Antimicrobials

Vestn Khir Im I I Grek, 1987 Jul, 139(7), 129 - 35
{Endotoxicosis in surgery}; D'iachenko PK et al.; The question of general toxemia as an important problem in acute surgery has first been raised . In addition to the infection component attention is called to the presence of a pathologic focus (diseased internal organ) which is the main cause of diffuse peritonitis . Attention is given to sepsis and basedowian goiter with the IV degree thyrotoxicosis followed by pronounced toxemia . In addition to antibacterial therapy the authors recommend transfusion of fresh blood with heparin, forced diuresis, peritoneal dialysis hemosorption, ganglionic blockade with venous antiseptics and other methods to struggle against toxemia . The active tactics of the surgeon is necessary aimed at elimination of the main cause of general toxemia--liquidation of the pathological focus.

Rev Infect Dis, 1987 Jul-Aug, 9(4), 713 - 8
Does serum protein binding inhibit tissue penetration of antibiotics?
Bergan T, Engeset A, Olszewski W.
Accumulated data on the penetration of 15 antibacterial agents into peripheral human lymph are reviewed . The major factor determining extravascular penetration is the level of serum protein binding . The penetration ratios of extravascular and serum levels diminish gradually as the level of protein binding increases . However, even at the highest protein-binding levels, distinct lymph concentrations are observed . The degree of penetration ranges from 100% for the antibiotic with the lowest level of serum protein binding (gentamicin, no drug bound) to 20% for that with the highest level of protein binding (flucloxacillin, 96% bound).

Vestn Khir Im I I Grek, 1987 Jul, 139(7), 57 - 61
{Peritonitis as aerobic-anaerobic infection}; Kolesov AP et al.; Results of clinico-microbiological examinations of 147 patients with peritonitis were analyzed . Strict anaerobic technique was used . It was established that in most cases peritonitis represented a mixed anaerobic aerobic infection (59.2%) . The coliform microorganisms were dominating among aerobic ones, bacteroids-among anaerobic ones . The microbic character of inflammation (from abacterial to mixed forms) is dependent on the level (localization) of the inflammation source, duration of the inflammatory process . Mixed aerobic-anaerobic peritonitis has characteristic clinical features and requires an adequate antibacterial therapy.

J Biochem (Tokyo), 1987 Jul, 102(1), 69 - 74
Purification of sarcotoxin III, a new antibacterial protein of Sarcophaga peregrina; Baba K et al.; A glycine-rich antibacterial protein with a molecular mass of 7,000 termed sarcotoxin III, was purified to homogeneity from the hemolymph of third instar larvae of Sarcophaga peregrina . When the hemolymph was fractionated, this protein was recovered in the same fraction as sarcotoxin I, a group of potent antibacterial proteins that have been purified . But, it was clearly different from sarcotoxin I in amino acid composition and molecular mass . Sarcotoxin III was shown to be induced in the hemolymph in response to injury of the larval body wall.

Int J Dermatol, 1987 Jul-Aug, 26(6), 389 - 93
Cefuroxime axetil in the treatment of cutaneous infections; Parish LC et al.; A multicenter clinical trial was conducted in 125 out-patients with skin and skin structure infections due to bacteria in order to compare the safety and efficacy of cefuroxime axetil and cefaclor . Patients with a median age of 32 years were randomly allocated to treatment for 10 days with one of three treatments: cefuroxime axetil 250 mg b.i.d., cefuroxime axetil 500 mg b.i.d., or cefaclor 250 mg t.i.d . Clinical evaluations of each patient were done pre-treatment, 2 to 4 days intra-treatment, and within 3 days post-treatment . One patient discontinued cefuroxime axetil due to severe urticaria and one patient discontinued cefaclor due to a persistent headache and vomiting . Cefuroxime axetil was an effective antibacterial agent for treatment of common skin infections . Clinically beneficial outcome was achieved for 92% (cefuroxime axetil 250 mg b.i.d.), 95% (cefuroxime axetil 500 mg b.i.d.), and 97% (cefaclor 250 mg t.i.d.) of patients . Since the study failed to demonstrate a significant advantage of higher dosage, cefuroxime axetil should be prescribed in a regimen of 250 mg twice a day for patients with skin infections.

Antibiot Med Biotekhnol, 1987 Jul, 32(7), 500 - 2
{Method of determining the antibiotic concentration in biological material}; Skala LZ et al.; To lower the role of natural antibacterial activity of biological substrates from humans and laboratory animals in microbiological assay of bleomycin (bleomycin) with B . subtilis ATCC 6633 as the test-microbe, it was suggested to increase the procedure sensitivity by using the medium modification . In determining concentrations of aminoglycosides by the agar diffusion method the use of B . pumilus NCTC 8241 as the test-microbe is recommended.

Clin Exp Immunol, 1987 Jul, 69(1), 157 - 65
The specificity of murine polyclonal and monoclonal antibodies to the haptenic drug chlorhexidine induced by chlorine-generated chlorhexidine-protein conjugates; Layton GT et al.; Polyclonal and monoclonal antibodies to the antibacterial agent chlorhexidine (1,1'-hexamethylene bis {5-(p-chlorophenyl)}biguanide, mol . wt = 505) were raised using a chlorine-generated N-chloro chlorhexidine-keyhole limpet haemocyanin (NCC-KLH) conjugate as the immunogen . Antibodies were detected by ELISA, using a semi-chlorhexidine derivative conjugated to human serum albumin (SC-HSA) as the antigen . Free chlorhexidine could completely inhibit both polyclonal and monoclonal antibody binding to SC-HSA . Direct binding and inhibition ELISA studies revealed that the N-chlorination of chlorhexidine does not significantly alter its specificity as an immunogen or antigen and that chlorhexidine has two identical epitopes . Each epitope consists of the p-chlorophenyl biguanide structure of which the terminal p-chlorophenyl group appears to be immunodominant . Chlorhexidine is, therefore, a symmetrical divalent hapten and this implies that it may be capable of eliciting immediate hypersensitivity reactions by divalent interaction with antibodies induced by chlorine-generated N-chloro-chlorhexidine-protein immunogens . The clinical significance of these findings is discussed.

Am J Med, 1987 Jun 26, 82(6B), 22 - 6
Norfloxacin: review of safety studies; Corrado ML et al.; The tolerability profile of norfloxacin, the first of a new generation of fluoroquinolone carboxylic acid antibacterials, has been defined in numerous laboratory animal and human trials . Whether administered for moderate or protracted periods, norfloxacin has been relatively safe in animals over a wide range of doses . There has been no evidence of a teratogenic effect in any of the animal species tested (rat, rabbit, mouse, monkey) at six to 50 times the human dose (400 mg twice daily) . However, norfloxacin has been shown to produce embryonic loss in monkeys when given in doses 10 times the maximal human dose, resulting in peak plasma levels that are two to three times those obtained in humans . Although there are no adequate and well-controlled studies in pregnant women, norfloxacin is not recommended for use in this population because it, like other drugs in this class, causes arthropathy in immature animals . In animals, norfloxacin is neither mutagenic nor carcinogenic, and, in clinical trials, norfloxacin-related adverse experiences have been uncommon . Those that have occurred have been generally mild, requiring discontinuation of therapy in less than 1 percent of patients . The most frequently reported side effects have been nausea, dyspepsia, headache, and dizziness . Administration of 400 mg of norfloxacin at two or three times a day has been associated with reasonably good gastrointestinal tolerance.

Med Hypotheses, 1987 Jun, 23(2), 187 - 93
Drugs, insecticides and other agents from Artemisia; Sherif A et al.; Essential oils from Artemisia (wormwood) are of botanical and pharmaceutical interest . They are used in traditional remedies in many parts of the world . In pure form the oil is a narcotic poison . Nearly all species are intensively bitter and strongly aromatic . Extracted substances from the plant have an antibacterial action and some of these substances have potential use in mosquito control . Other properties include toxicity to nematodes and inhibition of seedling growth of . Several chemical compounds have been isolated and identified.

J Antibiot (Tokyo), 1987 Jun, 40(6), 740 - 9
Studies on new antibiotics SF2415 . II . The structural elucidation; Gomi S et al.; Structures of new antibiotics SF2415A1, A2, A3, B1, B2 and B3 were deduced from spectroscopic analyses and degradation studies . The structure of SF2415A3, which has the most antibacterial activity, was proposed to be 3,4a-dichloro-9-diazo-3,4, 4a,10a-tetrahydro-6-hydroxy-2,2,7-trimethyl-10a-{(E)-3,7-dimethyl- 2,6-octadienyl}-(2H,9H)naphtho-{2,3-b}pyran-5,8,10-trione . All of antibiotics SF2415 have a semi-naphthoquinone structure.

Infect Immun, 1987 Jun, 55(6), 1375 - 80
Immunoregulatory role of the spleen in antibody responses to pneumococcal polysaccharide antigens; Cohn DA et al.; Antibody responses to two structurally different pneumococcal polysaccharides, type 3 (SIII) and type 14 (SXIV), were examined in intact and splenectomized (Sx) A/J mice to determine whether the role of the spleen in immune responses to these antigens varies with respect to the dosage, the antigenic structure, or the interval between immunization and assay . Antibody responses to SIII and SXIV, measured over a 4-week period by radioimmunoassay, differed in antigenic load requirements, kinetics, and extent of dependence upon the spleen . Intact mice given 50 or 100 ng of SIII produced peak antibody responses on day 5, which tapered off by days 14 and 21 . Intact mice given SXIV required doses 100 times greater than those of SIII to stimulate high levels of antibody response; antibody responses increased on day 5 and remained elevated through day 28 . In Sx mice given 50 or 100 ng of SIII, the peak antibody response on day 5 was obliterated, but extrasplenic sources produced low levels of antibody which peaked by day 14 . In Sx mice given SXIV, all anti-SXIV responses were abrogated regardless of the dose or day of assay . Differences between the anti-SIII and anti-SXIV responses in dependence upon the spleen were probably due to structural differences between the two antigens and to the localization of each to different sites in the reticuloendothelial system . These results attest to the importance of the spleen in antibacterial resistance . They show that, even in the presence of extrasplenic antibody synthesis, the spleen is required for early antibody production, the timing of which is critical for the effective clearance of bacteria.

Int J Clin Pharmacol Ther Toxicol, 1987 Jun, 25(6), 320 - 1
Effect of pectin and kaolin on bioavailability of co-trimoxazole suspension; Gupta KC et al.; Bioavailability of co-trimoxazole suspension was determined with and without concurrent administration of pectin and kaolin in 8 volunteers . Twenty ml suspension of co-trimoxazole containing 160 mg trimethoprim (TMP) and 800 mg sulphamethoxazole (SMX) and co-trimoxazole suspension along with 20 ml of pectin-kaolin suspension were administered in a random order with 7 days interval . Plasma estimation of trimethoprim and sulphonamide was carried out at serial intervals . Area under curve (AUC) and Cmax of TMP were significantly higher when co-trimoxazole suspension alone was used . No statistically significant changes were observed in case of sulphamethoxazole . Clinical study is necessary to verify whether concurrent administration of co-trimoxazole and pectin-kaolin leads to loss of antibacterial efficacy.

J Antibiot (Tokyo), 1987 Jun, 40(6), 803 - 22
Structure-activity relationships of 6-(heterocyclyl)-methylene penam sulfones; a new class of beta-lactamase inhibitors; Chen YL et al.; 6-(Heterocyclyl)methylene penam sulfones (1) are effective beta-lactamase inhibitors and potent ampicillin and cefazolin potentiators against both Gram-positive and Gram-negative beta-lactamase producing bacteria . Several of these analogs having a pi-deficient 2-heteroaryl substituent attached to the C6-methylene position showed better inhibitory activity than clavulanic acid, Ro 15-1903, 6 beta-bromopenicillanic acid, and sulbactam against a variety of beta-lactamases . The compounds were devoid of any antibacterial activity, but in combination with ampicillin or cefazolin, exhibited synergistic activity at least equal to clavulanic acid, Ro 15-1903, 6 beta-bromopenicillanic acid or sulbactam against beta-lactamase producing strains . Structure-activity relationships for a number of compounds are described . The structure-activity relationships can be rationalized by an enzyme inhibition mechanism which we have previously proposed on the basis of methanolysis of 6-(2-pyridyl)methylene penam sulfone (1a) . Two synthetic routes to prepare compounds of structural type 1 via either a Wittig reaction or an aldol condensation are reported . beta-Lactamase inhibition and MIC data are presented.

Pathol Biol (Paris), 1987 Jun, 35(5 Pt 2), 785 - 9
{Modulation by quinolones of the in vitro proliferative response of splenic cells of the mouse and IL 1 production}; Guenounou M et al.; Besides their antibacterial activity, antibiotics can modulate immune response . In this work, we studied the effects of 6 quinolones (nalidixic and pipemidic acid, pefloxacin, norfloxacin, ofloxacin, ciprofloxacin) on Con A or LPS induced mitogenic response in mice . Data presented here show that pefloxacin and ofloxacin enhanced Con A (1 microgram/ml) induced proliferative response when used at low concentrations (0.1 microgram/ml and 1 microgram/ml) . In the same conditions LPS induced response was not modified . When used at high concentrations (greater than 25 micrograms/ml), inhibition of both LPS and Con A induced responses was observed . Con A induced response needs interaction between macrophages and T lymphocytes . So, we investigated whether quinolones could act on interleukin 1 (IL 1) production by macrophages . Our results showed that pefloxacin and ofloxacin, used at low concentrations, enhanced LPS induced IL 1 production by macrophages.

J Antibiot (Tokyo), 1987 Jun, 40(6), 723 - 6
CV-1, a new antibiotic produced by a strain of Streptomyces sp . I . Fermentation, isolation and biological properties of the antibiotic; Ichimura M et al.; A new antibiotic, CV-1, was isolated from the culture broth of a Streptomyces sp . by various chromatographies . CV-1 showed antibacterial activity against Escherichia coli in cooperation with spiramycin, a macrolide antibiotic . The mode of action of CV-1 seemed to be the inhibition of lipopolysaccharide synthesis.

J Pharm Pharmacol, 1987 Jun, 39(6), 480 - 3
The oral clearance of zinc and triclosan after delivery from a dentifrice; Gilbert RJ; Oral delivery and retention of zinc and triclosan were measured in man after use of an anti-plaque dentifrice containing these antibacterial agents . Triclosan (25% of the dose) and zinc (24%) were retained in the mouth immediately after toothbrushing and a single mouthrinse . Salivary concentrations fell from 7.5 micrograms g-1 (triclosan) and 7.0 micrograms g-1 (zinc) after 5 min to 0.5 micrograms g-1 (triclosan) and 1.2 micrograms g-1 (zinc), 2 h after brushing.

Jpn J Antibiot, 1987 May, 40(5), 995 - 1000
{Clinical effect of cefuzonam against infectious diseases in obstetrics and gynecology}; Chimura T et al.; Clinical studies of cefuzonam (CZON, L-105) were performed in patients of obstetrics and gynecology, and the results obtained are summarized below . 1 . CZON was intravenously administered at a daily dose of 1-2 g to 11 cases including 3 cases with intrauterine infection (pyometra), 2 cases of intrapelvic infection (1 case of pelvic dead space infection and 1 case of pelvic peritonitis), 1 case of adnexitis, and others (2 cases of vaginal cuff infection, and 1 case each of vaginal abscess, Baltholin's abscess, and vulvar abscess) . Clinical efficacy was excellent in 1 case and good in 10 cases . 2 . CZON showed a good antibacterial effect in single and mixed infections . 3 . Neither side effects nor abnormal values in clinical laboratory findings attributable to the drug were observed.

Jpn J Antibiot, 1987 May, 40(5), 983 - 94
{Clinical evaluation on the usefulness and safety of norfloxacin in a twice-a-day regimen against upper respiratory tract infections}; Okubo T et al.; Sixty-six patients with tonsillitis or pharyngolaryngitis received oral norfloxacin (NFLX) 200 mg b.i.d . or 300 mg b.i.d . for not less than 3 days in general at School of Medicine, Yokohama City University, and 6 related hospitals . The results are summarized as follows: 1 . Ten patients were excluded from the study because 4 patients did not present at the follow-up visits, 4 patients did not follow the protocol and 2 patients had unclear infections . Thus, 56 patients were evaluated . 2 . The fifty-six evaluable patients were classified as follows: Twenty patients were with tonsillitis and 36 were with pharyngolaryngitis . Thirty-eight patients were treated with 200 mg b.i.d . while 18 patients received 300 mg b.i.d . Thirty-two patients were male and 24 patients were female . Three patients were inpatients and 53 patients were outpatients . Most of patients were light or moderate cases, and the 26 patients had mild underlying disorders . 3 . Clinical improvements were observed in 11 of 15 patients (73.3%) with tonsillitis and 25 of 30 patients (83.3%) with pharyngolaryngitis (80.0% overall) within 7 days administration . 4 . Clinical improvements were observed in 15 of all 20 patients (75.0%) with tonsillitis and 30 of all 36 patients (83.3%) with pharyngolaryngitis (80.4% overall) . 5 . Bacteriologically, "eradication", "decrease" and "replacement" were observed in 6, 2 and 1 patients, respectively . 6 . As for adverse effects, nausea and headache were observed in 1 patient and abnormal changes in laboratory findings were noted in 1 patient (slight elevations of GOT and GPT) . 7 . Oral NFLX 200 mg b.i.d . or 300 mg b.i.d . was as almost equally effective as 200 mg t.i.d . in tonsillitis or pharyngolaryngitis . Thus NFLX 200 mg b.i.d . or 300 mg b.i.d . appears to give sufficient clinical efficiency . 8 . When antibacterial activity and serum half-life of NFLX are considered, twice daily administration was confirmed to be sufficiently effective in the clinical application.

Jpn J Antibiot, 1987 May, 40(5), 1089 - 93
{Pharmacokinetics of cefuzonam in peripheral venous serum, uterine arterial serum and intrapelvic female organs}; Miyakawa I et al.; Concentrations of cefuzonam (CZON) in peripheral venous serum, uterine arterial serum and intrapelvic female organs of 29 women undergone simple total hysterectomy were determined by bioassay, using the cylinder-plate diffusion method . With an intravenous injection of CZON 1 g, the concentration at time 0 (Cp0) of peripheral venous serum and uterine arterial serum were 148.1 micrograms/ml and 155.4 micrograms/ml, respectively . Biological half-lives (T 1/2) of CZON were 1.07 hours in peripheral venous serum and 1.02 hours in uterine arterial serum . Concentrations in peripheral arterial serum were higher than 1.0 micrograms/ml at 4 hours after injection and remained at higher levels than minimal inhibitory concentrations necessary for most Escherichia coli strain for at least 4 hours . Concentrations of CZON in female organs were kept as high as peripheral venous serum, and ratios of CZON concentrations in uterine tube and endometrium to that in peripheral venous serum were 0.74 +/- 0.34 and 0.44 +/- 0.25, respectively . Since CZON is characterized by potent antibacterial activity and broad spectrum, it should be effective for infectious diseases of the female uro-genital tract.

J Antibiot (Tokyo), 1987 May, 40(5), 567 - 74
Tiacumicins, a novel complex of 18-membered macrolide antibiotics . I . Taxonomy, fermentation and antibacterial activity; Theriault RJ et al.; A complex of 18-membered macrolide antibiotics has been discovered in the fermentation broth of strain AB718C-41 . The producing culture, isolated from a soil sample collected in Hamden, Connecticut, was identified as a strain of Dactylosporangium aurantiacum and was designated D . aurantiacum subsp . hamdenesis subsp . nov . The antibiotic complex was produced in a New Brunswick 150-liter fermentor using a medium consisting of glucose, soybean oil, soybean flour, beef extract and inorganic salts . Several of the antibiotics were active against sensitive and multiple antibiotic-resistant strains of pathogenic Gram-positive bacteria.

Clin Allergy, 1987 May, 17(3), 209 - 16
An immunoassay for the detection of IgE antibodies to trimethoprim in the sera of allergic patients; Harle DG et al.; An immunoassay was developed to detect IgE antibodies to the widely used antibacterial drug trimethoprim . Significant levels of trimethoprim-reactive IgE antibodies were found in the sera of two patients who had experienced life-threatening allergic reactions following administration of a combination of trimethoprim and sulphamethoxazole . No IgE antibodies reactive with sulphamethoxazole were found in the sera of either patient . Inhibition experiments revealed that a high degree of cross-reactivity occurs between the drug-reactive IgE antibodies and two structural analogues of trimethoprim, 6-hydroxy- and 6-chlorotrimethoprim . These experiments also indicated that the combining sites of the trimethoprim-reactive IgE antibodies in the two sera were probably complementary to different parts of the trimethoprim molecule . The assay should supplement skin testing in determining the offending drug in patients with suspected allergic sensitivity to trimethoprim-sulphamethoxazole complex.

Appl Environ Microbiol, 1987 May, 53(5), 966 - 8
Phomenoic acid and phomenolactone, antifungal substances from Phoma lingam (Tode) Desm.: kinetics of their biosynthesis, with an optimization of the isolation procedures; Topgi RS et al.; Phomenoic acid and phomenolactone, previously isolated from the fungus Phoma lingam (Tode) Desm., have shown moderate antifungal and antibacterial properties in vitro . To rationalize the production of phomenoic acid, a kinetic study of its biosynthesis in the mycelium was performed . Phomenoic acid and phomenolactone appear in the mycelium after a prolonged incubation, a phenomenon which may be of particular interest for the production of these substances or in the study of the mechanism of their biosynthesis . The isolation procedure was optimized for phomenoic acid . Through a series of SiO2 column chromatographies, high-pressure liquid chromatography, and transformation of the mixture of phomenoic acid and phomenolactone into methyl phomenoate (BF3), the final yield of phomenoic acid reached 160 mg/liter of culture medium . An alternative method for the isolation of both phomenoic acid and phomenolactone is also reported in detail.

Antimicrob Agents Chemother, 1987 May, 31(5), 774 - 9
Effects of ciprofloxacin on eucaryotic pyrimidine nucleotide biosynthesis and cell growth; Forsgren A et al.; Several of the new 4-quinolones significantly increase the incorporation of {3H}thymidine into the DNA of mitogen-stimulated human lymphocytes . This study suggests that ciprofloxacin inhibits de novo pyrimidine biosynthesis, thereby resulting in a compensatory increase in the uptake of pyrimidine precursors through salvage pathways, and that additional effects may affect eucaryotic cell growth . Incorporation of deoxyuridine, uridine, and orotic acid as well as thymidine was increased in the presence of ciprofloxacin, one of the antibacterially most active of the new 4-quinolones . In contrast, the uptake was decreased in very high concentrations of the drug . Culture in HAT (hypoxanthine, aminopterine, thymidine) medium, which blocks de novo thymidylate synthesis, abrogated the increase in {3H}thymidine incorporation induced by ciprofloxacin . Ciprofloxacin also failed to increase the uptake of {14C}hypoxanthine or leucine, indicating a selective effect on pyrimidine and not on purine nucleotide biosynthesis . N-(Phosphonacetyl)-L-aspartate, an inhibitor of pyrimidine nucleotide biosynthesis, also increased {3H}thymidine incorporation in phytohemagglutinin-stimulated lymphocytes in a fashion similar to ciprofloxacin . The growth of several cell lines was partially inhibited by ciprofloxacin at 20 micrograms/ml and completely inhibited at 80 to 160 micrograms/ml . Growth inhibition by ciprofloxacin could not be restored by the addition of uridine to the medium . Chromosome breaks, gene amplification, or other genetic alterations could not be detected in human lymphocytes incubated with up to 25 micrograms of ciprofloxacin per ml.

Antimicrob Agents Chemother, 1987 May, 31(5), 768 - 73
4-Quinolone drugs affect cell cycle progression and function of human lymphocytes in vitro; Forsgren A et al.; Most antibacterial agents do not affect human lymphocyte function, but a few are inhibitory . In contrast, a pronounced increase in the incorporation of {3H}thymidine in the presence of 4-quinolones was observed in these studies . The uptake of {3H}thymidine into DNA (trichloroacetic acid precipitable) was significantly increased in phytohemagglutinin-stimulated human lymphocytes when they were exposed to eight new 4-quinolone derivatives, ciprofloxacin, norfloxacin, ofloxacin, A-56619, A-56620, amifloxacin, enoxacin, and pefloxacin, at 1.6 to 6.25 micrograms/ml for 5 days . Four less antibacterially active 4-quinolones (nalidixic acid, cinoxacin, flumequine, and pipemidic acid) stimulated {3H}thymidine incorporation only at higher concentrations or not at all . Kinetic studies showed that incorporation of {3H}thymidine was not affected or slightly inhibited by ciprofloxacin 2 days after phytohemagglutinin stimulation but was increased on days 3 to 6 . The total incorporation of {3H}thymidine from day 1 to day 6 after phytohemagglutinin stimulation was increased by 42 to 45% at 5 to 20 micrograms of ciprofloxacin per ml . Increased {3H}thymidine incorporation was also seen when human lymphocytes were stimulated with mitogens other than phytohemagglutinin . Ciprofloxacin added at the start of the culture had a more pronounced effect on {3H}thymidine incorporation than when added later . In spite of the apparent increase in DNA synthesis, lymphocyte growth was inhibited by 20 micrograms of ciprofloxacin per ml, and cell cycle analysis showed that ciprofloxacin inhibited progression through the cell cycle . In addition, immunoglobulin secretion by human lymphocytes stimulated by pokeweed mitogen for Epstein-Barr virus was inhibited by approximately 50% at 5 micrograms of ciprofloxacin per ml . These results suggest that the 4-quinolone drugs may also affect eucaryotic cell function in vitro, but additional studies are needed to establish an in vivo relevance.

Rev Infect Dis, 1987 May-Jun, 9 Suppl 3, S261 - 9
Policies, laws, and regulations pertaining to antibiotics: report of Task Force 3; Simon HJ et al.; A questionnaire survey-based study of 41 countries was conducted to determine the nature and extent of policies, laws, and regulations governing the prescription, sale, and use of antibacterial agents and the enforcement of and compliance with such policies, laws, and regulations . On the basis of responses adequate for analysis that were received from 35 countries, three groups were identified according to the availability of antibacterial agents to the general public in a country . In one group, access by the general public to these agents was severely restricted, and restrictions were effectively enforced . In the second group, restrictions were less stringent, and enforcement was less effective . In the third group, access was unrestricted . Still to be determined is whether this grouping bears any relation to patterns of antibacterial use, resistance to antibacterial agents, and other factors pertaining to the use of these drugs.

J Med Chem, 1987 May, 30(5), 900 - 6
A quantitative structure-activity relationship analysis of some 4-aminodiphenyl sulfone antibacterial agents using linear free energy and molecular modeling methods; Lopez de Compadre RL et al.; A set of 36 congeneric 4-aminodiphenyl sulfones with measured inhibition potencies of dihydropteroate synthase were studied by using both linear free energy and molecular modeling methods . The goals of the investigation were to identify the "active" conformation for these compounds as inhibitors and, correspondingly, to contruct a quantitative structure-activity relationship (QSAR) . These molecules are quite flexible and possess multiple conformational energy minima . Application of molecular shape analysis (MSA), using all intramolecular energy minima as part of the analysis, was not successful in generating a QSAR . However, the calculated intramolecular conformational entropy of these compounds was found to correlate with inhibition potency leading to a highly significant QSAR . Inhibition potency increases as entropy decreases . A decrease in entropy enhances the population of specific, symmetry-related minimum-energy conformations . In this indirect way, it was possible to postulate an "active" conformation . This investigation illustrates that specific knowledge of the "active" shape of a molecule may not provide the information needed to quantitatively explain the observed structure-activity relationship.

J Med Chem, 1987 May, 30(5), 839 - 43
Synthesis, absolute configuration, and antibacterial activity of 6,7-dihydro-5,8-dimethyl-9-fluoro-1-oxo-1H,5H- benzo{ij}quinolizine-2-carboxylic acid; Gerster JF et al.; The tricyclic quinolone antibacterial agent 6,7-dihydro-5,8-dimethyl-9-fluoro-1-oxo-1H,5H-benzo{ij}quinolizine -2-carboxylic acid has an asymmetric center at position 5 of the molecule . The R and S isomers of the compound have been prepared from the corresponding (R)- and (S)-2,5-dimethyl-6-fluoro-1,2,3,4-tetrahydroquinolines, which were separated via their diastereomeric amides of N-tosyl-(S)-proline . The absolute configuration was established by X-ray analysis of one of the diastereomeric amides . The 5-desmethyl analogue was prepared for antibacterial comparison with the isomers and the racemic mixture . It has now been established that the S isomer is much more active than the R isomer . The 5-desmethyl analogue was found to be more active than the R isomer but not as active as the S isomer or the racemic mixture . The importance of stereochemistry at position 5 in this system has been established.

J Med Chem, 1987 May, 30(5), 764 - 7
Synthesis and pharmacological evaluation of a new class of 2-(2-aminothiazol-4-yl)-2-hydrazonoacetamido cephalosporins; Brandt A et al.; A series of 2-(2-aminothiazol-4-yl)-2-hydrazonoacetamido cephalosporins 1a-h was prepared . Whenever possible, E and Z isomers were isolated, and their relative stabilities and their interconversions were tested . The antibacterial activity was tested against Gram-positive and Gram-negative bacteria . For compound 1c, whose Z and E forms do not interconvert rapidly, the Z form was the more active one . Among the other compounds, for which the E form is the only stable one for practical purposes, compound 1a was the most active . When compared with cefuroxime and cefotaxime, compound 1a showed slightly lower antibacterial activity but good serum level and half-life values.

