Pharmacoeconomics, 1992 Jun, 1(6), 409 - 37 Pharmacoeconomics of antibacterial treatment; Davey PG et al.; Antibacterial drugs account for between 3 and 25% of all prescriptions, between 6 and 21% of the total market value of drugs in a single country, and up to 50% of the drug budget in hospitals . Bacterial infection is widely perceived as disease caused by harmful outside agents which can be isolated and tested to select the best drug for treatment . In fact, the need for any treatment and the pros and cons of different drugs are just as debatable as in any other therapeutic area . Moreover, the bacteria which make up the normal flora of the body fulfil important roles, so that the ecological implications of treatment for the individual and for society should be considered in assessing the costs and consequences of antibacterial treatment . In this review we outline the most important issues relating to the treatment of bacterial infection in the community and in the hospital, contrasting information from developed and developing countries where appropriate . We review the existing literature on economic evaluation, but in general most of the literature deals with containing the costs of antibacterial drugs in hospitals, and there are many gaps in the literature on cost-effectiveness of treatment . Consequently there are still extreme variations in medical practice which present a challenge for future evaluation . As the outcomes of antibacterial treatment are apparent in a few weeks or months, this is an ideal field for testing pharmacoeconomic methodology . The desire to overcome medical practice variation through consensus statements should be avoided . Instead we recommend wider application of decision analysis to acknowledge that choices exist for the diagnosis and treatment of bacterial infection and to gather information about the implications of these choices . Much of the existing literature would be improved by a more explicit definition of costs . Direct costs to the health services should be distinguished from non medical costs . Moreover, the analysis should consider whether savings from one budget result in costs to another health service budget, or to the patient (transfer costs) . These deficiencies in cost analysis will be relatively easy to correct . Of more concern is the fact that the efficacy of much antibacterial treatment is either totally debatable, or variable, depending on factors such as the type of patient treated or the quality of delivery of treatment.(ABSTRACT TRUNCATED AT 400 WORDS) Zentralbl Veterinarmed B, 1992 May, 39(3), 165 - 74 Immunoglobulins, lysozyme and lactoferrin in the teat and udder of the dry cow during endotoxin-induced inflammation; Persson K et al.; Immunoglobulins (Ig) and antibacterial proteins like lysozyme and lactoferrin are components of the humoral defence against infections . Changes in Ig, lysozyme and lactoferrin concentrations during endotoxin-induced inflammation in the test cistern and udder quarter of the dry cow were studied . Surgical closure of the passage between teat and udder cisterns enabled studies of reactions in the teat cistern without interference of the mammary gland . After endotoxin infusion, IgG1, IgG2, lysozyme, and to some extent IgM, increased in the teats and udder quarters, and were positively correlated with changes in somatic cell counts . No significant changes were observed in IgA or lactoferrin . The origin and significance of Ig, lysozyme and lactoferrin in the bovine teat and udder are discussed . Ig probably originated both from serum and from local plasma cells, while leukocytes appeared to be the source of lysozyme during inflammation . Secretory epithelium appeared to be the source of lactoferrin . Support for this theory was the almost total absence of lactoferrin in teat cistern samples. J Antibiot (Tokyo), 1992 May, 45(5), 721 - 34 Studies on condensed-heterocyclic azolium cephalosporins . V . Synthesis and antibacterial activity of 3-(condensed-triazolo-pyridinium, -pyrimidinium, and -pyridazinium)-methyl cephalosporins; Yoshimura Y et al.; As a part of our studies on cephalosporins bearing condensed-heterocyclic azolium methyl groups at the 3 position in the cephalosporin nucleus, we describe here the synthesis and antibacterial activity of 7 beta-{2-(2-aminothiazol-4-yl)2(Z)-methoxyiminoacetamido} cephalosporins (1-16, 7 beta-{2-(2-amino-5-chlorothiazol-4-yl)-2(Z)- methoxyiminoacetamido} cephalosporins (17,18) and 7 beta-{2-(5-amino- 1,2,4-thiadiazol-3-yl)-2(Z)-methoxyiminoacetamido) cephalosporins (19-23) containing a variety of condensed-heterocyclic triazolium methyl groups at the 3 position in the cephalosporin nucleus . These cephalosporins exhibited potent antibacterial activity, and it appears that condensed-heterocyclic triazolium as well as condensed-heterocyclic imidazolium rings are effective moieties for improving antibacterial activity and the spectrum of activity . Among the cephalosporins tested, 7 beta-{2-(2-aminothiazol-4-yl)-2(Z)-methoxyiminoacetamido}-3-(5- methyl{1,2,3}triazolo-{1,5-alpha}pyridinium-1-yl)methyl-3-cephem-4- carboxylate (9) and 7 beta-{2-(2-aminothiazol-4-yl)-2(Z)-methoxyiminoacetamido}-3-(6- methoxy{1,2,4}triazolo{1,5-alpha}pyridinium-1-yl)methyl-3-cephem-4- carboxylate (11) showed good antibacterial activity. Diagn Microbiol Infect Dis, 1992 May-Jun, 15(4 Suppl), 77S - 79S Penetration of roxithromycin into gingival tissue; Jehl F et al.; Roxithromycin is a new macrolide with an antibacterial spectrum similar to that of erythromycin . Absorption is rapid and complete, resulting in high serum levels and a long half-life . Tissue distribution is extensive and sustained, as shown by the high concentrations measured in the lung, prostate, ovaries, liver, kidney, and skin . In this study, we measured the penetration of roxithromycin into gingival tissue at steady state in 30 patients treated orally with 150 mg every 12 hr for 5 days . Tissue specimens were sampled at 2, 4, 6, 8, or 12 hr (n = 6 each time) after dose 10, and blood samples were taken simultaneously . Serum and tissue concentrations of roxithromycin were measured by high-performance liquid chromatography . The peak serum level, reached 4 hr after dosing, was 6.60 +/- 1.15 micrograms/ml . The peak tissue level was 4.63 +/- 1.84 micrograms/g and was reached after 8 hr . From 4 to 10 hr after dosing, tissue concentrations were greater than 2 micrograms/g, that is, higher than the MIC90 of roxithromycin against most oral pathogens . These data support the use of roxithromycin in the treatment of oral infections. Orthop Rev, 1992 May, 21(5), 577 - 9 Tobramycin-impregnated cement in total hip replacements; Pritchett JW et al.; The clinical effect of adding 1.2 g of tobramycin powder to each 40-g pack of powdered polymethylmethacrylate used in hip replacement surgery was investigated . Fifteen patients underwent total hip replacement in which a cemented femoral prosthesis and a cementless acetabular prosthesis were used . Postoperatively, the tobramycin levels in the blood and in the wound drainage fluid were measured . The serum tobramycin concentrations were low, whereas the wound drainage fluid contained highly effective antibacterial concentrations . There was no evidence of reaction or toxicity to the antibiotic-impregnated bone cement. J Invest Dermatol, 1992 May, 98(5), 725 - 9 Quantitative in vitro assessment of phototoxicity by a fibroblast-neutral red assay; Lasarow RM et al.; We have adapted the neutral red uptake assay for quantitative assessment of injury to fibroblast cultures by potential phototoxins . Tetracycline derivatives, quinolone derivatives, and chlorpromazine were used as model compounds for development of the assay . Human fibroblasts were incubated with potential phototoxins, the cell cultures irradiated with UV, and the capacity for neutral red uptake determined . Demeclocycline and doxycycline, two known photosensitizers, showed a 94% and 95% decrease of neutral red uptake, respectively, indicating photo-induced cytotoxicity . Minocycline, a non-photosensitizing tetracycline derivative, showed no decrease in uptake . Tetracycline, a weak phototoxin, showed minor (10%) decrease at equivalent concentrations (20 micrograms/ml) . Microscopic observation of neutral red uptake and cell damage paralleled the spectrophotometric findings . Chlorpromazine, a non-tetracycline phototoxin, showed 91% decrease . An additional group of phototoxic drugs, quinolone antibacterials, were studied . Nalidixic acid, ofloxacin, ciprofloxacin, and norfloxacin all demonstrated phototoxicity, with nalidixic acid showing the greatest decrease in neutral red uptake . This methodology may provide a useful rapid method to quantify phototoxic potential of new drugs or suspected phototoxins. Jpn J Antibiot, 1992 May, 45(5), 569 - 75 {Penetration of levofloxacin in bile}; Mizuno A et al.; The penetration into bile of a new pyridonecarboxylic acid derivative, levofloxacin (LVFX), was studied in a closs-over method with ofloxacin (OFLX) as the control drug in 6 post-operative patients . The lengths of time to the maximum concentrations in bile and the total areas under the curves were both almost the same for these 2 compounds, although the maximum bile concentration of LVFX was slightly lower than that of OFLX . A stability test for LVFX in human bile revealed that over 95.4% of the initial amount was recovered up to 24 hours after commencement of incubation at a room temperature, thus the stability in bile was similar to that in water . The penetration of LVFX which possesses twice as strong antibacterial activities as OFLX was similar to that of OFLX, suggesting that LVFX is useful against bile duct infections. Jpn J Antibiot, 1992 May, 45(5), 557 - 68 {Chemotherapy of biliary tract infections (XXXVII) . Excretion into bile and gallbladder tissue levels of levofloxacin and its clinical effect in biliary tract infections}; Tanimura H et al.; Evaluations were made on biliary excretion and penetration into the gallbladder tissue of levofloxacin (LVFX, DR-3355), a new quinolone antibacterial agent, and its clinical efficacy in biliary tract infections . 1 . Gallbladder tissue concentrations and biliary concentrations of LVFX at 2-6 hours at oral administration of 100 mg were 0.58-1.99 micrograms/g and 0.49-5.63 micrograms/ml, respectively . These tissue and biliary levels are almost equal or somewhat higher than the serum levels (0.55-1.63 micrograms/ml) of the compound . 2 . The concentrations of LVFX and optical isomer DR-3354 in the serum, gallbladder tissue, and bile were determined after a single or a concomitant administration of LVFX 100 mg and/or ofloxacin (OFLX) 100 to 200 mg . The concentration ratio of LVFX to DR-3354 paralleled with the ratio of the 2 compounds administrated . 3 . At a dose of 100 mg, the glucuronide of LVFX in the common duct bile was detected at proportions between 0.9 and 36.0% . 4 . A total of 11 patients with biliary tract infections, including 6 cholecystitis 3 cholangitis, and 1 each of cholecystocholangitis and liver abscess was treated with LVFX at 100-200 mg t.i.d . for 3-14 days . Clinical results were excellent or good in 8 cases and fair in 3 cases, resulting in an efficacy rate of 72.7% . 5 . A side effect and an abnormal change in laboratory findings were observed in both 1 case each and they were both mild . It was concluded that LVFX showed good penetration to the biliary tract as does OFLX, and that it would be a useful oral agent for the treatment of biliary tract infections. Antimicrob Agents Chemother, 1992 May, 36(5), 942 - 8 Inhibitory potency of quinolone antibacterial agents against cytochrome P450IA2 activity in vivo and in vitro; Fuhr U et al.; Inhibition of cytochrome P450IA2 activity is an important adverse effect of quinolone antibacterial agents . It results in a prolonged half-life for some drugs that are coadministered with quinolones, such as theophylline . The objective of the study described here was to define the parameters for quantifying the inhibitory potencies of quinolones against cytochrome P450IA2 in vivo and in vitro and to investigate the relationship between the results of both approaches . Cytochrome P450IA2 activity in vitro was measured by using the 3-demethylation rate of caffeine (500 microM) in human liver microsomes . The inhibitory potency of a quinolone in vitro was determined by calculating the decrease in the activity of cytochrome P450IA2 caused by addition of the quinolone (500 microM) into the incubation medium . The mean values (percent reduction of activity without quinolone) were as follows: enoxacin, 74.9%; ciprofloxacin, 70.4%; nalidixic acid, 66.6%; pipemidic acid, 59.3%; norfloxacin, 55.7%; lomefloxacin, 23.4%; pefloxacin, 22.0%; amifloxacin, 21.4%; difloxacin, 21.3%; ofloxacin, 11.8%; temafloxacin, 10.0%; fleroxacin, no effect . The inhibitory potency of a quinolone in vivo was defined by a dose- and bioavailability-normalized parameter calculated from changes of the elimination half-life of theophylline and/or caffeine reported in previously published studies . Taking the pharmacokinetics of the quinolones into account, it was possible to differentiate between substances with and without clinically relevant inhibitory effects by using results of in vitro investigations . The in vitro test described here may help to qualitatively predict the relevant drug interactions between quinolones and methylxanthines that occur during therapy. Klin Med (Mosk), 1992 May-Jun, 70(5-6), 17 - 9 {Detoxication methods in pancreatogenic enzymatic peritonitis}; Medvedenko AF et al.; A therapeutic response was analyzed in 536 patients with acute destructive pancreatitis complicated by pancreatogenic enzymatic peritonitis . All the patients had the syndrome of endogenic intoxication