Antimicrobials

Pathol Biol (Paris), 1989 Dec, 37(10), 1090 - 3
{Inhibition by nifurzide of the adhesion capacity of enteropathogenic colibacillus to HEP-2 cells}; Darfeuille-Michaud A et al.; Enteropathogenic Escherichia coli (EPEC) adhere in vivo to enterocytes . This adhesion capacity can be obtained in vitro with Hep-2 cells on which a characteristic localized adherence (LA) is observed . We studied the effect of subinhibitory concentrations (SIC) of nifurzide, a nitrofurane derivative, on this bacterial adherence phenomenon . Three EPEC strains are used: 11201 (026 serogroup), 7958 (0128) and 7836 (0142) . Various SIC (MIC/2; MIC/4;...; MIC/32) were added either to the culture medium of bacteria or to the Eagle medium in which bacteria and Hep-2 cells were mixed during the adhesion experiments . In each case an adhesion index is determined . Nifurzide strongly inhibits the adherence capacity of the three strains when concentrations ranging from MIC/2 to MIC/16 where added in both culture media . On the other hand three other nitrofurane derivatives which have no antibacterial effect did not inhibit adherence . The mechanism of the adherence inhibition by nifurzide is discussed.

Vet Clin North Am Equine Pract, 1989 Dec, 5(3), 513 - 38
Equine bandaging techniques; Lindsay WA; Topical medications and bandages play an important role in the management of equine wounds . Certain water-soluble antibacterial ointments (povidone-iodine, polymixin-neosporin-bacitracin) may be appropriate for use on contaminated wounds . A well-designed equine bandage is usually composed of primary, secondary, and tertiary layers . Because so many different products are available, the practitioner is advised to become familiar with the handling characteristics of a few . Because of the irregular contours of the equine limb, only products that stretch and conform should be used . Bandages should be applied snugly and secured in such a fashion that they will not slip or ride up . The horse should be confined to a stall while bandaged, and, even then, bandages must be changed at frequent intervals.

Semin Oncol, 1989 Dec, 16(6), 543 - 60
Infectious emergencies in oncology patients; Lazarus HM et al.; The development of neutropenia in a patient undergoing therapy for cancer represents a serious medical problem that rapidly escalates if fever develops . A diligent history and physical examination cannot be overemphasized, since this maneuver may direct the medical person to quickly identify the source of the infection and initiate appropriate therapy . No time should be wasted, but every attempt should be made to quickly obtain body fluids or tissue for microbiologic culture purposes . Appropriate therapy should then be instituted in an empiric manner . The antibacterial agents that are chosen as initial therapy should be selected based on a knowledge of the current local ecology and the antibiotic resistances of endemic strains of bacteria . The empiric therapy should continue until the patient has evidence of recovery of bone marrow function . In those patients who have developed obvious tissue infection, such as pneumonia or bloodstream infection, the therapy should be continued until the infection is eradicated . In patients who have persistent fever despite broad-spectrum antibacterial agents, a painstaking search for the source and type of infection should continue, including repeated blood cultures and other tests . Additional antibiotic or fungal agents should be administered as the need arises . Such an approach to this group of patients has resulted in a significantly better outcome for cancer patients . With the advent of recombinant hematopoietic growth factors, which may allow for a more rapid marrow and immunologic recovery, the therapy for the neutropenic patient should continue to improve.

Pharmazie, 1989 Dec, 44(12), 817 - 20
{Azoles . 27 . Nitroimidazole derivatives, their antibacterial and fungicidal activity and electron affinity}; Zaprutko L et al.; Nitroimidazole derivatives 3a-3g, 4a-4g and 5-8 were synthesized by treating 4,5-dinitro- and 2-methyl-4,5-dinitroimidazole (1,2) with phenacyl bromide, its p-substituted derivatives or epichlorohydrin . 1-(3-Chloro-2-hydroxypropyl)-4,5-dinitroimidazole (5) and its 2-methyl derivative 6 have been converted to imidazo-oxazoles 7 and 8 or amino imidazole derivatives 9-14 by the action of potassium carbonate or cyclic amines (pyrrolidine, piperidine, morpholine and N-methylpiperazine) . Some of the newly synthesized nitroimidazole derivatives show antibacterial and fungicidal activity . The electron affinity of the nitroimidazole derivatives 1-24 is discussed on the basis of their half-wave potentials and in the connection with their eventual radiosensitizing properties.

Akush Ginekol (Mosk), 1989 Dec, (12), 36 - 8
{The treatment of pregnant women with pyelonephritis}; Arbuliev MG et al.; Results of combined therapy comprising laser treatment of acupuncture sites, venous blood and the renal pelvic mucosa approached through a nephrostomy drain and ureteral catheter have been analyzed in 80 pregnant women with pyelonephritis . Laser treatment supported by antibacterial, fluid, spasmolytic, antihypertensive and immunostimulator therapy proved to be an effective regimen.

J Antibiot (Tokyo), 1989 Dec, 42(12), 1817 - 22
Erythromycin A oxime 11,12-carbonate and its oxime ethers; Brain EG et al.; Erythromycin A oxime 11,12-carbonate (5a) and its oxime ethers 5b approximately 5p have been prepared and their antibacterial activities compared with those of erythromycin A (1) and its 11,12-carbonate 2 . The oxime 5a and many of its oxime ether derivatives showed good activity in vitro against Gram-positive and the more permeable Gram-negative organisms, in some cases being even more active than the carbonate 2.

J Chemother, 1989 Dec, 1(6), 369 - 73
Effect of slime production on the antibiotic susceptibility of isolates from prosthetic infections; Selan L et al.; The antibacterial activity of 6 antibiotics towards 10 gram-positive and 6 gram-negative glycocalyx-producing strains, has been evaluated by employing a method which partially simulates the in vivo colonization of prosthetic devices . The results showed that routine antibiotic sensitivity tests are not predictive about the response of the glycocalyx-embedded bacteria, and that prophylaxis may be useful with ofloxacin and clindamycin, before placing a prosthetic device . Once bacterial colonization had already occurred, however, none of the tested antibiotics was able to eradicate the sessile bacterial form . The minimum bactericidal concentration (MBC) values, indeed, were much higher than those determined on the planktonic form, and were much higher than serum and tissue levels that can be reached in vivo.

Acta Odontol Scand, 1989 Dec, 47(6), 361 - 6
The effect of chlorhexidine supplementation in a periodontal dressing; Othman S et al.; Most commercial periodontal dressings claiming antibacterial activity lose this activity shortly after application . Chlorhexidine (CH) is an antibacterial agent with long-term activity in the oral cavity owing to its substantiveness and slow-release properties . In a double-blind split-mouth-designed clinical trial the effect of incorporating CH acetate in periodontal dressing was tested on wound healing after gingivectomy . Eleven patients, each needing at least two gingivectomies, constituted the test panel . Wound healing, as assessed by bleeding tendency after removal of dressing 7 days postoperatively was significantly delayed when control dressings were applied as compared with test dressings . Variables with regard to patient comfort also yielded results in favor of the test pack . Incorporation of antibacterial agents with high retention and slow release properties in the mouth in surgical dressings seems advantageous.

Presse Med, 1989 Nov 25, 18(39), 1923 - 7
{Structure-activity relationship of oral cephalosporins}; Bingen E et al.; The advances achieved in the field of oral cephalosporins consist of improved bioavailability and enhanced intrinsic activity of the compounds . Oral absorption is facilitated either by creating prodrugs or by modifying the compound itself with addition of the alpha-amino group at position 7 on the cephem ring or of a vinyl group at position 3 . Antibacterial activity and resistance to beta-lactamases are facilitated by the presence of an amino-2-thiazole heterocycle at position 7, associated with a methoxy-imino group or an oxy-imino-acetoxy group.

Methods Find Exp Clin Pharmacol, 1989 Nov, 11(11), 697 - 701
Lack of cross-resistance between efrotomycin and antibacterial agents used in the therapy of human and animal infections; Jacks TM et al.; Efrotomycin is an N-methylhydroxypyridone glycoside antibiotic with activity primarily against Gram-positive bacteria . It is intended for use as a feed additive for swine . Although efrotomycin is unrelated to any antibacterial drug used in human or veterinary medicine, the possibility of cross-resistance with other antibacterials is of concern . The minimum inhibitory concentrations (MICs) of efrotomycin were determined for a broad panel of bacterial isolates . In addition, the susceptibility of each isolate to 12-15 antibacterials was determined using a standardized disk susceptibility test . No evidence of cross-resistance between efrotomycin and any of the 12-15 antibacterial compounds was observed . When the MIC of efrotomycin for nine selected isolates was increased from 16- to greater than 100-fold by serial passage in subinhibitory concentrations of efrotomycin, no increased resistance to the 15 antibacterials was noted . Subinhibitory concentrations of efrotomycin had no effect on the conjugative transfer of antibacterial-resistance plasmids between K-12 strains of Escherichia coli . The data from this study suggest that if resistance to efrotomycin should occur, it is unlikely to result in the appearance of multiply-resistant bacterial populations.

Jpn J Antibiot, 1989 Nov, 42(11), 2354 - 62
{In vitro susceptibility of pathogenic Nocardia to beta-lactam antibiotics, especially imipenem, a carbapenem antibiotic}; Yazawa K et al.; In vitro antibacterial activity of 30 beta-lactam antibiotics including 2 beta-lactamase inhibitors (clavulanic acid and sulbactam) against 2 major pathogenic Nocardia, i.e . Nocardia asteroides group and Nocardia brasiliensis was studied . Among the antibiotics tested, a newly developed carbapenem antibiotic, imipenem (IPM), was found to be the most active, followed by oxacephem group antibiotic flomoxef (FMOX) . IPM exhibited activity against only N . asteroides group (N . asteroides, Nocardia farcinica and Nocardia nova) . On the other hand, FMOX showed activity against all pathogenic Nocardia tested . A 2- to 30-fold decreases in minimum inhibitory concentration (MIC) for N . asteroides, N . brasiliensis and N . farcinica was noted when antibiotics and beta-lactamase inhibitors were combined compared to antibiotics alone . Further combination and enzymatic studies indicated that all pathogenic Nocardia possess beta-lactamase except for a half of the strains of N . nova . These species' specific sensitivity patterns of pathogenic Nocardia are discussed in this paper with references to their taxonomic positions.

J Clin Periodontol, 1989 Nov, 16(10), 630 - 5
Efficacy of Perimed antibacterial system on established gingivitis . (I) . Clinical results; Clark WB et al.; A 6-month, double-blind controlled study was conducted on 101 subjects to determine the effect of Perimed antibacterial system, containing povidone-iodine (PVP-I) and hydrogen peroxide (H2O2), on established gingivitis . Subjects were randomly assigned to one of 4 treatment groups: PVP-I/H2O2, PVP-I/H2O, H2O2/H2O or H2O . Gingivitis was assessed by the papillary bleeding score (PBS) and plaque by a modified Quigley-Hein plaque index (PI) at baseline, 3, 12 and 24 weeks . The average baseline PBS and PI for the 4 groups ranged from 2.16-2.31 and 2.87-2.90, respectively . After baseline evaluation, subjects received a supra-gingival scaling and a subgingival irrigation with their respective rinse . Daily rinses were supervised and subgingival irrigation was repeated every 3 weeks . Duncan's multiple range test determined which groups differed from each other . The mean PI at 24 weeks was lower than at baseline in all groups . PVP-I had the lowest PI at all time points . The mean PBS at 24 weeks was 1.48 for PVP-I, 1.62 for H2O2, 1.88 for H2O and 1.34 for PVP-I/H2O2, a reduction from baseline of 31%, 27%, 18%, and 38% respectively . The difference between the PBS for PVP-I/H2O2 and H2O control was significant at each evaluation . There was a 70% reduction in sites with PBS greater than or equal to 3 for PVP-I/H2O2 between baseline and 24 weeks compared to a 34% decrease in the H2O group . It was concluded that the use of Perimed could be a beneficial adjunctive treatment for the prevention and control of gingivitis when used with routine oral hygiene procedures.

Rev Infect Dis, 1989 Nov-Dec, 11 Suppl 7, S1572 - 81
Antibiotic therapy for the febrile granulocytopenic cancer patient: combination therapy vs . monotherapy; Wade JC; The specific composition of empiric antibiotic therapy to be implemented for patients with neutropenia and fever remains controversial . The available clinical data comparing antibiotic combination with monotherapy come from studies with a number of major differences in design and analysis that make it difficult to interpret relative efficacy . The standard practice has been to use an antibiotic combination demonstrating broad antibacterial coverage, additive or synergistic effects against the more virulent gram-negative pathogens, and potentially antibacterial activity that decreases the emergence of resistant organisms . Studies of monotherapy have been hindered by wide differences in study design, and few comparative data have been presented to substantiate the efficacy of the drug in question as "treatment of infection"--an exception being the new agent imipenem . The emergence of gram-positive organisms as frequent pathogens in neutropenic patients has raised concern regarding empiric gram-positive therapy . Clinical experience suggests that empiric therapy is unnecessary; rather, directed therapy with an agent such as vancomycin can be used in those situations in which clinical or microbiologic data suggest the need for such antibiotics . If the specifics of optimal management of infectious disease in patients with sustained neutropenia and fever are to be identified, many continuing clinical problems must be approached in a more systematic and defined manner . Defects in study designs of the past should be eliminated, with investigators taking a stronger stand in support of standardized design and analysis.

J Antimicrob Chemother, 1989 Nov, 24(5), 765 - 74
In-vivo and in-vitro interference of antibiotics with antigen-specific antibody responses: effect of josamycin; Villa ML et al.; The effects of josamycin on the antigen-specific primary antibody responses of human peripheral blood cells have been studied by the method of haemolytic colonies in soft agar . The tests were performed before and after the oral administration of 1 g of josamycin or by adding the drug directly to cultures of cells from untreated donors . The results demonstrate that josamycin, added in vitro or administered in vivo significantly depresses the primary antibody responses . The mechanism by which josamycin exerts its activity on antibody production has been partially elucidated . The immunodepression depends on the stimulation of hydrogen peroxide production by monocytes and requires the actual presence of josamycin during the immune response . The stimulation of the respiratory burst of the phagocytic cell is a common feature of macrolide antibiotics and suggests the need for more extensive clinical and preclinical trials on antibacterial antibiotics that alter the human immune responses.

Am Ind Hyg Assoc J, 1989 Nov, 50(11), 579 - 85
Hexamethylenetetramine: a review; Dreyfors JM et al.; The available literature on hexamethylenetetramine (hexamine) was reviewed with emphasis on its toxicology and epidemiology, its thermal decomposition and regulatory concerns related to its uses . Large quantities of hexamine are used in the foundry, tire and rubber, and phenolformaldehyde resins industries and in other diverse applications . Excessive exposure to solid hexamine or its vapor has been reported to cause dermatitis and respiratory allergies . Although hexamine produces a positive Ames test, most animal studies have shown hexamine to be of very low genetic risk even in very high doses . The effectiveness of hexamine as an antibacterial agent has been attributed to its slow hydrolysis to ammonia and formaldehyde . Concerns have developed in industries which use hexamine at high temperatures over emissions of HCN, NH3, CO, CO2, nitrogen oxides, and formaldehyde . The studies reviewed are in general agreement that hexamine thermal decomposition in the temperature range of 300-800 degrees C is characterized by an increase in HCN and a decrease in NH3 emissions with increasing temperature . At temperatures of 200-300 degrees C hexamine decomposition is reported to produce mainly ammonia and formaldehyde.

ZWR, 1989 Nov, 98(11), 962, 964 - 5
{Bactericidal effects of antiseptic gypsum}; Lotzmann U et al.; In tests with plaster models we inspected the antibacterial effect of the dental plasters Dento-rock and Dento-dur . The results show, that models consisting of plaster that contains Chloramin T 80 were free of bacteria, even when produced from bacterial contaminated alginate impressions . After separation of the plaster models from the alginate impressions, a bactericide effect could be traced to a layer of 220 microns below the surface of the alginate . By using dental plaster of the tested types, it is therefore possible to eliminate the risk of a bacterial infection through plaster models, without any extra investing in time or labor . There is no sign of a negative influence of chloramin on physical parameters of the tested plasters.

Chem Pharm Bull (Tokyo), 1989 Nov, 37(11), 3050 - 3
Biopolymers from marine invertebrates . X . Mode of action of an antibacterial glycoprotein, aplysianin E, from eggs of a sea hare, Aplysia kurodai; Kisugi J et al.; An antibacterial factor, aplysianin E, was purified from the eggs of a sea hare, Aplysia kurodai . Purified aplysianin E was a glycoprotein of 250 kilo daltons consisting of 3 subunits, and showed both antibacterial and antineoplastic activities . The two activities were lost in parallel on heating and at low and high pH . This factor was half-maximally active for gram-positive and -negative bacteria at 0.12-3.3 micrograms/ml and its action was not bactericidal but bacteriostatic . Aplysianin E did not induce morphological elongation of bacteria or their release of adenosine triphosphate (ATP), but it completely inhibited the syntheses of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) by E . coli within 10 min . These results suggest that aplysianin E, found in an invertebrate, the sea hare, is a new antibacterial protein and that it exerts its action by inhibiting nucleic acid synthesis, as a DNA-inhibiting chemotherapeutic drug does.

Arch Pharm (Weinheim), 1989 Nov, 322(11), 821 - 6
{Peroxides as plant constituents . 6 . Hydroperoxides from the blossoms of Roman camomile, Anthemis nobilis L}; Rucker G et al.; From the ethanol extract of the blossoms of Anthemis nobilis L . (syn . Chamaemelum nobile L.), six new hydroperoxides (1-6) were isolated, besides the known 1 beta-hydroperoxyisonobilin (7) . The structures were elucidated by spectroscopic methods and in some cases ascertained by synthesis . Compounds 2 and 3 show a medium antibacterial activity.

Stomatologiia (Mosk), 1989 Nov-Dec, 68(6), 10 - 1
{The use of the preparation baliz-2 in inflammatory processes of the maxillofacial area}; Bernadskaia GP et al.; Examinations of 137 patients with inflammatory diseases of the maxillofacial area and neck, treated with baliz-2, have shown that this agent is characterized by a manifest antibacterial action on the wound microflora, helps thinning the purulent exudate, and accelerates detachment of the necrotic mass . No cases of local irritation were recorded.

Arzneimittelforschung, 1989 Nov, 39(11), 1406 - 10
Synthesis, antibacterial activity and structure-activity relationships of N-substituted 3-methyl-4-diazo-5-pyrazolecarboxamides; Baraldi PG et al.; A number of N-substituted 3-methyl-4-diazo-5-pyrazolecarboxamides (IVa-p) have been synthesized and tested for their in vitro antibacterial activity . All the compounds have been assayed against several representative Gram-negative and Gram-positive bacteria, as well as against some intestinal bacterial species . Some of the 4-diazopyrazoles IVa-c have shown a quite interesting broad-spectrum activity, while they are ineffective against the "protective" intestinal flora . The structure-activity relationships of the series have been studied quantitatively, via both univariate and multivariate methods: the results are consistent and permit some rationalization of the behaviour of the compounds investigated.

Cardiovasc Res, 1989 Nov, 23(11), 960 - 4
Effects of antibiotics on cellular viability in porcine heart valve tissue; Hu JF et al.; The purpose of this study was to find an antibiotic disinfecting solution for cardiovascular tissues which would allow maximal cellular viability while maintaining antibacterial and antifungal activity . Cellular viability of porcine heat valves sterilised using antibiotics was assessed by radiolabelled proline transport assays . The results show that storage of valve tissues in RPMI 1640 tissue culture medium (4 degrees C) alone decreases the cellular viability by 50%, 60% and 90% within 12, 24, and 72 h, respectively . Amphotericin B was shown to be the toxic component of the antibiotic sterilising solution recommended by Strickett and coworkers, accounting for all the observed antibiotic toxicity . It reduced the cellular viability by 100% within 12 h of storage at 4 degrees C . Our study also showed that streptomycin is responsible for the loss of cellular viability in the antibiotic medium utilised by O'Brien's group . The results show that after storage of valve tissues for 12 h in O'Brien's antibiotic solution, the cellular viability was reduced by 60%, and after 24 h by 90% . Cefoxitin, lincomycin, polymyxin B, vancomycin and penicillin had no apparent effects on viability of cells in the cardiovascular tissues utilised in this study . In conclusion, heart valve tissue may be sterilised effectively using selective antibiotics without causing significant damage to cellular viability.

Z Gesamte Inn Med, 1989 Nov 1, 44(21), 658 - 60
{Lyme borreliosis with erythema chronicum migrans and Garin-Bujadoux-Bannwarth meningopolyneuritis}; Berthold F et al.; A case report is given on a Borrelia burgdorferi infection regarded to be typical because of its clinical course and the diagnosis lately made . The meningopolyneuritis was treated by use of corticosteroids before the serologic detection of Lyme disease . 21 months after infection our patient died of a colon carcinoma . Histological preparation of the brain showed a slight encephalitis we consider as third-stage Lyme borreliosis . We conclude that antibacterial therapy is necessary in the management of Lyme disease, especially after the administration of corticosteroids.

Pharmacol Biochem Behav, 1989 Nov, 34(3), 649 - 53
D-cycloserine, a positive modulator of the N-methyl-D-aspartate receptor, enhances performance of learning tasks in rats; Monahan JB et al.; Glycine has recently been shown to positively modulate the N-methyl-D-aspartate (NMDA) subclass of acidic amino acid receptors which are important in neural pathways involved in learning and memory . We report that d-cycloserine (DCS), an antimycobacterial agent known to cross the blood-brain barrier, binds with high affinity to this glycine modulatory site, functions as a positive modulator, and facilitates performance of learning tasks in rats . In addition, DCS appears to be a potent cognitive enhancer at doses lower than those required for antibacterial activity . Based on these data, we propose that modulation of NMDA receptors via glycinergic mechanisms may be a means of influencing cognitive processes.

J Antibiot (Tokyo), 1989 Nov, 42(11), 1684 - 97
Dechloro teicoplanin antibiotics; Malabarba A et al.; Mono- and didechlorinated derivatives of the antibiotic teicoplanin, its pseudoaglycones and aglycone, and of one amide and ester of deglucoteicoplanin were prepared under selective reductive conditions . The selectivity and rate of dehalogenation were studied and compared to those of vancomycin and deglucovancomycin . The influence of the chlorine substituents on the mechanism of action and antibacterial activity of teicoplanin antibiotics was also investigated.

Vrach Delo, 1989 Nov, (11), 39 - 40
{The optimization of the corticosteroid therapy of patients with destructive pulmonary tuberculosis}; Iareshko AG; Corticosteroids were administered in 120 patients with active pulmonary tuberculosis during the morning hours every other day in association with tuberculostatic agents . It was found that corticosteroids in a dose similar to 15 mg of prednisolone did not influence the efficacy of antibacterial agents while an increase to 20 mg used for not less than 2 months increases the treatment efficacy to 83.3% and over 3 months--to 89.5%.

Klin Med (Mosk), 1989 Nov, 67(11), 81 - 5
{The role of disorders of secretion of pancreatic enzymes and bile and bacterial contamination of the small intestine in the pathogenesis of diarrhea in patients with celiac disease}; Loginov AS et al.; The study of 53 patients with celiac disease provided evidence for the impotent role of the inhibited hyposecretion of pancreatic enzymes, atony of the gallbladder responsible for abnormal bile acids introduction into the intestinal lumen in digestion, elevated concentrations of free bile acids at the expense of lowjugated ones in duodenal and jejunal contents as well as bacterial dissemination of the proximal portion of the small intestine in pathogenesis of diarrhea observed in celiac disease . It is concluded that inclusion of continuous courses of enzyme preparations and light cholagogues in the treatment schemes of celiac disease and administration in its exacerbation of adsorbents, astringents, antibacterial preparations should be necessary therapeutic measures.

Biochim Biophys Acta, 1989 Oct 2, 985(1), 60 - 6
The lipopeptide antibiotic A21978C has a specific interaction with DMPC only in the presence of calcium ions; Lakey JH et al.; The A21978C group are lipopeptide antibiotics which kill Gram-positive bacteria only in the presence of calcium ions . The calcium requirement of the antibacterial activity of A21978C correlates well with an in vitro calcium-dependent insertion into phospholipid vesicles . In this paper the interaction of A21978C with phosphatidylcholine is investigated in mixed monomolecular films . The spontaneity of the antibiotic-lipid mixing was determined by calculating the free energy change . On a Ca2+ containing subphase there is a specific interaction between the components at all antibiotic-lipid ratios . This is not true on K+ subphases, where specific interactions never occur . On Mg2+ subphases specific interactions occur only in monolayers containing very little lipid . By analysing the fluorescence of the kynurenine residue we have followed the effects of two factors on the penetration of the antibiotic into lipid bilayer vesicles . Firstly, the phospholipid gel to liquid crystalline phase transition which in the absence of calcium leads to an exclusion of the antibiotic from the bilayer . This trend is completely reversed in the presence of Ca2+ . Secondly, the role of this lipopeptide's lipid tail was clarified by use of a series of versions of increasing fatty acyl chain length . The results indicate that the interaction promoted by calcium is not simply a hydrophobic attraction between fatty acyl chains but is more likely to be a specific interaction between polar headgroups.

J Antibiot (Tokyo), 1989 Oct, 42(10), 1489 - 93
LL-E19020 alpha and beta, animal growth promoting antibiotics: taxonomy, fermentation and biological activity; Maiese WM et al.; Antibacterial antibiotics LL-E19020 alpha and beta were isolated from the fermentation broth of an actinomycete strain . Based on cultural and physiological characteristics, culture LL-E19020 was identified as a new subspecies of Streptomyces lydicus . The LL-E19020 alpha and beta antibiotics were found to possess a very narrow antibacterial spectrum against human pathogens . In studies in chickens, LL-E19020 alpha demonstrated excellent growth promoting activity.

Am J Med Sci, 1989 Oct, 298(4), 252 - 5
Subacute disseminated mucormycosis in a diabetic male; Nolan RL et al.; Mucormycosis is an opportunistic invasive infection caused by fungi of the order Mucorales . Rhizopus, Absidia, and Mucor are the most commonly encountered genera . Disease is characterized by vascular invasion, thrombosis, and tissue necrosis . Rhinocerebral disease is the most common manifestation but pulmonary, cutaneous, gastrointestinal, and widely disseminated forms have been reported . Pulmonary and disseminated disease are usually seen in neutropenic patients with leukemia or lymphoma . Both present as fever and unexplained pulmonary infiltrates unresponsive to antibacterials and corticosteroids . Disease is usually fulminant and has a high mortality rate . Diagnosis is most commonly made at autopsy . A single case of disseminated disease is reported that is unusual in its subacute course and its occurrence in an otherwise healthy non-neutropenic diabetic male.

Dig Dis Sci, 1989 Oct, 34(10), 1576 - 80
Cholestatic hepatitis due to antibacterial combination of amoxicillin and clavulanic acid (augmentin)
Stricker BH, Van den Broek JW, Keuning J, Eberhardt W, Houben HG, Johnson M, Blok AP.
Five case histories are presented of patients developing cholestatic hepatitis associated with the intake of the antibiotic combination agent amoxicillin and clavulanic acid (Augmentin) . In two of these cases, signs of hepatic injury recurred after readministration of this combination but not after the intake of amoxicillin alone . In none of the patients was another cause for cholestatic hepatitis found and extrahepatic causes were excluded by ultrasonography, CT scanning, or ERCP . Most viral causes of hepatic injury were excluded in these patients . With the exception of one patient, who developed a transient rash, no immunoallergic signs were present . Biopsy in two patients showed extensive cholestasis without significant necrosis . Clavulanic acid seems to be responsible for this adverse effect.

Minerva Pediatr, 1989 Oct, 41(10), 515 - 20
{Clinical evaluation of letosteine activity in the treatment of acute febrile bronchitis in children . Double-blind controlled study versus placebo}; Nespoli L et al.; A double blind vs placebo study was carried out to study the effect of letosteine on the symptoms and clinical course of paediatric patients suffering from acute febrile bronchitis . Forty children were recruited for the research: 20 were treated with letosteine in a dose of 25 mg x 3 g/die and 20 with placebo; treatment lasted 10 days . The following parameters were assessed during the trial: body temperature, cough, thoracic objectivity, respiratory function indices . The results of the study show that in the letosteine treated group there is a statistically significant decrease in fever, a favourable evolution of thoracic objectivity and an improvement in certain respiratory function parameters (MEF 75, PEF) . It is concluded that treatment with letosteine leads to a significant increase in the rate of regression of thoracic symptomatology and a faster, more substantial reduction in fever in children suffering from acute bronchitis . This is probably the result of drug action on mucus viscosity, restoring optimal mucociliary clearance, and through action fostering the penetration of antibacterial substances into the mucus.

Am J Infect Control, 1989 Oct, 17(5), 258 - 63
Evaluation of the insulin jet injector as a potential source of infection; Price JP et al.; In recent years jet injection of insulin has been widely used by patients with diabetes mellitus . Jet injectors may become contaminated by bacteria because of repeated use without cleaning; cleansing every 2 weeks is recommended . We investigated the occurrence of bacterial contamination by culturing jet injectors in everyday use by 19 patients with diabetes . Swabs from the interior chambers were cultured on blood agar plates . Only one of 20 cultures yielded bacterial growth, and the organism recovered was a presumed contaminant that could not be identified as any common pathogen . No study patient, nor any of more than 70 patients whom we instructed in jet injection, showed any clinical evidence of infection attributable to jet injector use . Jet injectors are unlikely to become colonized by bacteria or to cause infection in patients using them for insulin administration . The low rate of colonization may be due to the antibacterial preservatives added to commercial preparations of insulin . Additional data based on larger numbers of patients would be useful in further clarifying the risk of infection associated with jet injectors.

