Empirical antibiotic therapy of wounds complicated by anaerobic non-clostridial infection

Antibacterial activity of 14 drugs against clinical strains of asporogenic anaerobes causing wound infections in the soft tissues i. e. Bacteroides fragilis and Bacteroides melaninogenicus as well as anaerobic gram-positive++ cocci was assayed with the method of serial dilutions in agar. It was shown that among the investigated species B. fragilis had the most marked resistance since out of the 14 drugs only 8 were sufficiently active against it i.e. carbenicillin, levomycetin, lincomycin, dioxidine, metronidazole, thinidazole, nitrazole and erythromycin. The choice of drugs for treating infections caused by B. melaninogenicus and anaerobic grampositive cocci unlike those caused by B. fragilis offered no difficulty since practically++ all the investigated drugs were highly active against the causative agents. There was observed relationship between the frequency of asporogenic anaerobes and the wound genesis. The characteristic features of the species composition connected with localization of the suppurative foci were indicated. The detected specific antimicrobial profiles of the asporogenic anaerobes causing wound infections and the peculiarity of their participation in development of purulent infections of the soft tissues provided a differential approach to empirical antibacterial therapy prior to the pathogen bacteriological investigation and availability of the antibioticograms.     

Efficacy of a combination of dioxidine with beta-lactam antibiotics in the prevention and treatment of purulent-inflammatory complications

Schemes for prevention and treatment of purulent inflammatory complications were developed on the basis of in vitro studies on antimicrobial activity of dioxidine and 7 beta-lactam antibiotics such as mezlocillin, carbenicillin, ampicillin, cefotaxime, cefoxitin, cefuroxime and cephalothin under conditions of aero- and anaerobiosis with an account of the isolated microflora, its sensitivity to antibacterial agents and conditions required for vital activity of obligate anaerobes in humans, i.e. decreased partial oxygen pressure, low oxidation-reduction potentials and high tissue concentrations of carbon dioxide. The use of dioxidine in combination with the antimicrobial drugs enabled one to decrease the number of cases with purulent inflammatory complications after large intestine esophagoplasty to 30.4 per cent against 67.5 per cent in the control group of the patients untreated preventively with the antibacterial drugs. The number of cases with similar complications after gastrectomy amounted to 16.1 per cent against 62 per cent in the control. The use of dioxidine+ in combination with ampicillin and cefotaxime in treatment of purulent necrotic affections of the foot in patients with diabetes mellitus enabled one to increase the number of satisfactory outcomes by 32 per cent, to decrease the number of high amputations by 21.9 per cent and to lower the number of deaths more than 2-fold as compared to the results in the control group of the patients subjected to chemotherapy based on sensitivity of the aerobic microflora alone.     

ANTIBIOTIC ANAPHYLAXIS

Anaphylactic reactions following the injection of penicillin or other antibiotics have increased greatly during the past several years. These untoward reactions to penicillin were infrequent during the first nine years of penicillin therapy and there can be no doubt that hypersensitivity to these drugs is developing in many people. Therefore promiscuous use of them is to be condemned. It is safer not to use antibiotics parenterally in patients with allergic conditions such as bronchial asthma. The further use of a particular antibiotic should be avoided if the patient has previously shown any hypersensitivity to that drug.A questionnaire was answered by more than 1,000 California physicians who reported that over 300 patients had severe anaphylactic reactions from parenteral penicillin and streptomycin. There were seven deaths.Since the antibiotics should still be used when needed, prevention of anaphylaxis is of fundamental importance. The frequency of these reactions can be greatly reduced by the use of antihistaminic solutions combined with the antibiotics. Treatment of these shock-like reactions demands the prompt administration of epinephrine intramuscularly, antihistaminic solutions intravenously and oxygen.     

