Therapy of sepsis should include at least two obligatory components -suppression of the pathogen and restoration of immunity.
Basis of sepsis therapy is oppression and liquidation of the pathogen. The means of syndromes treatment which restore immunity and all others if there is a necessity should not be ignored, but all of them can not cure the patient with sepsis without appropriate ethiotropic therapy.
Antibiotic therapy of sepsis may be successful, if:
1) It is carried out according to the agent definition and its antibiotic sensivity;
2) It will be carried out by bactericidal drugs. Bacteriostatic drugs are used only additionally;
3) It is applied at early septicemia (at this stage of illness recovery is achieved in 100 % with one antibiotic without all other means of treatment);
4) Dozes of antibiotics are maximum high, and p-lactamic antibiotics (penicillines, cephalosporines) are used in megadozes;
5) Empirical antibiotic therapy (if the agent is unknown) is carried out on the basis of the clinical supposition about a nature of the agent (empirical antibiotic therapy is should not be carried out by random);
6) Combination of antibiotics is carried out by a rule: bactericidal drugs with the various mechanism of action;
7) Usage of more than two preparations in one combination is not expedient, as with increase of number of drugs harmful actions grow faster, than therapeutic effect;
8) It is not necessary to start antibiotic therapy from reserve antibiotics (carbopenems, cephalosporines of 4th generation).
If treatment is successful,antibiotic therapy is cancelled last,after liquidation of all infection foci, but not earlier 5th day of a normal body temperature. Sepsis is a general clinical medical problem. Comprehension of sepsis should become the common medical property because such patients are in all medical establishments without exception.
Among various combinations of antibiotics the greatest recognition has received combination of cephalosporines of 3rd generation (ceftriaxoni, cefotaximi, ceftazidimi) with aminoglicosides (gentamicini, amikacinum). All these combinations are effective enough at patients with sepsis without a neutropenia. Appreciable interest to ceftriaxoni is caused by duration of its period of semiconclusion, that allows to apply preparation once per day. Other preparations have shorter period of semiconclusion and demand repeated injection during a day. At sepsis caused by Pseudomonas aeruginoza, high efficiency of combination of penicillines with antipyocyanic activity (ticarcilini, clavulanati, aztreonami) and aminoglicosides is marked.
At sepsis caused by Gram-positive flora (meticilini-resistant Staphylococcus aureus, coagulasenegative staphylococcuses, enterococcus), using of vancomycinum, rifampicinum is effective.
Sepsis
Carbapenemes (tienamicines) - special group of p-lactames antibiotics (imipenicemi, tienami, meropenemi, biapenemi), the infections created for empirical therapy with serious current, including leukopenia. Very wide spectrum of action, high bactericides, that is not accompanied by superfluous remission of endotoxins at destruction of bacteria, allow to use with success carbapenemes as monotherapy at the most severe infections, including sepsis.
After isolation and identification of the pathogen, definition of antibioticogram the choice of effective antibacterial therapy is considerably facilitated. In such cases monotherapy is frequently used. Nevertheless, the question of indication of monotherapy or a combination of antibacterial preparations remains debatable and, apparently, should be discussed in each concrete case. Determining arguments, probably, will be estimation of gravity of infectious process and condition of reactivity of organism, danger of occurrence of hospital infections in connection with invasive methods of diagnostics and treatment, transplantation of extraneous bodies. Nevertheless, at Gram-negative infections, in opinion of many scientists, the combined therapy is more expedient.
Antibiotics, as a rule, do not suppress immunity. It is proved, that lincosamides and macrolides have immunomodulative properties and are capable to stimulate the certain parts of the immune responce.
Duration of antibiotic therapy is determined by course of inflammatory process. As a rule, preparations cancel at proof normalization of temperature (absence of signs of generalized process), absence of the clinical and laboratory data on presence of the localized center of an infection or joining of nosocomial infections. At average therapy lasts 2-3 weeks. At revealing clinical efficiency of empirical or purposeful therapy by antibiotics change of a combination or separate preparation is inexpedient during all period of treatment.
The immunotherapy should be directed on blocking of effects of endotoxin and citocines. Application of pentoxifilini is perspective, which has protictive influence on lungs, systemic hemodynamics,' improves microcirculation and oxygenation of tissues, stabilizes electrolytic balance, preventing occurrence of hyponatremia.
