Pefloxacin in the treatment of chronic urinary infection]

This study aimed at determining sensitivity of the hospital isolates to pefloxacin compared with other urinary antiseptics and assessment of its efficiency in the treatment of the chronic urinary infections. Disc diffusion technique was used to determine bacterial sensitivity to pefloxacin and other agents. Bacteria were isolated from the urine of the hospitalized patients. All tested strains were sensitive to pefloxacin. Its sensitivity exceeded in vitro 80%. Fifteen patients full sensitive to pefloxacin were treated. No bacteria were seen in the urine of 8 patients in two bacteriological cultures following the treatment, 3 patients stopped therapy due to adverse reactions, and no sterile urine was noted in 4 patients despite following a complete cycle of therapy.     

New quinolones in urological diseases of an inflammatory nature]

New drugs of the group of the 3rd generation fluoroquinolones i. e. norfloxacin, ciprofloxacin, ofloxacin and pefloxacin possess a high antibacterial activity against the majority of the problem causative agents of urinary infections. This was confirmed by the studies on sensitivity of 950 clinical strains of the pathogens isolated from inpatients of an urological department. Sensitivity of the majority of the pathogens to the fluoroquinolones was the following: 80.3 to 100 per cent among enteric bacteria, 80.2 to 89.6 per cent among Pseudomonas spp. and 94.7 to 100 per cent among Staphylococci, 288 patients were treated with the fluoroquinolones. The patients were divided into 3 groups according to the urinary infection i. e. acute inflammatory diseases, chronic pyelonephritis and chronic inflammatory diseases of the genital tract. The results of the studies estimated by complex clinico-laboratory indices revealed a close efficacy of the drugs in the patients. This was due to their analogous antibacterial spectra and similar pharmacokinetic characteristics investigated in 23 patients after the drug administration by various routes: intravenous and oral. No differences in tolerance of the fluoroquinolones were observed.     

Evaluation of modern antibiotics efficacy at experimental Northern Asia rickettsiosis]

Comparative investigation of antibiotics therapy efficacy at experimental murine Northern Asia rickettsiosis was performed. The efficacy was evaluated by the determination of protective activity in per cent and by the pathogen erradication. The investigated antibiotics may be ranged in the following order (by the diminishing efficacy): ansamycins (azorif, rifapentine, rifampicin), tetracyclines (doxycycline), macrolides (azitromycin, sumamed), carbapenems (imipenem/cilastatin), fluoroquinolones (lomefloxacin, pefloxacin). Rifampicin and its derivatives--azorif, rifapentine, along with doxycycline and azitromycm can be recommended for clinical trials at experimental rickettsiosis profilaxy and treatment in natural infection focus.     

The experimental validation of the advantages of combined emergency (fluoroquinolones) and specific (EV Nalr) prevention of plague versus their sequential use]

Mice immunization with reference vaccine at the early stage of plague infection provided animals survival and prolonged mean survival period up to 2-5 days. Ciprofloxacin, ofloxacin and pefloxacin prevents development of post vaccine immunity at white mice, immunized by reference vaccine strain EV. Nalidixic acid and norfloxacin effect on post vaccine immunity was lower. Use of immunogenic strain EV Nafr (resistant to nalidixic acid and fluoroquinolones) provided antiplague immunity formation at the background of fluoroquinolones prophylaxis. Ciprofloxacin, ofloxacin and pefloxacin used for plague prophylaxis at white mice infected with Yersinia pestis (about 1000 LD50) inhibited postinfective immunity development. Nalidixic acid and norfloxacin didn't demonstrate such effect. Urgent (fluoroquinolones) and specific (EV Nalr) combined prophylaxis was evaluated as more effective for a 5-day period and provided the development of antiplague immunity.     

Efficacy of pefoxacin (abactal) in the complex treatment of patients with pancreonecrosis]

The efficacy of pefloxacin in the complex treatment of 28 patients with pancreatonecrosis of various etiology was estimated in a prospective trial. The diagnosis of pancreatonecrosis was verified by the data of the disease clinical progress, laboratory findings and instrumental examination. Pefloxacin (Abactal; LEK) was administered intravenously in a dose of 400 mg every 8 hours (1200 mg) in combination with metronidazole in a dose of 1.5-2.0 g a day intravenously. When indicated 3 days after the start of the pefloxacin therapy, the treatment was switched to the oral use of the drug in the same dosage. The positive clinical effect (cure and improvement) at the end of the treatment with pefloxacin was stated in 78 per cent of the patients in spite of the initial severity state of above 15 APACHE II. It was shown that in the treatment of patients with pancreatonecrosis when the severity state was not above 12 APACHE II the antibacterial therapy with pefloxacin in combination with metronidazole was optimal.     