Antibacterial therapy of pyelonephritis in pregnant women

To determine the optimal schemes of rational antibacterial therapy of pyelonephritis gravidarum with ampicillin and cephuroxim, assays of the patient urine and studies on the pharmacokinetics of the drugs were performed. The bacteriurea levels were estimated in 264 women with Gould's method in modification of Ryabinsky and Rodoman. The causative agents of the disease were isolated from the urine of 92 pregnant women. Sensitivity of the isolates to 9 antibiotics was tested with the use of standard paper disks and the method of serial dilutions in solid media. The pharmacokinetics of ampicillin and cephuroxim in the blood and urine of 97 patients was studied for 6-8 hours after parenteral administration of the antibiotics in doses of 500 mg. Comparative analysis of the pharmacokinetic parameters of the antibiotics in the blood and urine of the patients, the antibiotic MICs for the disease causative agents and the clinical course of the disease suggests that pyelonephritis gravidarum should be treated with ampicillin and cephuroxim on doses of 500 mg injected intramuscularly 4 and 3 times a day respectively for 7-8 days in combination with antiinflammatory therapy.     

Gentamycin sulfate effectiveness and tolerance in patients with myelotoxic agranulocytosis]

Patients with myelotoxic agranulocytosis were treated with gentamicin administered intravenously as drop-wise infusions in a dose of 5 mg/kg body weight a day every 8 hours. The treatment course consisted of 7--24 days. No toxic reactions were observed. The therapeutic efficacy of gentamicin depended on the neutrophilic level and amounted to 50--60 per cent when the drug was used without identification of the causative agent. The prophylactic use of gentamicin decreased the infection incidence in patients with myelotoxic agranulocytosis, while the prophylactic efficacy of gentamicin was evident only when the number of the granulocytes was higher than 100/mm3 of the blood.     

Detection of persistent resistance to antibacterial drugs in various strains of Francisella tularensis]

Under natural conditions, the Francisella tularensis strains AE-261 and P-13864 capable of forming the persist type of resistance to antibacterial drugs and being the cause of the infection in laboratory animals not responding to monotherapy with antibiotics were detectable. The antibioticograms of strains AE-261 and P-13864 under the in vitro conditions did not differ from those of the other studied strains responding to the antibiotic therapy. The observed phenomenon could be associated with individual peculiarities of the strains and their phenotypic variation in the host. Combinations of aminoglycoside antibiotics (streptomycin, gentamicin and amikacin) with rifampicin were shown to be highly active in the treatment of general forms of the infection due to such strains. The combined therapy of tularemia was also considered promising because of its high efficacy when the treatment was started at late periods as well as because unlike the monotherapy with the aminoglycoside antibiotics it provided complete elimination of the pathogen from the host.     

The augmentin (amoxicillin/clavulanate) prophylaxis of postoperative infectious complications in patients with acute surgical diseases of the abdominal cavity organs]

Augmentin was used prophylactically in 25 patients with an account of the infectious complication risk according to 4 regimens: ultrashort-term (1.2 g intravenously with initial narcosis), short-term (1.2 g intravenously with initial narcosis followed by intravenous administration in a dose of 600 mg in 8 and 16 hours), middle-term (1.2 g intravenously with initial narcosis followed by intravenous administration in a dose of 600 mg every 8 hours for 2 days) and long-term (1.2 g intravenously with initial narcosis followed by intravenous administration in a dose of 600 mg every 8 hours for 3 days). One complication episode as wound suppuration was recorded. The routine approach to the use of antibiotics in emergency abdominal surgery, when antibiotics are administered every day for several days after the operation, should be revised.     

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.     

Effect of various antibiotics on the circulation of proteins between the blood and lymph in macro-organisms

The effect of tetracycline, amphotericin B and kefzol on distribution of some proteins between the blood and lymph of the thoracic duct was studied on rabbits. Tetracycline was injected intramuscularly in the form of hydrochloride dissolved in 2% novocain in a dose of 25 mg/kg once or daily for 7 and 20 days. Kefzol (sodium cephazolin) was injected intramuscularly in a single dose of 100 mg/kg. Amphotericin B was injected intravenously in a dose of 1000 Units/kg once or for 5 days. The lymph samples were collected from the thoracic duct of rabbits treated with single doses of the antibiotics 1 and 24 hours after their injection. When the animals were treated with the antibiotics repeatedly the lymph samples were collected 24 hours after the last injection. The level of the total protein and the ratio of the protein fractions, i. e. albumins, alpha 1-, alpha 2-, beta- and gamma-globulins in the lymph and blood serum were determined. On the basis of these findings the protein coefficient (albumin/globulin) of the lymph and blood, the coefficients of the protein permeability of the blood vessels (R) and the constants of selective permeability of the blood capillaries (S) were calculated. It was shown that the shifts in the protein circulation between the blood and lymph had mainly the same trends independent of the antibiotics used and their retention time in the host. A significant decrease in the permeability of the blood vessel walls in respect to the total protein and gamma-globulins and a marked increase in their selectivity in passing of the protein molecules of different size were observed in all cases.     