and underwent intensive resuscitation with protease inhibitors, cytostatic agents, antibacterial, desensitization and detoxication treatment . If indicated, the patients with pronounced endogenic intoxication were subjected to forced diuresis, abdominal laparoscopic drainage and intraperitoneal dialysis, drainage of the thoracic lymphatic duct, hemosorption . Routine surgical intervention was performed . Up to 11% fell the general lethality due to a differentiated therapeutic approach. Clin Ter, 1992 May, 140(5), 481 - 5 {Short-term perioperative antibacterial prophylaxis using imipenem-cilastatin versus acylureide penicillins in pacemaker implantation . A 30-month follow-up}; Veneziani N et al.; The authors have evaluated the efficacy of short term treatment with an imipenem-cilastatin combination in a selected group of 72 patients undergoing implant or substitution of a pacemaker and with associated pathology potentially increasing the risk of infection . After 30 months' follow-up, the authors underline the efficacy and advantages of this treatment. Antibiot Khimioter, 1992 May, 37(5), 35 - 8 {Prevention of early inflammatory complications after transthoracic interventions and estimation of the degree of immunologic deficiency}; Radomskii VT et al.; An analysis of the results of the examination and treatment of 379 patients undergoing transthoracic interventions showed that the use of the target-aimed selective immunomodulation, short-term antibacterial prophylaxis, inhibitors of arachidonic acid metabolites, active elimination of the circulating immune complexes and medium-weight molecular peptides and adequate local analgesia after the interventions providing normalization of the laryngeal reflex and early activation of the patients permitted the incidence of the pulmonary complications to be decreased by 2.5 times, pleural complications by 1.7 times, suppuration of the postoperative wound by 1.8 times and the total expenses by 25.6 per cent. Pharmazie, 1992 May, 47(5), 340 - 3 Synthesis and biological activity of some heterocyclic systems containing anthraquinone; Berghot MA et al.; 2-Aminoanthraquinone (1) was reacted with ethyl chloroformate to afford 2 . The reaction between carbamate 2 and hydrazine hydrate gave semicarbazide 3, which on treatment with benzoic acid, phenyl isothiocyanate and carbon disulfide/potassium hydroxide furnished oxadiazoles 4, 6 and triazole 5, respectively . Also, treatment of 1 with chloroacetyl chloride gave chloroacetyl derivative 8 . The reaction of glycolic acid, thioglycolic acid, diethyl malonate and malononitrile with 8 has been investigated . Compound 8 was treated with potassium thiocyanate to give 12, which was cyclized to 13a, while the reaction between 8 and potassium cyanate gave 13b directly . The structures of hitherto unknown compounds were confirmed by analytical and spectral methods . Some of the synthesized compounds were screened to test their antibacterial and antifungal properties. Eur J Epidemiol, 1992 May, 8(3), 407 - 21 Drug resistance in human pathogenic fungi; Iwata K; Since the therapy of the mycoses, particularly the systemic mycoses, is relatively long-term in nature, emergence of resistance to antifungal drugs during the treatment of period would be of considerable clinical importance . However, most reports of resistance to antifungal agents among human pathogenic fungi indicate that naturally-occurring resistance is very rare, and that the induction of resistant mutants or variants is much more difficult to achieve in vitro and in vivo than with bacteria . As a matter of fact, amphotericin B and some other classic antifungals have not as yet posed a broadly significant problem relative to drug resistance despite their widespread and frequent use . Fungal resistance has thus received little attention, in contrast to the critical importance of bacterial resistance frequently caused by a variety of antibacterial chemotherapeutic agents, until a single exception to this generalization arose with the advent of flucytosine . This new development has aroused great interest in the problem of fungal resistance among the scientists involved with medical mycology . It is generally believed that fungi, like bacteria, are intrinsically capable of developing resistance to antifungal agents . As illustrated by flucytosine, inherently resistant mutants to antifungals occur within sensitive strains of human pathogenic fungi with significant frequency . Given the relatively high degree of such primary resistance, these mutants should develop secondary resistance during therapy, thus resulting in considerable limitations in the clinical usefulness of the antifungals . Virtually, all unsuccessful cases of mycoses treated with some of the recently exploited antifungal drugs, albeit scarce to date, would obviously be attributable to the occurrence of secondary resistance . The exploitation of new antifungal drugs thus requires investigations of their resistance as one of the most important research projects to be undertaken before receiving approval for use on humans . This paper reviews from various aspects the literature on resistance to various classic and novel antifungal agents among human pathogenic fungi . The resistance of some nonpathogenic fungi to these agents will also be described from genetic and biochemical points of view. J Biomol NMR, 1992 May, 2(3), 235 - 56 Two-dimensional 1H NMR study of recombinant insect defensin A in water: resonance assignments, secondary structure and global folding; Bonmatin JM et al.; A 500 MHz 2D 1H NMR study of recombinant insect defensin A is reported . This defense protein of 40 residues contains 3 disulfide bridges, is positively charged and exhibits antibacterial properties . 2D NMR maps of recombinant defensin A were fully assigned and secondary structure elements were localized . The set of NOE connectivities, 3JNH-alpha H coupling constants as well as 1H/2H exchange rates and delta delta/delta T temperature coefficients of NH protons strongly support the existence of an alpha-helix (residues 14-24) and of an antiparallel beta-sheet (residues 27-40) . Models of the backbone folding were generated by using the DISMAN program and energy refined by using the AMBER program . This was done on the basis of: (i) 133 selected NOEs, (ii) 21 dihedral restraints from 3JNH-alpha H coupling constants, (iii) 12 hydrogen bonds mostly deduced from 1H/2H exchange rates or temperature coefficients, in addition to 9 initial disulfide bridge covalent constraints . The two secondary structure elements and the two bends connecting them involve approximately 70% of the total number of residues, which impose some stability in the C-terminal part of the molecule . The remaining N-terminal fragment forms a less well defined loop . This spatial organization, in which a beta-sheet is linked to an alpha-helix by two disulfide bridges and to a large loop by a third disulfide bridge, is rather similar to that found in scorpion charybdotoxin and seems to be partly present in several invertebrate toxins. Curr Genet, 1992 May, 21(6), 443 - 6 Ofloxacin induces cytoplasmic respiration-deficient mutants in yeast Saccharomyces cerevisiae; Obernauerova M et al.; Ofloxacin, a new quinolone with potent antibacterial activity, was also found to be effective against yeast . At relatively high concentrations, and at mild alkaline pH, ofloxacin inhibited the growth of yeast cells in medium containing glucose, and prevented growth on glycerol, as carbon and energy source . The cells growing in the presence of ofloxacin exhibited abberrantly budded forms, lost their viability and many of them converted to cytoplasmic respiration-deficient mutants . Induction of mutants was also observed under non-growing conditions . The petite clones analysed exhibited suppressiveness and contained different fragments of the wild-type mitochondrial genome. Vestn Oftalmol, 1992 May-Jun, 108(3), 29 - 30 {Pathogenetic therapy of spontaneous corneal perforation after extracapsular cataract extraction}; Manukian ME; The author presents a case with spontaneous perforation of the cornea after extracapsular cataract extraction in a female patient with rheumatoid arthritis . Systemic disorganization of the connective tissue and elevated collagenase activity essentially contribute to the pathogenesis of corneal perforation . Therefore, besides antibacterial drugs, collagenase inhibitors, 3% aqueous solution of cysteine, antimeasles gamma-globulin, and a regeneration stimulant, 5% ascorbic acid aqueous solution, were used in the treatment . The pathogenetic therapy was conducive to early healing of the corneal defect and helped save the eye and preserve its good function (0.8 s + 10.0 diopters). J Med Chem, 1992 Apr 17, 35(8), 1385 - 92 Pyrimido{1,6-a}benzimidazoles: a new class of DNA gyrase inhibitors; Hubschwerlen C et al.; Substituted 4-quinolone- (1, A = CH) and 1,8-naphthyrid-4-one- (1, A = N) 3-carboxylic acids are currently the only classes of clinically useful antibacterial agents exerting their activity by inhibiting the subunit A of DNA gyrase . Pyrimido{1,6-alpha}benzimidazoles 11 have been found to be a new class of inhibitors of this enzyme . The design, synthesis, and biological activity of these compounds are reported. Rev Prat, 1992 Apr 15, 42(8), 943 - 5 {Principles of the treatment of ocular infections}; Bron A; Ocular infections are still quite common and their clinical presentation is variable; some of them may lead to blindness . In this paper only severe infections like keratitis and endophthalmitis are considered . The rationale for treatment and prophylaxis is based upon bacteriological findings, understanding of ocular barriers and pharmacokinetics of antibacterial agents. Med Klin (Munich), 1992 Apr 15, 87(4), 179 - 84 {Polymorphism in Helicobacter pylori--a key function in recurrence of infection?}; Bode G et al.; Despite the fact that Helicobacter (H.) pylori is ubiquitous throughout the world, little is known at present about the source of infection and mode of transmission . Person-to-person transmission may be of importance . The fact that Helicobacter pylori can revert to a coccoid form stimulated speculation about its role in transmission and as a possible cause of reinfection in duodenal ulcer disease . Various antibacterial agents (bismuth subcitrate 32 mg/l bismuth subsalicylate 64 mg/l, amoxicillin 0.05 mg/l, ampicillin 2 mg/l, erythromycin 4 mg/l, glycochenodeoxycholic acid 423 mg/l, ursodeoxycholic acid 540 mg/l) inhibit the growth of H . pylori and stimulate the formation of coccoid structures . Ultrastructural and biochemical results show that the coccoid form meets the necessary criteria for survival . Thus, to be successful, treatment must aim not only at eliminating the vegetative form, but also at preventing the development of the coccoid form. Am J Med, 1992 Apr 6, 92(4A), 91S - 97S Diagnosis and interventions in lower respiratory tract infections; Wijnands GJ; In the elderly and in immunocompromised patients, respiratory tract infections are still a major cause of morbidity and mortality . The choice of a specific antibiotic treatment in pneumonia depends on the identification of the causative pathogen or on a judgment concerning the probable causative micro-organism . This judgment should be based on all the information obtained from clinical signs and symptoms, laboratory investigations of sputum and blood, and the pattern of infiltrations on chest X-ray . Different causative pathogens can be expected in bacterial and "atypical" community-acquired pneumonia than in hospital-acquired pneumonia . For the same reason, immunocompetent and immunocompromised patients have to be distinguished from each other . In chronic obstructive pulmonary disease, bronchial defenses will be impaired . Exacerbations can result from different causes, including infections of the bronchial mucosa . Most of these infections are of viral origin . Exacerbated pulmonary disease will result from bacterial bronchitis only in some patients . It is often difficult to assess the diagnosis "bacterial bronchitis." Evaluation of the effect of antibacterial treatment in exacerbated pulmonary disease is also difficult . Therapeutic interventions for these clinical conditions have to be directed primarily toward restoring or improving pulmonary host-defense factors . Fluoroquinolones, including lomefloxacin, have been shown to be effective in the treatment of lower respiratory tract infections caused by susceptible bacteria . Lomefloxacin presents a number of advantages: the drug has good bioavailability after oral and parenteral administration and penetrates well into bronchial secretions and lung tissue . In addition, lomefloxacin has no influence on the metabolic clearance of the methylxanthines theophylline and caffeine, which has been demonstrated for enoxacin, ciprofloxacin, and pefloxacin. Am J Med, 1992 Apr 6, 92(4A), 8S - 11S Penetration of lomefloxacin into bronchial secretions following single and multiple oral administration; Bergogne-Berezin E et al.; The bronchial penetration of lomefloxacin, a new difluorinated quinolone, was evaluated in 36 patients who underwent bronchoscopies for diagnostic purposes . Patients were randomized into two groups, with 18 patients (Group I) receiving a single oral dose of 400 mg lomefloxacin and 18 patients (Group II) receiving 400 mg twice daily . Samples of serum and bronchial secretions were collected simultaneously in both groups at 1, 2, or 4 hours after lomefloxacin administration . The results of this study showed that bronchial penetration of lomefloxacin was rapid and yielded high concentrations; the mean bronchial levels of the drug reached 2.78 +/- 3.64 micrograms/mL in Group I 1 hour after the dose, and 2.84 +/- 1.73 micrograms/mL in