Blood, 1987 May, 69(5), 1441 - 9
Comparison of three remission induction regimens and two postinduction strategies for the treatment of acute nonlymphocytic leukemia: a cancer and leukemia group B study; Preisler H et al.; Patients with acute nonlymphocytic leukemia were randomized to receive remission induction therapy consisting of seven days of cytosine arabinoside and three days of daunorubicin ("7 + 3") or to receive the same regimen intensified by either the addition of 6-thioguanine or by extension of the administration of cytosine arabinoside to ten days . Additionally, all patients were randomized to receive or not to receive cotrimoxazole antibacterial prophylaxis during the remission induction phase . Neither an increase in intensity of chemotherapy nor the antibacterial prophylaxis increased the remission rate above the 53% for patients treated with the standard "7 + 3" regimen . The second part of this study addressed the issue of the utility of long-term maintenance chemotherapy . To this end, patients were randomized to discontinue all treatment after 8 months of maintenance chemotherapy or to continue maintenance therapy for a total of 3 years . Although there was a transient increase in the relapse rate for patients who discontinued therapy, the proportion of long-term remitters was identical in the two patient groups . Additionally, there is a suggestion of a survival advantage for patients randomized to discontinue all therapy at 8 months.

Clin Exp Immunol, 1987 May, 68(2), 313 - 9
Anti-cardiolipin antibodies in neurological disorders: cross-reaction with anti-single stranded DNA activity; Colaco CB et al.; Antiphospholipid (PL) antibodies have been detected in sera from patients with chronic neurological diseases associated with disorders of immunity . In an isotype specific radioimmunoassay for anti-cardiolipin (CL) antibodies, we found IgM anti-CL (greater than 2 s.d . above mean of controls) in 17/25 (68%) patients with myasthenia gravis (MG), 8/25 (32%) with the Lambert-Eaton myasthenic syndrome (LEMS), 5/17 (29%) with multiple sclerosis and 3/11 (27%) cases of migraine . IgG anti-CL was only found in low titres in sera from 10 patients with MG and three with LEMS . Significant anti-CL activity could not be detected in sera from nine patients with acute Guillain-Barre Syndrome (GBS), 12 chronic cases of epilepsy, 8/9 with oat cell carcinoma and 9/10 with acute stroke . Further tests on 39 sera with the highest anti-CL activity, from all of the above disease groups, showed a significant correlation between IgM anti-CL and IgM anti-ss DNA activities . In a series of competitive inhibition assays six sera from patients with MG were shown to have a proportion of both specific and cross-reactive IgM anti-CL and IgM anti-ss DNA antibodies . Anti-phospholipid antibodies occur in certain neurological diseases, at lower titres than seen in SLE, yet their cross-reactive binding to ss DNA suggests similar antibacterial origins as have been proposed for lupus auto-antibodies . In the absence of overt infection they might reflect a breakdown of tolerance for non-organ specific membrane antigens in diseases with predominantly organ specific membrane bound putative autoimmunogens.

Acta Otolaryngol, 1987 May-Jun, 103(5-6), 355 - 62
Immunobarriers of the tubotympanum; Lim DJ et al.; The tubotympanum is protected by an immune system in addition to the mucociliary, secretory (antibacterial substance), and phagocytic defense systems . The immune protection is provided by innate and adaptive immune systems . With the latter, the tubotympanum is protected by both the local (humoral and cellular) and the systemic immunity . The major immunoglobulins involved are IgG, IgM (SIgM), and SIgA, although IgE and IgD may also be involved.

Rehabilitation (Stuttg), 1987 May, 26(2), 70 - 4
{Historical development of rehabilitation of cancer patients in the Hamburg area}; Heyde W; It had been particularly noticeable in the post-war years that a surprisingly large number of women who had undergone cancer treatment (mostly for uterine and breast cancer) had to be readmitted in poor general health soon after their initial discharge home . Although the full treatment regimen then available was applied (such as blood transfusions, vitamin-glucose-infusions, and antibacterial medication), a larger number of deaths occurred, without any trace being found of the presence of residual cancer, early recidive, or second carcinoma . Close medical observation, finally, lead us to conclude that these patients' stamina had been too deeply undermined to be able to overcome the disease and treatment aftermath, caused mainly by chronic under-nourishment, both quantitatively and qualitatively, by often disastrous housing conditions (in refugee camps, cellars, etc.), the emotional strain experienced due to death or imprisonment of the closest relatives, and, in particular, by the resulting obligation to maintain the family, usually through work under very strenuous conditions, as well as by flight and hence loss of the accustomed environment . In cooperation with the social security administrations, these insights brought about the provision of "convalescent cures" of 4-6 weeks duration, with repeat health resort treatments being possible till the end of the third year post-discharge . Again involving the social security institutes, these measures, in the process of our growing knowledge of fact and inter-relationships, were extended to become the disease-specific aftercare treatment provided in rehabilitation clinics.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibiot Med Biotekhnol, 1987 May, 32(5), 357 - 60
{The type of interaction of polyene antibiotics with antifungal and antibacterial agents}; Potyl'chanskaia OL et al.; The combined effect of various polyenic antibiotics and other antifungal and antibacterial drugs on Candida was studied . The efficacy of the combinations was estimated with the method of square titration followed by quantitative plating out of the samples . By the interaction type the combinations were divided into 3 groups . The character of the drug interaction in these groups might be considered as indifferent, additive or synergistic . No antagonistic effect was observed in any of the combinations . The findings may be useful in more successful treatment of candidiasis when monotherapy is not sufficiently efficient, as well as in optimization of schemes for treating mixed infections.

Rev Infect Dis, 1987 May-Jun, 9 Suppl 3, S244 - 60
Resistance of bacteria to antibacterial agents: report of Task Force 2; O'Brien TF; The use of a growing number of antibacterial agents over the past half century has elicited a widespread deployment of genes for resistance to these agents in populations of bacteria throughout the world . Task Force 2 of the NIH Study on Antibiotic Use and Antibiotic Resistance Worldwide found that data on prevalence of resistance was fragmentary and underanalyzed but indicative of several trends . Resistance to older antibacterial agents appears to have stabilized overall, but shifts of resistance genes into new strains and species have continued to cause new clinical problems . Resistance to newer antibacterial agents has increased . Resistance is more prevalent in developing countries . Systematic surveillance of resistance integrated with understanding of its molecular basis is needed for control of resistance.

Pediatr Med Chir, 1987 May-Jun, 9(3), 281 - 2
{Splenectomy and infection in homozygous beta-thalassemia . The uselessness of penicillin prophylaxis}; Arigliani R et al.; To investigate the effective usefulness of penicillin prophylaxis in splenectomized patients, we retrospectively focused on a group of sixty-two splenectomized patients affected by thalassemia major . Thirty-six out of 62 has been receiving monthly 1.200.000 Us . of benzathine-penicillin as prophylaxis . The remaining 26 did not receive prophylaxis, but was treated with antibacterial drugs as soon as symptoms of upper respiratory tract infection occurred . During a total period of eleven years of observation we did not observe any pneumococcal sepsis; the incidence of bacterial infections within the two groups is not different . We conclude for the uselessness of penicillin prophylaxis in splenectomized beta-thalassemic patients.

Antimicrob Agents Chemother, 1987 May, 31(5), 679 - 85
Serum bactericidal rate as measure of antibiotic interactions; Briceland LL et al.; The serum bactericidal rate (SBR) assay was used to assess the antipseudomonal activity of gentamicin with or without piperacillin . Heat-inactivated donor serum was spiked with gentamicin, piperacillin, or a combination at concentrations representative of levels in serum and tested against five P . aeruginosa strains isolated from blood . The SBR assay was performed as follows: colony counts in test samples (control, gentamicin, piperacillin, and combination) were determined at 0, 2, 4, 6, and 8 h after inoculation of a test strain . Log10 CFU per milliliter was plotted versus time, and linear regression analysis was performed; the slope of the regression line was defined as the SBR . The SBRs of agents alone and in combination were compared statistically . The SBR of gentamicin was dependent on the serum concentration . The combination of gentamicin and piperacillin always resulted in a higher SBR than did either drug alone . However, this difference was not statistically significant for highly gentamicin-susceptible strains (MIC, less than or equal to 2 micrograms/ml) until the gentamicin concentration was reduced below the MIC . For a gentamicin-resistant strain (MIC, 8 micrograms/ml), the combination of gentamicin and piperacillin produced mean SBRs similar to that found with gentamicin-susceptible strains . These results provide evidence that the SBR assay may be a useful method of evaluating antibiotic interactions, since it can be done by using serum and since it compares the antibacterial activity of drugs statistically rather than requiring arbitrary criteria to define interactions.

Am J Med, 1987 Apr 27, 82(4A), 164 - 8
Controlled, comparative study of ciprofloxacin versus ampicillin in treatment of bacterial respiratory tract infections; Wollschlager CM et al.; The efficacy and safety of ciprofloxacin in bacterial bronchitis were compared with those of ampicillin in a double-blind, prospective clinical trial . Eighty-seven patients received either oral ciprofloxacin (750 mg twice daily) or oral ampicillin (500 mg four times daily) . Ciprofloxacin was as effective as ampicillin and produced a 98 percent clinical cure rate . Significantly more pretreatment bacterial isolates were susceptible to ciprofloxacin (p less than 0.05), and ciprofloxacin had a significantly higher rate of sputum sterilization than did ampicillin (p less than 0.05) . Ciprofloxacin showed broad in vitro antibacterial activity with particularly low minimal inhibitory concentrations for gram-negative organisms . Ciprofloxacin was well tolerated; there were few adverse effects, and patients had a significantly lower incidence of diarrhea with ciprofloxacin than with ampicillin (p less than 0.05) . Ciprofloxacin was an effective and well-tolerated treatment for bacterial bronchitis that had the advantages of broad in vitro antibacterial activity and twice-daily dosing.

Eur J Drug Metab Pharmacokinet, 1987 Apr-Jun, 12(2), 91 - 102
Pharmacokinetics of cefotaxime and its desacetyl metabolite in plasma and in cerebrospinal fluid; Beyssac E et al.; The aim of the study was to investigate the pharmacokinetic modelling of Cefotaxime (CTX) and its main metabolite Desacetyl Cefotaxime (DCTX) which has a less antibacterial activity than the CTX . After intravenous administration of 1g of CTX to 26 patients, the plasma concentrations determined by HPLC showed that the pharmacokinetics of CTX and transformation to DCTX can be described with an open five-compartment model . The implications of this are discussed from the clinical point of view.

Chemioterapia, 1987 Apr, 6(2), 85 - 7
Evaluation of the minimal bactericidal time (MBT) of sulbenicillin against multiresistant pathogens; Debbia E et al.; The in vitro antibacterial activity of sulbenicillin was evaluated against multiresistant strains isolated from in-patients and compared with that of carbenicillin and piperacillin . Sulbenicillin resulted in being as active as the other drugs against the strains tested, both at different pH, and at different bacterial inocula . In the time-kill tests sulbenicillin demonstrated bactericidal activity similar to that of piperacillin, and a higher killing rate when compared with that of carbenicillin.

Antibiot Med Biotekhnol, 1987 Apr, 32(4), 291 - 3
{Microbiological research on the secretion of the normal parotid glands and in acute and chronic non-mumps parotitis in children}; Savin VR et al.; The qualitative and quantitative compositions of the microbial flora of the parotid gland were investigated in 42 children with nonepidemic parotiditis . The pathogenic properties of the microbial flora were the most pronounced in acute purulent and purulent necrotic parotiditis as compared to those in aggravation and remission of chronic parotiditis . In children with acute or chronic recurring parotiditis during its aggravation there was observed a significant increase in the number of the coccal organisms in the mixture of saliva and secretion of the parotid gland . Direct relationship between the aggravation activity and the number of the microbes was noted which testified to lowering of the protective functions of the oral cavity tissues . With an account of the presence of microorganisms in the clinically intact salivary glands it was concluded that the microbial factor was secondary in etiology of parotiditis . Quantitative estimation of bacteria in the mixture of saliva and parotid gland secretion is important for antibacterial therapy of the disease which is advisable when 1 ml of secretion of the affected glands contains 10(5) microorganisms . Their antibiotic sensitivity tests are obligatory.

Pharmazie, 1987 Apr, 42(4), 251 - 2
Antibacterial and antitumor activity of platinum complexes of hydrazinopyrimidines and amidrazones; Pelova R et al.; Antibacterial and antitumor activity of 10 platinum complexes of N3-phenylsubstituted amidrazones and hydrazinopyrimidines has been studied . It has been found that the platinum complexes of amidrazones, containing substituents in the benzene nuclear or in the NH2-group, exhibit a better antibacterial activity while those without substituents in their benzene nuclears have a pronounced antibacterial activity mostly on bacterial test-systems used in the prescreening of antitumor agents (S . lutea and UV-2) . Most of the studid platinum complexes of hydrazinopyrimidines show inhibitory effect on the bacterial strains used in the prescreening of antitumor agents . The antitumor activity of platinum complexes has been tested on L1210 leukemia, adenocarcinoma 755 and Lewis carcinoma . An inhibitory effect is observed in the case of adenocarcinoma 755 with the cis-isomer of the platinum complex of N3-p-tolylbenzamidrazone (the tumor growth was 60% suppressed).

Arzneimittelforschung, 1987 Apr, 37(4), 467 - 71
An approach of the in vivo antibacterial activity of benzoxonium chloride and comparison with other buccopharyngeal disinfectants; Weibel MA et al.; Different pharmaceutical forms of N-benzyl,N-dodecyl-N,N-di(2-hydroxyethyl) ammonium chloride (benzoxonium chloride, Orofar) have been tested on the overall buccopharyngeal bacterial count in healthy volunteers, and compared to competitors . Gargle solutions are most effective in reducing initial bacterial count . An open repeated dose study has been performed on 38 patients with sore throat to assess the safety and the efficacy of benzoxonium chloride tablets and gelsolets at doses of 6 mg and 10 mg daily for 4 to 6 days . Pathogens disappeared or were clearly reduced and the syndrome resolved . Tolerance was good . Differences in methodologies are discussed.

Antimicrob Agents Chemother, 1987 Apr, 31(4), 630 - 1
In vitro activity of BMY-28100 against common isolates from pediatric infections; Scribner RK et al.; The antibacterial activity of BMY-28100, a new oral cephalosporin, was measured against 300 bacterial isolates from pediatric infections by standard agar dilution methodology . The effect of inoculum size on activity was also assessed . BMY-28100 was more active than cephalexin or cefaclor against all bacterial species tested.

J Antibiot (Tokyo), 1987 Apr, 40(4), 476 - 82
Syntheses of 23-C-alkylidene, and 23-N-containing derivatives of 5-O-mycaminosyltylonolide; Kajikawa N et al.; Several derivatives of 5-O-mycaminosyltylonolide substituted at C-23 have been prepared; these are 23-deoxy-23-C-methylene (3), 23-deoxy-23-C-(methoxycarbonylmethylene) (5), 23-deoxy-23-C-(ethoxycarbonylmethylene) (7), and 23-deoxy-23-C-(butoxycarbonylmethylene) (9), 23-deoxy-23-C-{(2E)-3-(ethoxycarbonyl)-2-propenylene} (11), and 23-deoxy-23-(dimethylaminoimino) (13), and 14-de(hydroxymethyl)-14-nitrile (16) derivatives . The key steps in these syntheses are the reactions of 2',4'-di-O-acetyl-3-O-tert-butyldimethylsilyl-23-deoxy-23-oxo-5-O- mycaminosyltylonolide diethyl acetal (1) with several Wittig reagents, 1,1-dimethylhydrazine and hydroxylamine . Antibacterial activities of these compounds are also described.

J Antibiot (Tokyo), 1987 Apr, 40(4), 443 - 9
Antibiotics from basidiomycetes . 26 . Phlebiakauranol aldehyde an antifungal and cytotoxic metabolite from Punctularia atropurpurascens; Anke H et al.; Phlebiakauranol aldehyde and the corresponding alcohol were isolated from cultures of Punctularia atropurpurascens . The aldehyde but not the alcohol exhibited strong antifungal activity against several phytopathogens as well as antibacterial and cytotoxic activities . Two acetylated derivatives prepared from the aldehyde showed only very weak antifungal and antibacterial and moderate cytotoxic activities . We therefore assume, that the aldehyde group together with the high number of hydroxyl groups are responsible for the biological activity of the compound.

Mikrobiyol Bul, 1987 Apr, 21(2), 151 - 7
{Fluoroquinolones}; Baykal M et al.; We reviewed, the structure, pharmacokinetic properties, mode of actions, antibacterial spectrum, therapeutic dosage and side effects of fluoroquinolones in this article.

Scand J Dent Res, 1987 Apr, 95(2), 104 - 11
Vascular and cellular responses to guanidino propyl piperazine CK0569A, a new anti-plaque agent; Hurttia H et al.; Guanidino propyl piperazine CK0569A (abbreviation piperazine) used as a 0.1% mouthrinse has been shown to be effective against plaque bacteria . In addition to its efficacy as an antibacterial agent, its safety should be taken into consideration . In this study the effect of piperazine on the microcirculation of the hamster cheek pouch was studied . The effect of this drug was also investigated on rat leukocytes in vivo and on macrophages and erythrocytes in vitro . Piperazine caused a distinct retardation in the microcirculation of the hamster cheeck pouch even at a low concentration (0.01%), but the effect was abolished in 5 min . The number of leukocytes decreased markedly in the experimentally induced inflammatory exudate in the presence of 0.05% piperazine as compared to the controls . The macrophages in vitro released their lysosomal and cytoplasmic enzymes and lost their viability . The erythrocytes in vitro were destroyed in the presence of 0.005% piperazine as well . Based on these results it can be suggested that 0.005-0.05% piperazine under experimental conditions causes changes that indicate loss of cell viability.

Antimicrob Agents Chemother, 1987 Apr, 31(4), 518 - 22
Comparative efficacy of cefotiam, cefmenoxime, and ceftriaxone in experimental endocarditis and correlation with pharmacokinetics and in vitro efficacy; Pangon B et al.; To determine the influence of in vitro activity, pharmacokinetic properties, and therapeutic regimen on the antibacterial effect in vivo, we compared three cephalosporins, cefotiam, cefmenoxime, and ceftriaxone, in a rabbit model of experimental Escherichia coli endocarditis after 4 days of treatment . The MBCs of cefotiam, cefmenoxime, and ceftriaxone for the E . coli strain were 0.5, 0.125, and 0.06 microgram/ml, respectively . Killing curves at 10 times the MBC were similar for the three cephalosporins . In serum, the elimination half-life of ceftriaxone was twice as much as the elimination half-life of cefotiam or cefmenoxime (2.8 +/- 0.45 versus 1.4 +/- 0.25 or 1.3 +/- 0.4 h, respectively) . Ceftriaxone was much more effective than cefotiam . The bacterial titer in the vegetations (log10 CFU per gram of vegetation) was 7.56 +/- 1 with cefotiam and 2.41 +/- 2.6 with ceftriaxone, as their concentrations were 18 and 466 times higher, respectively, than their MBCs . Although ceftriaxone and cefmenoxime exhibited a similar rate of killing and percentage of protein binding, ceftriaxone was more effective than cefmenoxime at the same regimen of 15 mg/kg twice a day (3.08 +/- 1.1 versus 4.82 +/- 3.2 log10 CFU/g of vegetation) . When antibiotic was given as a single daily injection of 30 mg/kg, the antibacterial effect persisted for ceftriaxone, but not for cefmenoxime . The longer elimination half-life and the higher local concentration/MBC ratio of ceftriaxone explained these results . The bacterial titer measured 24 h after the fourth injection of 30 mg of ceftriaxone per kg confirmed that this regimen prevented regrowth of bacteria . These results suggest that the local antibiotic level/MBC ratio roughly correlated with the antibacterial effect and could represent an adequate basis to explain the differences observed between the drugs in vivo . They also demonstrate that, provided that the dose is sufficient, a long-acting broad-spectrum cephalosporin may be effective in severe gram-negative infections, even when given at relatively long dosing intervals, in contrast with a rapidly cleared drug with the same intrinsic activity.

Chemioterapia, 1987 Apr, 6(2), 88 - 94
Microbiological properties of sulbactam combined with ampicillin; Barba D et al.; Several in vitro parameters of sulbactam combined with ampicillin (Sbt/Amp) were studied in order to evaluate and compare its microbiological properties with those of beta-lactamase stable beta-lactams (ceftriaxone, cefamandole, cefoxitin) . The intrinsic activity of Sbt/Amp was satisfactory and comparable to that of other beta-lactams and no significant difference was observed against beta-lactamase producing or non-producing bacteria . Besides, it was determined that sulbactam, when combined with ampicillin at different ratios (1:2, 5:1), with and without preincubation (60 min) reduces the hydrolysis of ampicillin determined by ten different standard beta-lactamases . The hydrolysis rates of ampicillin become as low as those of cefoxitin, cefamandole and ceftriaxone, which are beta-lactamase stable cephalosporins . In fact, all the antibiotics under examination were slightly hydrolyzed by several beta-lactamases, but such slight hydrolysis did not affect the antibacterial activity against beta-lactamase producing bacteria . About 50% of non-beta-lactamase producing bacteria (18 strains of different bacterial species) produced an inducible beta-lactamase after ten daily subcultures with sub-inhibitory concentrations of each antibiotic, but minimum inhibitory concentrations (MICs) of Sbt/Amp never increased after stimulation in contrast with other drugs whose MICs were much higher in consequence of this procedure . Finally, no spontaneous resistant mutant to Sbt/Amp was detected, but several mutants appeared in response to the other drugs . Sulbactam makes ampicillin as effective as beta-lactamase stable cephalosporins and its use does not determine an increase of resistance or selection of resistant mutants.

J Med Chem, 1987 Mar, 30(3), 528 - 36
Heteroatom-activated beta-lactam antibiotics: considerations of differences in the biological activity of {{3(S)-(acylamino)-2-oxo-1-azetidinyl}oxy}acetic acids (oxamazins) and the corresponding sulfur analogues (thiamazins); Boyd DB et al.; The considerable antibacterial activity of {{3(S)-(acylamino)-2-oxo-1-azetidinyl}oxy}acetic acids (oxamazins) in contrast to the lack of activity of the corresponding sulfur analogues (thiamazins) is examined in terms of physicochemical parameters, including electronegativity, IR carbonyl stretching frequencies, base hydrolysis rates, and three-dimensional molecular geometries . An X-ray structure determination of a protected thiamazin together with molecular graphics and molecular orbital calculations on model structures reveals that thiamazins would not fit as well as oxamazins in the active site of target bacterial transpeptidases . As a result of thiamazins' long N-S and S-C bond lengths, the pharmacophoric beta-lactam ring and carboxylate functionality cannot adopt the spatial relationship they have in penicillins and cephalosporins . The beta-lactam nitrogen of the monocyclic, crystalline thiamazin is 0.18 A out of the plane of its three substituents, and this distance (h) is predicted by computational chemistry methods to be higher in oxamazins . The rates of beta-lactam ring opening of an oxamazin, thiamazin, and aztreonam are comparable, even though the pyramidal character and IR data both indicate the electronegative oxygen analogue has reduced amide resonance . MNDO, AM1, and MINDO/3 correctly give a twofold potential for rotation about the N-S bond in model sulfenamides, with barrier heights ranging up to 12 kcal/mol.

J Med Chem, 1987 Mar, 30(3), 504 - 9
Synthesis and structure-activity relationship of 1-aryl-6,8-difluoroquinolone antibacterial agents; Chu DT et al.; A series of new arylfluoroquinolones has been prepared . These derivatives are characterized by having fluorine atoms at the 6- and 8-positions, substituted amino groups at the 7-position, and substituted phenyl groups at the 1-position . The in vitro antibacterial potency is greatest when the 1-substituent is 2,4-difluorophenyl and the 7-substituent is a 3-amino-1-pyrrolidinyl group . 1-(4-Fluorophenyl)-6,8-difluoro-7-piperazin-1-yl-1,4-dihydro-4-oxo quinoline-3- carboxylic acid (22) was found to possess excellent in vitro potency and in vivo efficacy.

J Med Chem, 1987 Mar, 30(3), 465 - 73
Quinolonecarboxylic acids . 2 . Synthesis and antibacterial evaluation of 7-oxo-2,3-dihydro-7H-pyrido{1,2,3-de}{1,4}benzothiazine-6-carboxylic acids; Cecchetti V et al.; A series of pyridobenzothiazine acid derivatives was synthesized and their in vitro antibacterial activity was evaluated . The 1,4-benzothiazine intermediates, which by Gould-Jacobs quinoline synthesis produced pyridobenzothiazine acids, were prepared by hydrolytic basic cleavage of substituted 2-aminobenzothiazoles and successive cyclocondensation with 1-bromo-2-chloroethane or alternatively with monochloroacetic acid, hence reduction by LiAlH4 . The pyridobenzothiazine acids 10c, 30, and 31 show potent antibacterial activities against Gram-positive and Gram-negative pathogens . Structure-activity relationships are discussed . The compound 9-fluoro-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H-pyrido{1,2,3-d e} {1,4}benzothiazine-6-carboxylic acid (31) (MF-934) has been found to possess, together with the antibacterial activity, a weak acute toxicity and interesting pharmacokinetic characteristics in several animal species (rat, dog, monkey, man).

Vestn Khir Im I I Grek, 1987 Mar, 138(3), 63 - 7
{Treatment of suppurative coxitis}; Nikitin GD et al.; An experience with the treatment of purulent coxitis in 56 patients is described . Acute coxitis was treated by arthrotomy, sequestrectomy and antibacterial therapy . Chronic forms of osteoarthritis consisted in the surgical treatment of the purulent focus and filling the cotyloid cavity with a muscular flap or the proximal end of the femoral bone.

Vestn Khir Im I I Grek, 1987 Mar, 138(3), 31 - 4
{Surgical tactics in destructive cholecystitis}; Arik'iants MS et al.; Bacteriological examinations of anaerobic and aerobic microflora of the bile, tissues of the gallbladder wall in 67 patients operated on with destructive cholecystitis have shown that surgical interventions should be performed within the first hours after admission to the hospital and must include special methods of purposeful antibacterial therapy during operation and in the postoperative period.

Pharmazie, 1987 Mar, 42(3), 160 - 1
Synthesis of 7 beta-(4-oxo-3,4-dihydrothieno{2,3-d} pyrimidyl-2-thioacetamido)cephalosporanic acid derivatives; Zekany A et al.; Synthesis of new cephalosporins possessing thieno {2,3-d}pyrimidine is described in the present paper . Potassium salts of 2-thio-4-oxo-3,4-dihydrothieno {2,3-d}pyrimidines, which gave then 2-carboxymethylmercapto-4-oxo-3,4-dihydrothieno {2,3-d}pyrimidines, were prepared from 2-amino-3-carbethoxythiophene derivatives . These compounds were allowed to react with 7-aminocephalosporamic acid (ACA) benzhydryl esters or with 7 beta-chloroacetamidocephalosporanic acid derivatives to obtain new cephalosporins . Antibacterial activities of these new cephalosporins are summarized in the present paper as well.

Rev Med Interne, 1987 Mar-Apr, 8(2), 173 - 9
{An intensive survey of drug surveillance in a medical admissions department}; Rostin M et al.; An intensive survey of pharmacovigilance was carried out in a medical admission department over a 4-month period . Out of 2,017 admissions to hospital, 23 (1,1 p . 100) were motivated by adverse reactions to drugs . Questioning brought out allergy and multiple drug therapy as important factors . Lesions of the skin and mucosae predominated, notably after treatment with antibacterial and non-steroidal anti-inflammatory agents . The categories of drugs involved were, in decreasing order of frequency: cardiovascular (6/23), anti-bacterial (5/23), neuropsychiatric (4/23) and non-steroidal anti-inflammatory drugs (4/23) . The fact that the patients had taken several products rendered evaluation difficult . Using imputability scales made it possible to reduce the cause-effect relationship in 26 p . 100 of the cases.

Antibiot Med Biotekhnol, 1987 Mar, 32(3), 227 - 30
{Modern diagnostic methods and the antibiotic sensitivity of the gram-negative causative agents of suppurative-inflammatory diseases of the extrahepatic bile ducts}; Bekbergenov BM et al.; Microscopic examination of native bile and smears stained with the Gram procedure rapidly provided information on the presence of bactericholia and the necessity of antibacterial therapy prior to closing of the postoperative wound in accordance with the drug spectrum . Determination of the phagocytic and bactericidal activity of the bile leukocytes was a significant adjuvant to routine microscopic examinations, whereas evaluation of the average cytochemical coefficient and phagocytosis intensity was an important factor in prognosis of postoperative pyoinflammatory complications . Gram-negative bacteria were the predominating causative agents of acute cholecystitis and cholangitis (89 per cent) . Among them Escherichieae, Klebsielleae and P . aeruginosa were isolated most frequently (32.4, 31.1 and 16.4 per cent, respectively) . Amikacin, tobramycin, sisomicin, gentamicin and cefotaxime showed the highest activity against the above pathogens . However, comparative analysis of the antibioticograms revealed differences in antibiotic sensitivity of separate bacterial species.