Therapy of urinary tract infections in patients with diabetes mellitus]

Clinical and microbiological efficacy of Cifran OD (Ranbaxy, India), a formulation with prolonged action and extended release of ciprofloxacin was studied in 22 patients with bacteriuria and lingering diabetes mellitus. Ciprofloxacin was used in doses of 500 or 1000 mg orally once a day depending on the severity of the disease singns for 2-3 weeks as etiotropic therapy and only in 2 cases with severe pyelonephritis it was used intravenously drop-wise and orally simultaneously. Twenty eight microbial strains isolated from urea of the patients were tested. The main species of the isolates belonged to the family Enterobacteriaceae. Twenty five isolates (89.3%) were susceptible to ciprofloxacin and 3 isolates (10.7%) were resistant. The clinical efficacy of ciprofloxacin was 90.9%.     

Spectrum of pathogens in hospital infections in onco-urologic patients and their sensitivity to antibacterial drugs

Retrospective examination of case records and laboratory findings related to 155 patients discharged from the Urological Department of the All-Union Oncology Research Centre, Academy of Medical Sciences of the USSR within a period of 3 months showed that 41.9 per cent of the oncourological patients had infectious processes requiring antibacterial therapy. Among 80 infectious episodes 62 or 77.5 per cent were of intrahospital origin. There was a relationship of the frequency of the infections to localization of the tumor process, a patient's age, the treatment character and some diagnostic and treatment procedures. 70 per cent of the hospital infections were urinary and 15 per cent referred to suppuration of the operative wounds. The predominant causative agents of the complications were Pseudomonas spp., Klebsiella tribe, Proteus spp. and Enterococci with the highest levels of resistance to antibacterial drugs. The drugs of choice for treating the infections in that group of the patients were ofloxacin and cefotaxime. Aminoglycosides, semisynthetic penicillins, cephalosporins and urological antiseptics were used in accordance with antibioticograms. In the treatment of severe gram-negative infections dioxydin was used. Since hospital infections in oncourological patients are usually caused by hospital multiple resistant strains of microorganisms, often present in associations, the adequate antibacterial therapy requires constant bacteriological surveillance providing not only the choice of the most efficient drug but also early correction of the therapy after the pathogen change.     

Fluoroquinolones and their importance in modern chemotherapy of infectious diseases

Experimental and clinical data on antibacterial drugs belonging to fluorine derivatives of quinolone carboxylic acid (quinolones of the third generation) were summarized. Brief characteristics of their antibacterial activity and experimental data on chemotherapeutic activity of pefloxacin, a fluoroquinolone on models of septicopyemia and meningoencephalitis in experiments with mice infected by P. aeruginosa, Staphylococcus and Klebsiella are presented. High efficacy of pefloxacin was shown and its advantages over dioxidine and gentamicin on the model of meningoencephalitis were revealed. The main indications to the use of fluoroquinolones, possible adverse reactions and contraindications to the use of the drugs of that group are described.     

The use of ampicillin/sulbactam (Unasyn) in treating inflammatory urological diseases

Unasyn is a combination of ampicillin, a bactericidal antibiotic, and sulbactam, an inhibitor of beta-lactamases. It was used in treatment of 36 patients with urogenital infections. The combination was administered intravenously and in the main intramuscularly. The treatment course amounted to 7-10 days. The average daily dose was 6 to 9 g. 22 patients with acute nonocclusive pyelonephritis were treated with the combination and its clinical and bacteriological efficacy was stated in 95 per cent of the cases. An excellent clinical effect of the combination was observed in 6 patients with acute epididymitis. A clinical improvement was also observed in the treatment of the patients with acute prostatitis and chronic renal infections. Unasyn proved to be a highly efficient antibacterial combination with regard to gram-positive flora and colon bacilli as representatives of gram-negative organisms. Satisfactory results were also stated in the treatment of infections caused by Proteus spp. Complete elimination of the pathogen was achieved in 57.7 per cent of the cases. No adverse reactions to Unasyn except pain in the site of the injection were recorded.     

