[Antibiotic pharmacokinetic indices and their significance in working out antibacterial therapy regimens and predicting their efficacy]. / Farmakokineticheskie pokazateli antibiotikov i ikh znachenie pri razrabotke skhem antibakterial'noi terapii, prognoze éffektivnosti.

The data on the value of pharmacokinetic parameters and pharmacologic properties of antibiotics for the development of optimal regimens of antibacterial therapy are presented. The impact of various symptoms and syndromes of purulent septic processes (uremia, anemia, obesity or hyperbilirubinemia) on antibiotic pharmacokinetics is discussed. Approaches to the improvement of schemes for antibiotic therapy of various pathological conditions are noted. Procedures (a microbiological one and those with the use of apparatus) for the determination of antibiotic concentrations in serum and tissues are described. Factors useful for the development of individual regimens of antibiotic therapy of various nosologic forms of infectious inflammatory diseases are indicated: some indices characterizing susceptibility of the pathogen to the drug used (minimum antibacterial, minimum inhibitory and bactericidal concentrations), difficulties with their interpretation (the phenomena of the pathogen persistence, microbial tolerance and Eagle's effect), environmental influences in the infection foci on the drug concentration.

[Semisynthetic penicillins: their importance in the current antibiotic therapy of infections. Penicillinase-resistant penicillins with predominantly antistaphylococcal action]. / Polusinteticheskie penitsilliny: znachenie v sovremennoi antibiotikoterapii infektsii. Penitsillinazoustoihchivye penitsilliny s preimushchestvenno antistafilokokkovym deistviem.

The status of isoxazolylpenicillins in the modern antibiotic therapy of staphylococcal infections is discussed from various viewpoints: the role and distribution of methicillin resistant staphylococci (MRSA), the methicillin tolerance, the clinical pharmacology and pharmacokinetics, the preferable administration routes and regimens depending on the disease severity and renal function, the prophylaxis of purulent infections, the indications to the combined therapy and possible side effects. It is indicated that one of the conditions providing the efficacy of penicillinase stable antistaphylococcal penicillins is the absolute knowledge of their properties and the joint efforts of the clinicians and bacteriologists in providing a rapid change of the drug after the detection of MRSA or methicillin tolerant staphylococci. This excludes any discredit of the drugs which are useful in the modern antistaphylococcal therapy.

[Sensitivity to cephalosporin antibiotics of infectious causative agents in surgery]. / Chuvstvitel'nost' k tsefalosporinovym antibiotikam vozbuditelei infektsii v khirurgii.

Comparison of antimicrobial effects of cephalosporins of the 1st and 2nd generations showed that the latter were advantageous with respect to gram-negative bacteria causing surgical infections. Three cephalosporins of the 3rd generation were characterized by the highest activity against such bacteria, including Enterobacter spp. and indole positive strains of Proteus spp., as well as non-enzymatic bacteria. The antimicrobial spectra and MICs of the new cephalosporins with respect to the cultures isolated from surgical patients were different which requires in vitro sensitivity assay of each antibiotic.

[Effect of pefloxacin on immune response]. / Vliianie perfloksatsina na immunnyi otvet.

The influence on cellular immune response of different doses of the pefloxacin was studied in vivo as well as in vitro experiments. The pefloxacin in super bactericidal concentrations (2.0 mg/ml and 0.4 mg/ml) possess pronounced supressing effect the T-lymphocyte proliferation in blast transformation reaction. While in concentration 0.08 mg/ml pefloxacin does not show such activity. The pefloxacin in maximal effective concentration (200 mg/kg) suppressed activity in delayed hypersensitivity skin reaction of intact mice towards sheep erythrocytes on 20.3 percent only.

[Pharmacokinetic study of implantable gentamycin preparations. I. Antibiotic pharmacokinetics in the implantation area and an evaluation of the prolonged effect of the preparations]. / Farmakokineticheskoe izuchenie implantiruemykh preparatov gentamitsina. I. Farmakokinetika antibiotikov v zone implantatsii i otsenka prolongiruiushchego éffekta preparatov.

Gentamicin pharmacokinetics was studied in the zone of subcutaneous implantation to rats of Septopal, a dosage form based on polymethylmethacrylate stable in vivo (4.5 mg of the antibiotic) and of preparations based on biodegradable polymers such as monocarboxycellulose, alginic acid, nonmodified and modified collagens (1 and 5 mg of the antibiotic). A three-phase pattern of gentamicin level changing in the implantation zone was observed: (1) rapid increasing and decreasing of the antibiotic concentration, (2) stabilization of the gentamicin content at a practically constant level and (3) slow lowering of the antibiotic level in the tissue. Comparison of the areas under the concentration/time curves showed that the modified collagen, alginic acid and monocarboxycellulose had the highest prolongation effect among the biodegradable polymers. Their use in the compositions provided during the first hours after the implantation the antibiotic concentrations in the administration site equal to tens micrograms per 1 g of the tissue. After that during 14 days the concentration of gentamicin in the implantation zone maintained at the level higher than its MIC for the main pathogens of wound infections.

[Effect of antibiotics on indices of immunologic reactivity in mice]. / Vliianie antibiotikov na pokazateli immunologicheskoi reaktivnosti u myshei.