J Med Chem, 1987 Mar, 30(3), 459 - 64
Quantitative structure-activity analysis in dihydropteroate synthase inhibition by sulfones . Comparison with sulfanilamides; De Benedetti PG et al.; A set of 25 4'-, eight 2',4'-, and five 2',4',6'-substituted 4-aminodiphenyl sulfones were tested for their inhibitory activity on dihydropteroate synthase of Escherichia coli . Linear regression analysis shows that enzymic inhibition indices correlate well with both quantum chemical and spectroscopic descriptors of the electronic structure of the common moiety 4-NH2-C6H4-SO2 of the sulfones (the above descriptors being expressed in relation to the electronic structure of the enzyme substrate, p-aminobenzoate) . Therefore, the biological activity of the sulfones can be related to the electronic structural resemblance between these inhibitors and the substrate of the target enzyme . Since a similar result was previously obtained for a wide series of sulfanilamides in their different (amidic, imidic, and anionic) forms, it appears possible to consider the antibacterial sulfones and sulfanilamides as a congeneric chemical series . On the basis of the present results, the classical theory of antimetabolites would appear to take on a quantitative and sound rationale.

Oral Surg Oral Med Oral Pathol, 1987 Mar, 63(3), 366 - 70
Bacteriologic evaluation of ultrasonic root canal instrumentation; Sjogren U et al.; The antibacterial effect of ultrasonic instrumentation in the treatment of infected root canals was clinically evaluated . Sodium hypochlorite solution (0.5%) was used as an irrigant, but no antibacterial intracanal dressing was used between the appointments . The ultrasonic technique eliminated the bacteria from the canals more efficiently than hand instrumentation alone . Even though ultrasonication definitely improves the procedure of root canal disinfection, the use of an antibacterial dressing between appointments is necessary to achieve as complete a reduction in bacterial levels as possible.

Med Radiol (Mosk), 1987 Mar, 32(3), 27 - 30
{67Ga-citrate in the diagnosis of lung diseases}; Vikman IaE et al.; Altogether 214 patients with different pulmonary diseases were examined using 67Ga-citrate scintigraphy . A high sensitivity of the method (94%) in the diagnosis of primary lung cancer and its high specificity (81.8%) in differential diagnosis of lung cancer and chronic non-specific lung diseases were established . The use of "positive" lung scintigraphy with 67Ga-citrate for diagnosis of metastatic pulmonary lesions as a result of a low sensitivity of the method in this pathology was found inappropriate . Differential diagnosis of lung cancer and acute inflammatory process by two investigations with 67Ga-citrate before and after a course of antibacterial and antiinflammatory therapy turned out possible; the preservation of a focus of raised accumulation of tumoritropic RP was typical of lung cancer whereas the disappearance of a focus or a decrease in the level of RP accumulation was typical of an acute inflammatory process.

J Vet Pharmacol Ther, 1987 Mar, 10(1), 17 - 22
Pharmacokinetics of phenoxymethyl penicillin (penicillin V) in calves; Soback S et al.; Phenoxymethyl penicillin (penicillin V) was administered intravenously (i.v.) and orally to pre-ruminant calves and the distribution and elimination kinetics, as well as the oral bioavailability, were determined . After i.v . injection, the drug was distributed rapidly in the body, the elimination half-life (t1/2 beta) was 34 min and the apparent volume of distribution at steady-state (Vd ss) was 0.30 l/kg . Mean peak serum drug concentrations were directly related to the oral dose administered, i.e . 0.22 microgram/ml, 1.06 micrograms/ml and 2.14 micrograms/ml after dosing at 10, 20 and 40 mg/kg, respectively . The elimination t1/2 of the drug after oral dosing varied between 90 and 110 min, and the oral bioavailability was approximately 30% of the dose . The co-administration of phenoxymethyl penicillin and probenecid resulted in elevation and prolongation of serum drug concentration . The percentage of drug bound to serum proteins was 78.8% +/- 8.2% . Phenoxymethyl penicillin was probably inactivated and degraded in the gastrointestinal tract of 6-week-old calves fed exclusively hay, silage and concentrates as very low and erratic serum drug concentrations were measured after these calves were dosed orally with the drug at 40 mg/kg . In view of the narrow antibacterial spectrum of the drug and the relatively high dose required, it appears that phenoxymethyl penicillin can only be of limited practical value for the treatment of bacterial infections in preruminant calves.

Gan To Kagaku Ryoho, 1987 Mar, 14(3 Pt 2), 858 - 64
{Studies on the new antibiotic kazusamycin and related substances}; Umezawa I et al.; Kazusamycins A and B and leptomycin B have a structure characteristic of an unsaturated, branched-chain fatty acid with a terminal delta-lactone ring, and show antibacterial activity on some kinds of fungi . Kazusamycin A (KZM-A) showed cytotoxic activity on mammalian cells at very low concentrations (ng/ml) in vitro . The antibiotic inhibited not only the growth of transplantable murine tumors and their metastases to the lung but also human mammary tumors inoculated into nude mice . KZM-A became immediately distributed to the main organs of mice, and a certain quantity of the antibiotic was inactivated by binding to high-molecular-weight substances such as albumin . A large quantity of KZM-A was carried to the liver and excreted into the bile, but was then reabsorbed by the small intestine . The growth of tumor metastases (L5178Y cells) in the liver was suppressed by KZM-A . The antibiotic induced severe diarrhea by causing necrosis and/or lysis of the mucous membrane of the small intestine . In contrast to this, the degree of myelotoxicity was relatively slight . The active site of the fatty acid of KZM-A appeared to consist of conjugated double bonds, carboxylic acid and hydroxyl moieties.

J Biol Chem, 1987 Feb 5, 262(4), 1665 - 9
Interaction between liposomes and sarcotoxin IA, a potent antibacterial protein of Sarcophaga peregrina (flesh fly); Nakajima Y et al.; The direct interaction between phospholipids and sarcotoxin IA, a potent bactericidal protein of Sarcophaga peregrina, was studied using authentic sarcotoxin IA, its synthetic derivatives, and various liposomes . Results showed that sarcotoxin IA interacted with liposomes constituted from acidic phospholipids, resulting in the release of glucose trapped in these liposomes . The amidated carboxyl-terminal of this protein was found to be important for this interaction . Liposomes constituted from total phospholipids of Escherichia coli became less susceptible to sarcotoxin IA with an increase in their cholesterol content . Since bacterial membranes do not contain cholesterol, this finding may partly explain the selective toxicity of sarcotoxin I to bacteria.

Clin Pharmacokinet, 1987 Feb, 12(2), 136 - 44
Comparison of the pharmacokinetics of cephradine and cefazolin in pregnant and non-pregnant women; Philipson A et al.; The pharmacokinetics of cephradine, a cephalosporin with a low degree of protein binding, was studied in 12 women after oral and intravenous administration of the drug during and after pregnancy . Six of the 12 women also received a cephalosporin with a high degree of protein binding, cefazolin, intravenously during and after pregnancy . For both drugs most pharmacokinetic parameters were altered in pregnancy . The area under the plasma concentration-time curve (AUC) following intravenous administration was smaller for both drugs during as compared to after pregnancy (mean change 39% for cephradine and 31% for cefazolin) . Half-lives of both drugs were significantly shorter during compared with after pregnancy (mean change 26% for cephradine and 35% for cefazolin) . Consequently, total body clearance was increased during pregnancy . A significant negative correlation between length of gestation and total clearance per kg bodyweight was seen for cephradine . The bioavailability of oral cephradine did not differ significantly during compared with after pregnancy . It is concluded that the dosage of both cefazolin and cephradine should be increased when treating infections in pregnant women in order to obtain the same antibacterial effect as when treating non-pregnant women.

J Antibiot (Tokyo), 1987 Feb, 40(2), 135 - 8
PB-5266 A, B and C, new monobactams . I . Taxonomy, fermentation and isolation; Kato T et al.; New monobactams, PB-5266 A, B and C were isolated from the culture filtrate of Cytophaga johnsonae PB-5266 by various types of column chromatography and preparative reverse phase HPLC . PB-5266 A, B and C exhibited weak antibacterial activity against a sensitive mutant of Escherichia coli to beta-lactam antibiotics.

Antimicrob Agents Chemother, 1987 Feb, 31(2), 333 - 4
Comparative antibacterial activity of Vancocin and generic vancomycin; Conte JE Jr; The in vitro antibacterial activity of generic vancomycin was compared with that of Vancocin (vancomycin hydrochloride; Eli Lilly & Co.) using macrotube dilution testing and subculture . There were no significant differences in MICs or MBCs of the two drugs when tested against a variety of recently isolated hospital pathogens.

Arzneimittelforschung, 1987 Feb, 37(2), 218 - 20
{Treatment of impetiginized eczema with prednicarbate in combination with a quarternary ammonium salt}; Wolbling RH et al.; After a brief account of the therapeutic problems with microbially superinfected eczemas, the results of a double-blind study of hospitalized patients are reported . Two concentrations of the antibacterial agent Bardac-22 (didecyl-dimethyl-ammonium chloride . Hoe S 2922) in combination with the steroid prednicarbate (prednisolone 17-(ethylcarbonate)-21-propionate, Hoe 777) were used . The quantitative determination of cutaneous bacteria was performed by a modified method of Faergemann . The double blind study did not reveal any significant differences in effectiveness, although a trend in favour of the higher concentration was apparent.

Vet Microbiol, 1987 Feb, 13(2), 159 - 66
Bacteriostatic activity of bovine lactoferrin in mastitic milk; Rainard P; The antibacterial activity of milk against a virulent strain of Escherichia coli was investigated using milk fractions from normal or inflamed glands . Mastitic whey exhibited either bactericidal or bacteriostatic activities, depending on whether bacteria were enumerated by the pour plate technique or by surface plating onto sheep blood agar . The former activity was not due to lactoferrin (Lf), which never exerted bactericidal activity, even when assayed in distilled water . Milk whey ultrafiltrate (UF) (mol . wt . less than 5000 d) was used to assay the ability of normal and mastitic milk to support the antibacterial activities of Lf against a strain of E . coli . The addition of purified Lf to UF from mastitic whey resulted in bacteriostasis, whereas Lf was without effect in UF from normal whey . It was concluded that Lf can actually slow down the growth of Lf-sensitive bacteria during mastitis, provided that plasma exudation takes place.

J Dent Res, 1987 Feb, 66 Spec No, 623 - 7
The functions of saliva; Mandel ID; Nature's demands on salivary glands are extensive and diverse and range from the reptilian need for a venomous drop to incapacitate its prey to the 100 quarts that ruminants require to digest a day's grazing . Other species depend on saliva not for survival, but for improving the quality of life, using the fluid for functions varying from grooming and cleansing to nest-building . Humans can manage without saliva; its loss is not life-threatening in any immediate sense, but it results in a variety of difficulties and miseries . Oral digestion per se is only of marginal importance in humans, but saliva is important in preparing food for mastication, for swallowing, and for normal taste perception . Without saliva, mealtimes are difficult, uncomfortable, and embarrassing . The complex mix of salivary constituents provides an effective set of systems for lubricating and protecting the soft and hard tissues . Protection of soft tissues is afforded against desiccation, penetration, ulceration, and potential carcinogens by mucin and anti-proteases . Saliva can encourage soft tissue repair by reducing clotting time and accelerating wound contraction . A major protective function results from the salivary role in maintenance of the ecological balance in the oral cavity via: (1) debridement/lavage; (2) aggregation and reduced adherence by both immunological and non-immunological means; and (3) direct antibacterial activity . Saliva also possesses anti-fungal and anti-viral systems . Saliva is effective in maintaining pH in the oral cavity, contributes to the regulation of plaque pH, and helps neutralize reflux acids in the esophagus . Salivary maintenance of tooth integrity is dependent on: (1) mechanical cleansing and carbohydrate clearance; (2) post-eruptive maturation of enamel.(ABSTRACT TRUNCATED AT 250 WORDS)

Jpn J Antibiot, 1987 Feb, 40(2), 325 - 30
{In vitro antibacterial activity and pharmacokinetics of ofloxacin in chronic respiratory tract infections}; Sugimoto Y et al.; Serum and sputum levels of ofloxacin (OFLX) were measured in 5 patients with chronic respiratory tract infections and were compared with antibacterial activity in vitro . Sputum OFLX levels higher than the MIC's against H . influenzae and K . pneumoniae were maintained during the period when daily oral administrations were continued . The MIC70 of OFLX against S . aureus was under 0.78 microgram/ml and the MIC70 of OFLX against P . aeruginosa was 1.56 micrograms/ml . The maximum OFLX levels in sputum were higher than these MIC's during the period when 200-300 mg X 2 times/day oral administrations were maintained . From these results, OFLX was considered to be effective and useful for the treatment of patients with chronic respiratory tract infections.

Hinyokika Kiyo, 1987 Feb, 33(2), 305 - 9
{Clinical experience of enoxacin in the treatment of nongonococcal urethritis}; Nakano E et al.; Enoxacin (ENX) is a new derivative of pyridonecarboxylic acid and has a broad spectrum antibacterial activity . In this study, the effects of ENX on nongonococcal urethritis (NGU) were examined in 20 patients . ENX was administered orally 3 times a day at a daily dose of 600 mg for 2-23 days . Before treatment, Chlamydia trachomatis was isolated from urethral epithelium in 5 of the 20 patients . Of the 18 patients evaluated in this clinical trial, 15 (83%) responded well, and ENX was effective in 3 of the 5 Chlamydia positive cases and in 12 of the 13 Chlamydia-negative patients . As adverse reactions, headache was observed in one case and numbness of limbs in another case . No abnormality induced by ENX was recognized in laboratory findings . It is concluded that ENX is a useful drug in the treatment of patients with NGU, particularly in whom Chlamydia trachomatis is not isolated.

Am J Reprod Immunol Microbiol, 1987 Feb, 13(2), 33 - 5
Phosphate content of human amniotic fluid and its relationship to bacterial growth inhibition; Tomblin J et al.; A sensitive method for assay of phosphate has been adapted for use with human amniotic fluid . The presence of an antibacterial factor in amniotic fluid inactivated by phosphate suggested that measurement of free phosphate may predict antibacterial activity and hence susceptibility to intrapartum infection . The intrinsic antibacterial activity of amniotic fluid was altered by addition of large amounts of phosphate, but the intrinsic concentration of free phosphate correlated poorly with antibacterial activity and organically combined phosphates did not appear to be related to the antibacterial property.

Antibiot Med Biotekhnol, 1987 Feb, 32(2), 151 - 5
{Microbiological methods of pharmacokinetic research on chemotherapeutic (antibacterial and antitumor) preparations}; Smolianskaia AZ et al.; Microbiological methods are the most accessible in clinical assay of drug concentrations in biological fluids . When a sensitive test system is available and the requirements for collection and investigation of the materials are observed such methods are applicable in studies of pharmacokinetics of both antibacterial and antitumor drugs.

Surg Gynecol Obstet, 1987 Feb, 164(2), 143 - 7
A new method for the direct incorporation of antibiotic in prosthetic vascular grafts; Modak SM et al.; A procedure for the bonding of antibacterial agents directly to prosthetic vascular grafts has been developed . This method does not involve the use of carriers or surfactants which may cause local toxicity or thrombogenesis . Using this procedure, antibiotics can be bonded to the graft alone or in combination with a metal, such as silver . Incorporation of silver along with the antibiotic enhances the antibacterial activity and prolongs retention of the antibiotics in the prosthetic grafts . Silver mediated bonding appears to release the antibiotic biphasically . In the initial phase (40 to 50 per cent), the drug is rapidly released and, in the second phase, the rest is diffused gradually enabling the graft to retain antibacterial activity for a longer period of time.

Biochemistry, 1987 Jan 13, 26(1), 226 - 30
Purification of sarcotoxin II, antibacterial proteins of Sarcophaga peregrina (flesh fly) larvae; Ando K et al.; Three antibacterial proteins with almost identical primary structures termed sarcotoxin IIA, IIB, and IIC were purified to homogeneity from the hemolymph of third instar larvae of Sarcophaga peregrina . The molecular masses of these proteins were about 24,000 . These proteins were found to have common antigenicity, and antibody against sarcotoxin IIA cross-reacted with sarcotoxin IIB and IIC . Radioimmunoassay using this antibody showed that these proteins are induced in the hemolymph in response to injury of the larval body wall.

Arkh Patol, 1987, 49(1), 50 - 3
{Aspergillotic septic endocarditis of the mitral and trigeminal valves as a complication of silicotuberculosis}; Vasin VA et al.; Fungal endocarditis is caused by fungi Candida and Aspergillus . Continuous intravenous infusions, catheterization, open-heart surgery, tracheal injuries, artificial heart valves can serve as predisposing factors . Aspergillus endocarditis is more common in severe infectious diseases after a prolonged use of antibiotics, cytostatics, glucocorticoids . A case of aspergillus endocarditis of mitral and tricuspid valves is described in a 55-year old patient . The man had been long suffering from silicotuberculosis and had been on a prolonged antibacterial therapy . The aspergillus endocarditis must have developed in the patient due to marked dysbacteriosis.

J Anim Sci, 1987 Jan, 64(1), 261 - 70
Relative contributions of ruminal bacteria and protozoa to the degradation of protein in vitro; Hino T et al.; Mixed ruminal microorganisms from a cow fed timothy hay and concentrate supplement (50:50) were incubated with various protein sources for 15 h (no carbohydrates or growth), and deamination was studied under enzyme-limiting substrate-excess conditions (n = 3) . Addition of amphotericin (10 micrograms/ml) killed protozoa and decreased (P less than .05) ammonia production from killed bacteria but it had no effect (P greater than .05) on casein deamination . Monensin (5 micrograms/ml) also killed protozoa; however, it decreased (P less than .05) casein deamination to a much greater extent than amphotericin . Antibacterial antibiotics (penicillin G, polymixin B, cephalosporin C and streptomycin) greatly reduced (P less than .05) ammonia formation from casein . Isolated bacteria always produced more ammonia than isolated protozoa, but the difference was less with heat-treated, particulate proteins . Heated soybean protein was as soluble as heated casein but it was deaminated (P less than .05) at a faster rate by bacteria . Nonammonia-nonprotein N accumulation was greater (P less than .05) with the protozoa than bacteria . When incubations containing bacteria or protozoa were compared with combinations of protozoa and bacteria, the combinations always caused a synergistic increase in ammonia and decrease (P less than .05) in nonammonia-nonprotein N . These results suggest: soluble proteins were primarily degraded by bacteria; protozoa could contribute to the degradation of insoluble, particulate proteins; protozoa were limited in their ability to assimilate peptides (or amino acids); low molecular weight products could be fermented more readily by bacteria and monensin was toxic to protozoa, but decreases in ammonia were primarily due to action of monensin on bacteria.

J Med Chem, 1987 Jan, 30(1), 46 - 9
Cluster significance analysis contrasted with three other quantitative structure-activity relationship methods; McFarland JW et al.; Cluster significance analysis (CSA), a new statistical method to analyze structure-activity relationships in graphically displayed data, is contrasted with linear discriminant analysis, SIMCA, and the method of "relative odds" . The data sets evaluated are as follows: antibacterial lasalocid derivatives, antimalarial naphthoquinones, and carcinogenic polycyclic aromatic hydrocarbons . CSA gives results comparable to these other methods, involves fewer assumptions, can be more reliable, and in general is easier to understand.

J Med Chem, 1987 Jan, 30(1), 205 - 8
Substituted 2-(2-hydroxyphenyl)benzimidazoles as potential agents for the control of periodontal diseases; Coburn RA et al.; A series of 16 substituted 2-(2-hydroxphenyl)benzimidazoles was synthesized and evaluated in vitro for antibacterial activity against bacteria associated with periodontal diseases . Several compounds demonstrated a high level of activity, in tube dilution assay, against Actinomycetes viscosus and Bacteriodes gingivalis . These results indicate that several of these compounds may serve as topical antibacterial agents for the control of acute marginal inflammatory gingivitis and periodontitis.

Chemotherapy, 1987, 33(5), 355 - 60
Bactericidal and antineoplastic effect of combination of norfloxacin and adriamycin; Castelli M et al.; Norfloxacin and adriamycin were tested alone and in combination for bactericidal activity against different strains of gram-negative bacteria . The antitumoral effect of a combination of norfloxacin and adriamycin was determined in mice bearing Ehrlich ascites carcinoma and in mice bearing P 388 leukemia . No interference with the antibacterial activity of norfloxacin or with the antitumoral activity of adriamycin was observed.

Biomed Biochim Acta, 1987, 46(5), 307 - 15
Biological activity and mode of action of some dihydroorotic and dihydroazaorotic acid derivatives; Miersch J et al.; The conversion of six dihydroorotate analogues by the dihydroorotate dehydrogenase (DHO-DH) of plant and animal mitochondria was studied . In the case of plant DHO-DH the dehydrogenation of analogues was as follows: Dihydroorotic acid (DHO) (control, 100%), DHO-hydrazide (40%), azaDHO (13%), azaDHO-ethyl ester (23%), azaDHO-hydrazide (11%), dihydrouracil (0%), dihydrothymine (0%) . When animal DHO-DH was used the analogues were practically not dehydrogenated . These compounds were also tested as inhibitors of DHO-dehydrogenation . AzaDHO, azaDHO-hydrazide and azaDHO-ethylester inhibited this reaction by 75, 70% and 60%, respectively, for plant DHO-DH . AzaDHO and azaDHO-ethylester inhibited this reaction to 90% and 70%, respectively, for animal enzyme . The other analogues had no effect . The compounds showed a moderate antibacterial activity . AzaDHO was more active than azaDHO-ethyl ester and azaDHO-hydrazide . A considerable inhibitory effect of azaDHO and azaDHO-ethyl ester was observed on the growth of St . aureus mutant UV-2 and S . lutea . The analogues were little active against the experimental mouse tumors leukemia L 1210, Lewis lung carcinoma (LLC) and B-16 melanoma . AzaDHO-ethyl ester and azaDHO-hydrazide inhibited the growth of LLC by 59% and 56%, respectively . In addition, the effect of analogues on the growth of plant cells was studied . AzaDHO and azaDHO-ethyl ester inhibited the growth of tomato cells in suspension culture by 10% and 41%, respectively.

Drugs Exp Clin Res, 1987, 13(4), 205 - 7
Antibacterial activity of ciprofloxacin, in particular against polyresistant strains; Sziegoleit A; The in vitro activity of ciprofloxacin was assessed against a wide range of bacterial isolates from patients of the University Hospital of Giessen . None of the 410 cultures proved to be insensitive although 85 polyresistant strains were included in the study.

Med Microbiol Immunol (Berl), 1987, 176(3), 123 - 30
The effect of saturation with Zn2+ and other metal ions on the antibacterial activity of ovotransferrin; Valenti P et al.; The antibacterial activity of metal complexes of ovotransferrin was tested "in vitro" against different bacterial species and the Zn2+ saturated ovotransferrin appeared to be the most active by comparison with the apo-protein and other metal complexes . Appropriate controls showed that such an effect was neither due to Zn2+ ions, nor to iron deprivation, but to a specific activity of the Zn-ovotransferrin complex . This antibacterial activity required a direct contact of Zn-ovotransferrin with the bacterial surface . In vivo experiments confirmed the higher antibacterial activity of Zn-ovotransferrin as compared with the apo-form.

Skeletal Radiol, 1987, 16(3), 183 - 9
Phosphorus-31 magnetic resonance spectroscopy of experimentally induced arthritis in rats; Blatter DD; Phosphorus-31 magnetic resonance spectroscopy (MRS) of the hind paws of rats was performed at 1.5 Tesla before and during the course of an experimentally-induced inflammatory arthritis . Arthritis was induced by daily subcutaneous administration of 6-sulfanilamidoindazole, an antibacterial sulfa known to produce an acute, self-limited arthritis and periarthritis in the hind paws of rats . Phosphorus-31 spectra obtained after the development of clinical arthritis showed a significant (p less than 0.01) increase in the intensity of a group of resonances occurring downfield from phosphocreatine as compared to spectra obtained before treatment . In all rats, this increase correlated well with histological evidence of inflammation as well as with the degree of inflammation judged clinically (r = 0.89, p less than 0.001), and was present before roentgenographic evidence of bony involvement . The use of 31P MRS may permit evaluation of the severity of an inflammatory arthritis with greater accuracy than the bony changes definable by plain roentgenograms.

Zh Nevropatol Psikhiatr Im S S Korsakova, 1987, 87(2), 188 - 90
{Early diagnosis and complex treatment of brain abscesses of paranasal sinus origin}; Mukhamedzhanov NZ; The article presents data on 22 inpatients with brain abscesses of rhinosinusogenic etiology who were treated at the Burdenko Institute of Neurosurgery . It was found important that X-ray examination of the paranasal sinuses be carried out in all patients of this group even if they present with no rhioscopic changes, which is explained by an elevated number of torpid and latent sinusites . To detect rhinosinusogenic brain abscesses at an early stage, examination including a series of such objective methods as EEG, Echo-EG, cerebral angiography, gamma-topography of the brain and computer-aided tomography was carried out . A multiple-modality treatment of brain abscesses of rhinosinusogenic etiology was employed: along with complete sanitization of the paranasal sinuses the patients received conservative therapy (antibacterial, antiinflammatory, dehydrational, detoxicational, roborant) combined with various neurosurgical interventions . Radical excision of the abscess together with the capsule was performed in 20 patients, and a puncture method was used in one case . As a result of this combined treatment 19 of the 22 patients in this series were cured and only 3 died.

J Toxicol Environ Health, 1987, 21(1-2), 99 - 112
Evaluating the toxicity of urban patterns of oxidant gases . II . Effects in mice from chronic exposure to nitrogen dioxide; Miller FJ et al.; The study reported herein evaluates the influence of a chronic exposure to an urban pattern of NO2 (continuous baseline exposure of 0.2 ppm, on which were superimposed two 1-h spikes of 0.8 ppm NO2, 5 d/wk) as compared to the baseline exposure to determine the contribution of the spikes to toxicity . Mice were exposed for up to 52 wk with interim examinations . Multivariate analysis of variance revealed a statistically significant treatment effect on infectivity (p = 0.05) and pulmonary function (p = 0.03) parameters . Infectivity mortality of mice in the spiked exposure regimen was significantly greater than that in either the NO2-background-exposed mice or in control mice . Four of the pulmonary function variables exhibited the greatest differences among the treatment groups: end expiratory volume, vital capacity, respiratory-system compliance, and multiple-breath nitrogen washout . Results from the pulmonary-function analyses indicate that the spiked exposures to 0.8 ppm NO2 may have induced a subtle lesion . The chronic study results indicate that the presence of spikes of NO2 is contributing significantly to effects on antibacterial lung defenses and pulmonary function of mice.

J Antibiot (Tokyo), 1987 Jan, 40(1), 29 - 42
Cefodizime, an aminothiazolylcephalosporin . V . Synthesis and structure-activity relationships in the cefodizime series; Blumbach J et al.; The synthesis as well as in vitro antibacterial activity and pharmacokinetic behavior of cefodizime (HR 221, 1a), its analogs and derivatives is described . In this comparison, cefodizime stands out for its balance between its high antibacterial activity, prolonged elimination half-life and high AUC in mice and dogs.

Cancer Metastasis Rev, 1987, 5(3), 271 - 93
Antibacterial therapy in patients with malignancies; Mayer KH et al.; Patients with malignant disease may be predisposed to bacterial infections because of neoplastic disruption of normal tissue barriers, exogenous immunosuppressive therapy (drugs with or without radiation), and intrinsic host immune deficits secondary to these diseases . Diminished polymorphonuclear leukocyte numbers or function and impaired humoral immunity are highly correlated with the development of serious bacterial infections . The usual signs and symptoms of infection may be absent or altered in a compromised host . Therapy must be instituted promptly upon clinical suspicion of bacterial infection, and empirical choices should usually include combinations that are synergistic for likely pathogens based on knowledge of the local predominant flora and susceptibility data . Synergism has most often been demonstrated in combinations that utilize a beta-lactam (semisynthetic penicillin or cephalosporin) and an aminoglycoside . Triple drug therapy has not been shown to be advantageous . Monotherapy with third generation cephalosporins, carbapenems, monobactams, or ureidopenicillins has not been proven to offer advantages over 2-drug regimens for these patients . Patients with blood deficient in granulocytes (granulocytopenic) who respond to 2-drug therapy but remain deficient in neutrophils (neutropenic) may need continued treatment until the neutropenia subsides . Those who do not respond and remain febrile with an unclear focus of infection may need to be started on antifungal therapy in addition to the antibacterial agent . The use of oral agents for the prophylaxis of neutropenic patients against bacteremia remains controversial . If drugs are used, co-trimoxazole and nystatin suspension may be preferable.

Vet Immunol Immunopathol, 1987 Jan, 14(1), 23 - 44
Neutrophil mediated and IgA dependent antibacterial immunity against enteropathogenic Escherichia coli in the porcine intestinal mucosa; Bhogal BS et al.; The role of polymorphonuclear neutrophils (PMN) in the antibacterial immunity against enteropathogenic Escherichia coli (EEC) 0:149 in the porcine intestine was studied using intestinal Thiry-Vella loop (T-V loop) as a model . Intraluminal immunizations of T-V loops resulted in elevated levels of immunoglobulin A (IgA) anti-EEC 0:149 antibody in the loop secretions, an infiltration of PMN in the lumen of the loops and an increase in the concentrations of lactoferrin (LF), lysozyme (LY), cationic proteins (CP), and a specific bactericidal response in the immunized loops . PMN were observed by electron microscopy (EM) to be actively phagocytic in the lumen of the immune loops . EM observations of loop fluids as well as the abrogating effect of iron on the in vivo bactericidal response strongly suggest that the pMN played an important role in the bactericidal response in the loops against EEC . In addition to phagocytosis by PMN and subsequent intracellular killing, disintegration of PMN in the lumen of the loops and extracellular killing of EEC by the antibacterial products of PMN such as LF, LY and CP, with and/or without synergistic effect of IgA antibodies, also contribute to the bactericidal response of the immunized loops.