Group II at the fourth hour . The ratio between bronchial and simultaneous serum concentrations was 89% at the first and second hours after the dose for Group I, and it was 77% 4 hours after oral administration in Group II . In comparing these results to previous reports of lomefloxacin penetration into bronchial mucosa or of concentrations of other new fluoroquinolones into bronchial secretions, it is to be noted that the local concentrations of the newer quinolones are of very similar values, ranging from 2.7 micrograms/mL (ofloxacin) to 4.46 micrograms/mL (pefloxacin) . This study confirms that lomefloxacin achieves high tissue concentrations in the respiratory tree; this characteristic, together with lomefloxacin's antibacterial spectrum, indicates promise in the treatment of many respiratory infections. J Antibiot (Tokyo), 1992 Apr, 45(4), 535 - 41 Synthesis and antibacterial activities of new 3-phenoxymethylcephalosporins; Koyama K et al.; The synthesis and biological properties of new 3-phenoxymethylcephalosporins (1) are described . These compounds exhibited good antibacterial activity against Gram-positive and Gram-negative bacteria. J Antibiot (Tokyo), 1992 Apr, 45(4), 500 - 4 New penem compounds with 5'-substituted pyrrolidinylthio group as a C-2 side chain; comparison of their biological properties with those of carbapenem compounds; Sunagawa M et al.; A series of new penem compounds with a C-2 side chain consisting of a pyrrolidin-3'-ylthio group substituted with various aminocarbonyl groups at the C-5' position have been prepared . Antibacterial activity, stability to renal dehydropeptidase-I and affinity to penicillin-binding proteins of these compounds were investigated and compared with the corresponding carbapenem compounds. J Antibiot (Tokyo), 1992 Apr, 45(4), 454 - 7 10'-Desmethoxystreptonigrin, a novel analog of streptonigrin; Liu WC et al.; 10'-Desmethoxystreptonigrin, a novel analog of streptonigrin produced by Streptomyces albus, was discovered in a screen for inhibitors of farnesylation of RAS p21 protein . The compound was isolated from the fermentation broth and its structure determined . It is markedly cytotoxic to several human tumor cell lines and also exhibits potent broad-spectrum antibacterial activity. Mol Gen Genet, 1992 Apr, 232(3), 335 - 43 The lysozyme locus in Drosophila melanogaster: different genes are expressed in midgut and salivary glands; Kylsten P et al.; As part of a study of the genes involved in antibacterial defense in Drosophila melanogaster, we have isolated genomic clones harboring a family of chicken-type lysozyme genes, using a lepidopteran lysozyme cDNA as probe . The locus was mapped to the cytological location 61F1-4 on the third chromosome and two of the genes at this locus, LysD and LysP, were analyzed in detail . In contrast to the bacteria-induced lysozymes in the hemolymph of many insects, the transcription levels of both Drosophila genes decrease after bacterial injections into the hemocoel . Apparently, these gene products, like the specifically adapted lysozymes in mammalian foregut fermenters, have been recruited for the digestion of bacteria present in fermenting food . The LysD gene is expressed in an anterior section of the midgut during all feeding stages of development in both larvae and adults . The LysP gene is only active in the adult where it is expressed in the salivary glands . The transcription units for both genes are very compact and they lack introns . Lysozyme D is unusual in that it is predicted to have an acidic isoelectric point whereas lysozyme P appears to be a typical basic lysozyme. J Leukoc Biol, 1992 Apr, 51(4), 316 - 23 A neutrophil-derived proteolytic inactive elastase homologue (hHBP) mediates reversible contraction of fibroblasts and endothelial cell monolayers and stimulates monocyte survival and thrombospondin secretion; Ostergaard E et al.; Human heparin-binding protein (hHBP) is a recently discovered proteolytically inactive neutrophil elastase homologue with sequence identity to azurocidin and CAP37 . The protein has antibacterial properties and chemotactic activity toward monocytes . In the present work, we show that monocytes, cultured under serum-free conditions, developed morphological changes and formed multicellular aggregates 4 h after the addition of hHBP at a concentration of 10 micrograms/ml . However, after prolonged incubation (11 days) with unchanged medium, the cells spread again . The hHBP-treated cells had a two- to threefold increase in survival compared to control cells, measured using trypan blue as an indicator of living cells . Differentiation of the alive cells to macrophages was detected by changes in morphology, a threefold increase in protein content, and a three- to fourfold increase in acid phosphatase activity . When monocytes in parallel experiments were labelled with {35S}methionine de novo synthesis and secretion of thrombospondin in a dose-dependent manner was observed after 16 h, with half-maximal secretion at 2 micrograms hHBP/ml and a maximal 12-fold increase in secretion with respect to controls at 16 micrograms/ml . Supplementary labeling with {35S}sulfate revealed that the same monocytes down-regulated the secretion of a large proteoglycan (300-400 kd), apparently also with a half-maximal decrease rate at 2 micrograms/ml hHBP . Exposure of confluent fibroblast and endothelial cell monolayers to hHBP (10 micrograms/ml) in the absence of fetal calf serum resulted in cell contraction leaving gaps between cells, the phenomenon being recognizable within 4 h after addition of hHBP . Addition of fetal calf serum to a concentration of 10% completely restored the monolayers . A unique role of hHBP in host defense involving recruitment of monocytes and a key function of hHBP in neutrophil extravasation in response to inflammatory chemotactic signals such as leukotriene B4, complement peptide C5a, and N-formyl-methionyl-leucyl-phenylalanine are suggested. J Antibiot (Tokyo), 1992 Apr, 45(4), 476 - 84 New polyenic antibiotics active against gram-positive and gram-negative bacteria . VIII . Construction of synthetic medium for production of mono-chloro-congeners of enacyloxins; Watanabe T et al.; New antibiotics enacyloxins (ENXs) are a family of non-lactonic polyene antibiotics produced by Frateuria sp . W-315 . For the production of antibiotics, we had to employ two-step fermentations, the first is the production of spent medium of Neurospora crassa and the second is the production of antibiotics by Frateuria . To simplify the production of antibiotics, systematic analyses have been done on the spent medium, and factors which affect the production of antibiotics characterized . From the above results, we constructed a new medium for antibiotic production . Moreover, we could get a new antibiotic named enacyloxin IIIa (1), C33H48O11NCl (m/z 669) . 1 was deduced to be one of the congeners of enacyloxins because it was similar to ENX IIa or ENX IVa both in biological and physico-chemical properties . Chlorine of 1 could be replaced by bromine, biosynthetically, and the resultant bromine-containing antibiotic also showed an antibacterial activity comparable to 1. Pharmazie, 1992 Apr, 47(4), 258 - 61 {Azoles . 34 . Nitroimidazole derivatives and their antibacterial and fungicidal action}; Zaprutko L et al.; Nitroimidazole derivatives 4a-4c, 5a-5c, 8a-8c and 9a-9c were synthesized by treating 4,5-dinitro- and 2-methyl-4,5-dinitroimidazole (1,2) or their silver salts {1.Ag,, 2.Ag) with chlorosubtituted phenacyl bromides 3a-3c, diethyl sulphate or ethyl iodide, allyl iodide and ethyl chloro-, azo- or bromoacetate . 2,4(5)-dinitroimidazole (10) has been converted to the 2,4-dinitroimidazole derivative 10a by the action of ethyl bromoacetate in the presence of sodium ethylate . A modified method for the synthesis of 6a and 6b has been described . 7a and 7b have been obtained by a known method . Some of the newly synthesized nitroimidazole derivatives show antibacterial and fungicidal activity. Antimicrob Agents Chemother, 1992 Apr, 36(4), 840 - 50 Iron transport-mediated antibacterial activity of and development of resistance to hydroxamate and catechol siderophore-carbacephalosporin conjugates; Minnick AA et al.; Peptides containing residues of N5-acetyl-N5-hydroxy-L-ornithine were evaluated as potential artificial siderophores of beta-lactam-hypersusceptible Escherichia coli X580 . Only those peptides which were capable of forming a hexadentate complex around ferric iron, which is analogous to the natural siderophore ferrichrome, were able to reverse the growth inhibition effects of the ferric iron chelator ethylenediamine di(o-hydroxyphenylacetic acid) . A synthetic bis(catechol) spermidine derivative, similar to the natural siderophores enterobactin and agrobactin, also exhibited siderophore activity with this strain . Conjugation of the N5-acetyl-N5-hydroxy-L-ornithine tripeptide and the bis(catechol) siderophore to the potent carbacephalosporin loracarbef and closely related analogs provided compounds which exhibited antibacterial activity against E . coli X580 . As was observed with the naturally occurring albomycins, the initial bactericidal effect was followed by the appearance of survivors that were resistant to the test compound . An enhanced killing effect was observed when the parent was incubated simultaneously with hydroxamate and catechol siderophore-antibiotic conjugates . Natural and synthetic siderophore growth promotion experiments with survivors resistant to the conjugates strongly suggested that disabled ferrichrome and enterobactin-catechol assimilation mechanisms may be responsible for the observed resistance . One isolated survivor was postulated to be a tonB mutant . The antibacterial activities of the described siderophore-carbacephalosporin conjugates appear to be related to an iron transport assimilation mechanism and would not have been detected during routine MIC testing procedures. Photodermatol Photoimmunol Photomed, 1992 Apr, 9(2), 86 - 8 Enoxacin-induced photosensitivity: study of two cases; Izu R et al.; Enoxacin is a second-generation quinolone derivative recently introduced in Spain . Its activity comes through the inhibition of bacterial DNA-gyrase and it has a good antibacterial capacity against a broad spectrum of gram-positive and gram-negative bacteria . It is presumed to be less toxic than the rest of the quinolones and its use is increasing, specially to treat infections of the urogenital tract . Cases of photosensitivity to enoxacin have been very rarely reported . We describe 2 patients with photosensitivity reactions due to this drug. Lik Sprava, 1992 Apr, (4), 65 - 8 {Secondary pneumonia in subjects with acute leukemia}; Mazurov VI et al.; Of 105 patients with acute leukoses secondary pneumonias were found in 47.6% . A dependence was found of the frequency of pneumonia on the severity of initial hyperleukocytosis and duration of post-cytostatic agranulocytosis . The efficiency of routine criteria of diagnosis was 66% and increased significantly in microbiological and cytological investigation of the bronchoalveolar lavage fluid . Treatment: combined antibacterial therapy, antifungal, desintoxicating agents; in severe cases--endobronchial administration of monogroup leucocytic mass. Bratisl Lek Listy, 1992 Apr, 93(4), 183 - 8 {Prophylactic administration of selected antibiotics in hospitals in the Slovak Republic}; Antal M et al.; Over a period of ten years prophylactic administration of selected antibiotics was evaluated three times (in 1973, 1983, and in 1988) in the same ten hospitals of the Slovak Republic . The study was focused on the use of gentamicin (GEN), cotrimoxasol (COT) and cephalosporins (CEP) . Prophylactic administration of antibiotics was found to be increasing . GEN is being given less frequently, while CEP are administered more often, which is considered to be a positive trend . The period of prophylactic administration of antibiotics is still inadequately long with an average of 10.7 days . Evaluation of antibiotic administration showed that antibacterial substances have the highest rate of prophylactic administration in patients with oncologic diseases, followed by patients with diseases of the urinogenital system . A positive development was recorded in the perinatal period with a decreasing trend in the prophylactic administration of antibiotics. EMBO J, 1992 Apr, 11(4), 1469 - 77 Insect immunity: developmental and inducible activity of the Drosophila diptericin promoter; Reichhart JM et al.; Diptericins are 9 kDa inducible antibacterial peptides initially isolated from immune haemolymph of Phormia (Diptera) . Following the isolation of a Drosophila cDNA encoding a diptericin homologue, we have now cloned a genomic fragment containing the Drosophila diptericin gene . To dissect the regulation of this gene, we have transformed flies with a fusion gene in which the reporter beta-galactosidase gene is under the control of 2.2 kb upstream sequences of the diptericin gene . We show that such a fusion gene is inducible by injection of live bacteria or complete Freund's adjuvant and respects the tissue specific expression pattern of the resident diptericin gene . Our analysis reveals at least four distinct phases in the regulation of this gene: young larvae, late third instar larvae, pupae and adults . This complexity may be related to the presence in the upstream sequences of multiple copies of response elements previously characterized in genes encoding acute phase response proteins in mammals (e.g . NK-kappa B, NF-kappa B related, NF-IL6 response elements). J Periodontol, 1992 Apr, 63(4), 280 - 2 Antibacterial activity of some triclosan-containing toothpastes and their ingredients; Wade WG et al.; The antibacterial activity of 4 triclosan-containing