J Anim Sci, 1989 Oct, 67(10), 2817 - 21
Sulfa residues in pork: an update; Augsburg JK; Sulfamethazine (SMZ) is an antibacterial drug used in approximately 75% of all hogs marketed in the U.S . The tolerance for residues of SMZ in uncooked tissues is .1 ppm, and the withdrawal time is 15 d . The rate of illegal residues in swine from the use of SMZ has continued to fluctuate between 4% and 5% from 1980 through 1987 . This was not acceptable . The Center for Veterinary Medicine (CVM) also has received from the National Center for Toxicological Research a report showing that SMZ produces a dose-related increase in follicular cell adenomas of the thyroid gland in rats and mice . The FDA has discovered three major causes of SMZ residues by investigating violators . The number one cause was a lack of sequencing, flushing, and cleaning of mixer equipment . Failure to follow withdrawal times was another major cause, and the third major reason was the use of a soluble powder solution . At least 16% of SMZ residue violations have resulted in no follow-up due to lack of animal identification . The FDA district offices are conducting on-farm investigations of swine producers who have caused SMZ violations . Repeat violators and those that produce higher residue levels will receive a higher priority . The FDA currently is attempting to obtain more state support, particularly for investigation of first-time violators . The CVM is serious about resolving the SMZ residue problem.

Endod Dent Traumatol, 1989 Oct, 5(5), 242 - 52
Pulpal response to an anhydrous glass ionomer luting cement; Tobias RS et al.; This investigation was designed to study the pulpal responses to Aquacem, an anhydrous glass ionomer luting cement, and to compare the results with those previously obtained for a conventional glass ionomer luting cement, Chembond . The study was carried out according to the BSI (1980) recommendations for testing restorative materials in vivo . Aquacem caused more pulpal inflammation than the control material, Kalzinol, though by an indirect mechanism . The statistical model demonstrated a significant association between bacterial presence within the experimental cavity and pulpal inflammation . The type of restorative material has no direct association with the degree of inflammation, but the model suggests that it exerts an indirect influence via its antibacterial properties and hence its influence on microbial microleakage.

Antibiot Khimioter, 1989 Oct, 34(10), 779 - 82
{Comparative evaluation of the embryotoxic effect of various antibiotics}; Skosyreva AM; A broad spectrum of antibacterial antibiotics used in treatment of purulent inflammatory diseases in pregnant women was studied experimentally . The antibiotics included oxacillin, fusidin, kanamycin, gentamicin, cefuroxime, cephalothin and tetracycline . The embryotoxic action of the antibiotics was investigated on embryos of rats cultivated in vitro . The mediated antenatal action of tetracycline and gentamicin was studied during various gestation terms before implantation (days 1 to 7), during organogenesis (days 8 to 14) and during fetal growth++ (days 14 to 20) . Prior to the delivery the data on the intrauterine death, development of the fetoplacental unit and the presence of external and internal anomalies were considered . The placenta, liver and kidneys of the fetus were examined morphologically . It was shown that tetracycline and gentamicin had embryotoxic properties as evidenced by a higher intrauterine death rate and congenital anomalies in individual fetuses.

Minerva Cardioangiol, 1989 Oct, 37(10), 443 - 9
{Surgical cardiac risk in patients with heart diseases . II . Perioperative treatment}; Caruzzo C et al.; An improvement can be obtained in the surgical prognosis of the cardiopathic by working on the main risk factors . Congestive decompensation must usually be treated with diuretics; digitalis in only indicated in certain cases . In patients with ischaemic cardiopathy, angina therapy should be continued during the perioperative period, replacing the oral route; in the postoperative period . ECG monitoring is advisable up to Day III-V . Valve defects should be assessed carefully, including haemodynamically (especially severe aortic stenosis) because correction of the defect may become a priority . In hypertrophic cardiomyopathy hypovolaemia and loss of sinus rhythm should be avoided . Valve prostheses involve particular problems represented by antibacterial prophylaxis and perioperative anti-coagulation . Congenital cyanogenic cardiopathies often require a lowering of the haematocrit and careful control of hypotension . Postoperative arrhythmias generally have medical causes and require control of the latter before possible antiarrhythmic therapy . The implantation of a temporary prophylactic pacemaker is rarely needed; for patients with definitive pacemakers, some precautions are needed for the use of the thermocautery . It is very important to deal with poor general medical conditions that might affect prognosis . Control of hypertension is less important than control of hypotension.

Int J Pept Protein Res, 1989 Oct, 34(4), 277 - 86
A common cytolytic region in myotoxins, hemolysins, cardiotoxins and antibacterial peptides; Kini RM et al.; Several proteins and polypeptides of reptilian, amphibian, insect, and microbial origin share a common cytolytic property . However, these cytolysins fulfill different objectives . They provide offensive armament in the case of toxins, but defensive systems in the case of antibacterial peptides . The sequences of several nonenzymatic cytolysins and their analogues were compared to identify the structural requirements for cytolytic activity . These cytolysins, although isolated from phylogenetically unrelated organisms, possess the common sequence features of a cationic site flanked by a hydrophobic surface . The presence of such a region apparently confers the cytolytic activity of various cytolysins . The concept of a cytolytic region is strongly supported by the existence of several natural and synthetic analogues of cytolysins and by chemical modification studies of these cytolysins . This prediction provides a new focus for cytolysin research . The understanding of this structure-function relationship should facilitate the design, synthesis, and development of better antibacterial and anticancer peptides.

Microbiologica, 1989 Oct, 12(4), 307 - 16
Antibacterial, antifungal and antitumoral activities of Micromycetes . I . Preliminary study; Steiman R et al.; The ability of 211 strains of Micromycetes to produce antibiotic, antifungal and antitumoral compounds has been investigated in vitro using test strains and P 388 leukemia cells . Cytotoxicity was determined on Vero cells . Convenient activities were obtained depending on the taxonomic group . Finally, 17 strains of Micromycetes were selected for their antibacterial or antifungal activities and 12 for their antitumoral properties . Investigations are in progress concerning these activities.

Arch Pharm (Weinheim), 1989 Oct, 322(10), 599 - 602
Synthesis and biological properties of novel triazolopyrimido-pyrimidine-5,8-diones; Dlugosz A; The synthesis of novel 1,2,4 triazolo{2,3,4-c,d}pyrimido{4,5-d}pyrimidine derivatives has been described from N-substituted amides of 1,2,3,4-tetrahydro-6-methyl-2-oxo-4-thio-5-pyrimidinecarboxylic acid 1 . Amides 1 treated with 80% hydrazine hydrate, followed by aqueous-ethanolic formaldehyde form substituted triazolo{4,3-c}pyrimidines which cyclize in pyridine to triazolopyrimidopyrimidine derivatives 4 . Attention has been paid to the synthesis of the 4-arylidenehydrazinopyrimidines 3 . Some compounds have been tested for antibacterial and anticancer activities and for action on CNS.

Antimicrob Agents Chemother, 1989 Oct, 33(10), 1697 - 703
Use of in vitro topoisomerase II assays for studying quinolone antibacterial agents; Barrett JF et al.; Several quinolones and antitumor compounds were tested as inhibitors of purified calf thymus topoisomerase II in unknotting, catenation, radiolabeled DNA cleavage, and quantitative nonradiolabeled cleavage assays . The antitumor agents VP-16 (demethylepipodophyllotoxin ethylio-beta-D-glucoside) and ellipticine demonstrated drug-enhanced topoisomerase II DNA cleavage (the concentration of drug that induced 50% of the maximal DNA cleavage in the test system {CC50}) at levels of less than or equal to 5 micrograms/ml . Nalidixic acid, norfloxacin, and oxolinic acid did not induce significant topoisomerase II DNA cleavage, whereas ciprofloxacin did induce some cleavage above background levels . CP-67,015, a new 6,8-difluoro-7-pyridyl 4-quinolone which possesses potent antibacterial activity, inhibited bacterial DNA gyrase at 0.125 micrograms/ml in a nonradioactive DNA cleavage assay . Unlike other quinolones characterized to date, CP-67,015 was shown to strongly enhance topoisomerase II-induced radiolabeled DNA cleavage with a CC50 of 33 micrograms/ml and demonstrated cleavage in a nonradiolabeled DNA cleavage assay with a CC50 of 73 micrograms/ml . The topoisomerase II-mediated cleavage of DNA by CP-67,015 is consistent with its reported clastogenic effect on DNA in cell culture and its positive mutagenic response in mouse lymphoma cells . In vitro topoisomerase II catalytic and cleavage assays are useful for gaining preliminary information concerning the possible interaction(s) of some quinolones with eucaryotic topoisomerase II which may relate directly to their safety (mutagenicity, clastogenicity, or both) in human and veterinary medicinal usage.

Akush Ginekol (Mosk), 1989 Oct, (10), 21 - 3
{Laparoscopic picture in patients with oligomenorrhea treated for chronic salpingo-oophoritis}; Gurtovaia NB et al.; Sixty patients with oligomenorrhea and the painful syndrome were examined to study the course of a chronic inflammatory process of the genitals . Laparoscopy has confirmed the initial diagnosis of salpingo-oophoritis in 24 of the 60 examinees . The authors call for a more thorough examination of this patient population, for an erroneous diagnosis of a chronic inflammation leads to erroneous therapeutic strategy, consisting in irrational administration of antibacterial, balneo- and physiotherapy.

Immun Infekt, 1989 Oct, 17(5), 169 - 74
{The granulomatous inflammation in bacterial infections}; Kaufmann SH; The relevance of the granuloma to protection against intracellular pathogens has been recognized for a long time . More recently, it has become clear that the cell interactions which take place in a granuloma are highly complex . It appears that not only activation of antibacterial function in infected macrophages by helper T cells, but also lysis of infected host cells is of importance and that a coordinated interplay between different populations of T cells and mononuclear phagocytes is required for effective host resistance.

Farmaco, 1989 Oct, 44(10), 997 - 1006
Biological studies on 1,2-benzisothiazole derivatives . II . Evaluation of antibacterial, antifungal and DNA-damaging activities of 3-amino, 3-acylamino, 3-alkylaminoacylamino derivatives; Zani F et al.; The in vitro evaluation of antibacterial, antifungal and DNA-damaging properties of some 3-amino, 3-acylamino and 3-alkylaminoacylamino derivatives of 1,2-benzisothiazole is described . Compounds 1-8, 38 and 48 exhibited a selective antifungal activity while the other compounds did not show any significative activity . None of the compounds tested turned out to have any genotoxic properties.

Presse Med, 1989 Sep 30, 18(30), 1466 - 8
{Prompt antibiotic prophylaxis in resection of the prostate and removal of the bladder catheter}; Duclos JM et al.; Several regimens of antibiotic prophylaxis have been used in transurethral prostatic resection . In this study 50 patients received 1 g of cefotaxime during resection and thereafter were divided at random into two groups: one group received another 1 g dose of cefotaxime when the bladder catheter was removed, while the other group was left untreated at that stage . The administration of cefotaxime during both prostatic resection and catheter removal resulted in a highly significant reduction of infection risk, duration of hospitalisation and cost of antibacterial treatment . The most important risk of sepsis seems to be related to an apparently innocuous procedure: removal of the bladder catheter with resumption of spontaneous micturition.

Tijdschr Diergeneeskd, 1989 Sep 15, 114(18), 939 - 48
{Escherichia coli mastitis in cattle . III . Antibacterial therapy}; Kremer WD et al.; This review paper is concerned with antibacterial therapy of mastitis caused by Escherichia coli . The choice of an antibacterial agent is discussed, and nine criteria are referred to, on which this choice should be based . In the second part possible forms of antibacterial treatment are discussed . Literature on parenteral and local treatment of mastitis due to E . coli is scarcely available . The evaluation of antibacterial drugs is mainly based on MIC values and pharmacokinetic studies in normal animals . Unfortunately, results of clinical trials are hardly available . Today combinations of trimethoprim/sulphonamide apparently are the best available choice for the parenteral treatment of mastitis caused by E . coli . Infusion of polymyxins or gentamycin is discussed as a method of intramammary therapy.

Med J Aust, 1989 Sep 4, 151(5), 269 - 72
How well are endoscopes cleaned and disinfected between patients?
Collignon P, Graham E.
A questionnaire was sent to 276 hospitals throughout Australia to obtain details on the methods that are used in these institutions for the cleaning and disinfection of endoscopes . A broad range of hospitals was surveyed and 145 responses were received . Endoscopies were performed in 123 of the responding hospitals . Only 45% (55/123) of these hospitals both cleaned and disinfected their endoscopes satisfactorily . Generally, such hospitals were larger (300-600 beds) than were those which did not do so (100-300 beds) and also they were busier as more endoscopies were performed on a weekly basis (30.2 endoscopies compared with 19.3 endoscopies, respectively) . Frequently (38% {47/123} of hospitals), the endoscopes were not disinfected between patients, or were disinfected for an insufficient time or were disinfected with an agent that did not have both antiviral and antibacterial activity . In a substantial proportion (40% {49/123}) of hospitals, endoscopes and their accessories appeared to be cleaned inadequately between patients . We conclude that in the majority of hospitals where endoscopies are performed that responded to our survey, there was considerable room for improvement in the cleaning and disinfection of endoscopes.

J Antimicrob Chemother, 1989 Sep, 24(3), 355 - 63
Cytotoxicity and uptake of pefloxacin, ciprofloxacin, and ofloxacin in primary cultures of rat hepatocytes; Nordmann P et al.; The cytotoxicity and the uptake of three 4-quinolones--pefloxacin, ciprofloxacin, and ofloxacin--were investigated in primary cultures of rat hepatocytes . As assessed by intracellular enzyme release in culture media, pefloxacin at concentration 400 mg/l and ciprofloxacin at 200 mg/l were found to be hepatotoxins . However, concentration ofloxacin up to 400 mg/l were not hepatotoxic . After 48 h incubation, the remaining antibiotic concentrations in the culture medium as determined by HPLC were 55%, 45%, and 35% for ofloxacin, ciprofloxacin, and pefloxacin, respectively . Comparisons of quinolone concentrations in the hepatocyte culture medium determined by HPLC and correspondent antibacterial activities determined by microbiological assays did not reveal any metabolites with antibacterial activity other than those which have been identified from intact animals.

J Antimicrob Chemother, 1989 Sep, 24(3), 317 - 24
In-vitro synergistic activity between ethambutol and fluorinated quinolones against Mycobacterium avium complex; Hoffner SE et al.; Ciprofloxacin, ofloxacin and norfloxacin were ineffective at clinically relevant concentrations against the Mycobacterium avium complex (MAC) in vitro as measured by radiometric respirometry . Only two of 30 clinical isolates of MAC were susceptible to any of the tested quinolones . By contrast good antibacterial activity was obtained when any of the quinolones was combined with ethambutol . The synergistic effect was most pronounced for the combination of ethambutol and ciprofloxacin, to which 76 of 100 strains were susceptible . It is suggested that the synergism is based on an enhanced penetration of the quinolones by ethambutol.

Photochem Photobiol, 1989 Sep, 50(3), 287 - 95
Spectroscopic studies of cutaneous photosensitizing agents--XIV . The spin trapping of free radicals formed during the photolysis of halogenated salicylanilide antibacterial agents; Chignell CF et al.; Several antibacterial halogenated salicylanilides, including 3,3',4',5-tetrachlorosalicylanilide (TCSA) and 3,4',5-tribromosalicylanilide (TBSA) are known to cause photoallergy . We have carried out photochemical and spin trapping studies to determine whether free radicals may be involved in the photoallergic response . Irradiation (lambda greater than 300 nm) of TCSA in buffered (pH 7.4) 50% ethanol resulted in the rapid loss of the 3-chloro atom, followed by the much slower release of 5- and then the 4'-chloro atoms to give 3'-chlorosalicylanilide as a stable photoproduct . Under the same conditions TBSA successively lost the 3-, 5- and 4'-bromine atoms to give salicylanilide . When TCSA or TBSA were irradiated (lambda = 356 nm) in buffered (pH 7.4) 50% ethanol containing 2-methyl-2-nitrosopropane (MNP) only solvent-derived free radicals were detected . However, irradiation (lambda = 356 nm) of TCSA and MNP in 0.1 N NaOH generated an ESR spectrum consisting of a broad triplet (aN = 15.6 G) . This spectrum was attributed to the adduct formed by the reaction of MNP with the aryl radical generated by the loss of a chlorine atom from the sterically hindered 3-(or 4'-)-position . Under the same conditions TBSA initially generated a broad triplet (aN = 15.5 G) similar to that observed for TCSA . However, upon further irradiation a 21-line spectrum (aN = 14.4 G, a2H = 2.0 G and a2H = 0.9 G) appeared.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibiot Khimioter, 1989 Sep, 34(9), 657 - 62
{A new drug sulfaton in the combined treatment of infections with sulfanilamide derivatives and diaminopyrimidine}; Padeiskaia EN; Derivatives of diaminopyrimidine as potentiators of the effect of the derivatives of sulfanilamide and other antibacterial drugs are discussed . Experimental data on sulfation, a new combined preparation, based on sulfamonomethoxine (a sulfanilamide derivative) and trimethoprim (a diaminopyrimidine derivative) are presented . Brief clinical characteristics of sulfation, its administration routes, doses, dosage advantages and better tolerance as compared to co-trimethoxazole+ (biseptol) are described.

Chest, 1989 Sep, 96(3), 528 - 37
Sequential intravenous-oral administration of ciprofloxacin vs ceftazidime in serious bacterial respiratory tract infections; Khan FA et al.; The efficacy and safety of sequential intravenous/oral ciprofloxacin in moderate to severe respiratory tract infections (RTI) were compared with those of ceftazidime in a prospective clinical trial . Sixty-six patients received IV ciprofloxacin (200 to 300 mg twice daily), followed by oral ciprofloxacin (500 mg twice daily) . Fifty-six patients received intravenous ceftazidime (1 to 2 g two to three times daily) . Ciprofloxacin was as effective as ceftazidime and produced a 91 percent clinical cure rate . Significantly more pretreatment bacterial isolates were susceptible to ciprofloxacin, and ciprofloxacin had a significantly higher rate of sputum bacterial eradication than did ceftazidime . 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 . Ciprofloxacin was an effective and well-tolerated treatment for severe RTI that had the advantages of broad in vitro antibacterial activity, twice-daily dosing, and sequential availability in an intravenous and oral formulation.

Antibiot Khimioter, 1989 Sep, 34(9), 696 - 9
{Combined antibacterial therapy of infectious complications in oncological patients}; Smolianskaia AZ; Rational antibacterial therapy of infections in oncological patients in relation to the polyetiological nature of the infections and polyresistance of their causative agents contemplates the use of drug combinations . The necessity of long-term antibacterial therapy in many oncological patients also predisposes to it . The choice of drugs for every patient should stem from bacteriological findings: isolation of the pathogen, its identification and assay of its antibiotic sensitivity . When isolation of the causative agent is not possible or could not be done immediately the drug should be chosen according to the general data on the etiological structure of infectious complications in the particular department and particular pathological process as well as antibiotic sensitivity of the bacteria isolated under such conditions.

Antibiot Khimioter, 1989 Sep, 34(9), 662 - 5
{Sensitivity spectrum of Francisella tularensis to antibiotics and synthetic antibacterial drugs}; Vasi'lev NT et al.; Sensitivity of 6 F . tularensis strains to 57 antibiotics and synthetic antibacterial drugs was studied . It was shown that the strains were highly sensitive to aminoglycosides, tetracyclines, anzamycins, quinolones, chloramphenicol, nitrofurantoin, nitroxoline, novobiocin and fusidin and resistant to penicillins, cephalosporins, polypeptides, vancomycin and sulfanylamides . The interrace differences in F . tularensis could be detected only by sensitivity to erythromycin, oleandomycin and spiramycin . There was observed no cross resistance to streptomycin and other aminoglycosides in F . tularensis . Assay of F . tularensis sensitivity to antibacterial drugs of various groups with the rapid photometric procedure and the agar diffusion method revealed that the results were highly comparable.

Pharmazie, 1989 Sep, 44(9), 632 - 3
Antibacterial, antifungal and antitumoral activities of 5-carbamoyloxy and 5-acyloxynaphthalene-1,8-carbolactones; Steiman R et al.; Naphthalene-1,8 carbolactone derivatives have been investigated in order to compare their activities using antitumoral, antibacterial and antifungal tests in vitro . The effect of 5-substitution is the reduction of the toxicity and the suppression of the antibiotic activity . The best results were obtained with the ester series (5-acetoxy and 5-propionyloxy) on both antitumoral and antifungal tests.

J Anim Sci, 1989 Sep, 67(9), 2341 - 6
Evaluation of a biological response modifier: effects on starter pig performance; Thaler RC et al.; The influence of a biological response modifier (FK-565) on weanling pig performance was evaluated . One hundred twenty-five weanling pigs (weaned at 21 +/- 3 d) averaging 6.3 kg were utilized in a 35-d growth trial . Dietary treatments included a basal diet (1.25% lysine, corn-soybean meal-dried whey), the basal plus .1, 1 or 10 ppm FK-565 and the control plus an antibacterial combination containing chlortetracycline, sulfamethazine and penicillin . Performance was recorded weekly, and on d 35 all pigs were bled for whole blood and serum chemistry profiles and then were euthanatized . Heart, liver, kidneys and spleen weights were recorded . Also, gross and histological examinations were made of these organs, as well as sections of lung, ileum, bone marrow, thymus and mesenteric lymph node . By d 14, pigs fed the antibacterial diet gained faster (P less than .06) than pigs fed the control and FK-565 diets . However, no differences (P less than .10) in feed intake at d 14 or efficiency of feed utilization at either d 14 or 35 were observed . For the overall 35-d trial, ADG was greater (P less than .01) for pigs consuming the antibacterial diet than for pigs consuming control and the FK-565 diets . Pigs consumed more of the antibacterial diet than of the other diets (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Z Orthop Ihre Grenzgeb, 1989 Sep-Oct, 127(5), 587 - 96
{Differentiated surgical and conservative treatment of spondylitis and spondylodiscitis}; Krodel A et al.; In the time from 1980 to 1987 58 patients underwent a conservative or operative treatment of spondylitis and spondylodiscitis according to the individual clinical and radiological features . In early or moderately advanced stages of the disease conservative therapy was performed . Under bedrest and antibacterial or tuberculostatic drug therapy bony fusion of the affected vertebral bodies was achieved in 50% of the pyogenic cases . In tuberculous spondylitis fusion rate was 83% . Persistent septic changes, progressive neurological symptoms and gross vertebral damage are indications for surgery . In those cases removal of the focus and intercorporal spondylodesis was performed . Bony union occurred in every cases . At follow-up examination, 3 years after the onset of therapy on an average, 42 patients had no complaints according to the vertebral column . As the results of our study show spondylitis and spondylodiscitis should according to the clinical and radiological features be lead to a differentiated operative or conservative treatment . Then good clinical results are to be supposed.

J Leukoc Biol, 1989 Sep, 46(3), 239 - 45
Lectin-mediated, nonopsonic phagocytosis of type 1 Escherichia coli by human peritoneal macrophages of uremic patients treated by peritoneal dialysis; Boner G et al.; Human peritoneal macrophages isolated from uremic patients undergoing peritoneal dialysis bind type 1 fimbriated Escherichia coli in the absence of opsonins . The number of bacteria bound per macrophage was 6.9, as determined by microscopic examination . Methyl alpha-mannoside (0.1 mM) and p-nitrophenyl alpha-mannoside (0.01 mM) inhibited this binding by about 66% . The ability of peritoneal macrophages to bind E . coli in a mannose-specific manner was confirmed in further experiments using an enzyme-linked immunosorbent assay (ELISA) with an antibacterial antibody, radiolabelled E . coli, and counts of colony-forming units (CFU) . The number of bacteria bound per macrophage was 7 to 12 in the ELISA and 5.5-8.5 in the CFU assay . Methyl alpha-mannoside caused 70% inhibition of binding in the ELISA and 84% in the CFU assay, whereas p-nitrophenyl alpha-mannoside showed inhibition of 79% and 90%, respectively . Most bound bacteria (76-80%) were subsequently killed . Nonfimbriated E . coli 827 bound poorly to the macrophages (approximately 22%) as compared to that of the fimbriated bacteria . Although this binding was not inhibited by methyl alpha-D-mannoside or p-nitrophenyl alpha-mannoside, the percentage of bacteria killed was similar to that of the fimbriated phenotype . The peritoneal macrophage is thus able to phagocytose E . coli in the absence of opsonins . This may explain the relative rarity of E . coli as an etiologic agent of peritoneal infections in the dialysed patient.

Am J Dent, 1989 Sep, 2 Spec No, 197 - 206
In vitro and in vivo studies on triclosan/PVM/MA copolymer/NaF combination as an anti-plaque agent; Nabi N et al.; A combination of triclosan, copolymer of PVM/MA and NaF has been optimized in vitro and in vivo for plaque effect . Triclosan (2, 4, 4' trichloro-2'-hydroxydiphenyl ether), a non-cationic antibacterial, was compatible with anionic surfactant, NaF and PVM/MA copolymer as evaluated by in vitro antibacterial tests . The in vitro uptake of triclosan on the saliva-coated hydroxyapatite disks, extracted human teeth and oral buccal epithelial cells was enhanced two fold in the presence of PVM/MA copolymer when compared to the uptake in the absence of the copolymer . The combination consisting of 0.3% triclosan/2% PVM/MA copolymer/1100 ppm NaF was found to be highly effective on reducing smooth and fissure caries, and plaque extent compared to to 1100 ppm/NaF by itself in rats when applied topically . The combination also showed significantly more fluoride uptake and reduction in enamel solubility than 1100 ppm/NaF . The results of these studies indicated that this optimized combination was an effective antiplaque/anticaries agent in vitro and in vivo.

Rev Med Chil, 1989 Sep, 117(9), 1037 - 43
{Cephalosporins: bacterial resistance measured by penicillin-binding proteins}; Garrido J et al.; Antibacterial potency of cephalosporins depends on inhibition (acylation) of one or more penicillin-binding proteins (PBP) . Recently, reduced affinity of PBP for cephalosporins and other B-lactam agents has been found in some cases . Mechanism for these changes in affinity are analyzed in this review.

West Indian Med J, 1989 Sep, 38(3), 142 - 7
ACTH--inosine pranobex in the treatment of AIDS . Encouraging results; Addo E et al.; Twenty patients with Acquired Immune Deficiency Syndrome (AIDS) received treatment with Inosine Pranobex and specific antibacterial and anti-parasitic therapy . Five died shortly after hospitalization, but a further fifteen who also received ACTH, survived, gained weight and improved clinically, biochemically and haematologically.

Philos Trans R Soc Lond B Biol Sci, 1989 Aug 31, 324(1224), 549 - 62
Antibiotics: opportunities for genetic manipulation; Hopwood DA; New antibiotics can still be discovered by the development of novel screening procedures . Notable successes over the last few years include the monobactams, beta-lactamase inhibitors (clavulanic acid) and new glycopeptides in the antibacterial field; antiparasitic agents such as avermectins; and herbicidal antibiotics like bialaphos . In the future we can expect the engineering of genes from 'difficult' pathogens, including mycobacteria and fungi, and cancer cells, to provide increasingly useful in vitro targets for the screening of antibiotics that can kill pathogens and tumours . There will also be a greater awareness of the need to reveal the full potential for antibiotic production on the part of microorganisms by the physiological and/or genetic awakening of 'silent' genes . Nevertheless, the supply of natural antibiotics for direct use or chemical modification is not infinite and there will be increasing scope for widening the range of available antibiotics by genetic engineering . 'Hybrid' antibiotics have been shown to be generated by the transfer of genes on suitable vectors between strains producing chemically related compounds . More exciting is the possibility of generating novelty by the genetic engineering of the synthases that determine the basic structure of antibiotics belonging to such classes as the beta-lactams and polyketides . Research in this area will certainly yield knowledge of considerable scientific interest and probably also of potential applicability . In the improvement of antibiotic titre in actinomycetes, protoplast fusion between divergent selection lines has taken a place alongside random mutation and screening . In some cases the cloning of genes controlling metabolic 'bottlenecks' in fungi and actinomycetes will give an immediate benefit in the conversion of accumulated biosynthetic intermediates to the desired end product . However, the main impact of genetic engineering in titre improvement will probably come only after a further use of this technology to understand and manipulate the regulation of antibiotic biosynthesis as a facet of the general challenge of understanding differential gene expression . Streptomyces offers a particularly fertile field for such research, following the isolation of DNA segments that carry groups of closely linked operons for the biosynthesis of and resistance to particular antibiotics, and of genes with pleiotropic effects on morphological differentiation and secondary metabolite formation.

J Chromatogr, 1989 Aug 30, 477(2), 397 - 406
Improvement of chemical analysis of antibiotics . XVI . Simple and rapid determination of residual pyridonecarboxylic acid antibacterials in fish using a prepacked amino cartridge; Ikai Y et al.; A simple and rapid method for the determination of residual pyridonecarboxylic acid antibacterials (PCAs) (oxolinic acid, nalidixic acid and piromidic acid) in fish was developed using a combination of high-performance liquid chromatography (HPLC) and clean-up with an amino-type prepacked cartridge . PCAs were extracted with n-hexane-ethyl acetate (1:3) and the extract was applied to a Baker 10 amino cartridge . PCAs were eluted from the cartridge with acetonitrile-methanol-0.01 M aqueous oxalic acid solution (pH 3.0) (3:1:6) and were determined by HPLC . The separations were performed on Nucleosil 3C18 (3 microns, 75 x 4.6 mm I.D.) using a mobile phase containing oxalic acid . The recoveries of PCAs from various fishes fortified at the level of 1.0 ppm were 77.1-95.5%, and the detection limits were 0.05 ppm . The analytical time per sample was less than 30 min.