Candiduria: problems of diagnosis and therapy]

Candiduria is rather common. Yeasts could be detected in urine that was contaminated during collection of the specimens in patients with urinary bladder colonization or the upper urinary tract infection due either to retrograde spread of the pathogen from the urinary bladder or hematogenous dissemination from a distant infection focus. Most patients with candiduria are asymptomatic. The rate of complications is not known but appears to be low since candidemia rarely results from asymptomatic candiduria unless obstruction is present or instrumental examination of the urinary tract was performed. Unfortunately, there are no reliable diagnostic tests distinguishing fungal infection and colonization. Guidelines for antifungal therapy of candiduria, based almost entirely on fantastic reports and expert opinions, rather than on controlled clinical trials, were proposed by the Infectious Diseases Society of America. Until reliable methods for distinguishing infection from colonization are developed, further use of antifungal therapy is unlike to provide information for clinicians on the pathogenesis and effective treatment of candiduria.     

Enhanced of norfloxacin bioavailability using conjugation of isosorbide <Emphasis Type="Italic">via</Emphasis> enzymatic catalysis

Norfloxacin is a broad-spectrum synthetic antibacterial agent that has been used to treat complicated urinary tract infections. However, the poor water-solubility of norfloxacin limits its bioavailability. The aim of the present study was to synthesize water-soluble norfloxacin derivate through adding isosorbide via enzymatic catalyst (Green chemistry) and to evaluate its physiological and biological properties. Isosorbide-dinorfloxacin (ISDNf) was synthesized by enzymatic esterification between the carboxyl group of norfloxacin and two hydroxyl groups of isosorbide. Chemical structure and water-solubility of ISDNf purified by HPLC was investigated by using ¹H NMR and MALDITOF, and optical spectrometry, respectively. Antibacterial effects of ISDNf were evaluated against 7 drug-susceptible and 7 drug-resistant bacteria. ISDNf, which was successfully synthesized, was water-soluble at 10,000 mg/L, compared that free norfloxacin was water-insoluble at 100 mg/L. The antibacterial efficiency of ISDNf was maintained in drugsusceptible bacteria, while that was enhanced in drugresistant bacteria. Additionally, its cytotoxicity in mammalian cells was remarkably reduced and its solid diffusion capacity was increased. The increased water-solubility, antibacterial efficacy, and diffusion capacity and reduced cytotoxicity of ISDNf suggests that it could potentially be developed as a novel prodrug.     

Effect of pefloxacin on immune response]

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.     

Chemoattracting effect of human urine on motile Escherichia coli

Abstract Human urine specimens were found to be strong attractants for the most common urinary tract pathogen, Escherichia coli , in an in vitro chemotaxis assay. This suggested that bacterial chemotaxis toward urine may be a virulence factor in urinary tract infection (UTI). If so, inhibition of urine taxis could offer a novel approach to prevent these infections.     

Chronic Sodium Benzoate Therapy in Children with Inborn Errors of Urea Synthesis: Effect on Carnitine Metabolism and Ammonia Nitrogen Removal

Sodium benzoate (SB) therapy is known to increase ammonia (NH₃) nitrogen elimination via conjugation with glycine and excretion as urinary hippurate. In 16 children with inborn errors of urea synthesis we studied two issues: (1) the effect of chronic SB administration upon carnitine metabolism and (2) the efficacy of chronic SB therapy as measured by the molar ratio of hippurate excretion to SB intake. Measurements were performed during elective hospitalizations when the patients were in stable metabolic condition. We found that chronic SB therapy is not associated with a constant level of hippurate elimination and that interindividual and intraindividual variability may result in irregular removal of NH₃nitrogen. This variability may be due to various factors including the formation of small quantities of benzoylcarnitine, which was detected in the plasma of three of four patients receiving SB and carnitine therapy and in one of two patients on SB therapy without carnitine supplementation. The ratios of acyl to free carnitine were elevated in both plasma and urine in patients not receiving carnitine supplementation, but were normal in patients receiving supplementation.     