toothpastes was compared to a conventional fluoride dentifrice and triclosan and sodium lauryl sulphate (SLS), both singly and in combination . A panel of 17 bacteria was tested by an agar dilution method . At concentrations typical of those found in toothpastes, triclosan and SLS displayed approximately equal antibacterial activity . A paste containing triclosan and zinc citrate appeared more active than the other triclosan pastes which, in general, showed marginal superiority over the conventional paste . SLS, although included in dentifrice formulations for its detergent properties, may significantly contribute to the antibacterial profile of a product . The need for appropriate controls when evaluating experimental toothpastes is emphasized. Rev Med Chil, 1992 Apr, 120(4), 439 - 44 {Mechanisms of the antibiotic activity of bacteriocins}; Garcia-Quintana H; Some bacteria possesses the genetic capacity to synthesize compounds referred to as bacteriocins; such compounds are antagonic for other closely related bacteria by inhibiting bacterial growth . These toxic substances are either simple polypeptides or very complex macromolecules . However the feature of being a "killer" strain is coded by chromosomal or plasmid genes . The mechanism of lethal action is carried out either directly or indirectly against certain functions of the target cell; death of the sensitive strain is produced as a consequence of transport collapse at membrane level resulting in a drastic drop of indispensable metabolites or ions; in other cases the antibacterial effect produces blocking of macromolecule synthesis; or loss of metabolite stabilization within the cell altering the basic metabolism . Repercussions of bacteriocinogeny may be: use as epidemiological tool through bacteriocin-typing techniques; biological control by means of specific bacteriocins; regulation of bacterial growth rate in a population as a competence mechanism for a given ecological habitat; genetic transfer between competent cells; study of superficial receptor sites and its role in natural immunity; use as therapeutic agents through a number of problems like cross-toxicity and specificity of action still remain unsolved. Antimicrob Agents Chemother, 1992 Apr, 36(4), 833 - 9 Efficacy and safety of temafloxacin versus those of amoxicillin in hospitalized adults with community-acquired pneumonia; Carbon C et al.; Temafloxacin, a new fluoroquinolone, was compared with amoxicillin in the treatment of adult hospitalized patients with community-acquired pneumonia . In this double-blind, multicenter study, patients were randomly assigned to treatment with temafloxacin at 600 mg twice daily (n = 125) or amoxicillin at 500 mg three times daily (n = 121); the average duration of treatment was 10 days . Clinical recovery rates were similar for patients treated with temafloxacin and amoxicillin (89 and 85%), as were bacterial eradication rates (99 and 97%) . This was also true for subgroups of patients with pneumococcal pneumonia (n = 100), nonpneumococcal pneumonia (n = 122), or atypical pneumonia (n = 12) . Outcomes for temafloxacin- and amoxicillin-treated patients were also similar in terms of defervescence, improvement in leukocytosis, and radiographic evidence of infection . The frequency and severity of adverse events were similar in both groups, consisting primarily of digestive disorders and skin manifestations . We conclude that temafloxacin may be recommended as an alternative antibacterial drug for patients with suspected pneumococcal pneumonia who fail to respond to benzylpenicillin or amoxicillin when the incidence of multiresistant pneumococcal strains is low . In countries where the incidence of these strains is high, temafloxacin may also be recommended. J Antibiot (Tokyo), 1992 Apr, 45(4), 527 - 34 Synthesis and antibacterial activity of O-methylazithromycin derivatives; Kobrehel G et al.; A series of O-methylazithromycin derivatives have been synthesized and their antibacterial activities were compared with those of azithromycin (1) . O-Methylation of 1 proceeded stepwise by the two main pathways beginning at the C-6 and C-11 hydroxyl groups, individually . Among O-methyl derivatives, 6-O-methylazithromycin A (11) was slightly less active than 1 . The methylation of the secondary hydroxyl group at the C-11 position resulted surprisingly in an increase of their in vitro activity . The antibacterial activities of novel azalides decreased with increasing the number of the methyl groups introduced. J Med Chem, 1992 Mar 6, 35(5), 953 - 8 Synthesis and antibacterial activity of some novel 6-methyl- and 6-propenyl-substituted carbapenems; Mastalerz H et al.; The synthesis and antibacterial activity of a number of 6-methyl- and 6-propenyl-substituted carbapenems is described . The 6-(hydroxymethyl)- and 6-(aminomethyl)carbapenems possessed more potent antibacterial activity in vitro than their respective 6-(1'(R)-hydroxyethyl) or 6-(1'(R)-aminoethyl) counterparts . However, because of reduced stability, the 6-(aminomethyl)carbapenem was found to be inactive in vivo . All 6-hydroxypropenyl or 6-aminopropenyl derivatives that were prepared were less active than their respective 6-heteroethyl-substituted analogues. J Med Chem, 1992 Mar 6, 35(5), 939 - 44 Secondary metabolites by chemical screening . 17 . Nigericinol derivatives: synthesis, biological activities, and modeling studies; Grabley S et al.; The synthesis and the biological activity of C-1-reduced nigericin derivatives (nigericinols) are described and discussed . The dichloronigericinol 7 impressively demonstrated that the C-1 carboxylic acid moiety was not required for a distinct activity against bacteria and viruses . Based on the correlation between K+/H+ antiport activities and antibacterial activities it was deduced that the mode of action of the described nigericinols are related to their ionophoric properties . Molecular modeling studies showed that the efficiency of the nigericinols as ionophores correlates, qualitatively, with the probability of forming a cyclic structure, with the exception of 7. J Pharm Sci, 1992 Mar, 81(3), 237 - 40 Effect of basic cholane derivatives on intestinal cholic acid metabolism: in vitro and in vivo activity; Roda A et al.; A representative series of hydroxy-5 beta-cholanyl-24-amines were tested both in vitro and in vivo with respect to their activity against the intestinal bacteria responsible for bile acid metabolism . For the in vitro studies, radiolabeled {14C}cholic acid was incubated with human stools both in aerobic and anaerobic conditions in the presence of the title compounds at a dose of 10 micrograms/mL, and the biotransformation of cholic acid into radiolabeled deoxycholic acid and other metabolites was followed by TLC-radiochromatography . Of the compounds studied, 3 alpha, 12 alpha-dihydroxy-5 beta-cholan-24-N-methylamine showed the highest activity . This compound was used for the in vivo studies and was shown to inhibit the formation of endogenous secondary bile acids when chronically administered to rats at a dose of 60 micrograms/day for 15 days . The treated rats showed an increased ratio of taurocholic acid (primary bile acid) to taurodeoxycholic acid (secondary bile acid) in bile, a fact further suggesting a potent antibacterial activity of the compound toward bacteria responsible for bile acid metabolism. Kansenshogaku Zasshi, 1992 Mar, 66(3), 349 - 53 {Contamination of endoscopes and endoscope washers by atypical mycobacteria}; Negayama K et al.; Contamination of endoscopes and endoscope washers by atypical mycobacteria was studied . Large amounts of atypical mycobacteria were detected with high frequency inside endoscopes and endoscope washers . The species of atypical mycobacteria was Mycobacterium chelonae subsp . abscessus . Antibacterial-effects of glutaraldehyde against isolated atypical mycobacteria were checked . Sufficient antibacterial-effect was not obtained by 2% glutaraldehyde solution for endoscope sterilization . However, after frequent manual washing and brushing of endoscopes, by using 3% glutaraldehyde solution and 70% alcohol, all endoscopic instruments were completely decontaminated . We must pay attention to contamination of endoscopes and endoscope washer at least once a month. Arzneimittelforschung, 1992 Mar, 43(3A), 406 - 8 Interaction of the new quinolone antibacterial agent levofloxacin with fenbufen in mice; Furuhama K et al.; The interaction of (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1- piperazinyl)-7-oxo-7H-pyrido{1,2,3-de} {1,4}benzoxazine-6-carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 100986-85-4) with fenbufen, a nonsteroidal anti-inflammatory agent, in mice was assessed by convulsive seizure and subsequent death in comparison with that of other new quinolones such as DR-3354 (the R-(+)-isomer of ofloxacin), ofloxacin, norfloxacin, enoxacin and ciprofloxacin . Although treatment with each quinolone or fenbufen alone at a dosage level tested in mice showed no changes, coadministration of a large dose of all quinolones and fenbufen caused convulsant death . When compared with the severity of this interaction, it was in the order of enoxacin greater than norfloxacin greater than ciprofloxacin greater than DR-3354 greater than ofloxacin greater than or equal to DR-3355 under these experimental conditions. Arzneimittelforschung, 1992 Mar, 43(3A), 404 - 5 Phototoxic potential of the new quinolone antibacterial agent levofloxacin in mice; Wagai N et al.; The phototoxic potential of (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4- methyl-1-piperazyl)-7-oxo-7H-pyrido{1,2,3-de}{1,4}benzoxazine-6- carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 100986-85-4) was evaluated by the mice ear swelling reaction . Results were compared with those for enoxacin (ENX) . Mice were orally administered DR-3355 or ENX and immediately exposed to ultraviolet-A for 4 h . Phototoxicity was determined by measuring ear thickness developing 24 h after irradiation . DR-3355 provided no changes in the ear at 200 mg/kg, but caused ear swelling at 800 mg/kg . ENX caused severe phototoxicity in a dose dependent manner from 50 mg/kg . These data suggest that DR-3355 has minor phototoxic potential, but is approximately 4-fold less toxic than ENX in these experimental conditions. Arzneimittelforschung, 1992 Mar, 43(3A), 398 - 403 Ophthalmotoxicity and ototoxicity of the new quinolone antibacterial agent levofloxacin in Long Evans rats; Nomura M et al.; An ophthalomo- and ototoxicity study of a new quinolone antibacterial agent, (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1- piperazinyl)-7-oxo-7H-pyrido{1,2,3-de} {1,4}benzoxazine-6-carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 100986-85-4) was investigated in Long Evans rats . The rats were orally administered 100 mg/kg of DR-3355, ciprofloxacin (CPFX), norfloxacin (NFLX) or nalidixic acid (NA) for 2 weeks, and the effects on visual and auditory functions were examined . Examination of electroretinograms (ERGs) revealed a decrease in the amplitudes of the a- and b-waves, a prolongation of the latency and diminution or disappearance of oscillatory potential waves in NA treated rats . Similar but milder changes were also noted in the NFLX treated rats . ERGs from DR-3355 or CPFX treated rats were normal . Histopathological examination revealed no changes suggestive of ophthalmotoxicity or ototoxicity in the rats treated with DR-3355, CPFX or NFLX . On the other hand, NA treated rats showed partial loss of the outer hair cells of the organ of Corti in the cochlea, suggesting that NA had slight ototoxicity . DR-3355 did not show any deleterious visual or auditory effects at the dose used in this study. Arzneimittelforschung, 1992 Mar, 43(3A), 395 - 7 Lack of nephrotoxic effects of the new quinolone antibacterial agent levofloxacin in rabbits; Inage F et al.; The nephrotoxicity of (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1- piperazinyl)-7-oxo-7H-pyrido {1,2,3-de}{1,4}benzoxazine-6-carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 100986-85-4), a new quinolone antibacterial agent, was evaluated in male New Zealand White (NZW) rabbits after oral administration of 30 or 120 mg/kg for 10 days . Although reduced body weight gain was observed in the 120 mg/kg, DR-3355 induced no change in function and morphology of the kidneys at both doses. Arzneimittelforschung, 1992 Mar, 43(3A), 385 - 9 Antigenicity of the new quinolone antibacterial agent levofloxacin; Wagai N et al.; An antigenicity study of a new quinolone antibacterial agent, (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo- 7H-pyrido{1,2,3-de}{1,4}benzoxazine-6-carboxylic acid hemihydrate (lefovloxacin, DR-3355, CAS 100986-85-4), was carried out in mice, guinea pigs and rabbits with passive cutaneous anaphylaxis (PCA), systemic anaphylaxis (SA) and enzyme linked immunosorbent assay (ELISA) . Mice were sensitized with DR-3355 (1-100 mg/kg) or DR-3355-ovalbumin (OA) conjugate (DR-3355-OA; 500 micrograms/kg) . No IgE antibodies to DR-3355 were detected in the sera obtained from the DR-3355-sensitized mice, indicating that DR-3355 has no immunogenicity in mice . By using DR-3355-OA as a sensitizing antigen, DR-3355-specific IgE was produced successfully in 7 out of 10 sera, and 4 sera showed positive responses in 24-h PCA on intravenous injection of DR-3355 (40 mg/kg) . These responses disappeared on challenge with a dose of 2.5 mg/kg . Guinea pigs or rabbits were sensitized with DR-3355 (2-100 or 2-20 mg/kg) or DR-3355-OA (2 mg/kg) . No SA was observed in the sensitized guinea pigs after the intravenous injection of DR-3355 (40 mg/kg) . No antibodies to DR-3355 were detected in the sera obtained from the sensitized guinea pigs and rabbits by PCA or ELISA . These results suggest that DR-3355 may not possess antigenicity in guinea pigs and rabbits . On the other hand, the results of PCA in mice suggest that DR-3355 may have eliciting antigenicity potential. Arzneimittelforschung, 1992 Mar, 43(3A), 378 - 85 Mutagenicity of the new quinolone antibacterial agent levofloxacin; Shimada H et al.; A new quinolone antibacterial agent (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10- (4-methyl-1-piperazinyl)-7-oxo-7H-pyrido{1,2,3-de}{1,4}benzoxazine-6- carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 100986-85-4), was studied for mutagenicity using the following short-term in vitro and in vivo tests . 