The effect of ristomycin, chloramphenicol, kanamycin, benzylpenicillin, streptomycin, and cephaloridine on the indices of cellular and humoral immunity was studied comparatively on intact animals and on animals with secondary immune deficiency. The study of the antibiotic effect on the count of rosette-forming lymphocytes (RFL) and the total count of lymphocytes showed that all the antibiotics except streptomycin induced a significant decrease in the count of RFL. The most active was kanamycin. It lowered the count of RFL 5-fold as compared to the control. The total count of lymphocytes was lowered after administration of ristomycin, chloramphenicol and kanamycin. In the animals with immune deficiency induced by cyclophosphamide benzylpenicillin potentiated the inhibitory effect of cyclophosphamide on the weight of the lymphoid organs, while streptomycin lowered the effect of cyclophosphamide. No such effect was observed with the use of the other antibiotics. The data indicated the necessity of taking into account the effect of various antibiotics on the immune system, especially under conditions of immune deficiency.

[Effect of lomefloxacin on the synthesis of antibodies to vaccine EV fraction I and hemagglutinins]. / Vliianie lomefloksatsina na sintez antitel k I fraktsii vaktsiny EV i gemaggliutininov.

Multifactor analysis of the lomefloxacin effect on the primary immune response to T-independent bacterial antigen (vaccine EV fraction 1) and to T-dependent cellular antigen (SRBC) in mice was performed with the use of a wide range of the antibiotic concentrations and the dosage time. It was shown that lomefloxacin in the doses corresponding to the average therapeutic ones used for 3-9 days had no effect on the content of the IgG antibodies, was able to increase the level of the IgM antibodies and insignificantly lowered the concentration of the IgA antibodies.

[Role of microbiological control in the choice of antibacterial therapy of respiratory infection in surgical patients during the postoperative period]. / Rol' mikrobiologicheskogo kontrolia v vybore antibakterial'noi terapii pri infektsii dykhatel'nykh putei u khirurgicheskikh bol'nykh v posleoperatsionnom periode.

The paper presents data on observation of 416 surgical patients subjected to investigation of sputum and washings from the tracheobronchial tree for estimating the role of clinico-microbiological study of respiratory tract excretions from surgical patients in choice of adequate therapy. On the basis of the obtained data and results of clinical observations a scheme of clinico-microbiological criteria was developed which would be of help for clinicians and microbiologists in difficult differential diagnosis of colonization and infection. The scheme will provide clinical microbiologists with possibility of correct interpretation of the results of studying respiratory tract excretions and presenting information containing preliminary positive or negative indications as to the presence of infection and recommendations for continuation or discontinuation of further clinico-microbiological investigations.

[Study of the immunotropic activity of aminoglycoside antibiotics]. / Izuchenie immunotropnoi aktivnosti antibiotikov iz gruppy aminoglikozidov.

The action of some aminoglycoside antibiotics on the immune system was studied on both intact mice and the animals with immune deficiency caused by administration of cyclophosphamide. The following tests were used: local hemolysis (the Herne test), lymphocyte transformation (LT), delayed hypersensitivity to sheep red blood cells and the local graft versus host reaction (GVHR). Amikacin was shown to have no significant action on the activity of lymphocytes in the intact mice and stimulated both cellular (LT and GVHR) and humoral (the Herne test) immunity in the animals with lowered immunological reactivity. Sisomicin had no significant action on the immune system of the animals. Gentamicin suppressed the immune response only in the intact mice. Kanamycin and streptomycin induced inhibition of humoral and cellular immunity in both the intact mice and animals with immune deficiency. On the basis of the results it was concluded that gentamicin, amikacin and sisomicin may be used in the treatment of diseases developing in the presence of immune deficiency whereas streptomycin and kanamycin should be recommended when inhibition of the immunity is needed.

[Use of pefloxacin in the treatment of patients with purulent wounds of soft tissues]. / Primenenie pefloksatsina dlia lecheniia bol'nykh s gnoinymi ranami miagkikh tkanei.

Pefloxacin was used in the treatment of 25 patients with wound infection in a dose of 400 mg orally twice a day for 10-12 days. As the monotherapy it was applied to 15 patients. 7 patients with clinical signs of non-clostridial anaerobic infection were treated with pefloxacin in combination with intravenous metronidazole. Pefloxacin was highly efficient in 96 per cent of the cases with extensive posttraumatic purulent wounds with and without bone affection, acute purulent wounds of the soft tissue, purulent wounds of the soft tissues in diabetic patients, trophic or decubitus ulcer. 266 clinical isolates of Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Proteus mirabilis, Enterobacter spp. and Acinetobacter spp, were tested and 75 to 100 per cent of them was shown to be susceptible to pefloxacin and ciprofloxacin. At the same time the isolates of Pseudomonas aeruginosa and Klebsiella spp. were more susceptible to ciprofloxacin. The pathogen eradication and eradication with superinfection in the cases treated with pefloxacin amounted to 92 per cent. The drug tolerance was good. No clinically significant adverse events were recorded.

[Antibacterial treatment of infectious-toxic shock]. / Antibakterial'naia terapiia pri infektsionno-toksicheskom shoke.

The studies enabled one to identify six leading clinicophysiological syndromes developing in patients with infective toxic shock (ITS). They include signs of purulent inflammatory processes, organ disorders and systems disturbances. Despite the clinical picture polymorphism, ITS has a clearly defined stage-by-stage process which makes it possible to determine hyperdynamic and hypodynamic phases of the pathological process within each stage. An absolute condition for antimicrobial drugs includes the following: drainage of the purulent inflammatory focus, arresting of pathogen discharge into the blood flow, recovery of host impaired functions and their maintenance. It was shown that a wrong choice of the drugs and antibacterial therapy regimens resulted in a 2-fold increase in fatal cases with ITS. Disorders in systemic and organ blood flows and microcirculation and coagulation disturbances played a particular role in decreasing antibacterial therapy efficacy. Further ways for optimizing antibacterial therapy are mainly connected with availability of efficient antibacterial drugs for practitioners and introduction of microbiological and pharmacokinetic monitoring of antibacterial therapy providing conditions for their rational and safe use.