Vet Res Commun, 1987, 11(5), 397 - 405
Animal consumption of antibiotics and chemotherapeutic drugs in Sweden during 1980, 1982 and 1984; Wierup M et al.; The total animal consumption of antibiotic and chemotherapeutic drugs in Sweden during 1980, 1982 and 1984 has been studied . The study also included coccidiostatic, antiparasitic and antimycotic drugs . The total animal consumption during the years mentioned was 66.1, 68.8 and 72.6 tons of active substance, respectively, and the amount of antibacterial drugs for therapy was 28.7 (43.4%), 29.1 (42.5%) and 34.1 (47.0%) tons, respectively . Tetracycline, penicillin, sulphonamide and aminoglycoside were the four major groups of antibiotics used for therapy of bacterial infections in animals . The consumption was related to the metabolic bodyweights of animals which were the potential consumers . A comparison was also made with the corresponding human consumption during 1980 . The data on antibiotic consumption can be divided by county and compared to the animal population and disease situation in each county . This study thus offers a good base for further investigations on different aspects of the use of antibiotics.

Eur J Clin Pharmacol, 1987, 33(5), 463 - 7
Steady-state levels of pefloxacin and its metabolites in patients with severe renal impairment; Jungers P et al.; Twenty patients (aged 26-70 years) with severely impaired renal function received pefloxacin twice daily for 5 days as 12 mg.kg-1 administered as a 1 h i.v . infusion, or 800 mg administered as tablets . On Day 5 the minimal and maximal plasma concentrations were 5.9 and 11.5 mg.l-1 respectively, after oral administration . The steady-state level of the N-desmethyl metabolite ranged from 0.9 (infusion) to 1.2 mg.l-1 (oral route), and that of the N-oxide metabolite ranged from 6.2 (infusion) to 9.0 mg.l-1 (oral route) . The minimal concentration of unchanged drug was related to the age of the patients (infusion), but the N-oxide concentration was influenced by the degree of renal impairment (both routes) . The pefloxacin levels were similar to those achieved in healthy subjects, but reduced renal function leads accumulation of its biotransformation products, especially of the N-oxide metabolite which lacks antibacterial activity.

Chemotherapy, 1987, 33(6), 402 - 11
Lack of effect of ofloxacin on theophylline pharmacokinetics in rats; Okazaki O et al.; Effect of ofloxacin, a new quinolone antibacterial agent, on the pharmacokinetics of theophylline was studied in rats in comparison with that of enoxacin and cimetidine . Ofloxacin by pretreatment with five oral doses of 50 mg/kg did not increase serum concentrations of theophylline (5 mg/kg, i.v . single) and showed no significant effect on total body clearance, serum half-life (T1/2) and AUC of theophylline, while enoxacin by the same pretreatment increased significantly serum theophylline concentrations and resulted in significant effect on all the pharmacokinetic parameters . Coadministration of ofloxacin (80 mg/kg, p.o . twice) did not induce a significant effect on the pharmacokinetic parameters of theophylline at repeated doses (50 mg/kg, i.v., twice daily for 3 days) . On the contrary, coadministration of enoxacin and cimetidine at the same dose as ofloxacin remarkably increased serum concentrations of theophylline at the same repeated doses, and caused a significant decrease in clearance and an increase in T1/2 and AUC . The three drugs had no influence on rat serum protein binding of theophylline . Ofloxacin exhibited a weak inhibitory effect on rat hepatic microsomal cytochrome P-450-dependent monooxygenases, whereas enoxacin and cimetidine induced a significant inhibition of the enzymes . Thus, it is concluded that ofloxacin has no significant effect on the pharmacokinetics of theophylline in rats, and that enoxacin raises serum theophylline concentrations and results in a significant effect on the theophylline pharmacokinetics by inhibition of the hepatic microsomal monooxygenases in rats.

Boll Ist Sieroter Milan, 1987, 66(2), 110 - 5
In vitro antibacterial activity of enoxacin, a new pyridonecarboxylic acid; Fabio U et al.; The antibacterial activity of enoxacin was determined against 1015 strains of Gram-positive and Gram-negative bacteria, mainly freshly isolated from clinical specimens . The minimum inhibitory concentrations (MIC 50-75-90) were determined in comparison to three commonly used antibiotics: ampicillin, cefotaxime and gentamicin . Enoxacin has shown a broad spectrum of action and antibacterial activity in general higher that than of three currently available antibiotics . The antibacterial activity seems similar to that of other quinolones of second generation.

J Dent Res, 1987 Jan, 66(1), 62 - 4
Proteolytic activity of bacteria isolated from the oral cavities of BALB/c mice toward salivary proteins; Dumas C et al.; The proteolytic activities of 350 bacterial isolates from different sites (saliva, tongue, teeth, and mucosa) of the oral cavities of BALB/c mice were tested against different proteins found in saliva (immunoglobulins A, M, G, albumin, lysozyme, mucin, lactoferrin, and lactoperoxidase), some of which are considered to possess antibacterial activity . The results indicate that: (1) lysozyme, lactoferrin, and lactoperoxidase are hydrolyzed by from 46 to 70% of the indigenous flora of the oral cavities of BALB/c mice; (2) IgA and IgM appeared less sensitive to the proteolytic activities of these strains than did the other proteins tested; (3) the colonization of the oral cavity does not seem to be correlated with the proteolytic activity; and (4) the presence of specific Ig proteases is relatively scarce within this population.

Vet Med Nauki, 1987, 24(10), 67 - 70
{Relation between molecular structure and the antibacterial activity of N4-substituted sulfanilamides}; Vurbanova S et al.; With the aim of establishing a correlation between chemical structure and biologic activity of series N, N'-replaced carbamide and thiocarbamide derivatives, containing sulfanilamide group their antibacterial activity has been studied . The microbiologic screening towards eight kinds of gram-positive and gram-negative microorganisms showed that the substitutes in N and N' in the carbamide or thiocarbamide structure influence the force of the effect as well as the kind of microorganisms in which that effect is exhibited . Ascertained was that together with the increase of the number of carbon atoms is strengthen the antibacterial activity (highest in C4) as the derivatives containing aryl radical show higher activity than those containing alkyl radical . The bringing of halogenic atoms in the molecule of the synthesized derivatives increases considerably the antibacterial activity which is expressed mainly in the combinations containing Cl-atom in m-position of the benzene nucleus.

Mikrobiyol Bul, 1987 Jan, 21(1), 16 - 9
{Comparison of the in vitro effectiveness of sulbactam/ampicillin and ampicillin}; Baykal M et al.; In this study, we compared the effectiveness of Sulbactam + Ampicillin compound and Ampicillin against to 1168 clinical isolates by means of disk diffusion technic . We observed that Sulbactam + Ampicillin compound is enhanced and regained the antibacterial activity of Ampicillin against some bacteria such as S . aureus, S . epidermidis and some gram negative microorganisms.

Ann Biol Clin (Paris), 1987, 45(5), 582 - 7
{Deep candidiasis in agranulocytic patients: mycological and serological surveillance in 91 febrile episodes and management of an antifungal and antibacterial protocol}; Lebeau B et al.; This study took place between February 1984 and February 1985 in 76 febrile neutropenic patients . We evaluated the whole mycological and serological results, in 91 febrile episodes . We separated two groups: group I (acute leukemia, chronic myeloid leukemia, medullar aplasia, lymphomas) and group II (chronic lymphoid leukemia, Hodgkin disease, myelomas, solid tumors) . Patients were included in this study if they developed a temperature of 38.5 degrees C or greater and if they had less than five hundred neutrophils per mm3 . They were treated with mono or bi-antibiotherapy . If the patient remained febrile more than 72 hours, an antifungal therapy was added (Amphotericin B IV) . Through these weekly results, we conclude: the high frequency of digestive tract candidiasis in such patients; disseminated candidiasis occurs only in the first group patients with fungal digestive colonization; the overall response rate in this study was 77 per cent . This underlines the interest of empiric treatment with amphotericin B IV.

J Perinatol, 1987 Winter, 7(1), 58 - 61
Intravenous immunoglobulin for prophylaxis or treatment of bacterial infection in neonates; Christensen RD; The high rate of bacterial infection in premature neonates has been correlated with low levels of opsonic antibody . Infants born at term who develop a bacterial infection generally have very low levels of antibody toward the organisms with which they are infected . In order to provide adequate levels of antibacterial antibody to neonates, several strategies have been devised and tested . In this report, studies on animal investigations and clinical trials are reviewed.

Arch Oral Biol, 1987, 32(11), 811 - 5
Hyaluronic acid and hyaluronidase activity in gingival exudate from sites of acute ulcerative gingivitis in man; Last KS et al.; Gingival exudates from sites of acute ulcerative gingivitis (AUG) and chronic gingivitis (CG) in adults were investigated by cellulose-acetate electrophoresis for the hyaluronic acid (HA) content and assayed for the levels of HA-degrading enzymes . HA was the only glycosaminoglycan (GAG) in gingival exudate from CG sites . HA was not detected at untreated AUG sites but was evident, at increasing levels, after two and seven days of effective antibacterial treatment . In AUG exudates, the total HA-degrading enzyme activity, of bacterial origin, decreased to approx . 30 and 10 per cent of the high initial levels after two and seven days of treatment respectively, to that level found at sites of CG . The specific activity of HA-degrading enzyme of lysosomal origin was low initially and increased with treatment to a level comparable to CG . The notable absence of HA from gingival exudate from sites of untreated AUG thus appears to result from the increased levels of bacterial hyaluronidase . Electrophoresis of gingival exudate may be an indirect method of monitoring the rate of response of AUG to different antibacterial treatments.

Drugs, 1987, 34 Suppl 1, 1 - 8
Development of resistance to ofloxacin; Crumplin GC et al.; As a member of the 4-quinolone group of antibacterial agents, ofloxacin shares the almost unique feature of being exempt from plasmid-borne resistance in either Gram-negative or Gram-positive bacteria . In the light of this feature, the development of resistance mediated through chromosomal mutation has been carefully studied, particularly the processes of mutation which confer resistance to levels of ofloxacin approaching those obtained at the site of infection after oral administration . With Escherichia coli strain KL16 being used as a model system, the genetics of the development of resistance to ofloxacin at least 2 mg/L have been studied . In common with many in vitro studies of the development of resistance to the newer 4-quinolones, it has been observed that the mutation frequency was extremely low (in the range 1 X 10(-10) to 1 X 10(-12) with bacteria grown under routine laboratory conditions . The resultant organisms were very slow growing, temperature sensitive and apparently auxotrophic . The mutation(s) were, however, very unstable and the mutants readily reverted to ofloxacin sensitivity in the absence of selection with ofloxacin . Subsequent studies of spontaneous mutation under growth conditions more closely related to the in vivo situation in the lumen of the gut, with limitation of oxygen supply, showed that mutation frequencies were in the order of 1 X 10(-8) . Mutants obtained under these conditions displayed the same phenotype as found previously and were equally unstable . Examination of the physiology of the ofloxacin-resistant mutants has shown that they display significant metabolic defects with regard to being able to cope with environmental fluctuations.(ABSTRACT TRUNCATED AT 250 WORDS)

Drugs Exp Clin Res, 1987, 13(10), 635 - 9
Mode of action of nitro-heterocyclic compounds on Escherichia coli; Hof H et al.; The inhibitory and bactericidal activities of several different nitro-heterocyclic compounds, such as nitrofuran, nitronaphthofuran, nitrobenzofuran, nitroimidazole and nitrothiazole, were assessed in vitro . All these substances except nitroimidazole were active against Escherichia coli, though to different degrees . Under anaerobic test conditions the antibacterial activity increased slightly . Nitroreductase-deficient mutants, however, were highly resistant to all nitro-compounds, indicating that only when the nitro-group is reduced to these agents get into an active antibacterial form . SOS repair-deficient strains were much more susceptible to the nitro-containing substances than repair-proficient counterparts, indicating that damage to bacterial DNA is the essential mechanism of antibacterial activity of all nitro-heterocyclic compounds.

Infection, 1987, 15(5), 385 - 96
High dose treatment with antibiotics in cystic fibrosis--a reappraisal with special reference to the pharmacokinetics of beta-lactams and new fluoroquinolones in adult CF-patients; Sorgel F et al.; In this review we analyzed the pharmacokinetic basis for high dose treatment with antibiotics of patients with cystic fibrosis . Both our results and those from other well designed pharmacokinetic studies do not support the view that low blood levels of antibacterials are a common feature of CF . We were unable to detect a decrease in absorption, nor could we find evidence for enhanced elimination of antibacterials in CF . Both these factors have been considered responsible for reducing the plasma (and tissue) levels of antibiotics . Most recent studies on kidney function are in agreement with these findings, since neither inulin nor creatinine clearance differ between CF-patients and healthy volunteers . In contrast to previous discussion, the volume of distribution (Vdss) was not elevated for any compound . The rational of weight correction of volume terms like Vdss or total clearance has never been clearly demonstrated and should therefore not be used without prior proof of relevance . Since the variability of pharmacokinetic parameters of antibiotics in CF-patients may be considerable, we suggest that a dose increase of 20-30% may be justified, but cannot agree with two to fourfold increases in dosage as previously proposed and applied in many CF-centers . Until more findings become available for non-adult CF-patients, these conclusions are only valid for adult CF-patients.

Drugs, 1987, 34 Suppl 2, 44 - 63
In vitro antibacterial effects of cephalosporins; Williams JD et al.; Data from many studies on the antibacterial effects of cephalosporins are reviewed . Variations in reports from different workers occur because of the composition of the strains used to carry out determination of minimum inhibitory concentrations (MICs) . For this reason, standard MIC50/MIC90 data are used sparingly . Where data are available, the activity has been expressed as the mode activity against fully sensitive strains of a species; and the activity against resistant strains is specified, as far as the data allow, for the mechanisms of resistance exhibited.

Ann Chir Gynaecol Suppl, 1987, 202, 14 - 6
Antibacterial capacity in amniotic fluid in normal and complicated pregnancies; Honkonen E et al.; The antibacterial activity against Escherichia coli K 12 in 153 samples of amniotic fluid (AF) in 15 to 40 weeks of pregnancy were investigated by a new micromethod . Fifty-six mothers had an uncomplicated pregnancy while various complications (maternal diabetes, cholestasis of pregnancy, pregnancy induced hypertension, blood group isoimmunization and fetal growth retardation) were present in 97 cases . A significant (p less than 0.001) improvement of antibacterial activity was observed with advancing pregnancy . The highest antibacterial activity in AF was observed in cases with intrauterine growth retardation . In other respects the effect of various diseases was negligible.

Zentralbl Gynakol, 1987, 109(6), 329 - 40
{Recommendations for the diagnosis and therapy of bacterial infections in premature and newborn infants}; Handrick W et al.; In a survey the authors present the most important facts of diagnostic and therapy of bacterial infections in term and preterm neonates . It is a synthesis of an extensive study of the literature and of own experiences . Besides microbiological diagnostic and antibacterial chemotherapy one can find also suggestions concerning hematological and chemical diagnostic methods as well as of parenteral and oral nutrition and immunotherapy.

Farmaco {Sci}, 1987 Jan, 42(1), 3 - 16
{Research on antibacterial and antifungal agents . VII . Synthesis of (1-pyrryl)methylquinolines acids}; Stefancich G et al.; Some (1-pyrryl)methyl derivatives of 1-ethyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acid were synthetized by the standard procedure involving Gould-Jacobs and Lappin reactions . The above derivatives were tested microbiologically as nalidixic acid analogs and compared with some clinically useful 4-oxopyridine-3-carboxylic acids (nalidixic acid, pipemidic acid, norfloxacin, enoxacin and ciprofloxacin) . Their antibacterial activities were very weak.

Ter Arkh, 1987, 59(7), 77 - 80
{Importance of microbiological research in correcting the antibacterial therapy of tuberculosis}; Dolzhanskii VM et al.; Long-term observations showed the importance of the phenomenon of the drug resistance of Mycobacterium tuberculosis in phthisiological clinical practice and its tendency in recent years . Methods for individual selection of an optimum drug combination were developed and tested, its efficacy was shown.

J Nat Prod, 1987 Jan-Feb, 50(1), 19 - 22
A direct bioautographic tlc assay for compounds possessing antibacterial activity; Hamburger MO et al.; A simple bioassay for the direct detection of antibacterial compounds on tlc plates has been developed . A series of natural products and different stationary phases were tested in order to establish the utility of the assay for the isolation of antibacterial compounds from higher plants.

Antibiot Med Biotekhnol, 1987 Jan, 32(1), 32 - 5
{Comparative evaluation of the antibacterial activity of aminoglycosides by means of microcalorimetry}; Chernykh VM et al.; 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.

Antibiot Med Biotekhnol, 1987 Jan, 32(1), 20 - 4
{Structural-functional research on polymyxins . 1H-NMR spectra of polymyxin B and its shortened analog}; Okhanov VV et al.; Polymyxin B and its shortened analog were studied comparatively by 1H-NMR spectroscopy . Analysis of the signal chemical shifts, constants of spin-spin interaction of 3J HN-C alpha H and temperature coefficients of the NH signal chemical shifts revealed absolute structural identity of both molecules cyclic parts . This proved that there was no conformative interaction between the cyclic and linear parts of the polymyxin B molecule . Comparison of the results with the data on the biological activity showed that the hydrophobic N-end moiety of the polymyxin B molecule played a specific role in its antibacterial effect and toxicity.

J Antibiot (Tokyo), 1987 Jan, 40(1), 49 - 59
Teicoplanin, antibiotics from Actinoplanes teichomyceticus nov . sp . VIII . Opening of the polypeptide chain of teicoplanin aglycone under hydrolytic conditions; Cavalleri B et al.; Hydrolysis of teicoplanin (a complex of five closely related factors plus one, more polar component) under selected conditions (acids in a biphasic hydroalcoholic medium) gives the single aglycone with good yields . When the reaction is carried out in homogeneous hydroalcoholic phase the removal of the sugars yields two new compounds . On the basis of fast atom bombardment mass spectra (FAB-MS), acid-base titration, IR, UV and 1H NMR analyses it has been demonstrated that these compounds are two diastereoisomers; they differ from the teicoplanin aglycone in having additional carboxyl and amino groups derived from the hydrolysis of an amide bond . Although the molecular shape of the new aglycones is greatly modified, they still maintain some antibacterial activity which might be correlated with residual binding ability towards the terminal D-alanyl-D-alanine residue of the cell-wall mucopeptides.

Ter Arkh, 1987, 59(3), 123 - 6
{Various problems in the diagnosis and treatment of the broncho-obstructive syndrome}; Boksha VG et al.; Clinico-x-ray-laboratory investigation, bronchoscopy were performed, respiratory function and ECG were studied in 212 patients with different forms of chronic bronchitis . Six groups of patients were defined with relation to the presence or absence of obstruction, its nature (permanent, transient), prevalence (small, medium and large bronchi), genesis of disease (inflammatory, allergic) . The characteristics of the groups and their clinico-x-ray, functional and immunological features were presented . Treatment including methods of climatotherapy, exercise therapy, pharmacological agents (antibacterial, broncholithic and antihistaminic), physiotherapy and administered with relation to the defined groups, proved to be effective . The improvement of bronchial permeability was noted in 49.5% (ranging from 40.0 to 68.7% in different groups).

J Hosp Infect, 1987 Jan, 9(1), 30 - 3
The effect of handcream on the antibacterial activity of chlorhexidine gluconate; Walsh B et al.; A series of handwashing experiments compared the residual effect on Escherichia coli of non-medicated soap, chlorhexidine detergent followed by an anionic handcream, chlorhexidine detergent followed by a non-ionic handcream and chlorhexidine detergent alone . Handcreams containing an anionic emulsifying agent reduced the antibacterial effect of chlorhexidine.

Folia Microbiol (Praha), 1987, 32(5), 438 - 47
The decreased antibacterial activity of oral polymorphonuclear leukocytes coincides with the occurrence of virus-carrying oral lymphocytes and epithelial cells; Ongradi J et al.; Patients suffering from periodontitis or periodontosis were selected for the study . Further subdivision of these groups was based on the presence or absence of herpes and/or adenoviruses in their oral lymphocytes and epithelial cells . The phagocytic and bactericidal activities of oral leukocytes isolated from the same individuals were compared with virus carriage . In the periodontitis group, 60.5%, and in the periodontosis group 61.5% of patients carried viruses, while this was established only in 21.1% of control cases . On the other hand, emigration and sulcular gathering of the less viable polymorphonuclear leukocytes was elevated but their phagocytotic activity was decreased among periodontitis patients . Bactericidal capacity was significantly lowered among those subjects who carried viruses in their cells, as compared with virus-free persons, especially in the periodontitis group . The functions of the polymorphonuclear leukocytes accumulated in the sulcus gingivalis may be modified by mediators released from the virus-carrying cells . These mediators could achieve a greater concentration locally, and the damaged leukocytes would not be able to eliminate the microbes continuously so that the accumulation of bacterial products, among them endotoxins, could lead to periodontal inflammation.

Acta Microbiol Pol, 1987, 36(3), 221 - 7
The influence of nalidixic acid on Escherichia coli growth in milk; Tyczynska B et al.; The high antibacterial activity of nalidixic acid against Escherichia coli, cultivated in raw and pasteurized milk has been shown . The low oxygen reduction potential had no influence on the antibacterial activity of this drug . The natural antibacterial agents in active milk from an inflamed udder have reduced the efficacy of nalidixic acid inhibition of the growth of E . coli.

Folia Haematol Int Mag Klin Morphol Blutforsch, 1987, 114(3), 338 - 47
Serum lysozyme activity in patients with Hodgkin's disease undergoing chemotherapy; Prokopowicz J et al.; Lysozyme activity was determined in undiluted and diluted sera of 41 patients suffered from Hodgkin's disease and of 40 healthy individuals . Blood was collected before chemotherapy, midway of its course, just after completion of chemotherapy and three weeks and three months later . Lysozyme activity was evidently increased as well in undiluted as in diluted sera in all our tested patients . These findings may be interpreted by the presence of immune complexes in sera which may stimulate the release of lysozyme from viable neutrophils . High activity in diluted sera probably is related to the increased concentration of lysozyme inhibitors . The applied chemotherapy did not significantly change the activity of the lysozyme during its course of even after its completion as found by three-month observation . The enhanced lysozyme activity in sera of patients may be at least in part to compensate decreased antibacterial and anticancer mechanisms.

Presse Med, 1986 Dec 20, 15(46), 2362 - 7
{Can piperacillin modify the experimental nephrotoxicity of gentamicin?}; Thomas N et al.; A synergistic effect of antibacterial activity has been demonstrated with piperacillin combined with an aminoglycoside . Four groups of 30 female Wistar rats were injected daily for 14 days with either gentamicin 50 mg/kg, or piperacillin 1,000 mg/kg, or both drugs combined; the control group received sodium chloride in solution . In all groups, creatinine clearance, lysosomal structural latency and renal cortex enzyme activities (alanine-aminopeptidase, N-acetyl beta D-glucosaminidase, sphingomyelinase, cathepsin B) were measured on days 2, 4, 7, 10 and 14 of treatment . Renal cortex concentrations of gentamicin were measured in the group that received gentamicin alone and in the group treated with both piperacillin and gentamicin . The renal functional changes usually induced by aminoglycosides were observed . Piperacillin administered alone reduced creatinine clearance and alanine-aminopeptidase activity . The piperacillin-gentamicin combination proved unable to prevent the fall in creatinine clearance; it also reduced the alanine-aminopeptidase, sphingomyelinase and cathepsin B activities, but the reduction was less pronounced than that induced by gentamicin alone.

Presse Med, 1986 Dec 20, 15(46), 2342 - 4
{Effectiveness of piperacillin in the antibacterial treatment of intra-abdominal infections in children}; Vergnaud M et al.; The effectiveness of piperacillin was investigated in 30 children operated upon for peritonitis: 13 had acute appendicitis with puriform peritoneal reaction, or a recently perforated appendix; 5 had generalized peritonitis of appendicular origin, and 13 had intraperitoneal abscess . In the 12 children who underwent right iliac appendicectomy (with post-operative drainage in 3), piperacillin was administered alone during 5 days; clinical and bacteriological cure was obtained in all cases; the mean duration of stay in hospital was 7 days . The 5 cases of generalized peritonitis required drainage; piperacillin was given alone in 4 of them and combined with an aminoglycoside and metronidazole in one who was in poor general condition . Bacteriology showed a predominance of Escherichia coli alone or associated with other organisms . Clinical and bacteriological cure was obtained in 3 patients; the mean duration of stay in hospital was 12 days . Seven of the 13 cases of intraperitoneal abscess needed drainage . Piperacillin was administered alone for 7 days on average in 10 cases and combined with an aminoglycoside and metronidazole in 2 cases . Eight patients had a favourable course, 5 developed complications . In all 3 groups piperacillin was tell tolerated . A patch of urticaria was noted in 2 cases and a transient skin rash in 2 other cases . No neutropenia was observed in these children whose treatment never exceeded 10 days.

Presse Med, 1986 Dec 20, 15(46), 2317 - 20
{Piperacillin in in vitro-in vivo combination}; Ferre B et al.; Launched two years ago, piperacillin is administered either alone or combined with other antibiotics . Broadening the antibacterial spectrum, looking for synergism and preventing the emergence of resistant mutants constitute a major preoccupation, especially in immunodepressed patients, and an indication for combined antibiotic therapy . The most effective combination, justified by in vitro tests, consists of a beta-lactam antibiotic and an aminoglycoside . In vitro studies have demonstrated an antagonistic effect between two beta-lactam antibiotics, and mutants have been isolated in vivo . The results obtained with the piperacillin-vancomycin combination are not as good as those obtained with previous combinations . The advent of new compounds, such as aztreonam, fluorinated quinolones and beta-lactamase inhibitors offers hopes of excellent results.

Presse Med, 1986 Dec 20, 15(46), 2290 - 6
{Mechanism of enzymatic resistance to beta-lactam antibiotics}; Philippon A et al.; The resistance of bacteria, particularly Gram-negative bacteria, to beta-lactam antibiotics is principally caused by enzymes . Beta-lactamases inactivate these antibiotics by opening, more or less rapidly, the beta-lactam ring . The chronology of therapeutic discoveries is governed by natural and acquired resistance . The first step was to establish the characteristics of beta-lactamases (location, biogenesis, enzymatic profile, affinity constant, inhibition profile, isoelectric point, molecular weight, genetic determination, etc.) . Advances in the selection of natural or semi-synthetic compound are centred on the following points: increased stability to beta-lactamases, inhibitory effect, reduced inducibility, low affinity for the enzyme, greater speed of penetration through the bacterial wall, increased tropism for targets . Notable among the new beta-lactam antibiotics are acylureidopenicillins, beta-lactamase inhibitors and carbapenems . The antibacterial activity of third generation cephalosporins is 10 to 1000 times higher than that of previous cephalosporins; the result is a wider spectrum including, in particular, cephalosporinase-producing organisms . Concerning acquired resistance, the behaviour of new antibiotics must be examined by comparing the minimum inhibitory concentrations of isogeneic and clinical strains, and according to phenotype or mechanism: sensitive, penicillinase producer, cephalosporinase producer or producer of both penicillinases and cephalosporinases . During synthesis of a penicillinase, penicillins and some cephalosporins are more or less inactivated . With a constitutive cephalosporinase, all cephalosporins are inactivated as are, to a lesser degree, penicillins and monobactams, e.g . aztreonam . The emergence of new enzymes, including broad-spectrum beta-lactamases, and their extension to sensitive bacteria show that the enzymatic mechanism still has potentials for development.

Biochim Biophys Acta, 1986 Dec 18, 868(4), 249 - 53
Photolabeling of protein components in the pactamycin binding site of rat liver ribosomes; Synetos D et al.; The antitumoral and antibacterial drug pactamycin can be radioactively labeled by iodination without loss of biological activity . Using the labeled pactamycin, the ribosomal binding site of the drug on rat liver ribosomes has been studied by affinity labeling techniques taking advantage of the photoreactive acetophenone group present in the molecule . When 40 S ribosomal subunits are labeled, one major spot of radioactivity is found associated to protein S25 . In addition, weaker spots related to proteins S14/15, S10, S17 and S7 can also be detected in the autoradiogram of the two-dimensional gel slab . Since pactamycin inhibits protein synthesis initiation, the proteins forming its binding site must be related to some step of this process . By comparison with results from pactamycin affinity labeling of Escherichia coli ribosomes (Tejedor, F., Amils, R . and Ballesta, J.P.G . (1985) Biochemistry 24, 3667-3672) these proteins could lie in the mRNA and initiation factors binding region of the rat liver ribosome.

Vestn Khir Im I I Grek, 1986 Dec, 137(12), 50 - 6
{Radical-preventive surgery in cavernous tuberculosis of the kidneys}; Shapkin AG; On the model of focal-caseous tuberculosis of kidneys in 210 rabbits it was proved that effects of antibacterial drugs in any concentration have their limits and fail to liquidate the cavernous injuries of the renal parenchyma . The investigation of long-term results of the conservative treatment of 153 patients with the cavernous tuberculosis of kidneys has completely confirmed the conclusions of experimental investigations . An analysis of long-term results of organ-preserving focal operations in experiments and clinic gave a substantial support to a real possibility to cure the pathological process . The author points to an importance to revise the idea of the leading role of the conservative antibacterial therapy in favor of wider using radical-prophylactic operations in limited cavernous tuberculosis of kidneys.