1 . In vitro studies: reverse mutation test (Ames method) on S . typhimurium and E . coli; and HGPRT forward mutation test, cytogenetic test, and sister chromatid exchange (SCE) test, all on Chinese hamster cells . 2 . In vivo studies: mouse micronucleus test, SCE test on mouse bone marrow cell, in vivo-in vitro unscheduled DNA synthesis (UDS) test on rat primary hepatocytes, and dominant lethal test in BDF1 mice . In the in vitro tests for SCE and for chromosomal aberration, DR-3355 gave dose-dependent positive responses, but no mutagenicity was observed in the same indicators of the in vivo studies, even at the maximum tolerated doses . This strongly suggested that DR-3355 would have no mutagenic effects when used in the treatment of infectious diseases . DR-3355 did not show any positive response in the reverse mutation test, the HGPRT mutation test, the in vivo-in vitro UDS test or the dominant lethal test . These results suggest that chemotherapy with DR-3355 should have no mutagenic effect in man. Arzneimittelforschung, 1992 Mar, 43(3A), 374 - 7 Reproductive toxicity of the new quinolone antibacterial agent levofloxacin in rats and rabbits; Watanabe T et al.; The reproductive toxicity of (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4- methyl-1-piperazinyl)-7-oxo-7H-pyrido {1,2,3-de}{1,4}benzoxazine-6-carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 100986-85-4) was investigated in rats and rabbits . DR-3355 was administered orally prior to and in the early stage of pregnancy to male and female rats at doses of up to 360 mg/kg . No adverse effects on fertility or teratogenicity were noted at any dose . DR-3355 elicited no evidence of teratogenicity when administered during the fetal organogenesis period to pregnant rats at doses of up to 810 mg/kg, or to pregnant rabbits at doses of up to 50 mg/kg . However, female rats receiving 810 mg/kg showed salivation, soiled coats, soft stools and decreases in body weight and food intake . Rat fetuses in the 810 mg/kg group exhibited decreased body weight and retardation of ossification, and showed increases in mortality and skeletal variations . Decreases in maternal body weight and food intake were observed in rabbits in the 50 mg/kg group . No adverse effects were observed in perinatal and postnatal toxicity studies in rats using doses of up to 360 mg/kg. Arzneimittelforschung, 1992 Mar, 43(3A), 365 - 6 Acute oral toxicity of the new quinolone antibacterial agent levofloxacin in mice, rats and monkeys; Kato M et al.; Acute oral toxicity of (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4- methyl-1-piperazinyl)-7-oxo-7H-pyrido {1,2,3-de}{1,4}benzoxazine-6-carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 100986-85-4), a new quinolone antibacterial agent, was studied in ddy mice, SD rats and cynomolgus monkeys . LD50 values were 1,881 mg/kg for males and 1,803 mg/kg for females in mice, 1,478 mg/kg for males and 1,507 mg/kg for females in rats and more than 250 mg/kg in females monkeys . Toxic signs included the decrease in locomotor activity, ptosis, tremor, tonic convulsion and respiratory depressed in rodents and soft feces or vomiting in monkeys . At necropsy, no treatment-related changes were observed in any species except for the enlargement of the cecum in rats. Drug Saf, 1992 Mar-Apr, 7(2), 116 - 34 Thalidomide in human immunodeficiency virus (HIV) patients . A review of safety considerations; Gunzler V; The sedative thalidomide was withdrawn from the market 30 years ago because of its teratogenic and neurotoxic adverse effects . The compound was later discovered to be extremely effective in the treatment of erythema nodosum leprosum, a complication of lepromatous leprosy . This effect is probably due to a direct influence on the immune system, because thalidomide possesses no antibacterial activity . The compound is presently used as an experimental drug in the treatment of a variety of diseases with an autoimmune character, including recurrent aphthosis of nonviral and nonfungal origin in human immunodeficiency virus (HIV) patients . This article reviews the most important chemical and pharmacokinetic properties of thalidomide . The possible mechanisms of the nonsedative effects of thalidomide with respect to the safety of its use in HIV patients are discussed . Because the mechanism of the immunomodulatory effect of thalidomide is unknown, the possibility that the administration of this compound will accelerate the deterioration of the immunological status of HIV patients cannot be excluded . Clinical evidence suggests that thalidomide may aggravate the condition of patients with preexisting peripheral neuropathy . Hypersensitivity reactions to thalidomide may occur more frequently in HIV patients than in other patient groups . Because of the teratogenic activity of thalidomide, reliable contraception must be provided to female patients of childbearing age . Before the introduction of thalidomide therapy to an HIV patient presenting with oral ulcers, a fungal or viral origin of the lesions should be excluded . Thalidomide should not be used in patients with preexisting HIV-related peripheral polyneuropathy, polyradiculopathy or encephalopathy . In patients experiencing a complete remission, the discontinuation of thalidomide treatment and its reintroduction in the case of a relapse are preferable to maintenance therapy. J Nat Prod, 1992 Mar, 55(3), 303 - 10 Constituents of Azadirachta indica: isolation and structure elucidation of a new antibacterial tetranortriterpenoid, mahmoodin, and a new protolimonoid, naheedin; Siddiqui S et al.; Mahmoodin {1}, a new limonoid, has been isolated from Azadirachta indica (neem) oil, along with seven known tetranortriterpenoids, azadirone, epoxyazadiradione, nimbin, gedunin, azadiradione, deacetylnimbin, and 17-hydroxyazadiradione . A new protolimonoid, naheedin {3}, has been obtained from the neem fruits along with azadirachtol . Their structures have been elucidated through chemical and spectral analyses including 2D nmr studies . The absolute configuration of 1 was established by comparison of its cd spectrum with those of the known tetranortriterpenoids . Mahmoodin showed significant antibacterial activity against various Gram-positive and Gram-negative organisms . Four hydrocarbons, icosane, docosane, 2-methyltricosane, and docosene, have also been identified by gc-ms of the EtOH extract of the fruit coats . Only docosane has earlier been reported from neem, while the remaining three are unreported from this plant. Klin Monatsbl Augenheilkd, 1992 Mar, 200(3), 182 - 6 {The effective antibacterial spectrum of sulfacetamide}; Roth HW et al.; Swabs of the anterior eye segment of 180 eyes (145 patients) taken in the time period between August 1, 1989 until August 30, 1989 were sent to an external, independent microbiological institute in order to verify in-vitro antibacterial properties of marketed sulfacetamide containing drugs . MIC test was performed with isolated pathogenic bacterial strains without knowledge of the underlying diagnosis . It was shown that sulfacetamide is able to inhibit the growth of all isolated strains . Depending on the type of bacteria concentrations of 0.006 up to 6.4% sodium sulfacetamide proved to be effective . Simultaneously, all patients were treated with sulfacetamide containing ointment and/or eye drops 4 times daily for maximum of 14 days . With swabs taken at intervals of 7 and 14 days no bacterial growth was detected. J Antibiot (Tokyo), 1992 Mar, 45(3), 380 - 5 Synthesis and activity of C-21 alkylamino derivatives of (9R)-erythromycylamine; Lartey PA et al.; Novel analogs of (9R)-9-deoxo-9-(N,N-dimethylamino)erythromycin A bearing N-alkylamino substituents at the C-21 position were synthesized . These compounds retained antibacterial activity . The C-21, N,N-dimethylamino analog showed a modest improvement in activity against some Gram-negative bacteria. Eur Respir J, 1992 Mar, 5(3), 343 - 58 Functions of proteins and lipids in airway secretions; Jacquot J et al.; Proteins and lipids synthesized by airway secretory cells or transudated are active components in the protection of respiratory epithelium . Proteins and ions are involved in the control of mucus hydration . Secretory proteins, such as secretory immunoglobulin A (IgA), transferrin and lysozyme, participate in the airway antibacterial defence . Other biochemical components found in secretions, such as anti-inflammatory and antioxidant agents as well as antiproteases, contribute significantly to the protection of the underlying epithelium. Lepr Rev, 1992 Mar, 63(1), 41 - 6 Treatment of multibacillary leprosy with a regimen of 13 weeks duration; Pattyn SR et al.; In a prospective study 559 multibacillary patients in Zaire were treated for 13 weeks with twice weekly rifampicin (600 mg) and daily ethionamide (500 mg) and dapsone (100 mg), 13-RED, or clofazimine (100 mg), 13-REC . The patients were followed for a total of 1418 person years, mean 3.2 years . The incidence of hepatitis was 3.3% . The incidence of relapses was 0.28 per 100 person years . Relapses were due to drug-sensitive organisms . In patients who received the same drug regimens but with a reduced dosage of ethionamide to 5 mg/k bodyweight, the incidence of hepatitis was significantly lower but the relapse rate was 7.8 per 100 person years of follow-up in the RED group, no relapses were diagnosed in the REC group . It is concluded that by the use of potent antileprosy drugs in suitable combinations and dosages, it will be possible to shorten the duration of antibacterial treatment in multibacillary leprosy to 3 months. Gastroenterol Clin North Am, 1992 Mar, 21(1), 257 - 75 Spontaneous bacterial peritonitis; Garcia-Tsao G; SBP is an infection of ascites that occurs in the absence of a local infectious source . It is mainly a complication of cirrhotic ascites, with a prevalence of 15% to 19% (when culture-negative cases are included) . Gram-negative enteric bacteria are the causative agents in more than 70% of cases . SBP is probably the consequence of bacteremia due to defects in the hepatic reticuloendothelial system and in the peripheral destruction of bacteria by neutrophils, with secondary seeding of an ascitic fluid deficient in antibacterial activity . Patients with advanced liver disease and low ascitic fluid protein concentrations seem to have an increased susceptibility to SBP . A diagnostic paracentesis should be performed in any cirrhotic patient who suddenly deteriorates or presents with any compatible symptom of SBP, most frequently fever or abdominal pain, or both . A PMN count greater than 500/mm3 is indicative of SBP, and treatment with intravenous broad-spectrum antibiotics should be initiated immediately . Although the mortality of an acute episode of SBP decreases with early therapy, it is still high (approximately 50%), and patients who survive an episode of SBP have a high frequency of recurrence . Mortality seems to be related to the severity of the underlying liver disease, because only a third of patients die from sepsis and prophylactic antibiotics decrease the frequency of SBP but do not seem to improve long-term survival. Gut, 1992 Mar, 33(3), 397 - 401 Erythromycin and the gut; Catnach SM et al.; The commonly reported gastrointestinal side effects that occur with erythromycin are related to its prokinetic action on the gut, mediated, at least in part, by its motilin receptor stimulating activity . This action may be of clinical use in conditions associated with gastrointestinal hypomotility such as diabetic gastroparesis and intestinal pseudo-obstruction, although further work needs to be done to establish the long term therapeutic uses of erythromycin in these disorders . Macrolide compounds with no antibacterial properties but which have a pronounced prokinetic action on the gut have already been synthesised and are currently being developed for future use in man . These 'motilides' should provide a useful addition to our rather limited armamentarium of effective gastrointestinal prokinetic agents. Clin Infect Dis, 1992 Mar, 14 Suppl 1, S154 - 60 Current role of therapy with amphotericin B; Meyer RD; Systemic antifungal chemotherapy frequently is more difficult to conduct than antibacterial therapy . Factors that make it difficult include, but are not limited to, common biosynthetic pathways among the eukaryotes and humans, a relative lack of agents, imprecise modes of use, general lack of standardization of in vitro susceptibility tests that have clinical correlations, and, with certain exceptions, lack of clinical correlations with in vitro results of combination antifungal chemotherapy . Amphotericin B has been available for intravenous administration for greater than 30 years and, despite its shortcomings, remains the drug of choice or reference agent in the therapy for many specific systemic fungal infections in various clinical settings . The current role of amphotericin B therapy in these situations and the need for additional controlled, comparative clinical trials with azoles, liposomal amphotericin B, and amphotericin B complex are discussed. Minerva Med, 1992 Mar, 83(3), 141 - 4 {Piperacillin: comparison of antibacterial activity in vitro during the triennium 1986-88 versus the biennium 1981-82}; Farris AG et al.; The antibacterial activity in vitro of piperacillin on strains commonly isolated in hospital practice in 1986-88 was compared with that obtained for piperacillin from 1981 to 1982 and with the activity of other antibiotics usually employed . Piperacillin showed a good antibacterial activity on Gram-positive and Gram-negative strains, while few resistant strains were found. Antibiot Khimioter, 1992 Mar, 37(3), 6 - 9 {A rapid method of evaluation of the effectiveness of antibacterial drugs}; Oborin VA et al.; Efficacy of antibiotics in the treatment of experimental tularemia was studied comparatively on various biological models . It was shown that the antibiotics which proved active against the tularemia microbe in albino mice when studied by the rapid and routine methods were highly efficient in the treatment and prevention of experimental tularemia in rabbits and baboons (hamadryas) . The experiments showed basic possibilities to perform rapid estimation (for at least 2 days) of drug efficacy in experimental glanders and melioidosis in golden hamsters . The rapid method developed by the authors was recommended for the use in primary estimation of the efficacy of new drugs in the treatment of tularemia, glanders and melioidosis. Jpn J Antibiot, 1992 Mar, 45(3), 285 - 92 {Pharmacokinetic and clinical evaluation of levofloxacin in obstetrical and gynecological field}; Matsuda S et al.; Levofloxacin (LVFX, DR-3355) a new synthetic antibacterial agent, was evaluated pharmacokinetic and clinically in the field of obstetrics and gynecology and the following results were obtained . 