccinate salts can maintain an equilibrium of ppm-ppb levels of cytotoxic Ag(I) ions when suspended in solution (335, 336). 

Chagas disease is caused by a kinetoplastid trypanosoma parasite and affects millions of people in Latin America. The disease is currently incurable. Chemotherapy is based mainly on nitrofuran and nitroimidazole compounds and sterol biosynthesis inhibitors such as ketoconazole (337). Toxicity and high doses are the major problems for these organic drugs. Urbina et al. (338, 339) have found that com-plexation of antiparasitic organic agents such as chloroquine (78) 

Malaria is still one of the world s most devastating infectious diseases. An estimated 270 million people are affected by the parasite every year, and close to 2 million children die. The most deadly species, Plasmodium falciparum, has become widely resistant to most of the available antimalarial drugs such as quinolines. 

This section covers parasitic (protozoa and helminths ( worms )), bacterial and viral diseases. The mechanisms of action of many of these agents are complex and diverse and, in some cases, not fully understood, but enzyme inhibition is common to many. 

The hisilory of work on the preveniiun uf bacterial infection eon be traced back to the I9ih century when Joseph Lister (in 1867) introduced antiseptic priticiples fur use in surgery imii posiirautnaiic injury. He u.sed phenol (carbolic acid) ns a wash fur the hands, as a spray un an incision site, and on bandages applied to wound.s. Lister s principles caused a dramatic decrease in the incidence of posisurgiual infections. 

Just prior to 1950. great strides were made in anti-infective therapy. The sulfonamides and. sulfones (this chapter), more effective phenolic compounds such as hcxachlorophcnc. synthetic antimalarial compounds (Chapter 9). and a number of antibiotics (Chapter 10) wen introduced to the therapeutic armamentarium. 

Deconiominulion Deittnictian or marked reduction in the number or activity of microoisanisms 

Dlslnlcclion Chemical or physical ifcatmeni that dcMtroys most vcguiativo microbes or viru but not spores, in or on inanimate surfaces 

Sanitization Reduction of microbial load on an inanimate surface to a level considered acceptable for public health purposes 

Recent advances on diverse and potent biological profiles of 1,2,3-triazolo-nucleosides along with emerging application of cHck chemistry in their synthesis and their perspectives have been reviewed [87]. In the article, the work is primarily addressed to antiviral, antimicrobial, and anticancer potency of these 

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Specific biological activity of carboxylic acids peroxide derivatives in compaiison with their oxidation ability and ionization degree in aqueous solutions has been considered. Peroxyoctanoic, diperoxynonandioic and diperoxydecandioic acids give the most intense bactericidal effect among researched cai boxylic acids peroxide derivatives. The perspectives of use of the aliphatic middle-chain peracid C8-C9 as anti-infective agents have been discussed. 

Condon SM, LaPorte MG, Herbertz T (2005) Allosteric inhibitors of hepatitis C NS5B RNA-dependent RNA polymerase, Curr Med Chem Anti-Infect Agents 4 99-110 Cooper CL, van Heeswijk RP, Gallicano K, Cameron DW (2003) A review of low-dose ritonavir in protease inhibitor combination therapy, Clin Infect Dis 36 1585-1592 Courcambeck J, Bouzidi M, Perbost R, Jouirou B, Amrani N, Cacoub P, Pepe G, Sabatier JM, Halfon P (2006) Resistance of hepatitis C vims to NS3 A protease inhibitors mechanisms... 

Reid E. Wilson D. (eds) 990) Analysis for Drugs and Metabolites including Anti-infective Agents. 

Beaulieu, P.L. and Llinas-Brunet, M. (2002) Curr. Med. Chem. Anti-Infect. Agents 1, 163-176. 

If the presence of SBP is suspected, empiric antibiotic therapy with a broad-spectrum anti-infective agent should be initiated until cultures and susceptibilities are available (Fig. 19-5).45,46 In the setting of presumed infection, delaying... 

Mustard RA, Bohnen JMA, Rosati C, Schouten D. Pneumonia com- Solomkin JS, Mazuski JE, Baron EJ, et al. Guidelines for the selection plicating abdominal sepsis. Arch Surg 1991 126 170-175. of anti-infective agents for complicated intraabdominal infec-... 

Zorf, D., and Roth, S. (1996). Oligosaccharides anti-infection agents. Lancet 347,1017-1021. 

For anti-infective agents, reports on the in vivo and in vitro tests and the... 

Joukhader C, Derendorf H, Muller M. 2001. Microdialysis. A novel tool for clinical studies of anti-infective agents. Eur J Clin Pharmacol 57(3) 211-219. 

Macrodantin is a proprietary preparation of nitrofurantoin, an anti-infective agent used in urinary tract infections. 

The application of a mild topical corticosteroid, such as hydrocortisone, is effective in patients presenting with multiple mosquito bites. Paracetamol, which is an antipyretic agent is not indicated in mosquito bites. Fusidic acid cream is an anti-infective agent and is indicated if the mosquito bites have been scratched and there is risk of infection. Benzocaine (anaesthetic) and mepyramine (antihistamine) may relieve itchiness but are less effective in multiple mosquito bites than hydrocortisone. 

C Go potent anti-inflammatory agent D an anti-infective agent... 

Fotie J, Bohle D S. (2006) Pharmacological and biological activities of xan-thones. Anti-Infect Agents Med Chem 5 15-31. 

Hudson AT, Dickins M, Ginger CD, Gutteridge WE, Holdich T, Hutchinson DBA, Pudney M, Randall AW, Latter VS. (1991) 566C80 A potent broad spectrum anti-infective agent with activity against malaria and opportunistic infections in AIDS patients. Drugs Exp Clin Res 17 427-35. 

Microbially produced secondary metabolites are extremely important to our health and nutrition. As a group, they have tremendous economic importance. In the year 2007, the market for all anti-infective agents was 66 billion, and most of this was represented by 160 antibiotics and their derivatives. In 1929, Alexander Fleming published his historic observation that a contaminating mold, identified as PenicilUum notatum, killed his... 

WIN 57294 137 is a potent inhibitor of DNA gyrase it is both clastogenic and mutagenic, which precluded its development as a human anti-infective agent [193]. This compound was subsequently found to possess moderate topo II inhibitory activity ( 50=7.6 pM). Structure activity relationship studies of WIN 57294 137 resulted in the discovery that the 3-CO2H group was not a requisite for topo II potency for 138, ( 50= 17 pM) [194]. A conformationally rigid quinolone derivative 139 has been reported to display better topo II potency ( 50=2.77 pM) [195]. 

Schlitzer M (2005) Curr Med Chem Anti-Infective Agents 4 277... 

In cases of bacterial infections, concomitant use of anti-infective agents is mandatory. 

Dentali, S. J., and J. J. Hoffmann. Potential anti-infective agents from Eriodictyon angustifolium and Salvia apiana. Int J Pharmacog 1992 30(3) 223-231. 

Manfredi and L. Calza, Anti-Infective Agents Med. Chem. 2007, 6, 63. 

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