Pharm Weekbl Sci, 1989 Aug 25, 11(4), 128 - 31
Antibacterial treatment in exacerbations of chronic obstructive pulmonary disease . Pitfalls in study design and evaluation; Wijnands WJ; In studies aimed at assessing the efficacy and safety of antibacterial agents used in treating infections of the respiratory tract, patients with exacerbations of a chronic obstructive pulmonary disease frequently are included . Both the indication for the prescription of an antibiotic and the evaluation of its effect can be difficult . As a general rule, treatment with steroids, bronchodilators and oxygen supply is indicated in cases of exacerbated pulmonary disease . These interventions will influence the clinical and bacteriological parameters usually used to evaluate the antibacterial effect . In a number of cases, non-antibacterial treatment will restore the bronchopulmonary defence sufficiently so that infection control is reached . In order to design meaningful efficacy studies, it is obligatory to understand the pathophysiological mechanisms in chronic obstructive pulmonary disease, to be aware of the pitfalls in making the diagnosis 'bacterial bronchitis' and to take into account the influence of co-medications on the clinical and bacteriological parameters . Some objections to comparative efficacy trials are raised.

Nippon Geka Gakkai Zasshi, 1989 Aug, 90(8), 1251 - 7
{Experimental and clinical studies on prevention of vascular prosthetic infection}; Kurata H; Since the treatment of infected vascular prosthetic graft is difficult, it is important to prevent graft infection . At the operation of aneurysmectomy, a part of aneurysmal wall was cultured . As a result, bacterial growth could be seen in 21 out of 58 cases (36%) . In this experiment, expanded polytetrafluoroethylene (E-PTFE) graft was soaked in a solution of tobramycin (TOB) and tested for the prevention of graft infection . First, this E-PTFE graft with a TOB solution was tested for antithrombogenicity and patency rate, and secondly its effect of preventing graft infection was evaluated . 1 . TOB had an effect of antithrombogenicity . 2 . Patency rates of the E-PTFE graft with a TOB solution were as good as those of the graft soaked in a saline solution . 3 . TOB concentration in the grafts was more than 100 micrograms/g after 6 hours from the implantation and more than MIC after 24 hours . 4 . E-PTFE graft with a TOB solution had an effect of antibacteria . This study suggested that E-PTFE graft soaked in a TOB solution was effective to prevent graft infection.

J Chemother, 1989 Aug, 1(4), 244 - 7
Antibacterial activity of the dialysates and sera during treatment with chemotherapeutic combinations in continuous ambulatory peritoneal dialysis (CAPD); Beader N et al.; In everyday clinical practice, different chemotherapeutics are mostly applied intraperitoneally in treating continuous ambulatory peritoneal dialysis (CAPD) peritonitis . Antibacterial activity of the dialysates and sera were studied, according to their bacteriostatic effect after the intraperitoneal and/or peroral administration of chemotherapy . All samples were tested by the two-fold dilution method . We found that the best therapeutical effect is obtained by applying the combination of two compatible chemotherapeutics, in which the first acts in the peritoneal cavity, and the other represents the "pool" of chemotherapeutics forming a barrier to the spreading of bacteria into other distant parts of the body.

J Chemother, 1989 Aug, 1(4), 223 - 5
Evaluation of ciprofloxacin's activity against recent clinical isolates; Nani E et al.; The in vitro antibacterial activity of ciprofloxacin, a new quinoline carboxylic acid, was tested against 1671 recently clinically isolated bacterial strains, by measuring the minimum inhibitory concentrations (MIC) . Comparisons were made with other quinolones: nalidixic acid, norfloxacin, and other drugs: piperacillin, cefoxitin, cefotetan, ceftazidime, tobramycin, rifampin, tetracycline, chloramphenicol . Ciprofloxacin was very active against the tested species and was the most active drug against all the bacterial strains, with a geometric mean, a MIC50 and MIC90 of 0.27, 0.12 and 2 micrograms/ml, respectively.

J Med Chem, 1989 Aug, 32(8), 1749 - 53
N-azamonobactams . 2 . Synthesis of some N-iminoacetic acid and N-glycyl analogues; Curran WV et al.; The synthesis of the title compounds has been accomplished . The N-iminoacetic acid analogues (12a and 12b) containing the aminothiazole type side chain exhibited good in vitro antibacterial activity against Gram-negative organisms . The corresponding N-glycyl derivative (17) was not active.

J Periodontol, 1989 Aug, 60(8), 435 - 40
A clinical comparison of antibacterial mouthrinses: effects of chlorhexidine, phenolics, and sanguinarine on dental plaque and gingivitis; Grossman E et al.; This study compared the clinical efficacy of three mouthrinses containing either 0.12% chlorhexidine, phenolic compounds, or sanguinarine, which were used unsupervised, in a placebo-controlled, double-blind study of 6 months' duration . The study was conducted according to ADA clinical guidelines for evaluation of antigingivitis agents and was completed by 481 adults . Following baseline exams and a prophylaxis, subjects were randomly divided into treatment groups matched for age, gender, and gingivitis severity, and were instructed to use the rinses in accordance with manufacturer's directions . Followup examinations evaluated supragingival plaque, gingivitis, and gingival bleeding . Compared to placebo at 6 months, the group rinsing with 0.12% chlorhexidine had significantly less gingivitis (31% reduction), gingival bleeding (39% reduction), and plaque (49% reduction) and was significantly better than any of the other treatment groups (P less than 0.05) . Both the phenolic and sanguinarine groups showed moderate, yet significant, reductions in plaque compared to placebo (24% and 12% respectively) yet were significantly less effective than the 0.12% chlorhexidine rinse (P less than 0.05) . However, neither the phenolic nor sanguinarine rinses were significantly different than placebo in their effects on gingivitis or gingival bleeding . These results support previous published results on the superiority of 0.12% chlorhexidine when used in conjunction with professional care and as an adjunct to routine oral hygiene practices.

EMBO J, 1989 Aug, 8(8), 2387 - 91
Apidaecins: antibacterial peptides from honeybees; Casteels P et al.; Although insects lack the basic entities of the vertebrate immune system, such as lymphocytes and immunoglobulins, they have developed alternative defence mechanisms against infections . Different types of peptide factors, exhibiting bactericidal activity, have been detected in some insect species . These humoral factors are induced upon infection . The present report describes the discovery of the apidaecins, isolated from lymph fluid of the honeybee (Apis mellifera) . The apidaecins represent a new family of inducible peptide antibiotics with the following basic structure: GNNRP(V/I)YIPQPRPPHPR(L/I) . These heat-stable, non-helical peptides are active against a wide range of plant-associated bacteria and some human pathogens, through a bacteriostatic rather than a lytic process . Chemically synthesized apidaecins display the same bactericidal activity as their natural counterparts . While only active antibacterial peptides are detectable in adult honeybee lymph, bee larvae contain considerable amounts of inactive precursor molecules.

J Med Chem, 1989 Aug, 32(8), 1942 - 9
2,4-Diamino-5-benzylpyrimidines and analogues as antibacterial agents . 12 . 1,2-Dihydroquinolylmethyl analogues with high activity and specificity for bacterial dihydrofolate reductase; Johnson JV et al.; Twelve 2,4-diamino-5-{(1,2-dihydro-6-quinolyl)methyl}pyrimidines containing gem-dimethyl or fluoromethyl substituents at the 2-position of the dihydroquinoline ring were prepared by condensations of dihydroquinolines with 2,4-diamino-5-(hydroxymethyl)pyrimidine . The dihydroquinolines were produced from the reaction of anilines with mesityl oxide or fluoroacetone . In some cases, 1-aryl-2,4-dimethylpyrroles were obtained as byproducts . Most of these pyrimidines were highly inhibitory to Escherichia coli dihydrofolate reductase (DHFR) and also had high specificity for the bacterial enzyme . 2,4-Diamino-5-{{1,2-dihydro-2,4-dimethyl-3-fluoro-2-(fluoromethyl)-8- methoxy-6(1H)quinolyl}methyl}pyrimidine had an apparent Ki value for E . coli DHFR 13 times lower than that of the control, trimethoprim (1), and was 1 order of magnitude more selective for the bacterial enzyme . It had outstanding activity against Gram-positive organisms in vitro, as well as broad-spectrum antibacterial activity equivalent to that of 1 . The results of in vivo testing will be reported elsewhere . The gem-dimethyl substituents of the dihydroquinoline derivatives are considered to be responsible for the high selectivity, as well as contributing to potent bacterial DHFR inhibition . Molecular models are presented which suggest the probable interactions with the bacterial enzyme.

J Gen Microbiol, 1989 Aug, 135 ( Pt 8), 2249 - 57
Antibodies to a common outer envelope antigen of Treponema hyodysenteriae with antibacterial activity; Sellwood R et al.; Outer envelopes of Treponema hyodysenteriae strains P18A and VS1 were prepared and characterized by SDS-PAGE . In Western blot analysis of eleven strains of T . hyodysenteriae and two intestinal non-pathogenic spirochaetes, polyclonal antiserum raised to the outer envelopes of strain P18A contained antibodies primarily to two polypeptides . A 45 kDa polypeptide was present in only two strains of T . hyodysenteriae, P18A and MC52/80, whereas another antigen of 16 kDa was common to all eleven strains of T . hyodysenteriae but was not present in the two nonpathogens . Immunogold labelling of whole organisms suggested that the 16 kDa antigen was present on the surface of the spirochaetes . In in vitro tests the serum agglutinated and inhibited growth of only the T . hyodysenteriae strains, suggesting that antibodies to the 16 kDa antigen were responsible for these activities . Serum from a gnotobiotic pig infected with T . hyodysenteriae strain P18A had antibodies to the 16 kDa antigen alone and also possessed agglutinating and growth-inhibitory activities.

Vestn Khir Im I I Grek, 1989 Aug, 144(8), 107 - 10
{Errors in the diagnosis and treatment of infection}; Bochorishvili VG et al.; The authors made an analysis of their experience with treatment of sepsis in a specialized center . Typical errors in treatment of the disease in the general public health service are: insufficient sanitation of septic foci, inadequate antibacterial therapy . Not all main possibilities of complex therapy are always used . The problem of struggle against sepsis can not be solved without organization of antiseptic centers.

J Antibiot (Tokyo), 1989 Aug, 42(8), 1276 - 82
An unexpected intramolecular cyclization of isothiouronium teicoplanins . II . Reaction mechanism and biological activity; Trani A et al.; N15-Isothiouronium derivatives of teicoplanin and its aglycone submitted to alkaline condition give rise to an intramolecular cyclization . The structures of the new gamma-lactam derivatives were determined by using 1H NMR, IR and fast atom bombardment mass spectra . The cyclization mechanism was interpreted on the basis of the identification of the intermediate structure . The poor in vitro antibacterial activity of the new cyclic compounds and the negligible affinity for the synthetic peptidoglycan model Ac2-L-Lys-D-Ala-D-Ala is probably due to the lack of the N-17 amidic proton and to the lack of the basic character of the nitrogen in position 15.

J Antibiot (Tokyo), 1989 Aug, 42(8), 1268 - 75
Thioureas and isothiouronium salts of the aglycone of teicoplanin . I . Synthesis and biological activity; Trani A et al.; A series of thiourea and isothiouronium salt derivatives of the aglycone of teicoplanin was prepared by reaction of the terminal amino group with isothiocyanates, followed by S-alkylation of the thiourea compounds . Unexpectedly, the two classes of derivatives show a similar in vitro antibacterial activity against Gram-positive bacteria . Thiourea compounds, due to the lack of a positively charged N-terminus group, have a 10-fold lower binding constant to Ac-D-Ala-D-Ala, a bacterial cell-wall model, than the parent antibiotic and isothiouronium salt derivatives.

J Exp Med, 1989 Aug 1, 170(2), 601 - 6
Prostaglandins from human T suppressor/cytotoxic cells modulate natural killer antibacterial activity; Garcia-Penarrubia P et al.; We have recently described potent antibacterial activity of purified human NK cells . Here we show that this function is regulated by T cytotoxic/suppressor CD8+ cells . Thus, coculture of NK and CD8+ cells for 3 h or longer times abrogated the expression of the NK antibacterial activity, and of two activation markers IL-2R and transferrin receptor (Tf-R) . The suppressive activity was mediated by PGE2 as demonstrated by direct PGE2 determination in CD8+ cell free supernatants, and by inhibition of CD8+ cell suppression with indomethacin or piroxicam in vitro . We also found that resting T cytotoxic/suppressor cells purified by negative selection produce higher amounts of PGE2 than adherent cells like monocytes and macrophages, and that these concentration levels are in the range of concentrations known to suppress a significant number of in vitro immunologic functions.

Acta Paediatr Jpn, 1989 Aug, 31(4), 377 - 80
Maternal health, breast-feeding and infant nutrition in Australian aborigines; Gracey M; PIP: Widespread nutritional deficiencies among Australian Aborigine infants are associated with high rates of gastrointestinal and respiratory infections . Also prevalent in this population is a high incidence of low birthweight, which often leads to growth retardation extending throughout the 1st 5 years of life . In a study conducted in Western Australia in 1980, Aboriginal infants were an average of 1.16 kg lighter than their non-Aboriginal counterparts at birth . By 1 year of age, this difference was 2.01 kg for males and 2.23 kg for females; by 5 years of age, the Aborigine differential had reached 3.78 kg for males and 3.15 kg for females . A neglected factor has been the impact of maternal health on this pattern . 1 study of Aborigine women in northwest Australia found that only 40% of women of childbearing age had a satisfactory nutritional status . 25% of these women were overweight . Concentrations of lactoferrin--an iron-binding protein with antibacterial activity--are significantly lower in the breast milk of undernourished mothers . Thus, although traditional Aborigines breastfeed for over 18 months, their milk may be of inadequate quality to confer the protection against infection that is usually a benefit of this form of infant feeding . Thus, an effective approach to reducing the high rates of mortality and morbidity among Aborigine infants would be to target the poor health and nutrition of Aborigine women of reproductive age .

J Med Chem, 1989 Aug, 32(8), 1936 - 42
2,4-Diamino-5-benzylpyrimidines and analogues as antibacterial agents . 11 . Quinolylmethyl analogues with basic substituents conveying specificity; Davis SE et al.; A series of nine 2,4-diamino-5-{6-( or 7-)quinolylmethyl}pyrimidines has been prepared by condensations of quinolinecarboxaldehydes with beta-anilinopropionitriles, followed by treatment with guanidine . All compounds has basic or methoxy substituents at the 2- or 4-positions of the quinoline ring . All of the 6-quinolylmethyl derivatives were highly inhibitory against Escherichia coli dihydrofolate reductase (DHFR), provided that an 8-substituent was present in the quinoline ring . Those compounds that had basic substituents in the 2-position of the quinoline ring were also highly specific for bacterial dihydrofolate DHFR, relative to a vertebrate counterpart . Protonation on the quinoline ring nitrogen is a possible cause of specificity.

J Med Chem, 1989 Aug, 32(8), 1927 - 35
2,4-Diamino-5-benzylpyrimidines and analogues as antibacterial agents . 10 . 2,4-Diamino-5-(6-quinolylmethyl)- and -{(tetrahydro-6-quinolyl)methyl}pyrimidine derivatives . Further specificity studies; Rauckman BS et al.; A series of 18 2,4-diamino-5-{(1,2,3,4-tetrahydro-6-quinolyl)methyl}pyrimidines has been prepared by the condensation of 2,4-diamino-5-(hydroxymethyl)pyrimidine with 1,2,3,4-tetrahydroquinolines in acidic medium . Several derivatives were catalytically aromatized; others were synthesized from these by routine aromatic substitution or by condensations of (anilinomethyl)pyrimidines to give quinolinylmethyl analogues . Compounds with 4-methyl-8-methoxy substitution are closely related to trimethoprim (1a) in structure and are excellent inhibitors of bacterial dihydrofolate reductase, with activity at least equivalent to that of 1a . The highest degree of inhibition was achieved with the rigid aromatic series, but greater specificity was accomplished among the tetrahydroquinoline derivatives . This was directly related to N-1 substitution of 4-methyl-8-methoxy derivatives . The spatial relationships around N-1 and protonation at this site may both affect selectivity . Such compounds also had excellent broad-spectrum in vitro antibacterial activity.

J Med Chem, 1989 Aug, 32(8), 1886 - 90
(3-Amino-2-oxoalkyl)phosphonic acids and their analogues as novel inhibitors of D-alanine:D-alanine ligase; Chakravarty PK et al.; The dipeptide D-alanyl-D-alanine is an essential precursor of bacterial peptidoglycan; thus, blocking its formation is a possible target for the design of novel antibacterial agents . The synthesis of this dipeptide by bacterial D-alanine:D-alanine ligase requires ATP . In analogy with glutamine synthetase, we hypothesized a mechanism for this enzyme involving the intermediacy of D-alanyl phosphate . Several (3-amino-2-oxoalkyl)phosphonic acids and their analogues have been synthesized as possible inhibitory mimics of this proposed intermediate . The most active of them, (3(R)-amino-2-oxobutyl)phosphonic acid (8a) and the corresponding aza analogue (22), were effective ligase inhibitors although they had no significant antibacterial activity . The ligase inhibition of these compounds is consistent with an acyl phosphate displacement step in the mechanism of DAla-DAla ligase.

Antibiot Khimioter, 1989 Jul, 34(7), 551 - 5
{Polyantibiotic therapy in the complex treatment of patients with acute diffuse peritonitis}; Bondarev VI et al.; On the basis of the analysis of 217 records of acute diffuse peritonitis peculiarities of the postoperative process of that complication in persons treated with 2 antibiotics (161) and 4 antibacterial drugs (56) were discussed . 4 risk levels were defined with an account of the inflammation process severity . The use of poly-antibiotic therapy was validated . The technique of its application is described in detail . The technique allowed to lower the frequency of postoperative complications and lethality 5-fold.

Antibiot Khimioter, 1989 Jul, 34(7), 549 - 51
{Antibacterial therapy in disseminated purulent peritonitis}; Sorokina MI et al.; Analysis of 156 records relating to patients at the age of 15 to 85 years with extended purulent peritonitis of the surgical and gynecological genesis (the toxic phase, VI category ASA) showed that combination of programmed sanitation laparotomy and intensive antibacterial therapy performed as short-term courses before, during and after the operation with an account of the information on the nature of the microbial associations and antibioticograms was an efficient procedure in treatment of severe peritonitis . It was indicated in treatment of patients with polyorgan deficiency . When the surgical treatment was adequate early antibiotic therapy allowed to decrease the number and intensity of postoperative complications: the frequency of abscessing in the abdominal cavity and formation of intestinal fistulas lowered 2 and 1.5 times respectively . Such a decrease was also observed in asthenic patients with lowered protective reactions to development of new infectious foci in the abdominal cavity complicating the peritonitis process . It was also possible to prevent with that procedure the infection generalization and development of peritoneal sepsis . With application of the procedure to such patients (20 per cent) lethality lowered 2-fold.

Ortop Travmatol Protez, 1989 Jul, (7), 1 - 4
{Complex prevention of suppurative complications of long surgical procedures using microsurgical technics}; Me'lnikova VM et al.; The authors have demonstrated the efficacy of complex approach to the solution of the problem of postoperative infectious complications in prolonged surgical interventions with application of microsurgical technique in orthopaedic and traumatologic patients . A reduction in the course of prophylaxis with antibiotics in this category of the patients has been substantiated . The use of metabolite therapy in the course of presurgical preparation of the patients under the control of cytochemical investigations allows to carry on the surgery with a more favourable state of the macroorganism . The use of supersonic cavitation for antibacterial treatment of the operative wounds in prolonged interventions with application of microsurgical technique has no specific contraindications . The complex of these measures has allowed to reduce the rate of suppurations after prolonged surgical interventions with application of microsurgical technique from 23.01 to 8%.

J Pharm Sci, 1989 Jul, 78(7), 585 - 8
Synthesis and in vitro antibacterial activity of some 1-(difluoromethoxyphenyl)quinolone-3-carboxylic acids; Xiao W et al.; We report on the synthesis of N-1-phenylquinolones in which the difluoromethoxy moiety is utilized as a halogen replacement . The antibacterial activity is discussed with reference to N-1-halophenylquinolones.

Jpn J Pharmacol, 1989 Jul, 50(3), 283 - 8
Studies on oxacephem antibiotics: comparison of the effects of 1-oxa and 1-thia cephalosporins on blood coagulation activities and vitamin K metabolism in rats; Uchida K et al.; Oxacephem antibiotics have been developed to increase the antibacterial activity of cephem antibiotics, but the effect of 1-oxygen replacement of cephem antibiotics on blood coagulation activities is not yet known . Therefore, latamoxef (LMOX), flomoxef (FMOX) and their 1-S congeners were examined for their effects on prothrombin time, activated partial thromboplastin time, plasma prothrombin and Factor VII levels, plasma and liver descarboxyprothrombin (PIVKA-II) levels, and liver microsomal vitamin K epoxide reductase activities in rats kept on a vitamin K-deficient diet . Under the vitamin-deficient states, LMOX, FMOX and their 1-S congeners inhibited the vitamin K epoxide reductase, although the effect of FMOX or its congener was much less than that of LMOX, and they decreased the blood clotting activities in rats fed a vitamin K-deficient diet . However, no difference was found in these effects between LMOX and its 1-S congener or between FMOX and its 1-S congener . This result suggests that the 1-oxygen replacement of cephem antibiotics is not responsible for the hypoprothrombinemic effect of the antibiotics.

J Antibiot (Tokyo), 1989 Jul, 42(7), 1114 - 23
Chemical modification of hitachimycin . III . Synthesis and antitumor activities of amino acyl derivatives; Shibata K et al.; Amino acyl derivatives of hitachimycin have been synthesized and evaluated their activities including antibacterial, cytocidal against HeLa cells and in vivo antitumor against sarcoma 180 . 15-O-(tert-Butoxycarbonyl(BOC)-glycyl)hitachimycin (2), 15-O-(BOC-beta-alanyl)hitachimycin (4), 15-O-(BOC-(O-tert-Bu)-glutamyl)hitachimycin (6) and 15-O-L-alanylhitachimycin (11) showed comparable in vivo antitumor activity with hitachimycin and the solubility of these compounds was improved.

J Antibiot (Tokyo), 1989 Jul, 42(7), 1100 - 13
Synthesis and antibacterial activity of 5-methylcarbapenems; Onoue H et al.; Four possible racemic isomers of N-acetyl-5-methylthienamycin derivatives were synthesized and their antibacterial activities are discussed in relation to their physico-chemical properties . 5-Methylcarbapenems having various C-2 side chains were also prepared.

J Antibiot (Tokyo), 1989 Jul, 42(7), 1037 - 42
Studies on a novel antitumor antibiotic, phenazinomycin: taxonomy, fermentation, isolation, and physicochemical and biological characteristics; Omura S et al.; A new antibiotic, phenazinomycin (C27H32N2O, MW 400), was isolated from the cultural mycelium of Streptomyces sp . WK-2057 . This antibiotic possesses antibacterial activities against Gram-positive bacteria in vitro, direct cytotoxic activities against HeLa S3, P388 and P388 doxorubicin-resistant cells in vitro and antitumor activities against experimental murine tumors in vivo.

Antibiot Khimioter, 1989 Jul, 34(7), 545 - 8
{Antibacterial prophylaxis and treatment of wound infection in the light of the development of the ideas of Z . V . Ermol'eva}; Mel'nikova VM et al.; At present we use antibiotics in treatment of wound infections on the basis of the teaching of Z . V . Ermolyeva on their prophylactic and therapeutic value developed during the Great Patriotic War . We consider that along with thorough primary surgical treatment the use of antibiotics in cases with open fracture is indicated . In "clear" operations on the bones and joints we use antibiotics only in patients with risk of infection . In cases with purulent infection and isolation of multicomponent microbial associations from the wound including also nonsporulating anaerobic organisms we mostly apply combined antibacterial chemotherapy with immunotherapy and surgical treatment.

Stomatologiia (Mosk), 1989 Jul-Aug, 68(4), 15 - 8
{The use of lysoamidase for treating complications of caries and diseases of the periodontium and oral mucosa}; Borovskii EV et al.; Antibacterial and proteolytic enzyme lysoamidase was used to treat periodontitis and a range of diseases of oral mucosa . The results displayed its major advantages over trypsin and allowed us to recommend it as an effective means of local treatment in the combined therapy of these disorders.

Rev Infect Dis, 1989 Jul-Aug, 11 Suppl 5, S979 - 84
Use of fluoroquinolones for intracellular pathogens; Pocidalo JJ; Current microbiologic techniques (determinations of minimal inhibitory and/or microbicidal concentrations) are unable to delineate the true role of anti-infectious drugs in the treatment of human infections due to intracellular pathogens . The prediction and evaluation of the efficacy of quinolones against intracellular pathogens requires information on four different steps . (1) Quinolones should be able to penetrate phagocytes; intramacrophagic concentration is highly dependent on serum pharmacokinetics; finally, the best quinolone should have the longest serum half-life and reach highest maximum serum concentrations . (2) The evaluation of antibacterial activity requires an adequate cellular model (e.g., multiplication of Legionella pneumophila within human monocyte-derived macrophages) . (3) The prediction of drug efficacy requires an experimental animal model . (4) Clinical trials in human disease are necessary . This stage is difficult when the evaluation concerns severe infectious diseases because the rarity of these diseases makes random clinical trials difficult . In this paper we describe methodologies for assessing the efficacy of quinolones against intracellular bacterial pathogens with a particular focus on Legionella pneumophila.

J Med Microbiol, 1989 Jul, 29(3), 221 - 7
Interactions of the 4-quinolones with other antibacterials; Lewin CS et al.; The effect of sub-inhibitory concentrations of 16 antibacterials on the bactericidal activity of the 4-quinolones nalidixic acid, ciprofloxacin and ofloxacin against Escherichia coli KL16 in nutrient broth was investigated . Sub-inhibitory concentrations of rifampicin, clindamycin, chloramphenicol, erythromycin or tetracycline antagonised the bactericidal activity of the 4-quinolones . Conversely, all seven aminoglycosides tested enhanced the bactericidal activity of the 4-quinolones whereas the cell wall antagonists, azlocillin, mezlocillin, ceftazidime and vancomycin had no effect on the bactericidal activity of the 4-quinolones.

Acta Haematol Pol, 1989 Jul-Dec, 20(2), 201 - 5
{Phagocytic activity of platelets in patients with pneumonia}; Kemona H et al.; In 22 patients with pneumonia the per cent of phagocytizing platelets and the phagocytosis index of the platelets were determined before treatment and in 14 patients this was done after treatment . Before treatment the per cent of phagocytizing platelets was 1.37%, on average, and after treatment it was 1.20, and it was thus much lower than in the control group X 2.33 . The phagocytosis index before treatment was 1.39 on average, and after treatment it was 1.28, while in the control group it was 1.54 . The obtained results seem to indicate that in pneumonia platelets participate in the antibacterial processes and the lungs as a thrombopoietic organ contribute to this phenomenon.

Farmaco, 1989 Jul-Aug, 44(7-8), 695 - 702
Individual degradation rate constants for cefotaxime, deacetylation profile; Fabre H et al.; The individual degradation rate constants for cefotaxime in aqueous solution were calculated within a pH range of 1.6-10.0 at 37 degrees C from high performance liquid chromatography data . This allowed the general degradation profile of cefotaxime to be decomposed into a degradation profile attributed to the opening of the beta-lactam nucleus and a degradation profile attributed to the deacetylation . From the calculations of the individual rate constants, the activity of degraded cefotaxime solutions could be predicted . In the pH range of injectable solutions of cefotaxime 5-7, roughly equivalent amounts of inactive beta-lactam cleavage products and deacetylated compound which has a different spectrum of antibacterial activity are formed.

Rev Infect Dis, 1989 Jul-Aug, 11 Suppl 5, S941 - 6
Quinolone uptake by bacteria and bacterial killing; Diver JM; A review of the mechanisms of the action of 4-quinolones is presented, concentrating on the process of uptake and bacterial killing . 4-Quinolones appear to cross the gram-negative outer membrane via diffusion through outer-membrane proteins, although disruption of the normal outer-membrane barrier by 4-quinolones may facilitate diffusion via a non-porin-mediated route . Accumulation in the cytoplasm may involve influx and efflux mechanisms . The inhibition of DNA synthesis by 4-quinolones has been investigated in Escherichia coli AB1157 and found to correlate with antibacterial activity (as measured by the minimal inhibitory concentration) . 4-Quinolones have other pleotropic effects on bacterial cells, such as induction of the SOS (DNA repair) response, filamentation, and direct effects on membranes.

Infect Immun, 1989 Jul, 57(7), 2196 - 202
Relationship between neutrophil-mediated oxidative injury during acute experimental pyelonephritis and chronic renal scarring; Meylan PR et al.; Previous experiments with rats have suggested that pyelonephritic scarring after acute ascending Escherichia coli pyelonephritis partly results from excessive polymorphonuclear leukocyte (PMN) infiltration and activation in the kidney parenchyma . We have studied the role of PMN oxidative metabolism in generating tissue injury during acute pyelonephritis . Rats with acute pyelonephritis were treated with dapsone (25 mg/kg twice daily for 3 days), a compound known to prevent PMN oxidant damage . In vitro, levels of dapsone easily achieved in vivo inhibited myeloperoxidase (MPO)-mediated reactions involving the oxidation of halides to reactive cytotoxic hypohalites (such as MPO-mediated iodination and luminol-enhanced chemiluminescence) . In contrast, dapsone had no effect on superoxide production, lysosomal enzyme release, or bacterial killing by activated PMN . In vivo, dapsone treatment had no significant effect on acute pyelonephritis with respect to (i) bacterial counts, (ii) inflammatory swelling, and (iii) PMN infiltration . However, dapsone-treated animals sacrificed 2 months after acute pyelonephritis had a 65% reduction of renal scars when compared with controls . Since dapsone had no antibacterial effect, this protection is compatible with the hypothesis that dapsone prevented oxidant-generated tissue injury due to the extracellular release of the MPO system by activated PMN during acute suppurative pyelonephritis.

J Antibiot (Tokyo), 1989 Jul, 42(7), 1124 - 32
Synthesis and biological activity of 7 alpha-hydroxyethyl-1-oxacephem derivatives; Nishimura S et al.; A series of 7 alpha-hydroxyethyl-1-oxacephems (1) was synthesized . The main focus of this study was to investigate biological activity relationships between 1-oxacephems (1) and the corresponding cephems (2) . Replacement of the sulfur atom of 2 by the oxygen atom caused an enhancement of antibacterial activity, although the antibacterial activity of 1 was not high enough . Additionally 1 showed beta-lactamase inhibitory activity, especially against cephalosporinase . However, the potency was lower than that of 2.