1 . The transport of LVFX into genital tissues (various regions in the uterus, ovary and oviduct) after a single oral administration of 200 mg was found to be good . 2 . Sixteen patients with genital infections (endometritis, salpingitis, cervicitis, mastitis) were treated with LVFX at daily doses of 200-300 mg for 5-15 days . The efficacy rate was 100% and no side effect was observed. Jpn J Antibiot, 1992 Mar, 45(3), 270 - 84 {Pharmacokinetic and clinical evaluation of levofloxacin in obstetrics and gynecology}; Cho N et al.; Levofloxacin (LVFX, DR-3355), a new synthetic quinolone derivative antibacterial agent, was evaluated for its pharmacokinetics and clinical efficacy in obstetric and gynecological infections, and the following results were obtained . Concentrations of LVFX in serum and intrapelvic genital organs such as uterine and adnexal tissues were determined following oral administration of 100 mg . Tissue penetration of LVFX was found to be good, with its tissue levels (Cmax) of 1.17-2.16 micrograms/ml or g after inhalation anaesthesia and 1.15-2.17 micrograms/ml or g after lumbar spinal anaesthesia . LVFX was given to 22 cases of obstetric and gynecological infections with a daily dose of 200-600 mg for 3-14 days and its clinical efficacy was 95% and bacteriological response was 100% . No side effect was observed . From these findings, we consider that LVFX will be a useful antibacterial agent against obstetric and gynecological infections. Farmaco, 1992 Mar, 47(3), 305 - 18 Synthesis, spectral studies and biological activities of some N-bridged heterocycles derived from 3-arylaminomethyl-4-amino-5-mercapto-1,2,4-triazoles; Holla BS et al.; Synthesis of four 3-arylaminomethyl-4-amino-5-mercapto-1,2,4-triazoles starting from substituted anilines is described . These triazoles were employed in the synthesis of some N-bridged heterocycles carrying arylaminomethyl substituents . All the newly synthesized compounds were characterized by analytical, NMR and mass spectral studies . Some of the newly synthesized compounds were screened for their antibacterial and antiviral properties. Ann Ital Chir, 1992 Mar-Apr, 63(2), 201 - 7 {Chemotherapeutic prophylaxis in the preparation of the large intestine for surgical interventions: rifaximin P.O . vs . cephalosporin I.V.}; Bresadola F et al.; 30 patients were examined: 17 males and 13 females aged between 53 and 83 years (average age 66 years), candidates for large intestine surgery . For 5 days before the operation, they were treated at random, in a balanced way, with cefotaxime (3 g/day intravenously), either alone or associated with rifaximin (1200 mg/day P.O.) . Rifaximin, an antibiotic drug endowed with a topical intestinal action, substantially increased the antibacterial activity of the well known and traditional third-generation cephalosporins therapy in the prevention of bacterial infections after major colic surgery . Intestinal bacterial load and pathogenic micro-organisms reduction was substantially increased . Furthermore, a more limited onset of post- surgical complications was observed, together with a better post-surgical clinical course, and a more rapid recovery of normal intestinal functions . The possibility of carrying out an effective chemoprophylaxis by means of an oral drug, such as rifaximin, must be encouraged as, among other things, it substantially reduces the intolerance risk at systemic level, which is nevertheless possible with parenteral antibiotic treatments. Anesteziol Reanimatol, 1992 Mar-Apr, (2), 70 - 1 {A case of successful treatment of a severe form of suppurative meningitis}; Kovrizhnykh NA et al.; A patient with severe meningoencephalitis has been treated using a combination of generalized and local mechanisms of antibacterial drug delivery to the inflammation focus, detoxication and brain circulation improvement . The management results have been analysed . Positive neurological dynamics, homeostasis recovery and shorter period of the patient's stay in an intensive care unit proved the efficacy of management . It is assumed that the improvement of brain perfusion is an important pathophysiological mechanism. Infection, 1992 Mar-Apr, 20(2), 89 - 93 Pharmacokinetics of rufloxacin once daily in patients with lower respiratory tract infections; Rimoldi R et al.; The pharmacokinetic properties of rufloxacin, a new quinolone antibacterial agent, were evaluated in ten patients with lower respiratory tract infections . Patients were given 400 mg of rufloxacin once a day for seven to nine days . Plasma concentrations of the drug were determined by high-performance liquid chromatography and bioassay at regular intervals during treatment . After the first administration, maximal plasma concentrations were 3.17 +/- 0.36 mg/l (mean +/- SEM) and were reached at 4.2 +/- 0.7 h . At the end of treatment peak plasma concentrations increased to 7.26 +/- 0.52 mg/l . Elimination half-life was 38.2 +/- 2.9 h, with a mean extent of accumulation of 2.96 +/- 0.30 . Treatment was well tolerated, with no abnormalities noted during routine laboratory examinations . Two days after the last administration, measurable levels of rufloxacin were still observed in plasma, indicating that the long half-life of rufloxacin assures valuable antibacterial activity even after discontinuation of treatment. J Med Chem, 1992 Feb 21, 35(4), 611 - 20 Synthesis and structure-activity relationships of 7-diazabicycloalkylquinolones, including danofloxacin, a new quinolone antibacterial agent for veterinary medicine; McGuirk PR et al.; A series of novel 6-fluoro-7-diazabicycloalkylquinolonecarboxylic acids substituted with various C8 (H, F, Cl, N) and N1 (ethyl, cyclopropyl, vinyl, 2-fluoroethyl, 4-fluorophenyl, 2,4-difluorophenyl) substituents, as well as, 9-fluoro-10-diazabicycloalkylpyridobenzoxazinecarboxylic acids, were prepared and evaluated for antibacterial activity against a range of important veterinary pathogenic bacteria . The diazabicycloalkyl side chains investigated at the 7-position (benzoxazine 10-position) include (1S,4S)-5-methyl-2,5-diazabicyclo{2.2.1}heptane (2), (1S,4S)-2,5-diazabicyclo{2.2.1}heptane (3), (1R,4R)-5-methyl-2,5-diazabicyclo{2.2.1}heptane (4), 8-methyl-3,8-diazabicyclo{3.2.1}octane (5), 9-methyl-3,9-diazabicyclo{4.2.1}nonane (6), 1,4-diazabicyclo{3.2.2}nonane (7), 1,4-diazabicyclo{3.3.1}nonane (8), and 9-methyl-3,9-diazabicyclo{3.3.1}nonane (9) . Among these side chains, in vitro potency was not highly variable; other properties therefore proved more critical to the selection of possible development candidates . However, the relative potencies observed for several of these compounds in mouse, swine, and cattle infection models correlated well with those seen in vitro . A combination of the N1 cyclopropyl group and the C7 (1S,4S)-5-methyl-2,5-diazabicyclo{2.2.1}hept-2-yl appendage conferred the best overall antibacterial, physiochemical, and pharmacodynamic properties . Hence, danofloxacin (Advocin, 2c) (originally CP-76,136, 1-cyclopropyl-6-fluoro-7-{(1S,4S)-5-methyl-2,5-diazabicyclo{2.2.1} hept-2-yl}-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid) was selected as a candidate for development as a therapeutic antibacterial agent for veterinary medicine. Eur J Biochem, 1992 Feb 15, 204(1), 395 - 9 CecC, a cecropin gene expressed during metamorphosis in Drosophila pupae; Tryselius Y et al.; Cecropins are antibacterial peptides, induced in insects in response to bacterial infections . In Drosophila, three cecropin genes have previously been characterized, CecA1, CecA2, and CecB, in a dense cluster at 99E on the third chromosome . From the same locus, we now describe a fourth member of the cecropin gene family, CecC, which is mainly expressed at the early pupal stage . In situ hybridization to immunized pupae show that CecC is induced in the anterior end of the larval hindgut and in other larval tissues that are undergoing histolysis . Within these other tissues it is often expressed in distinct foci that may correspond to hemocytes . A similar pattern of expression in the metamorphosing pupa is also observed for the CecA and CecB genes . Comparing the DNA sequences of the cecropin genes, a conserved region is observed about 30 bp upstream of the TATA box . It consists of three shorter motifs, two of which are reminiscent of a putative promoter element in immune protein genes from the cecropia moth. Clin Pharmacokinet, 1992 Feb, 22(2), 132 - 43 Considerations in dosage selection for third generation cephalosporins; Yuk-Choi JH et al.; Pharmacokinetic parameters of third generation cephalosporins vary widely, requiring different dosage regimens and adjustment methods for each agent . Although their antibacterial spectrum favours their usage in infections caused by aerobic Gram-negative organisms, due to their limited post-antibiotic effect against these organisms, dosage regimens should ensure that free drug concentrations at the site of infection remain above the minimum inhibitory concentration for as much of the dosage interval as possible in patients with normal host defence mechanisms and for the entire dosage interval in immunocompromised patients . Altered protein binding encountered in various disease states can affect both microbiological and pharmacokinetic properties especially for drugs with high protein binding . Since the concentrations at the site of action are often different from those in serum, a higher or lower range of dosages needs to be selected depending on the target site . Decreased renal function affects the elimination of most third generation cephalosporins, whereas the presence of hepatic disease does not generally necessitate dosage adjustment . Because of the complex age-related physiological changes in paediatric and elderly patients, dosage should be adjusted on the basis of the reported pharmacokinetic data in these populations . The usual recommended dose may or may not be optimal in a given condition depending on the complex interactions between pharmacokinetic, microbiological and other host factors. J Med Chem, 1992 Feb 7, 35(3), 518 - 25 Fluoronaphthyridines as antibacterial agents . 