J Vet Pharmacol Ther, 1986 Dec, 9(4), 446 - 54
Pharmacokinetics of trimethoprim/sulfadiazine in neonatal calves: influence of synovitis; Shoaf SE et al.; The effect of synovitis on the distribution of antibacterial drugs into the joint space was studied in 1-week-old calves . Sodium urate crystals were used to induce inflammation in the tibio-tarsal joint of calves and the antibacterial drug combination, trimethoprim/sulfadiazine (Tribrissen), 30 mg/kg, was administered intravenously 3 h after synovitis was induced . The degree of synovitis was monitored by serial WBC counts in synovial fluid . Trimethoprim (TMP) and sulfadiazine (SDZ) concentrations in serum and synovial fluid were measured and pharmacokinetic parameters were calculated . The results indicated that inflammation had no effect upon the concentrations of TMP/SDZ that reach the joint and that synovial fluid and blood are both representative of the central compartment as shown by the non-significant differences in selected pharmacokinetic parameters for TMP and SDZ in these two body fluids . The distribution and elimination of TMP and SDZ in serum were described by a two-compartment model.

J Histochem Cytochem, 1986 Dec, 34(12), 1687 - 90
Sponge secondary metabolites: biochemical and ultrastructural localization of the antimitotic agent avarol in Dysidea avara; Muller WE et al.; The secondary metabolite avarol, a potent cytostatic and antibacterial sesquiterpenoid hydroquinone, is present in large amounts only in the sponge Dysidea avara (2.7 g avarol/1 kg of fresh material) . The present study was designed to determine the storage site of this compound within the organism . Light and transmission electron microscopic studies revealed that avarol is probably stored only in spherular cells . The compound is compartmented in intracellular cytoplasmic vesicles in a paracrystalline form, and therefore can have no inhibitory effect on the sponge cells . Quantitative analysis utilizing high-pressure liquid chromatography revealed that avarol is present at a concentration of 3.2 micrograms/10(6) spherular cells . It appears that avarol is released from the cells into the extracellular space in a merocrine manner . We suggest that it is involved in regulating the bacteria with which the sponge is symbiotically associated.

Strahlenther Onkol, 1986 Dec, 162(12), 793 - 7
Therapeutic efficiency of olaquindox in gamma-irradiated mice; Pospisil M et al.; The antibacterial agent olaquindox (2-{N-(2-Hydroxy-ethyl)carbamoyl}-3-methyl-quinoxalin-1,4-dioxide) given in tap water at daily doses of 0.2 to 0.5 mg exerts beneficial effects on the body weight decrease and survival of gamma-irradiated mice . Beneficial effects are achieved especially by the postradiation administration of olaquindox . It is presumed that the mechanisms of the therapeutic effects of olaquindox are connected with its action on the composition of intestinal flora of mice.

J Pharm Sci, 1986 Dec, 75(12), 1185 - 7
Antibacterial activity of 6,8-disubstituted-quinolone-3-carboxylic acids; Krishnan R et al.; Twelve 6,8-disubstituted-1-ethyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acid derivatives were prepared and evaluated for their antibacterial activity . Among these, only the 6,8-difluoroquinolinone-3-carboxylic acid showed moderate activity.

Zentralbl Bakteriol Mikrobiol Hyg {B}, 1986 Dec, 183(1), 47 - 57
{Estimating the biological effect of detrimental substances on E . coli with flow microcalorimetry . II . Studies using 3 antibiotics}; Hartung J; The influence of three antibiotics (Penicillin G, Oxtetracycline, Polymyxin B), which show different modes of action against gram-negative bacteria, is tested on the growth of liquid E . coli cultures in a flow microcalorimeter . The antibiotics were added during the logarithmic growth phase of the culture when a heat flux of 40 mu W/ml was approached . A supply vessel and a reaction vessel were used for establishing of the baseline and for performing the test, respectively . When testing Oxytetracycline and Polymyxin B the germ content in the nutrient broth was determined, additionally . Some measurements of the optical density of the nutrient broth were carried out parallel to the microcalorimetric investigation on the effect of Polymyxin B . As was to be expected, Penicillin G shows an influence on E . coli at concentrations of about 50 microgram/ml medium, only . An influence of Oxytetracycline on the heat production can be observed at concentrations between 0.3 and 0.6 microgram/ml . Polymyxin B acts on the power-time-curve at 0.025 microgram/ml . The minimum doses of Oxytetracycline and Polymyxin B found by the microcalorimetric technique are distinctly lower than those found by bacterial count and by measuring the optical density . Microcalorimetric results are achieved within 2 hours after adding the test substance to the bacterial culture . Flow microcalorimetry seems to be a promising tool for testing antibacterial drugs.

Vestn Khir Im I I Grek, 1986 Dec, 137(12), 11 - 6
{Treatment of acute nonspecific pleural empyema}; Lytkin MI et al.; An analysis of the treatment of 240 patients with non-specific empyema of the pleura without bronchial fistula has shown the decisive significance of an adequate sanitation of the cavity by puncture or drainage . An expediency of associated use of the intrapleural antibacterial and proteolytic drugs is grounded . The general antibacterial therapy is necessary but under the threat of generalization of an infectious process and with clinical and roentgenological symptoms of the destructive process in the lungs.

Biochem J, 1986 Nov 1, 239(3), 717 - 22
Molecular cloning of a cDNA and assignment of the C-terminal of sarcotoxin IA, a potent antibacterial protein of Sarcophaga peregrina; Matsumoto N et al.; A previous paper described the complete amino acid sequences of sarcotoxins IA, IB and IC, which are a group of potent antibacterial proteins with almost identical primary structures produced by Sarcophaga peregrina (fleshfly) larvae {Okada & Natori (1985) J . Biol . Chem . 260, 7174-7177} . The present paper describes the cDNA cloning and complete nucleotide sequencing of a cDNA clone for sarcotoxin IA . The C-terminal amino acid residue of sarcotoxin IA deduced from the nucleotide sequence was glycine, whereas it was found to be arginine by amino acid sequencing of purified sarcotoxin IA . Analysis of the elution profiles on h.p.l.c . of the synthetic derivatives of sarcotoxin IA showed that the C-terminal amino acid residue of authentic sarcotoxin IA is amidated arginine, which is probably produced by enzymic cleavage of terminal glycine.

J Antimicrob Chemother, 1986 Nov, 18 Suppl D, 139 - 45
Treatment of respiratory tract infections with ciprofloxacin; Raoof S et al.; The efficacy and safety of ciprofloxacin in an oral dose of 750 mg twice daily, in the treatment of respiratory infections was studied in 129 patients . Ciprofloxacin showed broad in-vitro antibacterial activity and was highly effective in both Gram-negative and Gram-positive infections with a clinical cure rate of 96% . The major side effect was an interaction with theophylline particularly in the elderly patients.

J Antibiot (Tokyo), 1986 Nov, 39(11), 1509 - 14
Benzanthrins A and B, a new class of quinone antibiotics . I . Discovery, fermentation and antibacterial activity; Theriault RJ et al.; Nocardia lurida has been shown to produce two novel quinone antibiotics, benzanthrins A and B . The antibiotics were discovered in concentrated butanol extracts of fermentation broths and were separated by TLC and HPLC . Benzanthrins A and B were produced in a fermentation medium consisting of glucose, yeast, selected peptones and CaCO3 . The antibiotics were present primarily at 66 hours in shake flask fermentations and from 66 to 162 hours in 14-liter fermentors . Benzanthrins A and B inhibited a number of Gram-positive pathogenic bacteria but were inactive against Gram-negative bacteria.

J Med Chem, 1986 Nov, 29(11), 2363 - 9
Synthesis and structure-activity relationships of new arylfluoronaphthyridine antibacterial agents; Chu DT et al.; Novel arylfluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acids have been prepared and their antibacterial activity evaluated . These derivatives are characterized by having a fluorine atom at the 6-position, substituted amino groups at the 7-position, and substituted phenyl groups at the 1-position . The in vitro antibacterial potency is greatest when the 1-substituent is either p-fluorophenyl or o,p-difluorophenyl and the 7-substituent is a 3-amino-1-pyrrolidinyl group . 1-(2,4-Difluorophenyl)-6-fluoro-7-(3-amino-1-pyrrolidinyl)-1,4-dihydro- 4-oxo-1,8-naphthyridine-3-carboxylic acid (38) was found to possess excellent in vitro potency and in vivo efficacy.

J Med Chem, 1986 Nov, 29(11), 2212 - 7
Antibacterial activity of phosphono dipeptides related to alafosfalin; Lejczak B et al.; A series of dipeptides containing N-terminal alanine or leucine and a wide range of P-terminal racemic 1-amino-alkanephosphonates were prepared and tested in vitro for their ability to inhibit the growth of various bacterial species . The results demonstrate that peptides containing 4-amino-4-phosphonobutyric acid and 1-amino-1-methylethanephosphonic acid exhibit antibacterial activity comparable with that observed in the case of peptides containing P-terminal racemic 1-aminoethanephosphonic acid (analogue of alanine) used as a positive control.

J Appl Bacteriol, 1986 Nov, 61(5), 383 - 8
The action of various venoms on Escherichia coli; Stocker JF et al.; The antibacterial activity of honeybee venom (Apis mellifera), three snake venoms (Naja naja sputatrix, Vipera russellii and Crotalus adamanteus) and the polypeptide melittin was investigated against Escherichia coli . Minimum inhibitory concentration values, cell lysis and alterations in cell permeability were determined and action against E . coli was in the order: A . mellifera venom greater than melittin greater than N . naja sputatrix venom much greater than V . russellii venom greater than C . adamanteus venom . Cellular damage by A . mellifera and N . naja sputatrix venoms was evident in electron micrographs.

Am J Otolaryngol, 1986 Nov-Dec, 7(6), 410 - 25
Normal distribution of lysozyme- and lactoferrin-secreting cells in the chinchilla tubotympanum; Hanamure Y et al.; The distribution of the antibacterial enzyme lysozyme- and lactoferrin-secreting cells in the tubotympanum of normal chinchillas was studied using an immunohistochemical technique . The middle ear mucosa contained lysozyme-secreting cells and lactoferrin-secreting cells . The former were localized primarily in the columnar epithelium area and the latter primarily in the cuboidal epithelium area (that contains serous cells) of the transitional zone . In the eustachian tube, the lysozyme was localized in goblet cells of the mucosal epithelium and mucous cells of the glands, while lactoferrin was localized in serous cells of the glands . Our results indicate that secretory lysozyme and lactoferrin are secreted by different cell types (mucous or serous), supporting the notion of heterogeneity of the secretory cells of the tubotympanum . This finding is consistent with the concept that antibacterial enzyme secretion is an integral part of the normal mucosal defense system in the tubotympanum.

Drug Des Deliv, 1986 Nov, 1(2), 157 - 65
Studies on improvement of pharmaceutical preparations prescribed in hospitals . IV . Dibekacin sulfate viscous solution for treatment of mouth and throat wounds; Namiki N et al.; For the purpose of preventing suppuration of wounds of the oral cavity and throat, we attempted to develop a viscous solution of dibekacin sulfate (DKB) as a suitable medication . Solutions of different viscosity and antibacterial potency were prepared by mixing DKB, sodium carboxymethyl cellulose (CMC-Na), and water in varying proportions . Studies were then performed to ascertain relationships between the concentration of CMC-Na pH and viscosity, and between the viscosity and diffusion of DKB . The concentration of CMC-Na giving rise to optimal clinical efficacy was determined, and the concentration of DKB necessary for clinical treatment was estimated on the basis of the ionic binding constant between DKB and CMC-Na . As a result, the optimum CMC-Na concentration was found to be 2%, while the optimum DKB concentration was estimated to be 100 micrograms/ml.

Jpn J Antibiot, 1986 Nov, 39(11), 2869 - 76
{Laboratory and clinical studies on cefmenoxime in respiratory tract infections}; Ida S et al.; Cefmenoxime (CMX, Bestcall) was administered by drip infusion to 65 patients with various respiratory infections and its effect was evaluated . The rate of effectiveness was 86.2% in all cases including 40 cases of acute pneumonia and 12 cases of chronic bronchitis . CMX was examined comparatively with other drugs for antibacterial activity on clinically isolated strains of 2 bacterial species, i.e . H . influenzae and B . catarrhalis, each of which has a high frequency of clinical isolation from infected respiratory organs . On H . influenzae CMX exerted the strongest antibacterial activity among test drugs (ampicillin, piperacillin cefoperazone, latamoxef) regardless of the production of beta-lactamase by the organism, while on B . catarrhalis it also exerted an antibacterial activity strong enough to control the proliferation of all strains at a dose level of 0.39 microgram/ml . Drip infusion of this drug (2 gram) brought about an average maximum blood concentration of 127.2 +/- 21.5 micrograms/ml and an average half-life in blood of 1.10 +/- 0.28 hours . However, different values were obtained for different individual cases because these subjects were patients of chronic respiratory infections each having some underlying disease or other . Side effects of the drug were observed as allergic symptoms such as pyrexia, eruption and the like, but only 5 cases without any serious cases . Increases in transaminase suggestive of abnormal clinical test results were also observed in 5 cases . However, numerical recoveries to the normal values were obtained in all of these 5 cases with the withdrawal of the drug.

Rev Infect Dis, 1986 Nov-Dec, 8 Suppl 5, S612 - 6
Penetration of sulbactam into the cerebrospinal fluid of patients with bacterial meningitis receiving ampicillin therapy; Stahl JP et al.; Concentrations of sulbactam in the CSF of 18 patients with bacterial meningitis who were undergoing treatment with intravenous (iv) ampicillin were determined . Six patients received single doses of sulbactam (1 g) and 12 patients received multiple doses (four times daily) by the iv route at various intervals before lumbar punctures were performed to monitor their condition . Concentrations of sulbactam up to 12 micrograms/ml were detected in the CSF between 1 and 4 hr after dosing, the higher levels being present in the CSF of patients with the most severe meningeal inflammation . There were no significant differences in the concentrations achieved after single or multiple doses of sulbactam, and the concentrations were generally similar to the concurrent concentrations of ampicillin . It is concluded that these results as well as the antibacterial properties of sulbactam plus ampicillin support the evaluation of this combination as an alternative in the treatment of bacterial meningitis.

Rev Infect Dis, 1986 Nov-Dec, 8 Suppl 5, S589 - 92
Biliary pharmacokinetics of sulbactam plus ampicillin in humans; Morris DL et al.; The biliary pharmacokinetics of sulbactam and ampicillin was investigated in 19 patients with normal liver function who were undergoing surgery of the biliary tract . The combination of sulbactam (0.5 g) plus ampicillin (1 g) was given intravenously to five patients with T-tube drainage of the common bile duct . Mean peak concentrations of sulbactam (19.4 micrograms/ml) and ampicillin (471 micrograms/ml) in the bile occurred 0.5-1 hr after administration . Biliary excretion was estimated to account for approximately 0.24% of the sulbactam dose and 2.8% of the ampicillin dose . Fourteen other patients received the same dose of sulbactam/ampicillin immediately before elective cholecystectomy . Respective mean concentrations of sulbactam and ampicillin at the time of gallbladder removal were 4.3 micrograms/ml and 15.9 micrograms/ml in gallbladder bile and 6.3 micrograms/g and 7.7 micrograms/g in gallbladder wall tissue . These results, together with the antibacterial spectrum and potency of the combination, suggest that sulbactam/ampicillin is suitable for prophylactic use in biliary tract surgery.

Rev Infect Dis, 1986 Nov-Dec, 8 Suppl 5, S496 - 502
Sulbactam: biochemical factors involved in its synergy with ampicillin; Labia R et al.; Sulbactam is a time-dependent irreversible inhibitor of various beta-lactamases by reversible formation of a Michaelis-type enzyme-inhibitor complex and progressive evolution of this complex into inactivated protein(s) . This process is either irreversible (true inactivation) or quasi-irreversible (stable acyl-enzyme) . In this way, sulbactam efficiently protects ampicillin from degradation by beta-lactamases . Sulbactam itself exhibits a moderate antibacterial activity that is related to an affinity for the penicillin-binding proteins of various bacterial strains, which is similar to the affinity of penicillins such as ampicillin . However, sulbactam binding differs according to the bacterial species involved . In strains producing either low levels of beta-lactamase or none at all, a synergistic effect, minor but not negligible, can be observed when sulbactam is associated with a beta-lactam antibiotic with a complementary affinity for the target sites.

J Heart Transplant, 1986 Nov-Dec, 5(6), 430 - 6
Dermatologic complications following heart transplantation; O'Connell BM et al.; A total of 107 consecutive heart transplant recipients at Stanford University Medical Center were prospectively screened for dermatologic disease as part of their routine postoperative evaluation over a 6-month period . The incidence of nonmelanotic skin tumors and premalignant lesions was approximately 25-fold greater than expected in a normal population . Skin infections were seen in 55% of the patients and dermatologic drug side effects were almost universal including xerosis, hypertrichosis, and steroid acne . Successful excision or cryotherapy of all neoplastic lesions was achieved with no evidence of recurrence to date, a mean of 11 months . The skin infections responded to appropriate antiviral, antibacterial, and antifungal agents and the xerotic and acneiform lesions were successfully treated with emollients and topical retinoic acid, respectively . In addition, patients were instructed in preventive measures including the use of sunscreen agents and protective clothing . We conclude that heart transplant recipients have a significantly increased incidence of neoplastic, infectious, and drug-induced skin diseases . Routine dermatologic screening resulted in early identification and successful treatment of these lesions . We suggest that dermatologic screening is both feasible and valuable in this setting.

J Hosp Infect, 1986 Nov, 8(3), 263 - 7
Antiseptic toxicity in wounds healing by secondary intention; Brennan SS et al.; The effects of two commonly used antiseptics for chronic ulcer care, chloramine T and chlorhexidine, on the biochemical and histological parameters of healing have been examined . The antiseptics were compared with saline when applied to 10 mm skin defects on Sprague-Dawley rats . Chloramine T significantly delayed the production of collagen and prolonged the acute inflammatory response compared with saline . Chlorhexidine did not differ from saline . We conclude that hypochlorite antiseptics may adversely affect healing by secondary intention and the antibacterial and desloughing action of agents should be carefully balanced against their toxic effect.

Vet Rec, 1986 Oct 25, 119(17), 420 - 6
The ecology of Escherichia coli in animals including man with particular reference to drug resistance; Hinton M; The phenomenon of drug resistance among bacteria, particularly Escherichia coli, has been a major research interest of the University of Bristol's departments of microbiology and veterinary medicine during the past 15 years . Tens of thousands of E coli isolates from man and farm animals have been examined in studies of both the ecology of the species and the epidemiology of their resistance to therapeutic antibacterial agents . The principal findings obtained in these investigations are described.

J Antimicrob Chemother, 1986 Oct, 18 Suppl C, 255 - 60
Resistance as a cause of treatment failure; Phillips I; Clinicians and microbiologists both vary in their views on the usefulness of in-vitro antibacterial sensitivity tests, and on the significance of in-vitro resistance . This seems to relate to the fact that conditions in most in-vitro tests are remote from those in the patient, and that at best the designation 'resistant' depends on a pragmatic consensus . Furthermore, results of treatment are difficult to assess in infected patients because of the many variables that affect outcome . Well-designed clinical trials, when they are feasible, and the results of animal experiments, strongly suggest that, when it can be assessed, there is a good correlation between in-vitro and in-vivo results . There is a need to improve the content of clinical reports on the subject sent by microbiologists to clinicians.

Vestn Khir Im I I Grek, 1986 Oct, 137(10), 83 - 6
{Treatment of lung abscesses in children}; Mavliutova MG et al.; Treatment of 76 children aged from 1 month to 14 years with acute destructive pneumonia complicated by intrapulmonary abscesses is described . The treatment was complex, general, antibacterial and local . The authors have elaborated a method of percutaneous prolonged catheterization of lung abscesses in children which was used in 22 patients . The method resulted in sanitation of the blocked intrapulmonary abscesses, prevention of severe complications and shorter treatment of the patients at the hospital.

Monatsschr Kinderheilkd, 1986 Oct, 134(10), 733 - 7
{Cefotaxime monotherapy in bacterial meningitis in childhood}; Helwig H et al.; Bacterial meningitis in 20 children was treated with cefotaxime . 17 children received this antibiotic throughout the disease as monotherapy, three were changed to Penicillin G (2) or ampicillin (1), after sensitivity of the pathogen was known, although cefotaxime had been effective . All bacterial isolates were highly susceptible to cefotaxime . All CSF cultures were sterile at second tap, performed 24 to 48 hrs after therapy was started . Cefotaxime and desacetyl-cefotaxime concentrations in CSF, measured by HPLC in 9 patients were in the range of 4 to 34 (average 17.6) mg/l and 2.1 to 82 (average: 15.1) mg/l, representing a CSF-serum ratio of 8 to 74% (average 45.6%) for cefotaxime and 25 to 151% (average: 73.7%) for desacetyl-cefotaxime . Clinical outcome was favourable in 17 patients . There were one death and late neurological deficits in three . Cefotaxime monotherapy is recommended instead of standard therapy with chloramphenicol and/or ampicillin because of superior antibacterial activity, lower toxicity and lesser side-effects for primary meningitis in children caused by N . meningitides, S . pneumoniae, or H . influenzae type b.

Farmaco {Sci}, 1986 Oct, 41(10), 781 - 7
{Quinolizidine derivatives with antibacterial activity}; Sparatore A et al.; Six quinolizidinyl-derivatives were tested for antibacterial actvity against a large number of gram-positive and gram-negative strains . 9-Lupinyliden-fluorene (I) and its epimer (II) at concentrations between 12,5 and 100 mg/l inhibit all gram-positive strains, while they are only weakly active against a few gram-negative bacteria . The tertiary alcohols (III) and (IV) are inactive against the gram-positive strains, while still exhibiting weak activity on the gram-negative . Compounds (V) and (VI) are completely inactive . The values of minimal bactericidal concentrations for compound (I) against the sensitive strains are equal to or no more than 4 times higher than values of MIC . It is interesting to note that compound (I) is able to give rise to cellular lysis at MIC.

J Antibiot (Tokyo), 1986 Oct, 39(10), 1467 - 72
Antimycotic effects of the novel antitumor agents fostriecin (CI-920), PD 113,270 and PD 113,271; Mamber SW et al.; The novel fermentation products fostriecin and analogs PD 113,270 and PD 113,271 are structurally related polyene lactone phosphates that have antitumor activity in vitro and in vivo . They have no antibacterial effects, but they were inhibitory to yeasts (agar diffusion method) with MICs of 3 approximately 300 micrograms/ml . Fostriecin or its analogs were active vs . 29 of 46 yeast species (11 genera) . Ten of 12 cultures of Candida sp . were not sensitive to any of the analogs, while 11 of 14 cultures of Saccharomyces sp . were inhibited by one or more of the agents . Sensitivity patterns were of three types: Twelve cultures were sensitive only to PD 113,270; fostriecin and PD 113,271 (but not PD 113,270) were active vs . 7 cultures; and 9 cultures were sensitive to all three compounds . Dephosphorylation of the compounds resulted in the loss of antimycotic effects . Activity vs . the yeasts was related to studies of uptake and activity against cancer cells.

Minerva Med, 1986 Sep 29, 77(37), 1647 - 62
{Brucellosis therapy}; Di Nola F et al.; The reasons for the use of a fat-soluble drug with an in vitro activity against Brucella spp in the treatment of brucellosis are presented . After a review of the literature a series of 222 cases subjected to various treatments is presented and it is concluded that an RMV-minocycline association offers the best antibacterial and kinetic characteristics.

Vet Rec, 1986 Sep 6, 119(10), 233 - 5
Epidemiology and control of vaginal discharges in the sow after service; Muirhead MR; A syndrome associated with vaginal discharge, endometritis and reproductive inefficiency in the served sow is described . In some herds pregnancy failures exceeded 15 per cent with increased returns to service and sows not in pig . Predisposing factors included the age of the herd and the hygiene and management practices from weaning to service and during the 21 days after service . No one organism was implicated but venereal transmission was considered possible . One hundred and ten breeding herds were surveyed and in 26 of these control measures were necessary . These included antibacterial therapy of the prepuce of the boar and medication of the sow from weaning until 21 days after service . Such treatment together with management changes resolved the problem in 22 of the herds . The syndrome reappeared in four out of seven herds where treatment of the boar was not continued.

J Antibiot (Tokyo), 1986 Sep, 39(9), 1236 - 42
Semisynthetic beta-lactam antibiotics . II . Synthesis and antibacterial activity of 7beta-{2-(acylamino)-2- (2-aminothiazol-4-yl)acetamido}cephalosporins; Arimoto M et al.; Cephalosporin derivatives (I) substituted with a neutral, acidic or basic amino acid group as the terminal group attached to the 2-amino-2-(2-aminothiazol-4-yl)acetamido side chain at the C-7 position were synthesized, and the effect of each group on antibacterial activity was examined . The derivatives bearing an amidino or guanidino group showed broad spectra of antibacterial activity similar to those of cefotaxime, but they were relatively sensitive to beta-lactamases.

J Antibiot (Tokyo), 1986 Sep, 39(9), 1225 - 35
Semisynthetic beta-lactam antibiotics . I . Synthesis and antibacterial activity of 7 beta-{2-aryl-2-(aminoacetamido)acetamido}-cephalosporins; Furukawa M et al.; The synthesis and in vitro structure-activity relationships of cephalosporins having dipeptides substituted with various aryl groups as the side chain at the C-7 position have been outlined . Of these compounds, 2-aminothiazol derivatives showed a broad spectrum of enhanced antibacterial activity, and 7 beta-{DL-2-(D-aminopropionamido)-2-(2-aminothiazol-4-yl)acet amido}-3- {(1-methyl-1H-tetrazol-5-yl)thiomethyl}ceph-3-em-4-carboxyli c acid was the most balanced of these active derivatives with respect to both Gram-positive and Gram-negative strains.

J Inorg Biochem, 1986 Sep, 28(1), 57 - 65
Some transition metal chelates of 8-hydroxyquinoline-5-sulfonamides as possible drugs; Ibrahim SA et al.; Fe(II), Fe(III), Co(II), and Ni(II) chelates with three quinolinol sulfonamides have been prepared and characterized . Characterization of the solids so obtained was accomplished by elemental analysis, electronic and ir spectra, and conductivity measurements . It was found that the sulfonamide ligands act as monobasic bidentate ON donors . The bonding sites are ascertained, and the complexes were all six-coordinate assuming a distorted octahedral geometry . It was identified that the metal chelates possess enhanced antibacterial and antifungal activities relative to the free ligands.

Infection, 1986 Sep-Oct, 14(5), 212 - 5
Chlorhexidine: antibacterial action and bacterial resistance; Russell AD; Chlorhexidine is a clinically important antiseptic, disinfectant and preservative . It is a potent membrane-active agent against bacteria and inhibits outgrowth, but not germination, of bacterial spores, although it is not sporicidal . It shows high activity against wild-type and outer membrane mutants of Escherichia coli but some gram-negative bacteria are resistant to chlorhexidine by mechanisms not yet fully understood, although they appear to involve the outer, rather than the inner, membrane.

Vopr Med Khim, 1986 Sep-Oct, 32(5), 80 - 4
{Comparative characteristics of the activity of proteolytic enzymes and their inhibitors in the lung tissue of guinea pigs during development of generalized and destructive tuberculosis}; Zhukova NL et al.; Two series of experiments were carried out using 66 guinea pigs infected with tuberculosis . In the first experiment generalized tuberculosis was stimulated by means of subcutaneous administration of Mycobacterium tuberculosis H37RV strain at a dose of 0.0001 mg . In the second experiment destructive form of tuberculosis was developed after intrapulmonary administration of the bacteria (1 mg) followed by VCG vaccination . In both experiments the animals were divided into groups with spontaneous form of the infection and the group of animals treated with rifamycin and isoniazid . Total protein, elastolytic activity, cathepsins B and D, free antitryptic activity were estimated in lung homogenates . Generalized and destructive forms of tuberculosis were shown to induce an increase in content of soluble protein as well as in cathepsin D, elastolytic and antitryptic activities in tissues . Destructive form of tuberculosis was characterized by more than 4-fold increase in elastolytic activity and by a distinct activation of cathepsin B . The antibacterial drugs used affected only slightly the biochemical patterns studied in lung tissue.

J Antimicrob Chemother, 1986 Sep, 18(3), 335 - 43
Antibacterial activity of resolved temocillin epimers; White AR et al.; The antibacterial activity of pure resolved R and S epimers of temocillin was determined in a variety of in-vitro test systems, including those that allowed measurement of activity during the early period following exposure to the agents, thus minimising the effect of epimerization . In conventional agar- and broth-dilution susceptibility tests involving incubation at 37 degrees C for 18 h, little difference was evident between the activities of the individual epimers . In contrast, in other tests of antibacterial activity, such as time-kill and turbidimetric studies, the R epimer and temocillin (R/S mixture 1.8:1.0) were shown to be more rapidly bactericidal than the S epimer . Overall, the R epimer and temocillin (R/S) exhibited a similar degree of bactericidal activity in vitro.