Activity of 22 antibacterials against O1 and O139 serogroup Vibrio cholerae strains isolated from humans within 1927-2005 in various regions of the world]

Analysis of antibioticograms of 390 O1 and O139 serogroup Vibrio cholerae strains isolated from humans within 1927-2005 in various regions of the world showed that the strains of V. cholerae isolated within 1927-1966 were susceptible to 22 antibacterials, the strains isolated within 1938-1993 possessed 1-3 resistance markers and the strains isolated within 1994-2005 had 3-8 resistance markers including resistance to fluoroquinolones. All the strains of O139 serogroup V. cholerae isolated in 1993 and 1994 possessed 3 resistance markers. Studies on albino mice with generalized experimental cholera due to the V. cholerae eltor 1 strain (P-18826, 2005) isolated from a cholera patient, which was highly resistant to nalidixic acid, streptomycin, ampicillin and trimethoprim/sulfamethoxazole and showed cross resistance to fluoroquinolones (ciprofloxacin, ofloxacin, pefloxacin and norfloxacin) and moderate resistance to ceftriaxone and cefotaxime, revealed that the only efficient antibiotics were tetracyclines and aminoglycosides (except streptomycin). The investigation demonstrated an extension of the antibiotic resistance spectra of the epidemically significant strains of the cholera pathogen and the necessity of using antibacterial drugs in strict accordance with the antibioticograms in emergent prophylaxis and therapy of cholera and immediate replacement of the drug by a more active one.     

Using an Isolated Rat Kidney Model to Identify Kidney Origin Proteins in Urine

The use of targeted proteomics to identify urinary biomarkers of kidney disease in urine can avoid the interference of serum proteins. It may provide better sample throughput, higher sensitivity, and specificity. Knowing which urinary proteins to target is essential. By analyzing the urine from perfused isolated rat kidneys, 990 kidney origin proteins with human analogs were identified in urine. Of these proteins, 128 were not found in normal human urine and may become biomarkers with zero background. A total of 297 proteins were not found in normal human plasma. These proteins will not be influenced by other normal organs and will be kidney specific. The levels of 33 proteins increased during perfusion with an oxygen-deficient solution compared to those perfused with oxygen. The 75 proteins in the perfusion-driven urine have a significantly increased abundance ranking compared to their ranking in normal human urine. When compared with existing candidate biomarkers, over ninety percent of the kidney origin proteins in urine identified in this study have not been examined as candidate biomarkers of kidney diseases.     

The mechanisms of activation of normal human serum complement by<Emphasis Type="Italic">Escherichia coli</Emphasis> strains with K1 surface antigen

Ten E. coli K1 strains isolated from the urine of children with urinary tract infections were sensitive to the bactericidal action of normal human serum (NHS). The role of the particular mechanisms of complement activation was determined in the process of killing these strains, showing variable sensitivity to the bactericidal action of NHS; three mechanisms of activation of human complement were observed. Important role of alternative pathway activation in the bactericidal action of NHS against E. coli K1 strains independent of the classical and lectin pathways was not established.     

Use of cefoperazone in clinical practice]

The bacteriological and clinical efficacy and side effects of cefoperazone were studied in 45 patients with severe and moderate purulent inflammatory diseases. The study showed that its bacteriological and clinical efficacy was high in cases with peritonitis, cholecystitis, respiratory and urinary infections, as well as those of the eye and soft tissues. The general clinical efficacy amounted to 95.6 per cent. The number of the side effects was insignificant. This made it possible to recommend the use of cefoperazone in the therapy of many purulent inflammatory diseases, as well as in empirical therapy.     

Evaluation of tolerance and efficacy of pefloxacin in the treatment and prevention of severe infections in children with mucoviscidosis and aplastic anemia]

Pefloxacin (Abaktal) efficacy and safety were investigated at 21 children (7-16 years old) randomized in 2 groups: children with mucoviscidosis and children with aplastic anemia. The drug was used at the dose 15-20 mg/kg per day bid for 14-28 days. Pefloxacin was used in combination with ceftazidime and amikacin. Combined therapy demonstrated good clinical efficacy. Bacteriological efficacy was not uniform: staphylococci were not isolated from sputum since the 7th day of treatment, but pseudomonads were cultured even on the 14th day of the treatment (the sensitivity to pefloxacin remained). The only but frequent side-effect was arthropathy. The background and some peculiarities of arthropathy development were analyzed. This phenomenon is called quinolone-induced synovitis. The risk group for quinolone-induced synovitis was estimated--children elder than 10 years with allergic anamnesis. Good clinical efficacy and tolerability of pefloxacin at the children with mucoviscidosis or aplastic anemia is a reason and base to cancel the limits to its use in pediatrics.     