4 . Synthesis and structure-activity relationships of 5-substituted-6-fluoro-7-(cycloalkylamino)-1,4-dihydro-4-oxo-1,8- naphthyridine-3-carboxylic acids; Bouzard D et al.; A series of 5-substituted-6-fluoro-7-(cycloalkylamino)-1,4-dihydro-4-oxo-1,8- naphthyridine-3-carboxylic acids have been prepared and tested for their in vitro and in vivo antibacterial activities . The 5-methyl group gave better in vitro activity with the 1-cyclopropyl appendage, but poorer activity with the 1-tert-butyl moiety . With the 1-(2,4-difluorophenyl) substitution, the influence of the 7-cycloalkylamino group was determinant: a (3S)-3-amino-pyrrolidine was shown to enhance greatly the in vitro and in vivo activity of the 5-methyl derivative . Compound 33 (BMY 43748) was selected as a promising candidate for an improved therapeutic agent. J Med Microbiol, 1992 Feb, 36(2), 78 - 82 Induction of the SOS gene (umuC) by 4-quinolone antibacterial drugs; Power EG et al.; Induction by the 4-quinolone group of antibacterial drugs of the umuC gene, the SOS function most involved in error-prone DNA repair (together with umuD), was assessed in a strain of Escherichia coli harbouring a umuC::lacZ gene fusion . All 4-quinolones tested induced this umuC::lacZ fusion, with maximum induction at 4-quinolone concentrations close to their minimum inhibitory concentrations for this strain, and the SOS Inducing Potential (SOSIP) was closely related to antibacterial activity . Mitomycin C, a known mutagen, was a slightly better inducer (in terms of SOSIP) than any of the quinolones . In contrast, induction by 4-quinolones of the sfiA (sulA) gene, an SOS function involved in cell division inhibition, was better than induction by mitomycin C in an E . coli strain harbouring an sfiA::lacZ gene fusion . The umuC gene fusion was induced at lower concentrations of 4-quinolone than was the sfiA gene fusion. Pharmazie, 1992 Feb, 47(2), 98 - 101 Mechanism of the polarographic reduction of a new 5-nitrofuran derivative with antibacterial activity; Garcia Monteagudo JC et al.; The reduction at mercury electrodes of a new 5-nitrofuran derivative with antibacterial activity, N2-(5-nitrofurfurylidene)formohydrazide-4-(3,5-dicyanophenyl)-6-ethoxy-2- pyridyl)imide, was studied by conventional, normal pulse, reverse normal pulse and differential pulse polarography in water-dimethylformamide (30%) buffered media . The waves observed, whose number depended on pH, are attributed to the reduction of the nitro group (6 electrons) and the azomethinic unit (4 electrons) . The basic mechanisms of the electrode reactions have been deduced from the characteristics of the waves . Conditions for determining the formal potential of the nitroderivative/radical-anion system, a parameter related to pharmacological activity, are also reported. J Nat Prod, 1992 Feb, 55(2), 225 - 8 Isolation, NMR studies, and biological activities of onopordopicrin from Centaurea sonchifolia; Lonergan G et al.; A sesquiterpene lactone, onopordopicrin {1}, has been isolated from Centaurea sonchifolia . Its structure was established by 2D nmr (1H-1H and 13C-1H correlations), and the conformation in CHCl3 was examined by nOe studies . Cytotoxic, antibacterial, and antifungal activities are reported. J Nat Prod, 1992 Feb, 55(2), 174 - 8 Four new antibacterial sesterterpenes from a marine sponge of the genus Luffariella; Konig GM et al.; The structures of four new sesterterpenoid compounds 1-4 isolated from a marine sponge of the genus Luffariella, collected from The Great Barrier Reef, Australia, have been determined by analysis of their 1H-nmr, 13C-nmr, ir, uv, and eims spectral data . The new metabolites 1-4 were found to co-occur with the compounds manoalide, secomanoalide, Z-neomanolaide {5}, and E-neomanoalide. Indian Pediatr, 1992 Feb, 29(2), 181 - 8 Adverse drug reaction monitoring of ciprofloxacin in pediatric practice; Karande SC et al.; Ciprofloxacin, a fluoroquinolone antibacterial agent, is not recommended in pediatric population on account of its possible adverse effect on growing cartilage . It is being commonly used for treatment of variety of infections in children in our country and very little information is available on the risks involved in its use . A questionnaire was sent to 750 pediatricians in the last week of November 1990, to retrospectively judge over the previous 2 month period the extent of its use and identify the adverse drug reactions (ADRs) . One hundred and fifty-four pediatricians replied, of which 147 had prescribed ciprofloxacin in a total of 3341 patients under 18 years of age, enteric fever being the commonest indication for its use . One hundred and fifty-nine ADRs were reported in 104 (3.1%) patients . They were: gastrointestinal in 50% of these 104 patients, CNS in 23%, skin and allergic in 19.1%, musculoskeletal in 8.6%, hematological in 3.8%, CVS in 2.9% and nephrological in 0.9% cases . Of 159 ADRs, 8 (5%) were severe, 76 (47.8%) were moderate and 75 (47.2%) were mild . Therapy needed discontinuation in only 9 (0.3%) patients . Two new ADRs were identified, viz., sudden death after intravenous ciprofloxacin and sinus nodal arrest causing bradycardia. J Appl Bacteriol, 1992 Feb, 72(2), 146 - 53 Studies on the lactoperoxidase system: reaction kinetics and antibacterial activity using two methods for hydrogen peroxide generation; Dionysius DA et al.; Components of the lactoperoxidase system were measured during incubation in Isosensitest broth, with enzymatic (glucose oxidase, GO) or chemical (sodium carbonate peroxyhydrate, SCP) means to generate H2O2 . When low levels of thiocyanate (SCN-) were used in the GO system, H2O2 was detected and lactoperoxidase (LP) was inactivated when SCN- was depleted . With 10-fold higher SCN-, LP remained active and H2O2 was not detectable . The oxidation product of the LP reaction, most likely hypothiocyanite, was present in low concentrations . When SCP was used for the immediate generation of H2O2 in a system employing low SCN-, half the LP activity was lost within minutes but thereafter it remained stable . Low concentrations of oxidation product were measured and H2O2 was not detected during the course of the experiment . At high SCN- levels, relatively high concentrations of oxidation product were produced immediately, with H2O2 undetectable . The results suggest that the final product of the LP reaction depends on the method of H2O2 generation and the relative proportions of the substrates . Antibacterial activity of the two LPS was tested against an enterotoxigenic strain of Escherichia coli . Both systems showed bactericidal activity within 4 h incubation at 37 degrees C. J Antibiot (Tokyo), 1992 Feb, 45(2), 240 - 5 The synthesis, antibacterial, and beta-lactamase inhibitory activity of a novel asparenomycin analog; Bouthillier G et al.; An analog, 6-(2'-hydroxyethylidene)-4 beta-methyl-1-azabicyclo{3.2.0}hept-2-ene-2- carboxylate (11), of the carbapenem beta-lactamase inhibitor, asparenomycin A, was synthesized . It possessed a spectrum of antibacterial activity that was comparable to that of asparenomycin A but was less effective as a beta-lactamase inhibitor . With ampicillin, it only exhibited a moderate level of synergy against a variety of beta-lactamase-producing organisms . Although the presence of a 4 beta-methyl group in the analog brought about a significant increase in chemical stability relative to that of asparenomycin A, it did not result in an increase in stability to kidney dehydropeptidase enzyme. J Antibiot (Tokyo), 1992 Feb, 45(2), 227 - 34 Transformation of streptonigrin into streptonigrone; synthesis and biological evaluation of antibiotics streptonigrin and streptonigrone alkyl ethers; Preobrazhenskaya MN et al.; A method of synthesis of antibiotic streptonigrin 8'-O-alkyl ethers by alkylation of streptonigrin diphenylmethyl ester and consequent deprotection of carboxylic group with CF3COOH is developed . An attempt to deblock carboxylic group of 8'-O-methylstreptonigrin diphenylmethyl ester by hydrogenation over Pd produced 8'-O-methylstreptonigrone . Similarly streptonigrin was transformed into streptonigrone over Pd-black in H2 stream . Methylation of streptonigrone afforded 5',5'-N-dimethyl-2',8'-O-dimethylstreptonigrone and 1',5',5'-tri-N-trimethyl-8'-O-methylstreptonigrone . Alkyl streptonigrin ethers demonstrated lower antibacterial activity in vitro than the parent antibiotic. J Antibiot (Tokyo), 1992 Feb, 45(2), 213 - 26 N-acyl 3-alkylidenyl- and 3-alkyl azetidin-2-ones: a new class of monocyclic beta-lactam antibacterial agents . 1 . Structure-activity relationships of 3-isopropylidene and 3-isopropyl analogs; Brickner SJ et al.; The synthesis and antibacterial activity of a series of N-acyl 3-isopropylidenyl- and 3-isopropyl 2-azetidinones having potent in vitro antibacterial activity, particularly against anaerobic organisms, is described . A distinguishing structural feature of these compounds is the lack of any ionizable moiety appendant to the lactam nitrogen. Ophthalmology, 1992 Feb, 99(2), 192 - 6 Medical management of ocular malakoplakia; Simpson C et al.; A 14-year-old girl had a granulomatous conjunctival lesion, proven histologically to be malakoplakia . This is the first reported case of malakoplakia arising from conjunctiva, although three others have involved the ocular adnexa . Malakoplakia is a rare disease often associated with immunodeficiency and is characterized by the presence of intracellular inclusions and organisms due to deficient intracellular bacteriolysis . Medical management is difficult because an effective antibacterial agent requires three properties: activity against the organism involved, good intracellular penetration, and the capacity to maintain its effectiveness in the intracellular milieu . Escherichia coli was isolated from a biopsy specimen and from conjunctival swabs . Treatment with systemic ciprofloxacin, which has good intracellular penetration and activity, led to rapid resolution of the lesion . This is the first report concerning the successful use of this drug to treat malakoplakia of any organ. J Am Vet Med Assoc, 1992 Feb 1, 200(3), 366 - 7 Epistaxis in two horses with dacryohemorrhea; Schumacher J et al.; Unilateral epistaxis in 2 horses was caused by inflammation of the distal portion of the lacrimal system . The origin of epistaxis was identified during physical examination by observing hemorrhage emanating from the nasal opening of the nasolacrimal duct . Dacryohemorrhea caused by bacterial infection was successfully treated with antibacterial drugs administered systemically and instilled into the lacrimal system. Am J Obstet Gynecol, 1992 Feb, 166(2), 606 - 12 Direct inhibition of proteases and cervical plasminogen activator by antibiotics; Milwidsky A et al.; OBJECTIVES: Preterm premature rupture of the fetal membranes and premature delivery are sometimes linked to genital tract infection and activation of proteolytic enzymes that degrade the extracellular matrix . The possible beneficial effect of antibiotics in prevention of preterm premature rupture of fetal membranes and retardation of the onset of labor in some patients with clinical or subclinical infection was explained via their antibacterial efficacy . The aim of this study was to determine the effect of antibiotics on proteolytic enzymes as a possible explanation for the ability of antibiotics to retard preterm labor . STUDY DESIGN: The direct effect of four antibiotics on the proteolytic activities of purified collagenase, elastase, plasmin, trypsin, and chymotrypsin and on streptokinase and human cervical plasminogen activator was measured . RESULTS: The macrolide antibiotic erythromycin and the beta-lactam antibiotics penicillin G, cloxacillin, and ampicillin exerted, in most of the tested combinations with the different proteases, inhibitory effects on the proteolytic activities . CONCLUSION: The present finding that antibiotics directly inhibit proteases may offer an explanation for the beneficial response to antibiotic therapy in some cases of idiopathic preterm labor even in absence of pathogenic bacterial infection. Khirurgiia (Mosk), 1992 Feb, (2), 67 - 70 {The treatment of unformed intestinal fistulae}; Petrenko TF et al.; Experience in the treatment of 33 patients with unformed intestinal fistulas is discussed . The choice of the method for surgical management was determined by the localization of the fistulas, the possibility of their occlusion, and the severity of the patient's condition . Complex therapy included selective administration of antibacterial agents and extracorporeal detoxification by means of biohemosorption . Rational surgical tactics and complex treatment including extracorporeal detoxification in patients with unformed external intestinal fistulas made it possible to reduce the mortality rate from 33.4% to 21.2% (7 patients died). J Antimicrob Chemother, 1992 Feb, 29(2), 207 - 17 A comparison of the costs of ceftazidime therapy and gentamicin combinations in three UK hospitals; Malek M et al.; This study compares the utilization costs of ceftazidime therapy with those of gentamicin in combination with other antibacterial drugs . The results show that the relatively high purchase cost of ceftazidime compared to combinations is more than counterbalanced by the additional materials used for drug administration and serum antibiotic assays, even when other drugs were combined with ceftazidime . The average drug and equipment costs were 230.13 pounds for ceftazidime regimens and 253.94 pounds for gentamicin regimens . It is also shown that ceftazidime therapy is associated with a reduction in personnel time compared to gentamicin regimens . The average times per patient for administration and assay were 1 h 43 min for ceftazidime and 4 h 57 min for gentamicin regimens . We conclude that ceftazidime regimens are cheaper than gentamicin regimens when all drug and equipment costs are quantified . Moreover, the use of ceftazidime will release staff time for other purposes. Can J Microbiol, 1992 Feb, 38(2), 115 - 23 Mode of antibacterial action of dodine (dodecylguanidine monoacetate) in Pseudomonas syringae; Cabral JP; Treatment of Pseudomonas syringae cells with 50 microM dodecylguanidine monoacetate (dodine) resulted in the rapid degradation and release of RNA and cell lysis . Higher concentrations resulted in a progressive decrease in the intensity of these responses, and the appearance of extensive zones of coagulated cytoplasm, indicating that the decrease in RNA degradation probably resulted from an inhibition of the RNases, due to protein denaturation . Dodine also induced expansion of the outer membrane, with the formation of protuberances and intracellular myelin-like structures, which were already evident after 1 min of treatment, indicating that dodine is able to cross the outer and cytoplasmic membranes rather rapidly, and to form, alone or in combination with cell phospholipids and proteins, considerable amounts of triple-layered profiles . In P . syringae cells, saturation levels of dodine corresponded to more than five times the amount needed to form a close-packed monolayer of dodine on the cell surface . The different membranous structures formed in dodine-treated cells, and the coagulation of the cytoplasm, seem to be responsible for the uptake of such high amounts of dodine . The uptake isotherm was essentially Langmuirian . The results presented in this and previous reports indicate that the antibacterial activity of dodine on P . syringae is mainly the result of the action of micelles of the surfactant. Clin Infect Dis, 1992 Feb, 14(2), 608 - 15 Cytomegalovirus infection in patients with AIDS; Drew WL; Advances in the field of antiviral therapy are now occurring with increasing frequency and rapidity and often generate