Citoprotective antioxidantes (vitamin E, acetylcysteinum) oppress activity of free radicals and may improve the forecast at sepsis. Hyperproduction of free radicals which are metabolites of an arachidonic acid is lowered also by ibuprofenum.
In 70th years efficiency of polyclonal antibodies to E. coli and Salmonella
which at septic shock caused by Gram-negative bacteria's, reduce a lethality
almost on 50 % was proved. Now polymyxin  or neutrophile bactericidal
penetrating protein is used.
Efficiency of application for prophylaxis of the systemic responce on inflammation of vactination of patients by derivative of endotoxin - mono-phosphorolipides A is now studied. Monoclonal antibodies to interleucines,
362 Infectious diseases
phospholipase, to adhesive molecules and contact factors are received and pass clinical approbation of antibody to lipid A and endotoxin. It is possible,that in future by identification of mediators it will be possible to create "cocktail" from antibodies which block receptors and enable to stop progresive process at the systemic inflammatory answer.
Interferons - native and genoengineering preparations which concern mainly to IFN (roferoni A, introni A, realdironi, laferoni) - natural ways of imunocorection and protection against infections, with success are applied at present of acute and chronic infectious diseases.
Combined using of carbapenemes, roncoleucines or interferons is advanced achievement of modern therapy of septic diseases.
At serious course of a sepsis stabilization of hemodynamics has crucial importance. First of all it is necessary to restore volume of circulating blood. For this purpose cristaloides and colloid solutions are infused in ratio 2-4:1 under the control of hemodynamics parameters, including the central venous pressure.
The proof hypotension, even after fast restoration of blood volume circulation, may be connected with disorders of regulation of vascular tone. Application of inotropic preparations - dopaminum, dobutaminum, dobutrexi in this case is expedient. The clinical effect from dopaminum will increase the cardiac emission (p-adrenergic effect), rising of peripheric vessels tone (a-adrenergetic effect), improvement of circulation in parenchymatous bodies, first of all in kidneys (dopamineergetic effect). Using of a-adrenomimetics (epinephrine) may be necessary only in case of inefficiency of high doses of dopaminum.
Respiratory support is necessary for significant amount of patients with sepsis, however application of different methods of artificial ventilation of lungs is limited to cases of disease with development of acute respiratory insufficiency. In a combination of inotropic therapy ventilating support promotes decrease of work of muscles, improvement of oxygenation of blood and function of systemic circulation.
In support of appropriate level of metabolic and immune processes the important value has a feed of patients. The early high-caloric enteronutrition with the enlarged contents of fibers and amino acids (arginine, ornithine) reduces frequency of complications and duration of treatment. It is necessary to use enteral alimentary admixtures (enpites), balanced under the contents of fibers, adepses and carbohydrates.
It is expedient to use solutions of amino acids for parenteral feeding (alvesini, aminosoli-600, aminosoli-800, aminosoli KE, infesoli 40 etc), dextrosum, lipide emulsions (intralipid).
DIC demands correction only in stage of decompensation.
Prophylaxis
It is necessary to perform opportune treatment of primary foci. The measures, directing on increase of resistance of the organism have an important meaning. These measures are rational diet, regime of work and rest, physical training.
Sepsis
Staphylococci are more frequent etiological factor of sepsis, because prophylaxis of intrahospital staphylococcous infection is necessary. The early revealing and prohibition of work of medical personnel with purulent inflammatory diseases (sore throat, pyodermia) and opportune hospitalization of the patients with staphylococcal infection in special departments or wards. It is necessary the revealing of prolonged bacteriocarriers of hospital strains of staphylococcuses and its sanation for patients with immunodeficiency and operating-room.
The maintenance of sanitary-hygienic regime has leading meaning in the hospitals of different profile.
It is necessary to use remedies, increasing nonspecific resistance of the organism of the patients in the groups of risk (infants, patients with immunodeficiency and others).
Control questions:
1. Essential differences of sepsis from others diseases.
20. The Merck Manual of Diagnosis and Therapy. - Merck Sharp, 1987. - 2696 p.
21. Principles and Practice of Infectious diseases / Edited by Gerald L.,Mandel R.,Gordon Douglas, John E Bennett. - 3rd ed. - Churchill Livingstone Inc. - New York - 1990. - 2340 p.
22. Reese R.E. A Practical Approach to Infectious Diseases - Boston-Toronto: Little, Brown & Company, 1986. - 782 p.
23. Ellner P.D., Neu H.C. Understanding Infectious Diseases - Mosby Year Book, 1992. - 343 p.