Scand J Immunol, 1986 Sep, 24(3), 251 - 60
Antibodies to Escherichia coli and anti-adhesive activity in paired serum, hepatic and gall bladder bile samples; Dahlgren UI et al.; Human bile contains a mixture of immunoglobulins excreted through the liver and produced in the biliary tract . This study examines the specific antibody activity of the biliary immunoglobulins against Escherichia coli antigens . Paired samples of serum, hepatic bile, and gall bladder bile were obtained from 23 patients with gallstones and five patients with healthy gall bladders . Antibody activity against E . coli antigens was found in all the sera and most of the bile samples . The levels of IgA, IgM, IgG, and secretory component (SC)-combined antibodies were lower in bile than in serum . Selective treatment of IgA by the liver was suggested by the finding of a correlation between the serum and the bile IgA antibody activity . IgG antibodies were only found in inflamed gall bladders . The bile was shown to have antibacterial activity against E . coli, i.e . an ability to inhibit the attachment to epithelial cells, but the inhibitory activity was not restricted to the immunoglobulin fraction of the bile.

J Infect Dis, 1986 Sep, 154(3), 464 - 70
Release of 5'-guanosine monophosphate and adenine by Brucella abortus and their role in the intracellular survival of the bacteria; Canning PC et al.; Brucella abortus releases two components (fractions 3b and 10) that inhibit the myeloperoxidase-H2O2-halide antibacterial system of bovine neutrophils by inhibiting degranulation . Fractions 3b and 10 were analyzed by high-performance liquid chromatography and thin-layer chromotography and compared with nucleotide and base standards . These investigations indicated that fraction 3b coeluted and comigrated with 5'-guanosine monophosphate (GMP), whereas fraction 10 coeluted and comigrated with adenine . We determined the biologic effects of GMP, adenine, and B . abortus fractions 3b and 10 on neutrophil functions . Iodination activity of neutrophils was inhibited to approximately 65% of control by GMP (0.04 mg/ml) and by fraction 3b (0.04 mg/ml) . Iodination was also suppressed to approximately 80% of control by adenine (0.04 mg/ml) and by fraction 10 (0.04 mg/ml) . These results suggest that B . abortus produces GMP and adenine and that these substances contribute to the intracellular survival of the bacteria.

Antibiot Med Biotekhnol, 1986 Aug, 31(8), 588 - 92
{Selective modification of the free amino groups of the antibiotic ristomycin A}; Katrukha GS et al.; Selective chemical modification of ristomycin A (I) by the free NH2 groups was performed . 6 different N-acyl and N-aminoacyl derivatives of I were obtained . 5 of them showed antibacterial activity within 0.4-10.0 micrograms/ml against 4 test microbes . The biological activity of the derivatives depended on the substituent type and the molecule total charge: mono-N-L-isoleucyl-I with the charge of +2 had the highest activity and N,N'-disuccinyl-I had the lowest activity.

J Antibiot (Tokyo), 1986 Aug, 39(8), 1167 - 71
Enhancement of 5-fluorouracil uptake into the bacterial cell by piperacillin; Takahata M et al.; The antibacterial activity of 5-fluorouracil, an antineoplastic agent, was found to be enhanced by piperacillin, a beta-lactam antibiotic, resulting in a synergism . It was considered that the synergism was caused by an increase of 5-fluorouracil uptake into the bacterial cell . On the other hand, amount of piperacillin bound to penicillin binding protein (PBP) did not change when 5-fluorouracil was added . The morphological change of the cell was due to the 5-fluorouracil when synergism appeared between 5-fluorouracil and piperacillin.

J Med Vet Mycol, 1986 Aug, 24(4), 305 - 11
Improved method for estimation of azole antifungal inhibitory concentrations against Candida species, based on azole/antibiotic interactions; Odds FC et al.; Low, reproducible minimal inhibitory concentrations against Candida species, with sharp, precise end points in complex media were achieved for imidazoles (clotrimazole, econazole, miconazole, tioconazole and ketoconazole) and triazoles (fluconazole, itraconazole, vibunazole, ICI 153066) by including in the test medium antibacterial antibiotics that bind to the 80S eukaryotic ribosome and inhibit protein synthesis, i.e . blasticidin, cycloheximide, doxycycline, neomycin and gentamicin . The presence of these antibiotics reduced MICs, on average, by 50- to 250-fold . Other protein synthesis inhibitors (rifampicin, erythromycin, lincomycin, clindamycin, chloramphenicol and fusidic acid) were not effective, and the antibiotics did not affect MICs for Aspergillus species . The low azole MICs were in close agreement with MICs obtained in a defined, tissue culture-based medium lacking added antibiotics.

Jpn J Antibiot, 1986 Aug, 39(8), 2247 - 62
{Fundamental and clinical evaluation of ceftazidime in the perinatal period}; Matsunami K et al.; Following an intravenous injection of ceftazidime (CAZ) 1 g, the ratio of transfer of the drug into a fetus was 59.9%, and umbilical serum concentrations of the drug reached the peak of 18.2 micrograms/ml at 1.5 hours, and were slightly higher than maternal serum concentrations at 2.93 hours and after, with half-life of 1.37 hours, the same as in maternal serum . Following an intravenous injection of CAZ 1 g, concentrations of CAZ in mother's milk at 2 hours after injection were 1.16 micrograms/ml on the 4th day of the treatment of CAZ, and 0.86 micrograms/ml on the 7th day . The CAZ was administered to cases of premature rupture of membrane . The prophylactic efficacy against puerperal infections in mothers was 92%, and that against fetal infections in neonates was 96.7% . The CAZ was also administered after cesarean section, and the prophylactic efficacy against postoperative infections was 93.3% . Neither subjective/objective adverse effects nor abnormal laboratory findings for which CAZ was suspected were observed in any mothers or neonates . From the above results demonstrating satisfactory maternal transfer into fetuses and the high degree of safety in fetuses and neonates, as well as its high antibacterial activity, CAZ is considered to be a useful drug for the treatment of perinatal infections.

Antibiot Med Biotekhnol, 1986 Aug, 31(8), 624 - 8
{Mechanism of the antibacterial action of monocarboxycellulose and other ion-exchange derivatives of cellulose}; Abaev IuK et al.; The mechanism of the antibacterial effect of monocarboxyl cellulose (MCC) and other ion exchange derivatives of cellulose was studied . It was shown that MCC, cellulose phosphate and aminocellulose had a pronounced antibacterial effect due to the presence of the ionogenic group H+ or OH- in the initial drugs . A certain role in this process was played by sorption . The level of the antibacterial activity of MCC depended on the number of the carboxylic groups . MCC is promising as a dressing material.

J Bacteriol, 1986 Aug, 167(2), 535 - 43
Newly made enzymes determine ongoing cell wall synthesis and the antibacterial effects of cell wall synthesis inhibitors; Tuomanen E; Cell wall synthesis can continue with less than the total complement of cell wall synthetic enzymes present in normal growing cells . A method was developed to investigate whether there exists an excess of cell wall-synthesizing enzymes (penicillin-binding proteins {PBPs}) which all remain functional or whether a mixed population of functional and nonfunctional enzymes characterize normal cells . Surprisingly, cells in which less than 10% of the PBPs were functional could grow at a normal rate, as evidenced by increases in viable counts, culture turbidity, and rates of peptidoglycan, protein, and RNA synthesis . This subset of functional enzymes was biosynthetically new . Penicillin-induced lysis occurred contingent on the acylation of this same small fraction of PBPs, the copy number and affinities of which were below the level of detection by current fluorographic assay techniques . We propose that PBPs have a short functional half-life and that cell wall synthesis and bacterial lysis reflect the activity of newly synthesized PBPs.

Chemioterapia, 1986 Aug, 5(4), 273 - 7
In vitro microbiological properties of mezlocillin compared with four cephalosporins; Esposito S et al.; The intrinsic activity, antibacterial spectrum and beta-lactamase stability of mezlocillin were determined and compared with that of four other beta-lactams: ceftriaxone, ceftizoxime, cefotaxime, cefuroxime . These parameters were studied by determining the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) against 397 gram-negative bacteria including Pseudomonas sp . and 124 gram-positive cocci, utilizing 10(5) and 10(7) CFU/ml bacterial concentrations . The sensitivity to ten different standard beta-lactamases was determined by a spectrophotometric method that utilizes the velocity of cytochrome c reduction . Mezlocillin was hydrolyzed, at different degrees, by all the beta-lactamases under examination (TEM 1, TEM 2, OXA1, OXA2, OXA3, S + A, P99, STH4, SHV1, K1) but such hydrolysis did not affect its bactericidal activity which was similar to that of the other beta-lactamase-stable beta-lactams . In addition MBC/MIC ratios were very low and the differences of MIC values at different bacterial inocula were not significant . We also studied the stimulation of inducible beta-lactamases by subinhibitory doses of antibiotics, the eventual changes of antibiotic susceptibility after these stimulations and, finally, the frequency of spontaneous resistant mutants . Mezlocillin stimulated the production of inducible beta-lactamases in 50% of the bacteria examined, but in contrast with the other drugs tested, no increase of MICs occurred nor did mezlocillin select resistant mutants.

Hinyokika Kiyo, 1986 Aug, 32(8), 1213 - 23
{Therapeutic studies on chronic prostatitis--use of AT-2266--Sapporo Clinical Research Group for STD}; Kumamoto Y et al.; AT-2266 is a new antibiotic of the pyridone carboxylic acid class which possesses a broad, low-MIC antibacterial spectrum . Therapeutic studies were carried out on the use of this drug in the treatment of chronic prostatitis, and at the same time a pathological analysis was performed on chronic prostatitis . The subjects were 97 chronic prostatitis patients for whom the prostate fluid had been confirmed to contain at least 30 leukocytes per 400-power magnification field . An analysis of the background factors revealed that 71% of these patients had a past history of gonorrheal or non-gonorrheal urethritis . Culture of the prostate fluid yielded gram-positive cocci (S . epidermidis in most cases) in 44.1% of the patients . E . coli was detected in 3.2% of the patients, while the remaining cases gave negative cultures . In 53.9% of the patients who had not been receiving therapy prior to inclusion in this study, the subjective symptoms consisted of urethral irritation or irritation upon urination . In the other patients, the relationship of the complaints to the disease could not be clearly established . In the patients who had been receiving therapy, the majority did not complain of subjective symptoms . AT-2266 was administered in a daily dosage of 600 mg (in 3 divided doses) for 14 days . The therapeutic efficacy was evaluated . At the end of 7 days of AT-2266 therapy, 15.5% of the previously-untreated group and 8% of the previously-treated group were "excellent" cases, and the efficacy rate was 32.8% and 36%, respectively, when the "good" cases were also included . At the end of the full 14 days of therapy, the corresponding efficacy rates were 21.7% and 17.4%, and 54.3% and 56.5% . Considerable improvement was achieved in the subjective symptoms of urethral irritation and irritation upon urination at the end of 7 days of therapy, and the improvement was even greater following the next 7 days of treatment . With regard to the complaints for which the relationship to the disease could not be clearly established, however, the improvement was not very good: there was not much difference between the results on the 7th and 14th days, and the elimination rate even after 14 days was slightly below 30% . In the previously-untreated patients, improvement in leukocyte count in the prostate fluid to 10 or fewer cells per microscopic field was achieved in 15.6% at 7 days and 21.7% at 14 days . As side effects of AT-2266, mild symptoms were observed to occur in only 1.8% of the patients.

Arzneimittelforschung, 1986 Aug, 36(8), 1244 - 8
Reproductive toxicity of ofloxacin; Takayama S et al.; The reproductive toxicity of (+/-)-9-fluoro-2, 3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido{1,2,3-de} {1,4}benzoxazine-6-carboxylic acid (ofloxacin, Tarivid), a new antibacterial agent, was investigated in rats and rabbits after oral administration . Neither the male or female fertility nor the reproductive performance of the rats was affected by doses of up to 360 mg/kg . Ofloxacin elicited no evidence of teratogenicity when administered orally during the period of organogenesis to pregnant rats at doses of up to 810 mg/kg, or to pregnant rabbits at doses of up to 160 mg/kg . However, the female rats receiving 810 mg/kg showed salivation, dirty hair coats, soft stools, and decreases of body weight and food intake . The fetuses in the higher dose groups exhibited decreased body weight and retardation of ossification, and those in the highest dose group showed increased mortality and skeletal variations (cervical ribs, shortened 13th ribs) . Further investigation of the fetal skeleton revealed that the critical period of the occurrence of skeletal variations was on days 9 and 10 of gestation . The occurrence of cervical ribs and shortened 13th ribs was not an indicator of teratogenicity when ofloxacin was administered at doses of up to 1600 mg/kg during the critical period . Moreover, the shortening of the 13th ribs was the only type of retardation of ossification degree . Decreases of maternal body weight and food intake, and increased mortality of fetuses were observed in rabbits at a dose of 160 mg/kg . In a perinatal and postnatal toxicity study in rats using doses of up to 360 mg/kg, no adverse effects were observed.

Chemioterapia, 1986 Aug, 5(4), 283 - 4
Ceftriaxone kinetics after a single intravenous dose in leukemic children with fever and granulocytopenia; Rossi MR et al.; Ceftriaxone (CFX) is a new third-generation cephalosporin with interesting characteristics as regards both its antibacterial spectrum and kinetics which make it potentially useful in the empiric treatment of infections in neutropenic cancer patients . However, since its kinetic characteristics in children with leukemia are not known and its pharmacokinetics are reported to be altered in such patients, we studied ceftriaxone's activity in ten leukemic children with fever and neutropenia . Our findings seem to be confirm the potential efficacy of the drug also in this particular type of patient.

J Med Chem, 1986 Aug, 29(8), 1531 - 4
Synthesis and biological activity of benzothiazolo{3,2-a}quinolone antibacterial agents; Chu DT et al.; A new class of heterocyclic compounds with potent antibacterial activity, namely, 2-substituted amino-3-fluoro-5,12-dihydro-5-oxobenzothiazolo{3, 2-a}quinoline-6-carboxylic acids, is described . The compounds are conformationally restricted analogues of 7-substituted amino-6-fluoro-1-aryl-1, 4-dihydro-4-oxoquinoline-3-carboxylic acids . Compounds 7 and 10, having a 4-methylpiperazinyl and a piperazinyl substitution at the 2-position, respectively, possess in vitro antibacterial activities comparable to norfloxacin (15) . Compound 8, which has a 4-acetylpiperazinyl substitution at the 2-position, is active against Gram-positive organisms and nearly inactive against Gram-negative organisms . An efficient and short synthesis of this novel heterocyclic system via an intramolecular nucleophilic displacement cyclization reaction is reported.

Antimicrob Agents Chemother, 1986 Jul, 30(1), 170 - 1
Lack of antibacterial activity of pentoxifylline; Yu PK et al.; Pentoxifylline was inactive when tested against 70 fresh clinical bacterial isolates, as well as when tested alone and in combination with erythromycin, vancomycin, or rifampin against Escherichia coli PC1349 (wild type) and its heptose-deficient outer membrane mutant E . coli PC2040 . No antibacterial activity of pentoxifylline or its metabolites could be detected in sera from patients receiving pentoxifylline or its metabolites could be detected in sera from patients receiving pentoxifylline.

Zh Mikrobiol Epidemiol Immunobiol, 1986 Jul, (7), 100 - 2
{Leukocyte migration inhibition reaction--an index of the antibacterial effectiveness of stimulants of the body's nonspecific resistance}; Aptekareva MN et al.; The presence of correlation between the protective action of prodigiosane and yeast RNA and the character of reaction in the direct capillary variant of the leukocyte migration inhibition (LMI) test, made with the blood of mice immunized with tularemia vaccine, has been revealed . The possibility and expediency of using the LMI test for evaluating the effectiveness of the stimulators of the nonspecific anti-infective resistance of the body has been shown.

Pediatrics, 1986 Jul, 78(1), 113 - 4
Seat restraint contamination and cleaning; Paulson JA; This study was undertaken to demonstrate that seat restraints are unlikely vehicles for the transmission of pathogenic bacteria from infant to infant in seat restraint loaner programs . Simple surface cleaning with antibacterial solutions is sufficient to prepare seats for reloaning.

Ann Intern Med, 1986 Jul, 105(1), 67 - 81
Mitoxantrone: a new anticancer drug with significant clinical activity; Shenkenberg TD et al.; Clinical studies using mitoxantrone, an anthraquinone, were begun in the United States in 1979 . Subsequent phase II and III trials have shown that mitoxantrone has significant clinical activity in patients with breast cancer, acute leukemia, and lymphoma . The drug has antiviral, antibacterial, antiprotozoal, immunomodulating, and antineoplastic properties and is mutagenic in some animal systems . Its mechanism of action seems to involve both DNA intercalation and nonintercalative electrostatic interactions . The dose-limiting toxicity is myelosuppression when the drug is given on a single-dose, every-3-week schedule and mucositis when it is given daily for 5 days . Other toxicities include gastrointestinal and cardiac effects, the gastrointestinal toxicity being less severe and less frequent than that with the anthracycline anticancer drugs . Because of its low incidence of serious toxicities and effectiveness in treating certain solid tumors and leukemias, mitoxantrone is a promising new agent in the treatment of cancer.

Jpn J Antibiot, 1986 Jul, 39(7), 1947 - 59
{Effect of imipenem/cilastatin sodium in thirty cases of bone and joint infection}; Sakurai M; Thirty cases of bone and joint infections were treated by a chemotherapy with imipenem/cilastatin sodium (MK-0787/MK-0791) . An overall curative rate was 87% . It was 96% in cases of acute inflammatory state and 50% in cases of chronic state . Thirteen cases received surgical intervention with chemotherapy and showed complete healing, but curative rate of 16 cases without surgery was 76% . Twenty strains of microorganisms were isolated and identified from these patients . The MIC of MK-0787 against S . aureus was as small as less than or equal to 0.012 to 0.024 micrograms/ml to a 10(6)/ml suspension . Thus antibacterial action of MK-0787 was very strong . The MIC against E . coli was 0.20 micrograms/ml . Incidence of adverse reactions was small as only in two cases occurred slight nausea . Laboratory examinations of blood, liver and kidney function found no influence of the drug.

Rev Infect Dis, 1986 Jul-Aug, 8 Suppl 3, S260 - 78
Penicillin-binding proteins and the antibacterial effectiveness of beta-lactam antibiotics; Tomasz A; It is currently believed that both the antibacterial potency and the nature of the antibacterial effects of beta-lactam antibiotics are ultimately dependent on the inhibition (acylation) of one or more of the bacterial penicillin-binding proteins (PBPs) . Nevertheless, bacterial factors (e.g., autolysins) that do not directly react with the antibiotic molecule also profoundly influence the fate (inhibition of growth or lysis) of the antibiotic-treated bacterial cell . The quantitative relationship between the minimal inhibitory concentration of a beta-lactam antibiotic and its reactivity with certain PBPs is not well understood . Also poorly understood is the mechanism by which inhibition of PBP function causes triggering of suicidal autolytic activity . Much remains to be done before the structural basis of the highly selective PBP affinities observed with some beta-lactam antibiotics is understood . A new form of antibiotic resistance involving mutational alteration of PBPs (in the direction of lower antibiotic affinity) has emerged among clinical isolates of most of the major human pathogens.

J Antimicrob Chemother, 1986 Jul, 18(1), 9 - 15
Membrane-disorganizing property of polymyxin B nonapeptide; Lam C et al.; The possibility of improving the antibacterial activities of drugs normally excluded by Gram-negative bacteria with polymyxin B nonapeptide (PMBN) has been explored . In vitro, PMBN rendered clindamycin, erythromycin, novobiocin, rifampicin and vancomycin very active against a number of Gram-negative enteric bacteria . The drug also sensitized the previously resistant bacterial strains to human, mouse or guinea pig serum . However, parenterally administered PMBN failed to influence bacterial growth in chambers implanted into mice and guinea pigs . It was also ineffective in experimental septicaemia at a dose of up to 200 mg/kg or when combined with antibiotics with which it interacted synergistically in vitro.

J Antibiot (Tokyo), 1986 Jul, 39(7), 943 - 55
In vitro evaluation of SF-2103A, a novel carbapenem antibiotic, as a beta-lactamase inhibitor; Niwa T et al.; SF-2103A, a new carbapenem antibiotic, exhibited a broad antibacterial spectrum and a potent inhibitory activity against a wide range of beta-lactamases, in particular, against cephalosporinases, with lower I50 values than those displayed by sulbactam and clavulanic acid . Using a fixed combination and checkerboard titration, in vitro synergy against the majority of the beta-lactamase-producing strains tested was demonstrated between SF-2103A and various beta-lactam antibiotics, especially cefotaxime, ceftizoxime, and cefoperazone . The synergistic effect of SF-2103A was more pronounced than that of sulbactam . The in vitro synergy was also confirmed by bactericidal and bacteriolytic activities and morphological effects.

Antimicrob Agents Chemother, 1986 Jul, 30(1), 152 - 6
Pharmacokinetics of single-dose oral ciprofloxacin in patients undergoing chronic ambulatory peritoneal dialysis; Shalit I et al.; The prevention and treatment of peritonitis in patients undergoing peritoneal dialysis is often complicated by several factors, including nephrotoxicity, requirement for hospitalization, parenteral antibiotic therapy, and infection caused by resistant microorganisms . Ciprofloxacin, a new carboxyquinolone derivative, may offer the advantages of oral administration, a broad spectrum of antibacterial activity, and safety for the management of these patients . The pharmacokinetics of ciprofloxacin in serum and peritoneal fluid of eight adult patients undergoing chronic ambulatory peritoneal dialysis (CAPD) were investigated . Each patient ingested a single 750-mg dose of ciprofloxacin, and drug concentrations were measured by high-pressure liquid chromatography in serum and peritoneal fluid for 48 h after the dose . Serum concentrations reached a mean peak of 3.6 micrograms/ml 1 to 2 h after the oral dose . The mean terminal serum half-life was 16.8 h, and the mean peritoneal fluid/serum concentration ratio was 0.64 . The mean peak ciprofloxacin concentration in peritoneal fluid was 1.3 micrograms/ml, and the bioactivity of the drug in peritoneal fluid was confirmed . These data indicated that therapeutic concentrations of ciprofloxacin against bacterial pathogens commonly associated with peritonitis in CAPD patients may be achievable in the peritoneal fluid after oral administration to patients undergoing CAPD . In addition, the pharmacokinetic data provide guidelines for further clinical studies of oral ciprofloxacin in CAPD patients.

Zh Mikrobiol Epidemiol Immunobiol, 1986 Jul, (7), 106 - 8
{Dynamics of change in the antibacterial activity of mouse peritoneal cells during the development of experimental influenzal infection}; Teiber EL et al.; The method of the radiometric determination of the antibacterial activity of peritoneal cells in the process of the development of viral infection has been approved . The genetically determined specific level of the antibacterial activity of these cells in different strains of mice has been established . The development of the lethal form of experimental influenza A in mice has been shown to be accompanied by the mobilization of nonspecific protective factors, including the system of interferons and the antibacterial activity of peritoneal cells . The latter factor is, seemingly, insufficient for ensuring the necessary level of protection in the animals, whose death occurs at a shorter time than that necessary for the development of specific immune response.

Am J Med, 1986 Jun 30, 80(6B), 2 - 14
Aminoglycoside antibiotics in infectious diseases . An overview; Siegenthaler WE et al.; This article presents an overview of the aminoglycoside antibiotics used in clinical practice . Facts concerning the discovery and properties of the aminoglycosides are followed by information about spectrums of activity and mechanisms of action and resistance . Individual compounds are compared and proposals on the possibilities for their clinical use, both as single drugs and in combination with beta-lactam antibiotics, are made . The importance placed on measuring the serum concentrations of aminoglycoside antibiotics should serve as a remainder that this procedure is important, on one hand, to increase clinical efficacy and, on the other, to reduce the side effects of these antibiotics . Finally, the aminoglycosides are compared briefly with other antibacterial compounds, some of which are very new . There is no doubt that in the future the aminoglycosides will continue to occupy an important place in the treatment of severe infections, although newly developed agents appear to be effective complements.

J Biol Chem, 1986 Jun 15, 261(17), 7879 - 87
Reactions of Escherichia coli TEM beta-lactamase with cephalothin and with C10-dipeptidyl cephalosporin esters; Mobashery S et al.; Two novel C10-(dipeptidyl)cephalosporin esters (3-(beta-chloro-L-alanyl-beta-chloro-L-alanyloxymethyl)-7 beta-(2-thienylacetamido)-3-cephem-4-carboxylic acid (7) and sodium 3-(L-alanyl-L-alanyloxymethyl)-7 beta-(2-thienylacetamido)-3-cephem-4-carboxylate, toluene-sulfonic acid salt (18} were synthesized, and their reactions with Escherichia coli TEM beta-lactamase were examined . Kinetic parameters determined for the enzymatic reactions of 7 (Km = 0.32 mM; Vmax = 338 mumol min-1 (mg protein)-1) and of 18 (Km = 0.33 mM, Vmax = 338 mumol min-1 (mg protein)-1) demonstrate that both of the peptidyl esters are good substrates for the lactamase . In fact, the Vmax rates for 7 and 18 are each more than 4-fold greater than that obtained for cephalothin, 1 (Vmax = 78 mumol min-1 (mg protein)-1), a well characterized substrate for the lactamases . Analysis of the enzymatic reactions by high field (500 MHz) 1H NMR revealed similar patterns for fragmentation of the cephem nucleus of 1, 7, and 18 . However, while hydrolysis of 1 produces acetate, cleavage of 7 and 18 releases beta Cl-LAla-beta Cl-LAla and LAla-LAla, respectively, from the dipeptidyl cephalosporin esters . Based on these findings, a strategy for co-opting the beta-lactamases of Gram-negative bacteria for "delivery" of bactericidal agents is described, and an explanation for the previously reported (Mobashery, S., Lerner, S.A., and Johnston, M . (1986) J . Am . Chem . Soc . 108, 1685) antibacterial activity of 7 is offered.

J Biol Chem, 1986 Jun 5, 261(16), 7357 - 65
Primary structure of limulus anticoagulant anti-lipopolysaccharide factor; Aketagawa J et al.; A potent anticoagulant, anti-lipopolysaccharide (LPS) factor, found in limulus hemocytes inhibits the LPS-mediated activation of limulus coagulation cascade and shows an antibacterial action against R-types of Gram-negative bacteria (Morita, T., Ohtsubo, S., Nakamura, T., Tanaka, S., Iwanaga, S., Ohashi, K., and Niwa, M . (1985) J . Biochem . (Tokyo) 97, 1611-1620) . The complete amino acid sequence of this substance was determined by sequencing the peptides obtained by selective proteolytic cleavage . The NH2-terminal end of anti-LPS factor was pyroglutamic acid . Anti-LPS factor had two variant residues at position 36 and the COOH-terminal end, respectively . The following sequence was assigned to anti-LPS factor, and it was also confirmed by fast atom bombardment mass spectrometry . less than EGGIWTQLALALVKNLATLWQSGDFQFLGHE (formula; see text) Limulus anti-LPS factor consisted of a single chain of 102 residues with 2 half-cystines in disulfide linkage . Its NH2-terminal region up to 20 residues was highly hydrophobic, and positively charged residues were clustered mainly within the disulfide loop . By searching the homologous sequence in known protein sequences with that of anti-LPS factor, we found a structural homology between anti-LPS factor and alpha-lactalbumin/lysozyme family.

Vestn Khir Im I I Grek, 1986 Jun, 136(6), 20 - 4
{Experience in the treatment of acute purulent lactation mastitis}; Neimark II; An analysis of data of 228 patients with different pathomorphological forms of acute purulent lactation mastitis has shown that clinical manifestations of purulent mastitis are due to the pathomorphological form of the inflammation . Complex treatment of acute purulent lactation mastitis including the timely radical operations followed by antibacterial and detoxicating therapy and immunotherapy ensures recovery of the patients and maximal preservation of milk producing tissues . Selection of the magnitude of operation for purulent mastitis is made with regard for their form.

Burns Incl Therm Inj, 1986 Jun, 12(5), 307 - 11
Effect of Dazmegrel (UK-38,485) on immune function in a burned guinea-pig model; Wang SL et al.; We investigated the effects of Dazmegrel, a highly effective and selective thromboxane synthetase inhibitor, on the immune system in a bilateral 5 per cent total body surface area (TBSA) deep partial thickness scald in a guinea-pig model . The animals were randomized into two groups: one received Dazmegrel at 3.4 mg kg-1 day-1 by i.m . injection; the other received the same volume of saline . Cell-mediated immunity was evaluated by the response to the hapten dinitrofluorobenzene (DNFB), as measured by ear swelling in response to cutaneous application . The ear swelling of the Dazmegrel-treated group was 52.8 +/- 3.8 per cent, compared to 41.4 +/- 2.4 per cent for the control group (P less than 0.02) . Neutrophil bactericidal function was determined on post-burn day (PBD) 7 and opsonic function on both post-burns days 7 and 22 . The serum opsonic indices were nearly identical at both times, but the Dazmegrel-treated animals had a significantly improved neutrophil bactericidal index (1.15 +/- 0.05 v . 1.68 +/- 0.17, P less than 0.01) . Dazmegrel exerted a stimulating effect on the immune system in this burn model, improving neutrophil antibacterial function and cell-mediated immunity.