J Biol Chem, 1989 Jun 15, 264(17), 9768 - 71
Canavanine incorporation into the antibacterial proteins of the fly, Phormia terranovae (Diptera), and its effect on biological activity; Rosenthal GA et al.; In response to microbial infection or mechanical injury, larvae of the fly, Phormia terranovae (Diptera), can induce de novo production of a group of antibacterial proteins including: peak I protein, diptericin A, diptericin B, diptericin C, and peak V protein . Administration of L-canavanine at the time of mechanical injury results in the incorporation of this arginine antagonist into these proteins . Canavanine replacement for arginine causes a total loss of detectable antibacterial activity for diptericin B and diptericin C, whereas diptericin A and peak V protein are severely inhibited . This loss in biological activity occurs in spite of the fact that canavanine stimulates induced protein synthesis . Analysis of the hydrolysate of diptericin A reveals that one-third of the 3 arginyl residues are replaced by canavanine . This investigation provides the first evidence that canavanine incorporation into a protein can impair its function.

Eur J Biochem, 1989 Jun 15, 182(2), 423 - 7
Insect immunity . Isolation of cDNA clones corresponding to diptericin, an inducible antibacterial peptide from Phormia terranovae (Diptera) . Transcriptional profiles during immunization; Reichhart JM et al.; We have previously isolated and characterized a family of novel 8-kDa cationic antibacterial peptides synthesized by larvae of Phormia terranovae (Diptera) in response to various injuries . These molecules have been named diptericins . The peptide sequence of diptericin A was used to prepare oligonucleotides for screening cDNA libraries and we report in the present paper the isolation of several cDNA clones encoding diptericin . The analysis of the nucleotide sequences indicates that diptericin is synthesized as a prepeptide which is matured in two steps: (a) cleavage of a signal peptide and (b) amidation of the C-terminal residue . Interestingly, the 3' untranslated region of the mRNA contains a consensus sequence TTATTTAT which is also observed in the mRNA of another insect antibacterial peptide (attacin-related sarcotoxin IIA) and in mRNAs encoding proteins related to the inflammatory response in mammals . Our data illustrate that diptericins form a polymorphic family of immune peptides . The transcription of the diptericin genes is rapidly induced in the fat body after inoculation of bacteria, as evidenced by the transcriptional profile.

Yakugaku Zasshi, 1989 Jun, 109(6), 377 - 87
{Synthetic cephalosporins . III . Synthesis and antibacterial activity of 7-{2-(2-Aminothiazol-4-yl)-3-carboxy-2-propenoamido}cep hal osporins and related compounds}; Sakagami K et al.; Synthesis and antibacterial activity of 7-{2-(2-aminothiazol-4-yl)-3-carboxy-2-propenoamido}cepha los porins and their derivatives are described . These compounds are of interest as carbon analogues of oximecephalosporins, 7-{2-(2-aminothiazol-4-yl)-2(Z)-oxyiminoacetamido}cephalo spo rins having remarkable antibacterial activity . The synthesized 7-{2-(2-aminothiazol-4-yl)-3(Z)-carboxy-2-propenoamido}-c eph alosporins (14, 19) show improved activity especially against the beta-lactamase-producing strains . A 7-{2-(2-aminothiazol-4-yl) maleimido}cephalosporin (15) has been also prepared by cyclization of 7-{3-(2-aminothiazol-4-yl)-2-ethoxycarbonyl-2(Z)-propenoamido++ +}cephalosporin.

Antibiot Khimioter, 1989 Jun, 34(6), 420 - 5
{Micro-ecological aspects of studies on the effect of antibacterial drugs on intestinal microflora}; Mikel'saar ME et al.; Possible characterization of intestinal microflora as an integral system after exposure to antibacterial drugs was studied . Microflora of the contents and mucosa of the jejunum and large intestine in control rats and in rats exposed to metronidazole was studied and numerical indicators characterizing ratios of dominating and accompanying microbial groups in the intestine biotope++ were developed . With this purpose the proportion of the microbial groups in the total quantity of the microbes of a microbiocenosis was determined by the data on microflora quantitative composition . On the basis of detected wide species variety of microorganisms potentially dominating by their biotope numerical limits of the norm were determined only for the microbial groups of the accompanying microflora . The total proportion of the accompanying microbial populations under the normal conditions and the detected measure of deviation (reverse, partial) from the ratio of the dominating and accompanying microorganisms peculiar of the given biotope++ in separate subjects promoted estimation of microbiocenoses of definite biotope of the intestine as a whole.

Pathol Biol (Paris), 1989 Jun, 37(5 Pt 2), 517 - 22
{In vitro bactericidal effect of a piperacillin-pefloxacin combination against isolated strains of nosocomial pneumopathies in intensive care}; Simeon De Buochberg M et al.; Combinations of piperacillin and pefloxacin are evaluated in vitro using checkerboard and killing-curves methods against 19 clinical isolates: S . aureus, K . pneumoniae, K . oxytoca, C . freundii, P . stuartii, Ps . aeruginosa, Ps . maltophilia and Ac . anitratum . The static checkerboard method showed more synergistic antibacterial effects than the killing curves method . The best synergistic effects appeared against S . aureus, K . oxytoca, P . stuartii, Ps . aeruginosa Ac . anitratum, including a notable increase of the rapidity of bactericidal activity . The combination PIP 64 micrograms - PEF 4 micrograms prevents the frequent secondary regrowth seen after 6 hours with the antibiotics used alone . No activity is obtained against S . aureus meti-R and Ps . maltophilia.

Jpn J Antibiot, 1989 Jun, 42(6), 1346 - 57
{Laboratory and clinical investigations of cefodizime in infectious diseases in childhood}; Komada Y et al.; In this study, cefodizime (CDZM, THR-221) was administered to 34 children with infections and the efficacy was evaluated in 30 patients . The efficacy rate was 90.0% and CDZM was proved to be a highly effective antibiotic for infectious diseases in childhood . We also demonstrated that CDZM had strong antibacterial activities against both Gram-positive and Gram-negative bacteria . No severe toxicity related to intravenous injection of CDZM was observed in our 34 cases.

J Comput Aided Mol Des, 1989 Jun, 3(2), 149 - 64
Highly conformationally constrained halogenated 6-spiroepoxypenicillins as probes for the bioactive side-chain conformation of benzylpenicillin; Shute RE et al.; The halogenated 6-spiroepoxypenicillins are a series of novel semisynthetic beta-lactam compounds with highly conformationally restricted side chains incorporating an epoxide . Their biological activity profiles depend crucially on the configuration at position C-3 of that epoxide . In derivatives with aromatic-containing side chains, e.g., anilide, the 3R-compounds possess notable Gram-positive antibacterial activity and potent beta-lactamase inhibitory properties . The comparable 3S-compounds are antibacterially inactive, but retain beta-lactamase inhibitory activity . Using the molecular simulation programs COSMIC and ASTRAL, we attempted to map a putative, lipophilic accessory binding site on the PBPs that must interact with the side-chain aromatic residue . Comparative computer-assisted modelling of the 3R-, and 3S-anilides, along with benzylpenicillin, indicated that the available conformational space at room temperature for the side chains of the 3R- and the 3S-anilides was mutually exclusive . The conformational space for the more flexible benzylpenicillin could accommodate the side chains of both the constrained penicillin derivatives . By a combination of van der Waals surface calculations and a pharmacophoric distance approach, closely coincident conformers of the 3R-anilide and benzylpenicillin were identified . These conformers must be related to the antibacterial, 'bioactive' conformer for the classical beta-lactam antibiotics . From these proposed bioactive conformations, a model for the binding of benzylpenicillin to the PBPs relating the three-dimensional arrangement of a putative lipophilic S2-subsite, specific for the side-chain aromatic moiety, and the 3 alpha-carboxylate functionality is presented.

Int J Pept Protein Res, 1989 Jun, 33(6), 412 - 21
Design, synthesis and antibacterial activity of cecropin-like model peptides; Fink J et al.; In order to investigate structure-activity relationships of cecropins, model peptides that mimic certain structural features of the cecropin molecules were designed and synthesized . The conformational analysis of cecropins and the design of the model peptides were based on Chou-Fasman calculations . The peptides were synthesized by solid-phase methods and purified by reverse-phase liquid-chromatography on C18-silica columns . Their secondary structures were studied by circular dichroism measurements . Antibacterial activities against seven test organisms were determined and compared to the activities of the natural cecropins A and B . These results were discussed on the basis of structural features of the model peptides and on model mechanisms . It was concluded that high antibacterial activity for this class of compounds requires a basic helical amphipathic N-terminal segment that is connected to a hydrophobic helical C-terminal segment by a flexible non-helical hinge region.

Pharm Res, 1989 Jun, 6(6), 486 - 91
Prediction of the distribution volumes of cefazolin and tobramycin in obese children based on physiological pharmacokinetic concepts; Koshida R et al.; So as to estimate the appropriate dose of antibacterial drugs in obese children, prediction of the volume of distribution in these children was attempted based on physiological pharmacokinetic concepts which had been constructed from results in normal-weight children . Serum concentration-time data after intravenous drip infusions of tobramycin and cefazolin were analyzed using noncompartmental analysis of obese children in whom the degree of obesity ranged from 30 to 80% . Volume of distribution at steady state (Vss) per total body weight of tobramycin was significantly less than that for normal-weight children (P less than 0.05), whereas the value of cefazolin was almost equal to that for normal-weight children . The equation to express the difference of Vss between cefazolin and tobramycin obtained in normal-weight children failed in obese children, suggesting that there is a large decrease in the extracellular space in obese children exceeding the interindividual variations in normal-weight children . The Vss value (liter) for tobramycin was predicted by using the equation 0.261 . (ideal body weight (kg) + 0.4 . {total body weight (kg) - ideal body weight (kg)}) . The Vss value of cefazolin was predicted to be 0.3 . (predicted Vss of tobramycin) + 0.052 . total body weight (kg) . A good correlation between the predicted and the observed Vss values was obtained.

J Antibiot (Tokyo), 1989 Jun, 42(6), 993 - 9
Orally absorbable D-forphenicinol-cephalosporins; Koyama Y et al.; The synthesis and biological evaluation of D-forphenicinol-cephalosporins are described . 7-Amino-3-(substituted)-3-cephem-4-carboxylic acid esters were coupled with N-tert-butoxy-carbonyl-D-forphenicinol derivatives . Most of cephalosporin analogs in this series had good antibacterial activities and were well absorbed from the gastrointestinal tract in mice . Among them, 7-(mono-O-methyl-D-forphenicinol)-3-propenyl analog showed the most significant result in biological evaluations.

Clin Orthop, 1989 Jun, (243), 36 - 40
Factors influencing infection rate in open fracture wounds; Patzakis MJ et al.; Seventy-seven infections in 1104 open fracture wounds were evaluated to identify those factors that predisposed to infection . Factors could be placed into three categories: (1) increased risk, (2) no effect, and (3) inconclusive . The single most important factor in reducing the infection rate was the early administration of antibiotics that provide antibacterial activity against both gram-positive and gram-negative microorganisms . In this study, surgical debridement was performed on all open fracture wounds.

Antibiot Khimioter, 1989 Jun, 34(6), 409 - 14
{Effect of antibiotics on intestinal microflora and production of metabolites}; Tamm AO et al.; Methodical approaches to detection of relation between intestinal microflora and its metabolites are described . The microbial origin of certain compounds can be asserted by a decrease in their production after exposure to antibacterial drugs or the absence of their production in microbe-free animals . The authors consider that parallel investigation of intestinal microflora and its metabolites after exposure to various agents e.g . narrow spectrum antibiotics or specific substrates is the most accurate methodical approach to detection of their interrelations . Data on the effect of four drugs i.e . kanamycin, metronidazole, cefotaxime and bactrim on production of 10 bacterial metabolites: p-cresol, phenol, indican, acetic, propionic, butyric, isobutyric, valeric, isovaleric and caproic acids in rats are presented . Correlation between the metabolites and the intestinal microflora composition was revealed . It is concluded that detection of microorganisms responsible for production of definite metabolites requires at the maximum: (1) exposure to drugs of different spectra, (2) detection of changes in intestinal microflora by biotope++ and (3) investigation of mucosa microflora which more exactly characterizes metabolism of definite biotops.

Pathol Biol (Paris), 1989 Jun, 37(5 Pt 2), 664 - 7
{Quantitative study of the antibacterial effect of cefotaxime and ceftriaxone during experimental Escherichia coli K1 bacteremia in chickens}; Labarthe JC et al.; In order to assess the in vivo antibacterial activity of two cephalosporins of third generation, cefotaxime and ceftriaxone, we used the model of experimental bacteremia in chickens we had developed for a few years . 93 chickens were inoculated with 10(7) E . coli K1 coming from a meningitis in a new-born baby . 19 chickens were used as a control group; 29 were given ceftriaxone (50 mg/kg); 28 cefotaxime (50 mg/kg) and 17 cefotaxime (100 mg/kg) . The antibiotics were injected 4 hours after the inoculation . The bacterial concentrations found in capillaries by using quantitative blood cultures, were significantly lower in the 3 groups of chickens which were given antibiotics than in the control group, at 24, 48 and 72 hours after inoculation . At 24 hours after the inoculation, the bacterial concentration in the chickens treated by ceftriaxone (50 mg/kg) was significantly lower than that found in chickens treated by cefotaxime (50 mg/kg) . At 48 or 72 hours the differences of bacterial concentration in the three groups of chickens were not significant . Over 72 hours following inoculation, 4 control and only one treated chickens died . The efficient clearance of E . coli K1 by a single dose of ceftriaxone, found at 24 hours after inoculation, confirms the possibility of using ceftriaxone once daily for serious infections.

J Dairy Sci, 1989 Jun, 72(6), 1665 - 78
Immunological aspects of mammary involution; Nickerson SC; Frequency of new intramammary infection is greatest during early involution, decreases during middle stages, and then increases prepartum . Penetrability of the teat canal, antibacterial properties of keratin, bacterial adherence, and epithelial sensitivity to toxins play a role in resistance . Leukocytes phagocytose bacteria and regulate expression of immune mechanisms, although their function is compromised during certain stages of involution . These cells increase to millions per milliliter as involution progresses and then decrease prepartum . Macrophages predominate in lacteal secretions, followed by lymphocytes and neutrophils . Lactoferrin, a major whey protein and iron chelator, is also associated with resistance to infection during the nonlactating period and may have immunomodulatory properties . Lacteal immunoglobulins increase throughout involution peaking prepartum and function by opsonizing bacteria, neutralizing toxins, and preventing bacterial adherence . Immunoglobulins are derived from blood or are produced locally by plasma cells present in the subepithelial mammary stroma . Plasma cells, lymphoid cells, and other protective leukocytes present in teat end tissues accumulate during infection and concentrations increase in response to local antigenic stimulation . Various aspects of the mammary immune system are compromised during periods of functional transition . Thus, vaccination, immunostimulation, accelerated involution, and intramammary devices are some methods now being tested to amplify local immunity and protect the gland from bacterial infection.

J Antibiot (Tokyo), 1989 Jun, 42(6), 977 - 88
Studies on penem antibiotics . II . In vitro activity of SUN5555, a new oral penem; Nishino T et al.; The new oral penem antibiotic SUN5555 shows broad antibacterial activity against both aerobic and anaerobic Gram-positive and Gram-negative bacteria . SUN5555 is highly stable against various beta-lactamases . It binds preferentially to the penicillin-binding proteins 2 and 1A of Escherichia coli.

Pol Arch Med Wewn, 1989 Jun, 81(6), 368 - 72
{Conservative treatment of perforation of the transverse colon caused by a catheter for continuous peritoneal dialysis . A case report}; Grzegorzewska A et al.; In rare cases of intestinal perforation in patients dialysed peritoneally may be the dialyzing catheter introduced into the peritoneal cavity for repeated use . The therapeutic procedure (conservative or operative) is the matter of dispute . The authors present a female patient, aged 62, undergoing intermittent peritoneal dialysis for terminal renal failure . The perforation of the transverse colon due to the dialyzing catheter was successfully treated conservatively: the catheter was removed, antibacterial drugs, parenteral nutrition and bedrest were administered . Uraemia was controlled by haemodialysis.

Dtsch Zahnarztl Z, 1989 Jun, 44(6), 452 - 3
{Bacteriological studies on the use of sonic and ultrasonic units in endodontics}; Mayer R; Two units for root canal preparation operated in the sonic and ultrasonic range have been tested for their antibacterial action The Cavi-Endo-Unit (DeTrey/Dentsply) rendered the root canal absolutely sterile in less than 60s, while the Endo MM 3000 Sonic Air (Micro Mega) left the root canal with evident germs after as much as 5 min.

Boll Chim Farm, 1989 Jun, 128(6), 212 - 5
{Preparation and antileukemic activity of quinolizidinylalkyl-derivatives of 4-aminoquinoline and 9-aminoacridine}; Boido Canu C et al.; By reacting three quinolizidinylalkylamines with 4,7-dichloroquinoline and 6,9-dichloro-2-methoxyacridine six derivatives of 4-aminoquinoline and 9-aminoacridine were obtained . These compounds, which are of interest as potential antibacterial, antiprotozoarian, anti-helminthic and antitumoral agents, so far have been tested against lymphocytic leukemia P 388 and found to be inactive.

Boll Chim Farm, 1989 Jun, 128(6), 208 - 11
{Formulation and antileukemic activity of quinolizidinylalkylaminic derivatives of naphthoquinone and anthraquinone}; Boido Canu C et al.; By reacting three quinolizidinylalkylamines with 1,4-naphtoquinone, 2,3-dichloronaphto-1,4-quinone and 1-chloroanthraquinone nine compounds were obtained which are of interest as antitumoral, antiviral, antibacterial and antiparasitic agents . These compounds, so far, have been tested against lymphocytic leukemia P 388 in mice and found inactive.

Pathol Biol (Paris), 1989 Jun, 37(5 Pt 2), 600 - 4
{Relation of the chelating property of nitroxoline, the surface hydrophobicity and the inhibition of bacterial adherence}; Bourlioux P et al.; Nitroxoline or 5-nitro-8-hydroxyquinoline acts by a chelating effect with various metallic divalent cations . The chelating property of nitroxoline has been proposed as an hypothesis to explain the activity of this drug, at sub-MIC, on the inhibition of bacterial adherence . Nitroxoline (MIC/4) does not inhibit fimbriae synthesis but its antibacterial activity on E . coli 387 (MS/MS) was decreased by the addition of MgCl2 (50 mM) and CaCl2 (10 mM) . The chelating effect of nitroxoline is mainly due to the presence of the nitrous radical in position 5 . Nitroxoline would act at the outer membrane level of the bacterial cell-wall by a chelating effect preferentially with Mg++ than Ca++ . Furthermore, nitroxoline (MIC/8) increases the bacterial surface hydrophobicity of E . coli 38 in contrast to EDTA (MIC/4) . The both products inhibit the bacterial adherence to cells with the same manner.

Antimicrob Agents Chemother, 1989 Jun, 33(6), 886 - 94
Cloning and characterization of a DNA gyrase A gene from Escherichia coli that confers clinical resistance to 4-quinolones; Cullen ME et al.; Nalidixic acid, enoxacin, and other antibacterial 4-quinolones inhibit DNA gyrase activity by interrupting DNA breakage and reunion by A subunits of the A2B2 gyrase complex . Despite their clinical importance, the mode of quinolone action and mechanisms of resistance are poorly understood at the molecular level . Using a DNA fragment enrichment procedure, we isolated the gyrA gene from a uropathogenic Escherichia coli strain that encodes a gyrase A protein cross-resistant to a variety of quinolones . When complemented with gyrase B subunit, the purified A protein reconstituted DNA supercoiling activity approximately 100-fold more resistant to inhibition by enoxacin than the susceptible enzyme and failed to mediate quinolone-dependent DNA cleavage . Nucleotide sequence analysis revealed that the gene differed at 58 nucleotide positions compared with the K-12 gyrA sequence . The 875-amino-acid residue-resistant gyrase A protein differed at three positions from its wild-type E . coli K-12 counterpart: tryptophan, glutamate, and serine replaced serine, aspartate, and alanine residues at positions 83, 678, and 828, respectively . By genetic analysis of chimeric gyrA genes in a gyrA(Ts) background, we showed that the Ser-83----Trp mutation in the gyrase A protein was solely responsible for high-level bacterial resistance to nalidixic acid and fluoroquinolones.

Pathol Biol (Paris), 1989 Jun, 37(5 Pt 2), 573 - 7
{In vitro effect of various antibiotics: beta lactams, aminoglycosides and fluoroquinolones alone and in combination against P . aeruginosa isolated from patients with mucoviscidosis}; Croize J et al.; The antibacterial activity of fluoroquinolones (ciprofloxacin and ofloxacin) combined with beta lactams (ceftazidime and imipenem) or aminoglycosides (tobramycin and amikacin) against 22 P . aeruginosa isolated from the sputum of patients with cystic fibrosis was determined by the checkerboard method and compared with the combination of beta lactams (with ticarcillin) with aminoglycosides . Synergistic association (defined as FIC index less than ou = 0.5) was founded for 23 to 41% of strains with beta lactams (except imipenem)/aminoglycosides, in 18% with ceftazidime/ciprofloxacin, in 13% with imipenem/ciprofloxacin, in 0 or 13% with quinolones/aminoglycosides . For a FIC index less than ou = 0.75, the values are highest with 82% for ciprofloxacin/ceftazidime and 50% for ofloxacin/ceftazidime . The CMI's achieved in these combinations may allowed concentrations near to sputum concentrations.

J Med Chem, 1989 Jun, 32(6), 1313 - 8
Synthesis of novel 5-fluoro analogues of norfloxacin and ciprofloxacin; Moran DB et al.; A series of polyfluoro-3-quinolonecarboxylic acids have been synthesized and their in vitro antibacterial activity evaluated . The desired 7-(substituted amino) derivatives were prepared from the 5,6,7,8-tetrafluoroquinolone acids . Conversely, amine displacement occurred primarily at the 5-position when the ester was used . Structure-activity studies indicated that the antibacterial activity was greatest when the N-1 substituent was cyclopropyl and the 7-substituent was 4-methyl-1-piperazinyl . All 5-(substituted amino) derivatives showed poor in vitro activity.

Nippon Hotetsu Shika Gakkai Zasshi, 1989 Jun, 33(3), 571 - 6
{Antibacterial actions of denture base resin on oral bacteria}; Yamauchi M et al.; Antibacterial action of various denture base resins on thirteen species of bacteria were studied in vitro . Antibacterial effect of 5% tannin-fluoride preparation, 5% tannic acid and 5% chlorhexidine added to resins on these thirteen bacterial species were also investigated using heat-curing denture base resins . Fresh microwave-curing resin and pour-type resin each showed an antibacterial action on one bacterial strain . Fresh self-curing resins had antibacterial actions on several bacterial strains . However, after storage in water at 37 degrees C for one week, antibacterial action of microwave-curing and pour-type resin were diminished and self-curing resins partially lost their antibacterial actions . Denture base resin containing tannin-fluoride preparation or tannic acid showed an antibacterial effect on one bacterial strain . On the other hand, denture base resin containing chlorhexidine had an antibacterial action on eleven bacterial strains . However, color and mechanical properties of the drug-containing resins were not satisfactory.

Biochemistry, 1989 May 2, 28(9), 3886 - 94
Mechanism of inhibition of DNA gyrase by quinolone antibacterials: a cooperative drug--DNA binding model; Shen LL et al.; We have proposed a cooperative quinolone-DNA binding model for the inhibition of DNA gyrase . The essential feature of the model is that bound gyrase induces a specific quinolone binding site in the relaxed DNA substrate in the presence of ATP . The binding affinity and specificity are derived from two unique and equally important functional features: the specific conformation of the proposed single-stranded DNA pocket induced by the enzyme and the unique self-association phenomenon (from which the cooperativity is derived) of the drug molecules to fit the binding pocket with a high degree of flexibility . Supporting evidence for and implications of this model are provided.

Biochemistry, 1989 May 2, 28(9), 3879 - 85
Mechanism of inhibition of DNA gyrase by quinolone antibacterials: specificity and cooperativity of drug binding to DNA; Shen LL et al.; Although the functional target of quinolone antibacterials such as nalidixic acid and norfloxacin has been identified as the enzyme DNA gyrase, the direct binding site of the drug is the DNA molecule {Shen, L . L., & Pernet, A . G . (1985) Proc . Natl . Acad . Sci . U.S.A . 82, 307-311} . As described in this paper, binding specificity and cooperativity of quinolones to DNA were further investigated with the use of a variety of DNA species of different structures and different base compositions . Results show that the drug binding specificity is controlled and determined largely by the DNA structure . The drug binds weakly and demonstrates no base preference when DNA strands are paired . The drug binds with much greater affinity when the strands are separated, and consequently, binding preference emerges: it binds better to poly(G) and poly(dG) over their counterparts including poly(dI) . The results suggest that the drug binds to unpaired bases via hydrogen bonding and not via ring stacking with DNA bases . The weak binding to relaxed double-stranded DNA and the stronger binding to single-stranded DNA are both nonspecific as they do not demonstrate binding saturation and cooperativity . The specific type of binding, initially demonstrated in our previous publication with the supercoiled DNA and more recently with complex formed between linear DNA and DNA gyrase {Shen, L . L., Kohlbrenner, W . E., Weigl, D., & Baranowski, J . (1989) J . Biol . Chem . (in press)}, occurs near the drug's supercoiling inhibition concentration . As shown in this paper, binding saturation curves of this type are highly cooperative (with Hill constant greater than 4).(ABSTRACT TRUNCATED AT 250 WORDS)

Vopr Pitan, 1989 May-Jun, (3), 34 - 7
{Composition of the intestinal microflora in children with hypotrophy}; Smiian IS et al.; The intestinal microflora was investigated in 120 children aged 1 month to 2 years with different forms of hypotrophy . The majority of the children demonstrated an impairment of intestinal biocenosis manifesting by dysbacteriosis of different gravity . The relationship was discovered between the depth of the dysbiotic abnormalities and the underlying etiological factor that promoted the development of the chronic nutrition distress, hypotrophy gravity, the type of feeding, and treatment . The treatment of hypotrophy with bacterial drug inclusion made the children's intestinal microflora return to normal or appreciably improved it . The dysbiotic abnormalities in children with hypotrophy should be regarded as the result of the long-term use of antibacterial therapy (not justified in all the cases) in this patients' group, of inadequate feeding, and a considerable decrease of the body resistance.

Vestn Khir Im I I Grek, 1989 May, 142(5), 29 - 30
{Lysozyme-forming function of the liver in complicated acute cholecystitis}; Lokhvitskii SV et al.; An investigation of the lysozyme activity of the hepatic tissue, B-bile and C-bile has shown that in mechanical jaundice the lysozyme activity of the hepatic tissue is increased . A reliable decrease of the C-bile lysozyme activity is noted in patients with purulent cholangitis . In spite of adequate methods of external drainage of bile ducts in purulent cholangitis the bacterial activity of bile due to lysozyme is recovered slowly . The results obtained allow to make the degree of inflammation of bile ducts objective and to optimize the duration of antibacterial therapy.

Indian J Med Res, 1989 May, 89, 198 - 200
Preliminary investigation on antibacterial activity of some marine diatoms; Selvaraj R et al.; Seven species of marine diatoms were cultured under defined laboratory conditions . Air dried algal powder was used for extraction with different solvents in sequence . The algal extracts were tested against various bacteria by paper disc method . Nitzschia longissma, Skeletonema costatum and Biddulphia sinensis were effective against the test bacteria . Hemidiscus hardmannianus, Coscinodiscus centralis and Asterionella japonica showed moderate antibacterial activity . Pleurosigma elongatum exhibited no activity . The antibacterial substances were fully extracted by the organic solvents . Only in the active algal species, was activity noted in the aqueous extracts.

Stomatologiia (Mosk), 1989 May-Jun, 68(3), 21 - 3
{Validation of the choice of antibacterial agents for treating periodontitis}; Kononovich EF et al.; Sensitivity of microflora sampled from the dental root channels of periodontitis patients to chlorhexidine, dioxidine, quinosol, Metrodgile was investigated . Chlorhexidine and dioxidine were shown to act predominantly on gram-positive and gram-negative bacteria, Metrodgile most active against anaerobic flora . High antibacterial activity of quinosol and chlorhexidine was combined with their pronounced cytotoxic effects . Metrodgile could be successfully used for preventing purulent odontogenic inflammations caused by anaerobic flora.

J Antimicrob Chemother, 1989 May, 23(5), 681 - 9
The entry of antibiotics into human monocytes; Hand WL et al.; Effective therapy of infections due to facultative intracellular micro-organisms, which persist after ingestion by mononuclear phagocytic cells, requires the use of antibiotics with the ability to inactivate these intra-phagocytic bacteria . Since entry of antibiotics into mononuclear phagocytes is a pre-requisite for activity against such intracellular organisms, we have determined the uptake of 11 radiolabelled antibiotics by human peripheral blood monocytes . beta-Lactams (penicillin G, cefamandole and cefotaxime), gentamicin, and metronidazole had a limited ability to enter monocytes, achieving cellular concentrations which were equal to or less than extracellular levels (C/E less than or equal to 1) . Imipenem, a novel beta-lactam antibiotic, rapidly bound to monocytes, but cell-associated drug progressively declined during further incubation . Chloramphenicol, a lipid-soluble drug, and trimethoprim were concentrated three-fold by human monocytes . In comparison with the other antibiotics, roxithromycin (C/E = 14), clindamycin (C/E = 6 to 7) and erythromycin propionate (C/E = 4 to 5) were markedly concentrated by human monocytes . In contrast to our findings in other phagocytes, there was no evidence that active membrane transport was involved in monocyte uptake of clindamycin, erythromycin and roxithromycin . We have demonstrated that several antibiotics are highly concentrated within human monocytes, and it will be important to evaluate the effects of this antibiotic uptake on various monocyte functions, including intra-phagocytic antibacterial activity.

