[Kinetics of the antibacterial effect of ampicillin and sulbactam combinations in dynamic and static conditions]. / Kinetika antimikrobnogo éffekta kombinatsii ampitsillina s su'lbaktamom v dinamicheskikh i staticheskikh usloviiakh.

Kinetics of antimicrobial effect (AME) of ampicillin/sulbactam combinations (ratios of 4:1 to 1:2) on ampicillin resistant bacterial strains producing beta-lactamases of types II, III, IV and V according to Richmond classification was studied with using the computerized system MS-2 (turbidimetric recording) and an in vitro dynamic model (microcalorimetric recording). The concentrations of the drugs in system MS-2 (static conditions) corresponded to the maximum ones observed in serum of humans after bolus intravenous administration of ampicillin in a dose of 0.5 g and sulbactam in doses of 0.125 to 0.5 g. The pharmacokinetic profiles of the drugs observed in the human serum after their oral and intravenous administration and in the tissue-chamber fluid after intravenous administration of ampicillin (0.5 g) and sulbactam (0.125 g) were simulated in the dynamic model. The combination efficacy was estimated with using the parameter of AME duration (TE) reflecting shifts in the curves of the microbial regrowth in the presence of the drugs against the curve of the control growth (in the absence of the drugs) and the parameter of the AME intensity (IE) evaluated by the area between the curves. It was noted that increasing of the ampicillin/sulbactam ratio from 1:4 to 1:1 was accompanied by an increase in the AME. Further increasing of the sulbactam content in the combination did not result in higher AME. For combined ampicillin/sulbactam dosage forms the ratios of 1:1 to 2:1 should be recommended.(ABSTRACT TRUNCATED AT 250 WORDS)

[Antibiotic therapy of angiogenic sepsis]. / Antibiotikoterapiia angiogennogo sepsisa.

Introduction to medical practice of new penicillins, cephalosporins and aminoglycosides is one of the chief reserves for increasing efficacy of antibacterial therapy. The main schemes of antibiotic use in treatment of sepsis and individual regimens controlled by laboratory findings are discussed. Optimization of antibiotic therapy schemes is based on pharmacokinetic studies, quantitative assay of antibiotic sensitivity and determination of antibacterial activity of serum and other biosubstrates at definite periods after antibiotic administration. In vitro time course investigation of the bactericidal effect of gentamicin, azlocillin and cefotaxime on pathogens of purulent infections at various sizes of the inoculum provided prediction of the antibiotic therapy efficacy in various purulent septic infections. It is indicated that rational use of antibiotics markedly increases efficacy of sepsis therapy and improves social and economic indices of the treatment.

[Comparative activity of new semisynthetic penicillins and their combinations with gentamycin against gram-negative bacteria]. / Sravnitel'naia aktivnost' novykh polusinteticheskikh penitsillinov i ikh sochetanii s gentamitsinom v otnoshenii gramotritsatel'nykh bakterii.

Comparative antibacterial activity of two novel ureidopenicillins (azlocillin and piperacillin), carbenicillin and ampicillin against 170 clinical strains of Enterobacteriaceae and 43 strains of Pseudomonadaceae was studied. Higher antibacterial activity of azlocillin and piperacillin evident from lower frequency of resistant strains and lower MICs for the majority of the isolates was shown. Impact of the inoculum size on the MIC values was observed with respect to all the penicillins. The study on the kinetics of Pseudomonadaceae death under the effect of azlocillin and carbenicillin revealed an increase in the bacteria growth after 6- to 8-hour contact with therapeutic concentrations of azlocillin and 4-hour contact with carbenicillin. Nor renewal of the culture growth was observed within 10-hour contact with combinations of the penicillins and 2 micrograms/ml of gentamicin.

[Comparative evaluation of the antibacterial activity of aminoglycosides by means of microcalorimetry]. / Sravnitel'naia otsenka antibakterial'noi aktivnosti aminoglikozidov metodom mikrokalorimetrii.

Possible use of microcalorimetry for comparative investigation of antibiotics is exemplified by estimation of the kinetics of the antibacterial effect of netilmicin, sisomycin and gentamycin sulfate on moderately sensitive strains of E. coli and P. aeruginosa. It is suggested that the area under the curve of the kinetics of the rate of heat release by the bacterial cultures in the presence of antibiotics be used as a parameter characterizing the integral antibacterial effect. The parameter was used for demonstrating the differences in the antibacterial action of netilmicin, sisomycin and gentamycin sulfate on the strains tested with application of various inoculum sizes and antibiotic concentrations.

[Pharmacokinetics of cefazolin during hemosorption and hemodialysis]. / Farmakokinetika tsefazolina pri gemosorbtsii i gemodializa.

The influence of hemosorption and hemodialysis on the pharmacokinetics of cefazolin was studied in 20 patients with chronic and acute renal insufficiency. The integral mean value of the antibiotic extraction coefficient in hemosorption was approximately 2 times higher than that in hemodialysis. In the first case the value of this parameter systematically lowered with time (the constant of the process rate amounted to 0.89 h-1), while in the second case it was constant.

[Laboratory methods of controlling the effectiveness of antibacterial therapy]. / Laboratornye sposoby kontrolia éffektivnosti antibakterial'noi terapii.

