Gram-negative bacterial infections

One of the most serious consequences of (Gram-negative) bacterial infection is the possible development of septic shock. This is caused by the release of lipopolysaccharide (LPS endotoxin) from the bacterial cell surface. Various anti-LPS monoclonals (mainly targeted at its lipid A component Chapter 3) have been developed. It is hoped that administration of such monoclonals to affected individuals would effectively mop up free LPS, hence ameliorating the severity of the condition. Most trial results to date have proved disappointing in this regard. 

The endotoxlc activity associated with Gram-negative bacterial infections resides in the lipophilic lipid A part of the LPS molecule (1). This toxic activity manifests itself in a number of ways, e.g., pyrogenicity, transient leucopenla followed by leucocytosis, hypotension, bone marrow necrosis, abortion, the Shwartzman reaction, etc. As a consequence the commonly used killed whole cell enterobacterial vaccines have to be given in... 

As indicated in Chapter 33, metronidazole has bactericidal effects and is used in certain gram-negative bacterial infections. This drug may be administered orally or intravenously. Other agents have also been developed that are structurally and functionally similar to metronidazole. Tinidazole (Tindamax), for example, can be used in cases where metronidazole is not tolerated or is ineffective.24... 

Cross, A. S., and Opal, S. M. (1995). Endotoxin s role in gram-negative bacterial infection. Cwrr. Opin. Infect. Dis. 8, 156-163. 

Initial Studies of Anti-LPS Core Antibodies as Therapy for Gram-Negative Bacterial Infections... 

Christensen (8) prepared acetic acid derivatives, (VII), which were effective as fatty acid synthase inhibitors useful in the treatment of gram-positive and gram-negative bacterial infections such as E. coli and S. aureus and S. epidermidis. 

Marquez-DavUa G, Martinez-Barreda C, Suarez-Ramirez I. Capsulas de vibora desecada una fuente potencial de infec-cion por bacterias Gram negativas. [Desiccated rattlesnake capsules a potential source of Gram-negative bacterial infection.] Rev Invest Chn 1991 43(4) 315-17. 

Polymyxin E (colistin) is used in the treatment of serious Gram-negative bacterial infections, particularly those caused by Pseudomonas aeruginosa. It binds tightly to the lipid A component of LPS in the outer membrane of Gram-negative bacteria. The outer leaflet of the membrane structure is distorted, segments of which are released and the permeability barrier is destroyed. The polymyxin mole-... 

Indications Gram-negative bacterial infections, cystic fibrosis... 

Tetracyclines were the first broad-spectrum antibiotics and have been used successfully for decades to treat both gram-positive and gram negative bacterial infections (82). Chlortetra-cycline was the first tetracycline to be isolated, in 1948, from Streptomyces aureofaciens (83). Other common tetracyclines, such as oxytet-racycline and tetracycline, were isolated from Streptomyces sources in subsequent years. The abundance of natural, active tetracyclines, coupled with extensive synthetic alterations, provides a rich collection of compounds from which to build meaningful structure-activity relationships. As was found for the aminoglycosides, previous observations of tetracycline structure and activity can be rationalized from recent tetracycline/30S crystal structures (11,12). 

L Weinstein. Gram-negative bacterial infections a look at the past, a view of the present, and a glance at the future. Rev Infect Dis 7 (suppl 14) S538-544, 1985. 

Nikita D, Michalopoulos A. Colistin therapy for microbiologically documented multidrug-resistant Gram-negative bacterial infections a retrospective cohort study of 258 patients. Int J Antimicrob Agents 2010 35(2) 194-9. 

Gentamicin sulfate is an example for an aminoglycoside antibiotic formulated by fermentation of Micromonospora purpurea, used to treat Gram-negative bacterial infections. These antibiotics contain a mixture of active compounds as well as fermentation impimties and degradation products. The pharmaceutical... 

Kanamycin is used to treat a wide variety of serious gram-negative bacterial infections and is purified from fermentation of S. kanamyceticus. The main component of kanamycin is kanamycin A with minor structurally related constituents such as kanamycins B, C, and D. 

Jack, R.S., Fan, X., Bernheiden, M., Rune, G., Ehlers, M., Weber, A., Kirsch, G., Mentel, R., Furll, B., Freudenberg, M., Schmitz, G., Stelter and Schiitt, C. (19 Lipopolysaccharide-binding protein is required to combat a murine Gram-negative bacterial infection. Nature 389, 742-745. 

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