J Antibiot (Tokyo), 1989 May, 42(5), 718 - 26
Chemical modification of hitachimycin . II . Synthesis and antitumor activities of carbonate derivatives; Shibata K et al.; Several carbonate derivatives of hitachimycin have been synthesized and evaluated their activities including antibacterial, cytocidal against HeLa cells and in vivo antitumor against Sarcoma 180 . Some of these derivatives showed higher antitumor activity than hitachimycin . Among the derivatives, 11,15-di-O-methoxycarbonylhitachimycin (2), 11,15-di-O-ethoxycarbonylhitachimycin (3) and 15-O-methoxycarbonylhitachimycin (9) were most effective in in vivo assay.

J Dent Res, 1989 May, 68(5), 835 - 9
The modified model cavity method for assessing antibacterial properties of dental restorative materials; Meryon SD et al.; A new in vitro method for assessing the antibacterial properties of dental restorative materials is described with ratios of test material/culture medium volume aiming to simulate conditions around a restoration in vivo . Antibacterial activity is determined by the reduction in optical density of the test culture relative to controls . The method was used for assessment of the antibacterial activity of five dental materials of different composition against five oral bacteria . Release of zinc and fluoride from these materials was also measured and correlated with antibacterial activity . There was a general trend toward greater antibacterial activity with increased zinc release, while fluoride release had a significant effect on only one organism . While all the materials, when freshly mixed, were strongly toxic to three out of the five bacteria studied, much of this activity was lost after the materials had set.

Infect Immun, 1989 May, 57(5), 1457 - 64
Antipneumococcal effects of C-reactive protein and monoclonal antibodies to pneumococcal cell wall and capsular antigens; Briles DE et al.; Antibodies to pneumococcal capsular polysaccharides are well known for their ability to protect against pneumococcal infection . Recent studies indicate that antibodies to cell wall antigens, including pneumococcal surface protein A and the phosphocholine (PC) determinant of teichoic acids as well as human C-reactive protein (which also binds to PC), can protect mice against pneumococcal infection . In the present study we compared the protective effects of these agents as measured by mouse protection, the blood bactericidal assay, and clearance of pneumococci from the blood and peritoneal cavity . Our findings extend previous results indicating that human C-reactive protein and antibodies to noncapsular antigens are generally less protective than anticapsular antibodies . The new results obtained indicate the following: (i) mouse protection studies with intraperitoneal and intravenous infections provide very similar results; (ii) monoclonal immunoglobulin G2a (IgG2a) antibodies to PC, like IgG1, IgG2b, and IgG3 antibodies to PC, are highly protective against pneumococcal infection in mice; (iii) human antibody to PC is able to protect against pneumococcal infection in mice; (iv) antibodies to PspA are effective at mediating blood and peritoneal clearance of pneumococci; (v) complement is required for the in vivo protective effects of both IgG and IgM antibodies to PC; (vi) IgG1, IgG2b, and IgG3 anti-PC antibodies all mediate complement-dependent lysis of PC-conjugated erythrocytes; and (vii) antibodies and human C-reactive proteins that are reactive with capsular antigens but not cell wall antigens are able to mediate significant antibacterial activity in the blood bactericidal assay.

Ankara Univ Hekim Fak Derg, 1989 May, 16(1), 103 - 7
{Antibacterial properties of two conventional and two high copper dental amalgams}; Gunyakti N et al.; Two conventional and two high copper dental amalgams (Non gamma 2) has been investigated for their antibacterial properties . The high copper dental amalgam, Ana 2000 possessed a very small range of antibacterial propertie against Lac . acidophilus and Staph . epidermidis, while other amalgams found to have no antibacterial activity against the ten tested microorganism strains.

Chem Pharm Bull (Tokyo), 1989 May, 37(5), 1239 - 44
Synthesis and biological evaluation of 3-chloro-1-carbacephem compounds; Matsukuma I et al.; The 3-chloro-1-carbacephem nucleus was prepared for the first time from a 3H-1-carbacephem compound through a sequence of reactions involving addition of thiophenol, oxidation of sulfide to sulfoxide, and alpha-chlorination of the sulfoxide, followed by elimination of phenylsulfinic acid . The 2-beta-methyl analog was similarly prepared, but the 2 alpha-methyl analog was not obtained . Optical resolution of the 3-chloro-1-carbacephem compound was achieved by the employment of penicillin acylase . That is, the 7-phenylacetamido derivative was enantioselectively hydrolyzed to afford the optically active 7-amino-3-chloro-1-carbacephem compound . Carbacefaclor, the carbacephem analog of cefaclor, was directly and efficiently prepared by enzymatic phenylglycylation of the racemic 7-amino-3-chloro-1-carbacephem compound by using immobilized penicillin acylase . Carbacefaclor thus prepared exhibited comparable antibacterial activity against most gram positive bacteria tested and higher activity against typical gram negative bacteria as compared with cefaclor . Moreover, carbacefaclor possessed remarkably high chemical stability.

Nihon Kyobu Shikkan Gakkai Zasshi, 1989 May, 27(5), 597 - 603
{Luminol-amplified chemiluminescence evaluation of the microbicidal property of alveolar macrophages in response to drugs}; Chida K et al.; The present study was designed to evaluate the validity of luminol-dependent chemiluminescence (CL) to evaluate the microbicidal properties of alveolar macrophages (AM) in response to drugs . It was observed that production of CL is associated with H2O2 as well as O2-, 1O2, .OH . Furthermore, our data revealed that CL is dependent not only upon the extracellular release of these oxygen radicals, but also upon intracellular metabolic events, which thus allows a complete analytical study in any given state . It should also be noted from our data that the effect of antibacterial agents on CL was greatly affected by the source of the target cells . The defect of amplified CL in AM obtained from young rabbits might be attributable to immaturity of AM.

South Med J, 1989 May, 82(5), 563 - 9
Intracranial complications of sinusitis; Parker GS et al.; Sinusitis is a common problem that is routinely diagnosed and treated by most primary care physicians . Although most cases usually respond to appropriate therapy, some occasionally progress to the development of intracranial complications, including meningitis, osteomyelitis, epidural and subdural empyema, intracranial mucocele or polyps, and frank brain abscess . It is important to develop a rational approach to the diagnosis and treatment of these conditions . A high clinical index of suspicion must always be maintained, since symptoms are often masked by previous antibiotic therapy . Radiologic evaluation must always include computerized tomography (CT) for accurate diagnosis and surgical planning . Therapy includes surgical drainage and high doses of appropriate intravenous antibiotics . Cefuroxime and metronidazole provide excellent broad spectrum antibacterial coverage . Only early recognition and appropriate therapy can reduce the potential morbidity and mortality associated with these life-threatening complications.

Eur J Clin Microbiol Infect Dis, 1989 May, 8(5), 402 - 12
New antifungal agents; Graybill JR; For more than two decades, amphotericin B has been the single broad-spectrum agent for the treatment of systemic mycoses . Amphotericin B is not always effective, must be given parenterally, and is associated with a host of adverse reactions . Despite amphotericin B toxicity, until recently the systemic mycoses did not rate enough attention to prompt a search for new alternatives . However, three recent events have overcome this inertia: the gradually increasing use of potent immunosuppressive agents and broad-spectrum antibacterial drugs; the discovery of the relatively nontoxic azole classes of antifungal drugs in the 1980s and the rapid emergence of AIDS, with its severe accompanying opportunistic fungal infections . In just ten years we have seen the emergence of second-generation imidazole and third-generation triazole antifungal drugs and, most recently, entirely new classes of agents . It is remarkable that so many alternatives are becoming available just at the time when new antifungal drugs have become a major need . This discussion will concentrate on the new antifungal drugs of the past ten years, with the exception of developments in the polyenes and flucytosine, which are covered elsewhere.

J Chir (Paris), 1989 May, 126(5), 287 - 93
{Oxygen free radicals and inflammatory diseases of intestines}; Emerit J et al.; Free oxygen radicals (F.O.R.) belong to a very aggressive chemical species derived from molecular oxygen . Their role in inflammation is well established and Polymorphonuclear neutrophils (PMNS) make use of them as antibacterial weapons . Their role has been experimentally demonstrated in numerous ischemia-reperfusion models . Free radical scavengers such as the superoxide dismutase, allopurinol or desferrioxamine can prevent the occurrence of lesions . The essential role of PMNS in these models is demonstrated by the fact that previous depletion of the animal in PMNS also prevents such lesions . Histologically, in these ischemia-reperfusion models, PMNS infiltration may be quantified by assay of myeloperoxidase . In experimental models of inflammatory colitis (acetic acid, bacterial polysaccharides) intestinal wall infiltration by PMNS is a fundamental phenomenon and is also a characteristic of Crohn's disease and exacerbations of Ulcerative Colitis . Thus, it is probable in both disorders that F.O.R . play an important role since steroids inhibit their secretion by PMNS and 5-aminosalicylic acid has been shown to be a F.O.R . scavenger.

APMIS, 1989 May, 97(5), 447 - 51
Antibiotics and human monocyte function . II . Phagocytosis and oxidative metabolism; Nielsen H; The influence of thirteen commonly used antibacterial drugs on the phagocytic and oxidative burst responsiveness of human blood monocytes in vitro was investigated . Cefotaxime and rifampicin produced a significant inhibition of monocyte oxidative metabolism at therapeutic concentrations with increasing inhibition at higher concentrations . The effect of rifampicin was irreversible, which may reflect intracellular accumulation of the drug . Tetracycline, clindamycin, chloramphenicol and tobramycin at high concentrations produced a significant inhibition of monocyte superoxide anion release after stimulation, whereas normal therapeutic concentrations produced insignificant inhibition . Benzylpenicillin, ampicillin, fusidic acid, metronidazole, ofloxacin, sulfamethoxazole and trimethoprim did not alter monocyte oxidative metabolism in vitro . Phagocytosis of yeast cells was significantly suppressed by high concentrations of tobramycin, but otherwise unaffected by the drugs mentioned . These observations suggest that cefotaxime and rifampicin may interfere with blood monocyte oxidative metabolism in vivo, whereas it can be expected that at normal dosage it is unlikely that the other drugs will affect monocyte phagocytosis and oxidative burst activity.

Pathol Biol (Paris), 1989 May, 37(5), 386 - 9
{In vitro activity of miocamycin compared with four other macrolides and with pristinamycin against Branhamella catarrhalis}; Suermondt G et al.; The in vitro antibacterial activity of miocamycin was compared with four other macrolides (erythromycin, roxithromycin, josamycin, spiramycin) and pristinamycin against 90 clinical isolates of Branhamella catarrhalis by determination of minimum inhibitory concentrations . Sixty three strains were producing penicillinase . Fourteen carbons macrolides and pristinamycin are more effective than sixteen carbons macrolides . In this group, miocamycin have the best activity . There were no significant differences of susceptibility between penicillinase producing and non producing strains.

Pathol Biol (Paris), 1989 May, 37(5), 329 - 34
{Bactericidal synergy of josamycin and human polynuclear neutrophils in vitro}; Labro MT et al.; Due to their high intracellular uptake, macrolides may interfere with phagocytes antibacterial system . We have studied the interaction of josamycin with bactericidal activity of human neutrophils (PMNs) or whole blood, in vitro . PMNs preincubated with josamycin (100-0.1 mg/l) display an increased phagocytic ability for K . pneumoniae, independently of the concentrations of josamycin; this effect appears to correlate with the recruitment of an additional population of phagocytizing PMNs without alteration of the mean number of PMN-associated bacteria, whatever the experimental conditions (adherent or non adherent PMNs) . PMNs bactericidal function is also enhanced in the presence of josamycin in a dose-dependent manner (mean increase 60 to 370% for josamycin 0.1 to 10 mg/l) . Bactericidal activity of whole human blood for P . aeruginosa (a strain resistant to the lytic effect of serum) is increased with a mean survival (CFUt min/CFU 0 min) of 24 and 71% at 60 and 120 min respectively, in the presence of josamycin 10 mg/l, and 42 and 128% in the presence of josamycin 1 mg/l, compared to the survival of the control, 68 and 166% . PMNs functions are not altered by josamycin with the exception of an enhancement of the oxidative burst induced by formylmethionyl-leucyl-phenylalanine, a synthetic compound similar to bacterial derivatives . In conclusion, we have shown a synergic interaction between phagocytes and josamycin for the killing of bacteria resistant to this antibiotic (MiC greater than 128 mg/l) . This could be due either to an alteration of some PMN membrane receptors or to alterations of bacteria which render them more sensitive to natural bactericidal mechanisms and/or more able to activate these mechanisms.

Orthop Rev, 1989 May, 18(5), 617 - 23
Acute and subacute deep infection after uncemented total hip replacement using antibacterial prophylaxis; Hill GE et al.; Nine hundred thirty-two uncemented total hip replacement arthroplasties were studied . Seven hundred nineteen of these were primary operations with or without bone autograft . Two hundred thirteen were revisions with bone autograft and/or allograft . All were done by a single surgeon in a single operating theater . Prophylaxis included perioperative and postoperative antibiotics using either cefazolin or vancomycin, the use of a laminar flow room, and the use of total body exhaust systems . Aspiration of the hip with culture of the derived joint fluid was carried out preparatory to revision surgery . In each instance, the culture was negative . One acute infection and three subacute infections occurred three months and five months respectively after the index operation . One infection occurred seven months following complex revision surgery with bone allografting and autografting . The overall incidence of deep sepsis (four of 932 total cases) was 0.43% . The incidence of deep sepsis in the primary cases alone (three of 719) was 0.42% . In the revision series, the incidence of deep sepsis (one of 213) was 0.47% . No attempt was made to quantify the incidence of late sepsis . The incidence of acute and subacute postoperative deep sepsis after uncemented hip replacement, including revision surgery with major bone grafting, was comparable to other previously reported results on cemented hips.

J Immunol, 1989 Apr 15, 142(8), 2807 - 12
Preferential binding of the neutrophil cytoplasmic granule-derived bactericidal/permeability increasing protein to target bacteria . Implications and use as a means of purification; Mannion BA et al.; The specificity of the basic bactericidal/permeability increasing protein (BPI) of polymorphonuclear leukocytes (PMN) for gram-negative bacteria is attributable to its strong attraction for the negatively charged envelope LPS . The antibacterial activity of PMN homogenates or extracts toward Escherichia coli corresponds to their BPI content and is blocked by anti-BPI IgG, suggesting that BPI action is unaffected by the presence of other PMN proteins . To test if BPI is preferentially bound to E . coli when other antibacterial proteins are present, we have measured binding in buffered (pH 7.5) balanced salts solution of {125I} human BPI to E . coli J5 in the presence and absence of other human PMN granule proteins . BPI binding is saturable with an apparent K = 23 nM and 2.2 million binding sites/cell . While binding of {125I} human BPI is competitively inhibited by human or rabbit BPI, it is only weakly inhibited by myeloperoxidase, lysozyme, or cathepsin G . In contrast, myeloperoxidase binding to E . coli is strongly inhibited by BPI . Moreover, incubation of E . coli with crude extracts of PMN or CML spleen results in near quantitative binding of BPI, identified by silver staining and immunoblotting after SDS-PAGE of the washed E . coli pellet, without recognizable binding of other leukocyte proteins (greater than 98% of added total protein is recovered in supernatant) . After addition of 200 mM MgCl2, approximately 80% of bound BPI is released as fully active and pure protein (as judged by SDS-PAGE and HPLC) . Thus the selective and reversible binding of BPI in crude PMN extracts to target bacteria provides a one-step "affinity" purification procedure.

J Biol Chem, 1989 Apr 5, 264(10), 5852 - 60
Chemical synthesis and enzymic processing of precursor forms of cecropins A and B; Boman HC et al.; Radiolabeled preprocecropin B, with an alpha-amidated COOH terminus, and preprocecropin A, extended at the COOH terminus by a glycine residue, were synthesized by solid-phase methods . The respective syntheses were interrupted at intervals to allow the preparation of the predicted procecropins A and B as well as three other truncated derivatives of the cecropin A precursors . All the synthetic peptides were purified to near homogeneity by reverse-phase liquid chromatography and their purity was established by analytical high performance liquid chromatography, gel electrophoresis, and amino acid analysis . A dipeptidyl aminopeptidase was purified about 350 times from the hemolymph of cecropia pupae and characterized by its affinity for different substrates and inhibitors . The synthetic prepro peptides were tested for processing by an extract of dog pancreas microsomes and purified leader peptidase from Escherichia coli, with and without partly purified dipeptidyl aminopeptidase, and the two synthetic proforms were also processed with the dipeptidyl aminopeptidase alone . From these experiments we conclude that the signal/leader peptidase cleaves the peptide bond between Ala-5 and Ala-4 . This cleavage site is further substantiated by radio sequencing of procecropin A isolated after synthesis in a coupled system for in vitro transcription, translation, and processing . The two procecropins, which are stable to further digestion by the signal peptidase, are further processed by dipeptidyl aminopeptidase which removes, in two steps, the dipeptides Ala-Pro (residues -4 and -3) and Glu-Pro (residues -2 and -1) . Although the synthetic peptide with only one dipeptide (Glu-Pro) preceding the mature cecropin sequence could function as a substrate for dipeptidyl aminopeptidase, it could be demonstrated as an intermediate in the enzymatic reaction with the procecropins . Dipeptidyl aminopoptidase did not cleave the procecropin analog when it was preceded by a single alanine residue, i.e . preprocecropin (-5,38) . Antibacterial activity was demonstrated for the mature cecropin A-Gly obtained by processing of the synthetic preproprotein.

Pol Tyg Lek, 1989 Apr 3, 44(14), 327 - 31
{Clinical and hematological analysis of acute granulocytopenia}; Deptala A et al.; Retrospective analysis of 13 patients treated for the acute granulocytopenia at the Institute of Haematology for the last 10 years was carried out . Drugs were the most common causative factor . Comparing the results of the similar analysis several years ago in which the significant role was played by chloramphenicol, non-steroidal anti-inflammatory agents were the main cause . Infective complications were seen in all analysed patients . Broad spectrum antibiotics were used in all patients . Glycocorticosteroids were given to 9 patients while leucocytic concentrates to 7 patients . Remission was achieved in 12 patients, one female patient with the history of exposition to plant protection agents and increased levels of chlorinated aromatic hydrocarbons--died . Intensive antibacterial therapy significantly lowered mortality of the analysed patients in comparison with the similar group analysed earlier . Recurrence of granulocytopenia was seen in 5 patients following the contact with causative agent . Recurrencies were finished with remission.

Cornell Vet, 1989 Apr, 79(2), 161 - 71
Effect of experimental synovitis on disposition of penicillin and oxytetracycline in neonatal calves; Guard CL et al.; The effect of experimental synovitis on the distribution of antibacterial drugs into the joint space was studied in 7-day-old calves . Intrasynovial sodium urate was used to induce inflammation in the tibio-tarsal joint of calves and oxytetracycline (OTC) (11 mg/kg) or sodium penicillin G (PEN) (13.2 mg/kg) was administered intravenously 3 hours after synovitis was induced . Oxytetracycline and PEN concentrations were measured in serum and synovial fluid and pharmacokinetic parameters were calculated . The data indicate that synovitis neither enhanced nor impaired the levels of antibiotics achieved in the joint fluid . Mean peak concentrations (micrograms/ml) of the drugs in control and inflamed joints were, respectively, 8.04 and 8.79 for OTC and 9.35 and 8.92 for PEN . Rates of elimination of OTC and PEN were similar in joint fluid and serum; t1/2 beta ranged from 11.83-19.81 h for OTC and 0.980-1.125 h for PEN . The distribution and elimination of OTC and PEN from serum was described by a two-compartment model whereas elimination from joint fluid was described using a single-exponential model.

Rev Ig Bacteriol Virusol Parazitol Epidemiol Pneumoftiziol Bacteriol Virusol Parazitol Epidemiol, 1989 Apr-Jun, 34(2), 133 - 40
{Changes in the antibacterial activity of nitrofurantoin preparations induced by peptone and hydrolysates}; Marica D et al.; The determination of the activity of the product nitrofurantoin (10 and 100 mcg) versus 324 strains of Gram-negative bacteria showed that the diameter of the inhibition zones and the MIC values on a medium with a definite composition (7SG) are considerably larger than on the Mueller-Hinton (MH) medium, in the bacto-tryptose (BT) medium . An increase with 8-12 mm phi or with 2-4 binary dilutions changes the interpretation from resistant, on the MH and BT media into sensitive on the 7SG medium . The low results recorded on the conventional media reveal the existence of an antagonism between peptone and nitrofurantoin, similar to that known for sulfamides . The authors believe that the peptone antagonism has hindered the knowledge of the activity of the nitrofurfural derivatives and the correct assessment of the bacteria sensitivity . They also consider questionable the elimination tendency of the small dosage of microtablets of nitrofurantoin (10 mcg) and sulfamide (30 mcg), since their apparent insufficiency might be due less to the inadequate contraction of substances and more to the inadequate testing media . The results plead for the use of the media with definite chemical composition sulfamide and nitrofuran antagonists free and for reconsideration of several methodologic problems: use of the media with definite chemical composition; introduction of an intermediary dosage of maximum 100 mcg/microtablet; reassessment of the sensitivity categories for sulphafurazole and nitrofurantoin.

Jpn J Antibiot, 1989 Apr, 42(4), 910 - 20
{Effects of sulbactam/cefoperazone in patients with respiratory infections in aged and/or with underlying respiratory diseases}; Akutsu I et al.; Sulbactam/cefoperazone (SBT/CPZ), a new antibacterial drug, was administered to 14 cases with respiratory infections for a duration of 5 approximately 13 days at a daily dose of 4 g . Diagnoses of these patients were 7 respiratory tract infections, and 7 bronchopneumonias . The underlying diseases were chronic pulmonary emphysema in 6 cases, bronchial asthma in 2 cases, and one each of bronchiectasis, diffuse panbronchiolitis and lung cancer with bronchoesophageal fistula . All patients had underlying respiratory diseases and/or were more than 70 years old . The rate of clinical efficacy was 78.6% . The incidence of penicillinase production by isolated bacteria was 18.2% and that of cephalosporinase was 63.6% . SBT/CPZ was expected to be more effective than CPZ alone in 3 cases judging from the susceptibility of the bacterial strains concerned, to antibiotics . No side effects were observed . We conclude that SBT/CPZ is useful in the treatment of respiratory infections of patients of advanced age and/or with underlying respiratory diseases.

Jpn J Antibiot, 1989 Apr, 42(4), 831 - 53
{General pharmacology of T-3262, a new pyridonecarboxylic acid}; Hirai S et al.; General pharmacological activities of (+/-)-7-(3-amino-1-pyrrolidinyl)-6-fluoro-1-(2,4-difluorophenyl)-1,4- dih ydro- 4-oxo-1,8-naphthyridine-3-carboxylic acid p-toluenesulfonate hydrate (T-3262), which is a new pyridonecarboxylic acid, were examined with the following results . 1 . Central nervous system: T-3262 did not show any significant pharmacological effects at oral doses of 100-1,000 mg/kg but caused slow waves in spontaneous EEG in cats at intravenous doses of 10-30 mg/kg . 2 . Respiratory and cardiovascular system: T-3262 produced little effect in normotensive rats and anesthetized rabbits at oral doses of 100-1,000 mg/kg and intravenous doses of 3-30 mg/kg, respectively . But T-3262 caused, dose-dependently, an increase of respiratory rate, hypotension, decrease of heart rate and changes in ECG patterns (elevation of T waves, slow amplitudes of QRS complexes and prolongation of RR interval, etc.) in anesthetized dogs at intravenous doses of 3-10 mg/kg . 3 . Renal functions: T-3262 increased electrolyte excretions at oral doses of 300-1,000 mg/kg but did not affect PSP excretion in rats . 4 . Autonomic nervous system and smooth muscle organs: T-3262 exerted slight inhibition of gastric output in rats and slight miosis in mice at an oral dose of 1,000 mg/kg . But T-3262 did not affect the contraction of nictitating membrane in anesthetized cats at intravenous doses of 1-30 mg/kg . T-3262 increased spontaneous motilities of isolated stomach, ileum and uterus, but decreased that of isolated colon at concentrations of 10(-5)-10(-4) g/ml . 5 . Hematological examinations: T-3262 did not show any significant effects on bleeding time, blood coagulation, platelet aggregation and blood glucose level in rats at oral doses of 100-1,000 mg/kg . 6 . Miscellaneous effects: T-3262 exerted slight inhibitions of gastric secretion and of carrageenin-induced hind paw edema in rats at a dose of 1,000 mg/kg administered intraduodenally and orally, respectively . T-3262 did not affect neuromuscular junction and bile secretion in rats at intravenous doses of 3-30 mg/kg and oral doses of 100-1,000 mg/kg, respectively . From these results, it can be assumed that T-3262 has a wide safety margin as an oral antibacterial agent.

Jpn J Antibiot, 1989 Apr, 42(4), 817 - 30
{Nephrotoxicity test on T-3262 in rats with experimental nephropathy}; Nagai A et al.; The present study was carried out to examine the effect of orally administered T-3262, a new synthetic antibacterial agent, on the kidney of male rats with experimental nephropathy . These rats had been treated with single intramuscular injection of mercuric chloride (HgCl2, 3 mg/kg) or daily subcutaneous administration of puromycin-aminonucleoside (PAN, 15 mg/kg) for 11 days . T-3262 was administered orally to these pretreated rats at a dose of 1,000 mg/kg/day for 2 or 6 days . Twenty-four hours after the second or the sixth day of T-3262 administration, the kidneys of these rats disclosed similar biochemical and pathological findings as observed in the kidneys of the rats treated with HgCl2 alone . Thus, no T-3262-related alterations were demonstrated in renal functional test, kidney weight or histopathological examinations at a dose of 1,000 mg/kg of T-3262 . The HgCl2-induced nephropathy was not enhanced by the oral administration of T-3262 . Twenty-four hours after the second or the sixth day of T-3262 administration, the kidneys of the PAN-pretreated rats disclosed the biochemical and pathological findings largely similar to those with PAN-induced nephropathy . Enhancement of PAN-induced nephropathy by the oral administration of T-3262 was hardly evident.

Jpn J Antibiot, 1989 Apr, 42(4), 791 - 9
{Cytotoxicity studies on T-3262 in cultured Chinese hamster cells}; Yoneda T et al.; T-3262 is an antibacterial drug which belongs to the group of pyridonecarboxylic acids . In this study, we investigated cytotoxicity of T-3262 for inhibition of cell growth and effects on viability of, and morphological changes in cultured Chinese hamster cells (V79 cells) . The following results were obtained . 1 . The 50% inhibition dose of T-3262 for cell growth (ID50, cultured for 48 hours) was 12 micrograms/ml, showing that the inhibitory effect of T-3262 on the cell growth was stronger than that of enoxacin (ENX: ID50 44 micrograms/ml), norfloxacin (NFLX: ID50 105 micrograms/ml) or ofloxacin (OFLX: ID50 145 micrograms/ml) . 2 . The number of cells increased and dead cells were scarcely seen at the highest concentration tested in culture medium (40 micrograms/ml of T-3262 for 48 hours) . At this concentration, degeneration of cytoplasm (atrophy and round shape) and decrease of mitotic cells were observed . These morphological changes were similar to those of the cells treated 400 micrograms/ml of NFLX or OFLX for 48 hours . 3 . After the removal of T-3262 from culture medium, the cells began to grow actively and recovered from the morphological changes . The similar phenomenon was observed with ENX treated cells but not with fluorouracil or mitomycin C treated cells.

Jpn J Antibiot, 1989 Apr, 42(4), 1014 - 6
{Cefotiam concentration in the peritoneum in infants during surgery}; Obata K et al.; 1 . Supposing the hernia sac to be peritoneum, intraperitoneal transition of cefotiam (CTM) was examined on 57 cases of infantile inguinal hernia subdivided into 7 groups . 2 . After one shot intravenous injection, CTM showed rapid transition into the blood and the peritoneal tissue and even at a dose of 40 mg/kg and 120 minutes later . CTM exhibited an excellent antibacterial activity considering of MIC80 against clinically isolated bacterial strains . 3 . Healing by first intention of operative wounds was obtained in all of the cases given CTM without any case suggestive of postoperative infection . No clinical side effect was observed in any one of the cases.

Hinyokika Kiyo, 1989 Apr, 35(4), 727 - 34
{Diffusion of sulbactam and cefoperazone into the prostatic tissue}; Okamura K et al.; Diffusion of sulperazone (SBT) and cefoperazone (CPZ) into the prostatic tissue was studied in 20 cases . Two g of SBT/CPZ was injected intravenously and 1 hour later, prostatic tissue was obtained surgically and venous blood was drawn simultaneously . The serum concentration of CPZ (58.0 micrograms/ml +9.2) was higher than that of SBT (25.9 micrograms/ml +/- 9.3) and the prostatic tissue concentration of CPZ (14.9 micrograms/ml +/- 6.1) was higher than that of SBT (10.9 micrograms +/- 6.1) . However, the SBT concentration ratio of prostatic tissue to serum level (P/S ratio) was significantly higher (42.5%) than that of CPZ (25.9%) . The SBT concentration in the prostatic tissue was high enough to enhance the antibacterial activity of CPZ . SBT/CPZ was appraised to be an effective chemotherapeutic agent for infections of prostate caused by susceptible organisms, especially by beta-lactamase producing bacteria.