The presence of methionine-enkephalin in plasma and urine in normal human subjects and various patients

The present study was performed to investigate whether or not there were enkephalins in plasma and urine in normal subjects and in patients with various diseases. Two kinds of antisera were developed to detect M-enk and L-enk. One has specific affinity with the C-terminus of methionine-enkephalin sulfoxide (M-O-enk), the oxidized form of M-enk, and the other with the N-terminus of L-enk. M-enk-like substance (MELS) was present in blood and urine in normal subjects, but not L-enk-like substance (LELS). Plasma MELS and its urinary output averaged 38 +/- 14 pg/ml (N = 19) and 605 +/- 235 ng/day (N = 15, M. +/- S.D.), respectively. There was a significant increase in plasma MELS and its urinary output in patients with pheochromocytoma. Plasma MELS did not show any significant increase or decrease in Cushing's disease. Addison's disease, panhypopituitarism or chronic glomerulonephritis. The urinary output of MELS was significantly increased in patients with essential hypertension, renovascular hypertension and primary aldosteronism, but was decreased in central diabetes insipidus.     

Problems of etiotropic therapy of typhoid fever and approaches to their solution]

The main problems of etiotropic therapy for typhoid fever lie in underestimate of the characteristic features of its pathogenesis and particularly in development of typhoid granulomas and their histogenesis, as well as in wide spread of typhoid fever pathogenic strains resistant to the routine chemotherapeutics, i.e. polyresistant strains. Some problems are due to incorrect choice of the antimicrobials and their combinations, optimal doses, administration routes and pathogenetic therapy. In the XXth centure an increase in the emergence and a change in the nature of the typhoid fever pathogen resistance to antimicrobials were observed. It was shown that from the pharmacologic and pharmacodynamic viewpoints the highest efficacy of typhoid fever therapy should be provided by the following antimicrobials: fluoroquinolones (except for norfloxacin), 3rd and 4th generation cephalosporins, aminopenicillins, chloramhenicol (levomycetin), combinations of 2nd and 3rd generation aminoglycosides with biseptol, aminopenicillins or doxycycline, as well as chloramphenicol combinations with aminopenicillins or 2nd to 4th generation cephalosporins. Practical recommendations for the etiotropic therapy of patients with typhoid fever during its outbreak or epidemic are presented.     

Discovery of urinary biomarkers

A myriad of proteins and peptides can be identified in normal human urine. These are derived from a variety of sources including glomerular filtration of blood plasma, cell sloughing, apoptosis, proteolytic cleavage of cell surface glycosylphosphatidylinositol-linked proteins, and secretion of exosomes by epithelial cells. Mass spectrometry-based approaches to urinary protein and peptide profiling can, in principle, reveal changes in excretion rates of specific proteins/peptides that can have predictive value in the clinical arena, e.g. in the early diagnosis of disease, in classification of disease with regard to likely therapeutic responses, in assessment of prognosis, and in monitoring response to therapy. These approaches have potential value, not only in diseases of the kidney and urinary tract but also in systemic diseases that are associated with circulating small protein and peptide markers that can pass the glomerular filter. Most large scale biomarker discovery studies reported thus far have used one of two approaches to identify proteins and peptides whose excretion in urine changes in specific disease states: 1) two-dimensional electrophoresis with mass spectrometric and/or immunochemical identification of proteins and 2) top-down mass spectrometric methods (SELDI-TOF-MS and capillary electrophoresis-MS). These studies have been chiefly in the areas of nephrology, urology, and oncology. We review these applications, focusing on two areas of progress, viz. in bladder cancer and in acute rejection of renal transplants. Progress has been limited so far. However, with the advent of powerful LC-MS/MS methods along with methods for quantifying LC-MS/MS output, there is hope for an accelerated discovery and validation of disease biomarkers in urine.     

Study of normal and cancerous urine using photoacoustic spectroscopy

Photoacoustic spectroscopy (PAS) is a valuable technique, increasingly applied in clinical and biological analysis. Light absorption properties of urine and body tissue can be obtained more easily by the PAS technique because of its high sensitivity, than by the conventional optical techniques. By observing their absorption properties it is possible to diagnose some diseases and in this study we have used PAS to assess cancerous changes in urine and tissue. Three groups were studied: normal individuals; patients with cancer; and patients with cancer and subsequent inflammation; and the characteristic light absorption peaks obtained for a certain band (240–420 nm). These results were compared with the clinical diagnosis and proved consistent and reliable for the diagnosis of urinary tract cancer subsequently confirmed by operation. This method will probably be a useful tool for the early clinical diagnosis of cancer of the urinary system.