The serum antibacterial activity (SAA) against causative agent isolated after the use of antibiotics was studied in 68 patients with pyoseptic diseases. The SAA ranged from 1:2 to 1:512 and depended on the antibiotic sensitivity of the causative agents. Antibiotic therapy was effective, when the SAA was equal to 1:8-1:512. With the use of monotherapy the adequacy of the regimens was controlled by the relation between the maximal blood level of the antibiotic and its MIC for the causative agent. The favourable clinical effect of the treatment with aminoglycosides and beta-lactams corresponded to the SAA exceeding 4.

[Pharmacokinetics of sisomicin during hemosorption and hemodialysis]. / Osobennosti farmakokinetiki sizomitsina pri gemosorbtsii i gemodialize.

The effect of hemosorption and hemodialysis on the pharmacokinetics of sisomicin was studied in 17 patients with acute and chronic renal insufficiency. The value of the antibiotic extraction coefficient in hemosorption was almost 2 times higher than that in hemodialysis. In patients on hemosorption, extracorporeal elimination of the antibiotic was of the saturation nature. It was characterized by systematic diminishing of the extraction coefficient, while in patients on hemodialysis, it did not depend on the time (the value of the extraction coefficient was constant). In this connection it is recommended that the rate of diminishing of the extraction coefficient in hemosorption be estimated. Since sisomicin is rapidly absorbed by the column it is not advisable to administer sisomicin to patients before hemosorption.

[Use of antibioticograms for individual programs of antibacterial therapy]. / Ispol'zovanie antibiotikogrammy dlia individualizatsii rezhimov antibakterial'noi terapii.

The increasing role of antibiotic-resistant microorganisms in etiology of bacterial infections and the increased number of the antibiotics used for the treatment of patients with purulent infections require a rational approach to the choice of the optimal drug. Antibiotic sensitivity of the causative agents of bacterial infections is considered at present as one of the main indices determining the efficacy of antibacterial therapy. Determination of antibiotic sensitivity by the disk diffusion method with quantitative and semi-quantitative interpretation of the results provides information for choosing the most effective drug and calculating its optimal dose in control therapy. Equations for calculating the MICs antibiotics by the inhibition growth zones and the drug levels in blood and urine attained with the use of different doses and administration routes are presented.

[Pharmacokinetic basis for using tobramycin and sisomicin in treating pyelonephritis of the transplanted kidney]. / Farmakokineticheskoe obosnovanie skhemy primeneniia tobramitsina i sizomitsina v lechenii pielonefrita transplantirovannoi pochki.

The pharmacokinetics of tobramycin and sisomicin in patients after kidney transplantations was studied. A significant variability of the pharmacokinetic parameters of tobramycin and sisomicin under conditions of the changing function of the kidney transplant was shown. This required individual control of the drug serum levels in such patients. Linear correlation between the exponent (beta) and the clearance of endogenous creatinine was observed. On the basis of this correlation a nomogram providing a decrease in the percentage of the errors in determining the dosage intervals was plotted.

[Rapid microbiological method of determining the gentamicin, sisomicin and kanamycin concentrations in patients' serum]. / Uskorennyi mikrobiologicheskii metod opredeleniia kontsetratsii gentamitsina, sizomitsina i kanamitsina v syvorotke krovi bol'nykh.

A modification of the microbiological agar-diffusion method for rapid determination of gentamicin, sisomycin and kanamycin levels in the blood serum of patients is described. The decrease in the time for determination of the antibiotic levels in the serum specimens with the modified method was provided by the use of a higher inoculation dose of the test microbe, higher levels of the incubation temperature and an enriched nutrient medium. The assay time was decreased from 18 to 3--4 hours as compared to the routine agar-diffusion method.

[Comparative characteristics of the methods for assessing aminoglycoside extraction with the artificial kidney tobramycin clearance and dialyzability]. / Sravnitel'naia kharakteristika metodov otsenki ékstraktsii aminoglikozidov apparatom "iskusstvennaia pochka": klirens i dializuemost' tobramitsina.

The pharmacokinetics of tobramycin after its intravenous or intramuscular injection in a dose of 80 mg for 60 minutes was studied in 8 patients with chronic glomerulonephritis in the terminal stage of chronic renal insufficiency. The drug levels wee determined in the arterial (CA) and venous (CV) blood and dialyzates (CD) during the hemodialysis (6 hours) and 13-70 hours before the hemodialysis. The antibiotic was administered simultaneously with connection of the "artificial kidney" apparatus (KIIL) or 1 hour after it. The values of the clearance (CID) and dialyzing (D) of tobramycin were calculated with the following equations: (CID)1 equals Q(CA minus CV)/CA; (CID)4 equals FCD/CA; (D)2 equals Q(CA minus CV)/(CA minus CD); (D)5 equals FCD/(CA minus CD), where Q and F are the rates of the blood and dialysate flow respectively. In all cases the values of CID and D correlated and the difference between them was not significant. During the hemodialysis the values of (CID)1 varied to a greater extent than those of (CID)4. Irrespective of the procedure for estimation of CID the above variation was not pronounced, when tobramycin was administered simultaneously with initiation of the hemodialysis or during it than long before connection of the "artificial kidney" apparatus. In this connection it is recommended that antibiotic extraction be characterized by determination of (CID)4 on the drug administration long before the initiation of the hemodialysis. When Q equals 200 ml/min and F equals 600 ml/min, the average value of CLD for tobramycin was equal to 64 ml/min and the extraction coefficient was equal to 35 per cent.