Effects of antibiotics and anti-bacterial components of preparations for local treatment of suppurative wounds on pathogens of odonto- genic infections]

The results of identification and sensitivity assay of 156 strains of pathogens causing odontogenic infections are presented. In the sensitivity assay antibacterial drugs were used. 42.3 percent of the strains were obligate anaerobes belonging to Bacteroides, Fusobacterium, Peptococcus, Peptostreptococcus, Veillonella and Actinomyces. Significant differences in the microbial sensitivity to the drugs used for general and local therapy were detected. There was observed high sensitivity of the obligate anaerobes to gramicidin (0.02 micrograms/ml), nitazol (10 micrograms/ml), levomycetin and tetracycline (60 micrograms/ml). Antiseptics such as dioxidine and chlorhexidine used locally showed satisfactory results. The above mentioned drugs and especially levomycetin were also rather active against facultative organisms in associations of pathogens causing odontogenic infections: Bacillus coagulans, B. licheniformis, Pseudomonas sp., Acinetobacter calcoaceticus, Staphylococcus sp. and Streptococcus sp.     

Use of a semisynthetic broad-spectrum penicillin (ampicillin) in surgical practice]

Parenterally ampicillin was used for the treatment of 87 patients with lung and abdominal diseases, liver abscesses, extremity phlegmonas, osteomyelitis and other diseases. The antibiotic was administered intravenously and intramuscularly. High efficacy of the treatment was observed in all the cases with ampicillin sensitive microflora. In some cases a satisfactory therapeutic effect was observed only with the use of ampicillin in combination with other antibiotics and aminoglycosides in particular. No side effects of the antibiotic were registered.     

Pharmacokinetics of dioxidine in oncological patients in the postoperative period

Dioxidine pharmacokinetics was studied in 5 patients operated for cancer of the large intestine and treated prophylactically with the drug during the postoperative period. Dioxidine was administered intravenously for 10 minutes twice a day in an amount of 300 mg in 5 per cent solution of glucose. The drug concentrations in serum and urine were determined with a microbiological procedure. Escherichia coli AB 2472 rec A16, a strain deficient with respect to reparation was used as a test microbe. The plates with the dilutions were incubated under anaerobic conditions. The time course of the drug concentrations in serum was shown to be satisfactorily described by the following equation: C(t) = 3.125 . 1-2.57.t + 2.76 . 1-0.64.t. Within the first 1.5-2 hours after the administration the dioxidine concentrations in serum and urine amounted to 2.5-4 and 35-50 micrograms/ml respectively.     

The effect of O-betahydroxyethyl-rutosides (HR) on the number of platelet-leukocyte aggregates in patients with occlusive arterial disease.

The diagnostic value and the effect of the therapy on the number and kind of platelet-leukocyte aggregates in 68 patients with arteriosclerosis obliterans of the lower limbs were investigated. The modified SILBERGLEIT'S method was used. 8 types of aggregates were found. The means number of aggregates in 20 healthy subjects was 8.2 but in 46 patients suffering from obliterative arteriosclerosis of the lower limbs this number was significantly higher, i.e. about 62. A significant decrease in the number of platelet-leukocyte aggregates in the group of 14 patients receiving HR orally 1800 mg daily and 16 patients receiving HR intravenously 2000 mg daily was found. In 16 persons a lower HR dose (orally 900 mg daily and intravenously 500 mg daily) did not influence the number of rosettes. In 22 patients receiving nicotinic acid (orally 900 mg daily, intramuscularly 600 mg daily) no significant changes in the number of rosettes was observed.     