J Periodontol, 1989 Apr, 60(4), 199 - 204
Humoral immune response to selected subgingival plaque microorganisms in insulin-dependent diabetic children; Morinushi T et al.; Juvenile diabetics have been shown to have an increased susceptibility to gingivitis and periodontitis following puberty . However, little data are available on changes in the microbial flora that occur at the onset of puberty . This study was performed to determine if antibacterial antibody titers to selected periodontal disease-associated microorganisms might be helpful in revealing changes in plaque flora at the onset and conclusion of puberty . Sera was obtained from 35 subjects (ages 7 to 18 years) selected from a population of insulin-dependent diabetics . The subjects were given a thorough medical examination which included an assessment of sexual maturation and a dental examination which included the recording of onset and magnitude of bleeding according to the papillary bleeding score . Antibody titers to A . naeslundii (AN), B . intermedius (BI), B . gingivalis (BG), F . nucleatum (FN), A . actinomycetemcomitans (AA), C . ochracea (CO) and T . denticola (TD) were determined using the microELISA . Stratification of antibody titers by age groups (less than or equal to 12 years, 12 to 15 years, greater than 15 years) revealed that titers to AN increased significantly (P less than 0.025, ANOVA) and progressively (P less than 0.05, regression analysis) with increasing age . In contrast, the titers to FN were maximal in the under 12 year group and decreased with age (ANOVA, P less than 0.05; regression analysis, P less than 0.05) . There were no significant variations in titers observed for the other microorganisms . Stratification by sexual maturity revealed a similar progressive decrease of the titer to FN (ANOVA, P less than 0.05; regression analysis, P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Jpn J Antibiot, 1989 Apr, 42(4), 1025 - 50
{A comparative study on lomefloxacin and norfloxacin in the treatment of acute uncomplicated cystitis}; Ohmori H et al.; To objectively evaluate the efficacy, safety and utility of lomefloxacin (NY-198), a new quinolone antibacterial agent, in the treatment of acute uncomplicated cystitis, a comparative double blind trial was performed using norfloxacin (NFLX) as the control drug . In both groups, the drug was orally administered after meals for 3 days in a dose of 100 mg t.i.d . and clinical efficacies were assessed on the 3rd day (the 1st assessment) according to the criteria by the UTI Committee in Japan . Subsequently, either the active drug (NY-198 or NFLX) or placebo was administered for 4 days and the 2nd assessment was performed on the 7th day . Further, in patients who showed excellent responses at the 2nd assessment, recurrence was examined on the 14th day (the 3rd assessment) and on around the 21st day (the 4th assessment) following a subsequent 7-day placebo treatment . 1 . A total of 258 patients was treated, and among them clinical efficacies were evaluable in 207 patients (NY-198: 106, NFLX: 101) at the 1st assessment, and in 176 patients (NY-198-NY-198 which was the combination of the 1st and 2nd administrations: 47, NY-198-placebo: 43, NFLX-NFLX: 44, NFLX-placebo: 42) . 2 . In the evaluation of overall clinical efficacy by the committee at the 1st assessment, the overall efficacy rates in the NY-198 group and the NFLX group were 76.4% and 64.4% (excellent), respectively, or 100% and 99.0% (excellent and good), respectively . There was no statistically significant difference between the 2 groups . In the 1st assessment on effects of drugs on pain at micturition, pyuria and bacteriuria and on bacteriological response, no significant differences were observed between the 2 groups . 3 . In the 2nd assessment by the committee, there were statistically significant differences among the 4 groups in the overall clinical efficacies and the effects on bacteriuria (P less than 0.05) . No difference was observed between NY-198 group and NFLX group, but the groups administered with active drug for 7 days, i.e . NY-198-NY-198 group and NFLX-NFLX group were significantly superior to the groups administered with active drug for 3 days and placebo for subsequent 4 days, i.e . NY-198-placebo group and NFLX-placebo group (P less than 0.05) . There were no differences in the effects on pain at micturition and pyuria among the 4 groups.(ABSTRACT TRUNCATED AT 400 WORDS)

Vaccine, 1989 Apr, 7(2), 94 - 6
New cholera vaccines; Holmgren J et al.; Development of improved cholera vaccines has progressed rapidly in recent years . An oral killed vaccine, designed to evoke antibacterial as well as antitoxic intestinal immunity, has proved to be completely safe and to protect against cholera for at least 3 years . This vaccine also confers substantial though more short-lasting immunity against diarrhoea caused by enterotoxigenic Escherichia coli . Significant progress has also been made towards developing a live attenuated cholera vaccine using recombinant DNA techniques . The advent of effective oral cholera vaccines gives hope for improved control of cholera in the Third World.

Dtsch Tierarztl Wochenschr . 1989 Apr;96(4):168, 170, 172.
{Episodes of amyloidosis in young hens after repeated use of antibacterial oil emulsion vaccines}; Rampin T et al.; Outbreaks of systemic amyloidosis with moderate to high mortality in two young layer flocks are described . In both the cases anamnesis reported repeated vaccinations with oil-emulsified bacterins . Grossly, the liver was enlarged, friable and pale . Hepatic rupture and haemorrhages were frequently seen . Moreover heavy granulomatous reactions at the inoculation site was observed . Histologically amyloid deposition was present in the liver and the spleen of the animals from both of the flocks . Histochemical reactions confirm that it is type AA amyloidosis.

Proc Natl Acad Sci U S A, 1989 Apr, 86(8), 2809 - 13
Fluorinated 4-quinolones induce hyperproduction of interleukin 2; Riesbeck K et al.; The fluorinated 4-quinolones are a "new" group of antibiotics with a broad antibacterial spectrum . They are already widely used in clinical practice . Previous studies have shown that these drugs increase the uptake of {3H}thymidine into DNA of mitogen-stimulated lymphocytes but inhibit cell growth and immunoglobulin secretion . This study shows that the 4-quinolones strongly (up to 100 times) increase the recovery of interleukin 2 (IL-2) in culture supernatants of phytohemagglutinin (PHA)-stimulated normal human lymphocytes and also prolong the kinetics of IL-2 production . The effect was significant at clinically achievable concentrations (5 micrograms/ml) . In addition to hyperproduction of IL-2, the level of RNA hybridizing with a human IL-2 cDNA probe was also intensely elevated (16-32 times) in PHA-stimulated lymphocytes cultured with ciprofloxacin (80 micrograms/ml) . The mechanism responsible for 4-quinolone-mediated effects on T cells is at present unclear, but evidence is presented that suggests the effect is not exerted at the level of protein kinase C activation . Ciprofloxacin at 80 micrograms/ml also decreased the expression of IL-2 receptors measured by immunofluorescence with CD 25 antibodies and a radiolabeled IL-2 binding assay . At the same concentration of ciprofloxacin, there was a very low expression of the transferrin receptor and the cell size increased very little in human lymphocytes after PHA stimulation . The enhanced IL-2 production by 4-quinolones may contribute to side effects reported when these drugs are used for treatment of patients.

Eur J Clin Microbiol Infect Dis, 1989 Apr, 8(4), 310 - 3
Antibacterial prophylaxis with lactoferrin in neutropenic patients; Trumpler U et al.; The prevention of enterogenic infection by human lactoferrin was tested in five neutropenic patients receiving chemotherapy for acute myelogenous leukemia . Lactoferrin did not significantly delay the onset of infection but reduced its duration and severity as judged from the course of fever . Compared with nine matched controls, lactoferrin-treated patients had a lower incidence of bacteremia on the whole and of gram-negative bacteremia in particular.

J Med Chem, 1989 Mar, 32(3), 601 - 4
Synthesis and in vitro activity of 1 beta-methyl C-2 quaternary heterocyclic alkylthio carbapenems; Kim CU et al.; New 1 beta-methylcarbapenems having various (substituted) quaternary heterocyclic alkythio groups at the C-2 position were synthesized and tested for antibacterial activity and renal dipeptidase susceptibility . Compounds having the 1 beta-methyl substituent were found to possess an increased stability to the enzyme . In addition, combination of the 1 beta-methyl substituent and the C-2 quaternary heterocyclic alkylthio side chain generated compounds with excellent antipseudomonal activity and improved stability toward hydrolysis by renal dipeptidase.

J Cardiovasc Surg (Torino), 1989 Mar-Apr, 30(2), 250 - 6
Effects of preservative-free heparin on plasma histamine concentration and on hemodynamics in patients undergoing aortocoronary bypass surgery; Adt M et al.; Several reports, dealing with typical cardiovascular reactions immediately after injection of heparin during cardiac surgery, have been presented . A possible reason for these reactions is a short-lasting elevation of plasma histamine concentration following heparin injection . As most types of heparin contain antibacterial preservatives such as benzyl alcohol, which can cause adverse reactions, both substances, heparin itself and the preservative, can theoretically be responsible for this reaction . Therefore, this study was carried out in order to measure the effects of preservative-free heparin on plasma-histamine levels and on hemodynamic parameters . It became evident that preservative-free heparin also entails characteristical hemodynamic effects, such as a decrease in arterial mean pressure and peripheral vascular resistance as well as an increase in cardiac output . A significant increase in plasma-histamine concentration could be shown 20-120 seconds after injection of heparin . We conclude that benzyl alcohol is not the major reason for the hemodynamic effects and elevation of plasma-histamine concentration, following heparin injection, but we cannot exclude that benzyl alcohol does in fact play a minor role . The results of this study suggest that the cardiovascular reactions and the elevation of plasma histamine concentration following heparin injection are heparin-specific phenomena.

J Pharm Belg, 1989 Mar-Apr, 44(2), 121 - 6
Preparation of beta-aminomethyl-beta-benzoylpropionic acids and related cis beta-aminomethyl-gamma-phenyl-gamma-butyrolactones as potential antibacterial agents; Santana L et al.; The synthesis of beta-aminomethyl-beta-benzoylpropionic acids (V) and beta-aminomethyl-gamma phenylbutyrolactones (VI) is described . The cis stereochemistry of compounds VI was unambiguously established by NOE experiments carried out with Vla . Antibacterial activity was studied; MIC of each derivate was determined by agar dilution in Muller-Hinton medium and application of Steers' replicator.

Bull Assoc Anat (Nancy), 1989 Mar, 73(220), 11 - 5
{Ultrastructural study of the action of concentrated solutions of chlorhexidine digluconate on cocci in salivary flora in vitro}; Emmanouil-Nikoloussi E et al.; Chlorhexidine digluconate is a potent antibacterial compound widely used in stomatology . In this work the authors studied the ultrastructural alterations of cocci in salivary flora, treated "in vitro" with high concentrations of chlorhexidine digluconate (0.5%, 1% and 2%) . The effect of chlorhexidine 0.5% on the cocci revealed rarefaction of the cytoplasm, ruptures of the cellular wall and alterations of the protoplasm in the form of "plasmoptysis" and "plasmolysis" . Treatment of the cocci with higher concentrations (1% and 2%) of the drug caused a change in the appearance of the protoplasm, showing a general coagulation, damage of the cytoplasmic membrane and the cellular wall, malformation of the cell and disorganization of the nuclear chromatin . The ultrastructural alterations observed are in agreement with the results of preliminary biochemical studies.

Mycopathologia, 1989 Mar, 105(3), 129 - 33
Production of patulin by Micromycetes; Steiman R et al.; In the context of the screening for antifungal and antibacterial molecules among the Micromycetes, we investigated the ability of 850 strains grown in liquid medium to produce patulin . The compound was produced by 58 fungi, most of which had not been mentioned in the literature, especially Mucorales and Fungi Imperfecti . Biological tests showed that dermatophytes are the most sensitive to this molecule . It also appears that the origin of the producing strains influences their toxin producing activity.

Pharmazie, 1989 Mar, 44(3), 211 - 4
Evaluation of the release and efficacy of two new antibacterial agents from different ointment bases; el-Faham TH et al.; The in vitro release of rosoxacin (1) and oxolinic acid (2) from three different ointment bases including a revised water washable (NF), an oleaginous, and an O/W emulsion ointment base was studied . Among the bases evaluated, the revised water washable base provided the best release of the two drugs as revealed from the values of the release rate constant (K) . The amounts released of both drugs from the revised water washable base showed direct relationship with the concentration of the drug in the ointment . In addition, the effect of some additives on the amount released of both drugs from the different bases has been investigated . The release of 1 from the revised water washable base had been enhanced by adding 0.2% Tween 80 or 10% ethanol, but addition of 10% of N,N-dimethylacetamide and polyvinylpyrrolidone (PVP) led to retardation of the release of the drug . Furthermore addition of 10% polyethylene glycol (PEG) 200, N,N-dimethylacetamide, or ethanol led to enhancement of the release of the drug from both the oleaginous and the emulsion bases . On the other hand, the release of 2 from the revised water washable base had been enhanced only on addition of 0.2% Tween 80 and been retarded by adding 10% ethanol, N,N-dimethylacetamide or PVP to the formula . The release of 2 from the oleaginous, as well as the emulsion bases had been enhanced by 10% PEG 200 . However urea was found to show no pronounced effect on the release of the two drugs from the different ointment bases.(ABSTRACT TRUNCATED AT 250 WORDS)

Zh Mikrobiol Epidemiol Immunobiol, 1989 Mar, (3), 39 - 45
{Interaction of opportunistic bacteria and factors in the body's anti-infective resistance against a background of antibacterial therapy of children with acute pneumonia}; Savitskaia KI et al.; The aim of this investigation was the complex analysis of the dynamics of microflora at the focus of inflammation, the factors of the anti-infective resistance of the body and the clinical course of acute pneumonia in groups of children subjected to different kinds of antibacterial therapy (corresponding and not corresponding to the antibioticogram of the causative agent) or in the absence of antibacterial therapy, i.e . in groups 1, 2 and 3 respectively . As a result, differences in the change of microflora at the focus of inflammation were revealed . They were manifested, in particular, by the possibility of the development of microflora consisting of multiresistant strains as early as on day 7 of hospitalization . Different dynamics of the anti-infective resistance factors corresponded to changes in microflora at the focus of inflammation . No negative effect of antibiotics of the penicillin series and gentamicin on the levels of immunoglobulins, complement and on phagocytic activity was revealed.

Antimicrob Agents Chemother, 1989 Mar, 33(3), 404 - 5
Antibacterial activities of the antiparasitic drugs nifurtimox and benznidazole; Hof H; Both nifurtimox and benznidazole, which are used for the treatment of Chagas' disease, also display marked antibacterial activities . Characteristically for nitroheterocyclic compounds, they are much more active against anaerobic and microaerophilic bacteria than against aerobic bacteria . Nitroreductase-deficient aerobes are completely resistant, whereas SOS-repair-deficient strains are moderately susceptible . Those strains are rapidly killed.

Int J Clin Pharmacol Ther Toxicol, 1989 Mar, 27(3), 135 - 44
Biliary elimination of ticarcillin plus clavulanic acid (Claventin): experimental and clinical study; Brogard JM et al.; The aim of the present study was to assess the biliary elimination and disposition of Claventin, a combination of clavulanic acid (CA), a beta-lactamase inhibitor, with ticarcillin (TIC), resulting in an enhancement of the activity of the antibiotic and broadening of its antibacterial spectrum . This work was done experimentally and in humans . Assays of both molecules were performed by HPLC . During a 3 h perfusion of five isolated rabbit liver preparations, 1.3 +/- 0.2% and 0.4 +/- 0.1% of TIC and CA added to the circulating blood were eliminated in the bile . At the same time, 31.8% of TIC and 50.5% of CA were submitted to a hepatic biotransformation . In healthy subjects (n = 5), after a single i.v . injection of 3.2 g of Claventin (TIC: 3 g + CA: 0.2 g) mean peak concentrations of 66.8 +/- 31.9 micrograms/ml (TIC 4th h) and 0.3 +/- 0.1 microgram/ml (CA, 2nd h) were observed in the aspirated duodenal fluid where 0.07% and 0.01%, respectively, of the administered dose were recovered during the 4 h investigation period . In cholecystectomized patients (n = 10) provided with a T-tube, i.v . administration of Claventin, 3.2 g, resulted in biliary maximal levels of 177 +/- 49 micrograms/ml (TIC: 2nd h) and 2.7 +/- 0.5 microgram/ml (CA 1st h) . Total amount of each derivative eliminated in bile over 12 h averaged 0.28% (TIC) and 0.05% (CA) of the given dose . Hepatobiliary clearance was 20.5 ml/h (TIC) and 4.4 ml/h (CA) . In intra-operative simultaneously sampled specimens of serum, choledochal bile, gallbladder bile and gallbladder wall, the following concentrations were measured 1 h after i.v . administration of Claventin: TIC: 105 +/- 10; 386 +/- 66; 72 +/- 20 micrograms/ml and 36 +/- 11 micrograms/g, CA: 3.5 +/- 0.7; 5.9 +/- 1.5; 0.3 +/- 0.3 microgram/ml and 0.1 +/- 0.1 microgram/g . The biliary pharmacokinetics determined in humans makes it possible to consider favourably the prophylactic use of Claventin in surgery of the biliary tree and constitute a good prerequisite for a possible beneficial treatment of biliary tract infections.

J Antibiot (Tokyo), 1989 Mar, 42(3), 463 - 6
New antibiotics, resorcinomycins A and B: antibacterial activity of resorcinomycin A against mycobacteria in vitro; Masaki S et al.; Resorcinomycin A, N-{(S)-alpha-guanidino-3,5-dihydroxy-4-isopropylphenylacetyl}glyci ne, S-RSM-A, a new antibiotic produced by Streptoverticillium roseoverticillatum, has an antibacterial spectrum directed towards mycobacterial species . It is not active against Gram-negative and Gram-positive bacteria, except mycobacteria and weakly active against mycoplasmas . In vitro activities of the S-, R- and S,R-isomers of RSM-A against atypical mycobacterial strains were compared with those of streptomycin (SM) and kanamycin (KM) by 2-fold agar dilution methods using Middlebrook 7H10 agar medium . Although R-RSM-A and S,R-RSM-A were comparable or inferior to both antibiotics, the antimycobacterial activity of S-RSM-A was superior to that of SM and KM.

J Antibiot (Tokyo), 1989 Mar, 42(3), 367 - 73
Synthesis and biological activity of a series of piperazine-2,3-dione containing penicillins and 6 alpha-formamidopenicillins . I . Derivatives substituted at C(5) or C(6) of the piperazine ring; Davies DT et al.; The synthesis and antibacterial activity of a series of penicillins and 6 alpha-formamidopenicillins containing a C(5) or C(6)-substituted piperazine-2,3-dione moiety in the C(6)-beta-sidechain is described.

J Antibiot (Tokyo), 1989 Mar, 42(3), 347 - 56
Deacetylravidomycin N-oxide, a new antibiotic . Taxonomy and fermentation of the producing organism and isolation, structure and biological properties of the antibiotic; Narita T et al.; Streptomyces ravidus S50905 was found to produce a new antibiotic, deacetylravidomycin N-oxide, together with ravidomycin and deacetylravidomycin in a culture medium containing sodium anthraquinone-beta-sulfonate . The structure of this new compound was determined from NMR and mass spectrometric data, and further confirmed by chemical synthesis from deacetylravidomycin . Deacetylravidomycin N-oxide was antitumor active against P388 leukemia and Meth A fibrosarcoma in a wide range of doses, and considerably less toxic than deacetylravidomycin . Its antibacterial activity was less potent than deacetylravidomycin . Ravidomycin N-oxide was also synthesized from ravidomycin and its biological properties were tested.

J Vet Pharmacol Ther, 1989 Mar, 12(1), 25 - 30
The concentration of penicillin in bovine conjunctival sac fluid as it pertains to the treatment of Moraxella bovis infection . (I) Subconjunctival injection; Abeynayake P et al.; Single dose, subconjunctival injections of procaine penicillin using either skin or conjunctival routes of administration were evaluated in order to compare the duration of antibacterial concentrations at the site of Moraxella bovis infection . Samples of conjunctival sac fluid (CF) were collected using blunted capillary tubes and were periodically assayed for penicillin by an agar-well-diffusion technique . Linear regression lines were constructed for concentration of penicillin-time profiles . Similarity of the regression slopes for each treatment enabled the construction of three common lines by the method of co-variance analysis in order to represent each treatment . Treatments were thereafter compared by the slopes of the common regression lines . A subconjunctival injection of procaine penicillin at a dose of 6 X 10(5) iu in 2 ml, administered either through the skin or through the conjunctiva, produced a peak penicillin concentration in the CF of approximately 8 iu/ml for either route and a duration of therapeutic concentration (DTC) of 67.6 +/- 4.9 and 40 +/- 2.7 h respectively . A dose of 3 X 10(5) iu in 1 ml, administered through the conjunctiva, produced a similar peak but the DTC was reduced to 35 +/- 4.2 h . The results of this study support field practices, as adequate penicillin concentrations were maintained by both techniques investigated.

Steroids, 1989 Mar-May, 53(3-5), 363 - 91
Drug design based on biosynthetic studies: synthesis, biological activity, and kinetics of new inhibitors of 2,3-oxidosqualene cyclase and squalene epoxidase; Cattel L et al.; Various classes of inhibitor of 2,3-oxido squalene cyclase have been synthesized and tested on rat liver and Saccharomyces cerevisiae microsomes, 3T3 fibroblast cultures, and various bacteria, fungi, and yeasts . The compounds include azasqualenes, azasqualanes, bis-azasqualenes, bis-azasqualanes, and N-oxide and ammonium derivatives of squalene . In order to better mimic the transition state involved in the SN2-like opening of 2,3-oxidosqualene, we synthesized squalene N-methyloxaziridine . Other derivatives tested were N-methylimine, aminalic hydroperoxide, and N-methylamide . We also attempted to produce new "suicide" inhibitors of SO cyclase, such as a squalenoid epoxide vinyl ether . Many of the products described inhibited the various cyclases, the best having an IC50 of 0.3 microM on plants and 1.5 microM on rat liver microsomes, and good antibacterial and antifungal activity . In a search for inhibitors of squalene epoxidase, a series of mono- and bifunctional squalenoid acetylenes and allenes were synthesized . Some of them proved to be inhibitors of squalene epoxidase.

J Med Chem, 1989 Mar, 32(3), 694 - 8
Portage transport of sulfanilamide and sulfanilic acid; Hwang SY et al.; Sulfanilic acid, in contrast to sulfanilamide, has poor in vitro antibacterial activity . Paradoxically, it has been shown to be a more effective inhibitor than sulfanilamide of dihydropteroic acid synthase . In order to circumvent the presumed permeability barrier to sulfanilic acid, advantage was taken of the technique of portage transport . Derivatives of the compound were prepared in which it was linked via its primary amino group to the alpha-carbon of glycine residues in di- and tripeptides . L-Alanyl-L-alanyl-L-2-{(4-sulfophenyl)amino}glycine proved to be 207 times more potent than sulfanilic acid and 8 times more active than either sulfanilamide or L-alanyl-L-alanyl-L-2-{{4-(aminosulfonyl)-phenyl}amino}glycine when tested against Escherichia coli . These findings confirm that the weak in vitro activity of sulfanilic acid is due to its limited ability to penetrate the bacterial membrane . They also emphasize the ability of portage transport to reveal therapeutic capability that had been attenuated by poor drug permeation.

Nippon Shishubyo Gakkai Kaishi, 1989 Mar, 31(1), 256 - 65
{Topical chemotherapy of chronic periodontitis using controlled-release insert containing ofloxacin (PT-01) without root planing}; Takamori A et al.; Topical chemotherapy of periodontal disease using several drug delivery systems (DDS) is currently being attempted . PT-01 is a DDS which consists of fast- and sustained- release parts containing ofloxacin as an antibacterial agent . Since PT-01 was found to sustain the antibacterial effect for 7 days in a periodontal pocket, it was used tor periodontal patients without root planing or scaling in this study . PT-01 and a placebo were applied to two separate and opposite pockets of 46 patients, once a week from the first visit (week 0) to week 3 . The clinical parameters (plaque index, gingival index, tooth mobility, bleeding on probing, pus discharge, and probing depth) were evaluated from weeks 0 to 4 . At the end of the test (week 4), global improvement at the two sites was assessed . The clinical parameters and the global improvement of the PT-01 and placebo-treated sites were compared statistically . All parameters at the PT-01 sites except for tooth mobility showed much greater improvement than at the placebo sites . The global improvement of PT-01 sites was also significantly greater than that of the placebo sites . No side effects could be seen in patients treated with PT-01 . These results indicate that topical chemotherapy using PT-01 could be effective and safe for periodontal therapy.

Trans R Soc Trop Med Hyg, 1989 Mar-Apr, 83(2), 265 - 8
In vitro studies of antibiotic sensitivities of Streptomyces somaliensis--a cause of human actinomycetoma; Nasher MA et al.; Ten Streptomyces somaliensis strains isolated from mycetoma patients were tested in vitro against 13 antibacterial agents . Rifampicin was the most effective antibiotic in terms of low minimum inhibitory concentration (MIC) followed by erythromycin, tobramycin, fusidic acid and streptomycin sulphate . The S . somaliensis strains were all resistant to trimethoprim, even though the combination of sulphamethoxazole and trimethoprim is commonly used as treatment.

J Med Chem, 1989 Mar, 32(3), 625 - 9
A novel prodrug of an impermeant inhibitor of 3-deoxy-D-manno-2-octulosonate cytidylyltransferase has antibacterial activity; Norbeck DW et al.; Although 8-amino-2,6-anhydro-3,8-dideoxy-D-glycero-D-talo-octonic acid (2) is a potent inhibitor of 3-deoxy-D-manno-octulosonate cytidylyltransferase (CMP-KDO synthetase), it is unable to reach its cytoplasmic target and is therefore inactive as an antibacterial agent . However, esterification of 2 with 8-(hydroxymethyl)-1-naphthyl methyl disulfide (8) generates a prodrug (12), which gains entry into bacterial cells . Intracellular reduction of the disulfide leads to a rapid, intramolecular, displacement of the acid 2, which then inhibits the growth of Gram-negative bacteria by interfering with the biosynthesis of lipopolysaccharide.

Urol Nefrol (Mosk), 1989 Mar-Apr, (2), 17 - 21
{The role of a sanatorium-health resort factor in the complex treatment of patients with chronic prostatitis}; Darenkov AF et al.; The results of two-step treatment of 62 patients with chronic prostatitis are presented . The first-step treatment was given at the clinic of the Urologic Research Institute of the RSFSR Ministry of Health, and the second step was completed at the Zheleznovodsk Urologic Clinic of the Pyatigorsk Research Institute of Health Resort Treatment and Physiotherapy . In addition to its medical aspect, treatment for chronic prostatitis has significant social implications, as chronic prostatitis mostly affects males of young or middle age, with the inflammation persisting for long periods of time and leading to sexual and reproductive disorders as well as psychoneuroses . Since chronic prostatitis is regarded as an inflammatory disease of infectious-immunologic etiology, with both parenchymal and interstitial tissues of the prostatic gland affected, the patients underwent antibacterial treatment, adjusted to the causative agent's sensitivity to antibacterial drugs, and the availability of physiotherapeutic procedures in hospital as the first stage of treatment . Those to whom further rehabilitation was indicated were referred to the Zheleznovodsc Urologic Clinic where they were given a treatment course making use of the natural factors: oral and external administration of mineral waters of the Smirnovsky and Slavyanovsky springs, mud treatments and physiotherapy where indicated . Treatment was designed to improve microcirculation in prostatic tissues, and used natural factors, capable of normalizing and activating systemic protective potentials . There were good results (considerably improved general condition, both subjectively felt and objectively documented) in 78%.(ABSTRACT TRUNCATED AT 250 WORDS)

Nippon Shishubyo Gakkai Kaishi, 1989 Mar, 31(1), 184 - 99
{Effects of nicotinate ethyl ester treatment on gingival blood circulation of experimental gingivitis in monkeys}; Taguchi S et al.; The effects of nicotinate ethyl ester treatment on the gingival blood circulation of plaque induced inflammation in monkeys were determined . The blood flow, amount of hemoglobin and oxyhemoglobin rate (oxyhemoglobin/total hemoglobin) in gingival blood circulation in addition to bacterial colony forming units (CFU), gingival index (GI), probing depth (PD), loss of attachment (LA) and amount of gingival crevicular fluid (GCF) were used as parameters . Besides 1% nicotinate ethyl ester paste (nicotinate paste), 0.5% chlorhexidine (CHX) paste as an antibacterial agent, a mixture of the two pastes and the base alone as a control were used . 1 . The blood flow, amount of hemoglobin, CFU, GCF, PD and GI increased as inflammation developed, and these showed significant correlations . 2 . The oxyhemoglobin rate showed no corresponding change with inflammation . 3 . Nicotinate paste, CHX paste and the mixed paste seemed to reduce the inflammation of the gingiva as assessed by the blood flow, hemoglobin amount, CFU and GCF amount compared with the control paste.

Kansenshogaku Zasshi, 1989 Mar, 63(3), 173 - 81
{Immunotherapy by polyvalent bacterial antigen (Broncasma Berna) in the prevention of pneumonia in the elderly}; Suzuki K et al.; Pneumonia in the elderly often occurs repeatedly, and the mortality rate from pneumonia continues to remain high today despite the usual use of antibacterial chemotherapy . Therefore, we conducted immunotherapy using a polyvalent bacterial vaccine (broncasma Berna) . We treated 54 elderly patients with Broncasma Berna, containing chief bacterial pathogens responsible for pneumonia in the elderly . Clinical results obtained during 2 years were compared with those of 18 subjects not treated with Broncasma Berna . The survival rate was 64.8% for the group treated with Broncasma Berna and 50% for the group not treated . The frequency of contraction of pneumonia decreased significantly in the group treated . Clinical efficacy was obtained in 63% of the group treated to prevent pneumonia . The death rate from pneumonia was 17.6% for the group treated and 44.4% for the group not treated . Immunologically, reinforcement in humoral and cellular immunities was indicated by immunoglobulin values, positive tuberculin skin tests, and an increase in lymphocyte stimulation index values for Broncasma Berna . Significant pathogens in sputum disappeared or decreased in 6 (54.6%) out of 11 patients . Side effects such as pain or redness at the site of injection were observed in 6 patients . From the above results, it may be concluded that Broncasma Berna can be considered to be effective as a long-term immunoprophylactic agent in the prevention of pneumonia in the elderly.

