Spain, where a copy of pneumococcal resistance...

Although

S pneumonia in a sealed and razinkapsulirovat form only encapsulated strains were isolated from clinical material. The importance of the

capsule in pneumococcal virulence was first established enzymatic removal of capsule

and recently confirmed by genetic engineering, pneumococcus, which differ only in capsule type. >> << Virulence mutants relative to parental strains is determined, mainly, though not entirely, from capsular types. However, the capsule itself is not toxic. Consists of one 90 serologically different polysaccharides

virulence capsule lies mainly in its antiphagocytic properties (Fig.). The level of virulence more dependent on the chemical nature of the capsule then its size

production and serotype specific protective antibodies in response to the capsular polysaccharide is the basis of the current >> << anti-pneumococcal vaccine. Location, time and age differences in the distribution of 90 different serotypes

S pneumonia and the ability to transfer cassette capsule genes from one strain to another leads to specific changes in the capsule have potential implications for vaccine strategies. Currently 23 valent vaccine includes serotypes that cause 88% bacteraemic infections in the U.S. and 96% of those in the UK. In contrast to the capsule, cell wall is a potent inducer of inflammation,

, probably due to activation of complement and induction of cytokines. Active components of the cell wall polysaccharide complex teyhoevye acid whichBЂ "very unusual among bacteriaBЂ" contains fosforilholinom. As shown below, fosforilholinom is the site of adherence to activated endothelial cells during invasive disease

. Antibodies against cell wall polysaccharides or fosforilholinom protects against pneumococcal challenge, though

protective effect is much weaker than antibodies to the capsular polysaccharide. In addition to surface polysaccharides, pneumococcus contains several proteins that have been shown to promote

on virulence (Fig.

). They include pneumolysin, intracellular toxin, which is released only when exposed to cell wall lysis; autolysin,

enzyme responsible for lysis of cell wall, and pneumococcal surface protein (PVNS) protein on the cell surface

that high immunogenicity in mice. Other pneumococcal products that can contribute to pathogenicity of the organism, but their role in virulence is not set >> << include neuraminidase, hyaluronidase

neutrophil elastase inhibitor,,

,

inhibitor of neutrophil respiratory burst, and number

anticipated adhezyny protein. The most extensively studied virulence factors protein pneumolysin, a toxin that lysed cholesterol containing cells

membranes and activates complement. Pneumolysin has several harmful effects on the host cell and function in vitro,

and causes severe lobar pneumonia when injected into the apical bronchus of rats. More direct evidence of its role in pathogenicity comes from the demonstration that laboratory mutated strains of pneumococcus

lack pneumolysin have reduced virulence compared with wild-type organisms, and that immunization or pneumolysin toxoid protects mice from subsequent challenges with virulent pneumococci. Cytolytic and complement activating properties of pneumolysin has recently been mapped to specific regions of the molecule. Using strains of pneumococci with mutations in each of these molecular sites, it was shown that both sites contribute

to the pathogenesis of pneumococcal pneumonia at different stages of infection and by different mechanisms. Similar studies with antisera and genetically modified mutants showed deposits and autolysin in the pathogenicity of PVNS. Interest in pneumococcal proteins lies not only in their pathogenicity, and that, as whites, they are T-dependent antigens and have the potential to be used to improve pneumococcal vaccine. Currently, the vaccine based on capsular polysaccharides, which are T independent antigensBЂ "ie, they can cause the immune response by stimulating B cells directly, without the help of T cellsBЂ" have two disadvantages: very poor immunogenicity in children under two years and lack of response to memory steering perevyzov with antigen. By combination of polysaccharide antigens to protein, but they can be converted to T-dependent form that does not have these drawbacks. Despite the lack of immunological carrier protein need that from pneumococcal infection, pneumococcal protein

may be beneficial in the attribution of specific immunity. One of the potential drawbacks of new vaccines conjugate

is that only a limited number of serotypes can be included. To determine this outweighs the potential benefits

need to follow, as the incidence of pneumococcal infections, pneumococcus serotypes distribution after

enter conjugated vaccine. Another group of clinically important proteins in the cell wall transcarboxypeptidases that also bind penicillin (penicillin

proteins). Changes in penicillin-binding properties of these proteins caused by the transfer of genes >> << to penicillin binding proteins of other streptococcal species resulting mosaic genes and can occur without compromising

building the cell wall enzyme functions. Because only part of the transferred genes, and that

several penicillin binding proteins, which can be changed gradually, the level of resistance to penicillin may

significantly. This graded nature of penicillin resistance has direct relevance to clinical practice, for most BЂњresistantBЂ "types of pneumonia

S isolated from clinical samples show only intermediate resistance (minimum inhibitory concentration (MIC) 0. 12BЂ" 1. 0BЂ ‰ nјg / ml) to penicillin. These middle-income can easily be exceeded in light intravenous treatment of high doses of penicillin, and Pallaresa

and others recently showed that even strattera online in Spain, where a copy of pneumococcal resistance to penicillin is high, penicillin G or administration of ampicillin in high doses intravenously is still an effective treatment for pneumococcal pneumonia. These authors recommend alternativeBЂ "third generation cephalosporinBЂ" only in life-threatening pneumonia or when risk factors are present at high levels of resistance to penicillin (MIC B ‰ G2. 0BЂ ‰ nјg / ml). It should be noted that the same principles, not shown, used for treatment of pneumonia erythromycin resistant

S. While some of the newer macrolides better light penetration than erythromycin, clinical trials of these drugs in

not conducted in patients with resistant pneumococcal pneumonia erythromycin, and in these patients is recommended

non-macrolide agents be used. Resistance to penicillin in S pneumonia is increasing worldwide. This problem is particularly prevalent in Spain, Eastern Europe, South Africa, South America, New Guinea and Korea, where resistance to 30BЂ "50% usually reported. However, even in low total number of resistant organisms, including the UK, the proportion of pneumonia

, S, resistant to penicillin is increasing, along with resistance to erythromycin and other antibiotics (Fig.

). Most strains belong to a small number of serotypes (6, 14, 19 and 23), which are common in young children

and that will be included in the new combined vaccine. .