Am Surg, 1986 Jun, 52(6), 299 - 302
Candida species . Insignificant contaminant or pathogenic species; Rutledge R et al.; The pathogenicity of Candida species cultured from peritoneal fluid or from an intra-abdominal abscess is unknown . A review of cultures at NCMH from 1978 to 1983 showed that Candida species were cultured from the peritoneal fluid of 39 patients and from intra-abdominal abscesses in 24 patients . The average age was 49 (range 6 months to 102 years); there were 38 men and 25 women . None of the 39 patients with Candida species grown from the peritoneal fluid was treated with Amphotericin B and only 1 (2.6%) subsequently developed an abscess . This patient was treated by surgical drainage without Amphotericin B and recovered . Twenty-four patients had Candida cultured from an intra-abdominal abscess . Of these, 21 (87.5%) also grew other bacterial organisms . Twenty of these 24 patients were treated with surgical drainage and antibacterial antibiotics without Amphotericin B . Six (30%) died, but only one death was felt to be directly related to the Candida infection . The remaining four were treated with surgical drainage, appropriate antibacterial antibiotics, and Amphotericin B . Two of these four (50%) died; one of the two deaths was related to Candida infection . Candida species grown from the peritoneum were not related to later Candida infection . Treatment of patients with contamination of the peritoneum by Candida with Amphotericin B appears unnecessary and because of Amphotericin renal toxicity, may be potentially harmful . Patients with polymicrobial intra-abdominal abscesses that contain Candida species should be treated with surgical drainage and appropriate antibacterial antibiotics . The value of adding Amphotericin B therapy in patients with polymicrobial abscess containing Candida was not demonstrated in this study, and its role is unclear.

Infect Immun, 1986 Jun, 52(3), 650 - 6
Sensitization with Fusobacterium nucleatum targets antibody-dependent cellular cytotoxicity to mammalian cells; Lopatin DE et al.; Incubation of mammalian tumor cells with either soluble of insoluble fractions (10 to 100 micrograms/ml) of Fusobacterium nucleatum sensitizes them to the destructive activity of antibody-dependent cellular cytotoxicity (ADCC) effector cells in the presence of anti-F . nucleatum antisera . All three types of ADCC effector cells are capable of destroying F . nucleatum-sensitized target cells with varying degrees of effectiveness (lymphocytes much greater than monocytes greater than neutrophils) . Hyperimmune rabbit anti-F . nucleatum antisera were active at a dilution as high as 1/100,000 . Our studies indicated that F . nucleatum must be bound to the target cells since if either the effector cells are treated with F . nucleatum or F . nucleatum is directly to an ADCC reaction, there is no significant effect on cytotoxicity . The kinetics of F . nucleatum-targeted ADCC are identical to those of classical ADCC, suggesting a similar mechanism . The specificity of F . nucleatum-targeted ADCC was demonstrated by cold target inhibition studies and by showing that other antibacterial antisera were incapable of mediating the activity.

Plast Reconstr Surg, 1986 Jun, 77(6), 919 - 32
Capsular contracture: a prospective study of the effect of local antibacterial agents; Burkhardt BR et al.; In a prospective, random, double-blind, and concurrently controlled clinical study of 124 patients having augmentation mammaplasty, using multiple independent subjective judges as well as objective compressibility measurements, the use of a variety of local antibacterials in or around inflatable retromammary prosthetic implants reduced the early postoperative onset of class III to IV capsular contracture by sevenfold (85 percent) and the final incidence by more than half (50 percent) (p less than 0.01) . We believe this study provides the most unequivocal evidence to date that the cause of capsular contracture in retromammary augmentation is periprosthetic bacterial contamination . Irrigation with a 5 percent povidone-iodine (50 percent Betadine) solution was as effective as other techniques and is currently our procedure of choice.

Pediatr Clin North Am, 1986 Jun, 33(3), 481 - 501
Immunotherapy of neonatal septicemia; Yoder MC et al.; This chapter has reviewed the deficiencies in immune defense that place the neonate, particularly the premature infant, at increased risk of invasive bacterial disease . We also have reviewed the literature on the rationale for exchange transfusion, granulocyte transfusion, intravenous immunoglobulin, and fibronectin administration as immunotherapeutic agents in infected infants . There have been no randomized controlled trials of exchange transfusion, immunoglobulin, or fibronectin administration in human infants with infection . Granulocyte transfusion in the infected newborn infant has been studied in a controlled fashion, but the results of clinical trials are conflicting . Thus, all of these interventions appear to need further evaluation . We therefore recommend that in the septic newborn infant with neutropenia and an I/T ratio greater than or equal to 0.8, who fails to demonstrate a favorable response to conventional antibacterial chemotherapy and cardiopulmonary support, the administration of approximately 1 X 10(9) irradiated granulocytes per kg may be beneficial . In the absence of equipment to isolate the granulocytes, a double-volume exchange transfusion with fresh heparinized whole blood will provide a similar quantity of functional phagocytes.

J Clin Microbiol, 1986 Jun, 23(6), 1084 - 7
In vitro evaluation of combined usage of fosfomycin and 5-fluorouracil for selective isolation of Leptospira species; Oie S et al.; The combined usage of fosfomycin (FOM) and 5-fluorouracil (5-FU) as selective agents for the isolation of leptospires from contaminated materials was investigated . Additive or synergistic antibacterial activity was apparent with the combination compared with each agent used separately . Of 54 bacterial strains tested, 52 were inhibited, while all 5 Leptospira strains tested were unaffected by the combined addition of FOM (400 micrograms/ml) and 5-FU (100 micrograms/ml) to Korthof medium . Furthermore, this combination successfully supported the selective growth of Leptospira interrogans serovar copenhageni in experimentally contaminated specimens . This FOM-5-FU combination is surmised to be useful for the selective isolation of leptospires from contaminated clinical, pathological, or environmental materials.

Pathol Biol (Paris), 1986 Jun, 34(5 Pt 2), 549 - 53
{Contribution of potentiometry in the presence of lipoic acid to the study and evaluation of the in vitro antibacterial effects of betalactams}; Junter GA; We used potentiometry to assess the reduction of lipoic acid by a culture of Escherichia coli incubated with a beta-lactam . Two significant chronometric parameters were determined: one evaluates the antibiotic's killing effect, while the other reflects the stimulative effect exerted by the drug on cell reductive activity . For different beta-lactams, we did a quantitative study of the relationship between the concentrations of the antibiotic and each of the two potentiometric parameters . On the basis of our results we classified the different beta-lactams according to the degree of their killing and stimulative effects . Our study shows that potentiometry can provide original quantitative information on the in vitro antibacterial effect of beta-lactams.

J Med Chem, 1986 Jun, 29(6), 1023 - 30
The lysine pathway as a target for a new genera of synthetic antibacterial antibiotics?
Girodeau JM, Agouridas C, Masson M, Pineau R, Le Goffic F.
Unsaturated analogues of diaminopimelic acid have been synthesized . The amino acids were designed so that they would be reversible or irreversible inhibitors of both of the two last enzymes of the lysine pathway . The compounds were tested with meso-diaminopimelate decarboxylase . trans-3,4-Didehydrodiaminopimelic acid (2) was found to be the most potent inhibitor . The antibacterial activities did not correlate with enzyme inhibiting activities . 4-Methylenediaminopimelic acid 4 showed strong antibacterial properties . It is suggested that L,L-diaminopimelate epimerase could be the target enzyme.

Antibiot Med Biotekhnol, 1986 Jun, 31(6), 437 - 9
{Formulation of the composition of a polymyxin ointment using a mathematical experimental design}; Oganesian NR et al.; Mathematical design of the experiment permitted detection of the action of independent factors of the component composition on antibacterial activity and rheological properties of polymyxin ointment . Optimal compositions of polymyxin ointment based on polyethylene oxide emulsion were scientifically grounded and recommended for further experimental investigation on animals.

Ann Trop Paediatr, 1986 Jun, 6(2), 129 - 33
Drug prescribing in paediatrics at a teaching hospital serving a developing community; Summers RS et al.; Drug prescribing for paediatric inpatients at a teaching hospital serving a developing community was investigated . A list of 695 patient record numbers was randomly generated from the 7637 children admitted over the period examined (9.1%) . Prescribed drugs were computer-categorized and counted . Antibacterials (30.0%), vitamins, iron preparations and dietary supplements (20.0%), electrolytes (18.8%), analgesics (12.2%) and respiratory drugs (7.1%) comprised the most frequently-prescribed groups . The main (admitting) diagnoses of the sample were also classified . Infective diseases (42.0%), respiratory conditions (18.2%), perinatal disorders (14.9%) and nutritional deficiencies (9.9%) predominated . Data for individual drugs in the four dominant drug groups are presented . The margins between the top one or two drugs and the others in each therapeutic category are notable . Few drugs are extensively used . They include ampicillin, paracetamol, multivitamin syrup and Darrow's preparations . The implications of this picture in therapeutics are discussed.

J Environ Pathol Toxicol Oncol, 1986 May-Aug, 6(5-6), 109 - 25
Degeneration of the rat and canine adrenal cortex caused by alpha- (1,4-dioxido-3-methylquinoxalin-2-yl) -N-methylnitrone (DMNM); Yarrington JT et al.; The antibacterial drug alpha- (1,4-dioxido-3-methylquinoxalin-2-yl)-N-methylnitrone (DMNM) given at a dose of 22.5 mg/kg/bid to 4 dogs for 14 days caused diminished adrenal cortical reserves as determined by decreased plasma corticol (3 dogs) and lower aldosterone levels (4 dogs) following the intravenous infusion of ACTH . A dose of 100 mg/kg/day of DMNM administered to rats for 31 or 35 days resulted in significant decreases in blood glucose . Histologically, the adrenal glands of both species treated with DMNM for a maximum period of 21 days (dogs) and 35 days (rats) had widespread granular and vacuolar degeneration of the cortex . The degeneration, as demonstrated in treated rats, began in the zona reticularis and inner regions of the zona fasciculata and eventually involved the entire cortex including the zona glomerulosa . As a result of treatment, significant ultrastructural alterations within cells of the rat and canine adrenal cortex consisted of degeneration of the mitochondria and an increase in the numbers and lipolysis of lipid droplets . The ultrastructure of the zona reticularis and fasciculata was most severely affected.

Arzneimittelforschung, 1986 May, 36(5), 790 - 3
Synthesis of some new hydrazone derivatives as biologically active agents; Sen Gupta AK et al.; A series of {4-(6H/bromo-4-oxo-2-phenyl-3(4H)-quinazolinyl)phenoxy}acetic acid (1,2-dihydro-1-H/methyl-2-oxo-3H-indol-3-ylidene)hydrazides (VII1-16) were synthesised by condensing 1-H/methyl-5-substituted indoline-2,3-diones with {4-(6H/bromo-4-oxo-2-phenyl-3(4H)-quinazolinyl) phenoxy}acetic acid hydrazides (IV1-2) which in turn were obtained by reacting ethyl {4-(6H/bromo-4-oxo-2-phenyl-3(4H)-quinazolinyl)phenoxy}acetates (III1-2) with hydrazine hydrate . All the synthesised compounds (VIII1-16) were screened for their antibacterial, acetylcholinesterase enzyme inhibitory and antiviral activities.

J Med Chem, 1986 May, 29(5), 611 - 4
Aminoglycoside antibiotics . 6 . Chemical reactions of aminoglycosides with disodium carbenicillin; Iyengar BS et al.; Aminoglycoside antibiotics including kanamycin A, tobramycin, and the gentamicin C complex reacted with 1 mol of disodium carbenicillin to give products derived from acylation of their amino groups by the beta-lactam function of the carbenicillin . Amikacin was acylated by two carbenicillin units . Chromatographic analysis of fragments from the acid hydrolysis of these derivatives showed that the preferred site of acylation was in the 2-deoxystreptamine unit of the aminoglycosides . The two sites of acylation in amikacin were the 6'-amino group and the amino group in the aminohydroxybutyryl substituent . The derivatives had almost no antibacterial activity, and they were not toxic.

Pathol Biol (Paris), 1986 May, 34(5), 508 - 11
{Lymphatic and lymph node diffusion of ceftriaxone . Incidence in the treatment of typhoid fever}; Auvergnat JC et al.; Following intravenous administration of 2 g ceftriaxone, concentrations of the drug were assayed in serum, in thoracic duct lymph from dogs, and in mesenteric lymph nodes in patients . Antibacterial activity of lymph against S . typhi was also studied . Results show that ceftriaxone concentrations in serum and lymph are comparable; with a satisfactory antibacterial activity of both fluids against S . typhi . In mesenteric lymph nodes, mean ceftriaxone concentration was approximately 1000 times the MIC for S . typhi . Our data contribute to explain the successful clinical results achieved with ceftriaxone in patients with typhoid fever.

Rev Infect Dis, 1986 May-Jun, 8(3), 309 - 21
Fungal peritonitis in patients receiving peritoneal dialysis: experience with 11 patients and review of the literature; Eisenberg ES et al.; Despite progress in decreasing the incidence of and improving the therapy for bacterial peritonitis in patients receiving peritoneal dialysis, fungal peritonitis has emerged as a relatively common infection . Hospitalization, recent prior episodes of peritonitis, and antibacterial therapy appear to predispose patients to this infection . Clinically, fungal peritonitis cannot be differentiated from bacterial peritonitis except by gram stain and culture of the dialysate . The most commonly made serious error is the failure to initiate appropriate therapy quickly enough on the basis of these diagnostic parameters . For patients who no longer require dialysis, those for whom a change to hemodialysis is preferred, and those with concomitant life-threatening illness, the recommended therapy for fungal peritonitis is removal of the dialysis catheter and the institution of therapy with systemic antifungal agents . For patients who are hemodynamically and metabolically stable and for whom continued peritoneal dialysis is desirable, a trial of antifungal chemotherapy before removal of the catheter may be indicated.

Am J Otol, 1986 May, 7(3), 214 - 7
Preservation of otologic homografts; Sataloff RT et al.; Techniques for preservation of homografts for replacement of tympanic membranes, ossicles, closure of the oval window, and canalplasty remain controversial . Review of 300 articles reveals no evidence opposing the harvesting of grafts from living patients or cadavers, or the prolonged storage of these materials in antibacterial solutions . It appears to be important to store the grafting material long enough to reduce antigenicity . Numerous techniques and materials are being used with success . Additional research on antigens, histologic fate of grafts, long-term success, and complications is essential to determine ideal grafting materials, preservatives, and techniques.

Pediatr Infect Dis, 1986 May-Jun, 5(3 Suppl), S171 - 5
Intravenous immunoglobulin in the treatment of neonatal sepsis: therapeutic strategies and laboratory studies; Fischer GW et al.; IGIV appears to have a promising future in treating and perhaps preventing neonatal bacterial infections . However, all IGIV lots do not contain equal amounts of pathogen-specific IgG with functional opsonic activity . To ensure effective therapy it will be important to inform physicians that the IGIV lots available for use contain functional antibacterial antibody to the responsible pathogens . To optimize therapy IGIV may need to be given early in the infection and doses may need to be repeated if pathogen-specific antibody is rapidly depleted . Further, clinical studies will be necessary to determine if IGIV will be a valuable adjunct to antibiotic therapy in neonatal GBS infections.

Z Gerontol, 1986 May-Jun, 19(3), 158 - 61
Relationship between immunoglobulin levels and specific antibody titers in the elderly; Rajczy K et al.; A population of 228 healthy elderly subjects was studied for immunoglobulin levels, titers of antibacterial antibodies and the prevalence of auto-antibodies, to determine the possible associations between these humoral parameters and age . Serum levels of IgG and especially IgA and the incidence of auto-antibodies (antinuclear antibody and rheumatoid factor) were increased in aged subjects . Some differences were found between males and females . The levels of IgA and natural antibodies were significantly higher in males: the changes of prevalence of auto-antibodies with age were different in males and females; furthermore the correlation between the level of IgG and that of natural antibodies was significant in males . There was a slight positive relationship between the prevalence of auto-antibodies and the level of natural antibodies.

J Med Chem, 1986 May, 29(5), 665 - 70
Inhibitors of dihydropteroate synthase: substituent effects in the side-chain aromatic ring of 6-{{3-(aryloxy)propyl}amino}-5-nitrosoisocytosines and synthesis and inhibitory potency of bridged 5-nitrosoisocytosine-p-aminobenzoic acid analogues; Lever OW Jr et al.; We previously reported that 6-(methylamino)-5-nitrosoisocytosine (5) is a potent inhibitor (I50 = 1.6 microM) of Escherichia coli dihydropteroate synthase . It was noted that 6-amino substituents larger than methyl were detrimental to binding, although the adverse steric effect could be overcome by a positive ancillary binding contribution of a phenyl ring attached at the terminus of certain 6-alkylamino substituents . We selected the 6-{{3-(aryloxy)propyl}amino}-5-nitrosoisocytosine structure as a parent system and explored the effects of aromatic substituents on synthase inhibition . The nature of the aryl substitution influences binding, as shown by a 30-fold range of inhibitory potencies observed for the 15 aryl analogues (I50 values = 0.6-18 microM), although there is no apparent correlation between synthase inhibition and the electronic or hydrophobic characteristics of the aryl substituents . To explore the possibility that the aryl ring of these inhibitors might interact with the synthase binding site for the substrate p-aminobenzoic acid (PABA), three compounds were synthesized in which a PABA analogue is bridged to the nitrosoisocytosine moiety by linkage to an amino group at C-6 of the isocytosine . The bridged analogues significantly inhibited the synthase (I50 values = 2.5-8.9 microM) but were of unexceptional potency compared with other members of the (aryloxy)propyl series . Structure-activity considerations and inhibition kinetics did not support the PABA binding site as the synthase region that interacts with the aryl ring of these inhibitors . Despite the potent synthase inhibition exhibited by many of the nitrosoisocytosines studied, none of the 18 new analogues showed significant antibacterial activity.

Farmaco {Sci}, 1986 May, 41(5), 366 - 80
{Antibacterial and antifungal agents . VI . Pirfloxacin and related compounds: synthetic and microbiological studies}; Artico M et al.; A new route to pirfloxacin, a fluorinated pyrrylquinolone with high broad-spectrum antibacterial activities, is described starting from 7-amino-1-ethyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid and 2,5-dimethoxytetrahydrofuran . When the reaction with the latter compound was carried out using the ethyl ester of the above acid the related pyrryl ester formed, which on alkaline hydrolysis gave pirfloxacin . The synthesis and antibacterial activities of the 1-allyl analogue of pirfloxacin and of 7-{2-(1-pyrrolidinomethyl)-1-pyrryl}-1-ethyl-1, 4-dihydro-4-oxoquinoline-3-carboxylic acid and its 6-fluoroderivative are also reported.

FEBS Lett, 1986 Apr 7, 199(1), 61 - 7
Crystallographic investigation of the cooperative interaction between trimethoprim, reduced cofactor and dihydrofolate reductase; Champness JN et al.; The structure of the complex between E . coli (RT500) form I dihydrofolate reductase, the antibacterial trimethoprim and NADPH has been determined by X-ray crystallography . The inhibitor and cofactor are in mutual contact . A flexible chain segment which includes Met 20 is in contact with the inhibitor in the presence of NADPH, but more distant in its absence . By contrast, the inhibitor conformation is little changed with NADPH present . We discuss these observations with regard to the mutually cooperative binding of these ligands to the protein, and to the associated enhancement of inhibitory selectivity shown by trimethoprim for bacterial as opposed to vertebrate enzyme.

Antibiot Med Biotekhnol, 1986 Apr, 31(4), 291 - 4
{Comparative sensitivity of clinical strains of gram-positive and gram-negative microorganisms to antibacterial antibiotics}; Nekhorosheva AG et al.; Two hundred and thirty five microbial strains isolated from patients with different infections such as chronic nonspecific diseases of the lungs, diseases of the biliary tract, chronic pyelonephritis, osteomyelitis, peritonitis and soft tissue infections were tested for their sensitivity to 15 antibacterial antibiotics . Wide variability of the sensitivity of the isolates to the antibiotics, i.e . 0.24-0.5 to at least 128 micrograms/ml was observed . The gram-positive and gram-negative isolates were highly sensitive to the aminoglycoside antibiotics and first of all to tobramycin and sisomicin . Both the antibiotics preserved their pronounced activity against P . aeruginosa.

J Antibiot (Tokyo), 1986 Apr, 39(4), 487 - 93
Novel antibiotics napyradiomycins . Production, isolation, physico-chemical properties and biological activity; Shiomi K et al.; Novel antibacterial antibiotics napyradiomycins A, B1, B2, B3, C1 and C2 have been isolated from the culture broth of Chainia rubra MG802-AF1 . In this paper, taxonomy of the producer, and production, isolation, physico-chemical properties and biological activities of napyradiomycins are reported . They contain the naphtopyran chromophore and halogens, and inhibit the growth of Gram-positive bacteria including drug-resistant strains.

Chemioterapia, 1986 Apr, 5(2), 101 - 4
Inhibitory and bactericidal activity of cefmetazole and seven other beta-lactams against different bacterial inocula; Esposito S et al.; The determination of the minimal inhibitory concentrations (MICs) at different bacterial inocula represents an important factor in determining the potential effectiveness of new antibiotics . MICs at different inocula (10(5) and 10(7) CFU/ml) and minimal bactericidal concentrations (MBC) of cefmetazole and seven other new cephalosporins (ceftazidime, ceftizoxime, cefamandole, ceftriaxone, cefotaxime, cefuroxime, cefoxitin) were determined by a miniaturized dilution broth method against a wide range of gram-positive, gram-negative and non-fermentative bacteria . The results of the present investigation confirm that all the beta-lactams under examination including cefmetazole exert a good or satisfactory antibacterial activity against gram-positive and gram-negative bacteria; and that only ceftazidime possesses antipseudomonas activity . MBCs and MICs at heavy inoculum are two times higher than MICs at light inoculum . These results could explain the spread by different mechanisms of bacteria resistant to beta-lactam antibiotics.

Z Hautkr, 1986 Apr 1, 61(7), 487 - 9
{How do I treat acne and rosacea?}; Bocker KH; Regarding treatment of acne vulgaris and rosacea, there is not much difference between hospital and practice nor among practicing dermatologists . Most of the assistants performing the important physical-manual treatment have had the same training . After analytical conversation and etiologic as well as diagnostic classification, the patients undergo the following manual treatment: cleansing, astringing, removing of comedones, massage, face pack, and covering with tinted emulsion . At home, acne: cleansing, massage, skin lotion, vitamin A acid, benzoylperoxide, antibacterial therapy; in serious male cases of acne conglobata, Roaccutan . Rosacea: antiseptic (antibiotic) treatment (topically and systemically), metronidazole (Arilin); in serious male cases, Roaccutan.

Antibiot Med Biotekhnol, 1986 Apr, 31(4), 294 - 7
{Effect of terrilytin on tissue bacteriostatic activity in the chemotherapy of renal and female genital tuberculosis in an experiment}; Iagafarova RK et al.; The effect of terrilytin on the bacteriostatic activity of the tissues (BAT) under conditions of antibacterial therapy was studied on experimental models of tuberculosis of the kidneys and female genitalia in 46 rabbits . It was shown statistically that terrilytin promoted an increase in the BAT and might be used as an agent increasing the effect of antibacterial therapy of tuberculosis . The level of the increase of the BAT depended on its initial level which was inversely proportional to the level of the lesions . At the same time the effect of terrilytin was directly proportional to the level of these lesions unfavourable for the drug penetration into the tissues and tuberculous foci . The results of the study are promising in increasing the efficacy of antibacterial therapy of extrapulmonary tuberculosis of the above localizations by the use of terrilytin.

Plast Reconstr Surg, 1986 Mar, 77(3), 455 - 9
Inhibitory effects of electrically activated silver material on cutaneous wound bacteria; Falcone AE et al.; Silver has had a widespread application in the care of burn wounds and chronic skin ulcers . The in vitro evaluation of unbound ionic silver is reported in this study . A comparison is made between silver-coated fabric alone and the fabric acting under direct electric current anodization . A variety of commonly found predominant skin pathogens were tested in this comparative study . Our studies confirm previous reports demonstrating an effective penetration of the silver ion and its local antibacterial action . Accurate measurements of the bacteria-free "clear zones" surrounding the electrically activated silver-coated fabric showed these to be significantly larger than those of the silver fabric without electric stimulation . This method affords another option in the use of silver for its antibacterial property, i.e., by iontophoresis . Its potential clinical use awaits further in vivo trials.

J Ethnopharmacol, 1986 Mar, 15(3), 231 - 59
Preliminary screening of far-eastern ethnomedicinal plants for antibacterial activity; Moskalenko SA; The results of antibacterial screening of 308 ethanol extracts from 250 wild far-eastern plants belonging to 77 families are reported . Antibacterial activity of plant extracts was tested in vitro by the filter-paper disc assay method . The plants screened were reported to be used by the population of the Soviet Far East against some bacterial infections . Activity against gram-positive as well as gram-negative groups of microorganisms was tested.

J Pharm Sci, 1986 Mar, 75(3), 304 - 6
Intramolecular nucleophilic amino attack in a monobactam: synthesis and stability of (2S,3S)- 3-{(2R)-2-amino-2-phenylacetamido}-2-methyl-4-oxo-1- azetidinesulfo nic acid; Indelicato JM et al.; The potentially orally bioavailable arylglycine-substituted monobactam, (2S,3S)- 3-{(2R)-2-amino-2-phenylacetamido}-2-methyl-4-oxo-1- azetidinesulfonic acid, was prepared as a crystalline solid . No significant antibacterial activity {i.e., MICs were greater than 128 (micrograms/mL)} was found when the monobactam was tested against Gram positive and Gram negative bacteria . Solution instability (greater than 2,000 times less stable than aztreonam) due to intramolecular nucleophilic amine attack on the beta-lactam is believed to be a contributing factor to the poor microbiological activity.

J Antibiot (Tokyo), 1986 Mar, 39(3), 404 - 14
Studies on beta-lactam antibiotics . XIII . Synthesis and structure-activity relationships of 7 beta-{(Z)-2-aryl-2-carboxymethoxyiminoacetamido}-3-vinylcepha losporins ; Kawabata K et al.; The synthesis, antibacterial activity and oral absorption of the 7 beta -{(Z)-2-aryl-2-carboxymethoxyiminoacetamido}-3- vinylcephalosporins are described . Of these cephalosporin derivatives, 7 beta-{(Z)-2-(2-amino-4-thiazolyl)-2-carboxymethoxyiminoacetamido}- 3-vinylcephalosporin exhibited the highest activity against Gram-negative bacteria and showed also good excretion after oral administration to rats . In addition, the effects on the antibacterial activity and oral absorption of the amino function on the thiazole ring are discussed.

J Antibiot (Tokyo), 1986 Mar, 39(3), 380 - 3
Synthesis and antibacterial activity of C-3' isothiazolyl and related cephalosporins; Skotnicki JS et al.; The synthesis of C-3' isothiazolyl and related cephalosporins is presented . The compounds exhibit activity against a variety of Gram-positive and Gram-negative organisms.

J Antibiot (Tokyo), 1986 Mar, 39(3), 372 - 9
Synthesis and antibacterial activity of novel aminothiazolyl beta-lactam derivatives; Skotnicki JS et al.; The synthesis and in vitro antibacterial profile of a series of (Z)-(2-amino-4-thiazolyl)-{(2,3-dialkoxypropoxy)imino}acetyl derivatives of 7-aminocephalosporanic acid and 3-aminomonobactamic acid are reported.

Int J Dermatol, 1986 Mar, 25(2), 103 - 5
Contact hypersensitivity to topical antibacterial agents; Bajaj AK et al.; Three hundred ninety patients with suspected contact dermatitis to topical medicaments were patch tested with various commercially available antibacterial agents to evaluate the incidence of contact hypersensitivity . The common sensitizers were nitrofurazone, neomycin, oxytetracycline, cetrimide, and framycetin . The least common sensitizers were sodium fusidate, chlorhexidine hydrochloride, and gentian violet . Cross-sensitivity was observed between neomycin, framycetin, and gentamicin.

Vestn Khir Im I I Grek, 1986 Mar, 136(3), 47 - 51
{Choosing a method of treating suppurative lactational mastitis}; Rodionov VV et al.; The abscessing form of lactation mastitis as well as subaureolar abscesses with small foci (not more than 3-4 cm) should be expediently treated by a puncture method . In large foci permanent drainage should be used . Limited foci (up to 1-1.5 quadrants) in phlegmonous-abscessing form of mastitis must be carefully dissected . Treatment by incisions is indicated in cases with infiltrative-abscessing form of mastitis . Local treatment must be supplemented by antibacterial and detoxication therapy and by the means enhancing the organism resistance.

Antimicrob Agents Chemother, 1986 Mar, 29(3), 426 - 31
Novobiocin antagonism of amastigotes of Trypanosoma cruzi growing in cell-free medium; Pate PG et al.; Inhibitors of the enzyme bacterial topoisomerase II (DNA gyrase) were evaluated for activity against Trypanosoma cruzi (Brazil strain), based on the theoretical need for a topoisomerase II in the replication of the kinetoplast DNA network . Novobiocin (500 micrograms/ml) antagonized amastigotes of T . cruzi growing in a cell-free medium at 37 degrees C, as manifested by inhibition of multiplication, abnormal morphology of Giemsa-stained organisms, and delayed or absent growth of cells upon subculturing in a drug-free medium . In contrast, novobiocin (1,000 micrograms/ml) essentially had no effect on the multiplication and motility of epimastigotes growing in a cell-free medium at 27 degrees C . This resistance of epimastigotes represented a difference in the physiology of this morphologic stage and not in the temperature of experimentation, because novobiocin inhibited multiplication of amastigotes at 27 degrees C as well and accelerated transformation to epimastigotes . With T . cruzi growing within cultured human fibroblasts, novobiocin (200 micrograms/ml) markedly inhibited transformation of intracellular amastigotes to trypomastigotes . Clorobiocin, a structural analog of novobiocin and likewise an inhibitor of the B subunit of bacterial topoisomerase II, was five times more potent on a molar basis than novobiocin was in antagonism of amastigotes growing in a cell-free medium and did not antagonize epimastigotes . Coumermycin A1, another analog of novobiocin, and five 4-quinolone antibacterial agents, antagonists of the A subunit of bacterial topoisomerase II, inhibited neither amastigotes nor epimastigotes . These experiments indicate that novobiocin and clorobiocin represent a new structural class of drugs with activity against T . cruzi . Whether the mechanism of action of these drugs involves antagonism of a T . cruzi topoisomerase II or an unrelated target is yet to be determined.