J Dent Res, 1989 Mar, 68(3), 491 - 5
Inhibition of bacterial growth under composite restorations following GLUMA pretreatment; Felton D et al.; The purpose of this investigation was to test in five adult monkeys the effects of a glutaraldehyde-containing dentin bonding agent, GLUMA, on bacterial colonization in Class V cavities restored with composite resin . Experimental groups consisted of immediate placement of GLUMA and composite resin as well as placement of GLUMA or Scotchbond (control) in acid-etched cavities that had been left open to the oral environment for 48 hours . Various procedures for pretreatment of the cavities were included . Tissue specimens were prepared for light microscopy for observation of bacterial presence and pulp tissue reactions after eight days and 90 days . Bacteria were not detected in any of the 54 cavities treated with GLUMA regardless of observation period or use of enamel-etching procedure prior to placement of composite resin . When cavities were restored with composite resin without prior GLUMA pretreatment or with Scotchbond, bacteria were present under the majority of restorations at both time intervals . Pulpal inflammation of varying extent and character was seen after eight days in teeth that had been previously infected . At 90 days, pulps showed repair and healing regardless of treatment protocol . Data indicate that GLUMA has a distinct in vivo antibacterial effect that seems to prevent bacterial growth in tooth/restoration interfaces.

Rev Chil Pediatr, 1989 Mar-Apr, 60(2), 112 - 7
{Sinusitis}; Emhart O; Most frequently sinusitis in children is ethmoidal and maxillary in location by developmental reasons . Local symptoms include nasal obstruction and discharge, local pain and headache . Diagnosis is based on due consideration to signs and symptoms, microscopy, transillumination and x Ray examination . Treatment must be conservative, based on bed rest, analgesics, antibacterials, juditions use of local vasoconstrictor drugs and heat . Chronic forms may need surgical management . Frontoethmoidal mucocele and frontal osteomyelitis are frequent subjects of pitfalls and acute maxillary osteomyelitis is an important complication.

Zhonghua Zheng Xing Shao Shang Wai Ke Za Zhi, 1989 Mar, 5(1), 34 - 5, 77
{The use of immune RNA (i-RNA) to prevent and treat burn infection}; Han FY; The immune RNA was extracted from the spleens and livers of immunizing sheep with Ps . aeruginosa, E . coli and S . aureus . After animal trial, the i-RNA activity and its antibacterial protective effect has been demonstrated . 95 cases of burn infection treated with i-RNA plus antibiotics were compared with a concurrent control group treated with antibiotics alone . Clinical observation confirmed that an obvious effect on the prevention and treatment of burn infection with gram negative bacteria was manifested . Among them, 59 cases with burn area 15-49% II degrees, III degrees of total body surface, the ratio of incidence of gram negative septicemia and wound pyemia between i-RNA and control group was 1.69%: 22%, p less than 0.01 . In another 36 cases with burn area over 50% body surface II degrees, III degrees treated with i-RNA the gram negative septicemia or wound sepsis were found in 3 cases (morbidity 8.3%) . And one died overall mortality was 2.8% . Whereas, the morbidity and mortality were 51.4% and 45.9% respectively in 37 control cases . The ratio of morbidity between i-RNA and control group was 8.3%: 51.4%, p less than 0.01, and that of mortality was 2.8%: 45.9%, p less than 0.01.

J Immunol, 1989 Feb 15, 142(4), 1310 - 7
Experimental and theoretical kinetics study of antibacterial killing mediated by human natural killer cells; Garcia-Penarrubia P et al.; We have recently shown that purified human NK cells, both resting and activated, efficiently kill gram-negative and gram-positive bacteria in vitro . To investigate the mechanism of NK cell-mediated cytotoxicity against Escherichia coli we have developed a mathematical model of the kinetics using the experimental data . The kinetics of killing are characterized by initial target bacterial multiplication, followed by rapid bacterial death . Experiments demonstrates that for each donor there is a threshold number of effector cells necessary to observe a net killing effect . Below the threshold, even use of high effector-to-target ratios lack killing activity and the bacterial growth cannot be stopped . In contrast, if the number of NK cells is larger than the threshold, complete killing is achieved, even at ratios as low as 1/1000 . The threshold number varies among donors, ranging between 1200 and 12000 purified NK cells/tube, and provides a quantitative measure of antibacterial activity . Performing the assay at 4 degrees C raised the threshold number required for killing . Experiments performed in Boyden chambers confirm that NK cell-bacteria contact is not necessary for efficient killing, although the kinetics of bacterial lysis is slower . The fit between model and data supports the hypothesis that the bactericidal mechanism is extracellular and is mediated by an anti-microbial factor released from NK cells . Accumulated evidence also indicates that this factor is distinguishable from the mechanisms mediating tumor cell cytotoxicity.

J Biol Chem, 1989 Feb 15, 264(5), 2973 - 8
Mechanism of quinolone inhibition of DNA gyrase . Appearance of unique norfloxacin binding sites in enzyme-DNA complexes; Shen LL et al.; As a means of gaining additional information on the topoisomerase-mediated cytotoxicity induced by a variety of antibacterial and antitumor compounds we have examined the interaction of the quinolone anti-bacterial agent, norfloxacin, with the bacterial topoisomerase, DNA gyrase . Membrane filtration and spin-column techniques were used to study the binding of {3H}norfloxacin to purified plasmid DNA, DNA gyrase, and complexes formed by adding gyrase to different forms of plasmid DNA . Consistent with previous results (Shen, L . L., and Pernet, A . G . (1985) Proc . Natl . Acad . Sci . U.S.A . 82, 301-311) little {3H}norfloxacin binds to reconstituted gyrase, but significant levels of drug bind nonspecifically to relaxed DNA . However, when DNA and gyrase are incubated together additional norfloxacin binding sites are detectable . These complex-dependent sites are distinguishable from those sites involved in nonspecific DNA binding in that the complex-dependent sites are saturable and they retain bound norfloxacin after centrifuging the complex through a spin column . In addition, extent of binding is influenced by the topological state of DNA used to form the complex . The complex-dependent norfloxacin binding sites are likely involved in the inhibition of the enzyme since saturation of these sites occurs in the same norfloxacin concentration range as the inhibition of DNA supercoiling activity . Moreover, there is a close correlation of norfloxacin-induced DNA breakage with levels of norfloxacin bound to complexes of gyrase and relaxed DNA . These findings provide the first direct correlation of quinolone binding with inhibition of enzyme activity and induction of DNA breakage, and they suggest that the inhibition of DNA gyrase by norfloxacin occurs as a result of binding to a site which appears after the formation of a gyrase-DNA complex.

J Antibiot (Tokyo), 1989 Feb, 42(2), 293 - 8
9,11-cyclic acetal derivatives of (9S)-9-dihydroerythromycin A; Hunt E et al.; A series of 9,11-cyclic acetal derivatives of (9S)-9-dihydroerythromycin A (4) have been prepared and their antibacterial activities compared to those of erythromycin A and 9-dihydroerythromycin A . Many of the cyclic acetal derivatives showed better antibacterial activity than their parent 4 . In particular, the acetaldehyde acetal (9-O,11-O-ethylidene-9-dihydroerythromycin A) (8b) showed good antibacterial activity in comparison with erythromycin A but was not sufficiently improved in vivo to warrant progression.

J Antibiot (Tokyo), 1989 Feb, 42(2), 242 - 53
New cirramycin-family antibiotics F-1 and F-2 . Selection of producer mutants, fermentation, isolation, structural elucidation and antibacterial activity; Sawada Y et al.; Two new 16-membered macrolides, cirramycins F-1 and F-2, were isolated from the culture filtrate of a mutant strain B-1425 of Streptomyces cirratus JTB-3 . The antibiotics were also produced by bio-transformation of cirramycin A1 using a blocked mutant strain A-0033 . Structures of F-1 and F-2 have been elucidated by spectral interpretation and analysis of acid degradation products . Both involved isomeric modification of a neutral sugar; F-1 contained L-rhodinose, and F-2 L-amicetose . Based on spectral data, cirramycin F-1 and antibiotic A6888C were found to be identical . Cirramycins F-1 and F-2 are active against Gram-positive bacteria, but less active than cirramycin A1.

J Antibiot (Tokyo), 1989 Feb, 42(2), 179 - 88
New products related to kinamycin from Streptomyces murayamaensis . I . Taxonomy, production, isolation and biological properties; Cone MC et al.; Six new products of Streptomyces murayamaensis sp . nov . Hata et Ohtani, the producer of the kinamycins, were isolated by silica gel column chromatography . The antibacterial activities of the new products, as well as that of dehydrorabelomycin and murayaquinone, previously isolated products of the same organism, were compared to the kinamycins . Three of the products had antibacterial activities similar to the kinamycins, while two others had activity only against Gram-positive bacteria . Dehydrorabelomycin and one other metabolite had no detectable antibacterial activity . The organism was found to be capable of aerial mycelium formation, with sporophores branched at regular intervals bearing square-ended spores with smooth surfaces . The culture contains L,L-diaminopimelic acid in the cell wall (Type I), is highly resistant to lysozyme, and lecithinase- and melanin-positive, suggesting a relationship with the genus Streptoverticillium and the lavendulae group of the genus Streptomyces.

Mol Immunol, 1989 Feb, 26(2), 115 - 9
Oral immunization with a free peptide from cholera toxin: local protection and IgA production; Pedoussaut S et al.; It is frequently of great benefit for good protection against pathogens to elicit a local immunization . For example the importance of antibacterial as well as antitoxin local secretory IgA, for protection against cholera, has been underlined in several studies . We have already reported that oral administration of the peptide corresponding to the 50-75 sequence of cholera toxin (CT) B subunit elicits serum antibodies neutralizing CT activity . In this study we demonstrate that IgA with specificity to CT are present in intestinal secretions of mice immunized orally with the P50-75 or P30-50 peptides of CT B subunit . In addition local protection is observed in the intestine of P50-75 orally immunized mice . These results point out the potential of synthetic peptides as immunogens at the mucosal level.

Planta Med, 1989 Feb, 55(1), 35 - 7
The complex nature of the mechanism of toxicity of antibiotic dithiacyclohexadiene polyines (thiarubrines) from the asteraceae; Constabel CP et al.; Thiarubrine A, a dithiacyclohexadiene polyine from the roots of Chaenactis douglasii, and a related dithiacyclohexadiene from Rudbeckia hirta exhibit strong light-independent antibacterial and antifungal activity . This activity is enhanced by exposure to visible light . Visible light also converts the compounds to the corresponding thiophenes . These are antibiotic only when irradiated with UV-A . Dithiacyclohexadienes are the first polyines to exhibit such complex mechanisms of toxicity towards microorganisms.

Clin Invest Med, 1989 Feb, 12(1), 28 - 34
Adverse reactions and interactions of fluoroquinolones; Ball P; Recent research into fluoroquinolone antibacterials has led to the discovery of a number of compounds with greatly improved potency, spectrum, pharmacokinetics and clinical efficacy . In general their safety and tolerance mirrors these attributes . Like previous naphthyridines, cinnolines, and fluoroquinolones, these agents may cause gastrointestinal, central nervous system, and cutaneous reactions, but these are usually mild and self-limiting, affect 5-10% of patients only and rarely require withdrawal from therapy . Extremely rarely, more serious CNS effects including fits and psychosis may accompany high dose therapy . Potentially serious problems, predicted by animal testing and including erosive arthropathy in juvenile rats and dogs, cataract formation and renal damage secondary to crystalluria, have not been encountered in clinical use . All of the new agents give positive results in some tests for mutagenesis but there is no evidence for mutagenicity or carcinogenicity in man . However, the possibility of mutagenesis and joint damage restricts the use of fluoroquinolones in children to life-saving indications only . Interactions may occur with other drugs . Absorption of these agents is interfered with by co-administered antacids, although not by H2 antagonists . Oxo-metabolites of enoxacin and, to a lesser extent, pefloxacin and ciprofloxacin interfere with the hepatic elimination of theophylline and caffeine and may result in toxicity due to these agents if dosage is not modified . With the exception of these avoidable events, the fluoroquinolones have proved a particularly safe group of agents in clinical use.

Clin Invest Med, 1989 Feb, 12(1), 7 - 9
Structure--activity relationship of quinolones; Toma E; The understanding of some structure-activity relationships of quinolones allowed the development of the new fluorinated quinolones, compounds with a major clinical potential . The basic structure of these drugs consists of a substituted pyridine ring and a carboxylic acid ring . The substitution at the first position is vital for antibacterial activity, while the presence of a fluorine atom and a piperazine ring is responsible for a broader spectrum of activity and higher intrinsic potency . Further modifications at side-chains or on the ring structure provide compounds with different pharmacokinetic or/and antibacterial activity . A better understanding of these relationships and correlations with clinical results is essential for the design of new improved derivatives with therapeutic potential.

Biochemistry, 1989 Jan 24, 28(2), 748 - 50
On the formation of oxygenated radicals by fredericamycin A and implications to its anticancer activity: an ESR investigation; Dalal NS et al.; It has been recently suggested that the exceptionally high antitumor and antibacterial activity of natural fredericamycin A (FMA) is related to its ability to spontaneously generate the superoxide anion (O2-) and hydroxyl (.OH) radicals in aerobic solutions {Hilton, B . D., Misra, R., & Zweier, J . L . (1986) Biochemistry 25, 5533} . With a view to understand the mechanistic details, attempts were made to reproduce earlier electron spin resonance (ESR) evidence for the oxygenated free radical formation in well-aerated solutions of natural FMA in dimethyl sulfoxide and dilute H2O2 . Little or no evidence was obtained for the formation of the O2- and methoxy (.OCH3) radicals, while the detected formation of the .OH and methyl (.CH3) radicals was attributable largely to mechanisms not involving FMA . These results thus reopen the question regarding the mechanism of its exceptionally high tumoricidal-bacteriocidal activity.

Wiad Lek, 1989 Jan 15, 42(2), 101 - 5
{Antibiotics in the treatment of biliary tract infections}; Perkowski H; The bacteriological problems are presented of bile tract infections, reviewing also the antibiotics in the aspect of their secretion into bile, range of antibacterial activity and possibility of correct choice in particular clinical situations.

Hosp Pharm, 1989 Feb, 24(2), 116 - 9
Surgical antibiotic irrigations; Golightly LK et al.; Instillation of antibiotic solutions into surgical wound sites seems empirically attractive since relatively high concentrations of antibacterial agents can be applied directly to the probable site of infection . However, systemic effects provided by antibiotic assimilated from sites of application are responsible for much of the activity and toxicity of antibiotic irrigations . The most appropriate drugs and dosages for use as prophylactic antibiotic irrigations have not been determined . Most controlled trials conducted in recent years have utilized various cephalosporins in concentrations of 1 to 4 g/L . In some of these trials, surgical irrigation has been found as effective as prophylactic intravenous antibiotics, which are the proven and accepted standard . Reported cases of toxicity associated with antibiotic irrigations are few in number, excepting neomycin, which has caused postoperative respiratory depression/apnea, permanent deafness, and renal failure.

Pol Tyg Lek, 1989 Jan 9-16, 44(2-3), 50 - 2
{Extremely severe respiratory failure complicated by lactic acidosis}; Tomkowski W et al.; A case of a 48-year male patient with chronic cor pulmonale is presented . Exacerbation of the chronic respiratory failure was caused by pneumonia . The patient was treated with artificial ventilation for 22 days and stimulating aggressive antibacterial therapy . An improvement was achieved . Indications to the use of respirator in the exacerbated chronic respiratory failure have been discussed together with problem of the potential reversibility of the cause, gas and lactic acidosis and an important clinical problem of the respiratory muscles exhaustion.

J Antibiot (Tokyo), 1989 Jan, 42(1), 63 - 72
Synthesis and antibacterial evaluation of N-alkyl vancomycins; Nagarajan R et al.; Over eighty N-alkyl vancomycins were synthesized by reductive alkylation of vancomycin with the appropriate aldehydes . The N-alkyl vancomycins exhibit greater antibacterial activity than the corresponding N-acyl vancomycins and the parent antibiotic . Some of these semisynthetic vancomycins are five times more active than vancomycin . The N-alkyl vancomycins also show longer elimination half-lives in rats than vancomycin.

Proc Natl Acad Sci U S A, 1989 Jan, 86(1), 262 - 6
Insect immunity: isolation from immune blood of the dipteran Phormia terranovae of two insect antibacterial peptides with sequence homology to rabbit lung macrophage bactericidal peptides; Lambert J et al.; We have isolated from the hemolymph of immunized larvae of the dipteran insect Phormia terranovae two peptides that are selectively active against Gram-positive bacteria . They are positively charged peptides of 40 residues containing three intramolecular disulfide bridges and differ from one another by only a single amino acid . These peptides are neither functionally nor structurally related to any known insect immune response peptides but show significant homology to microbicidal cationic peptides from mammalian granulocytes (defensins) . We propose the name "insect defensins" for these insect antibiotic peptides.

Postgrad Med, 1989 Jan, 85(1), 40 - 7, 51, 53
Otitis media . Update on a common, frustrating problem; Stool S; Otitis media is extremely common in infants and young children and has important ramifications for the children, their families, and society in general . The essential elements of management are early diagnosis, adequate therapy with appropriate antibacterial agents, and conscientious follow-up to promptly detect and treat potential and actual complications . The primary care physician who treats young children is the critical health-care provider in the diagnosis of otitis media, initial treatment, and timely referral when appropriate.

Acta Pol Pharm, 1989, 46(1), 19 - 26
{Synthesis and biological activity of isomeric 5- and 6-nitro-1-alkylbenzimidazoles}; Domagalina E et al.; Either the alkylation of 5(6)-nitro-benzimidazoles (R = H, CH3) or the nitration of 1-alkyl-benzimidazoles afforded corresponding mixtures of 1-alkyl-5-nitro- and 1-alkyl-6-nitro-benzimidazoles (III, IV, VII, VIII, XI) . Fractional crystallization from water was employed for isolation of 6-nitro isomers V, VI and IX from mixtures III, IV and VII . On the other hand, application of this isolation method to mixtures VIII and XI proved unsuccessful . 6-Nitro-compound X and 5-nitro derivatives XIII and XV were obtained by direct syntheses . From calibration curves depicting dependence of absorbance of the mixtures upon their composition, percentage ratios of 5-nitro to 6-nitro isomers in the mixtures were estimated . Usefulness of thin-layer chromatography, and UV and IR spectrometry for identification of 5-nitro and 6-nitro isomers was stated; e . g . 5-nitro isomers have higher epsilon values, while 6-nitro isomers exhibit two vmax values of the benzene ring . Compounds IV, IX and X proved to exert antihelminthic, antibacterial and antiphlogistic activities.

Yao Xue Xue Bao, 1989, 24(4), 255 - 9
{Studies on pyridonecarboxylic acids as antibacterial agents . VIII . Synthesis and structure-activity relationships of 1-(P-fluorophenyl)-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl) cinnoline-3-carboxylic acid and analogues}; Mu YQ et al.; 1-(P-fluorophenyl)-6-fluoro-1,4-oxo-7-(1-piperazinyl) cinnoline-3-carboxylic acid and its quinoline, 1,8-naphthyridine and pyrido (2,3-c) pyridazine analogues were prepared for studies of structure-activity relationships . The antibacterial activities of these 16 compounds were tested and the values of their electron densities were calculated using Huckel molecular orbital theory method . The results showed that the electron densities on the oxygen atoms of 3-carboxyl and 4-oxo have influenced strongly antibacterial activity in vitro . The quinolines and 1,8-naphthyridines showed higher electron densities and more potent antibacterial activities in vitro . The cinnolines and pyrido (2,3-c) pyridazines showed lower electron densities and lower or no antibacterial activities in vitro.

Yao Xue Xue Bao, 1989, 24(3), 175 - 81
{Synthesis of 7-(4,7-di-substituted coumarin-3-acetamido)cephalosporins}; Fan HJ et al.; Seventeen derivatives of 7-(4,7-di-substituted coumarin-3-acetamido)cephalosporins were synthesized with acid chloride method, Vilsmeier reagent method and mixed anhydride method . Isolation and purification were fulfilled with Sephadex LH-20 column chromatography and centrifugal-TLC technique . Their chemical structures were identified by elemental analysis, IR and 1HNMR spectrum . The preliminary antibacterial activity tests showed that these cephalosporin derivatives exhibited good activity against Gram-positive bacteria and individual Gram-negative bacteria . Further experiments in pharmacology will be made.

Sov Med, 1989, (8), 19 - 21
{Ultrasonic medicinal aerosols in multimodal treatment of acute surgical diseases of the organs of the abdominal cavity}; Gadzhiev IS; Microbiologic studies have shown that ultrasonic aerosol treatment of E . coli reference culture with 0.02% furacillin solution for 3 min reduces its survival rate by 2 orders (240-fold) . Exposure to low-energy ultrasound increases 7-fold the antibacterial activity of furacillin solution . Experiments have demonstrated that 99mTc ionized particles diffusion via cadaver peritoneum is enhanced more than 5 times if Tc solution is spread via ultrasonic aerosol . A method for ultrasonic aerosol treatment of infected abdominal cavity has been developed . Clinical trials of the method have been carried out: it has been employed in multiple-modality treatment of acute surgical diseases of the abdominal organs in 6 patients and of postoperative peritonitis in 15 patients, as well as for the prevention of purulent complications after extensive abdominal surgery in 4 patients.

Pediatriia, 1989, (8), 19 - 22
{Indicators of local and general immunity in children with gastroduodenitis during its complex treatment}; Sheliapina VV et al.; The authors describe the time-course of changes in local and general immunity as influenced by multimodality treatment in different groups of patients suffering from CGD and concomitant pancreatoduodenal pathology . It has been found that associated microbial and inflammatory process in the biliary system exerts a pronounced effect on the changes in immunologic parameters and that antibacterial therapy produces a beneficial action on the normalization of the parameters under consideration.

Yao Xue Xue Bao, 1989 Jan, 24(1), 27 - 31
{Synthesis and bacteriostatic activity of 2-furanthiocarboxyhydrazones and their transition metal complexes}; Ge WY et al.; In this paper, 9 compounds of 2-furanthiocarboxyhydrazones and 13 of their transition metal complexes have been synthesized and tested for bacteriostatic activity against several kinds of bacteria . The results showed that all the compounds tested possessed antibacterial activity . The complexes of Cu(II), Ni(II) and Zn(II) ions display higher activity against gram-positive bacteria than 2-furanthiocarboxyhydrazones and the other complexes . The complex of Ag(I) ion is more active against gram-negative bacteria, as compared to 2-furanthiocarboxyhydrazones and the other complexes . The results are also in accord with the earlier idea that the "NCS" group is the active site and that their activity has certain relation with their complexing ability.

Acta Clin Belg, 1989, 44(2), 99 - 109
Imipenem/cilastatin versus piperacillin plus amikacin as empiric therapy in the treatment of febrile episodes in neutropenic patients with haematologic malignancies; Vandercam B et al.; Recently, new beta-lactam antibiotics, such as imipenem/cilastatin (IMP) with an unusually broad antibacterial spectrum and especially an adequate P . aeruginosa activity, have introduced the possibility of using prospective agent as empiric management of febrile granulocytopenic patients . We randomized 83 febrile neutropenic cancer patients for a prospective evaluation of two regimens: IMP versus piperacillin plus amikacin (PA) . Both patients groups were similarly distributed with regard to age, sex, primary diagnosis and degree of granulocytopenia . More than 20% of the 74 evaluable patients had bacteraemia . The overall response rate for clinically or microbiologically documented infections was 90% in the IMP regimen versus 76% in the PA regimen, but statistical difference was not achieved . All bacteraemias in the IMP group but only 60% in the PA group were cured, however statistical difference was not achieved . IMP had to be discontinued in only one patient and the most common side effects were nausea and vomiting; no seizures were noted . Nephro- and ototoxicity, skin rash and bleeding have been the major side effects requiring drug discontinuation in 6 patients treated by PA . In conclusion, these data suggest that IMP used alone is safe and as effective as the combination of P plus A for the management of febrile granulocytopenic patients with haematologic malignancies . Further studies on a larger number of patients are needed to confirm these findings.

Int J Clin Pharmacol Res, 1989, 9(4), 293 - 6
Miokamycin penetration into oral cavity tissues and crevicular fluid; Fraschini F et al.; Diffusion of miokamycin into gum, maxillary-mandibular bone and crevicular fluid was studied in human beings . The antibiotic concentrations were determined in specimens at different times after oral administration of 600 mg in a single dose of miokamycin . Peak serum levels (2.32 +/- 0.67 mcg/ml) were found at the first hour after dosage . In healthy gum tissue the highest antibiotic levels (1.44 +/- 0.34 mcg/gr) were observed at the second hour, while in the inflamed gum miokamycin penetrates more rapidly, being, as in serum at the highest levels detectable during the first hour . In the bone of the maxilla or mandible the highest levels of miokamycin (0.88 +/- 0.13 mcg/gr) were detected at the second hour after treatment . In the crevicular fluid miokamycin showed a similar profile as that in serum, since the peak levels were reached at the first hour (2.4 +/- 0.88 mcg/ml, but the decrease of the antibiotic occurred more slowly than in serum . Miokamycin rapidly penetrates into tissues and fluids of oral cavity . A single oral dose of 600 mg guarantees antibacterial levels against susceptible bacteria over six hours.

Life Sci, 1989, 44(23), 1803 - 6
Effect of enoxacin on theophylline neurotoxicity; Hoffman A et al.; Concomitant use of the bronchodilator theophylline and the antibacterial agent enoxacin has been associated with significant neurologic and other adverse effects . Enoxacin and certain other quinolones are known to inhibit the biotransformation of theophylline, thereby increasing the plasma concentrations of the bronchodilator . It was considered possible that this may not be the only interaction because theophylline as well as enoxacin are known to have neurotoxic potential . To explore the possibility of a pharmacodynamic interaction, rats pretreated orally with enoxacin or water (controls) were slowly infused i.v . with theophylline until the onset of a maximal seizure . Neither 100 nor 400 mg/kg enoxacin 1 hour before the infusion had any significant effect on the infused dose or on the concentrations of theophylline in serum, brain and cerebrospinal fluid at onset of seizures . On the other hand, 400 mg/kg enoxacin reduced the total serum clearance of a 12 mg/kg i.v . bolus dose of theophylline from 2.56 +/- 0.37 to 1.00 +/- 0.13 ml min-1kg-1 (mean +/- SD) . It is concluded that acutely administered enoxacin in a dose sufficient to inhibit the elimination of theophylline has no direct effect on theophylline neurotoxicity in rats.

Ter Arkh, 1989, 61(5), 125 - 30
{A rapidly progressing variant of subacute infectious endocarditis}; Mukhin NA et al.; A total of 122 patients with subacute infectious endocarditis (SIE) were examined . Of these, 33 patients demonstrated an extremely severe disease course . In spite of adequate antibacterial treatment, the lethal outcome ensued within the first 2-2.5 years of the disease . A rapidly progressing variant of SIE was characterized by persistent fever, predominance of aortal heart diseases, renal injuries with an early development of renal failure, hemorrhagic vasculitis, relapsing thromboembolism, refractory heart failure, persistent anemia, lymphopenia, and by the presence of large movable vegetations discovered on echocardiography.

Sov Med, 1989, (5), 29 - 32
{Evaluation of the excretory function of the liver in inflammatory diseases of the biliary tract (data of radioimmunologic analysis of cholylglycine level)}; Buianov VM et al.; Radioimmunoassays of ++choleglycine in 41 healthy donors, 37 patients with gastroduodenal diseases and 41 ones with inflammatory diseases of the bile ducts have revealed that impaired excretory function of the liver is associated with a reduced coefficient of the bile acid extraction and a decreased bactericidal activity of the bile . The latter fact is conducive to active growth of microorganisms in the bile and thus promotes postoperative septic complications . Early detection of cholestasis resultant from impaired excretory function with the use of choleglycine radioimmunoassays permits administration of early measures to restore the bile passage and of rational antibacterial therapy to prevent postoperative pyoseptic complications.

Vestn Dermatol Venerol, 1989, (5), 69 - 72
{Algimaf treatment of trophic ulcers}; Sogomonian LM et al.; A new biologically active preparation, algimaf, developed at the All-Union Research Institute for Medical Polymers, stimulates the regenerative processes, is characterized by analgesic, antiedematous, manifest antibacterial and hemostatic effects, promotes the formation of hardly visible cicatrices, and is a highly effective means for the management of trophic ulcers of the skin.

Probl Tuberk, 1989, (6), 52 - 5
{Biochemical bases of adverse reactions to antibacterial preparations used in renal tuberculosis and means of their prevention}; Kazakov KS et al.; Factors leading to development of adverse reactions to antituberculous drugs in patients with nephrophthisis were studied and complex treatment regimens to prevent the reactions were developed . The use of such regimens along with chemotherapy allowed the frequency of adverse reactions to be lowered almost 2-fold in patients with limited nephrophthises and to postpone the development of adverse reactions in patients with extended tuberculosis for 1-1.5 months.

Microbiol Immunol, 1989, 33(6), 509 - 14
Susceptibility of Mycobacterium avium and Mycobacterium intracellulare to various antibacterial drugs; Tomioka H et al.; Mycobacterium avium and M . intracellulare of human and natural sources, identified by the Gen-Probe Rapid Diagnostic System for M . avium Complex (MAC) were studied for susceptibility to eight different drugs . In the case of human isolates of MAC, the following was noted . M . avium showed nearly the same susceptibility to streptomycin, kanamycin, ethambutol, and clofazimine as was seen with M . intracellulare . M . avium was much more resistant to rifampicin and rifabutin than was M . intracellulare, and M . avium was more susceptible to quinolones such as ofloxacin and ciprofloxacin . Conversely, in the case of MAC from natural sources, there was no difference between the susceptibility of M . avium and M . intracellulare to these antibacterial agents.

