Gram-negative pathogens

Several Gram-negative bacteria express smooth lipopolysaccharide (LPS) which consists of repeating saccharide units beyond the core saccharide each repeat is called an O-unit that usually comprises two to six sugars and the entire structure made up of repeating units is called the 0-antigen. In addition, several of these pathogens express capsular polysaccharide which also plays a key role in virulence. 

C3 and C4 binding to baaeria because LOS has been identified as a tai et fi r these complement components on Neisseriae and Haemophilus. Increased f or H bindii upon sialyiation of the lacto-A neotetraose LOS structure is unique toiVi gonorrhoeaemd requires the concomitant 

Rather interestingly, protease-defident mutants of P. n vabs bind eater amounts of both C3b and C5b-9 and are ph ocytosed more readily, yet remain serum resistant. Recent data have shown that complement resistance in P.pnffvalis does not depend on protease production but requires expression of cell surface polysaccharide, which is an anionic branched mannan structure. Similarly, loss of Y.pestis Pla expression docs not affect resistance to human complement, although Pla-negative mutants show decreased virulence murine infection models. - Complement deaving proteases may serve to limit anaphylatoxin generation and neutrophil influx rather than serving as the primary mechanism of serum resistance. 

Binding of Complement Inhibitory Molecules to the Bacterial Surface 

Over the past decade numerous pathogens have been shown to bind to complement inhibitory molecules which results in complement regulation on the bacterial surfece. The main fluid-phase complement inhibitory molecules are C1 -INH, C4BP, factor H and its alternatively spliced variant, FHL-1. Table 2 lists the pathogens and the molecule(s) on these bacteria that bind to complement inhibitory molecules. The bacteria bind these inhibitors in a manner that permits bound proteins to remain functionally active and perform their complement regulation functions. 

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The biomedical importance of infections by gram-negative pathogens and the consequences of septic shock have drawn much attention to lipid A, the toxic subcomponent of the lipopolysaccharide endotoxin of these organisms. A comprehensive account of the chemical structures and biological behavior of the lipid A structures is presented here by Zahrihnger, Lindner, and Rietschel. The chapter incorporates much of their own work from the... 

Fourth-generation cephalosporins were developed such as cefpirome and cefepime with additional activity against gram negative pathogens and greater stability against beta-lactamases. 

Treatment should be guided by the local or hospital resistance patterns. Extensive use of a quinolone for selective decontamination will increase the incidence of quinolone-resistant gram-negative pathogens. Alternative regimens for gut decontamination are oral colistin with an oral aminoglycoside such as neomycin. 

The antipseudomonal penicillins have comparable spectra of activity against many gram-positive and gram-negative pathogens, including most anaerobes. Mezlocillin, piperacillin, and ticarcillin have similar clinical outcomes in patients with known or suspected P. aeruginosa infections. Antipseudomonal penicillins are used to treat pneumonias associated with cystic fibrosis or mechanical ventilation. 

As this enzyme does not exist in mammals and man, potential specific inhibitors could serve as non-toxic, no side effect antibiotics against gram-negative pathogenic organisms imder consideration. 

Selective decontamination of the gastrointestinal tract was conceptualised with a view to preventing nosocomial infection (mainly due to enterobacteriaciae), specifically ventilator-associated pneumonia, in intensive care units. Protocols typically included the prescription of an intravenous cephalosporin with good activity against such Gram-negative pathogens (e.g. cefotaxime) with co-prescribed, poorly... 

Penicillin-allergic patients tolerate aztreonam without reaction. Occasional skin rashes and elevations of serum aminotransferases occur during administration of aztreonam, but major toxicity has not yet been reported. In patients with a history of penicillin anaphylaxis, aztreonam may be used to treat serious infections such as pneumonia, meningitis, and sepsis caused by susceptible gram-negative pathogens. 

JP Quinn. Clinical problems posed by multiresistant nonfermenting gram-negative pathogens. Clin Infect Dis 27 (Suppl) 1 S117-S124, 1998. 

Reiter, B., Marshall, V.M.E., Bjorck, L., and Rosen, C.G. 1976. Nonspecific bactericidal activity of the lactoperoxidase-thiocyanate-hydrogen peroxide system of milk against Escherichia coli and some Gram-negative pathogens. Infect. Immun. 13, 800—807. 

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