varying degrees of confusion among those of us whose practices are focused primarily on therapy with antibacterial agents . How to treat cytomegalovirus infections in patients infected with the human immunodeficiency virus constitutes one of the best examples of the quandaries engendered by these advances, and the topic is reviewed in this first AIDS Commentary update . Given the U.S . Food and Drug Administration's recent approval of foscarnet, this discussion is very timely; it is particularly relevant for clinicians to be made aware of current lines of thought regarding induction versus maintenance therapy, the benefits of efficacy versus adverse effects of drug-related toxicity, and the interactions between antiretroviral drugs and ganciclovir or foscarnet . Dr . W . Lawrence Drew's career in this area has been long-standing and productive, and he is one of the leading experts in the field . In this update he addresses these perplexing issues. FEBS Lett, 1992 Jan 20, 296(2), 190 - 4 Shortened cecropin A-melittin hybrids . Significant size reduction retains potent antibiotic activity; Andreu D et al.; We have earlier reported two 26-residue antibacterial peptides made up from different segments of cecropin A (CA) and melittin (M) . We now report a substantial reduction in size at the C-terminal section of the highly active hybrid CA(1-8)M(1-18), leading to a series of 20-, 18- and 15-residue analogs with antibiotic properties similar to the larger molecule . In particular, the 15-residue hybrids CA(1-7)M(2-9), CA(1-7)M(4-11) and CA(1-7)M(5-12) are the shortest cecropin-based peptide antibiotics described so far, with antibacterial activity and spectra similar or better than cecropin A and a 60% reduction in size . Their reduced size and highly alpha-helical structure require an alternative mechanism for their interaction with bacterial membranes. J Pediatr, 1992 Jan, 120(1), 72 - 7 Measuring the comparative efficacy of antibacterial agents for acute otitis media: the "Pollyanna phenomenon"; Marchant CD et al.; In randomized, double-blind trials of antibiotic therapy for acute otitis media that determined both clinical and bacteriologic outcomes, clinical success rates were (93%) 236 of 253 for patients with bacteriologic success, (62%) 25 of 40 for those with bacteriologic failure, and (80%) 124 of 155 for those with nonbacterial acute otitis media . These rates were used to calculate the effectiveness of three strategies for assessing drug efficacy: (1) tympanocentesis and culture before and during therapy (bacteriologic efficacy), (2) tympanocentesis before therapy and assessment of clinical efficacy in bacterial acute otitis media, and (3) no tympanocentesis and assessment of clinical efficacy in clinical (total) acute otitis media . For a drug with a bacteriologic efficacy of 100%, calculated clinical efficacy was 93% for bacterial acute otitis media and 89% for clinical acute otitis media . For a drug with bacteriologic efficacy of 27%, a rate consistent with no antibacterial therapy, efficacy was 71% for bacterial acute otitis media and 74% for clinical acute otitis media . We conclude that if efficacy is measured by symptomatic response, drugs with excellent antibacterial activity will appear less efficacious than they really are and drugs with poor antibacterial activity will appear more efficacious than they really are . The predominant phenomenon is that drugs with poor antibacterial activity will appear to be clinically effective in the treatment of acute otitis media. J Infect Dis, 1992 Jan, 165(1), 34 - 45 Antibacterial and protective properties of monoclonal antibodies reactive with Escherichia coli O111:B4 lipopolysaccharide: relation to antibody isotype and complement-fixing activity; Oishi K et al.; In vitro and in vivo antibacterial and protective properties of murine monoclonal antibodies (MAbs) to Escherichia coli O111:B4 lipopolysaccharide (LPS) were evaluated in relation to antibody isotype and complement-fixing activity . Six O side chain-specific MAbs, including two IgMs and one of each IgG subclass, were analyzed for quantitative binding and C3 deposition on intact bacteria, complement-mediated bactericidal and opsonophagocytic activity, and protection against intraperitoneal infections in mice . Although C3 was deposited on bacteria in the presence of normal human serum (NHS) alone, LPS-specific MAbs increased C3 attachment in a dose-dependent manner . Bacterial killing occurred only in the presence of both antibody and complement NHS and required an intact alternative pathway . The efficiency of bacterial killing varied by antibody isotype (IgM greater than IgG2a greater than other IgG subclasses) and correlated with C3-fixing capacity . Opsonophagocytic activity of MAbs exhibited a similar isotype-related rank order . Likewise, IgM was more active than IgG, and IgG2a was superior to other IgG subclasses, in MAb-mediated protection against intraperitoneal infection . These data document the interdependent antibacterial and complement-fixing properties of LPS-reactive MAbs and the degree to which both activities are determined by antibody class and isotype. Ross Med Zh, 1992, (2), 6 - 8 {Ventricular ejection fraction in oxygen therapy of patients with pulmonary tuberculosis}; Ershov AI et al.; Radionuclide study of ejection fraction of the right heart ventricle was carried out in lung tuberculosis patients with respiratory insufficiency and cor pulmonale . Oxygen therapy was found to promote reduction of right ventricle heart failure in effective treatment of lung tuberculosis . The greatest reduction of heart failure was recorded in cases where oxygen therapy was combined with cardiac glycosides . As the tuberculosis process progresses, oxygen therapy does not decrease right ventricle heart failure . The treatment by antibacterial agents alone without using oxygen does not lead to the rise of ejection fraction of the right ventricle of the heart. Vet Med (Praha), 1992 Jan, 37(1), 21 - 31 {Tests of Milkofix, a new preservative preparation for milk samples used for infrared analysis of milk components . I . Verification of its bacteriostatic and bacteriocidal effects and its interference effects}; Hanus O et al.; Hygienic, ecological and health problems of sample preservation for an analysis of basic milk components make us continually to develop a safer chemical preservative substance which will preserve the original sample composition for the time required and which will not influence the analyses . Trzicky (1990) proposed Milkofix (M), a preservative substance on the basis of silver compound . The author reports on minimum risks of the use of this preparation, in comparison with traditional preservatives . Preservative efficiency of Milkofix was compared with other preservatives: K2Cr2O7 (C), NaN3 (A) and bronopol (B) . The following concentrations were used: A--0.0085 g NaN3 and 0.0630 g NaCl, B--0.0050 g bronopol and 0.0500 g NaCl, C--0.0330 g K2Cr2O7 and 0.0670 g KCl in tablet, M--0.1250 g of the mixture, all amounts are per 25 ml milk . The observed antibacterial efficiency of M could be seen in a slower decrease in actual acidity, and/or in an increase in titratable acidity in M-treated samples unlike untreated ones (N) . From the starting value pH 6.3 (Fig . 1), the value of N treatment dropped to 3.8 after two days, the values of M and A treatments dropped to 4.9 after nine days and to 5.7 after twelve days, respectively . As for SH, the values increased within the same interval from 6.5 (2.5 mmol/l) to 28.6 in N, and to 22.3 in M and 9.4 in A (Fig . 3) . There was a similar trend when the milk samples were stored at a temperature of 4 degrees C, but the differences between the preservation methods were not so clear in comparison with storage at a temperature of 20 degrees C (Figs . 1 and 3) . The standardized SH value of 9.0 (2.5 mmol) for infraanalyzer measurements was exceeded after 24 hours in N samples, after four days in M samples and after 12 days in A samples at a temperature of 20 degrees C . The observation of the growth of microorganism counts (CPM) showed that this growth was slower in M than in N, but faster in the samples of C treatment (Fig . 5) . The generative time of CPM in N made 1.6 hours, in M 2.4 hours and in C 7.9 hours . The lag phase of these mixed cultures was 24 hours in M, 60 hours in C and in N treatment the lag phase was zero.(ABSTRACT TRUNCATED AT 400 WORDS) Klin Khir, 1992, (4), 1 - 4 {Antibacterial and immunocorrective therapy of diffuse purulent peritonitis}; Zaitsev VT et al.; The effectiveness of surgical treatment of 193 patients with generalized purulent peritonitis was analysed . The complex of bacteriologic and immunologic investigations contributed to optimization of antibacterial and immunocorrective therapy . Rational antibacterial therapy should be based on the principle of the use of broad and super-broad spectrum antibiotics with mandatory inclusion into the programme for treatment of metronidazole, administration of antibacterial agents before, at the time and after the operative intervention before identification of microflora and determination of its sensitivity to antibiotics . The therapeutic and tactical approach developed permitted to reduce lethality in generalized purulent peritonitis from 39.5 to 24.9%. Respiration, 1992, 59(2), 116 - 8 Wegener's granulomatosis--treatment under revision? Puolijoki H, Liippo K, Raitio M, Tala E. A 44-year-old man with nasal and respiratory symptoms combined with positive serum antibodies to neutrophil cytoplasmic antigens (ANCA) suggestive of Wegener's granulomatosis was treated with antibacterial agents . Complete clinical response was achieved with co-trimoxazole, and the titer of ANCA declined . After a 12-month treatment period, the patient contracted fever and respiratory symptoms and fatigue again, and he had proteinuria and hematuria . After the institution of conventional treatment with oral prednisolone and cyclophosphamide, a favorable response was achieved . Wegener's-like granulomatosis is difficult to diagnose at its early stage, but the presence of ANCA may be helpful . We suggest that co-trimoxazole should be considered as a first-line treatment, under careful supervision, for young patients whose disease is limited to the respiratory organ. Chemotherapy, 1992, 38(1), 1 - 6 Oral disposition kinetics of ofloxacin in patients with compensated liver cirrhosis; Orlando R et al.; The disposition kinetics of ofloxacin, a quinolone antibacterial agent excreted essentially unmodified by the kidney, was studied after single oral administration in 8 patients with compensated liver cirrhosis and in 8 control subjects . Mean elimination half-life and apparent volume of distribution were significantly increased in the cirrhotic group (7.6 vs . 4.9 h and 1.6 vs . 1.2 liters kg-1, respectively) . A reduction in the renal clearance of ofloxacin was also observed in the cirrhotic patients, in spite of an apparently normal renal function . These observations indicate that also the pharmacokinetics of unmetabolized drugs may be altered in compensated liver cirrhosis . The serum concentration-time profiles of nearly all subjects exhibited a secondary peak 4-6 h after dosing . This double-peak behavior was interpreted as either enterohepatic circulation or biphasic gastric emptying of ofloxacin. Probl Tuberk, 1992, (1-2), 8 - 10 {Biochemical mechanisms of neurotoxic reactions to antibacterial preparations in patients with pulmonary tuberculosis}; Chelnokova NV et al.; Examination comprising the electrophysiologic method and study of the biochemical parameters of the antioxidant/lipid peroxidation system and metabolism of biologic amines in 163 patients with infiltrative pulmonary tuberculosis has revealed a clear interaction existing between the functional changes of the CNS state, the state of antioxidative defense (alpha-tocopherol) and serotonin . This allows an assumption that the antioxidant/lipid peroxidation system and serotoninergic system actively participate in the pathogenesis of development of neurotoxic reactions to antibacterial preparations in the clinical picture of tuberculosis. Pediatr Res, 1992 Jan, 31(1), 18 - 21 Defective production of interleukin-6 by monocytes: a possible mechanism underlying several host defense deficiencies of neonates; Schibler KR et al.; Several deficiencies in antibacterial defense have been described in neonates . Among those best characterized are delayed maturation of B cells into antibody producing cells, deficient T-cell maturation, and delayed cycling of hematopoietic progenitor cells after an infectious challenge . No unifying theory has been forwarded, however, to explain the concomitance of these three developmental deficiencies . IL-6, a cytokine produced primarily by monocytes and macrophages in response to stimulation by IL-1, is involved in the regulation of these three processes . Thus, we postulated that defective production of IL-6 could be a mechanism underlying these immune deficiencies of neonates . Indeed, we observed that a peak production, cells of five term neonates produced only one half as much IL-6 (14 120 +/- 2590 pg IL-6/10(6) monocytes) as those of five adults (28 940 +/- 1680 pg, p less than 0.001) . Peak production was lower still by monocytes of six preterm neonates (7190 +/- 1400 pg, p less than 0.001 versus term) . Production of IL-6 protein was inhibited by actinomycin D and the IL-6 mRNA content of monocytes from neonates, as assessed by competitive polymerase chain reaction, was less than that of adult monocytes . We speculate that defective IL-6 transcription might underlie some of the defects in immune regulation observed in neonates. Grud Serdechnososudistaia Khir, 1992, (1-2), 21 - 3 {Antibacterial prophylaxis in heart surgery inte