Efficacy and toxicity of pentavalent antimonials (Glucantime and Pentostam) in an American cutaneous leishmaniasis animal model: luminometry application

The pentavalent antimonial compounds Glucantime and Pentostam are the first line drugs used in anti-Leishmania treatment. However, no in vivo studies have compared the efficacy and toxicity of these drugs where host variability has been controlled. Biochemical studies of Leishmania have detected differences between the two drugs with regard to DNA topoisomerase I inhibition, a phenomenon that possibly impacts treatment efficacy. To evaluate the clinical efficacy, hamsters were infected intradermally in the right hind foot with 10(6) promastigotes of a wild type or luciferase-transfected Leishmania panamensis. At three weeks post-inoculation, the animals were treated intramuscularly with either Glucantime or Pentostam (30, 60 or 120 mg SbV/kg per day for 20 days). To evaluate parasitological efficacy a luminometry assay was standardized for quantitation of amastigotes in hamster tissues. To evaluate toxicity, hamsters were treated intramuscularly with Glucantime or Pentostam (120, 160 or 240 mg SbV/kg per day for 20 days). Animals inoculated with either of the parasite strains and treated with either drug, showed a similar rate of lesion reduction, as compared to untreated controls (p<0.01). Parasite burden was also comparable, and no significant differences were found in the cure rate. No renal or hepatic alterations occurred as evidenced by normal serum levels of creatinine, aspartate aminotransferase, alanine aminotransferase and amylase. Hamsters treated with 120 mg SbV/kg per day for 20 days or higher doses of Pentostam showed macro- and microscopic signs of inflammation at the site of injection. These effects were absent in the animals treated with Glucantime. The results confirmed clinical observations regarding the similar efficacy of the two drugs, as well as the higher local toxicity of Pentostam.     

Additive effect of pronase on the efficacy of eradication therapy against Helicobacter pylori

Background. Helicobacter pylori (H. pylori) colonizes not only the surface of the surface mucous cells but also the surface mucous gel layer (SMGL). Thus, we examined the possible value of pronase, a mucolytic agent, as a potential eradication therapy. Materials and Methods. One hundred and thirty‐five patients were randomly assigned to two treatment groups. Sixty‐eight patients received 30 mg of lansoprazole once daily, 500 mg of amoxicillin and 250 mg of metronidazole thrice daily for 2 weeks (LAM group), while the other 67 patients received the same dosage of those agents plus 18,000 tyrosine units of pronase thrice daily for 2 weeks (LAMP group). Eradication was assessed 4–6 weeks after treatment by immunohistochemical tests and cultures. We also determined the in vitro activity of pronase against H. pylori, and evaluated the synergistic effects between pronase and the other three drugs. To investigate the effect of pronase on the structure of the SMGL, surgically removed stomachs obtained from patients who had taken pronase were examined histopathologically. Results. The cure rates for H. pylori infection in the LAMP group were significantly higher than those in the LAM group (intention to treat analysis: 94.0 vs. 76.5%, p = .0041). Pronase exhibited no antibacterial activity against H. pylori., and no in vitro synergistic effects were observed. In the patients who took pronase before surgery, the SMGL was thinner than in the patients who did not take pronase, and the structure of the SMGL was markedly disrupted. Conclusions. Pronase has an additive effect in curing H. pylori infection. Pronase has no apparent in vitro activity against H. pylori, but may improve the local delivery of antibiotics by virtue of its removal and disruption of the SMGL.     

Antibacterial susceptibility/resistance of Vibrio cholerae eltor clinical strains isolated in the Caucasus during the seventh cholera pandemic

The data on antibacterial susceptibility and resistance of Vibrio cholerae eltor phenotypes with different sets of the susceptibility or resistance markers conditioning the outbreaks and sporadic cases of cholera in the Caucasus within 1970-1998 are presented. An increase of the number of the Vibrio cholerae phenotypes resistant to tetracycline and chloramphenicol usually used in the treatment of cholera was recorded in 1990-1994 vs. 1970-1989. The El Tor cholera vibrios stored on synthetic media lost some of their resistance markers, therefore the retrospective investigation of the antibioticograms was only of approximate prognostic value in the choice of the drugs for the etiotropic treatment of cholera in view of possible outbreak of the disease.