J Clin Microbiol, 1986 Mar, 23(3), 421 - 4
Tentative interpretive criteria for in vitro antibacterial susceptibility testing with imipenem; Shungu DL et al.; Imipenem is a member of a new class of highly potent beta-lactam antibiotics, carbapenems, with a very broad antibacterial spectrum . This study was undertaken to determine tentative interpretive criteria for in vitro susceptibility testing with 10-micrograms imipenem disks . A careful examination of the zone diameters and the corresponding MICs for 489 clinical isolates by regression-line analysis and the error rate-bounded classification scheme suggested the following guidelines: greater than or equal to 16 mm with an MIC correlate of less than or equal to 4 micrograms/ml for susceptible, 14 to 15 mm (8 micrograms/ml) for moderately susceptible, and less than or equal to 13 mm (greater than or equal to 16 micrograms/ml) for resistant . Lack of cross-resistance between imipenem and broad-spectrum cephalosporins such as cefotaxime and ceftazidime argues against their use as class disks to predict in vitro susceptibility of bacterial species to carbapenems.

J Oral Pathol, 1986 Mar, 15(3), 125 - 31
Chemiluminescence in the assessment of polymorphonuclear leukocyte function in chronic inflammatory periodontal disease; Seymour GJ et al.; Polymorphonuclear neutrophils (PMN's) constitute the primary host resistance factor against infection . They are prominent cells in both the gingival tissue and gingival sulcus in most forms of periodontal disease . Although defective PMN function has been implicated in the pathogenesis of localized juvenile periodontitis (LJP) and rapidly progressive periodontitis (RPP), this may not necessarily be the case in adult periodontitis (AP) . A number of studies have failed to detect PMN dysfunction in AP . However, it may be that in this form of chronic inflammatory periodontal disease (CIPD) the defects in peripheral blood PMN function are subtle and the methods used may lack the necessary sensitivity . Chemiluminescence (CL) is the light energy produced by the PMN during its interaction with bacteria or other particles and has been demonstrated to correlate well with antibacterial integrity . Measurement of CL produced by phagocytically challenged PMN's may provide a very sensitive assay of the functional ability of these cells, and, hence, may be useful in assessing PMN activity in CIPD . Recent studies using PMN's obtained from periodontal diseased patients challenged with the periodontopathic organism Fusobacterium nucleatum have revealed an elevated CL response compared to non-diseased controls . These results are reviewed and areas for future research discussed.

J Med Chem, 1986 Mar, 29(3), 394 - 404
New structure-activity relationships of the quinolone antibacterials using the target enzyme . The development and application of a DNA gyrase assay; Domagala JM et al.; A series of 60 newly synthesized and known quinolone antibacterials, including quinoline- and 1,8-naphthyridine-3-carboxylic acids, pyrido{2,3-d}pyrimidine-6-carboxylic acids, and some monocyclic 4-pyridone-3-carboxylic acids, were tested and compared in a newly established, easy to perform, DNA gyrase assay . The results were correlated with minimum inhibitory concentrations (MICs) against a variety of organisms . Among the known quinolones were 14 clinically significant drugs (oxolinic acid, norfloxacin, ciprofloxacin, enoxacin, etc.) which were used as standards and compared side-by-side . The study focused on the changes in DNA gyrase inhibition brought about by certain features of the molecules, namely, the C6-fluorine or the nature of the C7 substituent . The intrinsic gyrase inhibition of the fused parent rings, quinoline vs . naphthyridine vs . pyrido{2,3-d}pyrimidine, was also explored . In all cases, loss of enzyme inhibition produced poor MICs, but some compounds with good DNA gyrase inhibition did not correspondingly inhibit bacterial growth . Possible explanations for this phenomena and the benefits of a DNA gyrase-MIC strategy for developing future structure-activity relationships are discussed.

Pharm Weekbl Sci, 1986 Feb 21, 8(1), 42 - 5
The effect of the 4-quinolone enoxacin on plasma theophylline concentrations; Wijnands WJ et al.; In patients treated concomitantly with theophylline and enoxacin, a broad spectrum antibacterial agent for oral administration, unexpectedly high plasma theophylline concentrations were observed . In six patients receiving intravenous aminophylline under controlled conditions, enoxacin was started in a daily dose of 800 or 1200 mg . Plasma theophylline concentrations increased from 8.4 +/- 2.4 mg/l to 15.0 +/- 5.1 mg/l at day 3 of co-administration . Total body clearance of theophylline decreased significantly, whereas renal clearance and protein binding did not change . When enoxacin, 800 mg daily, was administered to seven patients with a stable chronic obstructive pulmonary disease, who were on long-term theophylline treatment a significant increase in plasma theophylline concentrations occurred as well: elimination half-life was prolonged . It is concluded that the rise of plasma theophylline concentrations is caused by a reduced metabolic clearance of theophylline . If concomitant use of both drugs is necessary, monitoring of plasma theophylline concentration and adjustment of the theophylline dose is recommended, to avoid toxicity.

J Antibiot (Tokyo), 1986 Feb, 39(2), 215 - 29
Studies on monocyclic beta-lactam antibiotics . V . Synthesis and antibacterial activity of 3-{2-(2-aminothiazol-4-yl)-(Z)-2-(O-substituted oxyimino)-acetamido}-1-(1H-tetrazol-5-yl)-2-azetidinones having various functional groups at C-4 position of beta-lactam; Yoshida C et al.; The synthesis and antibacterial activity of the 3-{2-(2-aminothiazol-4-yl)-(Z)-2-(O-substituted oxyimino)acetamido}-1-(1H-tetrazol-5-yl)-2-azetidinones++ + having various functional groups at C-4 position of beta-lactam are described . These compounds exhibited a strong activity against a variety of Gram-negative bacteria including beta-lactamase-producing strains . Among various C-4 substituents explored, the fluoromethyl and carbamoyloxymethyl moiety were found to increase the activity.

J Antimicrob Chemother, 1986 Feb, 17(2), 227 - 37
Kinetics and bactericidal effect of gentamicin and latamoxef (moxalactam) in experimental Escherichia coli endocarditis; Contrepois A et al.; The pharmacokinetics of gentamicin and latamoxef (moxalactam) were examined in serum, normal heart valves, sterile cardiac vegetations and vegetations infected with Escherichia coli . Penetration of antibiotics into heart valves and vegetations was rapid; the maximum concentration was achieved in both sites at the end of a 20 min iv infusion . However, both antibiotics penetrated better into vegetations than into normal heart valves . In rabbits with left-sided endocarditis, similar antibiotic levels were found in infected vegetations after one or 22 im injections . After 11 im injections (one every 8 h) of latamoxef (15 mg/kg) the bacterial titre (cfu/g) was significantly reduced, but not nil, despite concentrations about 40 times the MBC for this antibiotic in the vegetations . Afer 22 im injections, vegetations in rabbits receiving latamoxef were sterile and were significantly reduced in those receiving gentamicin (1.5 mg/kg/im), concentrations of which in the vegetations were inferior to the MBC . Our results suggest that the in-vivo antibacterial effect depends on local antibiotic levels, kinetics of killing and duration of contact between antibiotic and bacteria.

Tijdschr Diergeneeskd, 1986 Feb 1, 111(3), 115 - 8
{More than 10 years of kidney testing in the Netherlands, and now...?}; Engel HW et al.; A historical review of testing for antibacterial residues in slaughtered animals is presented . In recent developments, much attention was paid to microbiological methods . Because of changing views and new possibilities increasing attention is being paid to purely chemical methods of detection . However, so long as chemical multi-purpose methods are not available, there will be a need for microbiological methods . The common misunderstanding that prevention of residues of antibacterial compounds in slaughter animals will contribute to reduction of the problem of bacterial resistance to antibacterial agents, is warned against.

J Trauma, 1986 Feb, 26(2), 128 - 34
Microvascular reconstruction after electrical and deep thermal injury; Silverberg B et al.; Six cases are presented demonstrating uncomplicated primary healing following early microvascular reconstruction for complex electrical and deep thermal injuries . We advocate early preservation of eschar and the prevention of infection with the use of penetrating topical antibacterial agents, removal of the soft-tissue eschar when clinically indicated, and immediate coverage of the undebrided bone through the provision of well-vascularized tissue . Microvascular free tissue transfer should be considered as a primary method of reconstruction for complex electrical or thermal injury whenever clinically feasible . These reconstructive techniques offer an early, reliable means of definitive reconstruction, preserving function, providing uncomplicated healing, and promoting early rehabilitation.

Schweiz Med Wochenschr, 1986 Feb 1, 116(5), 142 - 5
{Exanthema during frequent use of antibiotics and antibacterial drugs (penicillin, especially aminopenicillin, cephalosporin and cotrimoxazole) as well as allopurinol . Results of The Berne Comprehensive Hospital Drug Monitoring Program}; Sonntag MR et al.; Of 19,653 patients hospitalized in the medical divisions of two teaching hospitals, 3980 were treated with an aminopenicillin, 808 with other penicillins, 427 with a cephalosporin, 2619 with cotrimoxazole and 846 with allopurinol . The first part of the study deals only with the incidence of exanthemas definitely or probably due to a specific drug on the basis of clinical considerations . The exanthema incidence is 8.0% for aminopenicillins, 4.7% for other penicillins, 1.9% for cephalosporins and 2.8% for cotrimoxazole . The second part of the study employs a cross-tabulation to determine the incidence of exanthemas definitely and probably drug-induced, and the temporal relationship of these reactions to aminopenicillin and allopurinol exposure . The observed risks of developing an exanthema are as follows: aminopenicillin without allopurinol 10.1%, aminopenicillin combined with allopurinol 7.2%, allopurinol without aminopenicillin 3.0%, neither of the two drugs 1.5% . The increased incidence of exanthemas observed by the Boston Collaborative Drug Surveillance Program (BCDSP) in patients concomitantly treated with aminopenicillin and allopurinol was not confirmed by our results . Our hypothesis is that the time of exposure to aminopenicillins might have been shorter for patients of the BCDSP who were not treated in connection with neoplastic disease and did not receive allopurinol . The incidence of aminopenicillin induced exanthemas increases severalfold with the duration of exposure time during the first 2-3 weeks . In the CHDMB, on the other hand, exposure time does not differ between the patients treated with aminopenicillin alone or in combination with allopurinol.

J Antibiot (Tokyo), 1986 Feb, 39(2), 281 - 5
Examination of model enzyme and penetration systems in relation to antibacterial activity; Boyd DB et al.; Recent work has shown that the activity of cephalosporins in inhibiting exocellular DD-peptidases from Streptomyces R61 and Actinomadura R39 are, at best, only poorly related to minimum inhibitory concentrations against pathogenic isolates . Taking into account the rate at which cephalosporins diffuse through porin channels, such as exist in certain Gram-negative organisms, does not help in establishing a relationship between MIC data and the kinetic data on the model enzymes . Most published cell wall permeability studies, the porin ones being a principal exception, have not examined long enough series of structurally related compounds to establish property-activity relationships.

Eur J Clin Microbiol, 1986 Feb, 5(1), 29 - 34
Factors influencing the activity of the trometamol salt of fosfomycin; Greenwood D et al.; The antibacterial activity of trometamol fosfomycin and its potentiation by glucose-6-phosphate were found to vary considerably in different culture media, although not all bacteria tested were equally affected . In general, the lowest MICs were obtained in the presence of glucose-6-phosphate in nutrient broth and Eugonbroth . The influence of inoculum size, pH and potentiation by glucose-6-phosphate were investigated by agar incorporation MIC titrations on nutrient agar . The activity of trometamol fosfomycin against many strains increased as the pH was lowered from 7.9 to 5.5 . Only 9% of the strains showed an inoculum effect when tested at pH 5.5 in the presence of glucose-6-phosphate compared with 37% of the strains tested at pH 7.1 and 22% of the strains tested at pH 7.9 . In the absence of glucose-6-phosphate, about 10% of the strains showed an inoculum effect at all three pH levels . The addition of glucose-6-phosphate to culture media seems reasonable for the testing of fosfomycin susceptibility.

J Antibiot (Tokyo), 1986 Feb, 39(2), 259 - 65
Biosynthesis of fluorothreonine and fluoroacetic acid by the thienamycin producer, Streptomyces cattleya; Sanada M et al.; An antimetabolite, THX, was isolated from fermentation broths of the thienamycin producer, Streptomyces cattleya, when the organism was grown in the presence of a fluorine-containing substrate . THX was subsequently identified as one of the four possible stereoisomers of 4-fluorothreonine . Inorganic fluoride or any one of a number of organofluorine compounds can be used as precursors of 4-fluorothreonine . In addition, 19F NMR has provided evidence that the organism synthesizes fluoroacetate under the same fermentation conditions . The in vitro antibacterial spectrum of 4-fluorothreonine is also presented.

Br Med J (Clin Res Ed), 1986 Jan 11, 292(6513), 81 - 3
Prospective survey of use of therapeutic drugs, alcohol, and cigarettes during pregnancy; Rubin PC et al.; Use of drugs during pregnancy was recorded prospectively in 2765 women attending the antenatal clinics of a general hospital from October 1982 to March 1984 . Of these women, 2588 (93.6%) avoided exposure to drugs during the first trimester, 1802 (65.2%) took no drugs at any stage, 963 (34.8%) took a total of 154 different drugs from 35 groups of drugs, and 243 (8.8%) took a self administered drug . The most commonly used drugs were non-narcotic analgesics, usually self administered, and antibacterials . The last survey of use of drugs in pregnancy in the United Kingdom 20 years ago showed fewer women avoiding drugs throughout pregnancy (195 of 911 (21.4%), p less than 0.001) and in taking a self administered drug (586 (64.4%), p less than 0.001) than at present . Most women nowadays abstain totally from alcohol (1786 (64.6%) v 109 (12.0%) previously, p less than 0.001), but while more women are non-smokers compared with previously (1811 (65.5%) v 392 (43%), p less than 0.001) the trend has been far less dramatic than that for use of alcohol.

J Antibiot (Tokyo), 1986 Jan, 39(1), 76 - 89
Studies on monocyclic beta-lactam antibiotics . III . Synthesis and antibacterial activity of N-(aromatic heterocyclic substituted)azetidin-2-ones; Yoshida C et al.; The relationship between structure and antibacterial activity among monocyclic beta-lactams having a pyridyl, pyrimidinyl, thiazolyl, imidazolyl, or a tetrazolyl group at N-1 position was investigated . N-(Tetrazol-5-yl)azetidin-2-ones were found to posses excellent activity.

J Antibiot (Tokyo), 1986 Jan, 39(1), 12 - 6
A new antitumor antibiotic, chromoxymycin . II . Production, isolation, characterization and antitumor activity; Hori Y et al.; Chromoxymycin is a new antitumor antibiotic produced by a new actinomycete named Streptomyces libani subsp . rubropurpureus No . 6362 . Chromoxymycin is active against P388 leukemia and B16 melanoma in mice, and has weak antibacterial activity against some Gram-positive bacteria.

J Antibiot (Tokyo), 1986 Jan, 39(1), 101 - 10
Studies on beta-lactam antibiotics . X . Synthesis and structure-activity relationships of 7 beta-{(Z)-2-(2-amino-4-thiazolyl)-2-(carboxymethoxyimino)acetamido} cephalosporin derivatives; Yamanaka H et al.; The synthesis of 7 beta-({Z) -2-(2-amino-4-thiazolyl)-2-(carboxymethoxyimino) acetamido}-cephalosporins (2a-h) modified at the C-3 position of a cephem nucleus and the effect of the C-3 substituents on the antibacterial activity, oral absorptivity and therapeutic activity are discussed . The cephems (2a and 2b) having a C-3 substituent such as hydrogen or vinyl were more potent than other cephalosporins against Gram-negative bacteria . However, the cephalosporin (2f) having methylthio group at the 3-position showed the highest absorption rate in rats . These three cephalosporins (2a, b and f) exhibited equally good protective activities in mice infected . Furthermore, the serum levels of these cephalosporins (2a, b and f) were examined in dogs, and 2b and 2f showed outstanding high and prolonged serum levels.

Antibiot Med Biotekhnol, 1986 Jan, 31(1), 43 - 9
{Antibiotic sensitivity of the causative agents of suppurative infections in cancer patients and its clinical significance}; Smolianskaia AZ; The poly-etiologic profile of cancer patients and poly-resistance of pathogens causing infections in them are the features defining disease-specific infectious complications . Such pathogens are isolated from both monocultures and associations depending on the infection localization . The taxonomic position of the pathogens defines the level of their poly-resistance . The etiologic structure of the infections and the pathogen sensitivity spectrum change in time . In this connection the choice of antibacterial drugs for treatment of infections in cancer patients should be grounded by the data on bacteriological assays of pathological specimens from individual patients or by the combined data on bacteriological assays of analogous pathological specimens from a group of similar patients.

Comp Biochem Physiol B, 1986, 83(1), 125 - 33
Antibacterial hemolymph proteins of Manduca sexta; Spies AG et al.; Exclusion column fractionated immune hemolymph of the M . sexta larva contains five peaks of anti-E . coli activity with molecular weights of greater than 140 kD and approximately 91, 54, 14 and 4 kD, plus one peak of lysozyme activity with a molecular weight of 17 kD . Purification of the 54 kD peak showed that this peak consists of the previously described M18 proteins which have monomeric weights of approximately 20 kD and had antibacterial activity against certain gram negative bacteria . Approximately 80% of the total hemolymph antibacterial activity was detected in the 14 and 4 kD peaks . These proteins, which kill both gram negative and gram positive bacteria, appeared to be directly analogous to the cecropins of H . cecropia . The greater than 140 and 91 kD peaks constituted only a minor part of the total antibacterial activity.

Ter Arkh, 1986, 58(10), 129 - 33
{Infectious endocarditis: its resistance to therapy, causative factors and means of combating it}; Butkevich OM et al.; Based on the data obtained during observation over 270 patients with infectious endocarditis the authors discuss factors that cause antibacterial therapy resistance encountered particularly often over the recent decade . Among the factors, the authors mark polyetiology of the disease over the recent years, "new" patterns of endocarditis in terms of the pathogenesis, predominance of primary endocarditis with highly virulent microorganisms, late disease diagnosis, inadequate antibacterial treatment, and so forth . Approaches to overcoming treatment resistance are also considered.

Dev Comp Immunol, 1986 Summer, 10(3), 311 - 30
Holothurian survival strategies: mechanisms for the maintenance of a bacteriostatic environment in the coelomic cavity of the sea cucumber, Parastichopus californicus; Dybas L et al.; The antibacterial responses of the coelomocytes and coelomic fluid of Parastichopus californicus to nine different species of marine bacteria were observed in vivo and in vitro . Five of the nine species of bacteria were cultured from P . californicus gut contents . Strong responses were directed against the bacterial species from the gut . Most bacteria agglutinated in coelomic fluid . Coelomocytes phagocytized and/or encapsulated the bacteria and showed a positive reaction for the lysosomal enzyme, acid phosphatase . Cell-free coelomic fluid exhibited less bactericidal activity against all of the marine species of bacteria than did complete coelomic fluid . Brown bodies, formed by coelomocytes surrounding foreign material, accumulated in the posterior region of the animal around the cloacal suspensors; these eventually were eliminated through a ringlet of ducts connecting the coelomic cavity with the external environment . Whole coelomic fluid inactivated endotoxin in vitro, but endotoxin did not initiate any detectable changes in the coelomocytes or coelomic fluid . Strong antibacterial response to the gut-associated bacterial species may well be essential to the survival of these animals, since during their seasonal visceral atrophy, gut-associated bacteria escape into the coelomic cavity.

J Int Med Res, 1986, 14(4), 205 - 9
Comparison of in vivo antibacterial activity of hydro-alcoholic solutions of hexamidine and of chlorhexidine; Michel G et al.; Samples of cutaneous flora were obtained from the antecubital fossa of 20 healthy volunteers before and after treatment with hydro-alcoholic solutions of chlorhexidine (CHX) and of hexamidine (HXM) . Percentage reductions in bacterial flora were statistically greater (p less than 0.001) after CHX (99 to 100%) than after HXM (about 70 to 90%) . Furthermore, CHX had a smaller disturbing effect upon the natural balance of the bacterial population than HXM with a more rapid return towards the initial proportions of the different organisms one hr after treatment.

J Antibiot (Tokyo), 1986 Jan, 39(1), 26 - 31
Isolation and structure of antibiotic U-68,204, a new thiolactone; Dolak LA et al.; A new thiolactone-containing antibiotic U-68,204 was found to be produced by a soil actinomycete identified as Streptomyces thiolactonus UC 8478 (NRRL 15,439) . The production, isolation, structure determination as well as the physical, spectroscopic and antibacterial properties of this C13H17NO3S compound are here reported . On the basis of these data, the antibiotic was identified as the 10-carboxamide of thiotetromycin.

Drugs, 1986, 31 Suppl 3, 132 - 41
Otitis media and sinusitis in children . Role of Branhamella catarrhalis; Bluestone CD; Otitis media and sinusitis are among the most common diseases of childhood and various treatment approaches have been advocated . This review focuses on current experience in Pittsburgh, both in terms of our methods of patient management and the changing aetiology of the underlying diseases . Special reference is made to the role played by Branhamella catarrhalis and the emergence of beta-lactamase-producing strains . Results from recently completed clinical trials would suggest that antibacterial therapy should be administered to children with these infections, to reduce morbidity and prevent the ever-present supportive complications associated with both diseases.

Vet Med Nauki, 1986, 23(3), 34 - 41
{Natural resistance and immunological reactivity in pigs weaned at various ages}; Arsov R et al.; Studies were carried out on the changes in some indices of the natural resistance and immunologic response (total protein, monoamino-oxidase, and lysozyme, antibacterial, and phagocytic activity, and erythrocyte-rosette forming cells and antibody activity) of the blood of pigs that were weaned and vaccinated at 42, 28, and 18 days . The dynamic of these indices in the process of weaning and vaccination as well as in a 3-week period pointed to certain advantages with pigs weaned at more advanced age.

Int Urol Nephrol, 1986, 18(2), 169 - 73
Anogenital syndrome; Bruhl P et al.; The diagnosis "prostatitis" is frequently a makeshift . It not uncommonly occasions long-term antibacterial chemotherapeutic measures which are often ineffective . The symptoms of "prostatitis" may be caused by an anogenital syndrome . This diagnosis can only be made on the basis of meticulous urological and proctological investigations . They frequently obscure the proctological cause of such symptoms (e.g . haemorrhoids).

Genet Epidemiol, 1986, 3(3), 147 - 52
Human parotid proline-rich proteins: correlation of genetic polymorphisms to dental caries; Yu PL et al.; Parotid saliva contains a variety of proline-rich proteins . This study found that, among 306 children between the ages of 5 to 15 years, there is a significant increase in the decayed-missing-filled tooth surface (DMFS) score of the permanent teeth with age in children with the specific proline-rich protein phenotypes Pa and Pr . However, the increase in DMFS score of the permanent teeth of children was significantly greater in children with Pa+ and Pr22 than in those with the other phenotypes (Pa- or Pr11 and Pr12) . The previously established close correlation between the Pa and Pr phenotypes and the genetic variants of salivary peroxidase (a powerful antibacterial system in the oral cavity) may provide an explanation for the relationship of certain proline-rich protein phenotypes to dental caries.

Ter Arkh, 1986, 58(4), 142 - 3
{Eosinophilic exudative pleurisy as a manifestation of drug allergy}; Anshelevich IuV et al.; The paper is concerned with a study in which eosinophilic exudative pleuritis was the first sign of drug allergy (penicillin, streptomycin, claphoran), also manifesting itself in fever, hemorrhagic eruption, eosinophilia in the blood . Fast recovery was achieved after discontinuation of antibacterial therapy and prescription of prednisolone . The problem of differential diagnosis of pleuritis in acute pneumonia is discussed.

Vestn Khir Im I I Grek, 1986 Jan, 136(1), 48 - 52
{Minor surgical procedures and bronchologic cleansing methods in the treatment of acute abscesses and gangrene of the lungs}; Ostrovskii VK; Easy means of "minor surgery" and bronchological methods of sanitation were used in 234 patients with acute purulent diseases with the aim of drainage and sanitation of purulent cavities and for bringing antibiotics to the pathological focus in addition to detoxification, stimulating and antibacterial therapy . It reduced lethality among these patients and restricted indications to radical operations.

J Nat Prod, 1986 Jan-Feb, 49(1), 56 - 61
Limonoids from the seeds of Melia azedarach; Srivastava SD; Evidence is presented for the structure of a new limonoid glycoside, 6-acetoxy-11 alpha-hydroxy-7-oxo-14 beta, 15 beta-epoxymeliacin-1,5-diene-3-O-alpha-L-rhamnopyranoside, which occurs together with salannin and meldenin in the seeds of Melia azedarach . The glycoside shows antibacterial activity against four organisms.

J Free Radic Biol Med, 1986, 2(5-6), 377 - 91
Mechanism of antibacterial action: electron transfer and oxy radicals; Ames JR et al.; Most of the main categories of bactericidal agents, namely, aliphatic and heterocyclic nitro compounds, metal derivatives and chelators, quinones, azo dyes, and iminium-type ions, are proposed to exert their action by a unified mechanism . The toxic effect is believed to result generally from the catalytic production of reactive oxygen radicals that usually arise via electron transfer . Cyclic voltammetry was performed on a number of these agents . Reductions were for the most part reversible, with potentials in the favorable range of -0.20 to -0.58 V.

Rev Pneumol Clin, 1986, 42(6), 284 - 91
{Thoracic actinomycoses . General illustrated review of 4 surgical cases}; de Fenoyl O et al.; Actinomycosis of the lung is rare and difficult to diagnose . Its good prognosis after medical treatment contrasts with the high frequency of surgical excision, due to the fact that pre-operative diagnosis is exceptional . Following a review of the recent bacteriological, radiological and therapeutic data available in the literature, 4 personal cases are presented . In all 4 cases actinomycosis was diagnosed post-operatively on the presence of yellow grains in the histological specimens . In 2 cases surgical excision proved impossible, but an almost complete radiological recovery could be obtained after prolonged treatment with co-trimoxazole . This shows how important it is to be aware of the disease, to improve its diagnostic approach and to remember its sensitivity to antibacterial agents, even in well organized forms.

Arch Orthop Trauma Surg, 1986, 106(1), 36 - 41
The sustained release of cefotaxim from a fibrin-cefotaxim compound in treatment of osteitis . Pharmacokinetic study and clinical results; Zilch H et al.; Following a survey of the literature regarding clinical examinations and experimental studies of local absorbable carrier for an antibiotic in treatment of osteitis, a study is presented concerning clinical experience with 46 patients treated with a cefotaxim-loaded fibrin sealant . In connection with simultaneous focal sanitation the clinical results were satisfying . When autogenous cancellous bone was added at the same time, only one surgical operation was necessary in some cases to show results equivalent to other methods . Postoperatively, the cefotaxim levels in the blood and in the wound drainage fluid were measured . The serum cefotaxim concentrations were low and only identifiable for a period of 36h, whereas the wound drainage fluid contained very highly effective antibacterial concentrations over a measured period of 3.5 days . The best results were seen in cases of hematogenic osteomyelitis . The disadvantage of this system is the quick release of the antibiotic by diffusion . Therefore, high concentrations can be obtained only for a short period of several days.

Acta Microbiol Hung, 1986, 33(3), 221 - 31
The effects of cannabispiro compounds and tetrahydrocannabidiolic acid on the plasmid transfer and maintenance in Escherichia coli; Molnar J et al.; Some cannabispiro compounds and tetrahydrocannabidiolic acid were tested for antibacterial plasmid curing activity and inhibition of plasmid transfer . MIC values of the compound were above 1500 micrograms/ml . Cannabispirol and tetrahydrocannabidiolic acid eliminated the F'lac plasmid from Escherichia coli, but acetylcannabispirol, cannabispirone and cannabispirenone were ineffective as curing agents . Each compound, except acetyl-cannabispirol, selectively killed plasmid carrying bacteria . The compounds inhibited R144 plasmid transfer from E . coli into E . coli cells via inhibition of mating pair formation, zygotic killing and inhibition of transconjugal DNA synthesis in a lesser extent . All of the cannabispiro compounds and tetrahydrocannabidiolic acid inhibited the transformation with pBR322 plasmid DNA when the bacteria were pretreated with the compounds, via inhibition of the DNA penetration or decreasing the synthesis of plasmid DNA during bacterial growth . Although each of the compounds, except acetyl-cannabispirol, had a weak antibacterial effect which was more definite on plasmid carrying bacteria than plasmidless ones, and inhibited intercellular plasmid transfer and transforming activity of plasmid DNA, only two of them were able to cure F'lac plasmid showing that plasmid elimination is a complex process which strictly depends on the stereochemical configuration of curing agents.

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