Dev Comp Immunol, 1989 Winter, 13(1), 17 - 23
Plasmatocyte depletion in larvae of Manduca sexta following injection of bacteria; Geng CX et al.; Injection of bacteria and bacterial cell walls into larvae of the tobacco hornworm elicits a rapid, specific depletion of plasmatocytes from circulation . Plasmatocyte depletion in response to injection of bacteria is dose dependent with a threshold for response between 10(3)-10(4) bacteria per insect and a maximal depletion at greater than 10(7) bacteria per insect . Injection of saline, latex beads that are phagocytized, or fragments of peptidoglycan that elicit antibacterial protein synthesis do not affect plasmatocyte abundance.

Pharm Acta Helv, 1989, 64(7), 183 - 7
Study in the chemical constituents of plantago cynops L . and antibacterial evaluation of verbascoside; Debrauwer L et al.; Oleanolic acid, verbascoside, plantarenaloside and four sterolic derivatives were isolated from the aerial parts of Plantago cynops L . These constituents in this species were determined and described for the first time . An antibacterial evaluation was carried out for verbascoside.

Khirurgiia (Sofiia), 1989, 42(1), 38 - 40
{Our experience in treating sub crustam skin burns}; Demirov D et al.; Alcoholic solution of chlorhexidine and methylene blue was used in 64 patients for local treatment of burned skin surfaces . The wounds healed under the crust, formed from denatured and desiccated fibrin coats and necrotic tissues . The two antiseptic agents (chlorhexidine and methylene blue) provided long-term antibacterial effect . The results were encouraging; epithelialization of rather deep burns was shortened by 4 or 5 days.

Chemotherapy, 1989, 35(2), 77 - 82
Study on the relationship between pharmacokinetics and antibacterial activity: comparison between ceftriaxone and cefotaxime within the respiratory tract; Fraschini F et al.; The aim of this research was to collect precise data on the antibacterial activity of ceftriaxone and cefotaxime in the respiratory tract . The diffusion into pulmonary tissue and bronchial secretion and the antibacterial activity of the two antibiotics were evaluated in vivo by means of the inhibitory quotient . Ceftriaxone administered at a dosage of 1 g (i.m.) every 24 h resulted in antibacterial levels against the sensitive pathogens over a period of 24 h after each dose . The antibacterial protection afforded by cefotaxime, given at the dosage of 1 g (i.m.) every 12 h, was not as marked and did not extend over the interval between two administrations.

Klin Khir, 1989, (4), 48 - 50
{Experience with the use of endolymphatic antibacterial therapy}; Spizhenko IuP et al.; In 98 patients with different purulent-inflammatory processes, the method of antegrad endolymphatic antibacterial therapy was used in the complex of treatment . One of the antibiotics (ampicillin, gentamycin, claforan), and metrogyl, dioxydin, contrical, heparin at the routine therapeutic doses 1 time at 24-48 h were introduced into the lymphatic vessel of the lower extremity via a catheter . The duration of treatment depended on the severity of the course of inflammatory process . In 74.4% of cases, the treatment was effective.

Drugs Exp Clin Res, 1989, 15(3), 115 - 8
Efficacy of dactimicin in the treatment of experimentally induced intra-abdominal infections; Nord CE et al.; A reproducible experimental model of intra-abdominal infections in rats has been worked out in order to simulate intra-abdominal sepsis in patients . A 1-cm segment of ileum was isolated on its vascular pedicle . The intestine was then divided at each end of the segment and intestinal continuity was reestablished by an end-to-end anastomosis . Dactimicin is a new aminoglycoside antibiotic and has a broad antibacterial spectrum including both Gram-positive and Gram-negative aerobic bacteria . The experimental model was used to compare the efficacy of dactimicin alone and in combination with metronidazole with the combination gentamicin and metronidazole in the treatment of intra-abdominal infections . Many of the untreated animals (70%) died within 2 days . Within 7 days 40% of the animals receiving dactimicin died . Animals treated with dactimicin plus metronidazole or gentamicin plus metronidazole had a significantly decreased mortality and increased cure rates during the experimental period . Only 5% of these animals died . Thus the combination dactimicin and metronidazole seems to be useful in the treatment of intra-abdominal infections.

J Antimicrob Chemother, 1989 Jan, 23(1), 43 - 51
Bactericidal effects of amoxycillin/clavulanic acid against Legionella pneumophila; Stokes DH et al.; The antibacterial activities of amoxycillin, clavulanic acid and the combination of both agents against Legionella spp . were compared in serial-dilution tests, time-kill curve studies and in turbidimetric studies in a continuous recording biophotometer . Both beta-lactam compounds showed high levels of activity against L . pneumophila in serial dilution tests, clavulanic acid (MIC 0.1-0.25 mg/l) being two-fold more active than amoxycillin . The combination of amoxycillin and clavulanic acid was more effective than either of the constituents and was two to four times more active than erythromycin . Clavulanic acid was shown to reduce the extent of inactivation of amoxycillin by L . pneumophila and amoxycillin/clavulanic acid was rapidly bactericidal against the organism in tests in which amoxycillin was ineffective . Microscopical examination showed distinctive morphological effects produced by amoxycillin and by clavulanic acid and synergy between the compounds could be attributed to beta-lactamase inhibition, or by binding to different penicillin binding proteins, or both . These results warrant further studies in vitro and in vivo to elaborate the bactericidal effects demonstrated by amoxycillin and clavulanic acid against Legionella spp.

Arkh Patol, 1989, 51(3), 49 - 54
{Structural bases of the decrease in nonspecific antibacterial resistance of the body, related to the functioning of the neutrophil system}; Galankin VN et al.; Light optic and ultrastructural examinations of neutrophilic phagocytosis in patients with phlegmons in test system revealed morphological changes in the cells . The changes were proposed by the authors to be regarded as a criterion for assessing the antibacterial resistance of the body . Moreover, a unique approach was developed to the overall assessment of phagocytic indices, providing characterization of two neutrophilic performance types: balanced and extensive . When neutrophils begin to function extensively, this may be considered as a reflection of their relative functional inadequacy.

Klin Khir, 1989, (1), 13 - 5
{Antibacterial sutures "Capromed DQ" in abdominal surgery}; Polous IuM et al.; In the work, the experimental substantiation and results of clinical approbation++ of the new Capromed DC antibacterial polymeric threads are given . It was established that the threads had no negative effect on reparative processes, created local concentration of an antiseptic, reduced the inflammatory reaction and microbial colonization . This contributed to decrease in the incidence of postoperative complications related to the quality of a suture material.

Eur Surg Res, 1989, 21 Suppl 1, 52 - 4
Antibacterial chemotherapy for treatment of infections in outpatient surgery; Flesch R; 126 patients with surgical infections of different severity were treated intravenously with ceftriaxone (Rocephin) 2 or 1 g once a day in less serious cases . We did not observe any severe drug reaction; the duration of therapy varied between 1 and 7 days . Ceftriaxone is a very powerful broad-spectrum antibacterial drug . Treatment with a single injection or infusion per day saves costs and avoids hospitalisation: ceftriaxone is thus the ideal antibacterial drug for the ambulatory patient.

Drugs Exp Clin Res, 1989, 15(2), 71 - 6
Cefroxadine in the treatment of children affected by respiratory and ENT diseases . A multicentre study involving 1072 in-patients; Scaglione F et al.; In this multicentre trial, 1072 hospitalized children, 573 boys and 499 girls (847 of whom were aged less than 6 years), affected by respiratory tract (376 patients) or ENT (696 patients) infections were treated for 10 days with cefroxadine per os, at an average dose of 650 mg/day (325 mg every 12 h corresponding to 25 mg/kg b.w.) . Most patients (1047; 97.7%) completed the trial, while 25 patients were withdrawn from the study (20 patients for viral diseases and 5 for side-effects) . Of the patients affected by respiratory tract infections, 361 completed the trial and 342 of them (94.7%) were cured in 6.0 days on average . Of the patients affected by ENT infections, 686 completed the trial and 649 of them (94.6%) were also cured in an average of 6.0 days . In the two groups the signs and symptoms of the disease significantly (p less than 0.001) decreased by the end of the study . Some patients (80; 7.6%) complained of side-effects, mainly gastric discomfort (4.9%), skin rash (2.2%) and glossitis (0.5%) . In conclusion, cefroxadine exerts a satisfactory antibacterial action with only a few days of treatment, and it appears to be very well tolerated.

Antibiot Khimioter, 1989 Jan, 34(1), 60 - 4
{Role of microbiological control in the choice of antibacterial therapy of respiratory infection in surgical patients during the postoperative period}; Bekbergenov BM et al.; The paper presents data on observation of 416 surgical patients subjected to investigation of sputum and washings from the tracheobronchial tree for estimating the role of clinico-microbiological study of respiratory tract excretions from surgical patients in choice of adequate therapy . On the basis of the obtained data and results of clinical observations a scheme of clinico-microbiological criteria was developed which would be of help for clinicians and microbiologists in difficult differential diagnosis of colonization and infection . The scheme will provide clinical microbiologists with possibility of correct interpretation of the results of studying respiratory tract excretions and presenting information containing preliminary positive or negative indications as to the presence of infection and recommendations for continuation or discontinuation of further clinico-microbiological investigations.

Chem Pharm Bull (Tokyo), 1989 Jan, 37(1), 93 - 9
Fluorocinnoline derivatives . II . Synthesis and antibacterial activity of fluorinated 1-alkyl-1,4-dihydro-4-oxocinnoline-3-carboxylic acids; Miyamoto T et al.; Chemical modification of cinoxacin was studied with the aim of improving its antibacterial activity and spectrum . Alkylation of ethyl 6,7,8-trifluoro- and 6,7-difluoro-4-hydroxycinnoline-3-carboxylates (1 and 7) with alkyl iodide or dialkyl sulfate gave ethyl 1-alkyl-6,7,8-trifluoro- and 6,7-difluoro-1,4-dihydro-4-oxocinnoline-3-carboxylates (2 and 8), together with the isomeric anhydro-bases 3 and 9 of 2-alkyl-3-ethoxycarbonyl-6,7,8-trifluoro- and 6,7-difluoro-4-hydroxycinnolinium hydroxides, respectively . Acid-catalyzed hydrolysis of the 1-alkyl derivatives 2 and 8 gave the corresponding carboxylic acids 4 and 10 . The same treatment of 3 and 9, accompanied with decarboxylation of the inner salts 5 and 11, afforded the anhydro-bases 6 and 12 of 2-alkyl-4-hydroxycinnolinium hydroxides, respectively . Displacement reactions of 4 and 10 with nucleophiles such as amine, alkoxide and thiolate gave 7-substituted 1-alkyl-6,8-difluoro- and 6-fluoro-1,4-dihydro-4-oxocinnoline-3-carboxylic acids (13 and 17-35) . Antibacterial activities of these compounds were evaluated and compared with those of cinoxacin and norfloxacin . Some compounds showed a broader spectrum and more potent activity than cinoxacin, but were considerably inferior in activity to norfloxacin.

Toxicon, 1989, 27(2), 179 - 88
Biological activity of saponins and saponin-like compounds from starfish and brittle-stars; Andersson L et al.; Twenty-four saponins and saponin-like compounds, isolated from starfish and brittle-stars, have been tested in four in vitro tests, based upon bacterial and cell tissue cultures . Saponin-like compounds from brittle-stars have previously not been tested for biological activity . In an antibacterial test based on an agar diffusion test, the Gram positive bacterium S . aureus was affected by the polyhydroxylated steroidal glycosides, polyhydroxylated sterols and disulfated sterols . However, none of the 21 compounds tested were active against the Gram negative bacterium E . coli . In a cytotoxicity test all 21 compounds tested influenced the cells at a concentration of 100 micrograms/ml, while the cells were unaffected at 1 microgram/ml . In an antitumor test, 16 compounds were tested on two lymphoma cell lines . Inhibition of cell growth, at a concentration of 5 ng/ml, was seen for three polyhydroxylated sterols, in one cell line . Weak activity was seen in an antiviral test at a concentration of 10 micrograms/ml.

Probl Tuberk, 1989, (1), 5 - 7
{Evolution of tuberculosis morbidity and the factors governing it at different stages of the anti-tuberculosis campaign}; Dvoirin MS et al.; Characteristics of the tuberculosis incidence in the Ukrainian SSR since the beginning of the wide use of antibacterial therapy were studied . It was shown that the delayed decrease in the incidence of tuberculosis in young persons observed lately did not correlate with further improvement of the epidemiological situation with respect to tuberculosis . It was indicated that the phenomenon stemmed from insufficient control of heavy alcohol drinking and alcoholism in the population and tuberculous patients.

Izv Akad Nauk SSSR Biol, 1989 Jan-Feb, (1), 144 - 7
{Antibacterial activity of coumarin derivatives}; Samokhvalov AN et al.; Preliminary tests of antibacterial activity of several coumarin derivatives, substituted at the positions of 3 or 4 of the pyrone cycle . Halogen-containing coumarins do not exhibit antibacterial properties . A sodium salt of 4-mercaptocoumarin is the most active bacteriostatic compounds among sulfur-containing derivatives.

Diagn Microbiol Infect Dis, 1989 Jan-Feb, 12(1), 67 - 72
Antibacterial activity of cefotaxime, desacetylcefotaxime, and the combination of the two; Friis H; Cefotaxime (CTX) is metabolized to desacetylcefotaxime (dCTX), which is antibacterially active . The combination of CTX and dCTX is synergistic in a 1:1 ratio, but in this study, a combination of CTX:dCTX in a fixed ratio of 5:1 was not found synergistic when tested on 120 recently isolated clinical strains . Zone diameters of disks containing pure CTX or dCTX 30 micrograms or the combination of CTX/dCTX in micrograms: 25/5, 20/10, 15/15, and 10/20, were compared . The correlation between the zone size of the pure CTX disk and the 25/5, 20/10, and 15/15 disks were high with correlation coefficients (r) 0.98 to 0.96 . Regardless of the metabolism and the potential synergy, no differences were found in the zone sizes comparing the pure CTX disk with the combination with a ratio from 5:1 to 1:1 . The clinical microbiological laboratory can go on using the pure 30 micrograms CTX disk for routine susceptibility testing.

Anesteziol Reanimatol, 1989 Jan-Feb, (1), 17 - 9
{Choice of antibacterial therapy with the use of a computerized consultation system}; Vrublevskii OP et al.; The principle for a consulting system ensuring selection of a "theoretically optimal" antibiotic or antibacterial drug combination for the treatment of severe pyo-septic conditions in critically ill patients is described . The system is an addition to an automated case history, which ensures its efficacy . The algorithms are based on the analysis of the literary data and the results of many years of studying microorganisms in infectious foci.

Anticancer Res, 1989 Jan-Feb, 9(1), 49 - 52
Bactericidal and cytotoxic effect of combination of norfloxacin and 5-fluorouracil; Castelli M et al.; Using the agar dilution technique, we examined the in vitro antibacterial activity of 5-fluorouracil and norfloxacin alone and in association against several bacterial strains . When administered in association, the two drugs did not antagonize each other in tests carried out on strains both sensitive and resistant to penicillins, cephalosporins, aminoglycosides, tetracyclines; furthermore their respective antibacterial properties remained largely unimpaired . The cytotoxic activity and the antitumoral effect of a combination of 5-fluorouracil and norfloxacin was determined in cultured tumor cells, and in mice bearing Ehrlich ascites carcinoma . No significant interference with the cytotoxic activity and antitumoral activity of 5-fluorouracil was observed.

Biotherapy, 1989, 1(4), 319 - 25
Stimulation of hematopoiesis and antibacterial resistance by interleukin-1; McIntyre KW et al.; The beneficial effects of IL-1 and other cytokines on hematopoiesis and on resistance to infection are profound . IL-1 stimulates proliferation of bone marrow cells in normal mice and potentiates the recovery of peripheral blood neutrophils in mice with drug-induced neutropenia . Prophylactic cytokine administration provides an elevated level of natural resistance to infections which is correlated with increased numbers of phagocytic leukocytes . These studies suggest that IL-1 has potential clinical application as a therapy to limit bone marrow dysfunction and immunosuppression and to augment hematopoiesis and natural immunity . Further research will continue to elucidate the mechanisms whereby interleukins and colony-stimulating factors act, and interact, to promote restoration of leukocyte production and to enhance host resistance.

Sov Med, 1989, (11), 30 - 4
{Rapid methods of detection of bacteria in the bile}; Buianov VM et al.; Rapid methods are described for assessing the bacterial contamination, using direct phase-contrast microscopy, triphenyltetrazolium chloride (TTC) test, and a standard loop 3 mm in diameter, or by the detection of the biliary 'active' leukocytes and the microflora sensitivity to antibacterial drugs with the use of the TTC test and turbidimetric technique . These methods permit getting an answer in 4-24 hrs, are simple, and do not require special bacteriologic equipment, this recommending them for routine clinical studies.

Eur J Cancer Clin Oncol, 1989, 25 Suppl 2, S37 - 42
Empiric single agent or combination antibiotic therapy for febrile episodes in neutropenic patients: an overview; Lieschke GJ et al.; Febrile episodes during chemotherapy-induced neutropenia are a frequent cause of morbidity and mortality in cancer patients . Empiric antibiotic therapy commencing at the onset of fever is selected according to three principles: intravenous therapy is used to rapidly achieve bactericidal serum levels, antibiotics with appropriate antibacterial spectra are required, and combinations of antibiotics have been preferred for their synergistic activity . Initial empiric monotherapy with single antibiotics such as imipenem which have a sufficiently broad antibacterial spectrum in their own right are potentially as efficacious as conventional combination therapies . Granulocytopenic periods complicated by fever are significantly longer in patients receiving chemotherapy for leukaemia than in patients undergoing treatment for lymphoma and solid tumours . However, defervescence of fever following commencement of antibiotic therapy occurs equally rapidly in these three groups . The persistent granulocytopenia leaves leukaemic patients at greatest risk of breakthrough or second infections . These patients therefore appear to be the most likely to benefit from the clinical use of haemopoietic growth factors such as granulocyte and granulocyte-macrophage colony-stimulating factor.

Nephrologie, 1989, 10 Suppl, 30 - 3
{Local immunologic reactions induced by CAPD}; Faller B et al.; During CAPD, the peritoneal cavity is submitted to situations such as the accidental bacterial contaminations and the continuous presence of dialysate, which stimulate immunological factors . The antibacterial defenses include opsonins and cells . Only IgG and fibronectin are present in the peritoneal effluent but they are diluted by the dialysate . Macrophages represent 70 to 80% of the peritoneal cells . Beside good phagocytic capacity, some may have a defective bactericidal activity . The continuous presence of dialysate leads to a chronic local inflammation . Macrophages and lymphocytes will synthesize IL-1, PGE2 and IFN-Y . These substances generate movement, attachment and proliferation of fibroblasts in the peritoneal submesothelial tissue, resulting in progressive fibrosis . This fibrosis, generally asymptomatic, may be responsible for loss of Ultrafiltration (UF) and Sclerosing Encapsulating Peritonitis (SEP).

Drug Des Deliv, 1989 Jan, 4(1), 1 - 12
Transdermal delivery of drugs by iontophoresis: a review; Singh J et al.; The advantages and limitations, theory, and factors in the use of electric current to deliver drugs across the skin are discussed . Application of the technique in the delivery of local anaesthetics, antibiotics/antibacterials, mydriatics, vinca alkaloids, non-electrolytes, biogenic amines, peptides, and other agents is reviewed . It is concluded that the method alone, or in combination with phonophoresis (delivery via ultrasonic perturbation), offers considerable scope in the transdermal delivery of drugs.

Arkh Patol, 1989, 51(5), 3 - 11
{Endotoxin and the polymorphonuclear leukocyte system}; Permiakov NK et al.; Due to its cell pool autoturnover, gram-negative intestinal microflora releasing the biologically active agent lipopolysaccharide may cause portal and systemic endotoxemias . Lipopolysaccharide may function in the activation of the polymorphonuclear leukocyte system and in complex antibacterial homeostatic processes, and, in some situations be the initiating factor in the development of various organ pathology, which is mediated by hyperactivated granulocytes.

Vestn Dermatol Venerol, 1989, (1), 29 - 34
{Effect of microfields of magnetically aligned media on Treponema pallidum . 1}; Milich MV et al.; An end ferromagnetic masking of T . pallidum has been revealed; this phenomenon appears to help the bacterium orientation in human body under the effects of both the external electromagnetic fields and the internal sources of such fields in the body . The studies have demonstrated the primary physicochemical mechanism of the magnetic field action of T . pallidum--human body biological system . A magnetically regulated medium (MRM) is a tool altering the characteristics of the biological material and revealing the new properties of the pathogenic bacterium . This latter fact promotes search for new approaches to the suppression of T . pallidum and, probably, other pathogens' infectious activities . Immediate degradation of T . pallidum in thin MRM suggests a possibility of creating potent antibacterial coating for working elements of medical instruments.

Probl Tuberk, 1989, (1), 44 - 7
{Indications for the use of prednisolone in tuberculosis}; Starostenko EV et al.; To study the nature of lesions in the lungs developing as a result of using glucocorticoids in combined therapy of tuberculosis, two groups of new cases of infiltrative tuberculosis were observed . 51 patients were treated with the use of prednisolone and 23 patients were treated with antibacterial drugs alone . In addition, studies were performed on two groups of noninbred albino rats infected with mycobacteria Bovinus-8 . It was shown that by changing the nature of the tissue reactions prednisolone promoted formation of tuberculoma type foci in the lung tissue and prolonged the periods of cavern closing.

Eisei Shikenjo Hokoku, 1989, (107), 29 - 36
{Combined long-term toxicity/carcinogenicity test of alpha-bromocinnamic aldehyde (BCA) applied to female mouse skin}; Momma J et al.; Bromocinnamic aldehyde (BCA), an antibacterial/antifungal agent, was tested for its chronic toxicity/carcinogenicity in female Slc:ddY mice . The animals received 0.25%, 1.0% and 4.0% of BCA dissolved in olive oil applied to the shaved back skin area twice a week for 79 weeks . The control group received olive oil alone under similar conditions . In addition to these animals, 5 animals in each group were killed at 6 and 12 months for investigation of the time-related toxic effect of BCA . A slight inhibition of body weight increase and a slight decrease in the survival rate were seen in the 4.0% BCA-treated group . No significant changes were observed in hematological parameters at 6, 12 and 18 months . In chemical biochemistry determination in the blood at 6 and 12 months, a significant decrease in non-esterified fatty acid and phospholipid values was observed in the experimental groups . Histopathologically, necrosis, scabbing, cell infiltration and thickening of the epidermis were noted at the site of application in the 4.0% BCA group . Moreover, extramedullary hematopoiesis and amyloid degeneration were detected in the spleen, while the incidence of adenomas in the lung decreased with a dose-response . These changes seemed to be the result of a non-specific inflammatory reaction to the irritation effects of the agent on the skin . No significant differences in the incidence of tumors were found between the control and experimental groups, not only at the site of application but also in other organs, although lung adenomas decreased dose-dependently in all treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Klin Khir, 1989, (12), 35 - 6
{Puncture scrotostomy--a treatment method in acute inflammatory diseases of the scrotal organs}; Shapoval VI et al.; A method for the treatment of acute inflammatory diseases of the scrotal organs by means of puncture scrotostomy, which consists in passing the indwelling micro-irrigator into a cavity of the serous sheath of the testis and epididymis and administration via this route of antibacterial and resolving preparations for 4-5 days, is suggested . A method approved in treatment of 45 patients permits to avoid surgical intervention, and is highly effective.

Drugs Exp Clin Res, 1989, 15(10), 483 - 5
Susceptibility of Brucella melitensis to fluoroquinolones; Qadri SM et al.; In vitro activity of four fluoroquinolones and four other antibacterial agents was tested against clinical isolates of Brucella melitensis . Initially all the 146 isolates studied were inhibited by 0.06-0.5 mg/l of ciprofloxacin and fleroxacin and 0.12-0.5 mg/l of pefloxacin or norfloxacin . One of these isolates developed resistance during therapy with ciprofloxacin, with a rise in MIC from 0.06 mg/l to more than 5.0 mg/l . This strain also showed cross-resistance to all other quinolones . All the isolates remained susceptible to tetracycline, gentamicin, rifampicin and trimethoprim-sulfamethoxazole . None of the quinolones showed in vitro synergy with other antibiotics.

Acta Pol Pharm, 1989, 46(2), 119 - 26
{Effectiveness of new quarternary ammonium chloride compounds against selected bacteria and fungi . XXI . Synthesis of alkoxymethyl-3,4-dimethyl- pyridine and 1-ethyloxymethyl-3-alkylthiomethylimidazole chlorides}; Pernak J et al.; Syntheses and antibacterial properties of alkoxymethyl-3,4-dimethylpyridinium chlorides and 1-ethyloxymethyl-3-alkylthiomethylimidazolium chlorides are described . Alkoxymetgyl-3,4-dimethylpyridinium chlorides were synthetized by reacting 3,4-dimethylpyridine with chloromethyl alkyl ethers, while 1-ethyloxymethyl-3-alkylthiomethylimidazolium chlorides were obtained in reactions of 1-ethyloxymethylimidazol with chloromethyl alkyl sulfides . Antibacterial properties of the obtained compounds were tested on 13 strains of bacteria and fungi . Strong bacteriostatic activity was found to be displayed by iminium chlorides with octyloxymethyl, decyloxymethyl, octylthiomethyl and decylthiomethyl groups.

Probl Tuberk, 1989, (12), 25 - 8
{The use of bronchological methods as the means for the intensive treatment of patients with severe manifestations of lung and pleural diseases}; Kazakov AF et al.; The results of using methods of intensive therapy, i.e . administration of antibacterial mixtures into the retrotracheal fat as well as temporary bronchial occlusion are presented . 49 patients with severe or torpid diseases of specific and nonspecific etiology whose treatment was difficult because of complications or concomitant diseases were included into the study . The methods of intensive therapy proved efficient in some patients with severe affections of the lungs and pleura . They should be widely used in clinical practice.

Vestn Akad Med Nauk SSSR, 1989, (11), 63 - 8
{Factors of antiviral resistance in the pathogenesis of influenza in mice}; Chetverikova LK et al.; Findings of original research on the factors of nonspecific resistance (interferon formation, antibacterial activity of peritoneal exudate cells, and natural cytotoxicity of splenocytes) and immunity (changes in sub-populational composition of spleen lymphocytes) in different types of influenza in mice are analysed . There was no infection-mediated suppression of the studied reactions, that could have been considered as a cause of death or a basis for immunodeficiency status . The correlation of the level of cerebral lipid peroxidation in mice with severe infection formed the basis for testing the synthetic antioxidant ionol as an anti-influenza agent . A prophylactic effect of ionol toward the development of influenza infection has been obtained . Its possible actions and the feasibility of search for prophylactic and therapeutic preparations among the agents with pathogenetic action is discussed.

J Reprod Fertil Suppl, 1989, 39, 225 - 9
A retrospective study of 40 cases of canine pyometra-metritis treated with prostaglandin F-2 alpha and broad-spectrum antibacterial drugs; Gilbert RO et al.; Bitches with pyometra were treated with dinoprost, a prostaglandin F-2 alpha-THAM salt or luprostiol, a synthetic PG analogue and oral broad-spectrum antibacterial drugs . PGF-2 alpha treatment lasted 2-26 days and dosage varied from 26.8 to 258 micrograms/kg . Clinical cure from symptoms was achieved in 33/40 bitches . Of 14 bitches from which the owners opted to breed, 9 eventually produced litters . Long-term complications were anoestrus, recurrence of metritis, failure to conceive and abortion . One or more of these complications were recorded in 9 of 20 bitches for which long term information was available.

Yao Xue Xue Bao, 1989, 24(7), 512 - 21
{Synthesis of 7-(1,7-disubstituted-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxamido) -cephalosporins}; Zhou JC et al.; A series of new 7-(1, 7-disubstituted-1, 4-dihydro-4-oxo-1, 8-naphthyridine-3-carboxamido)-cephalosporins has been prepared by acylation of the 7-amino group of 7-ADCA, 7-ACA, 7-ACT and 7-ACD with 1, 7-disubstituted-1, 4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid . Mixed carboxylic-carbonic anhydride method was adopted in the reactions . Isolation and purification were fulfilled with Sephadex LH-20 column chromatography and centrifugal-TLC technique . Twenty four new cephalosporin derivatives were synthesized . Their structures have been confirmed by elemental analysis, IR and 1HNMR . In preliminary In vitro antibacterial sensitivity tests, most of these new derivatives were found to show good sensitivity to Gram-positive bacteria . Bacteriostasis were also observed for some Gram-negative bacteria.

Yao Xue Xue Bao, 1989, 24(10), 744 - 8
{Studies on antibacterial constituents from Gerbera anandria (L.) Sch Bip . IV}; Gu LH et al.; Thirteen compounds have been isolated from Gerbera anandria (L.) Sch Bip . Among them, three new compounds were elucidated by chemical correlations and spectral analyses . They are 3.8-dihydroxy-4-methoxy-coumarin (XIX), 3,8-dihydroxy-4-methoxy-2-oxo-2H-1-benzopyran-5-carboxylic acid (XVII), and 5,8-dihydroxy-7-(4-hydroxy-5-methyl-coumarin-3-)coumarin (XXI).

Chemotherapy, 1989, 35 Suppl 2, 5 - 9
Ceftriaxone versus cefotaxime in the treatment of septicemia in adults; Ferencz A et al.; Two potent third-generation cephalosporins with similar antibacterial spectra but different pharmacokinetics were compared in patients suffering from septicemia due to different organismus . Sixty patients with a variety of underlying diseases were included in the study . They received either 2-4 g ceftriaxone (active ingredient of Rocephin) once a day or 2 g cefotaxime every 8 h for 10-15 days . Our data confirm that a single dose of 2 g ceftriaxone should be sufficient to treat septicemia.

Ann Pharm Fr, 1989, 47(2), 89 - 94
{Antibacterial activity of some lichens from southern Spain}; Rowe JG et al.; Antibacterial activity of some lichens from south Spain has been studied . High activity against Gram+ bacteria has been observed, although Parmelia caperata, Evernia prunastri and Usnea sp . are also active against Gram- bacteria.

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